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异丙肾上腺素和咖啡因对Wistar Kyoto大鼠左心室肥厚及肾血流动力学发展的影响

IMPACT OF ISOPRENALINE AND CAFFEINE ON DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY AND RENAL HEMODYNAMIC IN WISTAR KYOTO RATS.

作者信息

Ahmad Ashfaq, Sattar Munavvar Z A, Rathore Hassaan A, Khan Safia Akhtar, Lazhari Mohammed A, Hashmi Fayaz, Abdullah Nor A, Johns Edward J

出版信息

Acta Pol Pharm. 2015 Sep-Oct;72(5):1015-26.

Abstract

Left ventricular hypertrophy (LVH) is a compensatory mechanism in response to an increased work load on the heart. This study investigated the impact of chronic isoprenaline and caffeine (I/C model) administration on cardiac geometry, systemic hemodynamic and physiological data in rats as LVH develops. LVH was induced by administering isoprenaline (5 mg/kg s.c. every 72 h) and caffeine (62 mg/L) in drinking water for 14 days to Wistar Kyoto (WKY) rats. Mean arterial pressure (MAP), systolic blood pressure (SBP), heart weight, LV weight, LV chamber diameter and thickness of myocardium were observed as LVH indicators. MAP was significantly higher (142 ± 13 vs. 119 ± 2 mmHg, respectively) while heart rate (HR) in LVH was lower (314 ± 9 vs. 264 ± 18 BPM) compared to control WKY. Heart weight, LV weight and kidney weight were 31%, 38% and 7%, respectively, greater in the LVH group as compared to the control WKY (all p < 0.05).The myocardium thickness was 101% greater while LV chamber diameter was 44% smaller in the LVH group as compared to the control WKY (p < 0.05). The superoxide dismutase (SOD), glutathione reductase (GSH) and total antioxidant capacity (T-AOC) levels were significantly reduced while malonodialdehyde (MDA) level increased in LVH as compared to control WKY (all p < 0.05). In conclusion, isoprenaline and caffeine (I/C) induces LVH and cardiac hypertrophy with increases in blood pressure, fluid excretion and reduced renal hemodynamics. Prooxidant mechanism of the body and arterial stiffness are dominant in this disease model. This model of LVH is easily generated and associated with low mortality.

摘要

左心室肥厚(LVH)是心脏对工作负荷增加的一种代偿机制。本研究调查了慢性给予异丙肾上腺素和咖啡因(I/C模型)对大鼠左心室肥厚发展过程中心脏几何形态、全身血流动力学和生理数据的影响。通过向Wistar Kyoto(WKY)大鼠皮下注射异丙肾上腺素(每72小时5mg/kg)并在饮水中添加咖啡因(62mg/L),持续14天来诱导左心室肥厚。观察平均动脉压(MAP)、收缩压(SBP)、心脏重量、左心室重量、左心室腔直径和心肌厚度作为左心室肥厚指标。与对照WKY大鼠相比,左心室肥厚组的MAP显著更高(分别为142±13 vs. 119±2 mmHg),而心率(HR)更低(314±9 vs. 264±18次/分钟)。与对照WKY大鼠相比,左心室肥厚组的心脏重量、左心室重量和肾脏重量分别增加了31%、38%和7%(均p<0.05)。与对照WKY大鼠相比,左心室肥厚组的心肌厚度增加了101%,而左心室腔直径减小了44%(p<0.05)。与对照WKY大鼠相比,左心室肥厚组的超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GSH)和总抗氧化能力(T-AOC)水平显著降低,而丙二醛(MDA)水平升高(均p<0.05)。总之,异丙肾上腺素和咖啡因(I/C)诱导左心室肥厚和心脏肥大,同时伴有血压升高、液体排泄增加和肾血流动力学降低。在该疾病模型中,机体的促氧化机制和动脉僵硬度占主导地位。这种左心室肥厚模型易于建立且死亡率低。

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