Preconditioning improves cardioplegia-related coronary microvascular smooth muscle hypercontractility: role of KATP channels.
OBJECTIVE
The effect of preconditioning before hyperkalemic cardioplegia on the coronary smooth muscle remains to be elucidated. We tested the hypothesis that hypoxic preconditioning could protect coronary smooth muscle against subsequent hyperkalemic cardioplegia-induced coronary vasospasm and that this preconditioning effect could be mediated by K(ATP) channels.


METHODS
Rat coronary arterioles (endothelium-denuded) were studied in a pressurized, no-flow, normothermic state. Simultaneous monitoring of luminal diameter and intracellular calcium concentration of vascular smooth muscle loaded with fura-2 was made with microscopic image analysis. All vessels were subjected to 60 minutes of hypoxic hyperkalemic cardioplegia (K(+) = 25.0 mmol/L) and were then reperfused. Six groups were studied: (1) controls, no precardioplegic intervention; (2) preconditioning, achieved with 10 minutes of hypoxia (PO2 < 30 mm Hg) and 10 minutes of reoxygenation; (3) preconditioning plus glibenclamide (10 micromol/L), achieved with 10 minutes of preconditioning in the presence of K(ATP) channel blocker glibenclamide; (4) pretreatment with K(ATP) channel opener pinacidil (100 micromol/L); (5) pretreatment with pinacidil (100 micromol/L) plus glibenclamide (10 micromol/L); and (6) pretreatment with glibenclamide (10 micromol/L) alone.


RESULTS
Hypoxic preconditioning significantly (P <.01) reduced hyperkalemic cardioplegia-induced intracellular calcium concentration accumulation and prevented the hypercontractility during and after hyperkalemic cardioplegia compared with control vessels. Pinacidil provided effective microvascular protection similar to hypoxic preconditioning. These vasoprotective effects of preconditioning were significantly antagonized in glibenclamide-treated vessels.


CONCLUSIONS
Hypoxic preconditioning can prevent coronary microvascular hypercontractility during and after subsequent cardioplegia by a K(ATP ) channel mechanism that regulates intracellular calcium concentration of the vascular smooth muscle.
Matsuda
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N
Division of Cardiothoracic Surgery, Department of Surgery of Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Morgan
K G
KG
Sellke
F W
FW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002314:Cardioplegic Solutions / Q000633:toxicity; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005905:Glyburide / Q000494:pharmacology; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000633:toxicity*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology
D002314:Cardioplegic Solutions; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D011188:Potassium; D005905:Glyburide; D002118:Calcium