School of Medicine, Institute of Cardiovascular Physiopathology and Department of Pathology, University of Buenos Aires, and Laboratory of Oxygen Metabolism, University Hospital, JE Uriburu 950-2nd floor, 1114, Buenos Aires, Argentina.
Mol Cell Biochem. 2012 Jan;359(1-2):169-76. doi: 10.1007/s11010-011-1011-2. Epub 2011 Aug 13.
Hemorrhage (H) is associated with a left ventricular (LV) dysfunction. However, the diastolic function has not been studied in detail. The main goal was to assess the diastolic function both during and 120 min after bleeding, in the absence and in the presence of L-NAME. Also, the changes in mRNA and protein expression of nitric oxide synthase (NOS) isoforms were determined. New Zealand rabbits were divided into three groups: Sham group, H group (hemorrhage 20% blood volume), and H L-NAME group (hemorrhage treated with L-NAME). We evaluated systolic and diastolic ventricular functions in vivo and in vitro (Langendorff technique). Hemodynamic parameters and LV function were measured before, during, and at 120 min after bleeding. We analyzed the isovolumic relaxation using t ½ in vivo (closed chest). After that, hearts were excised and perfused in vitro to measure myocardial stiffness. Samples were frozen to measure NOS mRNA and protein expression. The t½ increased during bleeding and returned to basal values 120 min after bleeding. L-NAME blunted this effect. Data from the H group revealed a shift to the left in the LV end diastolic pressure-volume curve at 120 min after bleeding, which was blocked by L-NAME. iNOS and nNOS protein expression and mRNA levels increased at 120 min after the hemorrhage. Acute hemorrhage induces early and transient isovolumic relaxation impairment and an increase in myocardial stiffness 120 min after bleeding. L-NAME blunted the LV dysfunction, suggesting that NO modulates ventricular function through iNOS and nNOS isoforms.
出血（H）与左心室（LV）功能障碍有关。然而，舒张功能尚未得到详细研究。主要目的是评估在没有和存在 L-NAME 的情况下，出血期间和出血后 120 分钟时的舒张功能。还确定了一氧化氮合酶（NOS）同工型的 mRNA 和蛋白表达的变化。新西兰兔分为三组：假手术组、H 组（出血 20%血容量）和 H L-NAME 组（出血用 L-NAME 治疗）。我们在体内和体外（Langendorff 技术）评估收缩和舒张心室功能。在出血前、出血期间和出血后 120 分钟测量血流动力学参数和 LV 功能。我们使用体内的 t½分析等容松弛（闭胸）。之后，取出心脏并在体外灌注以测量心肌僵硬。将样品冷冻以测量 NOS mRNA 和蛋白表达。t½在出血期间增加，并在出血后 120 分钟恢复到基础值。L-NAME 减弱了这种作用。H 组的数据显示，LV 舒张末期压力-容积曲线在出血后 120 分钟向左移位，L-NAME 阻断了这种移位。iNOS 和 nNOS 蛋白表达和 mRNA 水平在出血后 120 分钟增加。急性出血导致早期和短暂的等容松弛受损，以及出血后 120 分钟心肌僵硬增加。L-NAME 减弱了 LV 功能障碍，表明 NO 通过 iNOS 和 nNOS 同工型调节心室功能。
