Abstract 2368: Long-term Apelin Infusion Rescues Chronic Cardiomyopathy and Potentiates the Effects of ACE-Inhibition
Introduction: We have previously shown an important role for apelin-APJ signaling in human heart failure and recently described in vivo effects of short term infusions of apelin in mice. Whether apelin can rescue chronic heart failure is not known.
Methods: Spontaneously hypertensive heart failure-prone rats were subjected to coronary artery ligation. Approximately 6 months later, when serial echocardiography had revealed decrements in cardiac function, the animals were randomized into 3 treatment groups (apelin, captopril, or apelin and captopril combined) and one control group (saline). Agents were infused by osmotic minipumps and echocardiography was repeated at 4 and 8 weeks.
Results: This model successfully reproduced chronic heart failure. After 240 days, there was a significant decline in fractional shortening (FS, pre: 0.47 0.001 post: 0.21 0.001, p<0.0001) associated with an increased in LV internal dimension. This was associated with an increase in body mass consistent with clinically demonstrated lethargy and peripheral edema. Overall, heart rate was not different between the groups (8 week time point: saline 329 4.2; apelin 335 4; captopril 340 5.1; combined 345 5.1; p=0.12). While both apelin and captopril independently prevented deterioration of cardiac function, in combination there was a synergistic effect (p <0.001; FS saline 0.15 0.01; apelin 0.21 0.01; captopril 0.25 0.01; combined apelin and captopril 0.27 0.01).
Conclusion: Apelin is a potent vasodilator, and can augment contractile reserve and inhibit vasopressin release making it an attractive therapeutic agent in heart failure. This is the first study to describe the effects of long term apelin administration in chronic heart failure. Long-term apelin infusion not only rescued chronic cardiomyopathy but showed a synergistic benefit when combined with captopril.