Hyperbaric and hyperoxic preconditioning may improve free flap survival. Hyperbaria/hyperoxia limit myocardial infarct size. Their relative contributions and underlying mechanisms are unknown. Using an established cardiac model, we determine if pretreatment with hyperoxia and hyperbaria improves myocardial infarct size and we propose a mechanism.
Adult Sprague Dawley rats (n=10/gp) were treated for 1 hour with (1) normoxia + normobaria, (2) hyperoxia + normobaria and (3) hyperoxia + hyperbaria. The heart was isolated, subjected to ischemia and reperfused. Infarct size and percent recovery of left ventricular developed pressure (LVDP) were quantified.
Infarct size decreased across all groups from 13±2% in controls to 9±2% (p<0.05) to 5±2% (p<0.05). Additionally, LVDP increased from 34±7% to 40±11% to 45±8% (p<0.05). To determine a role for NOS, hearts were perfused with L-NAME, a NOS inhibitor, prior to ischemia. L-NAME reversed the protective effect of hyperoxia + hyperbaria. Nitrite plus nitrate content increased from 12±3 to 26±6 nmoles/g in treated rats compared to controls. NOS3 protein expression increased 1.2 fold and association of hsp90 with NOS3 increased 4 fold in treated rats.
We conclude pretreatment with oxygen results in less ischemia and that both FiO2 and ATM influences cardioprotection via nitric oxide synthase activation.