The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide.

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. Research Abstract Details 

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The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. Abstract Text:

Edward O McFalls,Rosemary F Kelly,Qingsong Hu,Abdul Mansoor,Joseph Lee,Michael Kuskowski,Joseph Sikora,Herbert B Ward,Jianyi Zhang,Edward O McFalls,Rosemary F Kelly,Qingsong Hu,Abdul Mansoor,Joseph Lee,Michael Kuskowski,Joseph Sikora,Herbert B Ward,Jianyi Zhang,

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 on ATP-dependent potassium channel opening. In this study, 16 swine underwent a thoracotomy with placement of an external constrictor on the left anterior descending coronary artery (LAD) (hibernation model). Seven additional swine underwent a sham operation. At 10 wk, the myocardial energetic state in the LAD region was assessed by (31)P-NMR spectroscopy, and the ratio of phosphocreatine to ATP (PCr/ATP) was determined at baseline, during glibenclamide treatment (0.5 mg/kg bolus with 50 microg/min iv), and during addition of dobutamine (40 microg x kg(-1) x min(-1) iv). At baseline, transmural blood flow in the LAD and remote region was 0.75 +/- 0.11 and 0.88 +/- 0.09 ml x min(-1) x g(-1), respectively (P < 0.01), in hibernating hearts and 0.83 +/- 0.12 and 0.88 +/- 0.15 ml x min(-1) x g(-1), respectively (not significant), in sham-operated hearts. 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 (not significant). In sham pigs, addition of dobutamine to glibenclamide increased the double product from 10.4 +/- 0.8 to 23.9 +/- 4.0 mmHg x beats x min(-1) x 1,000 (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 PCr/ATP from 2.04 +/- 0.04 to 1.73 +/- 0.08 (P < 0.05). In conclusion, we found that, in chronic hibernating swine myocardium with reduced basal blood flow and perfusion reserve, the transmural energetic state, defined by PCr/ATP, is normal during addition of dobutamine, despite inhibition of ATP-dependent potassium channel opening with glibenclamide. These data suggest that important adaptations other than the 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.

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. Publishing Authors By Initials

EO McFalls,RF Kelly,Q Hu,A Mansoor,J Lee,M Kuskowski,J Sikora,HB Ward,J Zhang,EO McFalls,RF Kelly,Q Hu,A Mansoor,J Lee,M Kuskowski,J Sikora,HB Ward,J Zhang,

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The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: American journal of physiology. Heart and circulat

VOLUME: 293

Page Numbers: H2945-51

Journal Abbreviation: Am. J. Physiol. Heart Circ. Ph

ISSN: 0363-6135

DAY: 24

MONTH: 08

YEAR: 2007

The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide. Information

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LANGUAGE: eng

NlmUniqueID: 100901228

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Grant and Affiliation Information for The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide.

AFFILIATION: Veterans Affairs Medical Center - University of Minnesota, Minneapolis, MN, USA. mcfal001@umn.edu

Country: United States

AGENCY: United States NHLBI

GRANT: HL67828

ACRONYM: HL

MEDLINETA: Am J Physiol Heart Circ Physio

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