Genetic Predisposition for Exercise Capacity Affects Recovery of Cardiac Function after Ischemia

Background: Cardiac surgery causes global ischemia during cardioplegic arrest in most procedures. The genetic phenotype affects the hearts ability to generate power. However, it is not known how the genetic predisposition may influence cardiac function after ischemia and reperfusion.

Objective: We aimed to assess cardiac function and metabolism of rats with genetically determined high and low intrinsic exercise capacities during ischemia and reperfusion ex vivo.

Methods: Female 18 week old rats with high or low intrinsic exercise capacity were used. The hearts were excised and perfused as isolated working rat hearts with Krebs-Henseleit buffer containing glucose (5 mmol/l) plus oleate (0,4 mmol/l) for 20 minute to obtain baseline parameters. Subsequently they were subjected to 15 minute of ischemia followed by 40 minute of reperfusion. We measured cardiac power and substrate oxidation.

Results: Cardiac power of HCR and LCR was not different at baseline (HCR 5,29 mW±1,00 vs LCR 5,13± 0,61 mW). During reperfusion after 15 minute of total ischemia, cardiac power recovered significantly better in LCR than in HCR reaching 41,60 ± 4,81% of baseline in HCR and 56,35 ± 7,45% in LCR. Furthermore, the number of hearts not recovering at all tended to be higher in HCR (33%) than in LCR (16%). Postischemic glucose oxidation in HCR was higher than in LCR (180 ± 83 vs 168 ± 47 nmol/min/gdry). Oleate oxidation was higher in HCR than in LCR (783 ± 125 vs 573 ± 95 mol/min/gdry). ATP production calculated from substrate oxidation per cardiac power was higher in HCR (22,44 ± 4,14 versus 16,16 ± 1,79 µmol ATP/W).

Conclusion: We conclude that genetic predisposition significantly affects cardiac recovery after ischemia reperfusion. Rats with low intrinsic exercise capacity present with improved recovery of cardiac function during reperfusion compared with animals with high exercise capacity.