title: Benefits of supplementing St Thomas' Hospital cardioplegic solution with tetraethylammonium on functional and metabolic recovery of isolated rat hearts.
abstract: This study was designed to evaluate whether the addition of potassium channel blockers, tetraethylammonium, 4-aminopyridine or glibenclamide, to St Thomas' cardioplegia improved myocardial preservation over that achieved by St Thomas' cardioplegic solution alone. Initially, isolated rat hearts were subjected to 30 min of continuous normothermic hypoxic cardioplegia. Control hearts were arrested with St Thomas' cardioplegia followed by tetraethylammonium, glibenclamide or 4-aminopyridine-enriched cardioplegia. Subsequently, in a second experiment, hearts were subjected to 45 min of normothermic global ischaemia, after 3 min of cardioplegia with either tetraethylammonium-enriched or standard St Thomas' cardioplegia. In both regimens, hearts arrested with tetraethylammonium-enriched St Thomas' cardioplegia showed better recovery of contractile function than controls (P<0.001). Creatine kinase levels were significantly lower in the tetraethylammonium group (P<0.001). 4-Aminopyridine treatment caused similar contractility to that of the control group but raised creatine kinase and lactate dehydrogenase levels (P<0.001). Glibenclamide diminished coronary flow autoregulation, and increased lactate dehydrogenase leakage in reperfusion (P<0.05) with similar contractility to controls. The results of this preliminary in vitro study demonstrate that, in rat heart, St Thomas' cardioplegia enriched with tetraethylammonium improves post-ischaemic contractile function and reduces creatine kinase release. It is concluded that high potassium blocks the membrane at the rapid depolarization phase with rapid sodium influx and tetraethylammonium further prevents repolarization by blocking voltage-dependent potassium channels.
authors.affiliation: Department of Thoracic Surgery, Instanbul University Cerrahpaşa Medical Faculty, Turkey.
authors.forename: A K
authors.initials: AK
authors.lastname: Bozkurt
authors.forename: O
authors.initials: O
authors.lastname: Süzer
authors.forename: M
authors.initials: M
authors.lastname: Kaynar
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D026902:Potassium Channel Blockers; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
chemical_list: D001639:Bicarbonates; D002314:Cardioplegic Solutions; D026902:Potassium Channel Blockers; C041711:St. Thomas' Hospital cardioplegic solution; D013757:Tetraethylammonium Compounds; D012965:Sodium Chloride; D019789:Tetraethylammonium; D011189:Potassium Chloride; D015761:4-Aminopyridine; D008274:Magnesium; D002122:Calcium Chloride; D005905:Glyburide