Extracellular calcium modulates the effects of protamine on rat myocardium.
We studied the effects of protamine (10-300 microg. mL(-1)) as well as its interaction with heparin in rat left ventricular papillary muscles in vitro at calcium concentrations of 0.5 and 1 mM under low (isotony) and high (isometry) loads. Protamine induced a negative inotropic effect that was less pronounced at calcium 0.5 mM (active force at protamine 300 microg/mL, 84 +/- 20 vs 57 +/- 15% of baseline, P: < 0.05); whereas at calcium 1 mM there was a marked contracture of the muscle. For the smallest concentrations of protamine and at calcium 0.5 mM, we observed a moderate positive inotropic effect that was suppressed by nifedipine. Protamine induced a negative lusitropic effect under low load and decreased postrest potentiation, suggesting an impairment in the functions of the sarcoplasmic reticulum. Heparin was able to inhibit and reverse the negative inotropic effect of protamine. The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.


CONCLUSIONS
The negative inotropic effect of protamine is enhanced by an increase in extracellular calcium concentration. This negative inotropic effect is probably related to calcium overload and impairment in sarcoplasmic reticulum functions, and heparin can block these effects.
Department of Anesthesiology and Critical Care, Centre Hospitalier Universitaire (CHU) Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Pierre et Marie Curie, Paris, France.
J S
JS
David
B
B
Vivien
Y
Y
Lecarpentier
P
P
Coriat
B
B
Riou
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006494:Heparin Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D011479:Protamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000925:Anticoagulants; D002316:Cardiotonic Agents; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin; D002118:Calcium