Abstract 5389: Erythropoietin Receptor Deficient Mice Have Impaired Voluntary Wheel-running Performance
Introduction and hypothesis: Recently, we have demonstrated that erythropoietin (EPO) via its receptor (EPO-R) improves cardiac function in experimental heart failure mainly due to its angiogenic effects. Since it is believed that physiological hypertrophy of the heart is accompanied by compensatory angiogenesis, we hypothesized that cardiac EPO signaling is related to exercise capacity. Therefore, we employed mice that have no EPO-R in the heart, and subdued these mice to long-term exercise.
Methods: We employed transgene-rescued EPO-R-null mutant mice (EPO-R−/−rescued) that express EPO-R exclusively in the hematopoietic cells. These mice have normal development without overt pathology. In this model, EPO-R is not expressed in any other organ than the bone marrow. We used a model of voluntary wheel-running; mice had unlimited access to a running wheel for 28 days. We measured exercise performance: average distance, average daily speed, maximum speed and average run time. At sacrifice heart weight and hemodynamic parameters were measured: blood pressure, heart rate and intracardiac pressures.
Results: Control mice ran 6.5 ± 1.5 km/day, whereas EPO-R−/−rescued mice ran 1.7 ± 1.4 km/day (P<0.05). This was due to a lesser average speed (1.62 ± 0.03 km/hr vs. 1.02 ± 0.07 km/hr, P<0.01) and a reduced average running time (3:43 ± 0:30 hr vs. 1:45 ± 0:41 hr, P<0.05). Heart weight was not significantly increased after 28 days. Also we found no hemodynamic effects (blood pressure, heart rate, intracardiac pressures) after exercise.
Conclusions: In conclusion, lack of cardiac EPO-R expression leads to severely decreased voluntary wheel-running performance in a murine model of exercise. We postulate that EPO signaling is crucial for myocardial performance during sustained exercise.