The effects of Bay K 8644 on diastolic function in the dog heart.
The effects of increased cytosolic calcium on cardiac mechanics were studied in open chest dogs instrumented with ultrasonic crystals and a miniature pressure transducer. Calcium was increased either by promoting calcium influx with Bay K 8644 (Bay K) or by increasing extracellular calcium concentration. A single dose of Bay K (10 micrograms/kg/min) was administered to each dog. Bay K increased LV systolic pressure, maximal rate of rise of LV pressure (LV + dP/dt), mean velocity of circumferential fiber shortening (Vcf), and calculated LV end-systolic wall stress. The time constant of isovolumic pressure decay (T) was calculated following two different methods: (a) a semilogarithmic method (Tz), and (b) using the linear relation between LV - dP/dt vs LV pressure (T1). Whereas Tz decreased from 31.7 +/- 2.6 to 26.7 +/- 1.7 ms (P less than 0.05), no changes were detected in T1 (46.3 +/- 4.4 vs 50.9 +/- 4.0 ms N.S.) The asymptote value (PB) decreased after Bay K from -9 +/- 2.8 to -22.5 +/- 4.2 mmHg (P less than 0.05). The same results were obtained when the changes in the loading conditions of the heart produced by Bay K were controlled by mechanical manoeuvers or after beta-blockade with propranolol. When calcium chloride was administered in amounts that will produce equal contractile changes as Bay K, a decrease in PB was also observed (from -14.7 +/- 1.6 to -27.7 +/- 6.1 mmHg (P less than 0.05]. Tz decreased from 29.6 +/- 3.6 to 22.5 +/- 2.9 ms (P less than 0.05) and no changes in T1 (52.5 +/- 5 vs 52.4 +/- 7.3 ms, N.S.) were detected. The decrease in the asymptote reported herein could induce a false decrease in the time constant if the altered values of PB are not considered, or another method of calculation of the time constant is used. Neither Bay K nor elevated extracellular calcium concentration modified the diastolic compliance. Changes in loading conditions or a cAMP pathway can be ruled out as a cause of the decrease in PB, since the results were reproduced under controlled loading conditions and beta blockade. These data suggest that increasing cytosolic calcium does not alter either the relaxation rate or the diastolic compliance but does decrease the value toward left ventricular pressure decays.
Gelpi
R J
RJ
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, La Plata, Argentina.
Mosca
S M
SM
Cingolani
H E
HE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D003971:Diastole / Q000187:drug effects*; D004285:Dogs; D008954:Models, Biological; D011433:Propranolol / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011433:Propranolol; D002118:Calcium