Protective effects of histidine during ischemia-reperfusion in isolated perfused rat hearts.
We investigated the efficacy of histidine in reducing ischemia-reperfusion (I/R)-induced myocardial injury in isolated perfused rat hearts. In I/R hearts, the contractile function and coronary flow were 59 +/- 10 and 78 +/- 6% of control. Perfusion with histidine resulted in significant increase in contractility (94 +/- 4%) and coronary flow (92 +/- 4%). The incidence of arrhythmias during reperfusion was 100% (10 out of 10) in the I/R hearts with an average duration of 12.22 +/- 1.55 (SE) min. The duration of arrhythmias was shortened to 8.24 +/- 1.46, 2.15 +/- 0.9, and 2.49 +/- 1.50 min with 10, 25, and 50 mM histidine, respectively. The duration of sinus rhythm increased from 6.26 +/- 1.56 min in I/R hearts to 10.66 +/- 1.55, 14.99 +/- 1.61, and 17.18 +/- 0.95, and 11.73 +/- 0.93 min after perfusion with 10, 25, and 50 mM histidine, and superoxide dismutase (SOD)-catalase-mannitol, respectively. Electron microscopy revealed significant ultrastructural damage of myocytes in I/R hearts, which included swelling of the mitochondria and disruption of both the sarcolemma and the myofibrils. Histidine reduced the ultrastructural damage in a dose-dependent fashion. In general, the protective effect of histidine was superior than SOD-catalase-mannitol. We conclude that histidine protects myocardium against I/R damage most likely by a singlet oxygen scavenging mechanism.
Department of Medicine, Medical College of Virginia, Richmond 23298.
R C
RC
Kukreja
K E
KE
Loesser
A A
AA
Kearns
S A
SA
Naseem
M L
ML
Hess
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D006321:Heart / Q000187:drug effects*; D006639:Histidine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000648:ultrastructure; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D017382:Reactive Oxygen Species; D006639:Histidine