European Heart Journal Advance Access originally published online on August 25, 2007
European Heart Journal 2007 28(21):2589-2597; doi:10.1093/eurheartj/ehm340
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Urocortin 2 infusion in human heart failure
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch 8140, New Zealand
Received 28 February 2007; revised 5 July 2007; accepted 17 July 2007; online publish-ahead-of-print 25 August 2007.
* Corresponding author. Tel: +64 33641116; fax: +64 33641115. E-mail address: mark.richards{at}cdhb.govt.nz
See page 2561 for the editorial comment on this article (doi:10.1093/eurheartj/ehm413)
Aims: To document the haemodynamic, neurohormonal, and renal responses to Urocortin 2 (UCN2) infused in human heart failure (HF).
Methods and 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 µg [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/cm5; 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).
Conclusion: 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.
Key Words: Hormones • Cardiac output • Haemodynamics • Echocardiography • Vasodilation
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