Kazuhiko Kinoshita

Excess lactate modulates ionic currents and tension components in frog atrial muscle

Abstract Effects of lactate, an end-product of anaerobic metabolism, on electrical and mechanical activities in the myocardium of the bullfrog atrium were studied under voltage clamp and unclamped conditions using the double sucrose-gap method. Lactate (0.1 to 20 m m ), buffered to normal pH (7.4) was introduced into the perfusate. Levels of lactate over 1.0 m m produced a negative inotropic effect accompanied by a biphasic alteration of the action potential, initial transient prolongation and late shortening of the plateau. Voltage clamp studies on the membrane currents isolated in modified Ringer solutions showed that lactate decreased the slow inward calcium current (ICa) but markedly augmented the slow inward sodium current (INas), while the delayed outward current (Ix) was gradually increased. The fast inward sodium current (INaf) and the background current (IKl) remained unchanged. As for the tension under voltage clamp, application of lactate produced an immediate decrease in the ICa-dependent tension, while ICa-independent tonic tension was not modified appreciably. These findings suggest that lactate has a specific action which modulates the ionic currents responsible for cardiac action potential, and that the mode of action of lactate differs from that of protons.

Comparative study of cell saver and ultrafiltration nontransfusion in cardiac surgery

Hemoconcentration for the establishment of no-donor blood transfusion in open heart surgery was assessed in regard to both the saving of protein and platelets and the exclusion of free hemoglobin. Two different types of hemoconcentrator were compared: the ultrafilter (group I, 6 patients) and the Cell Saver (group II, 6 patients). The total serum protein level, expressed as the percent recovery of the preoperative value, after hemoconcentration was significantly higher in group I (group I versus group II: total serum protein, 118% versus 87% [p less than 0.05]; fibrinogen, 77% versus 50% [p less than 0.01]; immunoglobulin, 83% versus 60% [p less than 0.01]). The platelets also seemed to be well preserved after hemoconcentration in group I. Although the exclusion of free hemoglobin from plasma was inferior in group I compared with group II, the postoperative plasma free hemoglobin level did not increase in group I. We conclude that use of the Cell Saver in nontransfusion cardiopulmonary bypass might cause a severe depletion of various proteins and that the ultrafilter is both safer and more useful if employed routinely.

Reperfusion-induced arrhythmias in the conscious rat: A comparative study with three calcium antagonists

The effects of three calcium antagonists (diltiazem, verapamil, and nifedipine) on reperfusion-induced arrhythmias were compared in a conscious rat preparation with coronary artery occlusion and implanted electrocardiogram limb electrodes. Upon reperfusion after a 5-min period of occlusion, all (15/15) untreated control rats exhibited immediate ventricular tachycardia, which rapidly deteriorated to ventricular fibrillation; 87% (13/15) of the rats died as a consequence of these rhythm disturbances. In the groups treated with calcium antagonists, each drug (diltiazem, verapamil, or nifedipine) was given as an intravenous bolus 10 min prior to coronary occlusion (n = 12 in each group). The incidence of ventricular fibrillation was significantly reduced by all three calcium antagonists and this antifibrillatory effect resulted in a significantly lower mortality in all drug-treated groups. With diltiazem (0.5 and 2.0 mg/kg) mortality fell from 87 to 42% (P less than 0.05) and 35% (P less than 0.01), respectively; with verapamil (0.5 and 5.0 mg/kg) it fell to 25% (P less than 0.01) and 0% (P less than 0.001); and with nifedipine (5.0 and 50 micrograms/kg), it fell to 25% (P less than 0.01) and 8% (P less than 0.001). At a dose of 5.0 mg/kg, verapamil caused a large reduction in heart rate both prior to and during coronary occlusion and reperfusion; however, with other doses and drugs no significant changes in heart rate were observed. ST segment elevation during the 5-min ischemic period was reduced by pretreatment with all drugs. In conclusion, in the conscious rat, pretreatment with diltiazem, verapamil, or nifedipine affords some protection against reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

Importance of sodium ions in the protective effects of high-potassium, high-glucose solution on electromechanical activities in the guinea-pig myocardium

The protective effects of high-K, high-glucose solution (GK solution) on electromechanical activity in the isolated guinea-pig ventricular muscle were studied. The basal test solution (basal GK solution) contained 30 mM KCl, 230 mM glucose and 4 mM NaHCO3, that is nominally Ca-free. Various types of GK solutions were also prepared by modifying the composition of this solution. When the muscle was exposed to the basal GK solution, the resting potential fell to about -40 mV, the muscle lost the excitability, and an irreversible contracture gradually developed. This contracture was prevented by elevating [Na]o above 60 mM. Reduction of [K]o to 20 mM, addition of EGTA (0.4 mM), or lowering the temperature (23 degrees C) also suppressed the above contracture. When the GK solution with high Na (106-115 mM NaCl added to basal GK solution in exchange for glucose) was applied, contractures frequently developed upon reintroduction of Tyrode solution (Ca-paradox-like phenomenon). Thus the Ca-free GK solution with 60 mM Na (56 mM NaCl added to basal GK solution in exchange for glucose) induced no contracture, either during or after the test period. Recovery of the action potential after this application was all but complete. On the other hand, addition of 0.9 to 1.8 mM Ca to this solution produced another type of contracture which was sensitive to verapamil. The cardioplegic effects of the Ca-free GK solution with 60 mM Na persisted under hypoxic conditions, and glucose appeared to play a significant role in preventing the hypoxia-related contracture. In contrast, the high-Na (110 mM Na) GK solution containing 0.2 to 0.5 mM Ca and Tyrode solution, both of which produced no contracture under normoxic conditions, did produce contractures under hypoxic conditions. Therefore, Ca-free GK solution containing an appropriate concentration (around 60 mM) of Na may protect the normoxic and hypoxic myocardium against intracellular Ca overload. The related mechanisms involved were discussed with special reference to membrane functions and intracellular Ca-regulating systems.

A new aspect of coronary artery spasm induced by cardiac surgery

Five patients developed coronary artery spasm during open heart surgery in our institute between 1984 and 1988. One patient was undergoing coronary artery bypass grafting and the other four valvular surgery or surgery for congenital heart disease. In one of the patients undergoing non-coronary surgery, the preoperative induction of right coronary artery spasm by ergonovine had been documented angiographically while the remaining three patients did not possess organic or functional coronary disease. All five patients exhibited a sudden onset of hemodynamic collapse with ventricular tachyarrhythmias or ST elevation during the early period of reperfusion, the time to onset being 89.2±84.8 minutes after unclamping of the aorta. In addition, contraction of the right ventricular free wall was severely impaired. Although one patient died due to left ventricular rupture caused by direct cardiac massage, the early mortality thus being 20 per cent, the other four were successfully treated with the intravenous administration of nitroglycerin and diltiazem. Three patients required the assistance of intraaortic balloon pumping for severe cardiac failure. Thus, during open heart surgery, coronary artery spasm can occur even in patients without organic coronary lesions and the possible mechanisms of this condition are discussed herein.

The Protective Effects of Trimetazidine on Normothermic Ischemic Myocardium in Rats

The protective effects of trimetazidine on postischemic cardiac function were studied using isolated working rat heart preparations in which global ischemia had been induced with normothermic cardioplegia. After 30 minutes of reperfusion, following a 25 minutes period of ischemia, the addition of 10−6 M or 10−5 M trimetazidine to the cardioplegic solution significantly increased the per cent recovery of the cardiac output: from 54.8±4.1 per cent in the control group to 81.0±3.2 per cent (p<0.01) and 79.6±4.0 per cent (p<0.01), respectively, although lower (10−7 M) or higher (10−4 M) doses of the drug failed to result in any change. 10−5 M trimetazidine also produced a significantly greater recovery of both the postischemic aortic flow: from 47.8±4.9 per cent to 72.2±3.8 per cent (p<0.01) and the coronary flow: from 80.6±2.9 per cent to 105.2±6.3 per cent (p<0.002). However, trimetazidine did not influence the recovery of either aortic pressure or heart rate. These results suggest that trimetazidine does give some protection to the heart during ischemia and reperfusion.

Analysis of determinants of ventricular fibrillation induced by reperfusion: Dissociation between electrical instability and myocardial damage

To assess the underlying mechanisms of ventricular fibrillation induced by myocardial reperfusion after cardioplegic arrest, 62 patients undergoing an open heart operation were divided into two groups based on the absence (group 1, n = 37) or the development (group 2, n = 25) of reperfusion-induced ventricular fibrillation. There was no close relationship between the incidence of reperfusion-induced ventricular fibrillation and aortic clamp time. On reperfusion, the time to onset of cardiac activity was similar in groups 1 (2.4 +/- 1.8 minutes) and 2 (1.9 +/- 1.1 minutes). At that time, there was no significant difference in values of arterial oxygen and bicarbonate contents, pH, or base excess between the two groups, but myocardial temperature was significantly higher in group 2 (25.6 degrees +/- 3.4 degrees versus 27.6 degrees +/- 2.4 degrees C; p less than 0.05). In addition, serum levels of sodium (123.9 +/- 4.2 versus 126.1 +/- 3.7 mmol/L; p less than 0.05) and calcium (0.80 +/- 0.07 versus 0.84 +/- 0.05 mmol/L; p less than 0.05) were significantly higher and serum potassium levels (3.98 +/- 0.58 versus 3.55 +/- 0.61 mmol/L; p less than 0.02) and the serum potassium to calcium ratio (4.94 +/- 0.90 versus 4.29 +/- 0.72; p less than 0.01) significantly lower in group 2. Postoperative serum levels of the myocardial-specific isoenzyme of creatine kinase and myoglobin were similar in both groups. By multivariate analysis, shorter ischemic time, higher myocardial temperature, higher serum sodium concentration, and lower serum potassium to calcium ratio were found to influence induction of reperfusion-induced ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Double valve replacement for infective endocarditis in a hemodialysis patient: a case report.

A 57-year-old man who was in end stage renal failure underwent an aortic and mitral valve replacement for the progression of cardiac dysfunction, secondary to Staphylococcus aureus infective endocarditis. Cardiac surgery was performed using a Hemo-Concentrator during cardiopulmonary bypass, 82 months following the initiation of hemodialysis. This is the second report in the literature of a successful double valve replacement for infective endocarditis and congestive heart failure in a chronic hemodialysis patient.

Combined Method of Antegrade and Retrograde Cardioplegia in Double Valve Replacement.

大動脈弁と僧帽弁の二弁置換症例を対象に, 心筋保護液の順行性投与 (Ante) 法と逆行性投与 (Retro) 法の心筋保護効果を比較した. Ante 群15例, Retro 群 (Ante 法併用 Retro 法) 13例について, 術前および術中因子, 再灌流後CPK-MB値の推移, 術周期心筋梗塞の頻度, 術後血行動態を検討した. 術前因子は両群間に差を認めなかった. 大動脈遮断中の心筋保護液投与の間隔は Ante 群29.2±4.8分, Retro 群24.0±3.8分と Retro 群にて有意に (p<0.01) 短く, また大動脈遮断時間も Ante 群134±27分, Retro 群119±25分と Retro 群にて短い傾向を認めた. 再灌流6時間でのCPK-MB値はAnte 群120±80IU/l, Retro 群78±50IU/lと Retro 群にて少ない傾向を認めた. 術周期心筋梗塞の頻度と術後血行動態には両群間に差を認めなかった. 以上より弁膜症症例においても, Ante 法併用 Retro 法は Ante 法と同等以上の心筋保護効果を有し, 症例によっては推奨される有用な心筋保護法と考えられた.