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)

Changes in Global Left Ventricular Myocardial Work Indices and Stunning Detection 3 Months After ST-Segment Elevation Myocardial Infarction.

Global left ventricular (LV) myocardial work (MW) indices (GLVMWI) are derived from speckle tracking echocardiographic strain data in combination with non-invasive blood pressure measurements. Changes in global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) after ST-segment elevation myocardial infarction (STEMI) have not been explored. The aim of present study was to assess the evolution of GLVMWI in STEMI patients from baseline (index infarct) to 3 months' follow-up. Three-hundred and fifty patients (265 men; mean age 61 ± 10 years) with STEMI treated with primary percutaneous coronary intervention (PCI) and guideline-based medical therapy were retrospectively evaluated. Clinical variables, conventional echocardiographic measures and GLVMWI were recorded at baseline within 48 hours post-primary PCI and 3 months' follow-up. LV ejection fraction (from 54 ± 10% to 57 ± 10%, p < 0.001), GWI (from 1449 ± 451 mm Hg% to 1953 ± 492 mm Hg%, p < 0.001), GCW (from 1624 ± 519 mm Hg% to 2228 ± 563 mm Hg%, p < 0.001) and GWE (from 93% (interquartile range (IQR) 86%-95%) to 95% (IQR 91%-96%), p < 0.001) improved significantly at 3 months' follow-up with no significant difference in GWW (from 101 mm Hg% (IQR 63-155 mm Hg%) to 96 mm Hg% (IQR 64-155 mm Hg%); p = 0.535). On multivariable linear regression analysis, lower values of troponin T at baseline, increase in systolic blood pressure and improvement in LV global longitudinal strain were independently associated with higher GWI and GCW at 3 months' follow-up. In conclusion, the evolution of GWI, GCW and GWE in STEMI patients may reflect myocardial stunning, whereas the stability in GWW may reflect permanent myocardial damage and the development of non-viable scar tissue.

Myocardial stunning and hibernation revisited.

Unlike acute myocardial infarction with reperfusion, in which infarct size is the end point reflecting irreversible injury, myocardial stunning and hibernation result from reversible myocardial ischaemia-reperfusion injury, and contractile dysfunction is the obvious end point. Stunned myocardium is characterized by a disproportionately long-lasting, yet fully reversible, contractile dysfunction that follows brief bouts of myocardial ischaemia. Reperfusion precipitates a burst of reactive oxygen species formation and alterations in excitation-contraction coupling, which interact and cause the contractile dysfunction. Hibernating myocardium is characterized by reduced regional contractile function and blood flow, which both recover after reperfusion or revascularization. Short-term myocardial hibernation is an adaptation of contractile function to the reduced blood flow such that energy and substrate metabolism recover during the ongoing ischaemia. Chronic myocardial hibernation is characterized by severe morphological alterations and altered expression of metabolic and pro-survival proteins. Myocardial stunning is observed clinically and must be recognized but is rarely haemodynamically compromising and does not require treatment. Myocardial hibernation is clinically identified with the use of imaging techniques, and the myocardium recovers after revascularization. Several trials in the past two decades have challenged the superiority of revascularization over medical therapy for symptomatic relief and prognosis in patients with chronic coronary syndromes. A better understanding of the pathophysiology of myocardial stunning and hibernation is important for a more precise indication of revascularization and its consequences. Therefore, this Review summarizes the current knowledge of the pathophysiology of these characteristic reperfusion phenomena and highlights their clinical implications.

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.

High magnesium dialysate does not improve intradialytic hemodynamics or abrogate myocardial stunning.

BACKGROUND: Hemodialysis (HD) induces myocardial stunning and is associated with adverse cardiovascular outcomes. Intradialytic hypotension is a modifiable determinant of myocardial stunning. Magnesium (Mg) is reported to be valuable in maintaining intradialytic blood pressure, which potentially would protect against demand myocardial ischemia. This study aimed to compare high vs. low dialysate Mg effects on intradialytic hemodynamics and HD-induced myocardial stunning. METHODS: Twenty stable prevalent HD patients entered a randomized cross-over trial of low (0.5 mmol/L) vs. high (1.0 mmol/L) dialysate Mg. Patients were studied after 2 weeks of standard HD with each Mg concentration. Serial echocardiography assessed myocardial stunning, measured by left ventricular regional wall motion abnormalities (RWMAs). Continuous intradialytic hemodynamics were measured noninvasively using thoracic bioimpedance. FINDINGS: Median predialysis serum Mg was higher with high dialysate Mg (1.45[1.29-1.55] vs. 1.03[0.98-1.1] mmol/L, P < 0.0001). There was no significant difference in maximum intradialytic reduction in systolic BP. There was no significant difference in stroke volume, total peripheral resistance, and cardiac output. Overall ventricular global longitudinal strain (GLS) (as a sensitive marker of contractile function) was higher before dialysis in high Mg group, but there was no difference in GLS at peak stress. However, we showed a significant correlation between Mg changes and GLS changes, r = -0.47, P = 0.02. There was no difference in mean number of peak stress RWMAs per patient (4.0 ± 2.2 vs. 4.3 ± 2.9, P = 0.5). Ultrafiltration volume, a critical determinant of stunning, was not different between high and low dialysate Mg studies (1.35[0-3.3] vs. 1.5[0-2.8], P = 0.49). DISCUSSION: Manipulation of magnesium by altering dialysate magnesium concentration does not influence intradialytic hemodynamic response or HD-induced myocardial stunning in the short term. However, decreasing Mg changes appears to decrease GLS changes.

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.

Suppression of Superoxide-Hydrogen Peroxide Production at Site IQ of Mitochondrial Complex I Attenuates Myocardial Stunning and Improves Postcardiac Arrest Outcomes.

OBJECTIVES: Cardiogenic shock following cardiopulmonary resuscitation for sudden cardiac arrest is common, occurring even in the absence of acute coronary artery occlusion, and contributes to high rates of postcardiopulmonary resuscitation mortality. The pathophysiology of this shock is unclear, and effective therapies for improving clinical outcomes are lacking. DESIGN: Laboratory investigation. SETTING: University laboratory. SUBJECTS: C57BL/6 adult female mice. INTERVENTIONS: Anesthetized and ventilated adult female C57BL/6 wild-type mice underwent a 4, 8, 12, or 16-minute potassium chloride-induced cardiac arrest followed by 90 seconds of cardiopulmonary resuscitation. Mice were then blindly randomized to a single IV injection of vehicle (phosphate-buffered saline) or suppressor of site IQ electron leak, an inhibitor of superoxide production by complex I of the mitochondrial electron transport chain. Suppressor of site IQ electron leak and vehicle were administered during cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: Using a murine model of asystolic cardiac arrest, we discovered that duration of cardiac arrest prior to cardiopulmonary resuscitation determined postresuscitation success rates, degree of neurologic injury, and severity of myocardial dysfunction. Post-cardiopulmonary resuscitation cardiac dysfunction was not associated with myocardial necrosis, apoptosis, inflammation, or mitochondrial permeability transition pore opening. Furthermore, left ventricular function recovered within 72 hours of cardiopulmonary resuscitation, indicative of myocardial stunning. Postcardiopulmonary resuscitation, the myocardium exhibited increased reactive oxygen species and evidence of mitochondrial injury, specifically reperfusion-induced reactive oxygen species generation at electron transport chain complex I. Suppressor of site IQ electron leak, which inhibits complex I-dependent reactive oxygen species generation by suppression of site IQ electron leak, decreased myocardial reactive oxygen species generation and improved postcardiopulmonary resuscitation myocardial function, neurologic outcomes, and survival. CONCLUSIONS: The severity of cardiogenic shock following asystolic cardiac arrest is dependent on the length of cardiac arrest prior to cardiopulmonary resuscitation and is mediated by myocardial stunning resulting from mitochondrial electron transport chain complex I dysfunction. A novel pharmacologic agent targeting this mechanism, suppressor of site IQ electron leak, represents a potential, practical therapy for improving sudden cardiac arrest resuscitation outcomes.

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.

Neurogenic Stunned Myocardium in Severe Neurological Injury.

PURPOSE OF REVIEW: Neurogenic stunned myocardium (NSM) is a poorly recognized cardiac manifestation of neurological illness. This review addresses the contemporary understanding of NSM pathophysiology, epidemiology, diagnosis, and clinical management. RECENT FINDINGS: While the precise pathophysiology and diagnosis remain unclear, NSM is phenotypically atypical stress cardiomyopathy that can be partially attributed to excess catecholaminergic toxicity. NSM is a diagnosis of exclusion where electrocardiography, echocardiography, and cardiac biomarkers are frequently abnormal. Clinical expertise is crucial to evaluate and differentiate NSM from acute coronary syndrome and in the evaluation of potential cardiac transplantation donors after unsalvageable severe neurological injury. Neurogenic stunned myocardium is a relatively common and clinically impactful condition. More research is needed, particularly to refine clinical prognostication of NSM and rule out intrinsic cardiac injury in order to optimize donor candidacy in the event of brain death.

Neurogenic Stunned Myocardium: A Case Report and Brief Review.

BACKGROUND: Neurogenic stunned myocardium (NSM) is a condition in a group of stress cardiomyopathies with evolving nomenclature that includes Takotsubo cardiomyopathy. It manifests through electrocardiogram changes, cardiac enzyme elevation, and regional or global kinetic wall motion abnormalities. CASE REPORT: We present a 43-year-old female with a subarachnoid hemorrhage who developed persistent hypotension and tachycardia secondary to neurogenic stress cardiomyopathy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to consider NSM in any patient with neurologic pathology and undifferentiated shock. Early recognition in the emergency department setting can yield valuable data to guide the treatment and improve clinical outcomes in these patients.

Myocardial ischemia: lack of coronary blood flow, myocardial oxygen supply-demand imbalance, or what?

This opinionated article reviews current concepts of myocardial ischemia. Specifically, the historical background is briefly presented. Then, the prevailing paradigm of myocardial oxygen-supply-demand imbalance is criticized since demand is a virtual parameter that cannot be measured and data on measurements of myocardial blood flow and contractile function rather support matching between flow and function. Finally, a concept of myocardial ischemia that focusses on the reduction of coronary blood flow to below 8-10 µl/g per beat with consequences for myocardial electrical, metabolic, contractile and morphological features is advocated.

Predictors of left atrial appendage stunning after electrical cardioversion in patients with atrial fibrillation.

The transient left atrial appendage (LAA) dysfunction after electrical cardioversion (CV), which is called as LAA-stunning, was found to be an important etiology of thrombus formation. The aim of the present study was to investigate the risk factors of LAA-stunning. This study included 134 patients who underwent catheter ablation for non-paroxysmal, non-valvular, and symptomatic atrial fibrillation (AF). Internal-CV was performed, and LAA emptying fraction (LAA-EF) was assessed using LAA-angiogram before and just after CV. LAA-stunning (defined as 10% reduction of LAA-EF after CV) was observed in 45/134 patients (34%). Patients in LAA-stunning group had longer duration of AF prior to CV, higher brain natriuretic peptide (BNP), higher prevalence of patients taking calcium blocker, larger left atrial (LA) diameter, elevated E wave, and larger LA volume than those in non LAA-stunning group. Multivariate analysis showed that longer duration of AF prior to CV (p = 0.015, OR 1.033 for 1 month extend, 95% CI 1.006-1.073) and elevated BNP (p = 0.038, OR 1.041 for each 10 pg/mL increase, 95% CI 1.001-1.009) were associated with LAA-stunning. In addition, all patients were divided into four groups based on the combination between duration of AF prior to CV and BNP; group 1 (low BNP/short-lasting AF), group 2 (high BNP/short-lasting AF), group 3 (low BNP/long-lasting AF), and group 4 (high BNP/long-lasting AF). The rate of LAA-stunning was the highest in the group 4 (55.6%). Elevated BNP and long duration of AF were associated with LAA stunning after electrical cardioversion.

Percutaneous perfusion monitoring for the detection of hemodialysis induced cardiovascular injury.

INTRODUCTION: The safe delivery of hemodialysis (HD) faces dual challenges; the accurate detection of systemic circulatory stress producing cardiovascular (CV) injury, and the ability to enable effective preemptive intervention for such injury. We performed a pilot study to examine the capability of a new noninvasive, real-time monitoring system to detect the deleterious effects of HD on CV stability. METHODS: Eight patients were evaluated with echocardiography prior to the initiation of HD and again at peak HD stress. Continuous CV physiologic monitoring was performed throughout using oximeter-based pulse waveform analysis (CVInsight® Monitoring System, Intelomed, Inc., Warrendale, PA, USA). Longitudinal strain (LS) values for 12 left ventricular segments were generated using speckle-tracking software (EchoPac, GE), to assess the presence of HD-induced regional wall motion abnormalities (RWMA), indicative of myocardial stunning. FINDINGS: A reduction in pulse strength (PS) of ≥40% detected by CVI was associated with the development of RWMA (P = 0.005). This reduction occurred in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no significant reduction in PS nor evidence of myocardial stunning. In subjects with cardiac stunning, the decrease in PS was evident early during HD, 11.49 ± 10 minutes into HD treatment, prior to the detection of RWMA, which were assessed at peak HD stress, mean 210 ± 16.43 minutes into HD treatment. DISCUSSION: Percutaneous perfusion monitoring, using pulse wave analysis, appears to be useful in identifying circulatory stress during HD and predicting the development of HD-induced myocardial stunning with a lead time long enough to consider timely intervention.

Current interpretation of myocardial stunning.

Myocardial stunning is a temporary post-ischemic cardiac mechanical dysfunction. As such, it is a heterogeneous entity and different conditions can promote its occurrence. Transient coronary occlusion, increased production of catecholamines and endothelin, and myocardial inflammation are all possible causes of myocardial stunning. Possible underlying mechanisms include an oxyradical hypothesis, calcium overload, decreased responsiveness of myofilaments to calcium, and excitation-contraction uncoupling due to sarcoplasmic reticulum dysfunction. The aim of this review is to summarize the clinical conditions that may be responsible for stunned myocardium.

Brain-Heart Interactions in Traumatic Brain Injury.

The cardiovascular manifestations associated with nontraumatic head disorders are commonly known. Similar manifestations have been reported in patients with traumatic brain injury (TBI); however, the underlying mechanisms and impact on the patient's clinical outcomes are not well explored. The neurocardiac axis theory and neurogenic stunned myocardium phenomenon could partly explain the brain-heart link and interactions and can thus pave the way to a better understanding and management of TBI. Several observational retrospective studies have shown a promising role for beta-adrenergic blockers in patients with TBI in reducing the overall TBI-related mortality. However, several questions remain to be answered in clinical randomized-controlled trials, including population selection, beta blocker type, dosage, timing, and duration of therapy, while maintaining the optimal mean arterial pressure and cerebral perfusion pressure in patients with TBI.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

BACKGROUND: We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. METHODS AND RESULTS: Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end-diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). CONCLUSIONS: RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve.

Mitochondrial Bioenergetics During Ischemia and Reperfusion.

During ischemia and reperfusion (I/R) mitochondria suffer a deficiency to supply the cardiomyocyte with chemical energy, but also contribute to the cytosolic ionic alterations especially of Ca2+. Their free calcium concentration ([Ca2+]m) mainly depends on mitochondrial entrance through the uniporter (UCam) and extrusion in exchange with Na+ (mNCX) driven by the electrochemical gradient (ΔΨm). Cardiac energetic is frequently estimated by the oxygen consumption, which determines metabolism coupled to ATP production and to the maintaining of ΔΨm. Nevertheless, a better estimation of heart energy consumption is the total heat release associated to ATP hydrolysis, metabolism, and binding reactions, which is measurable either in the presence or the absence of oxygenation or perfusion. Consequently, a mechano-calorimetrical approach on isolated hearts gives a tool to evaluate muscle economy. The mitochondrial role during I/R depends on the injury degree. We investigated the role of the mitochondrial Ca2+ transporters in the energetic of hearts stunned by a model of no-flow I/R in rat hearts. This chapter explores an integrated view of previous and new results which give evidences to the mitochondrial role in cardiac stunning by ischemia o hypoxia, and the influence of thyroid alterations and cardioprotective strategies, such as cardioplegic solutions (high K-low Ca, pyruvate) and the phytoestrogen genistein in both sex. Rat ventricles were perfused in a flow-calorimeter at either 30 °C or 37 °C to continuously measure the left ventricular pressure (LVP) and total heat rate (Ht). A pharmacological treatment was done before exposing to no-flow I and R. The post-ischemic contractile (PICR as %) and energetical (Ht) recovery and muscle economy (Eco: P/Ht) were determined during stunning. The functional interaction between mitochondria (Mit) and sarcoplasmic reticulum (SR) was evaluated with selective mitochondrial inhibitors in hearts reperfused with Krebs-10 mM caffeine-36 mM Na+. The caffeine induced contracture (CIC) was due to SR Ca2+ release, while relaxation mainly depends on mitochondrial Ca2+ uptake since neither SL-NCX nor SERCA are functional under this media. The ratio of area-under-curves over ischemic values (AUC-ΔHt/AUC-ΔLVP) estimates the energetical consumption (EC) to maintain CIC. Relaxation of CIC was accelerated by inhibition of mNCX or by adding the aerobic substrate pyruvate, while both increased EC. Contrarily, relaxation was slowed by cardioplegia (high K-low Ca Krebs) and by inhibition of UCam. Thus, Mit regulate the cytosolic [Ca2+] and SR Ca2+ content. Both, hyperthyroidism (HpT) and hypothyroidism (HypoT) reduced the peak of CIC but increased EC, in spite of improving PICR. Both, CIC and PICR in HpT were also sensitive to inhibition of mNCX or UCam, suggesting that Mit contribute to regulate the SR store and Ca2+ release. The interaction between mitochondria and SR and the energetic consequences were also analyzed for the effects of genistein in hearts exposed to I/R, and for the hypoxia/reoxygenation process. Our results give evidence about the mitochondrial regulation of both PICR and energetic consumption during stunning, through the Ca2+ movement.