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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Myocardial oxygen consumption in the rabbit heart after ischemia: hyperpolarized arrest with pinacidil versus depolarized hyperkalemic arrest.

BACKGROUND: This study was designed to test the hypothesis that adenosine triphosphate-sensitive potassium channel opener (PCO)-induced hyperpolarized arrest with pinacidil minimizes cellular energy requirements during global ischemia compared with traditional, hyperkalemic depolarized arrest, which is known to be associated with ongoing energy-consuming ion transport. METHODS AND RESULTS: Using a blood-perfused parabiotic rabbit heart Langendorff model, myocardial oxygen consumption (MVO2) was compared in hearts protected with either Krebs-Henseleit solution (K-H), pinacidil (50 micromol/L in K-H), or hyperkalemic St. Thomas' solution during a 30-minute period of global, normothermic (37 degrees C) ischemia followed by 30 minutes of reperfusion. MVO2 (mL/100 g of myocardium per beat) was calculated at baseline and continuously during reperfusion with the use of an in-line flow probe and an in-line coronary sinus oximetric catheterizationeter. Systolic function (percentage recovery of developed pressure) was measured over a range of volumes using a balloon in the left ventricle. Percentage recovery of developed pressure with pinacidil (60.3%+/-3.1%) was not statistically different from that with St Thomas' solution (53.3%+/-2.8%). Pinacidil provided superior protection versus K-H (44.4%+/-4.8%, P<.05). The MVO2 was significantly (P<.05) elevated in the pinacidil group (0.77+/-0.12) compared with the St Thomas group (0.29+/-0.04) during the first 6 minutes of reperfusion. CONCLUSIONS: The cardioprotective properties of PCOs are associated with an increased myocardial oxygen demand on reperfusion. This may be related to reparative processes of viable myocytes or to a higher oxygen debt generated during ischemia that presents a significant limitation to PCO cardioplegia.[1]

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