Lack of involvement of mast cell degranulation in the antiarrhythmic effect of preconditioning in rats.
It has been proposed that the cardioprotective effects of myocardial ischaemic preconditioning may involve the release of mast cell mediators. The aim of the study was to determine whether mast cells are involved in the antiarrhythmic effect of ischaemic preconditioning in rat hearts. Preconditioning was achieved, both in anaesthetised rats and in rat isolated hearts, by a 3-min temporary occlusion of the left main coronary artery followed by 10 min of reperfusion before a 30-min permanent occlusion. Preconditioning had a marked antiarrhythmic effect, reducing the number of ventricular ectopic beats from 1,176 +/- 69 to 490 +/- 139 and the incidence of ventricular fibrillation from 40% to 0. Administration of the mast cell-stabilising drugs lodoxamide tromethamine and sodium cromoglycate (20 mg/kg/h i.v. 30 min before and throughout experimental protocol) did not modify the antiarrhythmic effect of preconditioning. Sodium cromoglycate, but not lodoxamide tromethamine, itself significantly reduced the number of ectopic beats that occurred over a 30-min period of ischaemia (from 760 +/- 181 to 153 +/- 33 in nonpreconditioned animals). Both drugs abolished the decrease in arterial blood pressure that occurred on coronary artery occlusion. The decrease in arterial blood pressure produced by the mast cell-degranulating compound 48/80 (50 microg/kg; i.v.) was attenuated to a similar degree by both drugs (decreases in pressure of 53 +/- 7, 31 +/- 1, and 25 +/- 3 mm Hg in control, sodium cromoglycate-treated, and lodoxamide tromethamine-treated animals, respectively). In rat isolated hearts, degranulation of mast cells with three consecutive doses of 50 microg of compound 48/80 had no antiarrhythmic effects and did not modify the antiarrhythmic effect of preconditioning. It is concluded that cardiac mast cells do not play a major role in the protection offered by ischaemic preconditioning on arrhythmogenesis in rat hearts.
Humphreys
R A
RA
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, Great Britain.
Kane
K A
KA
Parratt
J R
JR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000473:pathology*; D015550:Cell Degranulation; D004205:Cromolyn Sodium / Q000494:pharmacology; D006439:Hemodynamics; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D019194:Ischemic Preconditioning; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology*; D009570:Nitriles; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014325:Tromethamine / Q000031:analogs & derivatives / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D006634:Histamine H1 Antagonists; D009570:Nitriles; D014325:Tromethamine; D003189:p-Methoxy-N-methylphenethylamine; C022028:lodoxamide tromethamine; D004205:Cromolyn Sodium; D010072:Oxamic Acid