The Effects Of Carvedilol On L-type Calcium Current (I_{Ca, L}) During Ischemia/Reperfusion In Rabbits' Ventricular Myocytes With Or Without Diabetes

Objective: Coronary Heart Disease (CHD) has become "the biggest killer" ofthe pubic health. Especially when the patients are with diabetes, they have biggerrisks. The most severe outcome of the CHD is the ischemia/reperfusion injury in themyocardial infarction, which can induce the fatal arrhythmia and pump failurethrough the abnormality of the electrical and machinery activities. So it is the hottopic to prevent the acute oxidative stress injury activated by ischemia/reperfusion.Carvedilol is the latestβ-receptor blocker, which has the effect ofα-receptorblocker, calcium channel blocker and antioxidation. It has been proved that theantioxidative effect could reduced the ischemia/reperfusion injury of the normal ratmyocardial cells. So, we set up the model of ischemia/reperfusion to research thiseffect on normal and diabetes rabbits' myocardial cells by the change of L-typecalcium channel current (I_Ca,L).Method: There were 2 groups, normal rabbit group (N) and diabetes rabbitgroup (DM), which had 4 sub-group respectively. We used tetraoxypyrimidine tomake the model of diabetes and began the electrophysiologic experiments four weeksafter the model was successfully made. The 4 sub-groups:①control group: per-fused 10 minutes with normal extracellular solution;②ischemia/reperfusion group(IR): perfused 5 minutes with mimic ischemic solution, then perfused 5 minutes withreperfusion solution;③drug-using group (D): perfused 10 minutes with extra-cellular solution containing carvedilol;④drug+ ischemia/reperfusion group (DIR):perfused 5 minutes with mimic carvedilol-ischemic solution, then perfused 5 minuteswith carvedilol-reperfusion solution. We recorded I_Ca,L currents of 0 minute, 5 minuteand 10 minute.Result:Ⅰ.Blood glucose and blood insulin, there were no significantdifferences of blood glucose and insulin in baseline between the 2 groups (P＞0.05);there is no significant difference of blood insulin before and after model-making(P＞0.05); the blood glucose is increased after model-making (P＜0.05).Ⅱ.Thechanges of I_Ca,L current density of normal rabbits, (1) control group: there were no significance in the decrease of current density and the decrease rate (7.3%, P＞0.05),the decrease within 10min could be ignored, (2) IR: the current density decreasedfrom 8.09±1.38 pA/μF to 5.52±1.37 pA/μF after perfused with mimic ischemicsolution (P=0.001); then decreased to 3.984±0.96 pA/μF after perfused withreperfusion solution (0min and 10min P=0.000, 5min and 10min P=0.023), (3) the5min and 10min current density: there were statistic significant differences both afterischemia and after reperfusion (P＜0.05), there was no significant difference afterusing carvedilol (P＞0.05), carvedilol and ischemia/reperfusion had interaction effect(P＜0.05).Ⅲ.The changes of I_Ca,L current density of DM rabbits: (1) control group:there were no significances in the decrease of current density and the decrease rate(6.4%, P＞0.05), the decrease within 10min could be ignored, (2) IR: the currentdensity decreased from 7.594±1.71 pA/μt F to 5.894±1.57 pA/μF after perfused withmimic ischemic solution (P=0.026); then decreased to 4.574±0.84 pA/μF afterperfused with reperfusion solution (0min and 10min P=0.000, 5min and 10minP=0.080), (3) the 5min and 10min current density: there were statistic significantdifferences both after ischemia and after reperfusion (P＜0.05), there was nosignificant difference after using carvedilol (P＞0.05), carvedilol and ischemia/reperfusion had no interaction effect (P＞0.05).Ⅳ. The comparation between the 2groups: there were no significant difference of the I_Ca,L current densities between thecorrespond sub-groups (C,D,IR,DIR) (P＞0.05).Conclusions: (1) There was no significance in blood insulin before and aftermodel-making. And it had the trend of descending. After model-making, the value ofblood sugar increased. (2) There was no significant difference of I_Ca,L current inbaseline between normal and diabetes rabbits. The I_Ca,L of the diabetes rabbits wasslightly smaller than that of the normal rabbits. (3) After ischemia/reperfusion, thecurrent density of normal rabbits was decreased and theⅠ-Ⅴcurve was move up. (4)0.25μM Carvedilol had no effect on either normal rabbits' or diabetes rabbits' cells.(5) 0.25μM Carvedilol could protect the I_Ca,L current of normal rabbits from the isch-emia/reperfusion injury, possibly because of its effect of antioxidation. (6) After ischemia/reperfusion, the current density of DM rabbits was decreased and theⅠ-Ⅴcurve was move up. But there was no significant difference between 5min and 10min.(7) 0.25μM Carvedilol didn't display the protective effect to the I_Ca,L current of DMrabbits cells treated by the ischemia/reperfusion.