Manganese and the heart: acute cardiodepression and myocardial accumulation of manganese.
The aim of study was to assess acute effects of the divalent manganese ion (Mn2+) in an intact but isolated heart preparation. Rat hearts were perfused in the Langendorff mode at constant flow rate. Left ventricular (LV) developed pressure (LVDP). LV pressure first derivatives (LVdp/dt max and min), heart rate (HR) and aortic pressure (AoP) were recorded. Ventricular contents of high energy phosphate compounds (HEP) and Mn metal were measured at the end of experiment. Infusion of MnCl2 for 5 min with perfusate concentrations 1-3000 microM induced an immediate depression of contractile function at and above 30 microM and negative chronotropy at and above 300 microM. These IC50 values were found (microM): LVDP 250; LVdp/dt max 160; LVdp/dp min 120; HR 1000; and increase in AoP 80. Recovery of function during a 14 min washout period was rapid and extensive except for Mn2+ 3000 microM. Somewhat unexpected, Mr2+ 30-1000 microM raised coronary vascular resistance up to about twice the control level, whereas the vasoconstrictory response was overcome at 3000 microM. Mn2+ 3000 microM reduced tissue HEP Ventricular Mn content rose stepwise for perfusate Mn2+ above 1 microM up to about 55 times the control level for perfusate Mn2+ 3000 microM. It is concluded that: acute effects of Mn2+ like depression of contractility and rate is rapidly reversible; and rat hearts accumulate and buffer large amounts of Mn2+ without affecting cardiac function or energy metabolism in the acute stage.
Brurok
H
H
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Trondheim, Norway.
Schjøtt
J
J
Berg
K
K
Karlsson
J O
JO
Jynge
P
P
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D008297:Male; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008345:Manganese