Effects of in vivo manganese administration on calcium exchange and contractile force of rat ventricular myocardium

Abstract

The purpose of this study was to investigate the effect of prolonged (14 days) intragastric administration of Mn2+ (0.25 mmol/kg daily) on Ca2+ exchange and contractility of rat ventricular myocardium. Left-ventricular pressure and its first derivative (dP/dt) were recorded by means of a balloon catheter inserted via the left atrium into the left ventricle of the rat heart perfused by Langendorff method. Ca2+ exchange in the stimulated and rested ventricular myocardium was investigated with the aid of 45Ca under the conditions of complete equilibration of preparations with a solution containing 45Ca2+. The "cellular" 45Ca2+ content was calculated by subtraction of 45Ca2+ dissolved in the free water of extracellular space from the total tissue 45Ca2+ content. The cellular 45Ca2+ content in the stimulated (60/min) ventricles of control rats (without Mn2+) was 0.83 +/- 0.09 mmol/kg wet weight (w.w.). Ten minutes of rest resulted in a gain of 0.06 mmol 45Ca/kg w.w. (not statistically significant). Fourteen days' exposure to Mn2+ resulted in an increase of the mean 45Ca content to 1.61 +/- 0.09 mmol/kg w.w. in the stimulated preparations and to 1.35 +/- 0.06 mmol/kg w.w. in the rested ones (p less than 0.001). Thus, the control rest preparations did not change their Ca2+ content, while in the rats treated with Mn2+ the rest resulted in an increase at exchangeable Ca by 52%. The maximal ventricular developed pressure (Pmax) after 14 days of Mn2+ administration was increased by 35% and dP/dtmax was 228% of the value in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Toxicities Upon Manganese Exposure

“…Fourteen days following Mn exposure, the exchangeable Ca in the Mntreated group was increased by 52% as compared with controls. By recording the leftventricular pressure (dP/dt) via a balloon catheter inserted into the left ventricle, the authors also observed that the maximal ventricular developed pressure (P max ) and the maximal leftventricular pressure (dP/dt max ) were increased by 35% and 228%, respectively, in comparison with control rats, following 14 d of Mn administration (27).…”

Mortality from cardiovascular diseases and sudden death in ferroalloy plants

“…The effects of long-lasting exposures are however less clear. A Mn++, intragastric ratfeeding study over 14 days (0.25 mmollkg daily) resulted in increased myocardial contractility (4). Work exposure to manganese was estimated from 339 personal samples of total dust and total manganese during 1979-1991 in the largest of the FeMnISiMn plants; the results showed decreasing values during this period ( figure I).…”

“…possible with exposure to manganese alloys, as animal studies have shown that the divalent manganese ion (Mn++) may influence cardiac function (3,4).…”

Murine Cardiac Hemodynamics Following Manganese Administration Under Isoflurane Anesthesia

“…41,47 It is known as an intracellular agent, rapidly up-taken (within minutes 8,29,54 ) by L-type Ca 2+ channels, 26 and released extremely slowly [within time intervals ‡5-10 min] (with reported excretion half-times of a fast and a slow component of 4 and 39 days, respectively 29 ) from the intracellular space via the Na + -Ca 2+ exchanger. 14,28,34 In fact, Mn 2+ accumulation in rat myocardium has been associated with the Na + -Ca 2+ exchanger, based on its MRI T 2 * effects under experimentally induced hyperkalemic hypoxia conditions. 35 In support of such action by the exchanger for Mn 2+ transport kinetics, were also sodium-potassium ATPase blockade studies in bullfrog ventricles by Brommundt et al, 5 as well as evidence for bidirectional activity of the Na + -Ca 2+ exchanger, mediating cellular Mn 2+ influx, and efflux.…”

“…To date its exact mechanism of action is still not completely comprehended, but it is suggested to act as a Ca 2+ analogue. 14,26,56 Its effects on mouse cardiac function have not been addressed extensively, with its molecular mechanisms on intracellular targets being largely unknown and unproved. Based on experimental results from a series of invasive catheterizations, this study examines the temporal stability of hemodynamic indices of systolic and diastolic function in C57BL/6 mice under isoflurane (ISO) anesthesia conditions (employing the same protocol widely used in MRI/microCT studies), and the effects of Mn 2+ on the mouse hemodynamic response as a potential modulator of myocardial force generation.…”