Recovery of trout myocardial function following anoxia: preconditioning in a non-mammalian model

Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout ( Oncorhynchus mykiss) working heart preparation at 10°C to examine whether prior exposure to 5 min of anoxia (Po 2 ≤ 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low Pout [15 min of anoxia at an output pressure (Pout) of 10 cmH2O]; 2) anoxia with high Pout [10 min of anoxia at a Pout of 10 cmH2O, followed by 5 min of anoxia at Pout = 50 cmH2O]; and 3) preconditioning [5 min of anoxia at Pout = 10 cmH2O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high Pout group]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low Pout decreased maximum stroke volume (Vs max) by 15% and maximum cardiac output (Q˙max) by 23%. When the anoxic workload was increased by raising Pout to 50 cmH2O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in Vs max and Q˙max that were observed in the anoxia with high Pout group and any anoxia-related increases in the input pressure (Pin) required to maintain resting Q˙ (16 ml · min−1 · kg−1). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.