Biomedical subjects

G J Grover

Publications and source records attributed to G J Grover.

131 records · Page 8Linked to original sources

PubMedDate not supplied

The cardioprotective effects of the thromboxane receptor antagonist SQ 30,741 are not reversed by aspirin.

A previous study indicated that 5 mg/kg aspirin can reverse the cardioprotective effects of thromboxane A2 synthetase inhibitors. We determined in the present study if this dose of aspirin can also reverse the protective effects of the thromboxane A2/PGH2 receptor antagonist SQ 30,741 in the same model of coronary occlusion and reperfusion. Anesthetized dogs were subjected to 90 min of coronary occlusion and 5 h of reperfusion and were treated with vehicle or SQ 30,741 (1 mg/kg + 1 mg/kg/h) 10 min after the onset of coronary occlusion. SQ 30,741 was given to dogs pretreated with aspirin (5 mg/kg, 24 h presurgery) or vehicle. SQ 30,741 significantly reduced infarct size compared to vehicle treatment (58% vs 35% of the left ventricular area at risk for vehicle and SQ 30,741 groups respectively) and aspirin did not reverse this. These anti-ischemic effects occurred despite a lack of change in collateral flow. Thus, important differences in mechanism of action between thromboxane synthesis inhibitors and receptor antagonists seem to exist and further work in this area is warranted.

Animals↗

PubMedDate not supplied

Nitroglycerin improves the distribution of regional oxygenation in partially ischemic canine myocardium.

The effect of nitroglycerin administration on regional oxygen supply and consumption of partially ischemic areas of myocardium was investigated in 14 open-chest anesthetized dogs. Flow in the left anterior descending coronary artery (LAD) was reduced by 50% with the aid of a specially designed screw clamp placed below the first bifurcation. Seven animals received nitroglycerin (20 micrograms/kg i.v.) 5 min following partial occlusion. The remaining animals served as controls. Regional blood flow as measured with radioactive microspheres (15 +/- 3 micron in diameter) was determined before and 10 min following partial occlusion. Regional O2 saturations in small arteries and veins were determined using a microspectrophotometric technique. Oxygen supply, A-V O2 difference, and consumption were calculated in both subepicardial and subendocardial regions of ischemic and non-ischemic myocardium after occlusion. Tissue blood flow to the partially occluded regions was reduced by about 40% in both treated and untreated animals. Nitroglycerin prevented a significant reduction in arterial and venous O2 saturation of the partially occluded region. In the occluded subendocardium, nitroglycerin reduced the skewness of the venous O2 saturation distribution. The O2 supply/consumption ratio was significantly improved by nitroglycerin in the ischemic subendocardium, compared with the same region in the control group. It is suggested that nitroglycerin improves the microregional relationship between blood flow and metabolism even in the absence of a change in total regional blood supply.

Animals↗

PubMedDate not supplied

[The effect of K(ATP)-channel activation on the electrical stability of myocardium in rats with postinfarction cardiosclerosis].

Opening of the ATP-dependent K-channels (K(ATP) channels) upon intravenous administration of the cardioselective activator BMS 180448 (3 mg/kg) decreased the ventricular fibrillation threshold (VFT) in rats with postinfarction cardiosclerosis (PIC). Preliminary injection of the selective K(ATP) channel blocker glibenclamide (0.3 mg/kg, i.v.) completely abolished the profibrillatory effect of BMS 180448. At the same time, the mitochondrial K(ATP) channel blocker 5-hydroxydecanoic acid (5 mg/kg) did not influence the proarrhythmogen activity of BMS 180448. Simultaneous administration of the sarcoK(ATP) channel inhibitor HMR 1098 (3 mg/kg) and BMS 180448 increased the VFT up to a level in intact animals. Administration of the mitoK(ATP) channel activator diazoxide (5 mg/kg) after preliminary treatment with guanethidine (50 mg/kg) increased the VFT in rats with PIC. It is concluded that opening of the mitoK(ATP) channels increases the cardiac electrical stability in rats with PIC.

Adenosine Triphosphate↗

PubMedDate not supplied

Effect of beta-adrenoceptor stimulation or blockade on regional myocardial function and regional O2 consumption during myocardial ischemia.

The purpose of this study was to determine the effect of beta-adrenoceptor activation and blockade on the relationship between regional myocardial function and regional O2 consumption in ischemic and nonischemic myocardium. Myocardial regional segmental function was assessed in 28 open chest, anesthetized dogs using subepicardial dimension gauges. Ten min after LAD (left anterior descending coronary artery) occlusion, dogs were given i.v. saline, 2 mg/kg propranolol, 0.2 mg/kg pindolol, or 1 microgram/kg/min isoproterenol. Coronary blood flow was determined using radioactive microspheres before LAD occlusion, 10 min after occlusion, and 2 hr after LAD occlusion. Regional O2 consumption was determined using microspectrophotometry. LAD occlusion did not alter any index of myocardial function measured in the nonischemic region, but in the ischemic region, end systolic length (ESL) was increased 20% while shortening was converted to systolic bulging. No agent resulted in an improved ischemic regional function or an altered O2 consumption during LAD occlusion. In the nonischemic region the per cent shortening was increased 60% with isoproterenol compared to control. Propranolol and pindolol both increased the non-schemic regional ratio of per cent shortening vs O2 consumption significantly, suggesting an improved efficiency while isoproterenol lowered this ratio. When per cent shortening was plotted vs regional O2 consumption for all treatments, a significant linear relationship was observed in the nonischemic region. Thus, no drug treatment used in this study significantly improved central ischemic regional function, or O2 consumption, but both beta-adrenoceptor blockers seemed to result in an improved relationship between segmental shortening and O2 consumption in the nonischemic region.

Adrenergic beta-Agonists↗

PubMedDate not supplied

Effect of hypoxia and adenosine on the microvascular reserve in the rabbit heart.

This study was done to determine if the unperfused reserves of arterioles and capillaries in the rabbit heart can be utilized independently. Anesthetized, open-chest rabbits were subjected to control, hypoxia or adenosine treatment. The animals were given 100 mg/kg FITC-dextran and the hearts were removed and sectioned for analysis of perfused and total arteriolar and capillary morphology. The fluorescence was used to photograph the perfused microvessels and the slides were then stained for visualization of all microvessels. Standard morphometric techniques were used to determine total and perfused morphometric indices for these microvessels. Mean arteriolar total density (Na) was 4.4 arterioles/mm2 for control, adenosine, and hypoxia groups with approximately half (52%) of control arterioles perfused. Most of the adenosine (92%) and hypoxia (82%) group arterioles were perfused. Mean capillary total Na was 2143 capillaries/mm2 for all groups with approximately half (60%) of control capillaries being perfused. Nearly all capillaries were perfused during hypoxia (96%) while the percent perfused capillarity with adenosine (80%) was between those numbers for control and hypoxia groups despite completely perfused arterioles. The arteriolar and capillary reserves can be utilized independently as adenosine treatment resulted in complete arteriolar perfusion while not resulting in complete capillary perfusion.

Adenosine↗