Comparative Cardiac Effects of Terlipressin, Vasopressin, and Norepinephrine on an Isolated Perfused Rabbit Heart
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BACKGROUND: Terlipressin, a synthetic analog of arginine-vasopressin (AVP), has been proposed as an effective vasopressive therapy in catecholamine-resistant vasodilatory shock. Although beneficial effects of terlipressin on systemic arterial pressure have been clearly demonstrated, its intrinsic effects on coronary circulation and myocardial performances remain unknown. METHODS: The authors compared the coronary and myocardial effects of terlipressin (1-100 nM, n = 10), AVP (10-1000 pM, n = 10), and norepinephrine (1-100 nM, n = 10) on an erythrocyte-perfused isolated rabbit heart. The cardiac effects of terlipressin were also assessed in erythrocyte-perfused hearts in which the myocardial oxygen delivery was maintained constant and buffer-perfused hearts. Finally, the cardiac effects of terlipressin and AVP were studied in hearts pretreated by [d(CH2)5Tyr(Me)]AVP (0.1 microM), a selective V1a receptor antagonist. RESULTS: Norepinephrine induced a biphasic coronary effect associated with a concentration-dependent increase in myocardial performances. AVP and terlipressin significantly decreased coronary blood flow and impaired myocardial performances from 30 pM and 30 nM, respectively (P < 0.05). The cardiac side-effects of terlipressin were confirmed in buffer-perfused hearts but the maintenance of a constant myocardial oxygen delivery constant abolished its effects on myocardial performances. The cardiac effects induced by terlipressin and AVP were nearly completely abolished on hearts pretreated by [d(CH2)5Tyr(Me)]AVP. CONCLUSIONS: On isolated rabbit heart, terlipressin induced a coronary vasopressor effect and in turn myocardial depression only at supratherapeutic concentrations (> or =30 nM). Its effects are mainly mediated via V1a receptors. However, these potential negative side effects on the heart were less pronounced than were those of AVP.
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