AIMS: To test acute effects of the corticotropin-releasing factor-related peptide urocortin 2 (Ucn2) on left ventricular (LV) function and the propensity for ventricular arrhythmias in the isolated heart of an animal model of hypertension-induced heart failure. METHODS AND RESULTS: Hearts from Dahl salt-sensitive rats with severe LV dysfunction were perfused according to Langendorff. Left ventricular developed pressure and the positive and negative derivatives of LV pressure were analysed before and after perfusion with Ucn2 (n = 15) or normal perfusion solution (control, n = 9). Intracellular calcium cycling parameters were assessed by surface fluorometry. Furthermore, monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were determined, the latter by a train-of-pulses method at increasing voltage to scan the vulnerable period of repolarization. Urocortin 2 significantly affected intracellular calcium cycling and improved LV contractile function and relaxation. Compared with baseline values, Ucn2 significantly decreased MAPD at 30, 50, and 90% repolarization and significantly increased VFT compared with baseline values. No changes were observed in control experiments. CONCLUSION: Administration of Ucn2 rapidly improves LV function and increases VF threshold in failing, isolated rat hearts with increased propensity for ventricular arrhythmias. These observations suggest a potential use of Ucn2 as a safe and novel agent for the treatment of acute heart failure.
AIMS: To test acute effects of the corticotropin-releasing factor-related peptide urocortin 2 (Ucn2) on left ventricular (LV) function and the propensity for ventricular arrhythmias in the isolated heart of an animal model of hypertension-induced heart failure. METHODS AND RESULTS: Hearts from Dahl salt-sensitive rats with severe LV dysfunction were perfused according to Langendorff. Left ventricular developed pressure and the positive and negative derivatives of LV pressure were analysed before and after perfusion with Ucn2 (n = 15) or normal perfusion solution (control, n = 9). Intracellular calcium cycling parameters were assessed by surface fluorometry. Furthermore, monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were determined, the latter by a train-of-pulses method at increasing voltage to scan the vulnerable period of repolarization. Urocortin 2 significantly affected intracellular calcium cycling and improved LV contractile function and relaxation. Compared with baseline values, Ucn2 significantly decreased MAPD at 30, 50, and 90% repolarization and significantly increased VFT compared with baseline values. No changes were observed in control experiments. CONCLUSION: Administration of Ucn2 rapidly improves LV function and increases VF threshold in failing, isolated rat hearts with increased propensity for ventricular arrhythmias. These observations suggest a potential use of Ucn2 as a safe and novel agent for the treatment of acute heart failure.
Authors: Si Chen; Zhenhua Wang; Bo Xu; Xiangquan Mi; Wanqing Sun; Nanhu Quan; Lin Wang; Xingchi Chen; Quan Liu; Yang Zheng; Jiyan Leng; Ji Li Journal: Toxicol Sci Date: 2015-09-04 Impact factor: 4.849
Authors: Colin G Stirrat; Sowmya Venkatasubramanian; Tania Pawade; Andrew J Mitchell; Anoop S Shah; Ninian N Lang; David E Newby Journal: Br J Clin Pharmacol Date: 2016-07-28 Impact factor: 4.335