Center for Congenital Heart Diseases, Division of Pediatric Cardiology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands.
Am J Physiol Heart Circ Physiol. 2013 Aug 1;305(3):H354-64. doi: 10.1152/ajpheart.00180.2013. Epub 2013 May 31.
Right ventricular (RV) failure due to chronically abnormal loading is a main determinant of outcome in pulmonary hypertension (PH) and congenital heart disease. However, distinct types of RV loading have been associated with different outcomes. To determine whether the adaptive RV response depends on loading type, we compared hemodynamics, exercise, and hypertrophy in models of pressure overload due to pulmonary artery banding (PAB), pressure overload due to PH, combined pressure and volume overload, and isolated volume load. Ninety-four rats were subjected to either PAB, monocrotaline-induced PH (PH), aortocaval shunt (shunt), or combined monocrotaline and aortocaval shunt (PH + shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH + shunt to either isolated PH or shunt (part II). In part I, enhanced contractility (end-systolic elastance and preload recruitable stroke work) was present in PH and PAB, but strongest in PAB. Frank-Starling mechanism was active in both PAB and PH. In PAB this was accompanied by diastolic dysfunction (increased end-diastolic elastance, relaxation constant), clinical signs of RV failure, and reduced exercise. These distinct responses were not attributable to differences in hypertrophy. In part II, in PH + shunt the contractility response was blunted compared with PH, which caused pseudonormalization of parameters. Additional volume overload strongly enhanced hypertrophy in PH. We conclude that different types of loading result in distinct patterns of RV adaptation. This is of importance for the approach to patients with chronically increased RV load and for experimental studies in various types of RV failure.
由于慢性异常负荷导致的右心室（RV）衰竭是肺动脉高压（PH）和先天性心脏病患者预后的主要决定因素。然而，不同类型的 RV 负荷与不同的结果相关。为了确定适应性 RV 反应是否取决于负荷类型，我们比较了肺动脉结扎（PAB）、PH 导致的压力超负荷、压力和容量超负荷以及单纯容量负荷引起的 RV 血流动力学、运动和肥大模型。94 只大鼠分别接受 PAB、单克尿氨酸诱导的 PH（PH）、腔静脉-主动脉分流（分流）或单克尿氨酸和腔静脉-主动脉分流（PH + 分流）。我们在 4 周时进行压力-容积分析和自愿运动测量。我们将 PAB 与 PH（第 I 部分）和 PH + 分流与单纯 PH 或分流（第 II 部分）进行比较。在第 I 部分，PH 和 PAB 存在增强的收缩性（收缩末期弹性和预负荷可募集工作），但在 PAB 中最强。Frank-Starling 机制在 PAB 和 PH 中均起作用。在 PAB 中，这伴随着舒张功能障碍（增加舒张末期弹性、松弛常数）、RV 衰竭的临床症状和运动减少。这些不同的反应与肥大的差异无关。在第 II 部分，与 PH 相比，PH + 分流中的收缩性反应减弱，导致参数的假性正常化。在 PH 中，额外的容量超负荷强烈增强了肥大。我们得出结论，不同类型的负荷导致 RV 适应性的不同模式。这对于处理慢性 RV 负荷增加的患者和各种 RV 衰竭的实验研究都很重要。
