Comparative cardiac effects of terlipressin, vasopressin, and norepinephrine on an isolated perfused rabbit heart.
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.
Ouattara
Alexandre
A
Laboratoire d'Anesthésiologie, Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire Pitié-Salpêtrière, Université Pierre et Marie Curie, Assistance Publique-Hôpitaux de Paris, France. alexandre.ouattara@psl.ap-hop-paris.fr
Landi
Marc
M
Le Manach
Yannick
Y
Lecomte
Patrick
P
Leguen
Morgan
M
Boccara
Gilles
G
Coriat
Pierre
P
Riou
Bruno
B
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D002302:Cardiac Output / Q000187:drug effects; D004573:Electrolytes / Q000097:blood; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011817:Rabbits; D013318:Stroke Volume / Q000187:drug effects; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D002021:Buffers; D004573:Electrolytes; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D008236:Lypressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D000077585:Terlipressin; D009638:Norepinephrine