Kazumi Taki

Cardioprotective effects of various class I antiarrhythmic drugs in canine hearts

This study was designed to clarify the cardioprotective effects of various class I antiarrhythmic drugs, i.e., aprindine, disopyramide, flecainide, lidocaine, mexiletine, pentisomide and propafenone, on the ischemic heart. Sixty-one adult mongrel dogs were classified into eight groups according to premedication: 1) control group, physiologic saline solution was administered intravenously 25 min before left anterior descending coronary artery ligation; 2) aprindine group, 3 mg/kg body weight of aprindine intravenously; 3) disopyramide group, 2 mg/kg of disopyramide intravenously; 4) flecainide group, 2 mg/kg of flecainide intravenously followed by drip infusion of 100 micrograms/kg per min; 5) lidocaine group, 2 mg/kg of lidocaine intravenously followed by drip infusion of 100 micrograms/kg per min; 6) mexiletine group, 3 mg/kg per min of mexiletine intravenously followed by drip infusion of 15 micrograms/kg per min; 7) pentisomide group, 5 mg/kg intravenously; and 8) propafenone group, 2 mg/kg intravenously. Arterial blood pressure and electrocardiogram were monitored throughout the experiment. Two hours after coronary occlusion, the heart was excised. Myocardial mitochondria were prepared and mitochondrial function (the respiratory control index and the rate of oxygen consumption in state III) was measured polarographically. Fractionation of myocardial tissues was performed and the lysosomal enzyme (N-acetyl-beta-glucosaminidase and beta-glucuronidase) activities among fractions were measured. No significant hemodynamic changes were observed compared with the control group except for those in the disopyramide and flecainide groups; that is, decrease in heart rate without changes in blood pressure compared with the control group was observed. All antiarrhythmic drugs effectively prevented the development of ventricular arrhythmias associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of antiarrhythmic agents classified as class III group on ischaemia‐induced myocardial damage in canine hearts

1 The cardioprotective effects of antiarrhythmic agents classified as class III, amiodarone, sotalol and E‐4031, were investigated in anaesthetized dogs. 2 The left anterior descending coronary artery was occluded for 2 h. 3 Heart mitochondria were prepared from both the ischaemic and non‐ischaemic areas, and their function was estimated polarographically. 4 Activities of the lysosmal enzymes, N‐acetyl‐β‐glucosaminidase and β‐glucuronidase, were measured in each fraction. 5 Two hour occlusion induced ventricular arrhythmias, and amiodarone, sotalol and E‐4031 greatly suppressed the development of arrhythmias. 6 Amiodarone, sotalol and E‐4031 significantly protected mitochondria against ischaemia, and prevented ischaemia‐induced leakage of lysosomal enzymes. 7 Antiarrhythmic agents classified as class III show cardioprotective effects, which might participate in their antiarrhythmic effect.

The effects of SUN 1165, a novel sodium channel blocker, on ischemia-induced mitochondrial dysfunction and leakage of lysosomal enzymes in canine hearts.

The cardioprotective effect of SUN 1165, a novel sodium channel blocker, was investigated on ischemic myocardium. Nineteen anesthetized dogs were subjected to 2 hours coronary occlusion, and divided into 2 groups. In the control group, physiological saline was infused. In the SUN 1165 group, 2 mg/kg of SUN 1165 was injected intravenously. Two hours after occlusion, heart mitochondria were prepared from both ischemic and non-ischemic areas in each group, and their functions (RCI and St.III O2) were measured polarographically with succinate as a substrate. Fractionation of myocardial tissue from both non-ischemic and ischemic areas was performed according to the method of Weglicki et al., and the activities of lysosomal enzymes (NAG and beta-gluc) were measured. In the control group, mitochondrial dysfunction and leakage of lysosomal enzymes induced by 2 hours occlusion were observed. Administration of SUN 1165 maintained mitochondrial function, and prevented the leakage of lysosomal enzymes caused by ischemia significantly. These results indicated that SUN 1165 has a cardioprotective effect in ischemic heart.

Effects of neuropeptide Y on lung vascular permeability in the pulmonary circulation of rats

The effects of neuropeptides on the capillary filtration coefficient in the vessels of the pulmonary circulation were examined, using isolated lung perfusion preparations from rats. Neuropeptide Y and neurokinin A elevated the filtration coefficient, and calcitonin gene related peptide diminished it. Neurotensin and substance P did not affect the value at concentrations less than 10(-7) M. The number of extravasated carbon particle deposits subsequent to tracheal application of neuropeptide Y during spontaneous respiration increased in a dose-dependent manner. From these results, we conclude that neuropeptide Y may increase vascular permeability in the pulmonary circulation.

Cerebral blood flow during open-chest cardiac massage with occlusion of the descending aorta in dogs

Cerebral blood flow (CBF) and carotid blood flow (CAF) during open-chest cardiac massage with and without occlusion of the descending aorta was examined in 10 dogs to assess whether they were augmented by occlusion. In control measurements with a normally beating heart, CBF with and without occlusion of the descending aorta were 17.8 +/- 2.3 and 13.8 +/- 2.2 ml/min (+/- S.E.M.), which were not significantly different. Cerebral blood flow during open-chest cardiac massage were 6.1 +/- 1.0 with occlusion and 5.7 +/- 1.0 ml/min without occlusion of the descending aorta, which were also not significantly different. By contrast, CAF increased significantly with occlusion of the descending aorta both during control measurement, with mean increases of 61.1% and 92.2% during open-chest cardiac massage (P = 0.05). While occlusion generally failed to augment CBF; in two dogs resuscitation was successful by manual cardiac massage. With the restoration of cardiac activity it increased immediately to twice that of control blood flow, and then gradually returned to the control level. Based on these observations, it is the authors opinion that every effort should be directed toward the restoration of cardiac activity as quickly as possible during circulatory arrest, and to increase CBF which is essential for neurological recovery.

Differing time courses between Δlactate and mitochondrial respiration during coronary occlusion and after reperfusion in canine hearts

SummaryThe present study was designed to clarify whether or not a difference between arterial and venous lactate (Δlactate) levels is useful for evaluation of mitochondrial function in ischemia-reperfused myocardium. In the first experiment, 12 dogs were divided into 2 groups: 10-min occlusion of the left anterior descending coronary artery (LAD) followed by 10-min reperfusion, or 30-min occlusion followed by 40-min reperfusion, were performed. The lactate levels in the femoral artery and the great cardiac vein were measured enzymatically. ΔLactate was reversed immediately after occlusion. Ten min and 20 min were required for the recovery of Δlactate in the 10-min-occlusion with 10-min-reperfusion, and 30-min-occlusion with 40-min-reperfusion groups, respectively. In the second experiment, 36 dogs were divided into 6 groups: 10-min occlusion of LAD; 10-min occlusion with 10-min reperfusion; 30-min occlusion; and 30-min occlusion with 10-, 20-, or 40-min reperfusion were performed. Mitochondria from normal and occluded or reperfused areas were prepared, and the respiratory function of the mitochondria was measured polarographically. No significant decreases in the mitochondrial function were observed in the 10-min-occlusion, and 10-min-occlusion with 10-min-reperfusion groups. On the other hand, respiratory function of mitochondria was impaired by 30-min occlusion and was not improved by 10- or 20-min reperfusion. Significant recovery in the mitochondrial function was observed after 40-min reperfusion. That is, differing recovery time courses between Δlactate and the mitochondrial function were observed.

Effects of a new nitro compound on the systemic circulatory system in dogs.

The present study was undertaken to evaluate the effects of a newly synthesized nitro compound (E-4701) on the systemic circulatory system with special reference to venous return and vascular compliance. Dogs were anesthetized with sodium pentobarbital. After opening the chest, cannulae were inserted into the superior and inferior vena cavae and into the right atrial appendage. The venous flow from the caval veins was redirected to a blood reservoir with an outlet at a constant height. The blood was pumped into the right atrium at a constant flow rate. E-4701 had a hypotensive effect, and also caused a decrease in reservoir blood volume; i.e., a decrease in venous return. Venous return via the superior vena cava was increased, whereas return via the inferior vena cava was decreased. Similar effects on the systemic circulatory system were observed with nitroprusside. The lowest dose of nitroprusside that caused a significant reduction in blood pressure was the same dose as that which caused a decrease in reservoir blood volume. However, a low dose of E-4701 caused a significant reduction in reservoir blood volume without affecting the systemic blood pressure. Arterial and venous compliances were increased by both E-4701 and nitroprusside. Nitroglycerin and isosorbide dinitrate increased venous compliance. but did not affect arterial compliance. The results suggest that E-4701 caused an almost equipotent reduction in blood pressure and venous return by dilating the arterial and venous vascular beds. The capacitance vessels may be more sensitive to E-4701 than the resistance vessels.