title: Ischaemic endothelial dysfunction after single or multidose cardioplegia.
abstract: The effect of ischaemia, either alone or after a single or multidose infusion of St Thomas' Hospital cardioplegia solution (ST), on endothelial function was studied by examining its influence on 5-Hydroxytryptamine- (5-HT-) and nitroglycerine- (GTN-) induced coronary vasodilation in the isolated rat heart. Eighty rat hearts were perfused on a modified Langendorff preparation. Thirty minutes of unprotected ischaemia (N = 16) abolished the vasodilatory response to 5-HT but maintained the response to GTN (expressed as % of the control value 5-HT, pre 45.0 +/- 3.5, post 2.3 +/- 3.2, GTN, pre 42.3 +/- 4.4, post 39.8 +/- 4.0). The increase in coronary flow induced by either agent was unaltered following 30 or 60 min of ischaemia protected by a single dose of ST (N = 16 in each). Ninety minutes of ischaemia preceded by a single infusion of ST (N = 16) markedly reduced the 5-HT response but maintained the vasodilation induced by GTN (5-HT, pre 37 +/- 2.6, post 6.9 +/- 2.6, GTN, pre 40.1 +/- 2.5, post 37 +/- 2.8). During 90 min of ischaemia, infusion of an additional dose of ST after 45 min (N = 8) or two extra doses every 30 min (N = 8) maintained the 5-HT-induced increase in coronary flow (pre 39.5 +/- 3.9, post 36.4 +/- 3.5). It can be concluded that coronary vascular endothelium is more susceptible to ischaemic damage when compared with vascular smooth muscle. This results in early loss of endothelium-dependent vasodilation. Multidose infusion of St Thomas' Hospital cardioplegia solution is superior to a single infusion in protecting endothelial function following prolonged cardiac ischaemia.
authors.affiliation: National Heart and Lung Institute, London, U.K.
authors.forename: P S
authors.initials: PS
authors.lastname: Mankad
authors.forename: A H
authors.initials: AH
authors.lastname: Chester
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006324:Heart Arrest, Induced; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000503:physiopathology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D002314:Cardioplegic Solutions; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D005996:Nitroglycerin; D008274:Magnesium; D002122:Calcium Chloride