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Critical Care Medicine:
doi: 10.1097/CCM.0b013e31819b8199
Clinical Investigations

Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: Consequences on heart perfusion and performance*

Ryckwaert, Frédérique MD, PhD; Virsolvy, Anne PhD; Fort, Aurélie PhD; Murat, Brigitte; Richard, Sylvain PhD; Guillon, Gilles PhD; Colson, Pascal H. MD, PhD

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Abstract

Objective: Terlipressin has been proposed as an alternative treatment to catecholamines to restore blood pressure in septic shock. Terlipressin is considered as a vasopressin prodrug capable of releasing small but sustained amounts of [Lysine8] vasopressin (LVP) and to provide prolonged biological effect. However, terlipressin may act as a direct vasopressor beyond its conversion into LVP. We investigated terlipressin direct vasoconstrictive properties and consequences on myocardial perfusion and performance.

Design: Experimental studies.

Settings: National Research Institute Laboratories.

Subjects: Rat aorta and heart, human uterine artery.

Interventions: Studies of vasoconstriction on isolated vascular rings obtained either from rat aorta or human uterine artery, and of coronary flow, ventricular performance, and heart rhythm on rat hearts using a modified Langendorff heart apparatus.

Measurements and Main Results: Terlipressin induced a rapid, saturable, and dose-dependent contraction of rat aortas and human uterine arteries. Although the maximal terlipressin-induced vasoconstriction observed on rat arteries was weaker than LVP, or arginine-vasopressin, pharmacologic properties on human arteries, such as full agonism and strong maximal effect (900% of the maximal response obtained with phenylephrine), suggest a high potential of terlipressin to directly vasoconstrict human vessels. Similarly, terlipressin induced a saturable and dose-dependent vasoconstriction of coronary arteries that was reversible and antagonized by selective V1a antagonists. Maximum rates of left ventricle pressure rise (dP/dtmax) and fall (dP/dtmin) decreased both only in proportion to the decrease in coronary flow.

Conclusions: Besides long lasting effect through slow conversion into LVP, terlipressin is a fast acting vasopressor peptide per se that has an impact on coronary circulation and myocardial function.

© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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