Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide
Increased myocardial matrix metalloproteinases in hypoxic newborn pigs during resuscitation: effects of oxygen and carbon dioxide
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DOI：
10.1111/j.1365-2362.2004.01378.x
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发表时间：
2004-07-01
影响因子：
5.5
通讯作者：
Saugstad, OD
中科院分区：
文献类型：
--
作者：
Borke, WB;Munkeby, BH;Saugstad, OD
背景 围产期窒息与心脏功能障碍有关，在复苏过程中防止进一步的组织损伤非常重要。越来越多的证据表明心肌基质金属蛋白酶（MMP）参与心肌低氧血症-复氧损伤。 目的 评估新生猪全身缺血后的 MMP 和抗氧化能力，并随后在不同 PaCO2 水平下使用环境空气或 100% O-2 进行复苏。 方法 新生猪（12-36 小时龄）通过 21% 或 100% 通气复苏 30 分钟缺氧损伤后不同 PaCO2 水平下的 O-2，然后观察 150 分钟。在心肌组织提取物中，通过明胶酶谱和广泛基质降解能力（总 MMP）对 MMP 进行分析。通过氧自由基吸收能力 (ORAC) 测定来测量心肌组织提取物中的总内源抗氧化能力。 结果 基质金属蛋白酶-2 比基线值增加了一倍多 (P < 0.001)，并且使用 100% O-2 复苏的仔猪比使用环境空气复苏的仔猪更高 (P = 0.012)。 ORAC值显着降低（P<0.001）。在 PaCO2 升高的仔猪中，右心室的总 MMP 活性比左心室增加更多 (P = 0.008)。在左心室中，低 PaCO2 仔猪的总 MMP 活性高于 PaCO2 升高仔猪 (P = 0.013)。结论 在低氧血症-复氧损伤中，MMP-2 水平显着升高，并且在用 100% O-2 复苏的仔猪中升高最多。抗氧化能力显着下降。根据总 MMP 活性评估，复苏期间 PaCO2 升高可能会保护左心室，并可能增加右心室心肌损伤。
Background Perinatal asphyxia is associated with cardiac dysfunction, and it is important to prevent further tissue injury during resuscitation. There is increasing evidence that myocardial matrix metalloproteinases (MMPs) are involved in myocardial hypoxaemia-reoxygenation injury.Objectives To assess MMPs and antioxidant capacity in newborn pigs after global ischaemia and subsequent resuscitation with ambient air or 100% O-2 at different PaCO2-levels.Methods Newborn pigs (12-36 h of age) were resuscitated for 30 min by ventilation with 21% or 100% O-2 at different PaCO2 levels after a hypoxic insult, and thereafter observed for 150 min. In myocardial tissue extracts, MMPs were analyzed by gelatin zymography and broad matrix-degrading capacity (total MMP). Total endogenous antioxidant capacity in myocardial tissue extracts was measured by the oxygen radical absorbance capacity (ORAC) assay.Results Matrix metalloproteinase-2 more than doubled from baseline values (P < 0.001), and was higher in piglets resuscitated with 100% O-2 than with ambient air (P = 0.012). The ORAC value was considerably decreased (P < 0.001). In piglets with elevated PaCO2, total MMP-activity in the right ventricle was more increased than in the left ventricle (P = 0.008). In the left ventricle, total MMPactivity was higher in the piglets with low PaCO2 than in the piglets with elevated PaCO2 (P = 0.013).Conclusion In hypoxaemia-reoxygenation injury the MMP-2 level was highly increased and was most elevated in the piglets resuscitated with 100% O-2. Antioxidant capacity was considerably decreased. Assessed by total MMP-activity, elevated PaCO2 during resuscitation might protect the left ventricle, and probably increase right ventricle injury of the myocardium.