Cardiac physiologic-metabolic changes after chronic low-level heavy metal feeding

Abstract

Female Long-Evans hooded rats received 0 or 5 parts per million Cd, Pb, or Cd + Pb in the drinking water from weaning to 20 mo. Growth, measured as body weight, and organ weights were comparable among heavy metal and control animals. Indirect blood pressure responses measured trimonthly are discussed. Analysis of His bundle electrograms (HBE) and electrocardiograms recorded in sodium pentobarbital-anesthetized animals at 20 mo demonstrated that Cd selectively depressed conduction system excitability proximal to the common His bundle (atrioventricular node region), whereas Pb and Pb + Cd impaired conductivity distal to the common His bundle (His-Purkinje system). Perchloric acid extracts of liquid N2-freeze-clamped isolated perfused hearts, derived from a subpopulation of control and Cd-fed rats in which HBE analyses were not performed, were analyzed by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopic techniques to quantitate [31P]phosphate metabolite profiles. Cardiac active tension and atrioventricular node excitability were depressed in the Cd group. High-energy phosphate and glycerol 3-phosphorylcholine concentrations were depressed. Results demonstrate potentially significant pathophysiological changes within cardiovascular tissues that develop in the absence of overt heavy metal toxicity manifestations.

Effect of Mg deficiency on blood pressure in rats treated with cadmium.

“…Some workers have observed cardiotoxic effects in the rats with about 5ppm Cd in cardiac tissue (21,22). This value which may produce cardiotoxicity is higher than that of our present findings (1ppm).…”

In vitro Inhibition of Na-K-ATPase by Trace Metals: Relation to Renal and Cardiovascular Damage

“…Thus, it is well known that inhibition of Na-K-ATPase alters myo cardial function and, e.g., experimental chronic low Cd exposure without overt intoxication was found to depress cardiac function and metabolism [36]. In addition, a rise in vascular smooth muscle cell sodium concentration following inhibition of Na-K-ATPase results in in creased intracellular calcium [11] and leads to an elevated basal vascular tone [37,38] and to enhanced vascular responsiveness to vasoconstrictor hormones [39].…”

“…In addition, a rise in vascular smooth muscle cell sodium concentration following inhibition of Na-K-ATPase results in in creased intracellular calcium [11] and leads to an elevated basal vascular tone [37,38] and to enhanced vascular responsiveness to vasoconstrictor hormones [39]. In hy pertensive patients, elevated Cd levels in kidney tissue and increased urinary excretion of Cd have been found, and low Cd exposure enhances aortic plaque formation, arterial wall lipid deposition and hypertension in animals [36,[40][41][42][43]. Similar alterations were found with chronic Pb exposure [44] and, when fed lead acetate in the drink ing fluid to achieve blood concentrations similar to those found in some human populations living in urban envir onment, rats develop significant increases in systolic blood pressure.…”

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“…Oral administration of lead (5µg/ml drinking water) for 15 and 20 months has been reported to be associated with a significant slowing of aterioventricular conduction 18 . However there is not much data on cardiovascular effects of either low or moderate amounts of lead exposure 19 .…”