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Publisher Copyright: © 2022 The Authors Despite the development of device technology and operators' experience, access site vascular complications (VCs) remain one of the major concerns after transcatheter aortic valve implantation (TAVI). MANTA (Teleflex, Wayne, Pennsylvania) is a large-bore vascular closure device (VCD) with promising incidence of VC. Previously, we demonstrated that the ultrasound-guided MANTA (US-MANTA) technique further improved the outcomes compared with conventional MANTA (C-MANTA) without ultrasound guidance. The present study was established to prove the effectiveness of the technique in a larger population. In this study, we included 1,150 patients (335 patients with C-MANTA and 815 with US-MANTA) who received MANTA after TAVI from April 2017 to September 2021. The primary endpoint was MANTA-related VC. Overall VC, VCD failure, and bleeding complications were also assessed based on the Valve Academic Research Consortium 3 criteria. MANTA-related VC occurred in 12.5% in the C-MANTA group and 6.8% in the US-MANTA group (p = 0.001). VCD failure rate were 7.5% and 3.9%, respectively (p = 0.012). Valve Academic Research Consortium 3 major and minor VC were more frequent in C-MANTA group (major: 7.8% vs 4.4%, p = 0.023; minor: 8.1% vs 4.4%, p = 0.022). Multivariate analysis revealed US-MANTA as the negative predictor of MANTA-related VC (odds ratio 0.57, 95% confidence interval 0.36 to 0.89, p = 0.013). However, subgroup analysis showed the efficacy of the US-MANTA technique was limited to the patients without severely calcified puncture site (Pinteraction = 0.048). In conclusion, the US-MANTA technique was an effective strategy to reduce VC after transfemoral TAVI compared with C-MANTA. (c) 2022 The Authors. Published by Elsevier Inc.

The impact of mild paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) remains controversial. We evaluated the impact of mild PVR after TAVI on long-term clinical outcomes. We included patients who underwent TAVI for severe symptomatic aortic stenosis between December 2008 and June 2019 at 2 interna-tional centers and compared all-cause death between the group with mild PVR (group 1) and the group with none or trace PVR (group 2). PVR was categorized using a 3-class grading scheme, and patients with PVR >= moderate and those who were lost to follow-up were excluded. This retrospective analysis included 1,404 patients (mean age 81.7 +/- 6.5 years, 58.0% women). Three hundred fifty eight patients (25.5%) were classified into group 1 and 1,046 patients (74.5%) into group 2. At baseline, group 1 was older and had a lower body mass index, worse co-morbidities, and more severe aortic stenosis. To account for these differences, propensity score matching was performed, resulting in 332 matched pairs. Within these matched groups, during a mean follow-up of 3.2 years, group 1 had a significantly lower survival rate at 5 years (group 1: 62.0% vs group 2: 68.0%, log-rank p = 0.029, hazard ratio: 1.41 [95% confidence interval: 1.04 to 1.91]). In the matched cohort, patients with mild PVR had a significant 1.4-fold increased risk of mortality at 5 years after TAVI compared with those with none or trace PVR. Further studies with more patients are needed to evaluate the impact of longer-term outcomes.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) (Am J Cardiol 2023;191:14-22)

IMPORTANCE In cardiac surgery, albumin solution may maintain hemodynamics better than crystalloids and reduce the decrease in platelet count and excessive fluid balance, but randomized trials are needed to compare the effectiveness of these approaches in reducing surgical complications. OBJECTIVE To assess whether 4% albumin solution compared with Ringer acetate as cardiopulmonary bypass prime and perioperative intravenous volume replacement solution reduces the incidence of major perioperative and postoperative complications in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, single-center clinical trial in a tertiary university hospital during 2017-2020 with 90-day follow-up postoperatively involving patients undergoing on-pump coronary artery bypass grafting; aortic, mitral, or tricuspid valve surgery; ascending aorta surgery without hypothermic circulatory arrest; and/or the maze procedure were randomly assigned to 2 study groups (last follow-up was April 13, 2020). INTERVENTIONS The patients received in a 1:1 ratio either 4% albumin solution (n = 693) or Ringer acetate solution (n = 693) as cardiopulmonary bypass priming and intravenous volume replacement intraoperatively and up to 24 hours postoperatively. MAIN OUTCOMES AND MEASURES The primary outcomewas the number of patients with at least 1 major adverse event: death, myocardial injury, acute heart failure, resternotomy, stroke, arrhythmia, bleeding, infection, or acute kidney injury. RESULTS Among 1407 patients randomized, 1386 (99%; mean age, 65.4 [SD, 9.9] years; 1091 men [79%]; 295 women [21%]) completed the trial. Patients received a median of 2150 mL (IQR, 1598-2700 mL) of study fluid in the albumin group and 3298 mL (IQR, 2669-3500 mL) in the Ringer group. The number of patients with at least 1 major adverse event was 257 of 693 patients (37.1%) in the albumin group and 234 of 693 patients (33.8%) in the Ringer group (relative risk albumin/Ringer, 1.10; 95% CI, 0.95-1.27; P =.20), an absolute difference of 3.3 percentage points (95% CI, -1.7 to 8.4). The most common serious adverse events were pulmonary embolus (11 [1.6%] in the albumin group vs 8 [1.2%] in the Ringer group), postpericardiotomy syndrome (9 [1.3%] in both groups), and pleural effusion with intensive care unit or hospital readmission (7 [1.0%] in the albumin group vs 9 [1.3%] in the Ringer group). CONCLUSIONS AND RELEVANCE Among patients undergoing cardiac surgery with cardiopulmonary bypass, treatment with 4% albumin solution for priming and perioperative intravenous volume replacement solution compared with Ringer acetate did not significantly reduce the risk of major adverse events over the following 90 days. These findings do not support the use of 4% albumin solution in this setting.

Vertaisarvioitu. Näin hoidan. Vaikeaa trikuspidaaliläppävuotoa sairastaa noin 1 % väestöstä. Tyypillisiä oireita ovat turvotukset, maksan ja munuaisen kuormittuminen sekä rasituksen siedon heikkeneminen. Taustasyystä riippumatta vaikeaan trikuspidaalivuotoon liittyy suurentunut kuolleisuus. Kirurgia on vaikean läppävian ensisijainen hoito, mutta suuren leikkausriskin vuoksi siitä usein luovutaan. Valikoiduille potilaille voidaan harkita trikuspidaaliläpän katetritoimenpiteitä. Niitä on kymmenen viime vuoden aikana tehty yli 2 000 potilaalle suurissa ulkomaisissa keskuksissa. Jopa 80 % potilaista on saanut oirehyödyn toimenpiteestä. Vuonna 2020 toimenpiteet on aloitettu myös Suomessa.

Background Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). Methods and results Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively. Conclusions Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability.

The case provided suggests that an ultrasound-navigated Manta device works well in closing percutaneously the peripheral arterial extracorporeal membrane oxygenation cannulation site. Ultrasonography use during extracorporeal membrane oxygenation decannulation can further diminish the possible device-related technical failures (toggle or collagen protrusion through the vessel wall, toggle stacking into calcifications, or delivery failure of the collagen pad) leading to bleeding and vascular complications. Further studies are needed on this topic.

We evaluated the relationships between regional myocardial strain measured by speckle tracking echocardiography and viability, fibrosis, hypertrophy and oxygen consumption in the infarcted or remote myocardium in a pig model of chronic myocardial infarction (MI). Thirteen farm pigs with surgical occlusion of the left anterior descending coronary artery and five sham-operated pigs were studied 3 mo post-MI. Computed tomography revealed significant left ventricle remodeling. Reduced radial or circumferential strain identified areas of transmural infarction (area under the curve: 0.82 and 0.79, respectively). In the remote non-infarcted area, radial strain correlated inversely with the amount of fibrosis (r = –0.66, p = 0.04) and myocyte hypertrophy (r = –0.68, p = 0.03). Radial strain rate inversely correlated with myocardial resting oxygen consumption assessed with 11C-labeled acetate positron emission tomography (r = –0.71, p = 0.006). In conclusion, myocardial strain and strain rate reflect fibrosis, hypertrophy and oxygen consumption of the remote areas after MI.

A new plug-based MANTA (Teleflex, Morrisville, North Carolina) vascular closure device was recently introduced. Although prospective studies of MANTA have reported promising results of a 2% to 4% rate of major vascular complications (VCs) in selected patients who underwent transfemoral transcatheter

Background Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI). Methods and results Pigs underwent resting [15O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery. MBF, PTF, and PTI were compared with volume fraction of MI in matched segments as assessed by triphenyl tetrazolium chloride staining of LV slices. MBF and PTF were lower in infarcted than non-infarcted segments. Segmental analysis of MBF showed similar area under the curve (AUC) of 0.85, 0.86, and 0.90 with relative MBF, PTF, and PTI for the detection of viable myocardium defined as infarct volume fraction of < 75%. Cut-off values of relative MBF of ≥ 67% and PTF of ≥ 66% resulted in accuracies of 90% and 81%, respectively. Conclusions Our results indicate that resting MBF, PTF, and PTI based on [15O]water PET perfusion imaging are useful for the assessment of myocardial viability. Electronic supplementary material The online version of this article (10.1007/s12350-019-01818-5) contains supplementary material, which is available to authorized users.

Background Levosimendan is an inotropic agent with cardioprotective and vasodilating properties used for the management of acutely decompensated heart failure. We studied the effects of levosimendan treatment on the size of myocardial infarction (MI) and left ventricular (LV) function in experimental pig model of post MI heart failure. Methods After occlusion of the left anterior descending (LAD) coronary artery, animals received levosimendan 5 mg/kg/day orally for 8 weeks (n=7) or no treatment (n=18). One week after stopping treatment, transthoracic echocardiography, CT scan and positron emission tomography were performed to evaluate myocardial function, perfusion and oxidative metabolism. Histology was used to confirm the size of MI and features of LV remodelling. Results The size of MI was significantly smaller in the levosimendan group than in the controls (12±13% vs 27±15% of the LV, p=0.03). End-diastolic volume (EDV) and end-systolic volume (ESV) were smaller in the levosimendan than in the control group (EDV 161±29 mL vs 245±84 mL, p=0.06; ESV 81±18 mL vs 149±67 mL, p=0.03), whereas ejection fraction tended to be higher in the levosimendan group (50±6% vs 41±8%, p=0.06). Conclusions Eight weeks of levosimendan therapy after recent LAD occlusion decreases the size of MI and leads to better preservation of LV function as well as reduced LV remodelling.

Background Modifications of the Bjork-Shiley valve prosthesis have shown good long-term results. The convexo-concave model, however, was recalled 27 years ago because of a propensity for breakage due to outlet strut fracture. The objective of this study is to describe the 30-year outcome after implantation of the Bjork-Shiley convexo-concave mechanical heart valve prosthesis (Pfizer, Rye Brook, NY). Methods The study included 279 patients who were operated between 1979 and 1983 at Turku University Hospital. A total of 305 valves were implanted; 205 in the aortic position and 100 in the mitral position. Patient records were reviewed for baseline characteristics and late events, data on mortality were acquired from registries. Results Mean actuarial survival was 19.8 years and mean follow-up was 19.2 years (maximum 34 years). Freedom from reoperation was 91.3% at 30 years. There were 3 outlet strut fractures (2 fatal) during follow-up. Statistically significant predictors of mortality were age and concomitant coronary artery bypass grafting. Conclusions Despite the possibility of structural valve failure the Bjork-Shiley convexo-concave valve confers excellent 30-year survival.

The role of the intestine in the pathogenesis of metabolic diseases is gaining much attention. We therefore sought to validate, using an animal model, the use of positron emission tomography (PET) in the estimation of intestinal glucose uptake (GU), and thereafter to test whether intestinal insulin-stimulated GU is altered in morbidly obese compared with healthy human participants.In the validation study, pigs were imaged using [(18)F]fluorodeoxyglucose ([(18)F]FDG) and the image-derived data were compared with corresponding ex vivo measurements in tissue samples and with arterial-venous differences in glucose and [(18)F]FDG levels. In the clinical study, GU was measured in different regions of the intestine in lean (n = 8) and morbidly obese (n = 8) humans at baseline and during euglycaemic hyperinsulinaemia.PET- and ex vivo-derived intestinal values were strongly correlated and most of the fluorine-18-derived radioactivity was accumulated in the mucosal layer of the gut wall. In the gut wall of pigs, insulin promoted GU as determined by PET, the arterial-venous balance or autoradiography. In lean human participants, insulin increased GU from the circulation in the duodenum (from 1.3 ± 0.6 to 3.1 ± 1.1 μmol [100 g](-1) min(-1), p 0.05) and in the jejunum (from 1.1 ± 0.7 to 3.0 ± 1.5 μmol [100 g](-1) min(-1), p 0.05). Obese participants failed to show any increase in insulin-stimulated GU compared with fasting values (NS).Intestinal GU can be quantified in vivo by [(18)F]FDG PET. Intestinal insulin resistance occurs in obesity before the deterioration of systemic glucose tolerance.

Background We evaluated echocardiographic area-length methods to measure left ventricle (LV) volumes and ejection fraction (EF) in parasternal short axis views in comparison with cardiac computed tomography (CT) in pigs with chronic myocardial infarction (MI). Methods Male farm pigs with surgical occlusion of the left anterior descending coronary artery (n = 9) or sham operation (n = 5) had transthoracic echocardiography and cardiac-CT 3 months after surgery. We measured length of the LV in parasternal long axis view, and both systolic and diastolic LV areas in parasternal short axis views at the level of mitral valve, papillary muscles and apex. Volumes and EF of the LV were calculated using Simpson’s method of discs (tri-plane area) or Cylinder-hemiellipsoid method (single plane area). Results The pigs with coronary occlusion had anterior MI scars and reduced EF (average EF 42 ± 10%) by CT. Measurements of LV volumes and EF were reproducible by echocardiography. Compared with CT, end-diastolic volume (EDV) measured by echocardiography showed good correlation and agreement using either Simpson’s method (r = 0.90; mean difference −2, 95% CI −47 to 43 mL) or Cylinder-hemiellipsoid method (r = 0.94; mean difference 3, 95% CI −44 to 49 mL). Furthermore, End-systolic volume (ESV) measured by echocardiography showed also good correlation and agreement using either Simpson’s method (r = 0.94; mean difference 12 ml, 95% CI: −16 to 40) or Cylinder-hemiellipsoid method (r = 0.97; mean difference:13 ml, 95% CI: −8 to 33). EF was underestimated using either Simpson’s method (r = 0.78; mean difference −6, 95% CI −11 to 1%) or Cylinder-hemiellipsoid method (r = 0.74; mean difference −4, 95% CI–10 to 2%). Conclusion Our results indicate that measurement of LV volumes may be accurate, but EF is underestimated using either three or single parasternal short axis planes by echocardiography in a large animal model of chronic MI.

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.

Purpose We evaluated four potential gallium-68 ( 68 Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([ 15 O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study. Methods Following an evaluation of myocardial blood flow with [ 15 O]water PET, the pigs (total n =14) underwent a dynamic 90-min PET study with one of four 68 Ga-labeled BAPEN derivatives ( n =3–5 per tracer) either at rest or under adenosine stress. Serial arterial blood samples were collected during the imaging for the measurements of total radioactivity, radiometabolites, plasma protein binding and blood-to-plasma ratio for the 68 Ga chelates. Time–activity curves of the left ventricular blood pool and myocardium were derived from PET images, and metabolite-corrected arterial input function was used for kinetic modeling. Also, ex vivo biodistribution of 68 Ga radioactivity was analyzed. Results All four 68 Ga tracers showed undesirably slow myocardial accumulation over time, but their in vivo stability, clearance from blood and the kinetics of the myocardium uptake varied. [ 68 Ga][Ga-(sal) 2 BAPDMEN] 1+ showed the highest myocardial uptake in PET images and tissue samples (myocardium-to-blood ratio 7.63±1.89, myocardium-to-lung ratio 3.03±0.33 and myocardium-to-liver ratio 1.80±0.82). However, there was no correlation between the myocardial perfusion measured with [ 15 O]water and the net uptake rates or K 1 values of the 68 Ga chelates. Conclusion Our results revealed that myocardial accumulation of the 68 Ga chelates proposed for myocardial perfusion imaging with PET was slow and not determined by myocardial perfusion in a large animal model. These findings suggest that the studied tracers are not suitable for clinical imaging of myocardial perfusion.

Background Retrograde delivery is associated with inadequate perfusion of cardioplegia to all regions of the heart, but the effects on cardiomyocyte death and functional outcome remain unknown. We compared antegrade and retrograde cardioplegia in a randomized clinical trial to see whether it has effect on cardiomyocyte apoptosis and left ventricular function. Methods Patients underwent elective aortic valve replacement surgery due to aortic valve stenosis. They were randomly allocated to receive antegrade (n = 10) or retrograde (n = 10) cardioplegia. Apoptotic cardiomyocytes (terminal transferase-mediated dUTP nick end labeling, caspase activation) and RNA levels of apoptosis-regulating proteins were studied in transmyocardial biopsies obtained before and after the operation. Magnetic resonance imaging and transesophageal echocardiography were performed, and cardiac enzymes were measured. Results Clinical outcome and cardiac enzyme release were comparable between the groups. Cardiomyocyte apoptosis was significantly increased (terminal transferase-mediated dUTP nick end labeling) in the left ventricle after the operation in the retrograde, but not in the antegrade group (respectively, 0.00% [0.039%] versus 0.092% [0.205%], p = 0.01; and 0.00% [0.00%] versus 0.023% [0.054%], p = 0.14). Expression of apoptosis-regulating proteins BAX, BAD, and BCL-2 were comparable between groups. By transesophageal echocardiography, the systolic mitral annulus movement was decreased immediately after the operation in the retrograde group. By magnetic resonance imaging, the left ventricle mass index was reduced preoperatively to 9 months postoperatively in the antegrade group. Conclusions In contrast to antegrade cardioplegia, retrograde cardioplegia is associated with increased cardiomyocyte apoptosis, impaired immediate postoperative systolic function, and lack of long-term favorable left ventricle remodeling after aortic valve replacement, suggesting inadequate myocardial protection.

Background: Cardiomyocyte apoptosis might contribute to left ventricular (LV) dysfunction following cardiac surgery. Magnetic resonance imaging is considered the most accurate method of determining LV function. We compared apoptosis (by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, TUNEL, staining and detection of caspase 3 activation) and LV function after regional ischemia-reperfusion (I-R) and global cardioplegic ischemia. Methods: Pigs were randomized to undergo regional myocardial I-R for 20 + 20 min, global myocardial ischemia with cardiopulmonary bypass (CPB) for 40 min or CPB without ischemia (control), followed by 274 min of reperfusion. Results: Compared with the control group, the number of TUNEL-positive cardiomyocytes was higher in the global ischemia group with CPB (0.024 ± 0.014%; p = 0.02) and further increased in areas of unprotected regional I-R (0.444 ± 0.562%; p = 0.003, vs. control). Myocytes with active caspase 3 were detected after global and regional ischemia. The global ejection fraction did not differ between CPB and regional I-R groups. Conclusions: The use of cardioplegia and CPB efficiently protects the heart from global I-R-induced cardiomyocyte apoptosis during open heart surgery.

Objective: Apoptotic cardiomyocyte death is induced during open heart surgery, but its determinants are poorly understood. Prolonged aortic clamping time is associated with adverse clinical outcomes. The purpose of this study was to determine whether occurrence of cardiomyocyte apoptosis is related to the duration of aortic clamping in experimental pig model of cardiac surgery with cardiopulmonary bypass. Methods: The pigs (mean weight 29 1 kg) were randomly divided to undergo cardioplegic arrest for 60 (n =4 ) or 90 (n = 4) min followed by reperfusion period of 120 min.Controlgroup(n = 5)wasconnectedto cardiopulmonary bypass for120 min without cardioplegic arrest.Cardiomyocyte apoptosiswas detected (TUNEL assay and immunohistochemical staining of active caspase-3) in left ventricular tissue samples obtained before ischemia and after the ischemia-reperfusion period. Results: Apoptotic cardiomyocytes were found in all samples obtained after cardioplegic arrest and cardiopulmonary bypass alone with the TUNEL assay. The amount of apoptosis after the 120 min of cardiopulmonary bypass alone in the control group was 0.006 0.001%. Compared with this, cardiomyocyte apoptosis was increased after cardioplegic arrest. After 60 min of aortic crossclamp the amount of apoptosis was 0.019 0.004% (p = 0.031). After 90 min of aortic cross-clamp the amount was 0.042 0.005% (p < 0.001) beingsignificantlyhigherthan after60 min (p = 0.001). Aorticcross-clampof 90 min also resultedin a detectableincrease incaspase-3 activation when compared with controls. Conclusions: The occurrence of cardiomyocyte apoptosis increases with prolonged aortic clamping time during open heart surgery.

Objective Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model. Methods First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG). Results Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4). Conclusions We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques.

Introduction: Positron emission tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) can be used to detect atherosclerotic plaque inflammation. The degree of [18F]FDG uptake in different stages of coronary atherosclerosis remains largely unknown. Thus, we studied the amount of [18F]FDG uptake and feasibility of its in vivo quantification by combination of PET and computed tomography angiography (CTA) in a pig model of atherosclerosis. Methods: In order to induce coronary atherosclerosis, diabetes was caused by streptozotocin injections in farm pigs (n=10). After 6 months on high-fat diet, pigs underwent dual gated cardiac PET and CTA to measure [18F]FDG uptake in the proximal segments of coronary arteries as maximal target to background ratio (TBR = [18F]FDG uptake normalized to blood pool). Proximal coronary segments (n=33) were harvested for ex vivo measurement of radioactivity and for histology and measurement of tracer uptake into the vessel wall by autoradiography (ARG). Results: The pigs were hyperglycemic (12.3±4.7 mmol/L) and hypercholesterolemic (12.7±5.1 mmol/L) at the end of the study. The coronary arteries showed intimal thickening (n=16 segments) and atheroma (n=10 segments). Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher accumulation of [18F]FDG in intimal thickening and 4.1±2.3 in atheroma (p=0.004 and p=0.003, respectively). Ex vivo mean vessel to blood ratio of segments with atheroma was higher than non-atherosclerotic segments (2.6±1.2 vs. 1.3±0.7, p=0.04). In vivo PET imaging showed the highest TBR of 2.7. However, maximal TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, p=1.0) or atheroma (1.6±0.6, p=0.4) and no correlation was seen between the segmental TBR measured by in vivo PET-CT and [18F]FDG uptake measured by either biodistribution or autoradiography. Conclusions: We found increased [18F]FDG uptake in atherosclerotic lesions. However, quantification of [18F]FDG uptake in these relatively small and early stage atherosclerotic lesions by dual gated PET and CTA was not feasible. Further studies are needed to clarify feasibility of this approach in more advanced and highly inflamed atherosclerotic coronary plaques.

Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology.Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [(15)O]water and oxygen consumption using [(11)C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs.The chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

Adenosine (ADO) has been shown to have beneficial effects against tissue injury after myocardial ischemia. However, the timing and dose of ADO administration have not been defined. This study was designed to determine the cardioprotective effect of exogenous ADO in an experimental open heart surgery model in pigs.The animals were openly divided into two groups both undergoing 30 min of total cardiac arrest. In the control group animals received cold crystalloid cardioplegic solution. In the ADO group ADO was added to cardioplegic solution and in addition ADO was infused to the superior vena cava for 2 h starting 30 min before cardiac arrest. The pumping function of the heart was measured with echocardiography and myocardial blood flow was measured with microspheres and positron emission tomography (PET). Cardiomyocyte apoptosis was detected and tumor necrosis factor (TNF) levels were measured.Better post-ischemic pumping function was found in the ADO group (relative decrease 43.7% vs 55.4%, p = 0.20 between the groups). The cardiac output decreased significantly from the baseline values (p0.05 in both groups). There was a temporary decrease in myocardial blood flow post-ischemically, followed by a compensatory increase during the later reperfusion period. The cardiomyocyte apoptosis was induced significantly in both groups.In this experiment two important details were noticed. Firstly, cardiomyocyte apoptosis is involved in ischemia-reperfusion injury associated with open heart surgery. Secondly, PET is a comparable method with the microsphere technique when coronary flow is studied. No significant effects of ADO against ischemia-reperfusion injury could be shown. However, there were some signsof positive outcome, even though statistical significance could not be reached.

Cardiopulmonary bypass (CPB) is known to cause the systemic inflammatory reaction after cardiac surgery. New coated and closed loop circuit systems may reduce this inflammation response and improve the surgical outcome. This study was designed to evaluate the safety and efficacy of the mini-extracorporeal circulation system (ECC.O) in CABG patients.Forty patients undergoing elective coronary surgery were randomized into two groups, the ECC.O group and the standard CPB group. Routine hemodynamic monitoring and biochemical measurements were registered according to the hospital practice.The clinical outcome of the patients was similar in both groups. There were no significant differences between the groups in the duration of intubation following surgery, the length of intensive care unit-stay or the total hospital stay. The haemoglobin level was significantly higher (p=0.0069) during and after the perfusion in the ECC.O group.The ECC.O system can be safely used in CABG patients and it maintains haemoglobin level better than conventional CPB.

14( R, S)-[(18)F]Fluoro-6-thia-heptadecanoic acid ([(18)F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [(18)F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [(18)F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [(18)F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [(18)F]FTHA metabolite analysis. Fractional [(18)F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring (18)F in the tissue samples. Fractional [(18)F]FTHA uptake rates based on the analysis of tissue samples were 0.56+/-0.17 ml g(-1) min(-1) and 0.037+/-0.007 ml g(-1) min(-1) for myocardium and skeletal muscle (mean +/- SD), respectively. The myocardial results obtained from the PET data (0.50+/-0.11 ml g(-1) min(-1)) were similar to the values obtained from the tissue samples ( r=0.94, P=0.002). We also found that 89%+/-23% (mean+/-SD, n=7) of the (18)F entered mitochondria in myocardium, as compared with only 36%+/-15% (mean+/-SD, n=7) in skeletal muscle. Intracellular [(18)F]FTHA metabolite analysis showed that a major part of [(18)F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that ~89% of [(18)F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [(18)F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only ~36% of [(18)F]FTHA accumulated in skeletal muscle appears to directly enter mitochondria; the majority is taken up by the other cell fractions, suggesting that in skeletal muscle [(18)F]FTHA traces FFA uptake but not specifically FFA beta-oxidation.

Objectives: Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes catalyze the initial step in the formation of prostaglandins, which have a role in the regulation of circulation and in inflammatory reactions. As hypoxia is reported to stimulate the expression of COX-2, we have investigated the effects of bypass circulation and cardioplegic arrest on the expression COX-1 and COX-2 in the myocardium of porcine hearts. Methods: Anaesthetized pigs were connected to cardiopulmonary bypass and the hearts were arrested by cold crystalloid cardioplegia for 30 min and reperfused thereafter for 90 min. Then the mRNA and protein levels of COX-1 and COX-2 were measured from the transmural specimens of the left ventricular myocardium by Northern and Western blot analyses. Reference specimens were from the hearts of unoperated control pigs and from sham-operated pigs, which were connected to cardiopulmonary bypass for 120 min without any aortic clamping. Results: COX-1 mRNA was expressed in unoperated control porcine hearts, whereas the expression of COX-2 mRNA was weak in control hearts. The expression of COX-2 mRNA increased to 170% of the control level in the hearts of sham-operated pigs and to 180% in arrested hearts, while the level of COX-1 mRNA was not changed. Both COX-1 and COX-2 proteins were detected by Western blot analysis in the myocardial specimens of control hearts. After cardioplegic arrest, the level of COX-2 protein increased to 280% of the control level in arrested hearts, whereas the level of COX-1 protein remained unchanged. Conclusions: These results indicate that the expression of the COX-2 gene is stimulated in the ventricular myocardium of the porcine heart after bypass circulation and cardioplegic arrest. q 2001 Elsevier Science B.V. All rights reserved.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial glycoprotein which mediates leukocyte-endothelial cell interactions. To study the pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo immunodetection method was used to detect the regulation of luminally expressed VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and arthritis could be visualized by specifically targeted immunoscintigraphy. Moreover, the translocation of VAP-1 to the functional position on the endothelial surface was only seen in inflamed tissues. These results suggest that VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential target molecule for imaging inflammation.