L-Arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts.
OBJECTIVE
Ischaemic or pharmacological preconditioning with L-arginine has been reported to be insufficient for optimal cardioprotection. The ability of nitric oxide (NO) to enhance ischaemic preconditioning was assessed, and the role of L-arginine-induced ischaemic preconditioning in myocardial protection was determined.


METHODS
Isolated rat hearts were prepared and divided into six groups: control hearts (control, n=6) were perfused without global ischaemia at 37 degrees C for 160 min; global ischaemia hearts (GI, n=6) were subjected to ischaemia for 20 min and reperfusion for 120 min; ischaemic preconditioned hearts (IP, n=6) received 2 min of zero-flow global ischaemia followed by 5 min reperfusion, before 20 min of global ischaemia; L-arginine hearts (ARG, n=6) received 1 mmol/l L-arginine for 5 min, before 20 min of global ischaemia; ischaemic preconditioning plus nitro-L-arginine methyl ester hearts (IP+L-NAME, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 3 mmol/l L-NAME in Krebs-Henseleit buffer, before 20 min of global ischaemia; and ischaemic preconditioning plus L-arginine hearts (IP+ARG, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 1 mmol/l L-arginine in Krebs-Henseleit buffer. Haemodynamic parameters and coronary flow were recorded continuously. Nitrites and nitrates (NOx) were measured 5 and 60 min after reperfusion, and infarct size was also determined.


RESULTS
In the IP+ARG group, significant amelioration and preservation of left ventricular peak developed pressure and coronary flow was observed compared with the GI, IP, ARG and IP+L-NAME groups. Infarct size in the IP+ARG group was reduced significantly compared with that in the GI, IP, ARG and IP+L-NAME groups. Significant preservation of NOx was observed during reperfusion in the IP+ARG group compared with the GI group.


CONCLUSIONS
Inhibition of NO synthase with L-NAME had little impact on ischaemic preconditioning, suggesting that endogenous NO is not a major mediator of ischaemic preconditioning. Nevertheless, enhancement of the effects of ischaemic preconditioning can be achieved with L-arginine, a precursor of NO, improving post-ischaemic functional recovery and infarct size in the isolated rat heart.
Suematsu
Y
Y
Department of Cardiothoracic Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan. suematsu@aurora.dti.ne.jp
Ohtsuka
T
T
Hirata
Y
Y
Maeda
K
K
Imanaka
K
K
Takamoto
S
S
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D003326:Coronary Circulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester