Cazorla O, Aït Mou Y, Goret L, Vassort G, Dauzat M, Lacampagne A, Tanguy S, Obert P
INSERM, U 637, CHU Arnaud de Villeneuve, F-34295 Montpellier, France. Université MONTPELLIER1, UFR de Médecine, F-34295 Montpellier, France.
Cardiovasc Res. 2006 Sep 1;71(4):652-60. doi: 10.1016/j.cardiores.2006.06.020. Epub 2006 Jun 21.
Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level.
Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL).
Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data.
Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in this transmural gradient that may contribute to the lack of improvement in LV function via the Frank-Starling mechanism.
以往研究对高原训练后心脏功能是否改善提出了质疑。因此，本研究专门设计用于测试全心脏对训练这种明显减弱的反应是否可由细胞水平上改变的力学特性来解释。
成年大鼠在常氧（N，分别为久坐不动和训练动物的NT）或低压低氧（H，HT）条件下训练5周。通过超声心动图评估心脏形态和功能。在短和长肌节长度（SL）下，从左心室（LV）心外膜（Epi）和心内膜（Endo）分离的脱膜心肌细胞中估计收缩机制对钙（Ca2+）的敏感性。
NT大鼠的心脏重塑是协调的（心室扩张时壁厚增加），而HT大鼠的心脏重塑是不协调的（心肌肥厚但无心室扩张）。与NT大鼠相反，HT大鼠经超声心动图评估未表现出整体心脏功能增强。在N大鼠中，肌丝的牵张依赖性Ca2+敏化（Frank-Starling机制的细胞指标）从Epi到Endo增加。常氧条件下的训练进一步增加了这种牵张依赖性Ca2+敏化。慢性低氧对肌原纤维Ca2+敏感性无显著影响。相反，高原训练在两个SL下均降低了肌丝的Ca2+敏感性，主要是在内皮细胞中，导致牵张依赖性Ca2+敏化的跨壁梯度丧失。肌球蛋白重链亚型的表达受训练和慢性低氧两者影响，但与力学数据无关。
海平面训练增加了肌丝牵张依赖性Ca2+敏化的跨壁梯度，这解释了Frank-Starling机制的改善。高原训练抑制了肌丝对Ca2+的反应，尤其是在内皮层。这导致该跨壁梯度降低，这可能通过Frank-Starling机制导致左心室功能缺乏改善。
