Cardiorenal syndrome, de novo renal pathology arising secondary to cardiac insufficiency, is clinically recognised but poorly characterised. This study establishes and characterises a valid model representative of Type 2 cardiorenal syndrome. Extensive permanent left ventricular infarction, induced by ligation of the left anterior descending coronary artery in Lewis rats, was confirmed by plasma cardiac troponin I, histology and cardiac haemodynamics. Renal function and morphology was assessed 90-days post-ligation when heart failure had developed. The involvement of the paraventricular nucleus was investigated using markers of inflammation, apoptosis, reactive oxygen species and of angiotensin II involvement. An extensive left ventricular infarct was confirmed following coronary artery ligation, resulting in increased left ventricular weight and compromised left ventricular diastolic function and developed pressure. Glomerular filtration was significantly decreased, fractional excretion of sodium and caspase activities were increased and basement membrane thickening, indicating glomerulosclerosis, was evident. Interestingly, angiotensin II receptor I expression and reactive oxygen species levels in the hypothalamic paraventricular nucleus remained significantly increased at 90-days post-coronary artery ligation, suggesting that these hypothalamic changes may represent a novel, valuable pharmacological target. This model provides conclusive morphological, biochemical and functional evidence of renal injury consequent to heart failure, truly representative of Type-2 cardiorenal syndrome.

中文翻译：

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具有慢性缺血性心力衰竭导致的室旁变化的2型心肾综合征的临床相关功能模型。

心源性肾功能不全引起的从头开始的肾脏病理性肾脏病综合征在临床上得到公认，但特征不明确。这项研究建立并表征了代表2型心肾综合征的有效模型。血浆心肌肌钙蛋白I，组织学和心脏血流动力学证实了结扎Lewis大鼠左冠状动脉前降支引起的广泛性永久性左室梗塞。结扎后90天，当发生心力衰竭时评估肾功能和形态。使用炎症，凋亡，活性氧和血管紧张素II的标记物来研究脑室旁核的侵犯。冠状动脉结扎后证实有广泛的左室梗塞，导致左心室重量增加，左心室舒张功能受损和压力升高。肾小球滤过明显减少，钠的部分排泄和半胱天冬酶活性增加，基底膜增厚，表明肾小球硬化。有趣的是，在冠状动脉结扎后90天，下丘脑室旁核中的血管紧张素II受体I的表达和活性氧水平仍显着增加，表明这些下丘脑变化可能代表了一种新的有价值的药理学靶标。该模型提供了由心力衰竭导致的肾损伤的确凿的形态，生化和功能证据，是2型心肾综合征的真正代表。