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.


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.
Lawton
J S
JS
Department of Surgery, Medical College of Virginia, Richmond, USA.
Hsia
P W
PW
McClain
L C
LC
Maier
G W
GW
Damiano
R J
RJ
D000818:Animals; D003326:Coronary Circulation; D003971:Diastole; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006947:Hyperkalemia / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D013599:Systole
D006146:Guanidines; D015221:Potassium Channels; D020110:Pinacidil