Regulation of coronary myoplasmic Ca(2+)-myosin light chain phosphorylation pathway and vasomotor tone: hyperpolarizing versus depolarizing cardioplegia.
BACKGROUND
This study was designed to compare the effects of hyperpolarizing versus depolarizing cardioplegic solutions on the coronary vasomotor regulation, specifically focusing on coronary myoplasmic Ca2+-myosin light chain (MLC) phosphorylation pathway and beta-adrenergic signal transduction.


METHODS
With the use of an in vitro cardioplegic model, rat coronary microvessels loaded with fura-2 were subjected to simulated cold (20 degrees C) cardioplegia and reperfused with Krebs solution for 60 minutes at 37 degrees C. Cardioplegia consisted of either (1) Krebs solution alone (control), (2) Krebs plus adenosine triphosphate-sensitive potassium channel opener (100 micromol/L pinacidil [PCO-CP]), (3) hyperkalemic cardioplegia (K(+) = 25 mmol/L [K-CP]), or (4) K-CP plus magnesium (Mg(2+) = 25 mmol/L; [K/Mg-CP]).


RESULTS
At the endpoint of the cardioplegic period, K-CP resulted in a significant increase both in [Ca(2+)](i) and in MLC phosphorylation compared with control (both P <.05). In contrast, PCO-CP did not make any significant difference in these indices compared with control. After reperfusion, the relaxation responses to isoproterenol and forskolin after K-CP were significantly reduced (both P <.05 vs control) but were preserved after PCO-CP. K/Mg-CP provided comparable effects to PCO-CP.


CONCLUSIONS
These results suggest that neither an activation of the coronary myoplasmic Ca(2+)-MLC phosphorylation pathway nor beta-adrenergic desensitization seen after exposure to depolarizing cardioplegia occurs with exposure to hyperpolarizing cardioplegia and magnesium-supplemented depolarizing hyperkalemic cardioplegia.
Matsuda
N
N
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Sellke
F W
FW
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions; D005576:Colforsin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D006324:Heart Arrest, Induced; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism*; D010766:Phosphorylation; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002314:Cardioplegic Solutions; D006982:Hypertonic Solutions; D005576:Colforsin; D020110:Pinacidil; D009219:Myosin-Light-Chain Kinase; D008274:Magnesium; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium