Tian and colleagues highlight the importance of right and left ventricular interdependence in their article in this issue of Acta Physiologica. The role of the right ventricle is often underestimated in health and disease. In comparison with the left ventricle, the right ventricle is triangular shaped, whereas the left ventricle is conical. Right ventricular function has been shown to be an important determinant of outcome in many disease states. These range from paediatric disorders to adult acquired conditions. Paediatric conditions include congenital heart disease in which the right ventricle may supply output to the systemic circulation. Even though some children do not require a right ventricle, such as in single ventricle heart disease, bypassing the right ventricle allows for survival but it is fraught with many complications. In adults the right ventricle is important in outcome of many conditions including thromboembolic pulmonary hypertension, chronic obstructive pulmonary disease and left heart disease.

The right ventricle and left ventricle are different in many ways. The left ventricle is developed from the primary heart tube, whereas the right ventricle is developed from the anterior‐secondary heart field. These two ventricles differ in their anatomy, geometry, myocardial fibre orientation and response to increased afterload. The right ventricle pumps to a low pressure, high compliance system. The right ventricle must increase its output at least three to fivefold under normal exercise conditions. The left ventricle has a conical shape, is more muscular, and is adapted to routinely providing systemic levels of blood pressure. Measurements of left ventricular function are easier than measurement of right ventricular function because of uniform shape and accessibility to pressure haemodynamics. The right ventricle wraps as a crescent around the left ventricle and has been compared to a ‘glove around a baseball’. Standard imaging of the right ventricle is much more challenging because of its geometric shape, multiple trabeculations, and can be further limited by insufficient acoustic windows in patients with severe right ventricular dilation.

In spite of these differences, right ventricular function and left ventricular function are intertwined by several factors. The most obvious is the shared interventricular septum. Normally the intraventricular septum moves in concert with the left ventricular free wall. The right ventricle squeezes more in a longitudinal than the circumferential motion of the left ventricle. The shared fibres between the left ventricle and right ventricle contribute to ventricular interdependence. The left ventricle and right ventricle share helical fibres but, the right ventricle lacks a middle layer and must rely more heavily on longitudinal shortening than does the LV. Consequently, abnormal longitudinal myocardial deformation is an early sign of right ventricular dysfunction and compromised systolic function.1 Classic studies by Damiano showed that in the electrically isolated heart, the right ventricle contributes little to left ventricular function. However, the left ventricle contributes to a large portion of normal right ventricular function.2 As pressure increases in the pulmonary circulation, the right ventricle later adapts by dilation to further maintain cardiac output. Maladaptive responses include dilation as well as bulging of the interventricular septum into the left ventricle. This bulging provides a mechanism for several detrimental geometric responses.3 The left ventricle no longer has a conical shape and the bulging of the septum leads to abnormal inflow into the left ventricle during diastole. In severe RV dysfunction, RV systole may continue into LV diastole thus limiting LV filling. Torsion of the left ventricle is also decreased in paediatric pulmonary hypertension.4 Lastly, electro‐mechanical dyssynchrony and discoordination between both ventricles occur with disease progression most likely the result of myocardial remodelling further augmenting the pathologic right‐to‐left ventricular interdependency.5, 6 The ventricular interdependence of these two ventricles is crucial in normal and disease states.

Pulmonary arterial hypertension, an elevation of pulmonary artery pressure and impedance of the pulmonary circulation, leads to pathologic changes in the right ventricle. Right ventricular failure is the major cause of death in patients with pulmonary arterial hypertension.7 Today, therapies have focused on treatment of the afterload of the right ventricle rather than right ventricle function despite the fact that RV function is the major determinant of outcome. Medicines have targeted the pulmonary circulation in terms of reducing vasoconstriction and perhaps reducing vascular remodelling. For the last three decades, the major focus of treatment for pulmonary arterial hypertension has been the pathobiology of the endothelium and smooth muscle. The prostacyclin pathway has been used as a target for the pulmonary circulation since the 1980s and is a mainstay of severe PAH therapy. Increases in cyclic GMP have been produced using inhaled nitric oxide, blockade of type V phosphodiesterase and stimulation of soluble guanylate cyclase. Blockade of the endothelin receptors has been utilized for almost two decades.8 These medications have little direct effect on the failing right ventricle. Other attempts to improve RV function in this fatal disease including use of digoxin, beta blockers and renin‐angiotensin‐aldosterone inhibitors have been disappointing.

In this issue of Acta Physiologica,9 Tian and colleagues have studied a model of RV failure treated with increasing left ventricular afterload using banding of the aorta above the coronary arteries. They focused much of their attention on the effects of increasing coronary artery perfusion pressure on right ventricular function. Reduced right coronary artery flow by MRI has been shown to be associated with human pulmonary hypertension.10 The authors have used a common model of pulmonary arterial hypertension caused by monocrotaline (MCT) in the rat. MCT causes moderate to severe pulmonary arterial hypertension and leads to right ventricular dysfunction and ultimately failure. The authors proposed that improvement of right coronary perfusion pressure would lead to improved right ventricular function, decreased right ventricular fibrosis and improvement of metabolic derangements of the right ventricle. After one month of supra‐aortic banding, right ventricular systolic perfusion pressure was improved as well as direct measurement of right ventricular function. Measures of right ventricular function included improved tricuspid annular systolic excursion (TAPSE) and improved coupling between the right ventricle and the pulmonary circulation measured by the ratio of RV end‐systolic elastance to pulmonary arterial elastance. In addition to diminished right ventricular hypertrophy, myocardial perfusion was increased in the MCT with aortic band group in both the right and left ventricle during both systole and diastole using single‐photon emission computed tomography perfusion imaging. Finally, the authors evaluated changes in metabolism of the RV and showed a shift towards normal in the ratio of pyruvate kinase muscle isoform 1 (PKM1) and PKM2 using immunoblotting, suggesting a shift towards restoration of oxidative metabolism.

Previous studies have shown that aortic banding improves RV function.11 This article provides mechanistic insight into reasons that supra aortic banding causes improvement in RV function through multiple mechanisms, but primarily because of improved perfusion pressure of the right coronary artery. Associated improvements include a decrease in fibrosis and improvement in metabolic derangements. Tian and colleagues have shown that banding of the aorta leads to a potentially new target in clinical medicine. Although aortic banding has not been studied in humans with pulmonary hypertension, this study importantly leads the way to further consideration of mechanisms to improve right ventricular function in patients with pulmonary arterial hypertension or other diseases of the right ventricle. It is unlikely that aortic banding will be studied in humans with pulmonary hypertension, but in the clinical setting it is crucial to maintain coronary perfusion and the normal geometric relations of the right and left ventricle as much as possible. This study has implications not only in the chronic management of patients, but also in the acute management as well.

Tian及其同事在本期《生理学报》中的文章中强调了左右心室相互依存的重要性。在健康和疾病中，常常低估了右心室的作用。与左心室相比，右心室为三角形，而左心室为圆锥形。右心室功能已被证明是许多疾病状态下预后的重要决定因素。这些范围从小儿疾病到成人获得性疾病。小儿疾病包括先天性心脏病，其中右心室可为体循环提供输出。即使某些孩子不需要右心室，例如在单心室心脏病中，绕过右心室也可以生存，但是它充满了许多并发症。

右心室和左心室在许多方面有所不同。左心室从原发性心脏管发育而右心室则从前-次心脏场发育。这两个心室的解剖结构，几何形状，心肌纤维方向以及对增加的后负荷的反应均不同。右心室泵送至低压，高顺应性系统。在正常运动条件下，右心室必须将其输出至少增加三到五倍。左心室呈圆锥形，肌肉发达，适于常规提供全身性血压。左心室功能的测量比右心室功能的测量更容易，这是因为形状和压力血液动力学的可及性很统一。右心室像新月形缠绕在左心室一样，被与“棒球周围的手套”进行了比较。右心室的标准成像由于其几何形状，多个小梁而更具挑战性，并且对于严重的右心室扩张的患者，其声学窗口不足可能会进一步受到限制。

尽管存在这些差异，但右心室功能和左心室功能受多种因素影响。最明显的是共享的室间隔。正常情况下，脑室内间隔与左心室游离壁同步运动。与左心室的圆周运动相比，右心室在纵向上的挤压更多。左心室和右心室之间共享的纤维有助于心室相互依赖性。左心室和右心室共享螺旋纤维，但是右心室缺少中间层，必须比LV更依赖纵向缩短。因此，异常的纵向心肌变形是右心功能不全和收缩功能受损的早期迹象。1个Damiano的经典研究表明，在电隔离的心脏中，右心室对左心室功能的贡献很小。然而，左心室对正常的右心室功能有很大贡献。2随着肺循环压力的增加，右心室随后会通过扩张来适应，以进一步维持心输出量。适应不良反应包括扩张以及室间隔向左心室膨出。这种膨胀为几种有害的几何响应提供了一种机制。3左心室不再具有圆锥形，并且隔膜的隆起导致在舒张期间异常流入左心室。在严重的RV功能障碍中，RV收缩可能持续进入LV舒张期，从而限制了LV充盈。在小儿肺动脉高压中，左心室的扭曲也减少了。4最后，两个心室之间的机电不同步和失调可能随着疾病的进展而发生，这很可能是心肌重塑的结果，进一步增强了病理上从右到左的心室相互依赖性。5，6在正常和疾病状态下，这两个心室的相互依存关系至关重要。

肺动脉高压，肺动脉压力的升高和肺循环的阻抗，会导致右心室的病理变化。右心衰竭是肺动脉高压患者死亡的主要原因。7如今，尽管右室功能是决定结局的主要因素，但治疗方法仍侧重于右心室后负荷的治疗，而不是右心室功能的治疗。在减少血管收缩和也许减少血管重塑方面，药物已针对肺循环。在过去的三十年中，治疗肺动脉高压的主要重点一直是内皮和平滑肌的病理生物学。自1980年代以来，前列环素途径已被用作肺循环的靶标，并且是严重PAH治疗的支柱。吸入一氧化氮，V型磷酸二酯酶的阻断和可溶性鸟苷酸环化酶的刺激可增加循环GMP。内皮素受体的阻断已经使用了近二十年。8这些药物对衰竭的右心室几乎没有直接影响。在这种致命疾病中改善RV功能的其他尝试令人失望，包括使用地高辛，β受体阻滞剂和肾素-血管紧张素-醛固酮抑制剂。

在本期《生理生理学》中，9 Tian及其同事研究了一种通过使用冠状动脉上方的主动脉束带而增加左心室后负荷治疗的RV衰竭模型。他们将大部分注意力集中在增加冠状动脉灌注压力对右心室功能的影响上。MRI显示右冠状动脉血流减少与人肺动脉高压有关。10这组作者使用了由大鼠中的芥子油碱（MCT）引起的肺动脉高压的常见模型。MCT会导致中度至重度肺动脉高压，并导致右心室功能障碍，并最终导致衰竭。作者认为，改善右冠状动脉灌注压力将导致改善的右心室功能，减少的右心室纤维化以及改善右心室的代谢紊乱。主动脉上束扎1个月后，右心室收缩压得到改善，并且直接测量了右心室功能。右心室功能的测量包括改善的三尖瓣环收缩期偏移（TAPSE）和改善的右心室与肺循环之间的耦合（通过RV末梢弹性与肺动脉弹性之比来衡量）。除了减少右心室肥大外，使用单光子发射计算机断层扫描灌注成像，在MCT中，右心室和左心室的左，右心室主动脉带组的心肌灌注增加。最后，作者评估了RV代谢的变化，并使用免疫印迹法显示了丙酮酸激酶肌肉同工型1（PKM1）和PKM2的比例向正常的方向转变，表明向氧化代谢的恢复方向转变。除了减少右心室肥大外，使用单光子发射计算机断层扫描灌注成像，在MCT中，右心室和左心室的左，右心室主动脉带组的心肌灌注增加。最后，作者评估了RV代谢的变化，并使用免疫印迹法显示了丙酮酸激酶肌肉同工型1（PKM1）和PKM2的比例向正常的方向转变，表明向氧化代谢的恢复方向转变。除了减少右心室肥大外，使用单光子发射计算机断层扫描灌注成像，在MCT中，右心室和左心室的左，右心室主动脉带组的心肌灌注增加。最后，作者评估了RV代谢的变化，并使用免疫印迹法显示了丙酮酸激酶肌肉同工型1（PKM1）和PKM2的比例向正常的方向转变，表明向氧化代谢的恢复方向转变。

先前的研究表明，主动脉束带可改善RV功能。11本文提供了机械上的洞察力，探讨了主动脉上束带通过多种机制改善右室功能的原因，但主要是由于右冠状动脉的灌注压力提高。相关的改善包括纤维化的减少和代谢紊乱的改善。田（Tian）及其同事表明，主动脉束带可导致临床医学中潜在的新靶标。尽管尚未在患有肺动脉高压的人中研究主动脉束带，但这项研究仍为进一步考虑改善肺动脉高压或其他右心室疾病患者右心室功能的机制提供了途径。不太可能在患有肺动脉高压的人中研究主动脉束带，但在临床环境中，至关重要的是要尽可能保持冠状动脉灌注和左右心室的正常几何关系。这项研究不仅对患者的慢性治疗有影响，而且对急性治疗也有影响。