Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive

Possible involvement of nitric oxide

László Babai, Zsolt Szigeti, J. Parratt, A. Végh

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Dogs were subjected to exercise on a treadmill, using a protocol in which the speed and slope were increased every 3 min, and which elevated both heart rate (to a mean of 198±14 beats·min-1) and mean arterial blood pressure (to 150±4 mmHg). Then, 24 or 48 h later, the dogs were anaesthetized with a mixture of α-chloralose and urethane and subjected to a 25 min occlusion of the left anterior descending coronary artery. The control dogs (instrumented but not exercised) were subjected to the same procedure. In some dogs the nitric oxide synthase inhibitor aminoguanidine (50 mg·kg-1; intravenous) was administered 30 min before occlusion. Baroreflex sensitivity (BRS) was determined by the rapid bolus injection of phenylephrine 60 min before, and again 3 min after, the onset of occlusion. Exercise markedly reduced the consequences of coronary artery occlusion 24 h (but not 48 h) later, without modifying myocardial tissue blood flow. In the exercised dogs there were reductions in arrhythmia severity [ventricular fibrillation (VF) during occlusion, 0%; survival from the combined ischaemia/reperfusion insult, 70%] compared with controls (VF during occlusion, 36%; survival, 9%). BRS was preserved during occlusion in the exercised dogs (before occlusion, 1.60±0.54 ms·mmHg-1; 3 min after occlusion, 1.37±0.4 ms·mmHg-1), but not in controls (before occlusion, 1.28±0.29 ms·mmHg-1; 3 min after occlusion, 0.45±0.12 ms·mmHg-1; P <0.05), and other ischaemic changes (inhomogeneity of electrical activation and changes in the ST-segment, recorded over the ischaemic region) were also less marked in the exercised dogs. Exercise-induced cardioprotection was abolished by aminoguanidine (VF during occlusion, 25%; survival, 0%). The results show that even a single period of exercise affords delayed protection against ischaemia/reperfusion-induced VF and other ischaemic changes. Since this protection is abolished by aminoguanidine, and since (inducible) NO synthase activity was elevated 3-fold in left ventricular samples 24 h after exercise, we suggest that this protection is mediated by nitric oxide.

Original languageEnglish
Pages (from-to)435-445
Number of pages11
JournalClinical Science
Volume102
Issue number4
DOIs
Publication statusPublished - 2002

Fingerprint

Nitric Oxide
Dogs
Ventricular Fibrillation
Baroreflex
Nitric Oxide Synthase
Reperfusion
Coronary Vessels
Arterial Pressure
Ischemia
Chloralose
Coronary Occlusion
Urethane
Phenylephrine
pimagedine
Cardiac Arrhythmias
Heart Rate
Injections

Keywords

  • Baroreflex sensitivity
  • Exercise
  • Myocardial ischaemia
  • Nitric oxide synthase
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive : Possible involvement of nitric oxide. / Babai, László; Szigeti, Zsolt; Parratt, J.; Végh, A.

In: Clinical Science, Vol. 102, No. 4, 2002, p. 435-445.

Research output: Contribution to journalArticle

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