Browsing by Subject "mongrel dogs"
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Item Dobutamine Increases Mechanical Function and Cytosolic Phosphorylation Potential During Moderate Right Ventricular Hypoperfusion(2000-08-01) Yi, Kun Don; H. Fred Downey; Robert Mallet; Eugene E. QuistYi, Kun Don. Dobutamine increases mechanical function and cytosolic phosphorylation potential during moderate right ventricular hypoperfusion Master of Science (Biomedical Sciences), August, 2000, 101 pp, 4 tables, 18 figures, references, 108 titles. This study was conducted to investigate the functional and metabolic effects of regional inotropic stimulation with dobutamine during right ventricular (RV) hypoperfusion. Right coronary perfusion pressure was incrementally lowered to 40 mmHg from 100 mmHg, and two-doses of dobutamine (0.01 and 0.06 μg/kg/min) were continuously infused for 15 min into the right coronary artery in pentobarbital sodium-anesthetized mongrel dogs of either sex. Myocardial energy metabolites, glycolytic intermediates, glycogen, and phosphorylation potential were measured in freeze-clamped RV biopsies. RV hypoperfusion caused a 54% decrease in right coronary blood flow, a decrease in lactate uptake, and an increase in glucose uptake. Systolic segment shortening, isometric force, MVO2, and oxygen utilization efficiency (O2UE: power/MVO2) decreased significantly. Energy reserves were unaffected by the hypoperfusion. Low-dose dobutamine during hypoperfusion improved regional mechanical function without increasing MVO2, and thus, improved O2UE. Remarkably, low-dose dobutamine markedly increased phosphocreatine content and phosphorylation potential. In contrast, high-dose dobutamine produced only transient improvements in function and efficiency and sharp decreases in energy reserves. Analysis of glycolytic intermediates showed a sustained augmentation of glycolysis during low-dose dobutamine, but glycolysis was limited by high-dose dobutamine at the level of glyceraldehyde-3-phosphate dehydrogenase. Dobutamine is capable of improving both contractile function and cellular energetics in underperfused RV myocardium at low but not high dose dobutamine. Therefore, dosage should be carefully selected.Item Hypoxic Conditioning Suppresses Cytotoxic Nitric Oxide Production Upon Myocardial Reperfusion(2007-05-01) Ryou, Myoung-Gwi; H. Fred Downey; Rong Ma; Raghu KrishnamoortyRyou, Myoung-gwi. Hypoxia conditioning suppresses nitric oxide production upon myocardial reperfusion. Master of Science (Integrative Physiology), May 2007, 61pp, 2 tables, 9 figures. This study was conducted in mongrel dogs to test the hypothesis that 20 d normobaric intermittent hypoxic conditioning (IHC) evokes cardioprotective adaptations of the myocardial nitric oxide synthase (NOS) system. Specifically, the proposal that IHC suppresses myocardial NOS activity sufficiently to dampen the cytotoxic burst of NO formation upon reperfusion of ischemic myocardium was tested. Mongrel dogs were conditioned by a 20 d program of IHC (FIO2 9.5-10%; 5-10 min hypoxia/cycle, 5-8 cycles/d with intervening 4 min normoxia). On day 21, ventricular myocardium was sampled for measuring NOS activity (colorimetric assay) and endothelial NOS (eNOS) content (immunoblot). In separate experiments, myocardial nitrite (NO2) release, an stable product of NO oxidation, was measured at baseline and during reperfusion following 1 h occlusion of the left anterior descending coronary artery (LAD). Values in IHC dogs were compared with respective values in non-conditioned, control dogs. IHC lowered left and right ventricular NOS activity by 60%, from 100-115 to 40-45 mU/g protein (P [less than] 0.01), and decreased eNOS content by 30%. IHC dampened cumulative NO2 release during the first 5 min reperfusion from 32 ± 7 to 14 ± 2 μmol/g (P [less than] 0.05), but did not alter hyperemic LAD flow (15 ± 2 vs. 13 ± 2 ml/g). Attenuation of the NOS/NO system may contribute to IHC-induced protection of myocardium from ischemia-reperfusion injury.Item Leucine-Enkephalin and Sympathetic Control of Heart Rate(2001-12-01) Stanfill, Amber; Caffrey, James L.; Downey, H. Fred; Shi, XiangrongStanfill, Amber A., Leucine-enkephalin and Sympathetic Control of Heart Rate. Master of Science (Biomedical Sciences), December, 2001, 51 pp., 1 table, 4 figures, references, 48 titles. The following study examined the role of leucine-enkephalin in the sympathetic regulation of the cardiac pacemaker. Leucine-enkephalin (0.3 mM) was administered, by microdialysis into the interstitium of the sinoatrial node in 10 mongrel dogs in conjunction with either sympathetic nerve stimulation or infused norepinephrine. In study one, the right cardiac sympathetic nerves were isolated as they exit the stellate ganglion and stimulated to produce graded (low, 20-30; high 40-50 bpm) increases in heart rate. Once stimulation frequencies were determined, leucine-enkephalin (0.3mM) was added to the dialysis inflow and perfused at 5: 1/min thereafter. The sympathetic stimulations were repeated after 5 and 20 min exposure to leucine-enkephalin. The resulting increases in heart rate during sympathetic stimulation were attenuated at both low (18.2 ±1.3 to 11.4 ±1.4 bpm) and high (45 ±1.5 to 22.8 ±1.5 bpm) frequency stimulation. The degree of inhibition was nearly identical after 20 minutes exposure providing no evidence for a progressively evolving response and for desensitization. Vagal function was also evaluated at 5 and 20 min by stimulating the right cervical vagus at 1 and 3 Hz. Leucine-enkephalin reduced the vagal bradycardia approximately 50% at both time intervals. The administration of the delta-selective opioid antagonist, naltrindole, restored only one third of the sympathetically medicated tachycardia. The same dose of naltrindole completely reversed the coincident vagolytic of leucine-enkephalin. These observations suggested that the sympatholytic effect was either non-opioid or mediated by a different opioid receptor subtype. Study two was conducted to determine if the sympatholytic effect was prejunctional and post-junctional in character. Norepinephrine was added to the dialysis inflow into the SA node in a concentration (6-9 μM) sufficient to produce an intermediate increase in heart rate. The average increase in heart rate was 35.2 ±1.8 bpm. Leucine-enkephalin was then combined with norepinephrine and sympathetic and parasympathetic responses were recorded at 5-min intervals for 20 minutes. The tachycardia mediated by added norepinephrine was unaltered by leucine-enkephalin or the subsequent addition of naltrindole. At the same time intervals, vagal control of heart rate was reduced by more than 50% and then completely restored by naltrindole. When combined with observations in study one, the data support the conclusion that the local nodal sympatholytic effect of leucine-enkephalin was the result of a reduction in the effective interstitial concentration of norepinephrine and not the result of a post-junctional interaction between leucine-enkephalin and norepinephrine.