Abstract 1571: Hibernating Myocardium has Reduced High Energy Phosphate Levels and a Preconditioning-Like Effect with Slower ATP Depletion in Response to Acute Ischemia
Background. Pigs with a chronic LAD stenosis develop hibernating myocardium with contractile dysfunction and reduced resting flow. We hypothesized that this reduced energy utilization preserves ATP and protects the heart from irreversible injury during acute ischemia.
Methods. Pigs with hibernating myocardium were studied 3-months after instrumentation with a 1.5 mm proximal LAD stenosis (n=7). Hibernating myocardium was confirmed by reduced LAD wall thickening (2.4±0.2 vs.6.1±0.6 mm in remote, p<0.05) and reduced resting flow (0.95±0.15 vs. 1.66±0.29 ml/min/g in remote, p<0.05) without infarction. Subendocardial samples were rapidly excised from propofol anesthetized pigs and serial depletion of high energy phosphates quantified by HPLC (in μmol/g dry weight) during simulated total ischemia in vitro (37°C).
Results. At Baseline, ATP and ADP were significantly reduced in the hibernating LAD region in comparison to controls (n=8, Table⇓), with preserved CP/ATP and ATP/ADP ratios. During simulated ischemia, hibernating myocardium displayed a markedly reduced rate of ATP depletion (ΔATP), with ATP levels at 20 min significantly higher than control (Table⇓). Higher ATP levels were maintained throughout 80 min of ischemia. Interestingly, identical preservation of high energy phosphates occurred in the remote normally perfused region of hearts with hibernating myocardium (Table⇓).
Conclusion. These data indicate that there is a balanced reduction in high energy phosphate levels in hibernating myocardium with chronic protection from ischemia manifested by a slower rate of ATP depletion during acute ischemia. This preconditioning-like effect is global suggesting that it arises from stimuli that are not directly related to ischemia. This raises the possibility that stretch from cyclical elevations in LV filling pressure or a circulating factor released from the heart in response to ischemia can protect the heart in chronic coronary artery disease.