Ventricular Oxygen Consumption Research Articles

Myocardial External Efficiency in Asymptomatic Severe Primary Mitral Regurgitation Using 11C-Acetate PET.

Subjects with asymptomatic moderate-to-severe or severe primary mitral regurgitation are closely observed for signs of progression or symptoms requiring surgical intervention. The role of myocardial metabolic function in progression of mitral regurgitation is poorly understood. We used 11C-acetate PET to noninvasively measure myocardial mechanical external efficiency (MEE), which is the energetic ratio of external cardiac work and left ventricular (LV) oxygen consumption. Methods: Forty-seven patients in surveillance with mitral regurgitation and no or minimal symptoms prospectively underwent PET, echocardiography, and cardiac MRI on the same day. PET was used to simultaneously measure cardiac output, LV mass, and oxygen consumption to establish MEE. PET findings were compared between patients and healthy volunteers (n = 9). MEE and standard imaging indicators of regurgitation severity, LV volumes, and function were studied as predictors of time to surgical intervention. Patients were followed a median of 3.0 y (interquartile range, 2.0-3.8 y), and the endpoint was reached in 22 subjects (47%). Results: MEE in patients reaching the endpoint (23.8% ± 5.0%) was lower than in censored patients (28.5% ± 4.5%, P = 0.002) or healthy volunteers (30.1% ± 4.9%, P = 0.001). MEE with a cutoff lower than 25.7% was significantly associated with the outcome (hazard ratio, 7.5; 95% CI, 2.7-20.6; P < 0.0001) and retained independent significance when compared with standard imaging parameters. Conclusion: MEE independently predicted time to progression requiring valve surgery in patients with asymptomatic moderate-to-severe or severe primary mitral regurgitation. The study suggests that inefficient myocardial oxidative metabolism precedes clinically observed progression in mitral regurgitation.

Non-invasive quantification of pressure–volume loops in patients with Fontan circulation

BackgroundPressure–volume (PV) loops provide comprehensive information of cardiac function, but commonly implies an invasive procedure under general anesthesia. A novel technique has made it possible to non-invasively estimate PV loops with cardiac magnetic resonance (CMR) and brachial pressure which would enable good volume estimation of often anatomically complex ventricles without the need of anesthesia in most cases. In this study we aimed to compare how hemodynamic parameters derived from PV loops in patients with Fontan circulation differ to controls.MethodsPatients with Fontan circulation (n = 17, median age 12 years, IQR 6–15) and healthy controls (n = 17, 14 years, IQR 13–22) were examined with CMR. Short axis balanced steady-state free-precession cine images covering the entire heart were acquired. PV loops were derived from left ventricular volumes in all timeframes and brachial blood pressure from cuff sphygmomanometry.ResultsFontan patients had lower stroke work, ventricular mechanical efficiency and external power compared to controls. Fontan patients with dominant right ventricle had higher potential energy indexed to body surface area but lower contractility (Ees) compared to controls. Fontan patients had higher arterial elastance (Ea) and Ea/Ees ratio than controls. Contractility showed no correlation with ejection fraction (EF) in Fontan patients irrespective of ventricular morphology. No difference was seen in energy per ejected volume between Fontan patients and controls.ConclusionsThis non-invasive PV-loop method could be used in future studies to show the potential prognostic value of these measures and if changes in ventricular function over time can be detected earlier by this method compared to changes in ventricular volumes and EF. In contrast to patients with acquired heart failure, Fontan patients had similar energy per ejected volume as controls which suggests similar ventricular oxygen consumption to deliver the same volume in Fontan patients as in controls.

Myocardial efficiency in severe asymptomatic primary mitral regurgitation: relation to quantitative measures of regurgitation

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p&amp;lt;0.001) and showed weak but significant correlations (r2&amp;lt;0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p&amp;lt;0.05), while LVEF and NT-pro-BNP were not (p&amp;gt;0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Thigh intramuscular fat predicts the prognosis in patients in non-ischemic cardiomyopathy with reduced ejection fraction

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also intramuscular fat (IMF) has been pointed out. However, there is a lack of consensus on the implications of ectopic fat for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether ectopic fat in the thigh affects the prognosis with non-ischemic cardiomyopathy. Methods We recruited 105 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2019. Finally 73 patients with reduced EF (EF 40% or less) enrolled in this prospective study. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of epicardial fat and thigh IMF percentage (%IMF) using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients' medical records. Clinical endpoints were unexpected readmission. Results During the follow-up period 18 patients had adverse events. The %IMF was significantly higher in the group with adverse events than without (5.57±5.70 and 3.02±2.44%, respectively; p&amp;lt;0.01). Spearman correlation coefficient analysis showed a modest correlation between %IMF and lower limb extension strength (Spearman r=−0.280; p=0.0315), but there was no significant correlation between %IMF and exercise tolerance such as anaerobic threshold and peak oxygen uptake. Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p=0.033). Multivariate Cox regression analysis adjusted for left ventricular end-diastolic diameter and peak ventricular oxygen consumption found %IMF as an independent factor of adverse events (hazard ratio 1.545; 95% confidential interval 1.151–2.087; p=0.004). Conclusions In non-ischemic cardiomyopathy patients with reduced EF, %IMF may have important adverse consequences such as increased cardiac-related events. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Multiscale structure-function relationships in right ventricular failure due to pressure overload.

Right ventricular (RV) failure (RVF) is the major cause of death in pulmonary hypertension. Recent studies have characterized changes in RV structure in RVF, including hypertrophy, fibrosis, and abnormalities in mitochondria. Few, if any, studies have explored the relationships between these multiscale structural changes and functional changes in RVF. Pulmonary artery banding (PAB) was used to induce RVF due to pressure overload in male rats. Eight weeks postsurgery, terminal invasive measurements demonstrated RVF with decreased ejection fraction (70 ± 10 vs. 45 ± 15%, sham vs. PAB, P < 0.005) and cardiac output (126 ± 40 vs. 67 ± 32 ml/min, sham vs. PAB, P < 0.05). At the organ level, RV hypertrophy was directly correlated with increased contractility, which was insufficient to maintain ventricular-vascular coupling. At the tissue level, there was a 90% increase in fibrosis that had a direct correlation with diastolic dysfunction measured by reduced chamber compliance ( r2 = 0.43, P = 0.008). At the organelle level, transmission electron microscopy demonstrated an abundance of small-sized mitochondria. Increased mitochondria was associated with increased ventricular oxygen consumption and reduced mechanical efficiency ( P < 0.05). These results demonstrate an association between alterations in mitochondria and RV oxygen consumption and mechanical inefficiency in RVF and a link between fibrosis and in vivo diastolic dysfunction. Overall, this work provides key insights into multiscale RV remodeling in RVF due to pressure overload. NEW & NOTEWORTHY This study explores the functional impact of multiscale ventricular remodeling in right ventricular failure (RVF). It demonstrates correlations between hypertrophy and increased contractility as well as fibrosis and diastolic function. This work quantifies mitochondrial ultrastructural remodeling in RVF and demonstrates increased oxygen consumption and mechanical inefficiency as features of RVF. Direct correlation between mitochondrial changes and ventricular energetics provides insight into the impact of organelle remodeling on organ level function.

Evaluation of ECG-gated [11C]acetate PET for measuring left ventricular volumes, mass, and myocardial external efficiency

BackgroundNoninvasive estimation of myocardial external efficiency (MEE) requires measurements of left ventricular (LV) oxygen consumption with [11C]acetate PET in addition to LV stroke volume and mass with cardiovascular magnetic resonance (CMR). Measuring LV geometry directly from ECG-gated [11C]acetate PET might enable MEE evaluation from a single PET scan. Therefore, we sought to establish the accuracy of measuring LV volumes, mass, and MEE directly from ECG-gated [11C]acetate PET. MethodsThirty-five subjects with aortic valve stenosis underwent ECG-gated [11C]acetate PET and CMR. List mode PET data were rebinned into 16-bin ECG-gated uptake images before measuring LV volumes and mass using commercial software and compared to CMR. Dynamic datasets were used for calculation of mean LV oxygen consumption and MEE. ResultsLV mass, volumes, and ejection fraction measured by CMR and PET correlated strongly (r = 0.86-0.92, P < .001 for all), but were underestimated by PET (P < .001 for all except ESV P = .79). PET-based MEE, corrected for bias, correlated fairly with PET/CMR-based MEE (r = 0.60, P < .001, bias −3 ± 21%, P = .56). PET-based MEE bias was strongly associated with LV wall thickness. ConclusionsAlthough analysis-related improvements in accuracy are recommended, LV geometry estimated from ECG-gated [11C]acetate PET correlate excellently with CMR and can indeed be used to evaluate MEE.

PM120 Electrical Myostimulation Improves Quality of Life, Left Ventricular Function and Peak Oxygen Consumption in Patients With Chronic Heart Failure - Results From the EMS Study Comparing Different Stimulation Strategies

PM120 Electrical Myostimulation Improves Quality of Life, Left Ventricular Function and Peak Oxygen Consumption in Patients With Chronic Heart Failure - Results From the EMS Study Comparing Different Stimulation Strategies

Gender Differences in Ventricular-vascular Coupling Following Exercise.

To study the differences of cardiovascular system between men and women in response to exercise stress. Forty healthy youth were tested according to Bruce protocol of exercise stress. They were detected by ultrasonography during the rest, peak exercise, and recovery stages, respectively. The left ventricular diastolic elastance (Ed), effective arterial elastance (Ea), left ventricular end-systolic elatance (Ees), ventricular-vascular coupling index (VVI), and total stiffness index (TSI) were measured and calculated according to the formulas. The results of all stages were compared according to genders. All stages, the Ed, TSI, and VVI of women were higher than those of men, but the Ees was lower than that of men (all P<0.05); there was no significant difference in Ea between men and women. The Ed, Ees, Ea, and TSI were closely related with left ventricular oxygen consumption and heart function, and women showed more closely. Before and after exercise, the changes were different in Ed, Ees, Ea, TSI, and VVI (all P<0.05), and VVI changed least. Before and after exercise, the ventricular stiffness matched well with arterial stiffness and maintained within a narrow range. For women, the tolerance of exercise was lower than that of men.

Optimal Timing Algorithms of Para-Aortic Counterpulsation Device

Para-aortic counterpulsation device (PACD) is a promising therapy for severe heart failure (HF). However, the lack of knowledge about mechanisms has limited its clinical application. The aim of this study was to investigate the optimal timing algorithms. At the following four triggering algorithms, pre-R-wave-deflation and dicrotic notch-inflation (PD), pre-R-wave-deflation and postdicrotic notch-inflation (PP), R-wave-deflation and dicrotic notch-inflation (RD), and R-wave-deflation and postdicrotic notch-inflation (RP), hemodynamic effects of PACD were assessed in vivo. There was more significant promotion of left mean coronary artery flow (Q(LM)), carotid artery flow (Q(CA)), cardiac output (CO), pulmonary artery flow/LA pressure ratio (Q(PA)/LAP), left ventricular myocardial oxygen consumption (LVVO(2)), external LV work (ELVW), and cardiac mechanical efficiency (CME) at RD and RP models than PD and PP models. R-wave-deflation and postdicrotic notch-inflation model provided further benefits. There was significant correlation between LV functional parameters and carotid arterial reflux, but aortic pressure-related parameters. Filling at beginning of LV systolic phase and ejection at the end of isovolumic relaxation phase were the optimal triggering algorithms of PACD. It is suggested that carotid artery reflows and ventricular pressure-related parameters should be used as reference standard to adjust the timing of balloon inflation or deflation.

Heart Rate Reduction Induced by the If Current Inhibitor Ivabradine Improves Diastolic Function and Attenuates Cardiac Tissue Hypoxia

Enhanced heart rate (HR) is a compensatory mechanism in chronic heart failure (CHF), preserving cardiac output, but at the cost of increased left ventricular (LV) oxygen consumption and impaired diastolic function. The HR reduction (HRR) induced by the If current inhibitor ivabradine prevents LV systolic dysfunction in CHF, but whether HRR improves LV diastolic function is unknown. LV diastolic function and remodeling were assessed in rats with CHF after coronary ligation after long-term (90 days, starting 7 days after ligation) and delayed short-term (4 days, starting 93 days after ligation) ivabradine treatment (10 mg·kg·d). Long- and short-term HRR reduced LV end-diastolic pressure, LV relaxation, and LV end-diastolic pressure-volume relation. Simultaneously, LV hypoxia-inducible factor-1α expression was reduced. Long-term and, to a more marked extent, short-term HRR increased endothelial cell proliferation, associated after long-term HRR with the prevention of CHF-related LV capillary rarefaction. Long-term and, to a lesser extent, short-term HRR increased endothelial nitric oxide synthase expression, associated after long-term HRR with improved nitric oxide-dependent coronary vasodilatation. Long-term HRR induced by ivabradine improves diastolic LV function probably involving attenuated hypoxia, reduced remodeling, and/or preserved nitric oxide bioavailability, resulting from processes triggered early after HRR initiation: angiogenesis and/or preservation of endothelial nitric oxide synthase expression.

CASE 1—2011: The Challenges Posed by a Complicated Pulmonary Thromboendarterectomy

HEN DISCUSSING heart failure, the left ventricle normally takes center stage, and the right ventricle (RV) can become an afterthought. However, in patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH), the RV takes the lead role. These patients can present with increased right ventricular oxygen consumption with a concomitant decrease in right ventricular oxygen supply, placing them at high risk for right ventricular ischemia and failure. Fortunately, after a pulmonary thromboendarterectomy (PTE), rightheart hemodynamics greatly improve in most CTEPH patients, and right ventricular perfusion is no longer an issue. The authors, however, present a case discussing the management of a patient with severe pulmonary hypertension (PH) undergoing a PTE with residual severe PH even after their PTE.

The Use of Nitroprusside in the Treatment of Acute Myocardial Infarction

In 15 patients with acute myocardial infarction, intravenous infusion of the potent vasodilator, nitroprusside, produced an average 50% fall in the elevated left ventricular filling pressure and a modest reduction in arterial pressure (average, 15.5%) without a change in heart rate. Careful dose adjustment in several patients resulted in a significant fall in left ventricular filling pressure with little or no change in arterial pressure. Cardiac output consistently rose during nitroprusside infusion in patients with clinical signs of left ventricular failure or shock and low control cardiac output, whereas output changed little on those patients with normal cardiac index. A fall in pressure time per minute as well as the fall in left ventricular filling pressure indicated a reduction in myocardial oxygen consumption during the vasodilator infusion. Drug infusion was usually accompanied by subjective improvement, including relief of dyspnea and of chest pain, and reduction in ventricular irritability. These data suggest, that vasodilator therapy, by reducing left ventricular afterload, can improve left ventricular performance in patients with acute myocardial infarction. Such treatment may be a rational approach to the management of patients with heart failure, pulmonary edema, or early shock. 1 Commentary Until the publication of this manuscript, little attention was given to the reduction of the peripheral vascular resistance as a method of improving left ventricular function in patients with acute myocardial infarction. The concern about using vasodilators were either that reducing blood pressure will decrease coronary blood flow or because physicians were concerned that a decrease in blood pressure was associated with clinical deterioration. However, Dr Cohn and his colleagues hypothesized that increases in blood pressure in a failing ventricle is harmful and therefore a control decrease in blood pressure may be expected to decrease left ventricular filling pressure. This is the reason why they used nitroprusside in infusion rates between 30 lg ⁄min and 150 lg ⁄min to control blood pressure in these patients and demonstrated a striking fall in left ventricular filling pressure with very little decrease in blood pressure. They also caution that if patients are hypotensive, one should be careful. In this manuscript, the authors put forth a possible mechanism for why nitroprusside may be beneficial to these patients in decreasing left ventricular afterload more than left ventricular preload. In addition, they suggested that compared with inotropic agents, using nitroprusside in patients with acute myocardial infarction reduced left ventricular oxygen consumption. Finally, the authors conclude that nitroprusside may be beneficial in patients with acute pulmonary edema and those with heart failure or early shock. The next historical vignette will discuss the use of nitroprusside in the treatment of refractory heart failure.

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.

Cardiovascular disease in the dialysis population: prognostic significance of arterial disorders

Cardiovascular disease is a major factor in the high mortality of patients with end-stage renal disease, and this population is particularly appropriate to analyse the impact of cardiovascular risk markers on outcome. Cardiovascular risk markers in end-stage renal disease include age, left ventricular mass, carotid intima-media thickness, blood pressure and aortic stiffness (pulse wave velocity). Aortic pulse wave velocity has been shown to be an independent predictor of cardiovascular mortality in patients with end-stage renal disease and the general population. Aortic pulse wave velocity has the highest sensitivity and specificity as a predictor of cardiovascular death in end-stage renal disease patients. Pulse wave velocity is an integrated index of vascular function and structure, and is a major determinant of systolic hypertension, thereby increasing left ventricular afterload, left ventricular hypertrophy and left ventricular oxygen consumption. Decreased diastolic blood pressure, another consequence of arterial stiffening, is associated with decreased coronary perfusion contributing to ischaemic heart disease and evolution of adaptive into maladaptive left ventricular hypertrophy. Aortic stiffness measurements could serve as an important tool in identifying end-stage renal disease patients at higher risk of cardiovascular disease. The ability to identify these patients would lead to better risk stratification and earlier and more cost-effective preventive therapy.

Cardiopulmonary exercise testing in the evaluation of functional capacity after treatment of lymphomas in adults

The present study assessed several parameters of cardiopulmonary function in patients, after treatment for aggressive non-Hodgkin's lymphoma and Hodgkin's disease, to determine the influence of these parameters on patient's performance status. One hundred and six patients (66 male and 40 female) aged 40 ± 15 years were examined 1–2 years (median 14 months) after anticancer treatment. The patients were examined by means of rest and dynamic stress echocardiography and cardiopulmonary exercise. The rest and post-exercise ejection fraction (EF), Doppler parameters of left ventricular diastolic function and peak oxygen consumption (pVO2) were used as parameters of cardiopulmonary performance. The cumulative dose (CD) of doxorubicin (DOX) given was 240 ± 70 (240 mg/m2). Thirty-seven percent of patients received mediastinal irradiation in accordance with the used treatment protocol. Sixty-four patients (60%) experienced fatigue after the treatment. Three patients (3%) demonstrated an decreased EF <50%, 34 (32%) demonstrated impaired diastolic function, 14 (13%) demonstrated decreased pVO2<20 ml/kg/min and 15 (14%) demonstrated a value of pVO2 below the reference value, respectively. None of the patients exhibited clinical signs of heart failure. Apart from three patients with a rest EF<50%, all the other patients responded to stress echocardiography with an increment of EF > 5%. The parameter pVO2 significantly correlated with stress EF (0.58, P < 0.0002). A significant relationship was found with all parameters of diastolic function: to index E/A of diastolic filling (r = 0.67, P < 0.0001), isovolumic relaxation time (r = −0.56, P < 0.0009) and to deceleration time (r = −0.54, P < 0.009), respectively. A negative relationship was found with age (r = −0.74, P < 0.0001), CD of DOX (r = −0.53, P < 0.003) and radiotherapy-involving mediastinum (r = − 0.44, P < 0.04), respectively. Using multivariate analysis, a significant relationship was found between pVO2 and parameters of diastolic filling, age, female sex and CD of DOX, respectively (r = 0.58, P < 0.0001). Diastolic dysfunction was correlated with age, CD of DOX and radiotherapy-involving mediastinum, respectively (r = 0.51, P < 0.01). The results show that diastolic dysfunction was the most affected parameter of cardiopulmonary function in cancer survivors. This parameter negatively influenced cardiopulmonary performance and was significantly correlated with the cumulative dose of doxorubicin given and radiotherapy on mediastinum. Despite a high number of patients experiencing fatigue, the study demonstrates that only a relatively small number of patients show a depressed pVO2 on a cardiopulmonary stress test and other cardiac abnormalities. The results of the tests support the introduction of regular aerobic exercise for cancer survivors to increase their cardiopulmonary performance and well-being. Hypothetically, aerobic training may also positively influence diastolic function. However, this assumption warrants a prospective follow-up.

Nitric oxide contributes to oxygen demand?supply balance in hypoperfused right ventricle

The present study examined the role of nitric oxide (NO) in oxygen demand-supply balance in hypoperfused canine right ventricular myocardium. The right coronary artery of anesthetized, open-chest dogs was perfused at pressures of 80, 60, and 40 mm Hg, and right ventricular myocardial oxygen consumption, right coronary blood flow and other hemodynamic and cardiac function variables were measured. Right ventricular mechanical function was indexed as the product of heart rate x peak right ventricular systolic pressure x right ventricular dP/dt(max). NO synthesis blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 150 mug/min) was infused into the right coronary artery to block NO synthesis. Neither hypoperfusion nor L-NAME altered right ventricular function. Right ventricular myocardial oxygen consumption fell with coronary perfusion pressure, but less steeply after L-NAME, and at all perfusion pressures was elevated above control. The increase in myocardial oxygen consumption in the absence of NO was met by increased oxygen extraction and by non-NO dependent vasodilation, but the relationship between flow and oxygen consumption was displaced downward after L-NAME. As right coronary perfusion pressure was reduced, the relationship between right ventricular oxygen consumption and right coronary venous PO(2) became steeper after L-NAME, and right coronary venous PO(2) was significantly reduced. During right coronary hypoperfusion, right ventricular function is well maintained, but myocardial oxygen consumption falls, reflecting an increase in oxygen utilization efficiency. NO contributes to this adaptation to hypoperfusion by restraining myocardial oxygen consumption, and by promoting coronary vasodilation with less severe reduction in myocardial PO(2). NO has an important role in right ventricular oxygen demand-supply balance when right coronary perfusion pressure is reduced.

Myocardial O2 consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2 delivery.

Myocardial blood flow is unevenly distributed, but the cause of this heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of oxygen demand. The aim of the present study was to assess the relation between oxygen consumption and blood flow in small tissue regions in porcine left ventricle. In seven male, anesthetized, open-chest pigs, local oxygen consumption was quantitated by computational model analysis of the incorporation of 13C in glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate into the left anterior descending coronary artery. Blood flow was measured with radioactive microspheres before and during acetate infusion. High-resolution nuclear magnetic resonance 13C spectra were obtained from extracts of tissue samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean regional myocardial blood flow was stable [5.0 +/- 1.6 (SD) and 5.0 +/- 1.4 ml.min(-1).g dry wt(-1) before and after 30 min of acetate infusion, respectively]. Mean left ventricular oxygen consumption measured with the NMR method was 18.6 +/- 7.7 micromol.min(-1).g dry wt(-1) and correlated well (r = 0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 +/- 4.7 micromol.min(-1).g dry wt(-1)). Local blood flow and oxygen consumption were significantly correlated (r = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand.

Glucose-insulin-potassium solution improves left ventricular energetics in chronic ovine diabetes

Background Therapeutic modulation of myocardial metabolism improves outcomes in diabetic patients following myocardial infarction and coronary artery surgery. However, the mechanism of this beneficial effect has not been fully elucidated. This study evaluated the effect of glucose-insulin-potassium solution (GIK) on left ventricular (LV) energetics and oxygen utilization efficiency in a chronic ovine model of diabetes. Methods Diabetes was induced in sheep with streptozotocin. Experiments were performed following 12 months untreated diabetes (n = 6) and in controls (n = 6). Open-chest anesthetized sheep were instrumented to determine the LV pressure-volume relationship, oxygen consumption, and free fatty acid uptake. Glucose-insulin-potassium was infused at 1.5 mL · kg −1 · h −1 for 60 minutes and assessment repeated. Results Glucose-insulin-potassium decreased LV free fatty acid uptake in control: 0.090 ± 0.047 μg/beat/100 g to 0.024 ± 0.022 μg/beat/100 g, p = 0.02 and diabetes: 0.33 ± 0.32 μg/beat/100 g to 0.11 ± 0.13 μg/beat/100 g, p = 0.04. Similarly, GIK decreased unloaded left ventricular oxygen consumption (LVVO 2) in both control (0.42 ± 0.05 to 0.37 ± 0.13J/beat/100 g, p < 0.001) and diabetic sheep (0.40 ± 0.24 to 0.23 ± 0.23J/beat/100 g, p < 0.001). The slope of the LVVO 2-pressure-volume area relation (contractile efficiency) was unchanged in either group. Glucose-insulin-potassium improved LV contractility 58% ± 37% ( p = 0.005) and stroke work efficiency 18% ± 10% ( p = 0.009) in diabetic animals but not controls. Therefore, oxygen utilization efficiency (stroke work-LVVO 2) increased only in diabetic animals (16.6% ± 4.8% to 26.9% ± 3.6%, p = 0.002) following GIK. Conclusions This study provides in vivo evidence that GIK improves LV energetics in diabetes. Oxygen utilization efficiency is improved as a result of improved stroke work efficiency and decreased unloaded LVVO 2. Improved efficiency of oxygen utilization provides a physiologic rationale for the beneficial effect of GIK in diabetic patients.

Myocardial efficiency during levosimendan infusion

Levosimendan (LS) is a novel agent indicated for the treatment of acute decompensated heart failure. It has a dual mechanism of action, increasing cardiac contractility without increasing myocardial oxygen demand as well as demonstrating vasodilator properties. This double-blind, randomised, cross-over trial was conducted to assess the effects of LS on myocardial energetics in patients (n = 8) with New York Heart Association functional class III and IV heart failure. Patients initially received either placebo or intravenous LS (18 μg/kg bolus, followed by a continuous infusion of 0.3 μg/kg/min for 5 hours). The following day, patients who had received LS were given placebo and vice versa. Cardiac loading conditions and cardiac output (CO) were assessed using a Swan-Ganz catheter, thermodilution and echocardiography. Dynamic positron emission tomography (PET) with 11C-acetate and 15O-H2O was used to measure myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF), respectively. Myocardial efficiency was calculated as (heart rate × stroke volume × arterial pressure) / ventricular oxygen consumption. CO increased by 32% (P = 0.002) in patients receiving LS, mainly because of an increase in stroke volume. LS significantly reduced pulmonary capillary wedge pressure by 29% (P = 0.013), systemic vascular resistance by 26% (P < 0.001) and pulmonary vascular resistance by 28% (P = 0.025). Mean MBF was 0.76 ml/min/g with placebo and 1.02 ml/min/g with LS (P = 0.033). LS did not increase MVO2 significantly (8%). Left ventricular efficiency was comparable in LS-treated and placebo-treated patients, while right ventricular efficiency was improved by 24% (P = 0.012) with LS. In conclusion, LS as well as having beneficial haemodynamic effects, also has an energetically favourable profile.

Role of ketone bodies in perinatal myocardial energy metabolism

Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not available as an energy substrate for the fetal heart; however, when LCFA are supplied artificially in near-term fetal lambs, they are readily oxidized. Hence the myocardium has no limitation to its ability to use LCFA before birth. After birth, lactate remains an important energy source for the myocardium, whereas the contribution of glucose to myocardial energy production decreases despite an increase in the supply of glucose. The oxidation of ketone bodies increases after birth in relation to an increase in supply. However, ketone bodies account for only 7% of left ventricular oxygen consumption. The supply and contribution of LCFA to the myocardium increases after birth; the oxidation of LCFA accounts for most of the left ventricular oxygen consumption. Hence the role of ketone bodies in myocardial metabolism is limited. However, there are interesting observations on interference between the uptake of different substrates and the release of ketone bodies, which might have consequences for our interpretation of ketone body utilization.