Modulation of myocardial economy and efficiency in mammalian failing and non-failing myocardium by calcium channel activation and beta-adrenergic stimulation.
OBJECTIVE
We investigated the energy-metabolic consequences of positive inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison with isoprenaline, focussing both on the economy of force development and the efficiency of external work.


METHODS
In the first instance, heat liberation was measured in isometrically contracting right ventricular papillary muscles from guinea pigs by means of antimony-bismuth thermopiles; in the second instance, external work and myocardial oxygen consumption were analyzed in isolated failing and non-failing working rat hearts.


RESULTS
In the guinea pig muscle strip preparations BAY K 8644 (10(-5) M) and isoprenaline (10(-8 M) increased peak developed force from 13.7 +/- 2.7 to 37.6 +/- 14.9 mN/mm2 and from 13.6 +/- 5.2 to 38.8 +/- 3.3 mN/mm2, respectively (P < 0.01). Stress-time integral was increased from 10.3 +/- 3.0 to 34.7 +/- 19.2 mN.s/mm2 by BAY K 8644 and from 9.5 +/- 2.4 to 23.0 +/- 1.6 mN.s/mm2 by isoprenaline. Whereas a significant decrease in the ratio between stress-time integral and initial heat (integral of Pdt/IH) (i.e., economy contraction) was observed for isoprenaline (5.26 +/- 1.91 before and 3.11 +/- 0.72 N.m.s.J-1 after treatment (P < 0.01), BAY K 8644 did not significantly alter this index (5.26 +/- 2.39 before and 6.22 +/- 2.63 N.m.s.J-1 after treatment). Similar results were obtained for the ratio between stress-time integral and tension-dependent heat. Significantly more calcium ions were required for equieffective activation of the contractile proteins with isoprenaline as compared to BAY K 8644. In working preparations of sham-operated and infarcted rat hearts, the increase in myocardial oxygen consumption per minute (delta MVO2) for a given increase in external work per minute (delta P) was significantly higher with isoprenaline than with equipotent concentrations of BAY K 8644 or high calcium.


CONCLUSIONS
Inotropic mycardial stimulation by BAY K 8644 is associated with higher economy and efficiency than stimulation by isoprenaline when analyzed both by heat measurements in isometric preparations and by myocardial oxygen consumption in working heart preparations.
Ruf
T
T
Department of Cardiology and Angiology, University of Freiburg, Germany.
Hebisch
S
S
Gross
R
R
Alpert
N
N
Just
H
H
Holubarsch
C
C
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
D000318:Adrenergic beta-Agonists; D002120:Calcium Channel Agonists; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007545:Isoproterenol