Characterisation of the infarct-limiting effect of delayed preconditioning: timecourse and dose-dependency studies in rabbit myocardium

Abstract

The delayed phase ('second window') of protection induced by ischemic preconditioning in rabbit heart is observed as enhanced resilience to infarction 24 hours after repetitive brief cycles of ischemia. Here we provide a fuller physiological characterisation of this phenomenon in the open-chest rabbit model, examining temporal characteristics and dose-dependency of this adaptation. For examination of the timecourse of delayed protection, rabbits were pretreated with four 5 minute coronary artery occlusions (PC) or sham operation (SHAM). Twenty four, 48, 72 or 96 hours later, infarct size after 30 min coronary occlusion and 120 minutes reperfusion was assessed with TTC staining and expressed as a percentage of myocardial risk volume (I/R). I/R was reduced at 24 hours (SHAM 48.1 +/- 3.9% v PC 31.4 +/- 3.0%, P < 0.01), 48 hours (SHAM 41.9 +/- 3.0% v PC 19.6 +/- 6.3%, P < 0.01), and 72 hours (SHAM 39.8 +/- 3.4% v PC 17.2 +/- 2.5%, P < 0.01). No protection was observed 96 hours after preconditioning (SHAM 35.0 +/- 4.8% v PC 36.9 +/- 3.8%). In a further study, animals were pretreated with one, two or four 5 minute coronary occlusions (1 x 5 PC, 2 x 5 PC, 4 x 5 PC) and subjected to the infarction protocol 48 hours later. I/R was 44.5 +/- 4.3% in SHAM, 24.8 +/- 4.4% in 1 x 5 PC (P < 0.01), 27.4 +/- 2.9% in 2 x 5 PC (P < 0.05) and 24.4 +/- 4.8 in 4 x 5 PC (P < 0.01). Delayed protection in this rabbit model is prolonged, extending between 24 and 72 hours after the preconditioning stimulus. The threshold for eliciting the second window of protection in this model is as low as one 5 minute coronary occlusion.