Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706-1609, USA.
Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H2069-75. doi: 10.1152/ajpheart.00805.2010. Epub 2010 Oct 8.
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/dt(max))-end-diastolic volume (EDV) relationship increased with HPH (P < 0.05). Although HPH increased effective arterial elastance (E(a)) over fivefold (from 2.7 ± 1.2 to 16.4 ± 2.5 mmHg/μl), only a mild increase in the ventricular end-systolic elastance (E(es)) was observed. As a result, a dramatic decrease in the efficiency of ventricular-vascular coupling occurred (E(es)/E(a) 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 E(es) and dP/dt(max)-EDV but also increased E(a), causing a decrease in E(es)/E(a). In HPH mice, slight but nonsignificant decreases in E(es), PRSW, dP/dt(max)-EDV, and E(a) 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.
小鼠被广泛用作研究心血管疾病的动物模型。已经使用新技术来量化该物种的左心室功能，但用于确定右心室（RV）功能的技术则不太完善。检测 RV 功能障碍对于评估肺动脉疾病（如肺动脉高压）的进展至关重要。我们使用顺应性导管在麻醉、开胸的小鼠中测量腔静脉闭塞前后的压力-容积环。与对照（CTL）小鼠相比，暴露于 10 天慢性缺氧的小鼠会导致缺氧诱导的肺动脉高压（HPH）。HPH 导致 RV 质量增加 27.9%（P < 0.005），RV 收缩压增加 67.5%（P < 0.005），心输出量减少 61.2%（P < 0.05）。预负荷可获取的冲程工作（PRSW）和压力最大导数（dP/dt(max)）-舒张末期容积（EDV）关系斜率随 HPH 增加（P < 0.05）。尽管 HPH 将有效动脉弹性（E(a)）增加了五倍以上（从 2.7 ± 1.2 增加到 16.4 ± 2.5 mmHg/μl），但仅观察到心室收缩末期弹性（E(es)）的轻度增加。因此，心室-血管偶联的效率急剧下降（E(es)/E(a)从 0.71 ± 0.27 降低到 0.35 ± 0.17；P < 0.005）。通过多巴酚丁胺输注评估心脏储备的变化。在 CTL 小鼠中，多巴酚丁胺显著增强了 E(es)和 dP/dt(max)-EDV，但也增加了 E(a)，导致 E(es)/E(a)降低。在 HPH 小鼠中，仅观察到 E(es)、PRSW、dP/dt(max)-EDV 和 E(a)的轻微但无统计学意义的降低。因此，10 天的 HPH 导致 RV 肥大、心室-血管解偶联和 RV 收缩储备的轻度降低。本研究证明了在小鼠中获得 RV 压力-容积测量的可行性。这些测量为健康和患病状态下的心室-血管相互作用提供了深入了解。
