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 fur optimal cardioprotection. Tho ability of nitric oxide (NO) to enhance ischaemic preconditioning was assessed, an d the role of L-arginine-induced ischaemic preconditioning in myocardial pr otection was determined. Methods: Isolated rat hearts were prepared and div ided into six groups: control hearts (control, n = 6) were perfused without global ischaemia at 37 degreesC 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 glo bal ischaemia followed by 5 min reperfusion, before 20 min of global ischae mia; 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 eater hearts (IP + L-NAME, n = 6) received 2 min of ischaem ic preconditioning and 5 min reperfusion with 3 mmol/l L-NAME in Krebs-Hens eleit buffer, before 20 min of global ischaemia; and ischaemic precondition ing plus L-arginine hearts (IP + ARG, n = 6) received 2 min of ischaemic pr econditioning and 5 min reperfusion with 1 mmol/l L-arginine in Krebs-Hense leit buffer. Haemodynamic parameters and coronary Row were recorded continu ously. Nitrites and nitrates (NOx) were measured 5 and 60 min after reperfu sion, and infarct size was also determined. Results: In the IP + ARG group, significant amelioration and preservation of left ventricular peak develop ed pressure and coronary Row was observed compared with the CI, IF, ARG and IP + L-NAME groups. Infarct size in the IP + ARG group was reduced signifi cantly compared with that in the GI, IP, ARO and IP + L-NAME groups. Signif icant preservation of NOx was observed during reperfusion in the IP + ARG g roup compared with the GI group. Conclusions: Inhibition of NO synthase wit h L-NAME had little impact on ischaemic preconditioning, suggesting that en dogenous NO is not a major mediator of ischaemic preconditioning. Neverthel ess, enhancement of the effects of ischaemic preconditioning can be achieve d with L-arginine, a precursor of NO, improving post-ischaemic functional r ecovery and infarct size in the isolated rat heart. (C) 2001 Elsevier Scien ce B.V. All rights reserved.