Defects in myoglobin oxygenation in K(ATP)-deficient mouse hearts under normal and stress conditions characterized by near infrared spectroscopy and imaging.
BACKGROUND
Disruption of ATP-sensitive potassium (K(ATP)) channel activity results in the development of dilated cardiomyopathy in response to different forms of stress, likely due to the underlying metabolic defects. To further understand the role of Kir6.2-containing channels in the development of cardiac disease, we analysed the left ventricular (LV) wall oxygenation and the physiologic responses induced by acute stress in non-dilated Kir6.2(-/-) hearts.


METHODS
Control (C57BL6) and Kir6.2(-/-) mouse hearts were perfused in constant flow Langendorff mode with Krebs-Henseleit buffer. Myocardial oxygenation was evaluated using a newly developed technique, near infrared spectroscopic imaging (NIRSI) of the myoglobin (Mb) oxygen saturation parameter (OSP, ratio of oxy- to total Mb).


RESULTS
2,4-dinitrophenol (DNP, 50-µM) and isoproterenol (0.1-µM) failed to produce a transient vasodilatory response and caused a significant diastolic pressure increase in Kir6.2(-/-) hearts. DNP strongly suppressed contractile function in both groups and induced severe mean OSP decreases in Kir6.2(-/-) hearts. Isoproterenol-induced decreases in OSP were similar despite the lack of contractile function stimulation in the Kir6.2(-/-) group. The index of OSP spatial heterogeneity (relative dispersion, RD) was lower by 15% in the Kir6.2(-/-) group at the baseline conditions. Recovery after stress caused reduction of RD values by 20% (DNP) and 8% (isoproterenol) in controls; however, these values did not change in the Kir6.2(-/-) group.


CONCLUSIONS
1) NIRSI can be used to analyse 2-D dynamics of LV oxygenation in rodent models of cardiomyopathy; 2) Kir6.2-containing K(ATP) channels play an important role in maintaining myocardial oxygenation balance under acute stress conditions and in post-stress recovery.
Jilkina
Olga
O
Institute for Biodiagnostics, National Research Council of Canada, Winnipeg, MB, Canada. olga.jilkina@nrc-cnrc.gc.ca
Glogowski
Miriam
M
Kuzio
Bozena
B
Zhilkin
Peter A
PA
Gussakovsky
Eugene
E
Kupriyanov
Valery V
VV
D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000208:Acute Disease; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D014475:Uncoupling Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D000099161:Kcnj11 Channel
D019297:2,4-Dinitrophenol; D002316:Cardiotonic Agents; D007545:Isoproterenol; D009211:Myoglobin; D010100:Oxygen; D024661:Potassium Channels, Inwardly Rectifying; D014475:Uncoupling Agents; D000099161:Kcnj11 Channel