Short-duration metoprolol treatment did not improve mitochondrial function, regress right ventricular hypertrophy, or delay the onset of heart failure symptoms in rats with monocrotaline-induced pulmonary hypertension.
Does metoprolol improve right ventricular mitochondrial function or delay heart failure in rats with pulmonary hypertension?
Short-duration metoprolol treatment does not improve right ventricular mitochondrial function, regress hypertrophy, or delay heart failure in a rat model of pulmonary hypertension.
Absolute Event Rate: 182% vs 191%
p-value: p=ns
Pulmonary hypertension (PH) increases the work of the right ventricle (RV) and causes right-sided heart failure. This study examined RV mitochondrial function and ADP transfer in PH animals advancing to right heart failure, and investigated a potential therapy with the specific 1 -adrenergic-blocker metoprolol. Adult Wistar rats (317 4 g) were injected either with monocrotaline (MCT, 60 mg kg -1 ) to induce PH, or with an equivalent volume of saline for controls (CON). At three weeks post-injection the MCT rats began oral metoprolol (10 mg kg -1 day -1-) or placebo treatment until heart failure was observed in the MCT group. Mitochondrial function was then measured using high-resolution respirometry from permeabilised RV fibres. Relative to controls, MCT animals had impaired mitochondrial function but maintained coupling between myofibrillar ATPases and mitochondria, despite an increase in ADP diffusion distances. Cardiomyocytes from the RV of MCT rats were enlarged, primarily due to an increase in myofibrillar protein. The ratio of mitochondria per myofilament area was decreased in both MCT groups (p 0.05) in comparison to control (CON: 1.03 0.04; MCT: 0.74 0.04; MCT + BB: 0.74 0.03). This not only implicates impaired energy production in PH, but also increases the diffusion distance for metabolites within the MCT cardiomyocytes, adding an additional hindrance to energy supply. Together, these changes may limit energy supply in MCT rat hearts, particularly at high cardiac workloads. Metoprolol treatment did not delay the onset of heart failure symptoms, improve mitochondrial function, or regress RV hypertrophy.
Power et al. (Tue,) conducted a other in Pulmonary hypertension and right heart failure (n=18). Metoprolol vs. Untreated monocrotaline-induced pulmonary hypertension (MCT) and healthy saline controls (CON) was evaluated on Mitochondrial function (CI + CII OXPHOS O2 flux in pmol s-1 mg-1) (p=ns). Short-duration metoprolol treatment did not improve mitochondrial function, regress right ventricular hypertrophy, or delay the onset of heart failure symptoms in rats with monocrotaline-induced pulmonary hypertension.