Smith Scott A, Mitchell Jere H, Naseem R Haris, Garry Mary G
Department of Internal Medicine, Harry S. Moss Heart Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9174, USA.
Circulation. 2005 Oct 11;112(15):2293-300. doi: 10.1161/CIRCULATIONAHA.105.566745.
In heart failure, exercise elicits excessive increases in mean arterial pressure (MAP) and heart rate (HR). Using a novel rat model, we previously demonstrated that this exaggerated cardiovascular responsiveness is mediated by an overactive exercise pressor reflex (EPR). Although we previously determined that abnormalities in the group IV afferent neuron population (associated with the metabolic component of the reflex) initiate the development of the exaggerated EPR in heart failure, these fibers do not mediate the enhanced circulatory responses to exercise. Therefore, we hypothesized that the augmentation in EPR activity is primarily mediated by the mechanically sensitive component of the reflex (mediated predominately by activation of group III afferent fibers).
Male Sprague-Dawley rats were divided into 3 groups: sham (control), dilated cardiomyopathic (DCM), and neonatal capsaicin-treated animals (NNCAP, group IV afferent fibers ablated). Activation of the EPR by electrically induced static muscle contraction of the hindlimb resulted in larger increases in MAP and HR in DCM and NNCAP compared with sham animals. In all groups, administration of gadolinium (a selective blocker of mechanically sensitive receptors) within the hindlimb attenuated the MAP and HR responses to contraction. However, the magnitude of this reduction was greater in DCM and NNCAP compared with sham animals.
From these data, we conclude that the muscle mechanoreflex mediates the exaggerated EPR that develops in heart failure. Moreover, these findings suggest that mechanoreflex overactivity in heart failure may be a compensatory response to functional alterations in group IV fibers. Given these findings, the muscle mechanoreflex may serve as a novel target in the treatment of the abnormal circulatory responses to exercise in heart failure.
在心力衰竭中，运动可导致平均动脉压（MAP）和心率（HR）过度升高。我们先前使用一种新型大鼠模型证明，这种心血管反应性的过度增强是由过度活跃的运动升压反射（EPR）介导的。尽管我们先前确定IV组传入神经元群体的异常（与反射的代谢成分相关）启动了心力衰竭中过度增强的EPR的发展，但这些纤维并不介导对运动的循环反应增强。因此，我们假设EPR活动的增强主要由反射的机械敏感成分介导（主要由III组传入纤维的激活介导）。
雄性Sprague-Dawley大鼠分为3组：假手术组（对照组）、扩张型心肌病组（DCM）和新生辣椒素处理组动物（NNCAP，IV组传入纤维被切除）。通过电诱导后肢静态肌肉收缩激活EPR，与假手术组动物相比，DCM组和NNCAP组的MAP和HR升高幅度更大。在所有组中，在后肢内给予钆（一种机械敏感受体的选择性阻滞剂）可减弱对收缩的MAP和HR反应。然而，与假手术组动物相比，DCM组和NNCAP组这种降低的幅度更大。
根据这些数据，我们得出结论，肌肉机械反射介导了心力衰竭中发展的过度增强的EPR。此外，这些发现表明心力衰竭中机械反射过度活跃可能是对IV组纤维功能改变的一种代偿反应。鉴于这些发现，肌肉机械反射可能成为治疗心力衰竭中对运动的异常循环反应的一个新靶点。
