Berry Mark F, Pirolli Timothy J, Jayasankar Vasant, Burdick Jeffrey, Morine Kevin J, Gardner Timothy J, Woo Y Joseph
Department of Surgery, Division of Cardiothoracic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pa 19104, USA
Circulation. 2004 Sep 14;110(11 Suppl 1):II187-93. doi: 10.1161/01.CIR.0000138382.57325.5c.
Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter.
Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).
The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.
阿片肽在体外已被证明是一种强效的心脏正性肌力药。本研究采用血管周围血流探头和电导导管的新型组合,评估阿片肽对正常和缺血性心肌病大鼠心脏功能的体内作用。
正常大鼠(n = 32)和左冠状动脉前降支结扎6周后出现心力衰竭的大鼠(n = 22)接受正中胸骨切开术,在升主动脉周围放置血管周围血流探头,并将压力容积电导导管插入左心室。与假手术大鼠相比,结扎大鼠的基线Pmax和最大dP/dt显著降低。在正常和衰竭心脏中,以0.01μg/min的速率持续输注阿片肽20分钟,与单独输注载体相比,Pmax和最大dP/dt显著增加。阿片肽输注增加了心脏收缩力,表现为每搏输出量(SV)显著增加,而左心室舒张末期容积无变化(正常动物初始SV变化102±16%,结扎动物为26±20%;正常动物为110±30%,结扎动物为26±11%),以及可招募的前负荷每搏功增加(正常动物为180±24mmHg,结扎动物为107±9mmHg)。
本研究首次表明,阿片肽在正常大鼠心脏和心肌梗死后衰竭的大鼠心脏中均具有体内正性肌力作用。阿片肽可能作为缺血性心力衰竭患者的急性正性肌力药物。