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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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