Direct and interactive effects of cardioplegic arrest and protamine on myocyte contractility.
BACKGROUND
Cardioplegic arrest with rewarming and protamine administration have been implicated in causing transient left ventricular dysfunction perioperatively. However, whether interactive effects between cardioplegic arrest and rewarming with protamine occur with respect to myocyte contractile processes remains unclear. Accordingly, using an isolated myocyte model, the present study tested the hypothesis that simulated cardioplegic arrest with rewarming and protamine would have direct and interactive effects on myocyte contractile function.


METHODS
Left ventricular isolated myocyte contractile function was examined using computer-aided videomicroscopy under normothermic conditions (37 degrees C, cell medium; n = 183) and after simulated hypothermic, hyperkalemic cardioplegic arrest with rewarming (4 degrees C, 24 mEq/L K+, 2 hours; then 37 degrees C, cell medium, 5 minutes; n = 268). Myocyte function was then examined in the presence of protamine (10 to 40 micrograms/mL) under normothermic conditions (n = 102) and after cardioplegic arrest with rewarming (n = 175).


RESULTS
Myocyte contractile function decreased by 43% from baseline after simulated cardioplegic arrest with rewarming. Under normothermic conditions, protamine (20 micrograms/mL) reduced myocyte contractile function by 43.9% +/- 4.3%, whereas myocyte contractile function decreased by only 31.1% +/- 2.7% with protamine (20 micrograms/mL) after cardioplegic arrest with rewarming. Thus, the negative effects of protamine on myocyte contractility were attenuated after cardioplegic arrest when compared with normothermic conditions.


CONCLUSIONS
The present study demonstrated that simulated cardioplegic arrest with rewarming and protamine have direct and interactive effects on myocyte contractile function, which are not additive or synergistic.
O
S J
SJ
Department of Surgery, Medical University of South Carolina, Charleston 29425, USA.
Cox
M H
MH
Mukherjee
R
R
Clair
M J
MJ
Crawford
F A
FA
Spinale
F G
FG
D000818:Animals; D001831:Body Temperature; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D006324:Heart Arrest, Induced; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007036:Hypothermia, Induced; D007091:Image Processing, Computer-Assisted; D008297:Male; D008853:Microscopy; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D017694:Rewarming; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects; D014741:Video Recording
D002314:Cardioplegic Solutions; D003470:Culture Media; D006494:Heparin Antagonists; D011479:Protamines; D011188:Potassium