Compensatory changes in Ca(2+) and myocardial O(2) consumption in beta-tropomyosin transgenic hearts.
Transgenic mice overexpressing beta-tropomyosin have increased myofilament Ca(2+) sensitivity that we hypothesized would result in altered relationships among pressure and heart rates, intracellular Ca(2+), and myocardial O(2) consumption. In perfused hearts from transgenic mice there was a marked negative force-frequency response between 6 and 10 Hz with a 30 +/- 3% reduction in peak-positive first derivative of pressure development over time (dP/dt) compared with 14 +/- 2% in wild-type mice (P < 0.001). At 8 Hz systolic pressures were normal, though peak systolic intracellular Ca(2+) was significantly reduced in transgenic mice versus wild type (726 +/- 61 vs. 936 +/- 67 nM, P < 0.05) indicating an alteration in the pressure-Ca(2+) relationship. Over a wide range of positive and negative inotropic interventions there were normal developed pressures, though marked elevations in myocardial O(2) consumption (15-54%). Because pressures are normal and intracellular Ca(2+) decreased and myocardial O(2) consumption increased, this suggests that these abnormalities are at least in part compensatory mechanisms to the altered myofilament function.
MacGowan
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GA
Cardiovascular Institute of the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA. macgowanga@msx.upmc.edu
Du
C
C
Wieczorek
D F
DF
Koretsky
A P
AP
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion; D014335:Tropomyosin / Q000235:genetics*
D002316:Cardiotonic Agents; D014335:Tropomyosin; D004280:Dobutamine; D002118:Calcium