Modulation of myothermal economy of isometric force generation by positive inotropic interventions in the guinea pig myocardium.
Isometric force development has been measured simultaneously with liberated heat in papillary muscles from the right ventricle of the guinea pig, using rapid antimony-bismuth thermopiles. The following components of the contractile cycle and their relation to energy consumption were evaluated: (1) basal metabolism; (2) crossbridge cycling; (3) calcium cycling; and (4) recovery processes. The influences of isoproterenol, high calcium and UDCG-115, a calcium-sensitizing substance, on these four energy compartments of the muscle were studied relative to their positive inotropic effects. Isoproterenol increased initial heat per peak developed tension or per tension-time integral from 7.4 +/- 1.55 to 11.65 +/- 1.15 mucal/g cm (p less than 0.02) or from 4.52 +/- 0.79 to 8.14 +/- 0.77 mucal/g cm sec (p less than 0.01), respectively. In contrast, these ratios were unchanged from control values by positive inotropic interventions with 11 mM calcium or UDCG-115. The increase of initial heat for a unit of mechanical activity due to isoproterenol is attributable to activation and contractile protein processes, i.e. the activation heat increased from 0.24 +/- 0.05 to 0.68 +/- 0.13 mcal/g (p less than 0.01) and tension-dependent heat per tension-time integral increased from 2.24 +/- 0.60 to 5.18 +/- 0.89 mucal/g cm sec (p less than 0.01). We conclude that isoproterenol increases the number of calcium ions released into the sarcoplasm during each activation cycle. It also alters the rate of crossbridge cycling associated with a decreased economy of force generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Holubarsch
C H
CH
Dept. of Cardiology, University of Freiburg, F.R.G.
Hasenfuss
G
G
Just
H
H
Blanchard
E M
EM
Mulieri
L A
LA
Alpert
N R
NR
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology*; D013268:Stimulation, Chemical
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D007545:Isoproterenol; D002118:Calcium