Kolocassides K G, Galiñanes M, Hearse D J
Cardiovascular Research, Rayne Institute, St Thomas' Hospital, London, UK.
J Mol Cell Cardiol. 1996 Mar;28(3):623-34. doi: 10.1006/jmcc.1996.0058.
We compared the anti-ischemic efficacy of cardioplegia and ischemic preconditioning and whether their effects are additive for both myocyte and vascular protection. Isolated blood-perfused rat hearts were subjected to zero flow global ischemia (37 degrees C) for 30 min and reperfusion for 40 min. Left ventricular developed pressure (LVDP) was assessed with an intraventricular balloon. Coronary flow and vascular reactivity (percentage change in coronary vascular resistance, CVR) to 5-hydroxytryptamine (5HT; 0.0215 mmol/l) and sodium nitroprusside (SNP; 0.0160 mmol/l) were measured. Study 1; "dose" effect of preconditioning in four groups (n = 6/group): (i) controls (unprotected ischemia) and (ii, iii and iv) 1, 2, or 3 cycles of preconditioning (3 min ischemia + 3 min reperfusion) prior to ischemia. LVDP recovery in controls was 31 +/- 9%; preconditioning by 1, 2 or 3 cycles afforded significant (P < 0.05) improvements (58 +/- 6%, 54 +/- 3% and 54 +/- 5%, respectively). Overall, the pre-ischemic change of CVR to SNP was -28 +/- 1%. The post-ischemic response in controls was -4 +/- 7% (P < 0.05); with 1, 2, or 3 cycles of preconditioning the values were -23 +/- 4%, -24 +/- 5%, and -26 +/- 3%, respectively (P < 0.05 v controls). With 5HT the overall pre-ischemic change in CVR was -18 +/- 2%; after ischemia a vasoconstrictor response was seen in all groups. Study 2: the effect of preconditioning added to cardioplegia with four groups subjected to 35 min ischemia (n = 8/group): (i) controls, (ii) one cycle of preconditioning (3 min ischemia + 3 min reperfusion), (iii) cardioplegia with St Thomas' solution immediately prior to ischemia, and (iv) preconditioning followed by cardioplegia prior to ischemia. The recoveries of LVDP were 26 +/- 6%, 44 +/- 2%, 53 +/- 3% and 54 +/- 4%, respectively (P < 0.05 all interventions v controls). Post-ischemic CVR increased greatly in controls (+ 167 +/- 60% of its pre-ischemic value) but was little changed in groups (ii), (iii), and (iv) (+ 11 +/- 7%, + 27 +/- 10% and -2 +/- 6% respectively; P < 0.05 v controls). The post-ischemic change in CVR to SNP was protected by all interventions (-21 +/- 1%, -21 +/- 1% and -22 +/- 1% v -14 +/- 2% in controls; P < 0.05). Again, the post-ischemic response to 5HT was vasoconstriction in all groups. In conclusion, preconditioning and cardioplegia alone afford similar and substantial protection of post-ischemic contractile and vascular functions. In general, the combination of the two techniques afforded no significant additional protection.
我们比较了心脏停搏液和缺血预处理的抗缺血效果，以及它们对心肌细胞和血管保护作用是否具有相加性。将离体血液灌注大鼠心脏置于37℃零流量全心缺血30分钟，然后再灌注40分钟。用心室内球囊评估左心室舒张末压（LVDP）。测量冠状动脉血流量以及对5-羟色胺（5HT；0.0215 mmol/L）和硝普钠（SNP；0.0160 mmol/L）的血管反应性（冠状动脉血管阻力变化百分比，CVR）。研究1：四组（每组n = 6）预处理的“剂量”效应：（i）对照组（未保护的缺血组）和（ii、iii和iv）在缺血前进行1、2或3个预处理周期（3分钟缺血+ 3分钟再灌注）。对照组LVDP恢复率为31±9%；1、2或3个预处理周期可使恢复率显著提高（P < 0.05）（分别为58±6%、54±3%和54±5%）。总体而言，缺血前CVR对SNP的变化为-28±1%。对照组缺血后反应为-4±7%（P < 0.05）；1、2或3个预处理周期的值分别为-23±4%、-24±5%和-26±3%（与对照组相比P < 0.05）。对于5HT，缺血前CVR的总体变化为-18±2%；缺血后所有组均出现血管收缩反应。研究2：四组（每组n = 8）在35分钟缺血情况下，预处理加心脏停搏液的效果：（i）对照组，（ii）一个预处理周期（3分钟缺血+ 3分钟再灌注），（iii）在缺血前立即用圣托马斯液进行心脏停搏，（iv）在缺血前先进行预处理然后进行心脏停搏。LVDP恢复率分别为26±6%、44±2%、53±3%和54±4%（所有干预组与对照组相比P < 0.05）。对照组缺血后CVR大幅增加（为缺血前值的+ 167±60%），但在（ii）、（iii）和（iv）组变化很小（分别为+ 11±7%、+ 27±10%和-2±6%；与对照组相比P < 0.05）。所有干预措施均能保护缺血后CVR对SNP的变化（分别为-21±1%、-21±1%和-22±1%，对照组为-14±2%；P < 0.05）。同样，所有组缺血后对5HT的反应均为血管收缩。总之，单独的预处理和心脏停搏液对缺血后收缩和血管功能提供了相似且显著的保护。一般来说，两种技术联合使用并没有提供显著的额外保护。
