Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

Abstract

Mice are a widely used animal model for investigating cardiovascular disease. Novel technologies have been used to quantify left ventricular function in this species, but techniques appropriate for determining right ventricular (RV) function are less well demonstrated. Detecting RV dysfunction is critical to assessing the progression of pulmonary vascular diseases such as pulmonary hypertension. We used an admittance catheter to measure pressure-volume loops in anesthetized, open-chested mice before and during vena cava occlusion. Mice exposed to chronic hypoxia for 10 days, which causes hypoxia-induced pulmonary hypertension (HPH), were compared with control (CTL) mice. HPH resulted in a 27.9% increase in RV mass ( P < 0.005), a 67.5% increase in RV systolic pressure ( P < 0.005), and a 61.2% decrease in cardiac output ( P < 0.05). Preload recruitable stroke work (PRSW) and slope of the maximum derivative of pressure (dP/d tmax)-end-diastolic volume (EDV) relationship increased with HPH ( P < 0.05). Although HPH increased effective arterial elastance (Ea) over fivefold (from 2.7 ± 1.2 to 16.4 ± 2.5 mmHg/μl), only a mild increase in the ventricular end-systolic elastance (Ees) was observed. As a result, a dramatic decrease in the efficiency of ventricular-vascular coupling occurred (Ees/Ea decreased from 0.71 ± 0.27 to 0.35 ± 0.17; P < 0.005). Changes in cardiac reserve were evaluated by dobutamine infusion. In CTL mice, dobutamine significantly enhanced Ees and dP/d tmax-EDV but also increased Ea, causing a decrease in Ees/Ea. In HPH mice, slight but nonsignificant decreases in Ees, PRSW, dP/d tmax-EDV, and Ea were observed. Thus 10 days of HPH resulted in RV hypertrophy, ventricular-vascular decoupling, and a mild decrease in RV contractile reserve. This study demonstrates the feasibility of obtaining RV pressure-volume measurements in mice. These measurements provide insight into ventricular-vascular interactions healthy and diseased states.