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CARDIOVASCULAR ANESTHESIA

Extracellular Calcium Modulates the Effects of Protamine on Rat Myocardium

Jean-Stéphane David, MD^*, Benoît Vivien, MD^*, Yves Lecarpentier, MD, PhD, Pierre Coriat, MD^*, and Bruno Riou, MD, PhD^*

*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; Department of Anesthesiology and Critical Care, CHU Edouard Herriot, Lyon; Institut National de la Santé et de la Recherche Médicale (INSERM) LOA-ENSTA-Ecole Polytechnique, Palaiseau, and Service de Physiologie, Hôpital de Bicêtre, AP-HP, Université Paris Sud, le Kremlin-Bicêtre, France

Address correspondence to Pr. Bruno Riou, MD, PhD, Département d’Anesthésie-Réanimation, Groupe Hospitalier Pitié-Salpêtrière, 47 Boulevard de l’hôpital, 75651 Paris cedex 13, France. Address e-mail to bruno.riou{at}psl.ap-hop-paris.fr

We studied the effects of protamine (10–300 µg · 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 µg/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.

Implications: 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.