Effect of NO donors on LV diastolic function in patients with severe pressure-overload hypertrophy.
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BACKGROUND: Previous experimental studies have shown that nitric oxide (NO) modulates cardiac function by an abbreviation of systolic contraction and an enhancement of diastolic relaxation. However, the response to NO donors of patients with severe pressure-overload hypertrophy and diastolic dysfunction is unknown. METHODS AND RESULTS: Intracoronary NO donors were given to 17 patients with severe aortic stenosis. A dose-response curve was obtained with nitroglycerin (30, 90, and 150 microg) in 11 patients and sodium nitroprusside (1, 2, and 4 microg/min) in 6. Left ventricular (LV) high-fidelity pressure measurements with simultaneous LV angiograms were performed at baseline and after the maximal dose of NO. The dose-response curve for intracoronary NO donors showed a marked fall in LV end-diastolic pressure, from 23 to 14 mm Hg (-39%; P<0.0001), whereas LV peak systolic pressure fell only slightly, from 206 to 196 mm Hg (-4%; P<0.01). End-diastolic chamber stiffness decreased from 0.12 to 0.07 mm Hg/mL (P<0.0001) and end-systolic stiffness from 1.6 to 1.3 mm Hg/mL (P<0.01). Heart rate, right atrial pressure, LV ejection fraction, the time constant of isovolumic pressure decay (tau), and LV filling rates remained unchanged. CONCLUSIONS: In patients with severe pressure-overload hypertrophy, intracoronary NO donors exert a marked decrease in LV end-diastolic pressure without affecting LV systolic pump function. Thus, the hypertrophied myocardium appears to be particularly susceptible to NO donors, with a marked improvement in diastolic function. (+info)
Effects of leukocyte-depleted warm blood cardioplegia on cardiac and endothelial function.
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It has been reported that neutrophils and platelets have deleterious effects on myocardium and endothelium during and after ischemia. In this study we evaluated the effects of a leukocyte-depleting filter (Sepacell PLX, Asahi medical, Tokyo) during warm blood cardioplegia and early reperfusion on cardiac and endothelial function in the blood-perfused rat heart. Hearts (n = 7 per group) from donor rats were excised and perfused with blood at 37 degrees C from a support rat. After 10 min of stabilization, the hearts were arrested for 60 min with warm blood cardioplegia given at 20 min intervals. This was followed by 60 min of reperfusion. A leukocyte-depleting filter was used during the cardioplegia and the initial 10 min of reperfusion in the experimental group (Group F) and it was not used in the control group (Group N). Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dp/dt) and maximum rate of left ventricular pressure fall (-dp/dt) were measured as indices of left ventricular function before and after cardioplegic arrest. Coronary sinus effluent was obtained and the levels of MB isozyme of creatine kinase (CKMB), malondialdehide (MDA), elastase and thromboxane B2 (TXB2) were measured as indices of myocardial and endothelial injury. After 60 min of reperfusion, acetylcholine (Ach.) was administered to the coronary perfusate and the difference of nitric oxide (NO) concentration between inflow and outflow, and coronary blood flow were measured as an indication of endothelial function. Group F showed significantly lower LVEDP than Group N at 10 min of reperfusion. The elastase levels were significantly (p < 0.05) lower and the CKMB levels tended (p < 0.1) to be lower in Group F at 60 min of reperfusion. The administration of Ach. to the coronary perfusate showed significantly (p < 0.05) greater coronary blood flow and NO production in Group F. The results suggested that the use of a leukocyte-depleting filter during warm blood cardioplegia and early reperfusion preserves endothelial function and left ventricular diastolic compliance. The technique may provide beneficial effects by reducing reperfusion injury in patients undergoing cardiac surgery. (+info)
PET imaging of oxidative metabolism abnormalities in sympathetically denervated canine myocardium.
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This study was designed to test the hypothesis that regional sympathetic denervation produces perfusion and metabolic alterations in myocardial tissue under resting conditions. METHODS: PET studies of myocardial sympathetic innervation, myocardial perfusion and oxygen utilization using [11C]hydroxyephedrine (HED), [13N]ammonia and 1-[11C]acetate, respectively, were performed before and approximately 2 and 8 wk after surgical left thoracotomy and regional chemical sympathetic denervation (n = 5). A second group of animals underwent the same surgical procedure but, so that they could serve as a sham control group, were not sympathetically denervated (n = 5). The second group of animals was imaged before and 2 wk after surgery. Images of the retention of [11C]HED taken from 50 to 60 min postinjection were used to differentiate sympathetically innervated and denervated regions of the left ventricle. Regions of interest were defined on polar plots of the [11C]HED retention, including the sympathetically denervated territory and normally innervated regions. Regions defined on the HED polar plots were then transferred to the [13N]ammonia and 1-[11C]acetate image data, and tracer kinetic models were fit to the regional time-activity curves to generate estimates of myocardial perfusion and oxidative metabolism. RESULTS: The average percentage of the left ventricle denervated in the group I animals was 13.1% +/- 7.3%. Significant reductions in oxidative metabolism were observed in the sympathectomized tissue both at 2 and 8 wk after surgery (22% and 15% reductions, respectively). Significant alterations in regional perfusion were not observed. No significant changes in oxidative metabolism or perfusion were observed in the sham control group. CONCLUSION: Regional sympathetic denervation alters oxidative metabolism but not perfusion in the denervated region of the heart. (+info)
Iterative reconstruction based on median root prior in quantification of myocardial blood flow and oxygen metabolism.
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The aim of this study was to compare reproducibility and accuracy of two reconstruction methods in quantification of myocardial blood flow and oxygen metabolism with 15O-labeled tracers and PET. A new iterative Bayesian reconstruction method based on median root prior (MRP) was compared with filtered backprojection (FBP) reconstruction method, which is traditionally used for image reconstruction in PET studies. METHODS: Regional myocardial blood flow (rMBF), oxygen extraction fraction (rOEF) and myocardial metabolic rate of oxygen consumption (rMMRO2) were quantified from images reconstructed in 27 subjects using both MRP and FBP methods. For each subject, regions of interest (ROIs) were drawn on the lateral, anterior and septal regions on four planes. To test reproducibility, the ROI drawing procedure was repeated. By using two sets of ROIs, variability was evaluated from images reconstructed with the MRP and the FBP methods. RESULTS: Correlation coefficients of mean values of rMBF, rOEF and rMMRO2 were significantly higher in the images reconstructed with the MRP reconstruction method compared with the images reconstructed with the FBP method (rMBF: MRP r = 0.896 versus FBP r = 0.737, P < 0.001; rOEF: 0.915 versus 0.855, P < 0.001; rMMRO2: 0.954 versus 0.885, P < 0.001). Coefficient of variation for each parameter was significantly lower in MRP images than in FBP images (rMBF: MRP 23.5% +/- 11.3% versus FBP 30.1% +/- 14.7%, P < 0.001; rOEF: 21.0% +/- 11.1% versus 32.1% +/- 19.8%, P < 0.001; rMMRO2: 23.1% +/- 13.2% versus 30.3% +/- 19.1%, P < 0.001). CONCLUSION: The MRP reconstruction method provides higher reproducibility and lower variability in the quantitative myocardial parameters when compared with the FBP method. This study shows that the new MRP reconstruction method improves accuracy and stability of clinical quantification of myocardial blood flow and oxygen metabolism with 15O and PET. (+info)
Effects of sevoflurane on regional myocardial blood flow distribution: quantification with myocardial contrast echocardiography.
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BACKGROUND: Using myocardial contrast echocardiography, the authors tried to determine whether sevoflurane causes myocardial blood maldistribution in humans and dogs. METHODS: In animal experiments, 15 mongrel dogs were organized into dipyridamole (n = 6) and sevoflurane (n = 9) groups. Sonicated albumin was infused into the left main coronary artery. The peak gray level corrected for background was analyzed at the following intervals: (1) at baseline, (2) after stenosis of the left circumflex coronary artery (blood flow reduced by 40%), (3) after administration of dipyridamole (1 mg/kg given intravenously) or sevoflurane (1 minimum alveolar concentration) during stenosis, and (4) after phenylephrine during stenosis and administration of dipyridamole or sevoflurane. In human studies, nine patients undergoing coronary artery bypass grafting were studied. During partial extracorporeal circulation, the peak gray level was analyzed before and 20 min after sevoflurane (1 minimum alveolar concentration). RESULTS: In animal experiments, dipyridamole decreased significantly the inner:outer ratio of the peak gray level in the ischemic area and the ischemic:normal ratio of the peak gray level. After arterial pressure was restored with phenylephrine, neither the inner:outer ratio nor the ischemic:normal ratio improved. In contrast, after sevoflurane administration, the inner:outer ratio and the ischemic:normal ratio remained unchanged, but these increased with phenylephrine. In human studies, sevoflurane did not change the inner:outer ratio in the area supplied by the most stenotic coronary artery. CONCLUSION: These results suggest that dipyridamole, a potent coronary vasodilator, produces maldistribution of coronary blood flow in our dog models, whereas sevoflurane does not do this in animal or human studies. (+info)
Consumption of vitamin E in coronary circulation in patients with variant angina.
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OBJECTIVES: The plasma status of vitamin E has been suggested to be linked to the activity of coronary artery spasm. This study was designed to determine whether vitamin E is actually consumed in the coronary circulation in patients with active variant angina having repetitive spasm-induced transient myocardial ischemia and reperfusion. METHODS: Blood samples were obtained simultaneously from the aortic root, coronary sinus and right atrium in 12 patients with variant angina due to spasm of the left coronary artery, nine patients with stable effort angina and nine control subjects. Plasma vitamin E (alpha- and gamma-tocopherol) concentrations were determined by use of high-performance liquid chromatography and plasma lipid peroxides were measured as thiobarbituric acid-reactive substances (TBARS). RESULTS: At baseline, both plasma alpha- (p < 0.01) and gamma- (p < 0.05) tocopherol levels were significantly lower in the coronary sinus (5.50 +/- 0.50 and 0.55 +/- 0.07 mg/l, mean +/- SEM) than in the aortic root (6.63 +/- 0.57 and 0.63 +/- 0.08 mg/l) and also in the right atrium (6.44 +/- 0.61 and 0.63 +/- 0.09 mg/l) in the variant angina group. The TBARS level was significantly (p < 0.05) higher in the coronary sinus than in the aortic in this group. In contrast, these levels were not significantly different between the samples from the coronary sinus and the aortic root or the right atrium in the control group and also in the stable effort angina group. The coronary sinus-aortic difference in plasma vitamin E levels in the variant angina group was not significantly altered after left coronary artery spasm induced by intracoronary injection of acetylcholine. Also, the plasma vitamin E levels in the aortic root, coronary sinus and right atrium all remained unchanged in the stable effort angina group after pacing-induced angina and in the control group after intracoronary administration of acetylcholine. CONCLUSIONS: Transcardiac reduction in plasma vitamin E concentrations concomitant with lipid peroxide formation was demonstrated in patients with active variant angina, suggesting actual consumption of this major endogenous antioxidant. Oxidative stress and vitamin E exhaustion may be involved in the pathogenesis of coronary artery spasm. (+info)
Myocardial ischaemia in children with isolated ventricular non-compaction.
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AIMS: Isolated ventricular non-compaction is a rare congenital cardiomyopathy with a high morbidity and mortality due to malignant arrhythmias and pump failure. Areas affected by non-compaction are characterized by increased trabecularization and deep inter-trabecular spaces. We hypothesized perfusion defects in these areas and performed positron emission tomography to evaluate the myocardial perfusion in non-compacted areas. METHODS AND RESULTS: Five children (age 10-14 years) with isolated ventricular non-compaction underwent positron emission tomography using N-13-ammonia as flow marker and intravenous dipyridamole for stress testing. Myocardial blood flow was quantified using the positron emission tomography time-activity curves in non-compacted areas and normal myocardium, which were diagnosed by echocardiography, magnetic resonance imaging, and angiography. Coronary angiography, performed in two children with extensive forms of left ventricular non-compaction, demonstrated normal coronary arteries. Myocardial blood flow measurements at rest and after dipyridamole application demonstrated 16-33% and 32-57% perfusion impairment, respectively, in non-compacted areas compared to normal myocardium. Areas of restricted myocardial perfusion corresponded well to the non-compacted areas, defined echographically and by magnetic resonance imaging. CONCLUSION: Positron emission tomography demonstrates restricted myocardial perfusion and decreased flow reserve in areas of ventricular non-compaction in children. The myocardial perfusion defects in non-compacted areas may be the cause of myocardial damage and possibly form the basis of arrhythmias and pump failure. (+info)
Role of adenosine in local metabolic coronary vasodilation.
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Adenosine has been postulated to mediate the increase in coronary blood flow when myocardial oxygen consumption is increased. The aim of this study was to evaluate the role of adenosine when myocardial oxygen consumption was augmented by cardiac paired-pulse stimulation without the use of catecholamines. In 10 anesthetized closed-chest dogs, coronary blood flow was measured in the left circumflex coronary artery, and myocardial oxygen consumption was calculated using the arteriovenous oxygen difference. Cardiac interstitial adenosine concentration was estimated from coronary venous and arterial plasma adenosine measurements using a previously described multicompartmental, axially distributed mathematical model. Paired stimulation increased heart rate from 55 to 120 beats/min, increased myocardial oxygen consumption 104%, and increased coronary blood flow 92%, but the estimated interstitial adenosine concentration remained below the threshold for coronary vasodilation. After adenosine-receptor blockade with 8-phenyltheophylline (8-PT), coronary blood flow and myocardial oxygen consumption were not significantly different from control values. Paired-pulse pacing during adenosine-receptor blockade resulted in increases in myocardial oxygen consumption and coronary blood flow similar to the response before 8-PT. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the adenosine blockade by 8-PT. These results demonstrate that adenosine is not required for the local metabolic control of coronary blood flow during pacing-induced increases in myocardial oxygen consumption. (+info)