Open AccessEffects of Nitric Oxide Synthesis on Reperfusion Injury and Catecholamine Responsiveness in a Heterotopic Rat Heart-Transplantation Model
Author(s) -
Gábor Szabó,
Sándor Bátkai,
Susanne Bährle,
Thomas J. Dengler,
Christian F. Vahl,
Rainer Zimmermann,
S. Hagl
Publication year - 1998
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199802000-00007
Subject(s) - dobutamine , nitric oxide , reperfusion injury , transplantation , medicine , anesthesia , ventricular pressure , ischemia , heart transplantation , blood pressure , catecholamine , hemodynamics , cardiology
Global myocardial ischemia and reperfusion injury play a major role in early postoperative graft dysfunction. In this study, the influence of nitric oxide (NO) on reperfusion injury and catecholamine sensitivity after ischemia was investigated in a heterotopic rat heart-transplantation model. After a 1-h ischemic preservation, reperfusion was started either after application of saline vehicle (control, n = 8) or nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 8) for inhibition of NO synthesis or NO-precursor L-arginine (L-Arg; 40 mg/kg, n = 8), or L-NAME plus L-Arg (n = 8), respectively. After 60 min of reperfusion, continuous dobutamine infusion (5 microg/kg/min) was started. Myocardial blood flow was assessed by the hydrogen-clearance method. An intraventricular balloon was used to measure pressure-volume relations: peak left ventricular pressure, the rate of pressure development (dP/dt), end-diastolic pressure, and isovolumic relaxation constant. Myocardial blood flow was significantly reduced after L-NAME and increased after L-Arg in comparison with control (p < 0.05). The L-NAME group showed decreased systolic and diastolic functional recovery in comparison with control. Simultaneous infusion of L-Arg and L-NAME reversed these effects. L-Arg alone led to a further improvement of cardiac functional recovery. Whereas myocardial blood flow remained unchanged in the L-NAME group with dobutamine infusion, it significantly increased in the control group (p < 0.05). L-Arg antagonized this effect of L-NAME. Dobutamine increased peak left ventricular pressure and dP/dt and shortened the isovolumic relaxation constant in all groups; however, the changes of systolic hemodynamic indices were significantly smaller in the L-NAME group (p < 0.05) and significantly higher in the L-Arg group (p < 0.05). These results indicate that (a) NO production within the graft during reperfusion has a significant beneficial effect on graft function, and (b) NO formation may play an important role in beta-adrenergic responses after heart transplantation.