Monocrotaline-induced PAH in rats reduced right ventricular systolic function by over 45% as measured by TAPSE compared to controls at 24 days.
Does monocrotaline-induced pulmonary arterial hypertension alter cardiac tissue ionic distribution and impair right ventricular myocyte contractility in rats?
Monocrotaline-induced pulmonary arterial hypertension in rats leads to depletion of cardiac tissue calcium and sodium reserves, which disrupts excitation-contraction coupling and impairs right ventricular myocyte contractility.
Effect estimate: p < 0.05 (significant reduction in TAPSE in PAH group)
Absolute Event Rate: 1.2% vs 2.2%
p-value: p=<0.05
Calcium, sodium and potassium are essential for the contractile function of cardiomyocytes. In pulmonary arterial hypertension (PAH), intracellular calcium dynamics are impaired, affecting contractility and leading to heart failure. Energy-dispersive X-ray spectroscopy associated with scanning electron microscopy (EDS-SEM) technique can be useful for mapping the distribution of these minerals in cardiac tissue. This study aimed to investigate chronic ionic imbalances in the cardiac tissue of a monocrotaline (MCT) induced PAH model, using EDS-SEM, and to evaluate the impact of these imbalances on the contractile function of isolated RV myocytes. Twenty-eight Wistar rats were assigned to Control and PAH groups, with PAH induced by MCT. Right ventricular (RV) function was assessed by echocardiography at day 24. On day 25, cardiac tissue was analyzed by EDS-SEM to quantify electrolytes and by Western blotting, and RV myocyte contractility was measured. Student's t-test was performed to compare the groups. Animals with PAH showed reduced final weight, increased cardiac and RV weight, and reduced RV systolic function compared to controls. EDS-SEM analysis revealed lower Ca and Na density in cardiac tissue of PAH animals. The expression of Ca2+ regulatory proteins was reduced in the PAH group, and the contractility of isolated myocytes was impaired, exhibiting decreased amplitude, contraction velocity, and relaxation velocity. In conclusion, the study demonstrates that MCT-induced ionic imbalances, specifically reduced Ca and Na, disrupt excitation-contraction coupling proteins, leading to impaired cardiomyocyte contractility and contributing to the RV dysfunction observed in PAH.
Soares et al. (Sat,) conducted a other in Male Wistar rats aged 2 months (~200 g) with monocrotaline-induced pulmonary arterial hypertension (n=28). Monocrotaline (MCT) injection vs. Saline injection was evaluated on Right ventricular systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) at day 24 (p < 0.05 (significant reduction in TAPSE in PAH group), p=<0.05). Monocrotaline-induced PAH in rats reduced right ventricular systolic function by over 45% as measured by TAPSE compared to controls at 24 days.