Ischemic preconditioning, cardioplegia or both? Differing approaches to myocardial and vascular protection

Abstract

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.