L-Arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts.

Abstract

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.

• Authors: Y Suematsu, T Ohtsuka, Y Hirata, K Maeda, K Imanaka, S Takamoto
• Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (Eur J Cardiothorac Surg) Vol. 19 Issue 6 Pg. 873-9 (Jun 2001) ISSN: 1010-7940 [Print] Germany
• PMID: 11404145 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Nitrates
• Nitrites
• Arginine
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (administration & dosage, pharmacology)
• Coronary Circulation
• Enzyme Inhibitors (administration & dosage, pharmacology)
• Heart (drug effects)
• Hemodynamics (physiology)
• In Vitro Techniques
• Ischemic Preconditioning, Myocardial
• Male
• NG-Nitroarginine Methyl Ester (administration & dosage, pharmacology)
• Nitrates (analysis)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitrites (analysis)
• Rats
• Rats, Wistar