Günzinger Ralf, Wildhirt Stephen M, Schad Hubert, Heimisch Werner, Gurdan Manuela, Mendler Nikolaus, Grammer Joachim, Lange Rüdiger, Bauernschmitt Robert
Dept of Cardiovascular Surgery, German Heart Center Munich, Technical University of Munich, Munich, Germany.
Basic Res Cardiol. 2007 Nov;102(6):508-17. doi: 10.1007/s00395-007-0668-x. Epub 2007 Aug 2.
Cardiopulmonary bypass (CPB) is known to induce systemic inflammation and cardiac dysfunction associated with a significant morbidity. Aim of the study was to develop an in vivo model of rat CPB with hypothermic cardiac arrest and the use of cardioplegia.
The CPB circuit consisted of a venous reservoir, membrane oxygenator, heat exchanger, and roller pump. CPB was instituted in adult male Wistar rats (400-500 g) for 60 min at a flow rate of 120 ml x kg(-1) x min(-1), including 15 min cooling to 32 degrees C, 30 min cardiac arrest with the use of cold crystalloid cardioplegia after aortic cross clamping, and 15 min of reperfusion and rewarming to 37 degrees C. Arterial blood pressure (MAP) and heart rate (HR) were monitored, arterial blood samples were analyzed. Left ventricular (LV) function parameters were assessed by intraventricular conductance catheter. Important technical aspects are: ventilation is required during partial bypass; anticoagulation should be performed immediately prior to CPB to reduce blood loss; active suction on venous drainage allows higher pump flows; and the small priming volume of the extracorporeal circuit (8 ml) avoids the need for donor blood.
MAP remained stable prior to and during CPB.MAP and HR were significantly decreased 60 min after weaning from bypass. Hct was significantly lowered after hemodilution, but remained stable during CPB and 60 min after weaning from bypass. BE and pH remained stable throughout the experiment.Without inotropic support diastolic and systolic LV function parameters were impaired after 30 min of cardioplegic arrest followed by 15 min of reperfusion. Myocardial TNF-alpha mRNA levels were slightly increased (1.28-fold, p = 0.71), and IL-6 mRNA was significantly increased in the cardioplegia group (90.3-fold, p = 0.001). Both IL-6 and TNF-alpha plasma levels were significantly elevated in the cardioplegia group (TNF-alpha: 4.6-fold increase,p < 0.05; IL-6: 426.8-fold increase, p < 0.001).
We have developed a rat CPB with mild hypothermic cardioplegic arrest. This rodent model is suitable to study clinically relevant problems related to CPB,myocardial protection and systemic inflammation.
已知体外循环（CPB）会引发全身炎症反应和心脏功能障碍，并伴有显著的发病率。本研究的目的是建立一种大鼠低温心脏停搏并使用心脏停搏液的体外循环体内模型。
体外循环回路由静脉储液器、膜式氧合器、热交换器和滚压泵组成。在成年雄性Wistar大鼠（400 - 500克）中建立体外循环，持续60分钟，流速为120毫升×千克⁻¹×分钟⁻¹，包括15分钟降温至32℃，在主动脉交叉钳夹后使用冷晶体心脏停搏液进行30分钟心脏停搏，以及15分钟再灌注和复温至37℃。监测动脉血压（MAP）和心率（HR），分析动脉血样本。通过心室内电导导管评估左心室（LV）功能参数。重要技术要点包括：部分体外循环期间需要通气；应在体外循环前立即进行抗凝以减少失血；对静脉引流进行主动吸引可实现更高的泵流量；体外循环回路的预充量小（8毫升）避免了使用供血的需求。
体外循环前及期间MAP保持稳定。脱离体外循环60分钟后MAP和HR显著降低。血液稀释后Hct显著降低，但在体外循环期间及脱离体外循环60分钟后保持稳定。整个实验过程中BE和pH保持稳定。在未使用正性肌力药物支持的情况下，心脏停搏30分钟后再灌注15分钟导致舒张期和收缩期左心室功能参数受损。心脏停搏液组心肌TNF - α mRNA水平略有升高（1.28倍，p = 0.71），IL - 6 mRNA显著升高（90.3倍，p = 0.001）。心脏停搏液组IL - 6和TNF - α血浆水平均显著升高（TNF - α：升高4.6倍，p < 0.05；IL - 6：升高426.8倍，p < 0.001）。
我们建立了一种轻度低温心脏停搏的大鼠体外循环模型。这种啮齿动物模型适用于研究与体外循环、心肌保护和全身炎症相关的临床相关问题。
