Tsui S S, Kirshbom P M, Davies M J, Jacobs M T, Kern F H, Gaynor J W, Greeley W J, Ungerleider R M
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Eur J Cardiothorac Surg. 1997 Aug;12(2):228-35. doi: 10.1016/s1010-7940(97)00095-x.
Following the use of deep hypothermic circulatory arrest in cardiac surgery, cerebral blood flow and cerebral oxygen metabolism are impaired. These may result from abnormal cerebral vasospasm. Powerful vasoconstrictors including endothelins and thromboxane A2 could mediate these processes. We investigated possible involvement of these two factors by assessing the effects of (a) phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of cerebral blood flow and cerebral oxygen metabolism following deep hypothermic circulatory arrest.
A total of 18 1-week-old piglets were randomised into three groups (n = 6 per group). At induction, the control group received saline; group PHOS received phosphoramidon 30 mg kg-1 intravenously. Group VAP received vapiprost 2 mg kg-1 at induction and at 30 min intervals thereafter. All groups underwent cardiopulmonary bypass cooling to 18 degrees C, exposed to 60 min of deep hypothermic circulatory arrest, rewarmed and reperfused for 1 h. Cerebral blood flow was measured with radio-labeled microspheres: cerebral oxygen metabolism was calculated at baseline before deep hypothermic circulatory arrest and at 1 h of reperfusion and rewarming.
In the control group, cerebral blood flow decreased to 40.2 +/- 2.0% of baseline after deep hypothermic circulatory arrest and cerebral oxygen metabolism decreased to 50.0 +/- 5.5% (P < 0.0005). The responses in group PHOS were similar. In group VAP, cerebral blood flow and cerebral oxygen metabolism were 64.3 +/- 10.6 and 80.1 +/- 9.8% of baseline, respectively, after deep hypothermic circulatory arrest. Thus, treatment with vapiprost significantly improved recovery of cerebral blood flow (P = 0.046) and cerebral oxygen metabolism (P = 0.020) following deep hypothermic circulatory arrest. No such improvement was seen after treatment with phosphoramidon.
Thromboxane A2 mediates impairments in cerebral perfusion and metabolism following deep hypothermic circulatory arrest. These changes were attenuated by blockade of thromboxane A2-receptors using vapiprost. Endothelins are not shown to be involved. Better knowledge of injury mechanisms will enable development of more effective cerebral protection strategies and allow safer application of deep hypothermic circulatory arrest.
在心脏手术中使用深度低温循环停搏后，脑血流量和脑氧代谢会受到损害。这可能是由异常的脑血管痉挛引起的。包括内皮素和血栓素A2在内的强效血管收缩剂可能介导这些过程。我们通过评估（a）磷酰胺素（一种内皮素转化酶抑制剂）和（b）前列环素（GR32191B，一种特异性血栓素A2受体拮抗剂）对深度低温循环停搏后脑血流量和脑氧代谢恢复的影响，来研究这两种因素可能的参与情况。
总共18只1周龄仔猪被随机分为三组（每组n = 6）。诱导时，对照组接受生理盐水；磷酰胺素组静脉注射30 mg/kg磷酰胺素；前列环素组在诱导时及此后每隔30分钟接受2 mg/kg前列环素。所有组均进行体外循环降温至18℃，经历60分钟的深度低温循环停搏，复温并再灌注1小时。用放射性标记微球测量脑血流量；在深度低温循环停搏前的基线以及再灌注和复温1小时时计算脑氧代谢。
在对照组中，深度低温循环停搏后脑血流量降至基线的40.2±2.0%，脑氧代谢降至50.0±5.5%（P < 0.0005）。磷酰胺素组的反应相似。在前列环素组中，深度低温循环停搏后脑血流量和脑氧代谢分别为基线的64.3±10.6%和80.1±9.8%。因此，前列环素治疗显著改善了深度低温循环停搏后脑血流量（P = 0.046）和脑氧代谢（P = 0.020）的恢复。磷酰胺素治疗后未观察到这种改善。
血栓素A2介导深度低温循环停搏后脑灌注和代谢的损害。使用前列环素阻断血栓素A2受体可减轻这些变化。未显示内皮素参与其中。对损伤机制的更深入了解将有助于开发更有效的脑保护策略，并使深度低温循环停搏的应用更安全。
