Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats.

After myocardial infarction in rats, muscle performance in the remaining hypertrophied myocardium deteriorates and is associated with a decrease in myosin adenosinetriphosphatase (ATPase) activity and a shift to the V3 myosin heavy-chain isoform. We have previously shown in another model of hypertrophy, secondary to renovascular hypertension, that chronic intermittent adrenergic stimulation with dobutamine (Db) can prevent this biochemical adaptation. The present study was undertaken to assess the effects of chronic Db treatment on cardiac mass, function, metabolism, and myosin biochemistry in animals subjected to chronic myocardial infarction. Four groups of rats were studied: controls, animals treated with Db (2 mg/kg 2X daily for 4 wk), animals subjected to myocardial infarction and killed after 4 wk (MI), and MI animals concurrently treated with Db for 4 wk (MI-Db). The two MI groups were subdivided into those with and without congestive heart failure (CHF). Heart weight was increased by 13% with Db, unchanged in the infarct groups without CHF, and increased by 9 and 22% in the infarct groups with CHF. Db did not have any additional effect on heart weight in these later groups. Infarct weight was greatest in the animals with CHF, and viable myocardium was equivalent in all infarct groups suggesting that CHF was associated with a greater degree of hypertrophy. Ventricular performance, as assessed in an isovolumic heart apparatus, was markedly depressed in both infarct groups with CHF and was not affected by Db. Db increased myosin ATPase activity in control and infarcted animals both with and without congestive heart failure. Myosin oxygen consumption and lactate production were not adversely affected by Db.