Biomaterial Database

The effects of Bay K 8644 on diastolic function in the dog heart. 1990

R J Gelpi, and S M Mosca, and H E Cingolani

Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, La Plata, Argentina.

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.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011433	Propranolol	A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.	Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003971	Diastole	Post-systolic relaxation of the HEART, especially the HEART VENTRICLES.	Diastoles
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001498	3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester	A dihydropyridine derivative, which, in contrast to NIFEDIPINE, functions as a calcium channel agonist. The compound facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels, thereby causing vasoconstrictor and positive inotropic effects. It is used primarily as a research tool.	BK-8644,Bay R5417,Bay-K-8644,Bay-K-8644, (+)-Isomer,Bay-K-8644, (+-)-Isomer,Bay-K-8644, (-)-Isomer,Bay-K8644,Bay-R-5417,BK 8644,BK8644,Bay K 8644,Bay K8644,Bay R 5417,BayK8644,BayR5417,R5417, Bay
D016277	Ventricular Function, Left	The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.	Left Ventricular Function,Function, Left Ventricular,Functions, Left Ventricular,Left Ventricular Functions,Ventricular Functions, Left