Energetic aspects of inotropic interventions in rat myocardium.
Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances isoproterenol and UDCG-115 on myocardial energetics in isometrically contracting left ventricular rat papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. Isoproterenol increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat ("calcium cycling") and tension-dependent heat ("cross-bridge cycling") by means of a new method using 2,3-butanedione monoxime. Both tension-dependent heat per tension-time integral and tension-independent heat increased significantly, due to isoproterenol, from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor tension-dependent heat per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas isoproterenol significantly increased the energy necessary for activation, i.e. calcium cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.
Hasenfuss
G
G
Medizinische Klinik III, University of Freiburg, F.R.G.
Holubarsch
C
C
Just
H
H
Blanchard
E
E
Mulieri
L A
LA
Alpert
N R
NR
D000818:Animals; D002151:Calorimetry; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013816:Thermodynamics; D016276:Ventricular Function
D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D007545:Isoproterenol