Biomaterial Database

Mechanism of the negative inotropic effect of propofol in isolated ferret ventricular myocardium. 1994

D J Cook, and P R Housmans

Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota 55905.

BACKGROUND The aim of this study was to investigate propofol's effect on myocardial contractility and relaxation and examine its underlying mechanism of action in isolated ferret ventricular myocardium. METHODS The effects of propofol on variables of contractility and relaxation and on the free intracellular Ca++ transient detected with the Ca(++)-regulated photoprotein aequorin were analyzed. Propofol's effects were evaluated in a preparation in which the sarcoplasmic reticulum function was impaired by ryanodine. The effects of propofol's solvent, intralipid, on myocardial contractility, relaxation, and the intracellular Ca++ transient also were examined. RESULTS Propofol, at concentrations of 10 microM or greater, decreased contractility and, at concentrations of 30 of microns or greater, decreased the amplitude of the intracellular Ca++ transient. At equal peak force, control peak aequorin luminescence in [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM [Ca++]o = 2.25 mM and peak aequorin luminescence in 300 microM propofol in [Ca++]o > 2.25 mM did not differ, which suggests that propofol does not alter myofibrillar Ca++ sensitivity. After inactivation of sarcoplasmic reticulum Ca++ release with 1 microM ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++ influx, propofol caused a decrease in contractility and in the amplitude of the intracellular Ca++ transient. Under these conditions, propofol's relative negative inotropic effect did not differ from that in control muscles not exposed to ryanodine. Propofol's solvent, 10% intralipid, exerted a modest positive inotropic effect in this preparation. The intracellular Ca++ transient was unchanged by intralipid. Neither propofol nor intralipid altered the load sensitivity of relaxation. CONCLUSIONS These findings suggest that the negative inotropic effect of propofol results from a decrease in intracellular Ca++ availability with no changes in myofibrillar Ca++ sensitivity. At least part of propofol's action is attributable to inhibition of transsarcolemmal Ca++ influx.

UI	MeSH Term	Description	Entries
D007424	Intracellular Fluid	The fluid inside CELLS.	Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D008297	Male		Males
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010210	Papillary Muscles	Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae.	Muscle, Papillary,Muscles, Papillary,Papillary Muscle
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
D003864	Depression, Chemical	The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.	Chemical Depression,Chemical Depressions,Depressions, Chemical
D005289	Ferrets	Semidomesticated variety of European polecat much used for hunting RODENTS and/or RABBITS and as a laboratory animal. It is in the subfamily Mustelinae, family MUSTELIDAE.	Domestic Polecat,Domestic Polecats,European Polecat,European Polecats,Ferret,Mustela putorius,Mustela putorius furo,Polecat, Domestic,Polecat, European,Polecats, Domestic,Polecats, European
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right