Effects of tumour necrosis factor-alpha on left ventricular function in the rat isolated perfused heart: possible mechanisms for a decline in cardiac function.
作者信息
Edmunds N J, Lal H, Woodward B
机构信息
Department of Pharmacology, University of Bath, Claverton Down.
The cardiac depressant actions of TNF were investigated in the isolated perfused rat heart under constant flow (10 ml min(-1)) and constant pressure (70 mmHg) conditions, using a recirculating (50 ml) mode of perfusion. 2. Under constant flow conditions TNF (20 ng ml(-1)) caused an early (< 25 min) decrease in left ventricular developed pressure (LVDP), which was maintained for 90 min (LVDP after 90 min: control vs TNF; 110 +/- 4 vs 82 +/- 10 mmHg, P < 0.01). 3. The depression in cardiac function seen with TNF under constant flow conditions, was blocked by the ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, (LVDP after 90 min: TNF vs TNF with NOE; 82 +/- 10 vs 11 +/- 5 mmHg, P < 0.05). 4. In hearts perfused at constant pressure, TNF caused a decrease in coronary flow rate (change in flow 20 min after TNF: control vs TNF; -3.0 +/- 0.9 vs -8.7 +/- 1.2 ml min(-1), P < 0.01). This was paralleled by a negative inotropic effect (change in LVDP 20 min after TNF: control vs TNF; -17 +/- 7 vs -46 +/- 6 mmHg, P < 0.01). The decline in function was more rapid and more severe than that seen under conditions of constant flow. 5. These data indicate that cardiac function can be disrupted by TNF on two levels, firstly via a direct, ceramidase dependant negative inotropic effect, and secondly via an indirect coronary vasoconstriction.
摘要
在恒流（10 ml min⁻¹）和恒压（70 mmHg）条件下，采用50 ml循环灌注模式，在离体灌注大鼠心脏中研究了肿瘤坏死因子（TNF）的心脏抑制作用。2. 在恒流条件下，TNF（20 ng ml⁻¹）导致左心室舒张末压（LVDP）早期（< 25分钟）下降，并持续90分钟（90分钟后LVDP：对照组与TNF组；110 ± 4 vs 82 ± 10 mmHg，P < 0.01）。3. 在恒流条件下，TNF引起的心脏功能抑制被1 μM的神经酰胺酶抑制剂N-油酰乙醇胺（NOE）阻断（90分钟后LVDP：TNF组与TNF + NOE组；82 ± 10 vs 11 ± 5 mmHg，P < 0.05）。4. 在恒压灌注的心脏中，TNF导致冠状动脉血流速率下降（TNF后20分钟血流变化：对照组与TNF组；-3.0 ± 0.9 vs -8.7 ± 1.2 ml min⁻¹，P < 0.01）。这与负性肌力作用平行（TNF后20分钟LVDP变化：对照组与TNF组；-17 ± 7 vs -46 ± 6 mmHg，P < 0.01）。功能下降比恒流条件下更迅速、更严重。5. 这些数据表明，TNF可在两个水平上破坏心脏功能，首先是通过直接的、依赖神经酰胺酶的负性肌力作用，其次是通过间接的冠状动脉血管收缩。
