Effects of heart rate on cardiac function in normal mice and rats and in animal models of heart failure.

OBJECTIVES

To identify the practical heart rate measurement windows by examining the impact of various heart rate ranges on changes in cardiac function in small animal models of health and disease under isoflurane anesthesia using cardiac ultrasonography.

METHODS

Male Sprague-Dawley rats were used to produce a model of post-myocardial infarction heart failure by left anterior descending artery ligation. Each of the model and normal (control) groups included 11 rats. On days 7 and 28 after surgery, the model group showed dynamic alterations in cardiac function. A "dual-hit" strategy combining nitric oxide synthase inhibitors with high-fat diet was used to create a mouse model of heart failure with intact ejection fraction. In addition to comparing failed and normal hearts at the same heart rate loads, echocardiography was used to evaluate cardiac performance in normal and model rats and mice under various heart rate loads controlled by varying depths of anesthesia.

RESULTS

Under normal or pathological conditions, changes in heart rate had a minor impact on contractile performance; however, when the heart rate was reduced, the contractile function was markedly decreased. Both rats and mice exhibited diastolic dysfunction when their heart rates decreased.

CONCLUSIONS

Echocardiographic systolic function in rats is not significantly impacted by changes in heart rate under normal or pathological conditions. In contrast, bradycardia under isoflurane anesthesia easily causes diastolic dysfunction in both species, and systolic performance in mice decreases as the heart rate is reduced. Thus, the practical heart rate measurement windows for echocardiography under isoflurane anesthesia may be 390-450 bpm for rats and 450-480 and 510-550 bpm for mice.