title: Mechanisms causing coronary microvascular dysfunction following crystalloid cardioplegia and reperfusion.
abstract: OBJECTIVE
  The aim was to examine the mechanisms of coronary microvascular dysfunction during cardiopulmonary bypass and ischaemic arrest using a crystalloid cardioplegic solution.
  
  
  METHODS
  Porcine hearts were arrested with cold hyperkalaemic (K+ = 25 mmol.litre-1) cardioplegic solution for 1 h during cardiopulmonary bypass and then reperfused for 1 h. Selected hearts were arrested but not reperfused. Coronary vessels of non-instrumented pigs were used as controls. In vitro vascular responses of subepicardial and subendocardial arterioles were examined in a pressurised (40 mm Hg) no flow state with video microscopy.
  
  
  RESULTS
  Following 1 h of ischaemic cardioplegia, endothelium dependent relaxations of epicardial arterioles to the receptor mediated agent ADP and the non-receptor-mediated agent calcium ionophore A23187 were moderately reduced, and the contractile responses to KCl or the thromboxane A2 analogue U46619 were reduced compared to responses of vessels from control animals. After 1 h of reperfusion, U46619 caused contraction greater than control values, while contraction to KCl and endothelium dependent relaxations to ADP or A23187 were further reduced. Responses of endocardial microvessels to serotonin were slightly more affected by cardioplegia and reperfusion than were epicardial vessels, while the effect on responses of epicardial and endocardial vessels to bradykinin or A23187 were similar. Endothelium independent relaxation to sodium nitroprusside was not altered in any of the experimental groups. The addition of manganese superoxide dismutase to the cardioplegic solution markedly preserved endothelium dependent responses to ADP and A23187 and contractile response to U46619, compared to the responses of vessels from the plain crystalloid cardioplegia group, but had no effect on relaxation to sodium nitroprusside or on contraction to KCl. Five hours of normokalaemic hypothermia (5-10 degrees C) in Krebs buffer had minimal effect on vasodilator responses. Electron microscopy revealed preserved endothelial and smooth muscle cell structure, and focal mononuclear leucocyte-endothelium adherence following cardioplegic arrest and reperfusion.
  
  
  CONCLUSIONS
  Ischaemic cardioplegia-reperfusion induced endothelium dependent and direct smooth muscle microvascular dysfunction is at least partially mediated by prolonged exposure of vessels to hyperkalaemia and to the generation of oxygen derived free radicals. Leucocytes probably mediate injury during reperfusion, while hypothermia has minimal effect on recovery of vasomotor function.
authors.affiliation: Department of Surgery, Beth Israel Hospital, Boston, MA 02215.
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
authors.forename: M
authors.initials: M
authors.lastname: Friedman
authors.forename: H B
authors.initials: HB
authors.lastname: Dai
authors.forename: T
authors.initials: T
authors.lastname: Shafique
authors.forename: F J
authors.initials: FJ
authors.lastname: Schoen
authors.forename: R M
authors.initials: RM
authors.lastname: Weintraub
authors.forename: R G
authors.initials: RG
authors.lastname: Johnson
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002314:Cardioplegic Solutions / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D004699:Endocardium / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D008297:Male; D008833:Microcirculation / Q000648:ultrastructure; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D015425:Myocardial Reperfusion; D010496:Pericardium / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002314:Cardioplegic Solutions; D011450:Prostaglandin Endoperoxides, Synthetic; D000001:Calcimycin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid