Myocyte endothelin exposure during cardioplegic arrest exacerbates contractile dysfunction after reperfusion.
Transient left ventricular (LV) dysfunction can occur after cardioplegic arrest. The contributory mechanisms for this phenomenon are not completely understood. We tested the hypothesis that exposure of LV myocytes to endothelin (ET) during simulated cardioplegic arrest would have direct effects on contractile processes with subsequent reperfusion. LV porcine myocytes were randomly assigned to three groups: 1) CONTROL: normothermic (37 degrees C) cell media (n = 204); 2) Cardioplegia: simulated cardioplegic arrest (K(+) 24 mEq/L, 4 degrees C x 2 h) followed by reperfusion and rewarming with cell media (n = 164); and 3) Cardioplegia/ ET: simulated cardioplegic arrest in the presence of ET (200 pM) followed by reperfusion with cell media containing ET (n = 171). Myocyte contractility was measured by computer-assisted video microscopy. In a subset of experiments, myocyte intracellular calcium was determined after Fluo-3 (Molecular Probes, Eugene, OR) loading by digital fluorescence image analysis. Myocyte shortening velocity was reduced after cardioplegic arrest compared with controls (52 +/- 2 vs 84 +/- 3 microm/s, respectively; P < 0.05) and was further reduced with cardioplegic arrest and ET exposure (43 +/- 2 microm/s, P < 0.05). Intracellular calcium was significantly increased in myocytes exposed to cardioplegia compared with normothermic control myocytes and was further augmented by cardioplegia with ET supplementation (P < 0.05). Exposure of the LV myocyte to ET during cardioplegic arrest directly contributed to contractile dysfunction after reperfusion. Moreover, alterations in intracellular calcium may play a role in potentiating the myocyte contractile dysfunction associated with ET exposure during cardioplegic arrest.
Dorman
B H
BH
Department of Anesthesia & Perioperative Medicine, Medical University of South Carolina, Charleston 29425, USA. dormanhb@musc.edu
New
R B
RB
Bond
B R
BR
Mukherjee
R
R
Mukhin
Y V
YV
McElmurray
J H
JH
Spinale
F G
FG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000032:analysis; D019332:Endothelin-1 / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D018715:Microscopy, Video; D009200:Myocardial Contraction / Q000187:drug effects; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D013552:Swine
D000318:Adrenergic beta-Agonists; D019332:Endothelin-1; D007545:Isoproterenol; D002118:Calcium