title: The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide.
abstract: 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.
authors.affiliation: Veterans Affairs Medical Center - University of Minnesota, Minneapolis, MN, USA. mcfal001@umn.edu
authors.forename: Edward O
authors.initials: EO
authors.lastname: McFalls
authors.forename: Rosemary F
authors.initials: RF
authors.lastname: Kelly
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Hu
authors.forename: Abdul
authors.initials: A
authors.lastname: Mansoor
authors.forename: Joseph
authors.initials: J
authors.lastname: Lee
authors.forename: Michael
authors.initials: M
authors.lastname: Kuskowski
authors.forename: Joseph
authors.initials: J
authors.lastname: Sikora
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Ward
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004280:Dobutamine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects*; D005905:Glyburide / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D015640:Ion Channel Gating / Q000187:drug effects*; D017682:Myocardial Stunning / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
chemical_list: D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D004280:Dobutamine; D000255:Adenosine Triphosphate; D005905:Glyburide