Adrenergic regulation of coronary microcirculation after extracorporeal circulation and crystalloid cardioplegia.
The purpose of the present study was to examine whether adrenoceptor-mediated responses of porcine coronary resistance arteries are affected by cardioplegic arrest under conditions of extracorporeal circulation (cardiopulmonary bypass; CPB). Pigs were placed on CPB. The hearts were arrested with a cold hyperkalemic crystalloid cardioplegic solution for 1 h, then were reperfused for 1 h. In vivo and in vitro beta-adrenoceptor-mediated responses were compared before CPB and 2 min and 1 h after initiation of reperfusion. In vitro responses were studied in a pressurized no-flow state with video microscopy. Isoproterenol (0.02 micrograms.kg-1.min-1, intracoronary) increased coronary blood flow by 100 +/- 32% (P < 0.001) before CPB and cardioplegic arrest, 17 +/- 7% 2 min postcardioplegia (P < 0.01), and 71 +/- 9 (P < 0.001) after 1 h of reperfusion. Relaxation of precontracted microvessels (90-180 micron) to isoproterenol, NaF, forskolin, and adenosine was reduced after cardioplegic arrest (all P < 0.001). After 1 h of postcardiolegia-reperfusion, relaxation responses to forskolin and adenosine were completely restored, whereas the responses to isoproterenol (P < 0.05) and NaF (P < 0.10) were only partially recovered. Cardioplegic arrest and postcardioplegia-reperfusion blunted the alpha 2-adrenoceptor-mediated endothelium-dependent relaxation to clonidine (P < 0.001) but did not affect the minimal (< 4%) contractile response to the alpha 1-adrenoceptor agonist phenylephrine or the relaxation to nitroprusside. These results show that hyperkalemic cardioplegia results in the generalized defect in the beta-adrenoceptor-GS protein-adenylate cyclase pathway, which is significantly restored after reperfusion.
Wang
S Y
SY
Department of Surgery, Beth Israel Hospital, Boston, Massachusetts 02215.
Friedman
M
M
Johnson
R G
RG
Weintraub
R M
RM
Sellke
F W
FW
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D005576:Colforsin / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology*; D003460:Crystallization; D005112:Extracorporeal Circulation; D005260:Female; D006324:Heart Arrest, Induced; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology; D012969:Sodium Fluoride / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D002314:Cardioplegic Solutions; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009599:Nitroprusside; D005576:Colforsin; D012969:Sodium Fluoride; D000241:Adenosine; D007545:Isoproterenol