title: Myogenic and agonist induced responses of coronary venules after cold hyperkalaemic cardioplegia.
abstract: OBJECTIVE
  The aim was to examine agonist induced and myogenic venular responses after crystalloid cardioplegia in conditions simulating cardiopulmonary bypass.
  
  
  METHODS
  Hearts of pigs were arrested with cold hyperkalaemic ([K+] = 25 mM) crystalloid cardioplegic solution for 1 h under conditions of cardiopulmonary bypass. In another group, hearts were arrested and then reperfused with warm blood for 1 h while being separated from cardiopulmonary bypass. In a third group, animals were supported on cardiopulmonary bypass for 75 min without diversion of coronary blood flow. Hearts from non-instrumented animals served as controls. Coronary venules (91-197 microns in internal diameter) were studied in vitro in a pressurised no flow state using video microscopy. Agonist induced responses were assessed in vessels precontracted with the thromboxane A2 analogue U46619.
  
  
  RESULTS
  Endothelium dependent relaxations to adenosine diphosphate (ADP, P = 0.11 v control), or serotonin (P = 0.67), and endothelium independent relaxations to the beta adrenergic cyclic AMP mediated agonist isoprenaline (P = 0.20), adenosine (P = 0.98), or the KATP channel opener pinacidil (P = 0.40) were not significantly altered after cold cardioplegia alone. After cardioplegia followed by 1 h of warm blood reperfusion, venular responses to ADP (P = 0.003 v control), isoprenaline (P = 0.013), adenosine (P = < 0.001), and pinacidil (P = 0.005) were reduced compared to the respective control responses, while the response to serotonin (P = 0.97) remained unchanged. Endothelium independent cyclic GMP mediated relaxation to sodium nitroprusside was similar in all groups (P > 0.90). Myogenic reactivity was assessed after incremental increases in the intraluminal pressure from 2-40 mm Hg. As intraluminal pressure was increased, the diameter of control venules increased and reached a plateau. Following cardioplegia, the pressure-diameter relationship of venules was shifted upward (P = 0.04 v control) suggesting impaired myogenic tone. After reperfusion, myogenic tone partially recovered. Extracorporeal circulation without diversion of coronary perfusion did not significantly affect venular responses.
  
  
  CONCLUSIONS
  Ischaemic cardioplegia using a cold hyperkalaemic solution under conditions of cardiopulmonary bypass does not significantly alter agonist induced venular responses, whereas myogenic contraction is slightly reduced. After 1 h of reperfusion, agonist induced relaxations of coronary venules are significantly impaired, whereas myogenic contraction recovers. These findings may have implications for the control of myocardial perfusion and diastolic properties of the heart after ischaemic cardioplegia under conditions of extracorporeal circulation.
authors.affiliation: Division of Cardiothoracic Surgery, Beth Israel Hospital, Boston, MA 02215, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Banitt
authors.forename: H B
authors.initials: HB
authors.lastname: Dai
authors.forename: S Y
authors.initials: SY
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Friedman
authors.forename: F W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002315:Cardiopulmonary Bypass; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006324:Heart Arrest, Induced; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil; D012701:Serotonin / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D006146:Guanidines; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D000244:Adenosine Diphosphate; D020110:Pinacidil; D000241:Adenosine; D007545:Isoproterenol