Shohachi Suzuki

Recovery time course of ventricular vulnerability after coronary reperfusion in relation to mitochondrial function in ischemic myocardium

This experiment was designed to investigate the effect of the duration of occlusion time and the infusion of fatty acid emulsion or that of coenzyme Q10 on myocardial mitochondrial function and on the recovery time course in VMRT following coronary reperfusion. Forty-eight anesthetized mongrel dogs were divided into four groups based on the duration of the occlusion time and the infused drug: Group 1 was the saline + 15-minute occlusion group; Group 2 was the fatty acid emulsion (1 ml./kg.) + 15-minute occlusion group; Group 3 was the saline + 30-minute occlusion group; and Group 4 was the coenzyme Q10 (5 mg./kg.) + 30-minute occlusion group. After the drug administration (saline, fatty acid emulsion, or coenzyme Q10), the left anterior descending coronary artery was ligated for 15 or 30 minutes. In one-half of each group, canine hearts were isolated immediately at 15 or 30 minutes after ligation to prepare myocardial mitochondria. In the other half of each group, the ligation was released, and coronary flow was reperfused. VMRT was measured before, during, and after the ligation. The recovery time course of the saline + 15-minute occlusion group was similar to that of the coenzyme Q10 + 30-minute occlusion group; and the recovery time course of the fatty acid + 15-minute occlusion group was similar to that of the saline + 30-minute occlusion group. This relationship of the two groups was recognized in the mitochondrial damage. It is suggested that mitochondrial damage, in other words, energy supply dysfunction, is one of the determining factors of recovery in VMRT after coronary reperfusion.

Mechanism of free fatty acid-induced arrhythmias

Summary This study was designed to shed light upon the mechanism of free fatty acid-induced arrhythmias, and to examine the effects of carnitine and its derivatives on such arrhythmias. Forty-two mongrel dogs were anesthetized and divided into six groups of seven animals each. The control group received only isotonic saline, while the lipid 1 ml/kg group and lipid 2 ml/kg group received lipid emulsions of 1 ml/kg and 2 ml/kg, respectively. The carnitine, acetylcarnitine or propionylcarnitine groups were given, respectively, 300 mg/kg of D,L-carnitine, 200 mg/kg of acetylcarnitine, and 100 mg/kg of D,L-propionylcarnitine, 10 min before they received 2 ml/kg infusions of lipid emulsion. The ventricular multiple response threshold (VMRT) of the animals was monitored over the course of time, and after the last measurement of VMRT, myocardial mitochondria were prepared, and their Ca ++ -binding activities were measured. Concentrations of acyl-CoA and free L-carnitine in each mitochondrial sample were also measured. There was no significant difference in VMRT between the control group and the lipid 1 ml/kg group. In the lipid 2 ml/kg group, the VMRT was significantly lower than that of the control group, while it was found that premedication with carnitine or its derivatives significantly protected the VMRT against the effects induced by the infusion of 2 ml/kg of lipid emulsion. The mitochondria of the lipid 2 ml/kg group showed a markedly high accumulation of acyl-CoA, along with a concomitant decrease in Ca ++ -binding activity. The 1 ml/kg infusion caused relatively small increase in acyl-CoA and had little effect on mitochondrial Ca ++ -binding activity. The premedication with carnitine or its derivatives prevented the accumulation of acyl-CoA and preserved mitochondrial Ca ++ -binding activity. These results suggest that free fatty acid-induced arrhythmias are closely related to the disturbance of mitochondrial Ca ++ -binding activity induced by the accumulation of acyl-CoA, and that carnitine, especially propionylcarnitine, is effective in preserving the VMRT and mitochondrial Ca ++ -binding activity despite subsequent 2 ml/kg lipid infusion.

Effects of verapamil and propranolol on ventricular vulnerability after coronary reperfusion

This study was designed to determine whether or not verapamil and propranolol affect the lowering of the ventricular multiple response threshold (VMRT) that is seen following release of a previously ligated coronary artery. In mongrel dogs, the left anterior descending coronary artery was occluded for 15 min and then the ligation was released. The dogs were divided into three groups: in the control group, saline was administrated immediately before the release of ligation; in the two other groups, verapamil or propranolol were administrated immediately before the release of ligation. In the control group, VMRT was decreased during coronary occlusion and did not recover immediately after coronary recirculation. That is, significantly lowered values were observed at 5 and 10 min after reperfusion. The administration of verapamil prevented the lowering of VMRT after reperfusion, whereas propranolol had no effect. In all three groups, an increase in the difference of the concentration of K+ between the great cardiac vein and the femoral vein (delta K+) was observed soon after occlusion; however, delta K+ returned to normal soon after reperfusion. These results and the known anti-arrhythmic mechanism of verapamil suggests that Ca++-dependent action potentials might play an important role in lowering VMRT after release of a previously occluded coronary artery, whereas the effects of K+ and catecholamine do not play a role in causing the lowering of VMRT.

An experimental study of release arrhythmia: Occlusion time-dependent changes in ventricular fibrillation threshold

There have been many reports about ventricular arrhythmias during acute coronary occlusion. Nevertheless, it is only recently that interest has been taken in the occurrence of ventricular arrhythmia after reperfusion following coronary occlusion. To investigate the mechanism of the latter kind of arrhythmia, we studied the effect of changing the duration of occlusion time on the recovery time courses of the VMRT (Ventricular Multiple Response Threshold), and of the A-V differences in the serum K+ concentration across the heart. The time course of delta K+ recovered soon after reperfusion, while changes in VMRT needed more time for recovery to the initial state. Concerning heart rate, blood pH, and the levels of Na+, Cl-, and Ca++, no significant changes were detected. There was no relation between the time courses of VMRT and those of the A-V differences in serum K+. Consequently, time courses in VMRT were dependent upon the duration of coronary occlusion time. A possible explanation for these results may be that the longer the duration of the preceding occlusion time, the more severe the myocardial damage due to myocardial ischemia.

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.

Origin of the basal systolic murmurs in mitral stenosis. A study with intracardiac phonocardiography

In order to study the origin of the basal systolic murmurs in mitral stenosis, left and right heart catheterization was performed in 18 patients with mitral stenosis using intracardiac phonocardiography. Our data revealed that the basal systolic murmurs originated in the aorta, the pulmonary artery, and the outflow tract of the right ventricle. In 14 cases, we noted the maximal ejection systolic murmur in the aorta near the aortic valve. However, in two cases, there was a loud systolic murmur in the pulmonary artery. These murmurs occurred in early to mild-systole and were crescendo-decrescendo in configuration. The pitch of the murmur ranged from low to medium frequency in the majority of cases. They are produced by the turbulence of blood flow in the aorta and the pulmonary artery. A late systolic murmur was also recorded in the outflow tract of the right ventricle in two patients. This is thought to occur due to functional or relative infundibular stenosis of the right ventricle. It differs in location and timing from those in the aorta and the pulmonary artery. The outflow tract of the right ventricle is regarded as the third origin of the basal systolic murmur in mitral stenosis.