心脏停搏与血管损伤。缺血效应与心脏停搏液效应的分离。

Cardioplegia and vascular injury. Dissociation of the effects of ischemia from those of the cardioplegic solution.

作者信息

Saldanha C, Hearse D J

机构信息

Rayne Institute, St. Thomas' Hospital, London, United Kingdom.

出版信息

J Thorac Cardiovasc Surg. 1994 Aug;108(2):279-90.

PMID:8041176

Abstract

Although cardioplegic solutions successfully protect myocardial contractile cells against ischemic injury, their effect on the vasculature remains controversial. To address this we used a vascular bed preparation (isolated rat mesentery) that permits the study of vascular function without the coincident changes in contractile status that affect vascular tone (and hence the assessment of vascular function in isolated hearts). Smooth muscle cell contraction was assessed by measurement of the vasoconstrictor response to phenylephrine, and relaxation was assessed by measurement of the vasodilator responses to sodium nitroprusside and the endothelium-dependent relaxant adenosine triphosphate. After characterization of basal vascular function, mesenteries were subjected to normothermic ischemia for 60, 90, 120, 150, and 180 minutes (n = 12 for each time period; 6 preparations were subjected to ischemia alone and 6 to ischemia preceded by a 3-minute infusion of the St. Thomas' Hospital cardioplegic solution). The tissue was then reperfused for 20 minutes and vascular function reassessed. Ischemia alone caused progressive time-dependent deterioration in vasoconstrictor responses (99% +/- 13%, 90% +/- 10%, 63% +/- 6%, 51% +/- 10%, and 27% +/- 4%), endothelium-independent vasodilation (93% +/- 3%, 86% +/- 2%, 78% +/- 5%, 61% +/- 5%, and 38% +/- 9%), and endothelium-dependent vasodilation (93% +/- 3%, 96% +/- 2%, 94% +/- 2%, 87% +/- 7%, and 62% +/- 11%). There were similar time-dependent deteriorations in mesenteries subjected to ischemia coupled with cardioplegic solution that were not significantly different from any of the ischemia-alone groups when matched for ischemic times. Thus, for example, after 180 minutes of ischemia alone, the vasoconstrictor response was 18% +/- 3%, endothelium-independent vasodilation was 44% +/- 7%, and endothelium-dependent vasodilation was 40% +/- 9%. The results demonstrate that under the conditions of this experiment, the St. Thomas' Hospital cardioplegic solution neither protects nor injures the vasculature during an episode of ischemia and reperfusion. However, in studies with 150 minutes of normothermic ischemia, multiple infusions of cardioplegic solution (given every 30 minutes during ischemia) resulted in protection of smooth muscle and endothelial function. Thus, after multiple infusions, vasoconstriction to phenylephrine was 74% +/- 4%, vasodilation to nitroprusside was 81% +/- 6%, and vasodilation to adenosine triphosphate was 89% +/- 5%. In conclusion, when the St. Thomas' Hospital cardioplegic solution is used as a single infusion and coupled with ischemia, the solution fails to protect smooth muscle and endothelial function against ischemic injury, but some protection is obtained when the solution is infused intermittently throughout the ischemic period.

摘要

尽管心脏停搏液能成功保护心肌收缩细胞免受缺血性损伤，但其对脉管系统的影响仍存在争议。为解决这一问题，我们采用了一种血管床制备方法（分离的大鼠肠系膜），该方法可在不伴随影响血管张力的收缩状态变化（从而避免影响离体心脏血管功能评估）的情况下研究血管功能。通过测量对去氧肾上腺素的血管收缩反应来评估平滑肌细胞收缩，通过测量对硝普钠和内皮依赖性舒张剂三磷酸腺苷的血管舒张反应来评估舒张功能。在对基础血管功能进行表征后，将肠系膜进行常温缺血60、90、120、150和180分钟（每个时间段n = 12；6份标本仅进行缺血处理，6份标本在缺血前先输注3分钟圣托马斯医院心脏停搏液）。然后将组织再灌注20分钟并重新评估血管功能。单独缺血导致血管收缩反应呈时间依赖性逐渐恶化（分别为99%±13%、90%±10%、63%±6%、51%±10%和27%±4%）、非内皮依赖性血管舒张（分别为93%±3%、86%±2%、78%±5%、61%±5%和38%±9%）以及内皮依赖性血管舒张（分别为93%±3%、96%±2%、94%±2%、87%±7%和62%±11%）。接受缺血加心脏停搏液处理的肠系膜也出现了类似的时间依赖性恶化，与缺血时间匹配的任何单独缺血组相比无显著差异。因此，例如，单独缺血180分钟后，血管收缩反应为18%±3%，非内皮依赖性血管舒张为44%±7%，内皮依赖性血管舒张为40%±9%。结果表明，在本实验条件下，圣托马斯医院心脏停搏液在缺血再灌注期间既不能保护也不会损伤脉管系统。然而，在常温缺血150分钟的研究中，多次输注心脏停搏液（在缺血期间每30分钟输注一次）可保护平滑肌和内皮功能。因此，多次输注后，对去氧肾上腺素的血管收缩反应为74%±4%，对硝普钠的血管舒张反应为81%±6%，对三磷酸腺苷的血管舒张反应为89%±5%。总之，当将圣托马斯医院心脏停搏液单次输注并与缺血联合应用时，该溶液无法保护平滑肌和内皮功能免受缺血性损伤，但在整个缺血期间间歇性输注该溶液可获得一定保护作用。