A phenotype of increased sleepiness in a mouse model of pulmonary hypertension and right ventricular hypertrophy

Abstract

The relationship between cardiovascular disease and abnormalities in sleep architecture is complex and bi-directional. Sleep disordered breathing (SDB) often confounds human studies examining sleep in the setting of heart failure, and the independent impact of isolated right or left heart failure on sleep is difficult to assess. We utilized an animal model of right heart failure using pulmonary artery banding (PAB) in mice to examine the causal effect of right heart failure on sleep architecture. Four weeks after PAB or sham (control) surgery, sleep was measured by polysomnography for 48 hours and right ventricular (RV) hypertrophy confirmed prior to sacrifice. PAB resulted in right ventricular hypertrophy based on a 30% increase in the Fulton Index (p < 0.01). After PAB, mice spent significantly more time in NREM sleep compared to the control group over a 24 hour period (53.5 ± 1.5% vs. 46.6 ± 1.4%; p < 0.01) and exhibited an inability to both cycle into REM sleep and decrease delta density across the light/sleep period. Our results support a phenotype of impaired sleep cycling and increased ‘sleepiness’ in a mouse model of RV dysfunction.

Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery

“…Previous data have shown that apoE-knockout mice on an HFD developed PH; clearly, these animals also developed an evident level of pulmonary atherosclerosis, which may be a bias in the correlation of IR with PH ( 12 ). Our model of obesity-induced IR showed an increase in pulmonary artery pressure, with an RVSP variation of 6–9 mmHg and also confirmed after catheterization, which was not based on left ventricular dysfunction and seems to be similar to other PH animal models induced by other methods ( 30 , 31 ).…”