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

A. A. Alousi, A. M. Grant, P. D. Allen, E. D. Pagani

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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 P(i) per mg of protein per min at pCa 6.73 (N = 9, P <.05) and from 32.9 ± 2.1 to 37.3 ± 2.2 nmol of P(i) per mg of protein per min at pCa 6.16 (N = 9, P <.05), whereas total Mg-ATPase activity increased from 23.4 ± 1.5 to 33.6 ± 2.6 nmol of P(i) per mg of protein per min at pCa 6.73 (N = 9, P <.05) and from 45.2 ± 2.2 to 52.2 ± 2.5 nmol of P(i) per mg of protein per min at pCa 6.16 (N = 9, P <.05). In human myofibrils, the calcium-dependent Mg-ATPase activity increased from 9.2 ± 2.2 to 13.7 ± 3.3 nmol of P(i) per mg of protein per min at pCa 6.73 (N = 4, P <.05) and from 22.4 ± 1.9 to 25.0 ± 1.4 nmol of P(i) per mg of protein per min at pCa 6.28 (N = 4, P <.05), whereas total Mg-ATPase activity increased from 21.4 ± 3.8 to 32.8 ±6.2 nmol of P(i) per mg of protein per min at pCa 6.73 (N = 4, P <.05) and from 34.6 ± 3.5 to 44.2 ± 4.3 nmol of P(i) per mg of protein per min at pCa 6.28 (N = 4, P <.05). Milrinone at concentrations of 1 x 10-7 to 1 x 10-5 M had no significant effect on canine or human Mg-ATPase sensitivity to calcium. At concentrations of 1 x 10-6 to 1 x 10-5 M, milrinone tended to increase the Ca++-sensitivity of the canine myofibrils to the higher calcium concentrations. However, these increases were not stastistically significant. The data indicate that the inotropic action of milrinone does not include the sensitization of the myofibrils to calcium especially at diastolic calcium concentration.

Original languageEnglish (US)
Pages (from-to)30-37
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume246
Issue number1
StatePublished - 1988
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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