Krogmann O N, Tjon-A-Meeuw L, Hess O M, Jacob M, Grimm J, Leskosek B, Pasic M, von Segesser L
Department of Internal Medicine, University Hospital, Zurich, Switzerland.
Cardiovasc Res. 1993 Mar;27(3):531-6. doi: 10.1093/cvr/27.3.531.
The aim was to assess the effect of nisoldipine on left ventricular systolic and diastolic function during prolonged myocardial ischaemia.
The left circumflex coronary artery was ligated for 2 h and reperfused for 4 h in 12 calves. The animals were randomised to a control group (n = 6) or to treatment with 1.25 mg.h-1 intravenous nisoldipine (n = 6) during 2 h of ischaemia. Circulatory support by a ventricular assist device was performed throughout the experiment except for the time of haemodynamic measurements. Regional wall thickening of a normal and an ischaemic left ventricular region was determined using pairs of ultrasonic crystals. Left ventricular pressure was measured by micromanometry. Left ventricular wall thickness and regional wall stiffness at a common preload of 10 mm Hg were calculated using an elastic model with shifting asymptote.
Ten animals survived after 6 h. No difference was observed in systolic function between controls and nisoldipine treated animals. Systolic thickening of the ischaemic wall remained depressed 4 h after reperfusion and showed some recovery after dopamine infusion. Ischaemic wall stiffness at a common preload was lower after nisoldipine during ischaemia and reperfusion than in controls. Control wall stiffness remained unchanged during the whole experiment with and without nisoldipine. Diastolic thinning of the ischaemic wall was prevented by nisoldipine during ischaemia and after reperfusion.
Prolonged myocardial ischaemia is associated with increased myocardial stiffness of the ischaemic wall. Mechanical unloading can help to bridge the acute phase but cannot prevent postischaemic diastolic dysfunction of the ischaemic wall. Nisoldipine has a beneficial effect on regional diastolic function during ischaemia and reperfusion by decreasing regional wall stiffness and preventing diastolic thinning of the ischaemic wall.
评估尼索地平在长时间心肌缺血期间对左心室收缩和舒张功能的影响。
对12头小牛结扎左旋冠状动脉2小时,再灌注4小时。在缺血的2小时内,将动物随机分为对照组(n = 6)或接受1.25 mg·h⁻¹静脉注射尼索地平治疗的组(n = 6)。除血流动力学测量时间外,在整个实验过程中均使用心室辅助装置进行循环支持。使用成对的超声晶体测定正常和缺血左心室区域的室壁增厚情况。通过微测压法测量左心室压力。使用具有移动渐近线的弹性模型计算在10 mmHg的共同预负荷下的左心室壁厚度和区域壁硬度。
6小时后10只动物存活。对照组和尼索地平治疗组之间在收缩功能方面未观察到差异。缺血壁的收缩增厚在再灌注后4小时仍处于抑制状态,多巴胺输注后有所恢复。在缺血和再灌注期间,尼索地平治疗后在共同预负荷下的缺血壁硬度低于对照组。无论有无尼索地平,对照组壁硬度在整个实验过程中均保持不变。尼索地平在缺血期间和再灌注后可防止缺血壁的舒张期变薄。
长时间心肌缺血与缺血壁心肌硬度增加有关。机械卸载有助于度过急性期,但不能预防缺血壁缺血后的舒张功能障碍。尼索地平通过降低区域壁硬度和防止缺血壁的舒张期变薄,对缺血和再灌注期间的区域舒张功能具有有益作用。