Nicardipine hydrochlorideの虚血心筋保護作用

Protective effect of Nicardipine hydrochloride in the ischemic reperfuised canine myocardium

　虚血心筋は再灌流期に心筋細胞膜のAutoregulationの崩壊^1）により水，電解質の移動に異常がみられ，細胞障害を著しく増強する。特にCa^2＋の流入は，ミトコンドリア内への結晶沈着を起こし，ミトコンドリアの不可逆性障害の原因となる^2）。

　Ca^2＋拮抗剤は，現在数種類のものが臨床上利用されている。抗不整脈効果^3），平滑筋弛緩による冠動脈拡張作用^4）や，同様の機序による降圧効果^5），さらに虚血—再灌流に伴うCa^2＋による心筋障害の防止作用^6〜9）など多彩な薬理臨床効果が判明しつつある。

Twenty-nine anesthetized open chest mongrel dogs were studied to evaluate the effect of nicardipine hydrochloride on the reperfused ischemic myocardium in assessing hemodynamic changes, coronary blood flow by magnetic flow meters, coronary sinus c-AMP and GMP, myocardial ATP and creatine phosphate as well as myocardial water content. Regional ischemia was produced by occlusion of the left anterior descend-ing coronary artery (LAD) for 40 minutes then reperfusion was given for 15 minutes by releasing occlusion of LAD. Nicardipine was given in 10 dogs with a dose of 5 μg/kg, bolus IV 15 minutes prior to LAD occlusion, and then 0.09 μg/kg/min by continuous drip infusion during LAD occlusion and reperfusion. No significant difference in hemo-dynamics and coronary blood flow was documented between control and nicardipine-treated dogs. There is no significant difference in plasma c-AMP and GMP concentration in coronary sinus venous blood between control and nicardipine-treated dogs. However, nicardipine preserved myocardial ATP and creatine phosphate in the ischemic myocardium in significantly higher levels compared to control group. Myocardial edema was signifi-cantly suppressed in nicardipine-treated ischemic myocardium compared to control group.

These results suggest that nicardipine hydro-chloride is effective to preserve high energy stores and viability of cell membranes in the ischemic myocardium without increasing in coronary blood flow.