Search

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent wit

Background - No information is available on the long-term results of radial artery (RA) grafts used as coronary artery bypass conduits. Methods and Results - In this report, we describe the long-term (105±9 months) angiographic results of a series of 90 consecutive patients in whom the RA was used as a coronary artery bypass conduit directly anastomosed to the ascending aorta. The long-term patency and perfect patency rates of the RA were 91.6% and 88%, respectively, versus 97.5% and 96.3% for internal thoracic artery grafts. The severity of stenosis of the target vessel clearly influenced long-term RA patency, whereas location of the target vessel and long-term use of calcium channel blockers did not influence angiographic results. Preserved endothelial function and absence of flow-limiting, fibrous, intimal hyperplasia were also documented. Conclusions - Ten years after surgery, RA grafts have excellent patency and perfect patency rates. Appropriate surgical technique and correct indication are the key factors for long-term RA patency.

Objective: To evaluate the flow reserve and adequacy to meet myocardial requests in stress conditions of mammary artery-left anterior descending (IMA-LAD) grafts using a non-invasive method. Methods: Patients (20) with angiographic evidence of normofunctioning left IMA-LAD grafts were submitted to dypiridamole Tl201 myocardial scintigraphy and concomitant transthoracic echo-doppler evaluation of the IMA flow at a mean interval of 32.5 months after surgery. Results: Under basal conditions, the mean peak and end flow velocities in systole were 0.39 and 0.06 m/s, respectively In diastole, the mean peak and end flow velocities were 0.27 and 0.02 m/s and mean tele-diastolic flow velocity was 0.14 m/s, with a mean systolic/diastolic ratio of 1.51. After dypiridamole infusion, mean systolic velocities were 0.47 (peak) and 0.23 (end) m/s, respectively +20 and +283%, whereas mean diastolic velocities were 0.56 (peak) and 0.06 (end) m/s, +107 and +200%, respectively. Mean tele-diastolic flow velocity increased to 0.32 m/s (+ 128%) and the systolic-diastolic index changed to 0.85. In all cases no significant scintigraphic evidence of induced ischemia was demonstrated in the LAD region. Conclusions: Transthoracic echo-doppler evaluation combined with Tl201 myocardial scintigraphy is a useful tool for the assessment of IMA flow reserve and adequacy to stress conditions. In the late postoperative period, the IMA shows the possibility of increasing the flow velocity, almost 2-fold; the increase in flow is prevalently diastolic and leads to a complete reversal of the physiological systolic/diastolic flow ratio. The flow reserve of IMA is always able to meet the augmented myocardial oxygen demand after dypiridamole infusion.

Background: No data are available on the early vasoreactive profile of skeletonized internal thoracic artery grafts. Methods: Fifteen patients undergoing primary isolated coronary artery bypass grafting were randomly assigned to receive a skeletonized or pedicled internal thoracic artery graft. On the second postoperative day all patients were subjected to follow-up angiography and endovascular infusion of serotonin, acetylcholine, and isosorbide dinitrate. Results: Internal thoracic artery grafts were widely patent in all cases. Mean diameters of the internal thoracic artery were 1.95 ± 0.17 mm in the pedicled group and 2.26 ± 0.40 mm in the skeletonized group. After serotonin challenge, mean internal thoracic artery diameters were reduced to 1.44 ± 0.34 mm and 1.64 ± 0.14 mm, respectively; acetylcholine challenge lead to a moderate degree of vasoconstriction (1.55 ± 0.59 mm in the pedicled group and 1.84 ± 0.15 mm in the skeletonized group). No statistically significant difference was evident between the two groups at any step. Conclusion: Skeletonization does not affect the early vasoreactive profile of internal thoracic artery grafts used for surgical myocardial revascularization.

Background: Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and Results: The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P < .0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 ± 0.34, 0.99 ± 0.44, and 10.1 ± 7.8 mg/dL versus 0.18 ± 0.14, 0.15 ± 0.48, and 2.6 ± 4.1 mg/dL for GG versus non-GG carriers (P < .0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 ± 0.8 and 2.8 ± 0.3 versus 2.1 ± 0.5 and 1.3 ± 0.1, respectively (P < .0001). The mean duration of mechanical ventilation was 22.5 ± 2.1 versus 12.7 ± 6.7 hours (P < .01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. Conclusion: The interleukin 6 - 174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

Background: Despite its common acceptance in clinical practice, the effective benefits of normothermic systemic perfusion during coronary artery bypass operations are far from established. Methods: A total of 113 patients undergoing primary isolated coronary artery bypass were randomly assigned to normothermic (37°C) or hypothermic (26°C) systemic perfusion. The clinical course of the patients was prospectively recorded, and several inflammatory and fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen activator inhibitor 1, prothrombin time, activated partial thromboplastin time, platelets, and white blood cell counts) were determined before surgical intervention; 24, 48, and 72 hours thereafter; and at hospital discharge. Results: Postoperatively, 2 in-hospital deaths occurred in the normothermic series and none in the hypothermic series. Four patients had a myocardial infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft malfunction, and none had renal insufficiency in the hypothermic group versus 1 patient with each of these complications in the normothermic series. Mean blood loss in the first 24 hours was 766 ± 223 mL in the normothermic group and 740 ± 220 mL in the hypothermic group. None of these differences was statistically significant. Similarly, no significant difference in the postoperative level of any of the measured variables at any time point was evident between the patients in the normothermic and hypothermic groups. Conclusion: Normothermic systemic perfusion does not influence the clinical course or the extent of inflammatory and hemostatic activation in patients undergoing primary isolated coronary artery bypass.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels - measured daily up to 72 hours before surgery, after surgery, and at discharge - showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 ± 3.4 vs 1.4 ± 0.9 days, p = 0.02) and in the hospital (6.7 ± 4.0 vs 5.3 ± 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization. © 2001 by Excerpta Medica, Inc.

Background: The purpose of this study was to elucidate the midterm endothelium-dependent vasodilatory capacity of radial artery grafts anastomosed to the aorta, as well as their morphometric evolution with the time. Methods: Five years after surgery we evaluated the response of aorta-anastomosed radial artery grafts to the endovascular infusion of acetylcholine in 11 of the first 61 patients operated on at our institution, and we compared it to the response with that of internal thoracic artery grafts. Moreover, the first 20 patients who had a perfect radial artery graft on angiography at 1 year were restudied at 5 years and subjected to a comparative analysis of the diameters of the radial artery graft and the grafted coronary arteries. Results: At midterm angiography, dilation of the 2 types of grafts was similar in response to acetylcholine administration (radial artery, from 2.61 ± 0.39 to 2.90 ± 0.34 mm; internal thoracic artery, from 2.68 ± 0.21 to 2.93 ± 0.27 mm; P = .01 for both). The diameters of aorta-anastomosed radial artery grafts and grafted coronary arteries increased between both 1 and 5 years according to angiographic studies (radial artery grafts, from 2.08 ± 0.45 to 2.54 ± 0.53 mm; grafted coronary arteries, from 1.92 ± 0.47 to 2.18 ± 0.41 mm; P < .001 for both), but the increase was greater for the radial artery grafts (P < .001). Conclusions: Aorta-anastomosed radial artery grafts maintain an appreciable capacity for endothelium-dependent vasodilatation 5 years after implantation and undergo a progressive increase in luminal diameter with time. These observations contradict the presumed tendency for progressive fibrous intimal hyperplasia to develop in radial artery grafts.

Objective: To evaluate the midterm angiographic results of the use of radial artery grafts for myocardial revascularization. Methods: The first 68 consecutive surviving patients who received a radial artery graft proximally anastomosed to the aorta at our institution were studied again at 5 years (mean 59 ± 6.5 months) of follow-up; 48 of these patients had previously undergone an early angiographic examination. The response of the radial artery to the endovascular infusion of serotonin was evaluated 1 and 5 years after the operation, and the midterm status of the radial artery graft was correlated with the degree of preoperative stenosis of the target vessel and with calcium-channel blocker therapy. Results: The patency and perfect patency rates of the radial artery grafts 5 years after the operation were 91.9% and 87.0%, respectively. All radial artery grafts that were patent early after the operation remained patent at midterm follow-up, and early parietal irregularities in 7 patients were seen to have disappeared after 5 years. The early propensity toward graft spasm after serotonin challenge was markedly decreased at midterm follow-up. The continued use of calcium- channel antagonists after the first postoperative year did not influence the radial artery graft status, whereas the preoperative severity of the target- vessel stenosis markedly influenced the angiographic results. Conclusions: The midterm angiographic results of radial artery grafts used for myocardial revascularization are excellent. The correct surgical indication is essential. Continued therapy with calcium-channel antagonists after the first year does not influence the midterm angiographic results.

Background. The hemodynamic significance of patent mammary graft side branches is still controversial. This study was designed to evaluate the potential for flow steal of patent mammary side branches in different hemodynamic conditions. Methods. Echo-Doppler measurement of mammary graft flow was performed at rest and after dipyridamole-induced coronary vasodilatation in 10 patients with angiographic demonstration of evident mammary graft side branches (study group) and in 10 matched control patients (control group). Concomitant thallium-201 myocardial scintigraphy was performed to assess the adequacy of mammary flow to the myocardial oxygen demand. Patients of the study group were also submitted to flow evaluation in condition of selective muscular or combined systemic and coronary relaxation. Results. No difference in mammary flow and adequacy to myocardial oxygen demand was detected between patients of the study and control groups both at rest and after dipyridamole infusion. In patients with patent side branches the systolic-to-diastolic flow ratio was maintained in case of combined coronary and peripheral vasodilatation, whereas selective muscular relaxation led to an increase in the systolic and a reduction in the diastolic flow. Conclusions. Flow steal from patent mammary graft side branches is possible only in case of selective muscular vasodilatation. As this situation is unlikely to occur in the clinical setting, the potential for flow steal of mammary side branches in cardiac surgery patients seems to be minimal.