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 [Lysine] 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.
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 [Lysine] 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.
Authors: Andrea Morelli; Abele Donati; Christian Ertmer; Sebastian Rehberg; Alessandra Orecchioni; Alessandro Di Russo; Paolo Pelaia; Paolo Pietropaoli; Martin Westphal Journal: Intensive Care Med Date: 2011-02-19 Impact factor: 17.440
Authors: Douglas G Tilley; Weizhong Zhu; Valerie D Myers; Larry A Barr; Erhe Gao; Xue Li; Jianliang Song; Rhonda L Carter; Catherine A Makarewich; Daohai Yu; Constantine D Troupes; Laurel A Grisanti; Ryan C Coleman; Walter J Koch; Steven R Houser; Joseph Y Cheung; Arthur M Feldman Journal: Circulation Date: 2014-09-09 Impact factor: 29.690