Determination of viable myocardium through delayed enhancement cardiac magnetic resonance imaging combined with 18F-FDG PET myocardial perfusion/metabolic imaging before CABG.

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.

Viabilidade miocárdica na prática clínica / Assessing myocardial viability in clinical practice

Embora a avaliação da viabilidade miocárdica seja comum na prática do cardiologista, muitos médicos têm dúvidas a respeito dos resultados dos métodos diagnósticos. A medicina nuclear tem papel importante nos estudos de viabilidade, mas os laudos precisam ser interpretados num contexto clínico e fisiopatológico. Este artigo teve o objetivo de revisar a origem e a evolução do conceito da viabilidade miocárdica. São expostos os métodos diagnósticos com ênfase na medicina nuclear com uma explicação funcional sobre cada tipo de exame. A partir disso, são mostradas imagens como exemplos e é proposta uma maneira de atuar nesses casos baseada na clínica, na porcentagem de miocárdio acometido e na topografia das lesões coronarianas (proximais ou distais). (AU)

Although assessing myocardial viability is a common cardiology practice, many physicians question the results of diagnostic methods. Nuclear medicine plays an important role in viability studies, but the reports require interpretation in a clinical and pathophysiological context. this article was aimed at reviewing the origin and evolution of myocardial viability. Here we present diagnostic methods by emphasizing nuclear medicine and provide a functional explanation of each test type using example images. We also propose how to act in these cases based on clinic examination findings, the percentage of affected myocardium, and coronary lesion topography (proximal or distal).(AU)

Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery.

OBJECTIVE: This study aims to investigate the utility of mesenchymal stem cells (MSCs) applied as an epicardial patch during coronary artery bypass graft (CABG) to target hibernating myocardium; that is, tissue with persistently decreased myocardial function, in a large animal model. METHODS: Hibernating myocardium was induced in juvenile swine (n = 12) using a surgically placed constrictor on the left anterior descending artery, causing stenosis without infarction. After 12 weeks, single-vessel CABG was performed using left internal thoracic artery to left anterior descending artery graft. During CABG, an epicardial patch was applied to the hibernating myocardium region consisting either of MSCs grown onto a polyglactin mesh (n = 6), or sham polyglactin mesh without MSCs (n = 6). Four weeks after CABG and patch placement, cardiac magnetic resonance imaging was performed and cardiac tissue was examined by gross inspection, including coronary dilators for vessel stenosis and patency, electron microscopy, protein assays, and proteomic analysis. RESULTS: CABG + MSC myocardium showed improvement in contractile function (78.24% ± 19.6%) compared with sham patch (39.17% ± 5.57%) during inotropic stimulation (P < .05). Compared with sham patch control, electron microscopy of CABG + MSC myocardium showed improvement in mitochondrial size, number, and morphology; protein analysis similarly showed increases in expression of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (0.0022 ± 0.0009 vs 0.023 ± 0.009) (P < .01) along with key components of the electron transport chain, including succinate dehydrogenase (complex II) (0.06 ± 0.02 vs 0.14 ± 0.03) (P < .05) and adenosine triphosphate synthase (complex V) (2.7 ± 0.4 vs 4.2 ± 0.26) (P < .05). CONCLUSIONS: In hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function.

Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction.

BACKGROUND: Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). METHODS: We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. RESULTS: Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126-450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). CONCLUSIONS: Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

The mKATP Channels and protein-kinase C Are Involved in the Cardioprotective Effects of Genistein on Estrogen-Deficient Rat Hearts Exposed to Ischemia/Reperfusion: Energetic Study.

Estrogenic deficiency is considered a risk of coronary disease in women. The phytoestrogen genistein could be a safe preventive strategy. The first aim of this work was to validate a model of cardiac stunning in which natural estrogenic deficiency rats, ie, adult young male (YM) and aged female (AgF), are compared with young female rats (YF). The second aim was to study whether the in vivo administration of genistein prevents the stunning in estrogenic deficiency rats. The third aim was to evaluate whether in our estrogenic deficiency model exists a synergy between genistein and estradiol. The fourth aim was to characterize the underlying mechanisms of genistein. Stunning was induced by ischemia/reperfusion (I/R) in isolated hearts inside a calorimeter. The left ventricular pressure (P) and total heat rate (Ht) were simultaneously measured, while diastolic contracture and muscle economy (P/Ht) were calculated. During R, P/Ht and P recovered less in AgF and YM than in YF rat hearts. Genistein through i.p. (GST-ip) improved P and P/Ht in AgF and YM, but not in YF. In YM, the cardioprotections of GST-ip and estradiol were synergistic. After ischemia, GST-ip increased SR Ca leak causing diastolic contracture. The GST-ip cardioprotection neither was affected by blockade of PI3K-Akt, NO synthases, or phosphatases, but it was sensitive to blockade of protein-kinase C and mKATP channels. Results suggest that (1) estrogenic deficiency worsens cardiac stunning, (2) GST-ip was more cardioprotective in estrogenic deficiency and synergistic with estradiol, and (3) cardioprotection of GST-ip depends on the protein-kinase C and mKATP channel pathway activation.

The clinical usefulness of phase analysis in detecting coronary artery disease using dipyridamole thallium-201-gated myocardial perfusion imaging with a cadmium-zinc-telluride camera.

BACKGROUND: Previous studies have demonstrated left ventricular mechanical dyssynchrony (LVMD) in patients with severe coronary artery disease (CAD) with ≥ 70% stenosis. The aim of this study was to evaluate the clinical usefulness of stress/rest LVMD in the diagnosis of CAD with ≥ 50% stenosis using dipyridamole thallium-201 (Tl-201) myocardial perfusion imaging (MPI) with a cadmium-zinc-telluride camera. METHODS AND RESULTS: A total of 476 patients without known CAD who underwent dipyridamole Tl-201 MPI and coronary angiography within 6 months were retrospectively reviewed. LVMD parameters including phase standard deviation and phase histogram bandwidth, phase skewness and phase kurtosis, as well as myocardial perfusion and myocardial stunning were assessed in post-stress and rest MPI. Relationships between the presence of CAD on coronary angiography and single photon emission computerized tomography (SPECT) parameters were evaluated. The presence of perfusion abnormalities was the best diagnostic tool in detecting CAD. Although less left ventricular synchrony was observed post-stress in the CAD group compared to the non-CAD group, no significant dyssynchrony was noted. CONCLUSIONS: The addition of phase analysis to help diagnose CAD in Tl-201-gated SPECT with dipyridamole stress may have limited value in patients with CAD with ≥ 50% stenosis.

Correlation between the high-frequency content of the QRS on murine surface electrocardiogram and the sympathetic nerves density in left ventricle after myocardial infarction: Experimental study.

Denervated post-infarct scar is arrhythmogenic. Our aim was to compare QRS frequency content in denervated and innervated left ventricular (LV) scar. In-vivo single lead ECG telemetry device was implanted in 17 heterozygous PTPσ (HET) and 7 lacking PTPσ (KO) transgenic mice. Myocardial infarction (MI) with reperfusion and sham surgery was performed. HET mice developed a denervated scar, whereas KO mice developed innervated scar. The power spectral density was used to assess the QRS frequency content. Denervated as compared to innervated post-MI scar was characterized by the higher relative contribution of 300-500 Hz (14 ± 1 vs. 9 ± 1%; P = 0.001) but reduced relative contribution of 200-300 Hz (86 ± 1 vs. 91 ± 1%; P = 0.001). Norepinephrine concentration in peri-infarct zone correlated with both 1-200 Hz (r = 0.75; P = 0.03) and 200-500 Hz QRS power (r = 0.73; P = 0.04). Sympathetic fiber density within the infarct correlated with 200-300/200-500 Hz QRS power ratio (r = 0.56; P = 0.005). Intracellular sigma peptide injections in post-MI HET mice restored the QRS power.

Diabetes Mellitus-Induced Microvascular Destabilization in the Myocardium.

BACKGROUND: Diabetes mellitus causes microcirculatory rarefaction and may impair the responsiveness of ischemic myocardium to proangiogenic factors. OBJECTIVES: This study sought to determine whether microvascular destabilization affects organ function and therapeutic neovascularization in diabetes mellitus. METHODS: The authors obtained myocardial samples from patients with end-stage heart failure at time of transplant, with or without diabetes mellitus. Diabetic (db) and wild-type (wt) pigs were used to analyze myocardial vascularization and function. Chronic ischemia was induced percutaneously (day 0) in the circumflex artery. At day 28, recombinant adeno-associated virus (rAAV) (5 × 1012 viral particles encoding vascular endothelial growth factor-A [VEGF-A] or thymosin beta 4 [Tß4]) was applied regionally. CD31+ capillaries per high power field (c/hpf) and NG2+ pericyte coverage were analyzed. Global myocardial function (ejection fraction [EF] and left ventricular end-diastolic pressure) was assessed at days 28 and 56. RESULTS: Diabetic human myocardial explants revealed capillary rarefaction and pericyte loss compared to nondiabetic explants. Hyperglycemia in db pigs, even without ischemia, induced capillary rarefaction in the myocardium (163 ± 14 c/hpf in db vs. 234 ± 8 c/hpf in wt hearts; p < 0.005), concomitant with a distinct loss of EF (44.9% vs. 53.4% in nondiabetic controls; p < 0.05). Capillary density further decreased in chronic ischemic hearts, as did EF (both p < 0.05). Treatment with rAAV.Tß4 enhanced capillary density and maturation in db hearts less efficiently than in wt hearts, similar to collateral growth. rAAV.VEGF-A, though stimulating angiogenesis, induced neither pericyte recruitment nor collateral growth. As a result, rAAV.Tß4 but not rAAV.VEGF-A improved EF in db hearts (34.5 ± 1.4%), but less so than in wt hearts (44.8 ± 1.5%). CONCLUSIONS: Diabetes mellitus destabilized microvascular vessels of the heart, affecting the amplitude of therapeutic neovascularization via rAAV.Tß4 in a translational large animal model of hibernating myocardium.

Magnetic resonance imaging assessment of cardiac function in a swine model of hibernating myocardium 3 months following bypass surgery.

OBJECTIVE: Clinical studies demonstrate delayed recovery of hibernating myocardium (HM) following coronary artery bypass graft (CABG) surgery. Cardiac magnetic resonance (CMR) imaging is effective in identifying HM in clinical settings. Our animal model of HM shows partial but incomplete functional recovery 1 month following CABG using echocardiography. This study uses CMR imaging to determine completeness of recovery 3 months post-CABG. METHODS: Swine (N = 12) underwent left anterior descending artery (LAD) 1.5-cm constrictor placement creating a territory of HM over 12 weeks. CMR at 12 weeks confirmed hibernation without infarction (N = 12). Off-pump left internal thoracic artery (LITA) to the LAD was performed in 9 animals. Three animals were killed as HM controls. CMR imaging was repeated in revascularized animals before death at 1 (n = 4) or 3 months (n = 5). CMR imaging was performed at baseline and with dobutamine infusion (5 µg/kg/min). RESULTS: Twelve weeks after constrictor placement, CMR imaging confirmed viability in LAD region and LAD stenosis in all animals. In HM, wall thickening is reduced at baseline but with contractile reserve present during dobutamine infusion. Following revascularization, CMR imaging confirmed patent LITA graft (n = 9). Analysis of baseline regional function shows incomplete recovery of HM following CABG, with reduced contractile reserve at both 1 and 3 months post-CABG. CONCLUSIONS: CMR imaging provides accurate spatial resolution of regional contractile function and confirms the presence of HM at 12 weeks following instrumentation of the LAD. Three months following CABG, partial recovery of HM with contractile reserve is present in the single LAD territory.

Atrial Strain and Strain Rate: A Novel Method for the Evaluation of Atrial Stunning / Strain Atrial e Strain Rate: Novo Método para Avaliar Atordoamento Atrial

Abstract Background: Atrial fibrillation (AF) is the most common arrhythmia seen in adults. Atrial stunning is defined as the temporary mechanical dysfunction of the atrial appendage developing after AF has returned to sinus rhythm (SR). Objectives: We aimed to evaluate atrial contractile functions by strain and strain rate in patients with AF, following pharmacological and electrical cardioversion and to compare it with conventional methods. Methods: This study included 41 patients with persistent AF and 35 age-matched control cases with SR. All the AF patients included in the study had transthoracic and transesophageal echocardiography performed before and after. Septum (SEPsSR), left atrium (LAsSR) and right atrium peak systolic strain rate (RAsSR) were defined as the maximum negative value during atrial contraction and septum (SEPε), left atrium (LAε) and right atrium peak systolic strain (RAε) was defined as the percentage of change. Parameters of two groups were compared. Results: In the AF group, 1st hour and 24th hour LAε, RAε, SEPε, LAsSR, RAsSR, SEPsSR found to be significantly lower than in the control group (LAε: 2.61%±0.13, 3.06%±0.19 vs 6.45%±0.27, p<0.0001; RAε: 4.03%±0.38, 4.50%±0.47 vs 10.12%±0.64, p<0.0001; SEPε: 3.0%±0.22, 3.19%±0.15 vs 6.23%±0.49, p<0.0001; LAsSR: 0.61±0.04s-1, 0.75±0.04s- 1 vs 1.35±0.04s-1, p<0.0001; RAsSR: 1.13±0.06s-1, 1.23±0.07s-1 vs 2.10±0.08s- 1, p<0.0001; SEPsSR: 0.76±0.04s- 1, 0.78±0.04s- 1 vs 1.42±0.06 s- 1, p<0.0001). Conclusion: Atrial strain and strain rate parameters are superior to conventional echocardiographic parameters for the evaluation of atrial stunning in AF cases where SR has been achieved.

Resumo Fundamento: A fibrilação atrial (FA) é a arritmia mais comum em adultos. Define-se atordoamento atrial como a disfunção mecânica temporária do apêndice atrial que se desenvolve depois de reversão da FA ao ritmo sinusal (RS). Objetivos: Avaliar as funções atriais contráteis através de strain atrial e strain rate em pacientes com FA, após cardioversão farmacológica e elétrica, assim como compará-los com os métodos convencionais. Métodos: Este estudo incluiu 41 pacientes com FA persistente e 35 controles com RS e pareados por idade. Todos os pacientes com FA incluídos neste estudo foram submetidos a ecocardiografia transtorácica e transesofágica antes e após. Strain rates de pico sistólico do septo (SEPsSR), do átrio esquerdo (LAsSR) e do átrio direito (RAsSR) foram definidas como o máximo valor negativo durante contração atrial. Strains de pico sistólico do septo (SEPε), do átrio esquerdo (LAε) e do átrio direito (RAε) foram definidas como porcentagem de mudança. Resultados: No grupo com FA, os parâmetros LAε, RAε, SEPε, LAsSR, RAsSR e SEPsSR da 1a hora e da 24a hora foram significativamente mais baixos que no grupo controle (LAε: 2,61%±0,13; 3,06%±0,19 vs 6,45%±0,27; p<0,0001; RAε: 4,03%±0,38; 4,50%±0,47 vs 10,12%±0,64; p<0,0001; SEPε: 3,0%±0,22; 3,19%±0,15 vs 6,23%±0,49; p<0,0001; LAsSR: 0,61±0,04s-1; 0,75±0,04s-1 vs 1,35±0,04s-1; p<0,0001; RAsSR: 1,13±0,06s-1; 1,23±0,07s-1 vs 2,10±0,08s-1; p<0,0001; SEPsSR: 0,76±0,04s-1; 0,78±0,04s-1 vs 1,42±0,06 s-1; p<0,0001). Conclusão: Os parâmetros strain atrial e strain rate são superiores aos parâmetros ecocardiográficos convencionais para avaliar atordoamento atrial em pacientes com FA que reverteram ao RS.

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery.

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (-14.7 ± 0.6 versus -14.8 ± 0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14 ± 0.36 and 5.05 ± 0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.

Sex differences in the mechano-energetic effects of genistein on stunned rat and guinea pig hearts.

Although the phytoestrogen genistein (Gen) is considered protective in cardiovascular diseases, its direct effects on stunned hearts after transient ischemia-reperfusion (I/R) are unknown. This report studied the effects of 20 µmol/L Gen on the mechano-calorimetric behaviour during I/R of rat and guinea pig hearts to evaluate the energetics of Ca(2+) homeostasis. Isolated beating hearts were perfused with control Krebs solution inside a calorimeter with or without perfusion of Gen before a transient period of I/R. Left ventricular pressure development (P) and total heat rate (Ht) were continuously measured. At 37°C, Gen did not change post-ischemic contractile recovery (PICR), but it increased the relaxation rate. However, PICR was reduced in hearts of male rats and guinea pigs at 30°C. Total muscle economy (P/Ht) showed the same behaviour as P at each temperature. Inhibition of phosphatases with orthovanadate during Gen perfusion prevented a decrease in PICR in male rat hearts, suggesting that this effect is due to tyrosine kinase inhibition. Reperfusing ischemic hearts with 10 mmol/L caffeine-36 mmol/L Na(+)-Krebs induced contracture dependent on the sarcoreticular Ca(2+) content. Contracture relaxation depends on mitochondrial Ca(2+) uptake and Gen reduced the relaxation rate. Moreover, Gen prevented the increase in Rhod-2 fluorescence (free [Ca(2+)]m) of rat cardiomyocytes. In guinea pig hearts, Gen maintained ischemic preconditioning, but was reduced by 5-hydroxydecanoate, suggesting the participation of mitochondrial adenosine triphosphate (ATP)-dependent K channels. Results suggest that Gen acts on several mechanisms that regulate myocardial calcium homeostasis and energetics during I/R, which differ in a temperature- and sex-dependent manner.

Recovery of hibernating myocardium: what is the role of surgical revascularization?

Myocardial responses to chronic ischemia represent a continuum of adaptations resulting, over time, in a stress-resistant phenotype. One such adaptation, hibernating myocardium (HM), has increased antioxidant capacity that protects against ischemia-induced oxidative stress. Studies have suggested that revascularization alone may not fully restore cardiac function, highlighting the need for targeted therapies to serve as adjuncts to the innate healing process following revascularization. In our review, we discuss current understanding of HM and the recovery process following surgical revascularization, focusing on animal models of HM to understand implications for human patients.

Thyroid hormone and the stunned myocardium.

Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. Medical management may range from aspirin alone to placement of a left ventricular assist device. With adequate supportive therapy, recovery usually occurs within days or weeks. The effect of T3/T4 therapy has been studied in three conditions in which the ESS and myocardial functional depression have been documented - i) transient regional myocardial ischemia and reperfusion, ii) transient global myocardial ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and iii) transient inadequate global myocardial perfusion in brain-dead potential organ donors. Under all three conditions, myocardial ischemia leads to rapid loss of high-energy phosphates, accumulation of myocardial tissue lactate, and probably loss of homeostasis of cytosolic calcium, which may further increase cell injury. There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium.

Stab wound of the heart with unusual sequelae.

A 31-year-old woman was admitted to the emergency department with a stab wound to the heart. She was initially stable but rapidly developed hypotension. While the operating room and staff were in preparation, she underwent pericardiocentesis. She was then rushed to the operating room by the general surgical trauma team, who performed a bilateral anterior thoracotomy to control the bleeding. In the recovery room, the patient was still hypotensive, so cardiothoracic surgery was consulted. An echocardiogram revealed severe hypokinesis of both ventricles. The cardiothoracic surgeons returned her to the operating room and discovered that the anterior pericardium had been completely removed by the trauma team. This had caused the posterior pericardium to form a "bowstring" that almost totally obstructed pulmonary venous return and restricted right ventricular outflow of blood, inducing right-sided heart failure. This pericardial string also strangulated the left atrium posteriorly, forming 2 compartments. We repositioned the patient's heart and implanted ventricular assist devices bilaterally to provide temporary circulatory support. The patient made a good recovery. We suggest that bilateral assist device placement can be beneficial in the recovery of a stunned but otherwise normal heart.

Right ventricular hypertrophy and failure abolish cardioprotection by ischaemic pre-conditioning.

AIMS: We aimed to investigate the response to ischaemia-reperfusion (IR) and ischaemic pre-conditioning (IPC) in the hypertrophic and failing right heart. METHODS AND RESULTS: Male Wistar rats underwent sham operation, moderate pulmonary trunk banding (mPTB), or severe PTB (sPTB). Four weeks after surgery, hearts were quick-frozen (n = 28) for biochemical analysis of key salvage pathways or isolated and perfused in a Langendorff set-up (n = 46). We randomized perfused hearts to IPC (2 × 5 min of global ischaemia) or no preceding ischaemia (CON), before 40 min of global ischaemia and 120 min of reperfusion. The infarct size/area at risk (IS/AAR) ratio and post-ischaemic right ventricular (RV) function were used to evaluate the effect of IPC. mPTB induced compensated RV hypertrophy and sPTB induced RV hypertrophy with failure. Hypertrophy of the right ventricle increased IS in hearts from mPTB and sPTB animals compared with sham (IS/AAR, 73.1 ± 2.9% and 59.3 ± 2.4% vs. 35.6 ± 2.9%, P < 0.0001). IPC reduced IS in sham and mPTB hearts (IS/AAR, 35.6 ± 2.9% vs. 17.4 ± 1.2% and 73.1 ± 2.9% vs. 56.9 ± 3.5%, P < 0.01) and improved recovery of RV contractile function. IPC did not alter IS/AAR (59.3 ± 2.4% and 59.3 ± 2.9%, P = 0.999) or haemodynamic recovery in sPTB hearts. RV cyclic guanosine monophosphate (cGMP) and the cGMP-dependent protein kinase were increased after sPTB. CONCLUSION: Right ventricular hypertrophy increases IR injury. Cardioprotection by IPC is abolished in the failing but not the compensated hypertrophic right ventricle of the rat heart.

High-dose erythropoietin during cardiac resuscitation lessens postresuscitation myocardial stunning in swine.

We investigated the metabolic and functional myocardial effects of erythropoietin (EPO) administered during resuscitation from cardiac arrest using an open-chest pig model of ventricular fibrillation and resuscitation by extracorporeal circulation, after having reported in rats a reversal of postresuscitation myocardial dysfunction associated with activation of mitochondrial protective pathways. Ventricular fibrillation was induced in 16 male domestic pigs and left untreated for 8 minutes, after which extracorporeal circulation was started and maintained for 10 additional minutes, adjusting the extracorporeal flow to provide a coronary perfusion pressure of 10 mmHg. Defibrillation was accomplished and the extracorporeal flow was adjusted to secure a mean aortic pressure of 40 mmHg or greater during spontaneous circulation for up to 120 minutes. Pigs were randomized 1:1 to receive EPO (1200 U/kg) or 0.9% NaCl before starting extracorporeal circulation. Severe postresuscitation myocardial dysfunction developed in both groups. However, recovery of myocardial function-comparing baseline with 120 minutes postresuscitation-was better in pigs treated with EPO than NaCl, as shown for left ventricular ejection fraction (from 45 ± 8% to 36 ± 9% in EPO, not significant; and from 46 ± 8% to 26 ± 8% in NaCl, P < 0.001) and for peak systolic pressure/end-systolic volume (from 2.7 ± 0.8 mmHg/mL to 2.4 ± 0.7 mmHg/mL in EPO, not significant; and from 3.0 ± 1.1 mmHg/mL to 1.8 ± 0.6 mmHg/mL, P < 0.001 in NaCl). The EPO effect was associated with significantly higher myocardial O2 consumption (12 ± 6 mL/min/unit of tissue vs 6 ± 2 mL/min/unit of tissue, P < 0.017) without effects on myocardial lactate consumption. Thus, EPO administered during resuscitation from ventricular fibrillation lessened postresuscitation myocardial stunning-an effect that could be useful clinically to help promote postresuscitation hemodynamic stability.

The amount of dysfunctional but viable myocardium predicts long-term survival in patients with ischemic cardiomyopathy and left ventricular dysfunction.

To evaluate the prognostic significance of combined myocardial perfusion SPECT and [18F]FDG PET viability scanning for the prediction of survival in patients with ischemic cardiomyopathy (iCMP) and left ventricular dysfunction. 244 patients (64.0 ± 10.6 years, 86 % men) with iCMP and LVEF ≤ 45 % underwent SPECT/PET. Percent scar tissue and SPECT/PET-mismatch (%-mismatch) were calculated and correlated with event-free survival according to the type of therapy (medical therapy with/out revascularization) provided after imaging. Death from any cause was defined as the primary endpoint. Early revascularization (ER) was performed in 113/244 (46 %) patients within 32 ± 52 days (26 bypass surgeries and 87 percutaneous coronary interventions). 65 patients died during follow-up for a median of 33 months. Kaplan-Meier analysis showed that those patients with ≥ 5 % mismatch not undergoing ER had significantly higher mortality than did the group with similar mismatch who did receive ER. Cox analysis identified both SPECT/PET-mismatch and the interaction of SPECT/PET-mismatch with ER as independent predictors for death due to all causes. A threshold of ≥ 5 % SPECT/PET-mismatch predicted best which patients with iCMP and LV dysfunction would benefit from ER in terms of long-term survival.

Hot shot induction and reperfusion with a specific blocker of the es-ENT1 nucleoside transporter before and after hypothermic cardioplegia abolishes myocardial stunning in acutely ischemic hearts despite metabolic derangement: hot shot drug delivery before hypothermic cardioplegia.

OBJECTIVE: Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)-sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. METHODS: Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 µM EHNA and 25 µM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. RESULTS: Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. CONCLUSIONS: Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery.

The involvement of AQP1 in heart oedema induced by global myocardial ischemia.

Aquaporin-1 (AQP1) is a member of aquaporin family that was previously proven to be involved in myocardial dysfunction; however, the role of AQP1 in myocardial stunning is less clear. To determine the change of AQP1 expression level in the heart and its effect on oedema after global myocardial ischemia, 40 adult goats underwent cardiopulmonary bypass (CPB) with an aortic cross-clamp time of 2 h and total bypass time of 6, 12, 24, 48 and 72 h followed by subsequent reperfusion. AQP1 function of eight goats was inhibited by HgCl(2) during the 24 h on CPB. All groups were compared with eight sham bypass control goats. Myocardial water content was measured, and the APQ1 mRNA and protein levels were detected by RT-PCR and immunoblotting, respectively. The results showed that the degree of myocardial oedema increased significantly at 6, 12, 24 and 48 h of reperfusion after CPB as compared with the control and recovered at 72 h of subsequent reperfusion. Expression levels of AQP1 mRNA and protein began to increase at 12 h and peaked at 24 h of CPB following reperfusion. Furthermore, myocardial oedema was reduced in the HgCl(2) group compared with the time-matched CPB and control groups. These data suggested that AQP1 expression increases in CPB and AQP1 plays an important role in myocardial oedema during CPB.