Ventricular Oxidative Metabolism Research Articles

Exhaled Acetone and Pentane in Patients Undergoing Cardiopulmonary Exercise Testing

Introduction: Pentane is generated from the perioxidation reaction of free radicals with cellular membrane lipids, and may be a marker of inflammation. On the other hand, acetone is synthesized by liver cells by the decarboxylation of excess acetyl-CoA via fatty acid β-oxidation. Both pentane and acetone are readily detectable as volatile organic compounds in exhaled breath. Since prior studies have implicated that minute ventilation/carbon dioxide production (VE/VCO2) slope can be associated with elevated right ventricular oxidative metabolism (Ukkonen et al, Eur J Heart Fail 2008), we sought to investigate the relationships between exhaled pentane and acetone and dynamic nature ofmeasures of cardiopulmonary exercise testing (CPET). with sampling of VOCs. Traditional parameters of CPET such as minute ventilation/carbon dioxide production (Ve/VCO2) and peak oxygen consumption (peak VO2) are used as indicators of severity in heart failure. Methods: In a cohort of 50 patients undergoing CPET with a history of heart failure, exhaled levels of acetone and pentane were collected before and after exercise stress testing. SIFT-MS mass spectrometry was used to quantify twenty-two VOCs in the breath sample. Results: To determine if levels of exhaled VOCs correlated with traditional clinical indicators of heart failure severity, such asIn our study cohort (mean age 59 + /- 6 years, 70% male, mean LVEF 32%), we observed that compared to those with below median Ve/VCO2 (</=35.5), patients with above median Ve/VCO2 (>35.5) had significantly higher median initial resting exhaled acetone levels (211.95 ppb vs 118.19 ppb, P = .034), as well as significantly higher initial resting pentane levels (15.95ppb vs 11.68 ppn, P = .049). Post- exercise median level of acetone was also significantly higher in Group C compared to Group Dthose with above median Ve/VCO2. In contrast, baseline and post-exercise pentane and acetone were similar between those with higher vesus lower peak VO2. Summary: Baseline exhaled pentane and acetone levels were elevated in those with higher VE/VCO2 levels but not in those with lower peak VO2 levels. These findings corborrated with prior reports implicating elevated VE/VCO2 slope with elevated right ventricular oxidative metabolism.

Right Ventricular Energetics in Patients With Hypertrophic Cardiomyopathy and the Effect of Alcohol Septal Ablation

Diastolic dysfunction in hypertrophic cardiomyopathy (HCM) is accompanied by augmented left ventricular (LV) end-diastolic pressure, above all in the presence of LV outflow tract (LVOT) obstruction. Increased back-pressure may augment right ventricular (RV) afterload and induce an oxidative metabolic imbalance between the 2 ventricles. The aim was to study right-to-left ventricular oxidative metabolism in HCM and the effects of alcohol septal ablation (ASA). Twenty-one HCM patients were enrolled. Eleven healthy subjects served as a control group. Subjects underwent 2-dimensional echocardiography to assess LVOT gradient, left atrial size, and diastolic function. [(11)C]Acetate positron-emission tomography (PET) was performed to determine RVk(2) and LVk(2), as a noninvasive index of oxidative metabolism. Seven HCM patients with LVOT obstruction, scheduled to undergo ASA, were also studied 6 months after the procedure. RVk(2) was higher in HCM patients than i control subjects (0.081 ± 0.021 min(-1) vs. 0.061 ± 0.017 min(-1); P= .05), whereas LVk(2) was similar between groups. Consequently, RVk(2)/LVk(2) was increased in the patients (0.85 ± 0.19 vs 0.59± 0.13; P= .004). In patients with obstructive HCM, ASA reduced RVk(2) (0.085 ± 0.021 min(-1) to 0.072 ± 0.022 min(-1); P= .001). Inasmuch as LVk(2) remained unaffected by the procedure, RVk(2)/LVk(2) was decreased after ASA (0.66 ± 0.18; P= .03). The absolute change in LVOT gradient was related to the absolute change in RVk(2) (r= 0.77; P= .044). In HCM patients, RV oxygen consumption is increased in relation to the LV. ASA reduces RV oxygen consumption in HCM patients with LVOT obstruction, suggesting that increased LV loading conditions and diastolic dysfunction play a predominant role in augmenting RV workload in these patients.

Effects of CRT on myocardial innervation, perfusion and metabolism

Heart failure leads to specific changes in cardiac perfusion, metabolism, and innervation. Typically, in the early phase of heart failure, left ventricular (LV) efficiency of forward work is compromised and right ventricular oxidative metabolism increased while resting myocardial perfusion is normal. With advancing disease, LV perfusion and especially the perfusion reserve and oxidative metabolism also become compromised. In addition to the abnormalities linked with the heart failure itself, commonly co-existing left bundle branch block leads to striking, mainly regional imbalance in these parameters. Recent studies have documented that cardiac resynchronization therapy (CRT) has prominent effects on myocardial perfusion, metabolism, and innervation. Cardiac resynchronization therapy normalizes many of these parameters and these changes can be considered to be the signs of successful resynchronization. In contrast, a significant number of patients do not respond to CRT. Some of the metabolic parameters, such as existing glucose metabolism as a marker of viability as well as those related to right ventricle function, may also be linked to the response to CRT.

Is ventilatory efficiency (VE/VCO2 slope) associated with right ventricular oxidative metabolism in patients with congestive heart failure?

The relationship between minute ventilation and the rate of CO2 elimination (VE/VCO2 slope) is associated with mortality in patients with congestive heart failure (CHF). The VE/VCO2 slope > or =34 denotes a poor prognosis and has been proposed to reflect abnormalities in pulmonary perfusion. To study whether increased VE/VCO2 slope is associated with elevated right ventricular (RV) oxidative metabolism relative to the left ventricle (LV). 21 patients with stable NYHA II-III CHF underwent symptom limited cardiopulmonary exercise testing. Dynamic [(11)C]acetate positron emission tomography (PET) was used to measure oxidative metabolism (k(mono)) of the LV and RV. Corrected RV oxidative metabolism (RVOx) was calculated as RV/LV k(mono) ratio. Peak VO2 was 16.2+/-4.1 ml/min/kg and the VE/VCO2 slope was 33.4+/-6.1. LV and RV k(mono) were 0.046+/-0.009 and 0.037+/-0.007 min(-1), respectively, with a RVOx of 0.83+/-0.17. There was a good correlation between RVOx and the VE/VCO2 slope (r=0.61, p=0.0034). RVOx was 0.77+/-0.16 in patients with a VE/VCO2 slope <34 and 0.93+/-0.16 in patients with VE/VCO2 slope > or =34 (p=0.047). RVOx correlates with VE/VCO2 slope in CHF patients. This supports the hypothesis that pulmonary vascular resistance is a determinant of the VE/VCO2 slope.

Myocardial perfusion reserve and oxidative metabolism contribute to exercise capacity in patients with dilated cardiomyopathy

Exercise intolerance is a hallmark symptom in patients with heart failure; however, myocardial factors contributing to the limited exercise capacity are not fully characterized. Twenty patients with stable heart failure resulting from idiopathic dilated cardiomyopathy (DCM) and 13 controls were studied. Myocardial perfusion, biventricular oxidative metabolism, and insulin-stimulated glucose uptake were measured using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate, and [(18)F]FDG. Hyperemic perfusion and perfusion reserve were significantly lower in the DCM patients compared with the healthy subjects. There was no difference in left ventricular oxidative metabolism between the 2 groups; however, the patients had a 19% higher right ventricular oxidative metabolism (P=.005). Consequently, the ratio of right to left ventricular oxidative metabolism was also higher (31%) in the patients. There was a strong inverse association between decreased exercise capacity and the ratio of right to left ventricular oxidative metabolism (r=-.68, P<.01) and a positive association with myocardial perfusion reserve (r=.62, P<.01) in the patient group. These 2 parameters along with resting left ventricular work explained 57% of the variability in peak exercise capacity. Impaired perfusion reserve and an exaggerated imbalance in right to left ventricular oxidative metabolism appear to significantly contribute to the impaired exercise capacity in these DCM patients.

804-4 The relationship between minute ventilation and the rate of CO2elimination reflects the right ventricular oxidative metabolism in heart failure

804-4 The relationship between minute ventilation and the rate of CO2elimination reflects the right ventricular oxidative metabolism in heart failure

Assessment of right ventricular oxidative metabolism by positron emission tomography with C-11 acetate in aortic valve disease

Evaluation of right ventricular (RV) oxidative metabolism is limited by the inability to easily determine oxygen extraction by the RV myocardium and the complex morphology of this ventricle. Because left ventricular C-11 clearance rate constants closely correlate with myocardial oxygen consumption, it was postulated that C-11 clearance rate constants for the RV free wall should also reflect its oxygen consumption. Therefore, RV C-11 clearance rate constants were compared with RV loading in 21 patients with aortic valve disease to assess the possible use of this technique for noninvasive evaluation of RV oxidative metabolism. RV free wall C-11 clearance rate constants correlated with the product of systolic pulmonary artery pressure and heart rate for all patients (r = 0.65, p = 0.002), but the relation was stronger if 2 patients with overt RV dysfunction were excluded (r = 0.83, p = 0.001). On the basis of mean pulmonary artery pressures, patients were stratified into subgroups with normal (group I, n = 8) and elevated (group II, n = 13) pulmonary pressures and were compared with 10 normal control subjects. RV C-11 clearance rate constants were significantly higher in group II than in group I and in normal control subjects (p less than 0.05). These data suggest that RV C-11 acetate clearance rate constants can provide noninvasive evaluation of RV oxidative metabolism. This technique may allow serial assessment of RV performance in various cardiac and pulmonary diseases, and particularly of changes associated with therapeutic interventions.

Interrelationship of architecture and function of the right ventricle.

Interrelationship of architecture and function of the right ventricle.