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冠状动脉内超饱和氧疗法对猪缺血/再灌注模型ST段抬高型心肌梗死心肌血流、微血管阻塞及心肌挽救的影响

Effects of Intracoronary SuperSaturated Oxygen Therapy on Myocardial Blood Flow, Microvascular Obstruction, and Myocardial Salvage in ST-Segment-Elevation Myocardial Infarction in Swine Ischemia/Reperfusion Model.

作者信息

Melo Pedro H C, Kachel Mateusz, Nowak Kacper, Cheng Yanping, Wilburn Paul, Blum Donald, Perumal Ramu, Creech Jeffrey L, Barone-Rochette Gilles, Kloner Robert A, Granada Juan F, Burkhoff Daniel, Kaluza Grzegorz L

机构信息

Skirball Center for Innovation Cardiovascular Research Foundation Orangeburg NY USA.

Hospital Sírio-Libanês São Paulo Brazil.

出版信息

J Am Heart Assoc. 2025 Aug 5;14(15):e038891. doi: 10.1161/JAHA.124.038891. Epub 2025 Jul 17.

Abstract

BACKGROUND

Early reperfusion after ST-segment-elevation myocardial infarction is essential for limiting infarct size. However, reperfusion injury can lead to progressive microvascular obstruction (MVO), reducing myocardial blood flow (MBF), aggravating ischemia and myocardial necrosis. We hypothesized that SuperSaturated Oxygen (SSO) Therapy may reduce infarct size by alleviating MVO, so we evaluated the effects of SSO on the time course of MBF and MVO in a preclinical ischemia/reperfusion model.

METHODS

Twelve swine surviving 90 minutes of balloon-induced anterior ST-segment-elevation myocardial infarction and 15-minute auto-reperfusion, were assigned to 120 minutes of SSO (n=6) or further 120 minutes of auto-reperfusion (control, n=6). Microspheres were injected into the left ventricle at multiple time points to assess MBF, calculated as the total blood flow within areas at risk normalized to the total flow within remote zones. An angiography-derived index of microcirculatory resistance was analyzed. MVO and infarct zones were identified using thioflavin-S and 2,3,5-triphenyl tetrazolium chloride staining and quantified with ImageJ software.

RESULTS

SSO Therapy significantly reduced MVO compared with controls (4.64% versus 13.00% of left ventricular area; <0.001) and improved myocardial salvage index (MSI, 64.76% versus 43.11%; =0.03). MBF was significantly higher in the SSO group compared with controls at the end of therapy (1.1 versus 0.59; =0.03). In the controls, following initial hyperemia, flow decreased significantly at 165, 195, and 225 minutes (=0.01). Conversely, the SSO group showed no significant decrease in MBF in the same interval (=0.38). Median angiography-derived index of microcirculatory resistance values showed a nonsignificant trend of reduced final microvascular resistance in the SSO group only.

CONCLUSIONS

In a translational ST-segment-elevation myocardial infarction model, SSO prevented a reduction in MBF during the 120-minute reperfusion period, with significantly increased MBF at the end of the experiment. MBF improvement was translated to a 64% relative reduction in the extent of MVO, and a 50% relative increase in the myocardial salvage index.

摘要

背景

ST段抬高型心肌梗死后的早期再灌注对于限制梗死面积至关重要。然而,再灌注损伤可导致进行性微血管阻塞(MVO),减少心肌血流量(MBF),加重缺血和心肌坏死。我们假设超饱和氧(SSO)疗法可能通过减轻MVO来减小梗死面积,因此我们在临床前缺血/再灌注模型中评估了SSO对MBF和MVO时间进程的影响。

方法

12头猪在球囊诱导的前壁ST段抬高型心肌梗死90分钟并自动再灌注15分钟后存活,被分配接受120分钟的SSO治疗(n = 6)或再进行120分钟的自动再灌注(对照组,n = 6)。在多个时间点将微球注入左心室以评估MBF,计算方法为将危险区域内的总血流量标准化为远隔区域内的总血流量。分析了血管造影衍生的微循环阻力指数。使用硫黄素-S和2,3,5-三苯基氯化四氮唑染色识别MVO和梗死区域,并用ImageJ软件进行量化。

结果

与对照组相比,SSO疗法显著降低了MVO(左心室面积的4.64%对13.00%;<0.001),并改善了心肌挽救指数(MSI,64.76%对43.11%;=0.03)。治疗结束时,SSO组的MBF显著高于对照组(1.1对0.59;=0.03)。在对照组中,初始充血后,血流量在165、195和225分钟时显著下降(=0.01)。相反,SSO组在相同时间段内MBF没有显著下降(=0.38)。血管造影衍生的微循环阻力值中位数仅显示SSO组最终微血管阻力有不显著的降低趋势。

结论

在一个转化性ST段抬高型心肌梗死模型中,SSO在120分钟的再灌注期内防止了MBF的降低,实验结束时MBF显著增加。MBF的改善转化为MVO范围相对降低64%,心肌挽救指数相对增加50%。

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