Abstract 1422: Postconditioning Does Not Reduce Myocardial Infarct Size in an in-vivo Regional Ischemia Rodent Model
Studies with stuttering reperfusion, postconditioning, consistently showed reductions of necrosis in isolated heart models. There are fewer studies that have examined the effect of postconditioning on in-vivo regional ischemia models, although some have suggested a benefit on infarct size. In our own laboratory postconditioning reliably reduces lethal ventricular arrhythmias in an in-vivo rat model but its effect on necrosis in our model was unknown. Therefore we subjected 20 female rats, anesthetized with ketamine/xylazine, intubated and ventilated, to 30 minutes of proximal left coronary artery occlusion and either 120 minutes of reperfusion (control) or 4 cycles of 10 seconds reperfusion/10 seconds reocclusion (a regimen that previously was reported to have optimal benefits in rats) followed by 120 minutes of reperfusion (postconditioning; PoC). Area at risk (measured with blue dye during brief occlusion) was 31 ± 4% (mean ± SEM) of the left ventricle (LV) in the control group (n =10) and 28 ± 4% in the PoC group (n =10; p =NS). Area of necrosis (by TTC technique) was 26 ± 4% of the risk zone in controls and 37 ± 5% of the risk zone in PoC group (p =NS). We repeated the study in pentobarbital/isofluorane anesthetized rats. Area at risk was 27 ± 3% of the LV in control animals (n =15) and 30 ± 4% in PoC animals (n =15). Infarct size as a percentage of the risk zone was 31 ± 4% in controls versus 27 ± 4% in PoC animals (p =NS). There were no significant differences in hemodynamics or temperature between treatment groups. In a third study ketamine/xylazine anesthetized rats (n =30) were subjected to 45 minutes of coronary occlusion and 120 minutes of reperfusion with and without PoC. Again there was no effect on infarct size (45 ± 5% of risk zone in controls vs. 47 ± 4% in PoC; p =NS). In contrast, preconditioning ischemia in our rat model consistently reduces infarct size by up to 70%.
Conclusion: Postconditioning did not reduce ischemia/reperfusion induced necrosis in an in-vivo rodent model of regional ischemia which contrasts to the consistent infarct sparing effect of preconditioning. While postconditioning would be more practical to administer in a clinical setting compared to preconditioning (requiring pretreatment), it lacked efficacy compared to preconditioning.