Hypoxia Induces Late Preconditioning in the Rat Heart In Vivo

Background Although hypoxic late preconditioning (LPC) limits ischemia-reperfusion injury in vitro, its cardioprotective effect is not established in vivo Methods In part 1, rats were exposed to 4 h of hypoxia (16% 12%, 8% oxygen) before 24 h of reoxygenation In part 2, normoxic rats received early preconditioning with sevoflurane (1 minimum alveolar concentration [MAC] for 3 X 5 min) continuous administration of 1 MAC sevoflurane, or 11 mg kg h propofol Thereafter, all rats underwent 25 min of regional myocardial ischemia and 120 min of reperfusion After reperfusion, hearts were excised for infarct staining The expression of protein kinase C (PKC)alpha and PKC epsilon was assessed by Western blot analysts and the expression of heme oxygenase-1 and vascular endothelial growth factor by reverse transcriptase polymerase chain reaction Results In normoxic control rats, infarct size was 62 +/- 6% of the area at risk Hypoxic LPC reduced infarct size (LPC16 36 +/- 11%, LPC12 38 +/- 10%, LPC8 39 +/- 11%, each P <0 001) to approximately the same magnitude as sevoflurane-preconditioning (40 8%, P <0 001) Combined LPC16 and sevoflurane preconditioning was not superior to either substance alone Continuous sevoflurane or propofol was not protective The PKC inhibitor calphostin C abolished the cardioprotective effects of LPC16 PKC epsilon, but not PKC alpha, expression was increased 6 and 28 h after hypoxic LPC Heme oxygenase-1 and vascular endothelial growth factor were transiently up-regulated after 6 h Conclusion Hypoxic LPC at 8%, 12%, and 16% oxygen reduces infarct size in the rat heart in vivo This effect is as powerful as sevoflurane-preconditioning PKC epsilon is a key player in mediating hypoxic LPC