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Related Experiment Videos

Beneficial effects of the Ca2+ sensitizer EMD 57033 in exercising pigs with infarction-induced chronic left

D J Duncker1, D B Haitsma, D A Liem

  • 1Experimental Cardiology, Thoraxcenter, Erasmus University Rotterdam, Rotterdam, The Netherlands. Duncker@tch.fgg.eur.nl

British Journal of Pharmacology
|October 6, 2001
PubMed
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Calcium sensitizer EMD 57033 effectively improves cardiac function in myocardial infarction (MI) models during rest and exercise. Unlike pimobendan, its positive inotropic effects are unmitigated in depressed left ventricular function.

Area of Science:

  • Cardiovascular Physiology
  • Pharmacology

Background:

  • Chronic depressed left ventricular (LV) function post-myocardial infarction (MI) impacts cardiovascular response to exercise.
  • The specific effects of calcium (Ca2+) sensitization on cardiac stimulation during exercise in MI are not well understood.

Purpose of the Study:

  • To investigate the effects of the Ca2+ sensitizer EMD 57033 on cardiovascular response at rest and during exercise in a porcine model of chronic MI.
  • To compare these effects with those of pimobendan, a mixed Ca2+ sensitizer/phosphodiesterase-III inhibitor.

Main Methods:

  • Pigs underwent chronic instrumentation and coronary artery ligation to induce MI.
  • Cardiovascular performance was measured at rest and during treadmill exercise in both MI and normal (N) pigs.
  • Intravenous administration of EMD 57033 and pimobendan was performed.

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Main Results:

  • MI pigs exhibited reduced resting cardiac output, stroke volume, and LVdP/dt(max), with elevated LV end-diastolic pressure compared to normal pigs.
  • EMD 57033 increased LVdP/dt(max) and stroke volume in resting MI pigs without affecting heart rate or myocardial oxygen consumption.
  • The positive effects of EMD 57033 on stroke volume and LVdP/dt(max) were maintained during exercise in MI pigs, whereas pimobendan's effects were blunted.

Conclusions:

  • The positive inotropic actions of the Ca2+ sensitizer EMD 57033 are preserved in resting and exercising myocardial infarction models.
  • In contrast, the cardiostimulatory effects of the mixed Ca2+ sensitizer/phosphodiesterase-III inhibitor pimobendan are diminished in myocardial infarction.