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Sympathomimetic amines, including β-phenylethylamine (PEA), constrict animal blood vessels but their mechanism of action is not now thought to be through α-adrenoceptors and release of noradrenaline but via trace amine-associated receptors (TAARs). This information is not available for human blood vessels. Functional studies were therefore performed on human arteries and veins to establish whether they constrict to PEA and whether any constrictions are adrenoceptor-mediated. Isolated internal mammary artery or saphenous vein rings were set up in Kreb's-bicarbonate solution at 37 ± 0.5 °C gassed with O 2 :CO 2 (95:5) under class 2 containment. Isometric contractions were measured and cumulative concentration-response curves for PEA or the α-adrenoceptor agonist, phenylephrine were established. PEA showed concentration-related contractions. The maximum was significantly greater in arteries (1.53 ± 0.31 g, n = 9) than veins (0.55 ± 0.18 g, n = 10), but not when plotted as % of KCl contractions. PEA showed slowly developing contractions plateauing at 17,3 ± 3.7 min in mammary artery. The reference α-adrenoceptor agonist, phenylephrine, exhibited more rapid onset (peak 5.0 ± 1.2 min) but non-sustained contractions. In saphenous veins, PEA (62.8 ± 10.7%) and phenylephrine (61.4 ± 9.7%, n = 4) displayed the same maximum, but phenylephrine was more potent. The α 1 -adrenoceptor antagonist, prazosin (1 μM), blocked phenylephrine contractions of mammary arteries but not PEA contractions in either vessel. PEA causes substantial vasoconstriction of human saphenous vein and mammary artery, which explains its vasopressor actions. This response, however, was not mediated via α 1 -adrenoceptors, but likely due to TAARs. The classification of PEA as a sympathomimetic amine on human blood vessels is therefore no longer valid and requires revision., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Internal mammary artery, by far, is the gold standard and first conduit for surgical revascularization especially when it comes to bypassing a lesion in the left anterior descending coronary artery. Several factors behind using this artery have been established, including but not limited to, the anatomical location, the course and flow, the elastic nature of the artery as well as the physiological characteristics that make this conduit to yield excellent long-term patency rates. This review aims to thoroughly examine current literature and establish the facts behind using this conduit in our daily surgical revascularization practice.

Objective: Minimally invasive multivessel coronary artery bypass grafting (MIM CABG) has demonstrated its safety, effectiveness and high rate of reproducibility. However, minithoracotomy CABG is still rarely performed. In this study, we retrospectively analyze the CT-angiographic graft patency rates for the patients subjected to this operation., Methods: A total of 245 patients were subjected to MIM CABG by a left minithoracotomy approach between 2014 and 2018. The left internal thoracic artery (LITA) harvesting, proximal, and distal anastomoses were performed under direct vision. The patients then underwent 128-slice computed tomography coronary angiography (CTA). The angiographic results were obtained for 127 (51.8%) patients (the follow-up period of 31.1 ± 7.8 months, from 15 to 45 months). Of the total patients, 204 (83.2%) were followed clinically during the time period from 12 to 56 months., Results: Complete revascularization was performed for all the patients. The mean number of grafts was 2.6 ± 0.5. The perioperative mortality was 0.4% (1 patient). There were two conversions to sternotomy (0.8%), four reopenings for bleeding (1.6%), three myocardial infarctions (1.2%), and one stroke (0.4%). Twenty-two patients (9.0%) received transfusions. The long-term mortality was 4.4% (nine patients). Three patients (1.5%) suffered from a stroke during the follow-up period. For five patients (2.4%), repeat revascularization was necessary. For the examined patients, the overall graft patency rate was 89.8%, the LITA graft patency rate was 98.4%, the radial artery patency was 100%, and the saphenous vein graft patency was 84.0%., Conclusions: MIM CABG allows complete surgical revascularization with excellent clinical outcomes and promising angiographic graft patency rates., (© 2020 Wiley Periodicals, Inc.)

Introduction: Arterial graft physiology influences the long-term outcome of coronary artery bypass grafting (CABG). We studied factors that can affect the overall resistance to flow using internal mammary artery grafting to the left anterior descending artery., Methods: This was a prospective, nonrandomized observational study of 100 consecutive patients who underwent elective on-pump isolated or combined valve surgery and CABG. Coronary stenoses were assessed using conventional and quantitative coronary angiography assessment. The flow and pulsatility index (PI) of the grafts were assessed by transit-time flowmetry during cardioplegic arrest and at the end of the operation. Fractional polynomials were used to explore linearity, followed by multivariable regression analysis., Results: Univariate analysis demonstrated higher flows at the end of the operation in patients who had higher flows with the cross-clamp on (P < .001), in males (P = .004), in patients with a low PI at the end of the operation (P = .04), and in patients with a larger size of the recipient artery (P = .005). Multivariable regression analysis showed that the graft flow at the end of the operation was significantly associated with the mean flow with the cross-clamp on (P < .001), sex (P = .003), and PI at the end of the operation (P = .003). Concomitant valve surgery did not influence flows. Male patients had 18 mL/min higher flow., Conclusions: The graft flow at the end of the operation can be determined by the flow with the cross-clamp on, the PI with the cross-clamp off and coronary artery. We reported differences in the graft flows between sexes, and for first the time, we introduced the concepts of "adequate flow" and "resistance-to-forward-flow" for patent coronary grafts., (© 2019 Wiley Periodicals, Inc.)

Background: Conduits used in coronary artery bypass artery grafting (CABG) have different properties and flow profiles. We compared intraoperative mean graft flow (MGF) between arterial and venous conduits, off-pump CABG (OPCABG) and on-pump CABG (ONCABG) procedures, skeletonized and pedicled internal mammary artery (IMA) grafts, and pulsatility index (PI) between OPCABG and ONCABG, in pairwise meta-analyses., Methods: Following a systematic literature search, all studies comparing MGF in arterial and venous grafts, were included. The primary endpoint was comparison of pooled MGF between arterial and venous grafts. Secondary endpoints were comparisons of pooled MGF in OPCABG vs ONCABG, anastomosed skeletonized vs pedicled IMA grafts, free skeletonized vs pedicled IMA grafts and PI in OPCABG versus ONCABG., Results: A total of 25 studies with 4443 patients were included. Compared with venous grafts, arterial grafts had lower MGF (standardized mean difference [SMD], -0.28; 95% confidence interval [CI, -0.34; -0.22]; P < .001). OPCABG was associated with significantly lower MGF compared to ONCABG (SMD, -0.29; 95%CI, -0.50; -0.08]; P = .01). No differences were found in MGF between skeletonized vs pedicled IMA after anastomosis (SMD, 0.32; 95%CI [-0.08; 0.71]; P = .11) or in free flow (SMD, 0.76; 95%CI [-0.14; 1.65]; P = .10). No difference was found in PI between OPCABG and ONCABG. At meta-regression, age was associated with higher MGF, while OPCABG was associated with lower MGF., Conclusions: Intraoperative flow of venous conduits is higher than that of arterial grafts. Compared to OPCABG surgery, graft flow is higher in ONCABG. In skeletonized and pedicled IMA conduits, no difference in flow profiles was found., (© 2019 Wiley Periodicals, Inc.)

In the existing patency prediction model of coronary artery bypass grafting (CABG), the characteristics are based on graft flow, but no researchers selected hemodynamic factors as the characteristics. The purpose of this paper is to study whether the introduction of hemodynamic factors will affect the performance of the prediction model. Transit time flow-meter (TTFM) waveforms and 1-year postoperative patency results were obtained from 50 internal mammary arterial grafts (LIMA) and 82 saphenous venous grafts (SVG) in 60 patients. Taking TTFM waveforms as the boundary conditions, the CABG ideal models were constructed to obtain hemodynamic factors in grafts. Based on clinical characteristics and combination of clinical and hemodynamic characteristics, patency prediction models based on support vector machine (SVM) were constructed respectively. For LIMA, after the introduction of hemodynamic factors, the accuracy, sensitivity and specificity of the prediction model increased from 70.35%, 50% and 74.17% to 78.02%, 70% and 78.89%, respectively. For SVG, the accuracy, sensitivity and specificity of the prediction model increased from 63.24%, 40% and 76.91% to 74.41%, 60.1% and 82.73%, respectively. The performance of the prediction model can be improved by introducing hemodynamic factors into the characteristics of the model. The accuracy, sensitivity and specificity of the prediction results are higher with the addition of hemodynamic characteristics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Migraine is associated with activation of the trigeminovascular system, release of calcitonin gene-related peptide (CGRP) and dilation of dural arteries. Novel treatments target calcitonin gene-related peptide or its receptor, which are present in all vascular beds, raising cardiovascular concerns. Erenumab is a human CGRP-receptor antibody approved for the prophylactic treatment of migraine., Methods: We characterised the relaxant responses to CGRP in the absence and presence of erenumab (1 μM) in isolated human middle meningeal, internal mammary and (proximal and distal) coronary arteries. Furthermore, in human internal mammary arteries from cardiovascularly-compromised patients, we assessed the pharmacological specificity of erenumab by investigating whether the vasodilatory responses to acetylcholine, sodium nitroprusside, pituitary adenylate cyclase activating polypeptide-38 (PACAP), vasoactive intestinal peptide and nicardipine, along with the vasoconstrictor responses to dihydroergotamine, were modified by erenumab., Results: Calcitonin gene-related peptide induced concentration-dependent vasodilatory responses in all vessels studied that were significantly antagonised by erenumab. In human internal mammary arteries from cardiovascularly-compromised patients, the responses to acetylcholine, sodium nitroprusside, PACAP, vasoactive intestinal peptide, nicardipine and dihydroergotamine were unaffected by erenumab., Conclusion: Erenumab inhibits calcitonin gene-related peptide-induced vasodilatory responses in human middle meningeal arteries, human internal mammary arteries and human coronary arteries. Moreover, erenumab shows functional specificity as no interaction was observed with the relaxant responses to several vasodilators, nor the dihydroergotamine-dependent vasoconstrictor responses.

Objectives: The aim of this study was to investigate the vascular effects and mechanisms of propofol in the human internal mammary artery (IMA)., Design: In vitro experimental study., Setting: The study was conducted in the research laboratory of a pharmacology department., Participants: IMA segments were obtained from 52 patients undergoing coronary artery bypass surgery., Interventions: The IMA rings were suspended in isolated organ baths, and the changes in the tension were isometrically recorded. The antagonistic effect of propofol (1 μM, 10 μM, and 100 μM) on contractions induced by potassium chloride (45 mM), phenylephrine (1 μM), 5-hydroxytryptamine (30 μM), and calcium chloride (10 μM-10 mM) was investigated. The relaxations induced by propofol also were tested in the presence of the nitric oxide synthase inhibitor, nitro-L-arginine methyl ester (100 mM); the cyclooxygenase inhibitor, indomethacin (10 mM); and the potassium ion channel inhibitors, tetraethylammonium (1 mM), iberiotoxin (20 nM), glibenclamide (10 µM), 4-aminopyridine (1 mM), and barium chloride (30 µM)., Measurements and Main Results: Propofol caused a significant concentration-dependent vasorelaxation, which was endothelium independent. It inhibited the contractions induced by potassium chloride, phenylephrine, 5-hydroxytryptamine, and calcium chloride (p < 0.001), but it did not affect the basal tension. Propofol-induced relaxation was significantly inhibited by iberiotoxin and tetraethylammonium (p < 0.001); however, it was not affected by 4-aminopyridine, glibenclamide, and barium chloride., Conclusion: This study clearly reveals that propofol relaxes the IMA, and propofol-induced vasodilation may be related to large conductance calcium ion-activated potassium ion channel activation. Propofol use in coronary artery bypass surgery can be valuable via its favorable vasodilator effect to overcome perioperative vasospasm of IMA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

At arterial sites of endothelial denudation and dysfunction, activated platelets contribute to vascular injury through the release of potent contracting factors such as serotonin (5-HT). This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs), known to protect the vascular system, are able to prevent platelets-induced contractile responses in isolated arteries and, if so, to investigate the underlying mechanism and the importance of the omega-3 PUFAs formulation. Porcine coronary arteries (PCA), human internal mammary arteries (IMA) and washed human platelets were prepared and vascular reactivity was studied in organ chambers. In PCA rings, aggregating platelets caused concentration-dependent contractions that were significantly inhibited by the 5-HT 2A receptor antagonist ketanserin, and by EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v. EPA:DHA 6:1 also prevented the 5-HT-induced contractions but affected only slightly those to the thromboxane A 2 analogue U46619. The inhibitory effect of EPA:DHA 6:1 on platelets-induced contractions was not observed in rings without endothelium, and prevented by an eNOS inhibitor but not by inhibitors of endothelium-dependent hyperpolarization. In IMA rings, EPA:DHA 6:1 but not EPA:DHA 1:1 at 0.4% v/v significantly prevented the 5-HT-induced contraction, and induced greater endothelium-dependent relaxations than bradykinin and acetylcholine sensitive to an eNOS inhibitor. EPA:DHA 6:1 strongly inhibits platelets- and 5-HT-induced contractions in PCA rings and those to 5-HT in IMA rings most likely through an increased endothelial formation of NO. These findings suggest that the omega-3 PUFAs EPA:DHA 6:1 formulation may be of interest to prevent platelets-induced vascular injury at arterial sites of endothelial dysfunction., (Copyright © 2019. Published by Elsevier B.V.)

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a popular recreational drug of abuse. In addition to its characteristic psychotropic effects, important cardiovascular effects have been described such as increased blood pressure and heart rate. MDMA was previously shown to behave as a partial agonist on 5-hydroxytryptamine (5-HT) receptors in the human internal thoracic artery in vitro, involving the 5-HT 2A subtype. Here, we studied the interaction of MDMA (400, 800 and 1600 μM) with the following 5-HT receptor agonists: 5-carboxamidotryptamine (5-CT, full agonist for the 5-HT 1 , 5-HT 2 , 5-HT 5 , 5-HT 6 and 5-HT 7 receptors) and sumatriptan (selective 5-HT 1B/1D receptors agonist). The results showed the ability of MDMA to influence the concentration-dependent response of 5-CT (97.3% of maximal reduction for 1600 μM of MDMA) and sumatriptan (72.43% of maximal reduction for 1600 μM of MDMA). The lower concentration of MDMA (400 μM) produced a significant potentiation of the response to sumatriptan thus suggesting an interaction of MDMA with the activation of 5-HT receptors, namely of the 5-HT 1 subtype, in the peripheral vasculature. Together our results further support the importance of the affinity of MDMA to 5-HT receptors in the vascular effects of this drug., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The increased adverse cardiac events in women undergoing coronary artery bypass grafting are multifactorial and may include clinical, psychosocial, and biological factors. Potential contributing biological factors could include vascular hyperreactivity of the internal mammary artery (IMA) to endogenous vasoconstrictors in women, resulting in a predilection to myocardial ischemia. This study evaluated sex differences in serotonin and thromboxane A 2 dependent vasoconstriction in human isolated IMA, with the mechanistic role of (1) the endothelium, (2) nitric oxide (NO), (3) prostaglandins, and (4) receptor activity investigated for any observed sex difference., Methods and Results: Viable isolated human IMA segments were obtained from 116 patients (44 women [mean age, 66.8±12.2 years] and 72 men [mean age, 66.6±10.4 years]) undergoing coronary artery bypass grafting. Cumulative concentration-response curves for serotonin and thromboxane A 2 mimetic, U46619, were determined and revealed an increased sensitivity to serotonin but not U46619 in women. This sex difference to serotonin was further assessed by the following: (1) endothelial denudation, (2) endothelial NO synthase inhibition and NO quantification using electron paramagnetic resonance, (3) cyclooxygenase inhibition and prostaglandin metabolite quantification using mass spectrometry, and (4) quantification of receptor activity status. The female hyperreactivity to serotonin was (1) abolished by endothelial denudation; (2) unaffected by NO synthase inhibition, with no difference in electron paramagnetic resonance-assessed NO levels; (3) abolished by cyclooxygenase inhibition (quantification of prostaglandins in IMA revealed a trend towards reduced 6-keto prostaglandin F1α in female IMA; P =0.08); and (4) unrelated to receptor activity., Conclusions: These data indicate that female IMAs are hyperreactive to serotonin but not U46619, with the former attributable to an endothelium-dependent cyclooxygenase pathway., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Studies indicate that 5-hydroxytryptamine (5-HT) released from activated platelets in coronary artery bypass grafting (CABG) induces 5-HT 2A receptor-mediated graft spasm. We previously reported that 5-HT-induced constriction of human endothelium-denuded saphenous vein (SV) was significantly augmented in patients with diabetes mellitus (DM) than in patients without DM (non-DM), without changes in the levels of the membrane-bound 5-HT 2A receptor of their smooth muscle cells. Although the internal thoracic artery (ITA) is the key graft conduit for CABG, the effect of DM on the ITA graft spasm is still unclear. Therefore, in this study, we investigated the effect of DM on 5-HT-induced vasoconstriction and the level of membrane-bound 5-HT 2A receptor in ITA grafts. 5-HT-induced constriction of the isolated human endothelial-denuded ITA was significantly higher in patients with DM than in patients without DM. In addition, the level of the 5-HT 2A receptor in the membrane fraction of human ITA smooth muscle cells was significantly higher in patients with DM than in those without DM. These results demonstrate that DM is a risk factor for CABG in both venous and arterial conduits, and that it differentially affects the level of the membrane-bound 5-HT 2A receptor in the venous and arterial smooth muscle cells.

The "Achilles heel" of coronary artery bypass graft (CABG) surgery is graft patency. While long-term patency is determined by the type of conduit and the progression of graft and native vessel disease, short-term patency is affected by intra-operative technical issues. Transit-time flow measurements and epicardial ultrasound have been shown to accurately assess intra-operative graft patency. This review will examine the evidence to support the premise that intra-operative graft assessment is essential in determining graft patency and should be the standard of care when performing CABG surgery., (© 2018 Wiley Periodicals, Inc.)

Background and Purpose: The side effects of cyclooxygenase-2 (COX-2) inhibitors on the cardiovascular system could be associated with reduced prostaglandin (PG)I 2 synthesis. Microsomal PGE synthase-1 (mPGES-1) catalyses the formation of PGE 2 from COX-derived PGH 2 . This enzyme is induced under inflammatory conditions and constitutes an attractive target for novel anti-inflammatory drugs. However, it is not known whether mPGES-1 inhibitors could be devoid of cardiovascular side effects. The aim of this study was to compare, in vitro, the effects of mPGES-1 and COX-2 inhibitors on vascular tone in human blood vessels., Experimental Approach: The vascular tone and prostanoid release from internal mammary artery (IMA) and saphenous vein (SV) incubated for 30 min with inhibitors of mPGES-1 or COX-2 were investigated under normal and inflammatory conditions., Key Results: In inflammatory conditions, mPGES-1 and COX-2 proteins were more expressed, and increased levels of PGE 2 and PGI 2 were released. COX-2 and NOS inhibitors increased noradrenaline induced vascular contractions in IMA under inflammatory conditions while no effect was observed in SV. Interestingly, the mPGES-1 inhibitor significantly reduced (30-40%) noradrenaline-induced contractions in both vessels. This effect was reversed by an IP (PGI 2 receptor) antagonist but not modified by NOS inhibition. Moreover, PGI 2 release was increased with the mPGES-1 inhibitor and decreased with the COX-2 inhibitor, while both inhibitors reduced PGE 2 release., Conclusions and Implications: In contrast to COX-2 inhibition, inhibition of mPGES-1 reduced vasoconstriction by increasing PGI 2 synthesis. Targeting mPGES-1 could provide a lower risk of cardiovascular side effects, compared with those of the COX-2 inhibitors., Linked Articles: This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.22/issuetoc and http://onlinelibrary.wiley.com/doi/10.1111/bcp.v82.4/issuetoc., (© 2017 The British Pharmacological Society.)

Background: The proximal ends of internal mammary (IM) vessels are now the most common recipient vessels for breast reconstruction. On the other hand, bilateral deep inferior epigastric artery perforator (DIEP) flaps are often needed according to the territory and the volume required for reconstruction. The usefulness of retrograde IM vessels as second recipients has recently been reported, but there are very few quantitative studies on the hydrodynamics of the retrograde IM vessels. Because the flow is dependent on the pressure differential, the blood pressures of the antegrade IM artery (AIMA), antegrade IM vein (AIMV), retrograde IM artery (RIMA), retrograde IM vein (RIMV), and recirculated intraflap vein (FV) were investigated to solve this question and to confirm the reliability and usefulness of the retrograde IM vessels., Methods: Ten free flap breast reconstructions were included in this study. The IM vessels were exposed, and the pressures were measured. After recirculation, the FV pressures were measured when the flap was not ischemic or congestive. Systemic blood pressure was also recorded during the whole measurement period., Results: The AIMA and RIMA pressures were 70.4 ± 8.2 mmHg and 54.0 ± 8.6 mmHg (p = 0.000003), respectively, while the systemic pressure was 65.1 ± 10.0 mmHg. The AIMV pressure was always smaller than the RIMV pressure; the mean AIMV pressure was 5.3 ± 1.6 mmHg. In addition, the FV pressure was greater (p = 0.03) than the RIMV pressure (17.7 ± 9.9 mmHg), while the RIMV pressure was 8.7 ± 2.0 mmHg., Conclusions: Both the RIMA and RIMV are useful and reliable as second recipients for bipedicled free flap transfers. This is a great benefit because it would provide two recipients in one surgical site and would be especially useful in thin patients or patients with previous abdominal scars requiring double pedicled DIEP flaps., Level of Evidence: Therapeutic Study, Level IV., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To find out any differences in free flow of internal mammary artery among different ethnic groups., Methods: This observational, cross-sectional study was conducted at the Civil Hospital, Karachi, from January 2013 to December 2015, and comprised patients who underwent coronary artery bypass grafting. The participants were divided into 5 groups, i.e. Sindhi, Muslim migrants from India, Punjabi, Pathan and Balochi patients. Free flow of internal mammary artery was measured immediately after harvesting within a syringe, and its flow was measured in 30 seconds. SPSS 18 was used for data analysis., Results: Of the 158 patients, 44(27.8%) were Sindhi, 33(20.9%) Punjabi, 8(5%) Baloch, 21(13.3%) Pathan and 52(32.9%) were migrants. The overall mean age was 52±8 years and the mean flow was 11.6±9.6ml per 30 seconds. The flow was 9.3±6 ml, 10±8ml, 13±11ml, 17±14ml and 15±13 ml in 30 seconds among migrants, Sindhi, Punjabi, Pathan and Baloch patients, respectively, with significant higher flow in Pathan patients compared to Sindhi and migrant patients (p<0.05). A flow of less than 5ml/30 sec was mostly found in migrants or Sindhi subjects 30/40(75%), and flow more than 30ml/ 30 seconds was found mostly in Baloch or Pathan patients 4/8(50%). Low flow internal mammary artery, which was used on left anterior descending artery, showed significantly higher need of inotropic support as compared to high flow internal mammary artery (p=0.004), more low cardiac output syndrome (p=0.022) and more use of intra-aortic balloon pump (p=0.028)., Conclusions: Internal mammary artery flow was higher in Pathan and Baloch patients and low in migrants and Sindhis.

This study investigates the extent of cell seeding as well as lumen patency in acellular Internal mammary artery (IMA) scaffolds that have been re-cellularized by omentum as a natural bioreactor. Sixteen Virgin female Wistar rats were selected for implantation of acellular scaffold in omentum. Following laparotomy omentum was retracted to the outside of the abdomen and the more vascularized portion of it was selected for the experiment. The scaffold was wrapped by omentum and placed between two layers of rectus muscles that have been previously dissected. Samples were taken from scaffolds at 2 and 3 months for histopathological evaluation. All the grafts were explanted at 2 and 3 months and the lumens were completely patent compared to the native scaffold. The histology of implanted IMA after 2 and 3 months showed progressive recellularization especially by smooth muscle cells over the media layer. CD 34 staining was positive adjacent to the grafts which showed well angiogenesis. Trichrome and Movat's Pentachrome staining showed normal collagen formation in the inner media layer. Promising results obtained from the introduced protocol for in vivo recellularization, including patent lumen and proper cell seeding, encourages application of the mentioned technique for experimental vascular graft application. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2685-2693, 2017., (© 2017 Wiley Periodicals, Inc.)

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K + channel blockers, iberiotoxin, a selective blocker of large conductance Ca 2+ -activated K + channels (BK Ca ), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K + (K ATP ) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K + (K V ) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca 2+ -free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BK Ca and K ATP , as well as K V and IK Ca channels in high concentrations of procyanidin B2., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The internal mammary vessels are the most common recipient vessels in free flap breast reconstruction. The literature on internal mammary vascular anatomy is limited by small sample sizes, cadaveric studies, or intraoperative changes. The purpose of this study is to analyze internal mammary anatomy using computed tomographic angiography. A retrospective review of 110 consecutive computed tomographic angiography studies of female patients was performed. Measurements of vessel caliber, distance of internal mammary vessels to sternum, location of internal mammary vein bifurcation, intercostal space height, and chest width were analyzed. Patient demographics and comorbidities were reviewed. The right internal mammary artery and vein were larger than the left in all intercostal spaces (p = 0.02 and p < 0.001, respectively). A significant correlation was found between both skeletal chest width and body mass index with internal mammary vessel caliber at the third intercostal space (p ≤ 0.02). The internal mammary vein bifurcated at the third intercostal space bilaterally, 4.3 and 1.2 mm caudal to the third rib on the right and left sides, respectively. The third intercostal space was <1.5 cm in 25% of patients. Understanding the anatomy, bifurcation, and caliber of internal mammary vessels can aid preoperative planning of autologous, free flap breast reconstruction. On average, the internal mammary vein bifurcates at the third intercostal space; patients with larger chest widths and body mass index had larger caliber internal mammary vessels, and 25% of patients had third intercostal space <1.5 cm and, thus, may not be suitable candidates for rib-sparing techniques., (Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: Composite graft of left internal thoracic artery and great saphenous vein in revascularization of the left coronary system is a technique well described in literature. The aim of this study is to analyze blood flow dynamics in this configuration of composite graft especially in what concerns left internal thoracic artery's adaptability and influence of great saphenous vein segment on left internal thoracic artery's flow., Methods: Revascularization of left coronary system with composite graft, with left internal thoracic artery revascularizing the anterior interventricular artery and a great saphenous vein segment, anastomosed to the left internal thoracic artery, revascularizing another branch of the left coronary system, was performed in 23 patients. Blood flow was evaluated by transit time flowmetry in all segments of the composite graft (left internal thoracic artery proximal segment, left internal thoracic artery distal segment and great saphenous vein segment). Measures were performed in baseline condition and after dobutamine-induced stress, without and with non-traumatic temporary clamping of the distal segments of the composite graft., Results: Pharmacological stress resulted in increase of blood flow values in the analyzed segments (P<0.05). Non-traumatic temporary clamping of great saphenous vein segment did not result in statistically significant changes in the flow of left internal thoracic artery distal segment, both in baseline condition and under pharmacological stress. Similarly, non-traumatic temporary clamping of left internal thoracic artery distal segment did not result in statistically significant changes in great saphenous vein segment flow., Conclusion: Composite grafts with left internal thoracic artery and great saphenous vein for revascularization of left coronary system, resulted in blood flow dynamics with physiological adaptability, both at rest and after pharmacological stress, according to demand. Presence of great saphenous vein segment did not alter physiological blood flow dynamics in distal segment of left internal thoracic artery., Competing Interests: No conflict of interest.

Since the late 1980s numerous reports have detailed adverse reactions to the use of 3,4-methylenedioxymethamphetamine (MDMA) associated with cardiovascular collapse and sudden death, following ventricular tachycardia and hypertension. For a better understanding of the effects of MDMA on the cardiovascular system, it is critical to determine their effects at the vasculature level, including the transporter or neurotransmitter systems that are most affected at the whole range of drug doses. With this purpose in mind, the aim of our study was to evaluate the contractile effect of MDMA in the human internal mammary artery, the contribution of SERT for this effect and the responsiveness of this artery to 5-HT in the presence of MDMA. We have also studied the possible involvement of 5-HT2 receptors on the MDMA contractile effect in this human blood vessel using ketanserin. Our results showed that MDMA contracted the studied human's internal mammary artery in a SERT-independent form, through activation of 5-HT2A receptors. Considering the high plasma concentrations achieved in heavy users or in situations of acute exposure to drugs, this effect is probably involved in the cardiovascular risk profile of this psychostimulant, especially in subjects with pre-existing cardiovascular disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Graft spasm is a common problem in coronary artery bypass grafting (CABG). In this study, we aimed to investigate the interaction of levosimendan, a novel inodilator, with vasodilator agents that are clinically used for the treatment of graft spasm and with endogenous vasoconstrictors that are thought to play a role in graft vasospasm, in human internal mammary artery (IMA) and saphenous vein (SV). Isolated human IMA and SV segments derived from patients undergoing CABG were suspended in an organ bath. Responses to cumulative concentrations of noradrenaline (NA), serotonin (5-HT), papaverine, nitroglycerin (NG), and diltiazem were recorded before and after 10(-5) m levosimendan incubation (30 min). In addition, cumulative levosimendan responses were taken in vessels precontracted with NA or 5-HT. 10(-5) m levosimendan reduced NA Emax and sensitivity in IMA and SV, and 5-HT Emax responses in IMA. Moreover, levosimendan caused concentration-dependent relaxation in both grafts. Papaverine Emax or sensitivity was not altered by levosimendan neither in IMA nor in SV. Levosimendan diminished NG sensitivity in IMA and Emax responses in SV and decreased diltiazem Emax responses both in IMA and SV. Our results suggest that levosimendan may be used alone for prevention or treatment of graft spasm in IMA or in combination with papaverine in IMA and SV grafts. However, as concurrent administration with diltiazem or NG causes a reduction in relaxation in vitro, we suggest caution should be exercised when using levosimendan in combination with these agents., (© 2016 Société Française de Pharmacologie et de Thérapeutique.)

Purpose: The internal thoracic artery is the choice of graft for coronary artery bypass grafting due to the excellent long-term patency. However internal thoracic artery graft failures still occur due to diffuse narrowing, known as the string phenomenon. Studies suggest that the string phenomenon is caused by competitive flow when the coronary stenosis is not serious, but the hemodynamics of the string phenomenon are still unclear. The purpose of this study is to clarify the hemodynamic characteristics of the string phenomenon., Materials: A patient-specific 3-dimensional model of the aortic arch and coronary arteries was reconstructed. A moderate stenosis was applied to the left anterior descending artery. The internal thoracic artery was used to bypass the stenosis. Two further 3D models were built to study the hemodynamics of the string phenomenon., Methods: A numerical study was performed by coupling the 3D artery model with 0-dimensional lumped parameter model of the cardiovascular system., Results: The graft flow, native coronary flow, wall shear stress and oscillatory shear index were calculated and illustrated. Inverse flow and high oscillatory shear index appeared on the internal thoracic artery graft when the stenosis was moderate., Conclusion: High oscillatory shear index might be the major hemodynamic characteristic of the string phenomenon in internal thoracic artery graft. The inverse graft flow and the difference in graft flow caused by clamping the stenosis can be used to evaluate the probability of observing the string phenomenon., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The use of bilateral internal thoracic arteries (BITA) in coronary artery bypass graft surgery improves patient survival. The optimum BITA graft configuration is unknown. This study evaluates outcomes after the use of bilateral internal mammary Y grafting as the primary grafting strategy., Methods: Patients who underwent BITA composite Y grafting (n = 1,011) between October 1994 and March 2009 were identified from a cardiac surgical database. Follow-up (mean 12 years) was obtained by cross-reference with the state death registry and local cardiology databases., Results: Perioperative mortality was 1.6%. Kaplan-Meier 10-year survival was 87.2%. There were 464 episodes of postdischarge angiography in 296 patients, at an average of 5.5 years to first angiography. Graft failure occurred in 151 patients, predominately affecting the right ITA limb (n = 139). Degree of native vessel stenosis (odds ratio [OR] 0.66 per 10% increase), anatomic territory grafted (circumflex OR 2.64, right coronary OR 6.73 versus anterior), and end-to-side free wall anastomoses (OR 1.98) predicted anastomotic occlusion. The left anterior descending artery graft patency was unaffected by sequential grafting. Progression to graft failure after the first angiogram was rarely seen in the 111 patients who had serial angiography., Conclusions: Outcomes of BITA Y grafting are similar to those for other BITA configurations. The rate of presentation with arterial graft dysfunction decreases over time. Although competitive flow affects anastomotic patency, there is no threshold at which risk of occlusion substantially increases., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: We investigated the hypothesis that elevated glucose increases contractile responses in vascular smooth muscle and that this enhanced constriction occurs due to the glucose-induced PKC-dependent inhibition of voltage-gated potassium channels., Experimental Approach: Patch-clamp electrophysiology in rat isolated mesenteric arterial myocytes was performed to investigate the glucose-induced inhibition of voltage-gated potassium (Kv ) current. To determine the effects of glucose in whole vessel, wire myography was performed in rat mesenteric, porcine coronary and human internal mammary arteries., Key Results: Glucose-induced inhibition of Kv was PKC-dependent and could be pharmacologically dissected using PKC isoenzyme-specific inhibitors to reveal a PKCβ-dependent component of Kv inhibition dominating between 0 and 10 mM glucose with an additional PKCα-dependent component becoming evident at concentrations greater than 10 mM. These findings were supported using wire myography in all artery types used, where contractile responses to vessel depolarization and vasoconstrictors were enhanced by increasing bathing glucose concentration, again with evidence for distinct and complementary PKCα/PKCβ-mediated components., Conclusions and Implications: Our results provide compelling evidence that glucose-induced PKCα/PKCβ-mediated inhibition of Kv current in vascular smooth muscle causes an enhanced constrictor response. Inhibition of Kv current causes a significant depolarization of vascular myocytes leading to marked vasoconstriction. The PKC dependence of this enhanced constrictor response may present a potential therapeutic target for improving microvascular perfusion following percutaneous coronary intervention after myocardial infarction in hyperglycaemic patients., (© 2015 The British Pharmacological Society.)

Perivascular tissue (PVT) modulates vascular tone, releasing adventitia/adipocyte derived relaxing factor (ADRF). Its physiological role remains unclear. We studied isolated internal thoracic artery (ITA) segments obtained from 132 patients subjected to coronary artery bypass grafting. The vessels were skeletonized in vitro and the ITA rings and PVT were incubated in separate isolated organ baths. Skeletonized ITA segments were first precontracted with 10(-5.5)mol/L 5-hydroxytryptamine hydrochloride. The PVT was next transferred to the ITA tissue bath. This resulted in relaxation of ITA, presumably related to ADRF release from PVT which was floating freely in the tissue bath. The in-vitro relaxation responses were then correlated to patients' characteristics - including demographics, clinical and laboratory data, as well as therapy. Perivascular tissue transfer resulted in 49.7 ± 26.2% relaxation of precontracted ITA segments. In multiple linear regression modelling, the relaxation of ITAto PVT was negatively related to patient age (β = -0.67; 95% CI -1.17 - -0.17; P = 0.009), symptoms of CCS class 4 angina (β = -20.11; 95%CI -32.25 - -7.97; P = 0.001), and positively to body mass (β = 0.37; 95%CI 0.08 - 0.67; P = 0.01) and lack of heart failure symptoms (NYHA class 1) (β = 9.06; 95%CI 0.33 - 17.79; P = 0.04). The relaxation response to PVT was not related to patients' sex, diabetes, hypertension, lipid profile or therapy in both univariate and multivariate analysis. PVT might play an important role in regulating vascular tone in humans as exemplified by its changing physiological function with age and in atherosclerosis.

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To evaluate breast ultrasonographic features and hemodynamic indexes of the internal mammary arteries in normal pregnant women, and their correlation with the gestational periods., Methods: Observational and cross-sectional, epidemiological, study, conducted between August 2013 and February 2015, with 93 women divided into three groups: first trimester, second trimester and third trimester. The dependent variables were thickness of the skin, of subcutaneous tissue, fibroglandular tissue, and retrommamary adipose tissue, the diameter of the ducts, as well as the pulsatility and resistance indexes of the internal mammary arteries. Independent variables were the three periods of gestation. Repeated measures ANOVA with the multiple comparison Tukey test and a test of contrasts were used for statistical analysis. The Levene test was used to test the homogeneity of variances between periods of gestation. Student's t-test was used to evaluate the difference between nulliparous and non -nulliparous women, and Pearson's correlation coefficient was used for correlation analysis between the two breasts. The level of significance was set at 5%., Results: Mean age was 26.6±4.6 years, with no significant difference among groups. Breast location (right/left) and gestational period had no significant effect on the thickness of the skin, of subcutaneous tissue and adipose retromammary tissue. However, the thickness of fibroglandular tissue and the diameter of the ducts showed a significant difference according to gestational period (p<0.001), i.e., from the first to the second and to the third trimesters. Doppler flowmetry of the internal mammary arteries showed a difference between breasts and between gestational periods, i.e., the measurements of the right breast were greater than those of the left, and these values decreased throughout pregnancy (p<0.001)., Conclusion: The average thickness of fibroglandular tissue and the diameter of the ducts showed significant differences from the first to the second and to the third trimesters, with no differences being observed between the two breasts. The pulsatility and resistance indexes of the internal mammary arteries decreased progressively throughout pregnancy.

Many surgeons are concerned about the flow capacity of a skeletonized internal thoracic artery (ITA) in comparison with a pedicled ITA used during coronary artery bypass graft (CABG). This work aims to summarize the evidence comparing the flow capacity of a skeletonized versus pedicled ITA during CABG. We performed systematic review and meta-analysis according to the PRISMA statement based on a search in MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, Google Scholar and reference lists of relevant articles. Studies included were original studies whose populations comprised patients undergoing CABG; compared outcomes between skeletonized versus pedicled ITA; the outcomes included data regarding intraoperative flow capacity of the grafts; the studies were prospective or retrospective or non-randomized or randomized controlled trials. In total, eight studies were identified and reviewed for eligibility and data were extracted. Forest plots and the summarized difference in means including 95% confidence intervals (CIs) were estimated and meta-regressions were performed. There was a statistically significant difference in favour of the skeletonized ITA compared with the pedicled ITA in terms of flow capacity (random-effect model: additional 20.8 ml/min, 95% CI 6.6-35.0, P = 0.004), being the summary measures under the influence of heterogeneity of the effects, but free from publication bias. We observed a difference with regard to the type of study, since non-randomized studies together demonstrated the superiority of a skeletonized ITA (random-effect model: additional 32.3 ml/min, 95% CI 21.0-43.6, P < 0.001), but the randomized studies together did not show it (random-effect model: additional 13.2 ml/min, 95% CI -1.1 to 27.6, P = 0.071). Meta-regression demonstrated some modulation influence by female gender, age and diabetes on the flow capacity of grafts. In summary, in terms of flow capacity, a skeletonized ITA appears to be superior in comparison with a pedicled ITA during CABG., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Coronary artery bypass graft (CABG) surgery remains the preferred mode of revascularization in patients with complex multi-vessel coronary artery disease. The left internal mammary artery (IMA) and saphenous vein are the most commonly utilized conduits in CABG surgery and are still considered to be the gold standard by most surgeons. However, there is emerging evidence that use of bilateral IMAs is associated with significantly better long-term outcomes and the benefit increases with time from surgery. In spite of this incremental beneficiary effect, most surgeons are reluctant to use both IMAs, because it is technically more demanding, time-consuming and is associated with marginally higher sternal wound infection rates. This review highlights the histological features, physiological characteristics and genomics of IMAs that provide the basis for the use of these vessels during CABG surgery. Additionally, the superiority of the bilateral IMAs with regard to patency and long-term outcomes is also discussed in detail. Furthermore, the safety of using bilateral IMAs with regard to early postoperative outcomes with special reference to deep sternal wound infections has been addressed. The present review provides enough evidence to convince more surgeons about the advantages of bilateral IMA grafting., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Objective: Taurine is an abundant amino acid that is widely distributed in human and animal tissues. Pharmacodynamic studies show that taurine has hypotensive and myocardial protective effects. Studies in isolated tissue baths show that taurine relaxes precontracted arteries. This study aimed to show the effects of taurine on human internal mammary artery (IMA) in vitro and to explain the mechanisms of its effects., Methods: The response in the IMA was recorded isometrically by a force displacement transducer in isolated organ baths. Taurine (20, 40, 80 mM) was added to organ baths after precontraction with KCl (45 mM) or serotonin (5-HT, 30 µM). Taurine-induced relaxations were also tested in the presence of the cyclooxygenase inhibitor indomethacin (10 µM), the nitric oxide synthase inhibitor L-NAME (100 µM), the large conductance Ca2+-activated K+ channel inhibitor tetraethylammonium (TEA, 1 mM), the ATP-sensitive K+ channel inhibitor glibenclamide (GLI, 10 µM), the voltage-sensitive K+ channel inhibitor 4-aminopyridine (4-AP, 1 mM) and the inward rectifier K+ channel inhibitor barium chloride (BaCl2, 30 µM)., Results: Taurine did not affect the resting tone of IMA. However, it produced relaxation in the 5-HT and KCl -precontracted preparations. The relaxation to IMA was not affected by GLI, 4-AP, BaCl2, indomethacin and L-NAME. But, TEA inhibited taurine -induced relaxations significantly (p < 0.05)., Conclusions: The preincubation of IMA with taurine antagonized KCl and 5-HT induced contractions in a concentration dependent manner, while it did not affect the resting tone. The relaxations to taurine were significantly antagonized by pretreatment with TEA. These results suggest that mechanism of vasodilator effect of taurine in IMA may be the activation of large conductance Ca2+-activated K+ channels.

Coronary subclavian steal syndrome associated with upper extremity arteriovenous fistula is an uncommon but potentially life-threatening condition. We present a case of a 65-year-old male on hemodialysis with a left upper extremity arteriovenous fistula who underwent coronary revascularization involving bypass with the left internal thoracic artery to the left anterior descending artery. Intraoperative transit-time graft flow measurements and fluorescence imaging showed a reversed flow in the left internal thoracic artery, and the left internal thoracic artery was successfully converted as a free graft from the ascending aorta to the left anterior descending artery., (© 2014 Wiley Periodicals, Inc.)

The aim of this study was to generate extended length, small diameter vascular scaffolds that could serve as potential grafts for treatment of acute ischemia. Biological tissues are considered excellent scaffolds, which exhibit adequate biological, mechanical, and handling properties; however, they tend to degenerate, dilate, and calcify after implantation. We hypothesized that chemically stabilized acellular arteries would be ideal scaffolds for development of vascular grafts for peripheral surgery applications. Based on promising historical data from our laboratory and others, we chose to decellularize bovine mammary and femoral arteries and test them as scaffolds for vascular grafting. Decellularization of such long structures required development of a novel "bioprocessing" system and a sequence of detergents and enzymes that generated completely acellular, galactose-(α1,3)-galactose (α-Gal) xenoantigen-free scaffolds with preserved collagen, elastin, and basement membrane components. Acellular arteries exhibited excellent mechanical properties, including burst pressure, suture holding strength, and elastic recoil. To reduce elastin degeneration, we treated the scaffolds with penta-galloyl glucose and then revitalized them in vitro using a tunic-specific cell approach. A novel atraumatic endothelialization protocol using an external stent was also developed for the long grafts and cell-seeded constructs were conditioned in a flow bioreactor. Both decellularization and revitalization are feasible but cell retention in vitro continues to pose challenges. These studies support further efforts toward clinical use of small diameter acellular arteries as vascular grafts.

In order to expand the revascularization of the left anterior descending coronary artery, we have applied the inverted left internal thoracic artery (left internal thoracic artery [LITA] transected near its origin, thus supplied by retrograde flow from superior epigastric and musculophrenic arteries) in carefully selected cases (four patients). The 64-slice multidetector row computed tomographic scans performed postoperatively (range, 6 to 40 days), as well as the scans performed in the follow-up period (range, 18 to 35 months) showed preserved inverted LITA conduits with thrombolysis in myocardial infarction (TIMI) 3 flow in all patients., (© 2014 Wiley Periodicals, Inc.)

Background: The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown., Methods and Results: The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions., Conclusion: There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCTO1676207., (© 2014 American Heart Association, Inc.)

Background: Phenotypic modulation or switching of vascular smooth muscle cells from a contractile/quiescent to a proliferative/synthetic phenotype plays a key role in vascular proliferative disorders such as atherosclerosis and restenosis. Although several calcium handling proteins that control differentiation of smooth muscle cells have been identified, the role of protein phosphatase inhibitor 1 (I-1) in the acquisition or maintenance of the contractile phenotype modulation remains unknown., Methods and Results: In human coronary arteries, I-1 and sarco/endoplasmic reticulum Ca2+ -ATPase expression is specific to contractile vascular smooth muscle cells. In synthetic cultured human coronary artery smooth muscle cells, protein phosphatase inhibitor 1 (I-1 target) is highly expressed, leading to a decrease in phospholamban phosphorylation, sarco/endoplasmic reticulum Ca2+ -ATPase, and cAMP-responsive element binding activity. I-1 knockout mice lack phospholamban phosphorylation and exhibit vascular smooth muscle cell arrest in the synthetic state with excessive neointimal proliferation after carotid injury, as well as significant modifications of contractile properties and relaxant response to acetylcholine of femoral artery in vivo. Constitutively active I-1 gene transfer decreased neointimal formation in an angioplasty rat model by preventing vascular smooth muscle cell contractile to synthetic phenotype change., Conclusions: I-1 and sarco/endoplasmic reticulum Ca2+ -ATPase synergistically induce the vascular smooth muscle cell contractile phenotype. Gene transfer of constitutively active I-1 is a promising therapeutic strategy for preventing vascular proliferative disorders.

Perivascular adipose tissue (PVAT) surrounds most vessels and has now been recognized as a regulator of vascular functions. This effect of PVAT has been mostly demonstrated in vessels obtained from rats and mice. Thus, the aim of this study was to investigate anti-contractile effect of PVAT surrounding human coronary bypass grafts such as saphenous vein (SV) and internal mammary artery (IMA). Moreover, we aimed to determine the involvement of prostanoids in the anticontractile effect of PVAT. Human SV and IMA preparations were set up in an organ bath. The presence of PVAT in SV and IMA preparations significantly attenuated the contractile response to noradrenaline (NA). Preincubation with indomethacin, a cyclooxygenase inhibitor, increased NA contraction in SV preparations with PVAT. This effect was not observed in IMA preparation with PVAT incubated with indomethacin. The lower measurements of prostaglandin E2 (PGE2) released from PVAT surrounding IMA versus SV supported these effects. In conclusion, our results show that PVAT of SV could attenuate NA-induced contraction by releasing both PGE2 and prostacyclin (PGI2). In contrast to SV, PVAT of IMA exerts its anti-contractile effect independently from prostanoids. These observations suggest that retaining PVAT in human SV and IMA preparations may have potential clinical implications to improve coronary bypass graft patency., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Graft spasm remains challenging in coronary artery bypass graft (CABG) surgery. Calcium antagonists are commonly used in patients with coronary artery disease. We investigated the inhibitory effect of the new third-generation dihydropyridine calcium antagonist azelnidipine on the vasoconstriction in human internal mammary artery (IMA) from patients undergoing CABG., Methods: Isolated IMA rings (n = 68, taken from 28 patients) were studied in myograph in two ways: the relaxing effect of azelnidipine on vasoconstrictor-induced precontraction by potassium chloride (KCl) and U46619; and the depressing effect of azelnidipine at plasma concentrations on the contraction., Results: Azelnidipine caused full relaxation in KCl-contracted (96.5% ± 0.7%) and in U46619-contracted (96.5% ± 1.4%) IMA rings (n = 8), with 28.8-fold higher potency to KCl than to U46619 (EC50 -7.49 ± 0.21 versus -6.03 ± 0.11 log M, p < 0.01). Pretreatment of IMA with plasma concentrations of azelnidipine (-6.1 log M) significantly depressed subsequent contraction to KCl (from 25.8 ± 2.2 mN to 16.0 ± 1.5 mN, p < 0.01) and U46619 (from 30.6 ± 4.0 mN to 16.5 ± 2.2 mN, p < 0.05)., Conclusions: We conclude that in human IMA, azelnidipine has a potent inhibitory effect on the vasoconstriction mediated by a variety of vasoconstrictors. Thus, use of azelnidipine in CABG patients is favored for treating and preventing graft spasm., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This work aims to study comparatively the free flow and the Doppler flowmetry of the internal thoracic artery in anesthetized dogs, with and without continuous intravenous administration of norepinephrine., Methods: The sample was made up of ten mongrel dogs, which dissected the left and right internal thoracic arteries and evaluated your stream; first, by Doppler flowmetry and then by free flow. The mean arterial pressure and the diameter of the arteries at the beginning of the procedure were registered. The workflow checks by two methods occurred in three times: time zero, 10 and 25 minutes. After the first check in time zero, the continuous infusion of norepinephrine in the right atrium; other checks were made in the same way that the first time, to 10 and 25 minutes, in the same arteries and by two methods, each one in his artery, noting the results, as well as the corresponding average blood pressure., Results: The results of the scan of the stream, between Doppler flowmetry and free flow, there were similar; being the first, zero times, ten and twenty-five minutes, respectively, 183, 230.1 and 237 ml/min compared to seconds, 168.6, 226.8 and 226.4 ml/min (P = 0.285). The mean arterial pressures of three times and the average diameter of the arteries, showed no statistically significant differences between the methods, so did not influence on the comparison of the results., Conclusion: The evaluations, both from Doppler flowmetry and free flow, were similar in three times checked.

It has beed showed that perivascular adipose tissue (PVAT) of human internal thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown. It was suggested that various potassium channels may be involved in the action of ADRF. The aim of this study was to assess the involvment of potassium channels in the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA rings were studied in vitro. First the ability of perivascular tissue of human ITA to release ADRF to the bath was checked. In subsequent experiments two fragments of skeletonised ITA were used to assess the involvement of various potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first without and then in the presence of appropriate potassium channel blocker. Second segment served as a control (no addition of PVAT). The magnitude of relaxation was measured and compared between preparations. This protocol was used to analyze the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5 mM), BaCl₂ (100 uM) and glibenclamide (10 uM). The addition of PVAT to precontracted skeletonized ITA caused significant vasorelaxation (54.6±8.03 mN versus 33.7±6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from separate incubation of PVAT was added (36.3±5.45 mN versus 20.7±3.02 mN; p<0.001). PVAT dependent relaxation was blocked in the presence of Ca⁺² dependent potassium channel blocker iberiotoxin (47.4±16.67 mN versus 43.3±14.54 mN; p=0.36) and 4-aminopyridine (5 mM) (59.3±3.54 mN versus 51.6±4.77 mN; p=0.12). We conclude that perivascular adipose tissue of human ITA releases relaxing factor that seems to act with the involvement of Ca⁺² dependent potassium channels.

Aim: NG solution composed of nicardipine and nitroglycerin is a new anti-spastic solution for arterial grafts. We investigated its efficacy on the left internal thoracic artery (LITA) during off-pump coronary artery bypass grafting (OPCAB)., Methods: The free flow of LITA in 41 OPCAB patients was measured. The patients were divided to four groups: LITA pedicle wrapped with normal saline (Group I, N.=10) or NG (Group II, N.=11); or in addition to wrapping, 2 cc NG (Group III, N.=10) or normal saline (Group IV, N.=10) injected into LITA. After 30 min, the distal end free flow and the graft flow by an ultrasound probe were measured., Results: The free flow significantly increased in Group II (30.0±4.7 vs. 21.6±4.5 cc/min, P=0.007) and III (70.0±11.5 vs. 24.5±6 cc/min, P=0.001) but not in Group I (20.8±4.7 vs. 19.4±4.1 cc/min, P=0.33) or IV (35.8±7.5 vs. 29±9.2 cc/min, P=0.06) with significant differences between the Group III to all other groups (P=0.016-0.001). The graft flow by ultrasound probe was significantly higher in Group III (41.2±6.2 cc/min) than that in Group IV (24.1±3.1 cc/min, P=0.028)., Conclusion: Use of NG solution for LITA graft preparation is a choice of antispastic protocol. NG solution used either topically or intraluminally significantly increases the blood flow of IMA grafts with the best effect obtained by intraluminal injection. The present study provides an additional anti-spastic method by using second generation of calcium antagonists and nitric oxide donor in coronary artery bypass surgery.

Background and Objective: As low-level laser irradiation (LLLI) seems to induce vasodilation besides many other known biological effects, LLLI has been increasingly used in therapy of medical conditions with various irradiation parameters. The aim of this study was to investigate the effect of LLLI on photorelaxation of human coronary and internal thoracic arteries (ITA)., Materials and Methods: Thirty vessel segments of ITA used for routine coronary artery bypass grafting as well as left anterior descending coronary arteries (LAD) of patients undergoing cardiac transplantation were cut into 4-mm rings stored in a modified Krebs-Henseleit solution and evaluated in a myograph. Both types of vessel segments were irradiated by a semiconductor non-thermal GaAs diode laser operating at a wavelength of 680 nm. After precontraction with thromboxane agonist U44619, respective relaxation responses were evaluated and compared to pharmacological dilatation induced by substance P., Results: Mean pharmacological vasodilation by substance P was 22.6 ± 3.3%, 12.8 ± 1.4%, and 20.4 ± 3.2% in macroscopic healthy LAD, LAD with atheromatous plaque, and ITA, respectively. Average photorelaxation induced by LLLI was 16.5 ± 2.0%, 1.9 ± 1.7%, and 6.8 ± 4.7%, accordingly. Vasodilatatory responses induced either by substance P or administration of LLLI were significantly decreased in LAD with atheromatous plaque (P < 0.0001). Vasospasms of ITA segments occurring during experiments could be abandoned when LLLI was administered., Conclusion: Macroscopic healthy LAD exposed to LLLI revealed significant photorelaxation. With the administration of LLLI, 73% of the maximal obtainable effect by an endothelium-dependent vasodilator could be reached. Furthermore, LLLI has the potential to overcome vasospasms of ITA., (Copyright © 2012 Wiley Periodicals, Inc.)

An 85-year-old woman had a history of coronary artery bypass grafting (CABG) performed 7 years ago, and dyspnea on effort had been worsening recently. Since echocardiography showed severe mitral valve regurgitation( MR), mitral valve repair was suggested. Preoperative enhanced computed tomography (CT) showed the patent functioning left internal thoracic artery (LITA) graft. Mitral valve replacement (MVR) using a 25 mm CEP bioprosthesis was performed successfully via resternotomy without any intraoperative injury of the heart. Myocardial protection without clamping of functioning LITA was done by both antegrade and retrograde continuous coronary perfusion (RCCP) under mild hypothermia. The postoperative clinical course was uneventful without any hemodynamic compromise. She was discharged on postoperative day 21 without any cardiac events following early introduction of cardiac rehabilitation. From these results, mitral valve reoperation by RCCP under mild hypothermia without control of functioning internal thoracic artery( ITA) grafts could be a safe option in some cases.

Background and Aims: Intracellular calcium regulation in endothelial cells depends on transient receptor potential channels (TRPs). Canonical TRPs (TRPCs) are now recognized as the most important Ca(2+)-permeable cation channels in vascular endothelium and TRPC3 channel is reported to play a role in vasodilation in animal vessels. However, little is known about the role of TRPCs in human arteries. We therefore tested the hypothesis that TRPCs play a role in human arteries., Methods: Cumulative concentration-relaxation curves to acetylcholine (-11 to -4.5 log M) were established in the human internal mammary artery (IMA) rings (n = 42) taken from 28 patients undergoing coronary artery bypass grafting in precontraction induced by U46619 (-8 log M) in the absence or presence of SKF96365 (10 μmol/L) or Pyr3 (3 μmol/L). Protein expressions of TRPC3 were determined by Western blot and immunohistochemistry staining., Results: The maximal relaxation induced by acetylcholine was significantly attenuated by the nonspecific cation channels inhibitor, SKF96365 (48.2 ± 3.7 vs. 66.0 ± 0.9% in control, p <0.01) or the selective TRPC3 blocker, Pyr3 (58.4 ± 2.3% vs. 67.7 ± 1.1% in control, p <0.01). Protein expression of TRPC3 was detected in human IMA., Conclusions: TRPC3 exists and plays a role in the acetylcholine-induced endothelium-dependent relaxation in the human IMA. This study suggests that TRPC3 may be a potential new target in endothelial protection in patients with endothelial dysfunction such as in patients with coronary artery disease in order to improve the long-term patency of the grafting vessels., (Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.)

Aims: Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans., Methods and Results: A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001)., Conclusion: Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.

The role of internal mammary artery grafts in facilitating retrograde chronic total occlusion interventions is controversial. We describe two cases demonstrating: (a) retrograde wiring via a left internal mammary artery graft; and (b) using the left internal mammary graft for vessel visualization while retrograde crossing to the right coronary artery was achieved via the native left main coronary artery (triple arterial access). The internal mammary artery grafts can facilitate retrograde chronic total occlusion interventions, but should be used with caution to minimize the risk of injury.

Some small molecular weight peptides possess potent vasoactive properties. Herein we have identified the laminin nonapeptide (LNP) CDPGYIGSR as a novel vasoconstrictive agent. Isometric force measurements revealed that LNP induced vasoconstriction in small and large murine arteries in a dose-dependent fashion; LNP also increased vascular tone in human mammary arteries. The vasoactive response was specific for the nonapeptide, because neither scrambled nor very similar peptide sequences modulated vascular tone. As an underlying mechanism we found in [Ca(2+)](i) imaging experiments that the nonapeptide induced transmembrane [Ca(2+)](i) influx in vascular smooth muscle cells. Patch clamp experiments showed that LNP activated nonselective cation channels, causing depolarization of the membrane potential and opening of L-type Ca(2+) channels. The functional effect of LNP was also assessed with catheter measurements in mice in vivo and confirmed vasoconstriction. This effect was restricted to the systemic circulation, because measurements with the perfused lung system demonstrated that LNP did not alter vascular tone in pulmonary arteries. Thus, LNP is a vasoconstrictor in mouse and human arteries, and its vasoactivity is restricted to the systemic vasculature.