Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction.
Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction.
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使用一氧化氮供体 SPM-5185 增强血液停跳液可抵消缺血后内皮和心室功能障碍。
DOI：
10.1016/s0022-5223(95)70198-2
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
HammonJr,JW
中科院分区：
文献类型：
--
作者：
Nakanishi,K;Zhao,ZQ;Vinten-Johansen,J;Hudspeth,DA;McGee,DS;HammonJr,JW
这项研究验证了一氧化氮供体SPM-5185增强血液停搏液可抑制缺血后左心室和冠状动脉内皮功能障碍的假说。18只麻醉犬在全通气式体外循环支持下，常温缺血30min，4℃多剂量血液停搏液。心脏分别接受标准血停搏液(载体组，n=6)、含1μm ol/L SPM-5185的血停搏液(低剂量组，n=6)和10μm ol/L停搏液(高剂量组，n=6)。停跳60分钟后，心脏再灌流共60分钟，先处于空跳状态30分钟，然后停止转流30分钟。通过收缩末期压力-容量(阻抗导管)关系的斜率来评估基线和缺血后的左心功能。给药组缺血后收缩末期压力-容量比缺血前降低53.7%(8.2±1.0~3.8±0.3 mm Hg/ml)，低剂量组降低33.7%(9.2±1.1~6.1±0.5 mm Hg/m l)。而大剂量组大鼠脑缺血后功能完全恢复(从7.6±1.1至7.2±1.2 mm Hg/ml)。在这些心脏分离的冠状动脉中，赋形剂组和低剂量组对乙酰胆碱的内皮依赖性最大松弛分别受损27%和18%，而高剂量组表现出完全的内皮依赖性松弛。缺血后心肌髓过氧化物酶活性升高(3.36±0.58和2.56±0.68U/100 mg组织)，高剂量组显著降低至1.27±0.45U/100 mg组织。我们的结论是，在含血停搏液中加入10μ摩尔/L一氧化氮供体SPM5185可能通过抑制中性粒细胞介导的损伤而改善缺血损伤心脏的缺血后心室功能和内皮功能。(J T HORAC心血管疾病杂志1995；109：1146-54)
This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4° C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 μmol/L SPM-5185 (low-dose group; n = 6), or 10 μmol/L SPM-5185 (high-dose group; n = 6). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 60 minutes, first in the beating empty state for 30 minutes and then after discontinuation of bypass for 30 minutes. Baseline and postischemic left ventricular function was assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation. Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preischemic values in the vehicle group (from 8.2 ± 1.0 to 3.8 ± 0.3 mm Hg/ml) and by 33.7% (from 9.2 ± 1.1 to 6.1 ± 0.5 mm Hg/ml) in the low-dose group. In contrast, there was complete postischemic functional recovery in the high-dose group (from 7.6 ± 1.1 to 7.2 ± 1.2 mm Hg/ml). In coronary arteries isolated from these hearts, endothelium-dependent maximal relaxation to acetylcholine was impaired by 27% in the vehicle group and by 18% in the low-dose group, whereas the high-dose group showed complete endothelium-dependent relaxation. Myeloperoxidase activity, an index of neutrophil accumulation in postischemic myocardium, was elevated in the vehicle and low-dose groups (3.36 ± 0.58 and 2.56 ± 0.68 U/100 mg tissue) but was significantly reduced in the high-dose group to 1.27 ± 0.45 U/100 mg tissue. We conclude that inclusion of 10 μmol/L nitric oxide donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly via inhibition of neutrophil-mediated damage. (J T HORAC CARDIOVASC SURG 1995;109:1146-54)