Effects of milrinone on Ca++-sensitivity of myofibrillar Mg-adenosine triphosphatase isolated from normal human and canine hearts

Sensitization or desensitization of cardiac actomyosin to calcium has been demonstrated with several pharmacological agents. The effect of milrinone on the sensitivity of cardiac Mg-adenosine triphosphatase (ATPase) activity to calcium was studied in purified myofibrils isolated from normal human hearts (after accidental death or trauma that caused no cardiac damage as established by the attending physician) and from normal canine hearts (established by echocardiography), over a range of calcium concentrations (pCa, 8 to 5). Caffeine, a cardiac stimulant that has been shown to increase the sensitivity of myofibrillar Mg-ATPase activity to calcium in rat ventricle, was used in this study to establish its effect on canine and human myofibrils in comparison with that of milrinone. Caffeine, at concentrations of 40 mM, caused statistically significant sensitization of canine and human myofibrils to calcium. In canine myofibrils, the calcium-dependent Mg-ATPase activity increased from 11.0 +/- 1.2 to 18.8 +/- 2.6 nmol of Pi per mg of protein per min at pCa 6.73 (N = 9, P less than .05) and from 32.9 +/- 2.1 to 37.3 +/- 2.2 nmol of Pi per mg of protein per min at pCa 6.16 (N = 9, P less than .05), whereas total Mg-ATPase activity increased from 23.4 +/- 1.5 to 33.6 +/- 2.6 nmol of Pi per mg of protein per min at pCa 6.73 (N = 9, P less than .05) and from 45.2 +/- 2.2 to 52.2 +/- 2.5 nmol of Pi per mg of protein per min at pCa 6.16 (N = 9, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)