MYOCARDIAL PROTECTION WITH PINACIDIL CARDIOPLEGIA IN THE BLOOD-PERFUSED HEART

Background. Adenosine triphosphate-sensitive potassium-channel openers are potent vasodilators that have been found to be cardioprotective d uring myocardial ischemia. The potassium-channel opener pinacidil was investigated to determine its efficacy as a cardioplegic agent. Method s. A blood-perfused, parabiotic, isolated rabbit heart Langendorff pre paration was used. Fifty-six hearts underwent 30 minutes of global nor mothermic ischemia after a 50-mL infusion of cardioplegia, followed by 60 minutes-of reperfusion. The cardioplegia consisted of Krebs-Hensel eit solution with either vehicle alone (control), 20 mmol KCl, or pina cidil (10, 50, 100, 150, or 200 mu mol/L). The developed pressure was measured at baseline and after reperfusion. Coronary blood flow was me asured with an in-line ultrasonic probe. Results. Pinacidil (50 mu mol /L), as opposed to potassium cardioplegia, provided significantly bett er postischemic percentage recovery of developed pressure compared wit h controls (68.3% +/- 4.0% versus 44.6% +/- 5.5%; p< 0.05). The time u ntil electrical arrest was significantly shorter in the hyperkalemic g roup than in all other groups. Linear end-diastolic pressure-volume re lationships revealed an increase in slope after ischemia in all groups . Coronary flow after 5 minutes of reperfusion was significantly highe r in both the 50-mu mol/L and 100-mu mol/L pinacidil groups compared w ith traditional hyperkalemic arrest, and this returned to baseline aft er 15 minutes. Conclusions. The potassium channel opener pinacidil pro vided dose-dependent myocardial protection during global ischemia in t he blood-perfused rabbit heart model. Potassium-channel openers are a promising class of drugs that may provide an alternative to traditiona l hyperkalemic cardioplegia.