限制心脏缺血再灌注损伤的多种治疗方法。

Davies James E, Digerness Stanley B, Killingsworth Cheryl R, Zaragoza Corinne, Katholi Charles R, Justice Robert K, Goldberg Steven P, Holman William L

Department of Surgery, University of Alabama, Birmingham, Alabama 35294-0007, USA.

Ann Thorac Surg. 2005 Oct;80(4):1408-16. doi: 10.1016/j.athoracsur.2005.04.022.

BACKGROUND

This study evaluates a multiple treatment approach (ie, pharmacologic preconditioning [diazoxide], sodium-proton exchange inhibition [cariporide], and controlled reperfusion) to improve the outcome from severe cardiac ischemia-reperfusion injury that occurs during a cardiac operation.

METHODS

Five groups of 10 pigs (group 1: control, group 2: diazoxide, group 3: cariporide, group 4: controlled reperfusion, and group 5: combination of diazoxide and cariporide-controlled reperfusion) underwent 75 minutes of left anterior descending occlusion, 1 hour of cardioplegic arrest, and 2 hours of reperfusion. Prior to occlusion, each group received an infusion of vehicle alone (ie, dimethylsulfoxide for the control and the controlled reperfusion groups) or vehicle with drug (ie, diazoxide or cariporide, or both for all other groups). Infarct size (primary outcome) was measured and was normalized to the region at risk. Regional function (secondary outcome) was measured using preload recruitable work area.

RESULTS

Infarct size as a function of area at risk was decreased by cariporide-controlled reperfusion, and combination treatment compared with the control group (14 +/- 6%, 15 +/- 8%, and 9 +/- 4% vs 24 +/- 9%; p < 0.02), and variation in infarct size was decreased by combination treatment compared with the controlled reperfusion group alone (p < 0.02). Recovery of systolic function during reperfusion significantly improved in the left anterior descending region in the cariporide and combination groups compared with the control, controlled reperfusion, or diazoxide groups (group-time effect, p < 0.05).

CONCLUSIONS

Combined use of controlled reperfusion, cariporide, and diazoxide decreases myocyte necrosis and loss of systolic function compared with an untreated control group. Combination treatment has the potential to improve the results of cardiac surgery, however further improvements are needed before clinical application.

背景

本研究评估了一种多治疗方法（即药物预处理[二氮嗪]、钠-质子交换抑制[卡立泊来德]和控制性再灌注），以改善心脏手术期间发生的严重心脏缺血-再灌注损伤的预后。

方法

将五组，每组10头猪（第1组：对照组，第2组：二氮嗪组，第3组：卡立泊来德组，第4组：控制性再灌注组，第5组：二氮嗪与卡立泊来德-控制性再灌注联合组）进行75分钟的左前降支闭塞、1小时的心脏停搏和2小时的再灌注。在闭塞前，每组单独输注载体（即对照组和控制性再灌注组输注二甲亚砜）或载体加药物（即二氮嗪或卡立泊来德，或其他所有组两者都用）。测量梗死面积（主要结局）并将其标准化为危险区域。使用预负荷可募集工作面积测量区域功能（次要结局）。

结果

与对照组相比，卡立泊来德-控制性再灌注组和联合治疗组的梗死面积占危险区域的比例降低（分别为14±6%、15±8%和9±4%，对照组为24±9%；p<0.02），与单独的控制性再灌注组相比，联合治疗组梗死面积的变异性降低（p<0.02）。与对照组、控制性再灌注组或二氮嗪组相比，卡立泊来德组和联合组在再灌注期间左前降支区域的收缩功能恢复明显改善（组-时间效应，p<0.05）。