Dose-response to lead-induced alterations in right atrial and ventricular myocardial contractility in adult rats

Lead is a widespread environmental xenobiotic known to adversely affect cardiovascular health. This study is the first to systematically assess the impact of subchronic lead acetate exposure (5.5, 11, and 22.88 mg/kg body weight, administered via intraperitoneal injections three times a week for six weeks) on the contractile properties of the right atrial and right ventricular myocardium in 12-month-old male rats, using both in vitro motility assays and physiological contraction measurements on myocardial strips from the same hearts. Lead exposure produced a dose-dependent decrease in thin filament sliding velocity over right atrial myosin, whereas the effects on right ventricular myosin were nonlinear. Higher doses of lead significantly reduced the fraction of motile filaments in the atrium, while lower doses affected the ventricle. Under physiological loading mode, right atrial myocardial strips generated approximately 20 % of the mechanical work produced by right ventricular strips. Increasing lead doses further reduced mechanical work in both chambers, with a more pronounced reduction in the atrium (≈65 %) than in the ventricle (≈17 %) at the highest dose. Maximum shortening velocity also declined with increasing lead concentration, particularly in the atrium at low afterloads. These findings demonstrate that the right atrial myocardium is more sensitive to subchronic lead intoxication than the right ventricular myocardium. Overall, this study provides the first comprehensive analysis of lead's differential effects on atrial and ventricular contractility under physiological loading conditions.