Urocortin 2 infusion in human heart failure.
OBJECTIVE
To document the haemodynamic, neurohormonal, and renal responses to Urocortin 2 (UCN2) infused in human heart failure (HF).


RESULTS
Eight male patients with HF [left ventricular ejection fraction (LVEF) < 40%, NYHA class II-III] received placebo and 25 [low dose (LD)] and 100 microg [high dose (HD)] of UCN2 intravenously over 1 h in a single-blind, placebo-controlled, dose-escalation design. UCN2 increased cardiac output (CO) (mean peak increments +/- SEM; placebo 0.3 +/- 0.1; LD 1.0 +/- 0.3; HD 2.0 +/- 0.2 L/min; P < 0.001) and LVEF (0.0 +/- 1.5; LD 5.9 +/- 2.1; HD 14.1 +/- 2.7%; P = 0.001) and decreased mean arterial pressure (placebo 6.7 +/- 1.3; LD 11.4 +/- 1.7; HD 19.4 +/- 3.3 mmHg; P = 0.001), systemic vascular resistance (SVR) (placebo 104 +/- 37; LD 281 +/- 64; HD 476 +/- 79 dynes s/cm(5); P < 0.003), and cardiac work (CW) (placebo 48 +/- 12; LD 66 +/- 22; HD 94 +/- 13 mmHg/L/min; P < 0.001). No significant effect on vasoconstrictor/volume-retaining neurohormones was noted. UCN2 decreased urinary volume (P = 0.035) but not creatinine excretion (P = 0.962).


CONCLUSIONS
Intravenous UCN2 in HF induced increases in CO and LVEF with falls in SVR and CW. No hormone response occurred. The role of UCN2 in circulatory regulation and its potential therapeutic application in heart disease warrant further investigation.
Davis
Mark E
ME
Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8140, New Zealand.
Pemberton
Christopher J
CJ
Yandle
Timothy G
TG
Fisher
Steve F
SF
Lainchbury
John G
JG
Frampton
Christopher M
CM
Rademaker
Miriam T
MT
Richards
Mark
M
D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D054832:Urocortins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D002316:Cardiotonic Agents; D054832:Urocortins