Functional and metabolic responses to ischemia/reperfusion in the isolated, working rat heart: Effect of exercise training

The effect of prior exercise training on the ability of the heart to recover contractile and hemodynamic function following ischemia and subsequent reperfusion was determined in isolated, working rat hearts. Male F344 rats, 8-9 weeks of age, underwent 11-16 weeks of treadmill training at three intensities; low and moderate steady-state endurance as well as high-intensity interval training. Hearts from all trained groups, independent of training intensity, showed dramatically ({dollar}sim{dollar}2-fold) improved cardiac function upon reperfusion following 25 minutes of global, normothermic ischemia. Recovery of cardiac output relative to pre-ischemic values increased from 36 {dollar}pm{dollar} 7% in the sedentary group to 61 {dollar}pm{dollar} 7%, 68 {dollar}pm{dollar} 9% and 73 {dollar}pm{dollar} 5% in low, moderate and interval trained groups, respectively. Increased intensity of training was associated with an improved post-ischemic work production. However, the greatest benefit of training occurred in the transition from a sedentary state to the lowest intensity of physical activity. Several known pathologic mechanisms affecting post-ischemic contractile function were evaluated prior to ischemia, at the end of ischemia prior to reperfusion, and during reperfusion. Hearts from trained animals were characterized by improved reperfusion coronary flow and lower coronary resistance. Relative to pre-ischemia, both ATP (62% vs. 44%) and PCr (107% vs. 56%) were higher during reperfusion in trained vs. sedentary hearts, respectively. In addition, training reversed the 2-fold increase in reperfusion calcium uptake found in sedentary hearts while increasing efficiency of work and a lowering diastolic stiffness. No differences due to training were seen in the metabolic response to ischemia alone nor in the indices of free-radical generation at any time.; In conclusion, prior exercise training appears to attenuate or reverse the pathologic response to ischemia/reperfusion. These data support epidemiological evidence in humans of a greater survivability following heart attack in trained individuals.