Y. Suematsu et al., L-arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts, EUR J CAR-T, 19(6), 2001, pp. 873-879
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.