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Am J Physiol Heart Circ Physiol (August 24, 2007). doi:10.1152/ajpheart.00012.2007
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Submitted on January 4, 2007
Accepted on August 16, 2007

The Energetic State Within Hibernating Myocardium is Normal During Dobutamine Despite Inhibition of ATP-Dependent Potassium Channel Opening With Glibenclamide

Edward O McFalls1*, Rosemary F Kelly2, Qingsong Hu3, Abdul Mansoor3, Joseph Lee4, Michael Kuskowski5, Joseph Sikora6, Herbert B Ward6, and Jianyi Zhang3

1 Cardiology, VA Medical Center, Minneapolis, Minnesota, United States
2 CV Surgery, VA Medical Center, Minneapolis, Minnesota, United States
3 Magnetic Resonance Unit, University of Minnesota, Minneapolis, Minnesota, United States
4 Magnetic Resonance Unit, University of Minnesota, minneapolis, Minnesota, United States
5 GRECC, VA Medical Center, minneapolis, Minnesota, United States
6 CV Surgery, VA Medical Center, minneapolis, Minnesota, United States

* To whom correspondence should be addressed. E-mail: mcfal001{at}umn.edu.

Background. Within hibernating myocardium, it is uncertain whether a normal energetic state is present at baseline and whether maintaining that energy state during a catecholamine challenge is dependent upon ATP-dependent potassium channel opening. Methods and Results. Sixteen swine underwent a thoracotomy with placement of an external constrictor on the LAD artery (Hibernation model). Seven additional swine underwent a sham operation. At 10 weeks, the myocardial energetic state in the LAD region was assessed by 31P-NMR spectroscopy and the phosphocreatine to ATP (PCr/ATP) ratio was determined at baseline, during glibenclamide (0.5 mg/kg-bolus with 50 µg/min; iv) and during addition of dobutamine (40 µg/kg/min;iv). At baseline, transmural blood flow in the LAD and remote region from the Hibernating hearts was 0.75 ±0.11 and 0.88 ±0.09 ml/min/g respectively (P<0.01) and from the Sham-operated hearts was 0.83 ±0.12 and 0.88 ±0.15 ml/min/g respectively (NS). Under basal conditions, PCr/ATP in the LAD region of Hibernating and Sham pigs was 2.15 ±0.04 and 2.11 ±0.05 respectively (NS). In Sham pigs, addition of dobutamine to glibenclamide increased the double product from 10.4 ±0.8 to 23.9 ±4.0 mmHg-beats/minX1000 (P<0.05) and decreased transmural PCr/ATP from 2.06 ±0.06 to 1.69 ±0.06 (P<0.05). Dobutamine increased the double product in Hibernating pigs in a similar fashion and despite a 40% lower blood flow response, induced an equivalent decrease in the PCr/ATP ratio from 2.04 ±0.04 to 1.73 ±0.08 (P<0.05). Conclusions. In chronic hibernating swine myocardium with reduced basal blood flow and perfusion reserve, the transmural energetic state, defined by the PCr/ATP ratio, is normal during dobutamine, despite inhibition of ATP-dependent potassium channel opening with glibenclamide. These data suggest that important adaptations other than ATP-dependent potassium channel opening allow hibernating myocardium to operate over a lower range of the oxygen supply-demand relationship to protect against myocardial ischemia.




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Am. J. Physiol. Heart Circ. Physiol.Home page
Q. Hu, G. Suzuki, R. F. Young, B. J. Page, J. A. Fallavollita, and J. M. Canty Jr.
Reductions in mitochondrial O2 consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H223 - H232.
[Abstract] [Full Text] [PDF]




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