Pedro H C Melo, Mateusz Kachel, Kacper Nowak, Yanping Cheng, Paul Wilburn, Donald Blum, Ramu Perumal, Jeffrey L Creech, Gilles Barone-Rochette, Robert A Kloner, Juan F Granada, Daniel Burkhoff, Grzegorz L Kaluza
{"title":"冠状动脉内过饱和氧治疗对猪缺血/再灌注模型st段抬高型心肌梗死心肌血流、微血管阻塞和心肌挽救的影响","authors":"Pedro H C Melo, Mateusz Kachel, Kacper Nowak, Yanping Cheng, Paul Wilburn, Donald Blum, Ramu Perumal, Jeffrey L Creech, Gilles Barone-Rochette, Robert A Kloner, Juan F Granada, Daniel Burkhoff, Grzegorz L Kaluza","doi":"10.1161/JAHA.124.038891","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sub>2</sub>) Therapy may reduce infarct size by alleviating MVO, so we evaluated the effects of SSO<sub>2</sub> on the time course of MBF and MVO in a preclinical ischemia/reperfusion model.</p><p><strong>Methods: </strong>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<sub>2</sub> (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.</p><p><strong>Results: </strong>SSO<sub>2</sub> Therapy significantly reduced MVO compared with controls (4.64% versus 13.00% of left ventricular area; <i>P</i><0.001) and improved myocardial salvage index (MSI, 64.76% versus 43.11%; <i>P</i>=0.03). MBF was significantly higher in the SSO<sub>2</sub> group compared with controls at the end of therapy (1.1 versus 0.59; <i>P</i>=0.03). In the controls, following initial hyperemia, flow decreased significantly at 165, 195, and 225 minutes (<i>P</i>=0.01). Conversely, the SSO<sub>2</sub> group showed no significant decrease in MBF in the same interval (<i>P</i>=0.38). Median angiography-derived index of microcirculatory resistance values showed a nonsignificant trend of reduced final microvascular resistance in the SSO<sub>2</sub> group only.</p><p><strong>Conclusions: </strong>In a translational ST-segment-elevation myocardial infarction model, SSO<sub>2</sub> 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.</p>","PeriodicalId":54370,"journal":{"name":"Journal of the American Heart Association","volume":" ","pages":"e038891"},"PeriodicalIF":5.0000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Pedro H C Melo, Mateusz Kachel, Kacper Nowak, Yanping Cheng, Paul Wilburn, Donald Blum, Ramu Perumal, Jeffrey L Creech, Gilles Barone-Rochette, Robert A Kloner, Juan F Granada, Daniel Burkhoff, Grzegorz L Kaluza\",\"doi\":\"10.1161/JAHA.124.038891\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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<sub>2</sub>) Therapy may reduce infarct size by alleviating MVO, so we evaluated the effects of SSO<sub>2</sub> on the time course of MBF and MVO in a preclinical ischemia/reperfusion model.</p><p><strong>Methods: </strong>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<sub>2</sub> (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.</p><p><strong>Results: </strong>SSO<sub>2</sub> Therapy significantly reduced MVO compared with controls (4.64% versus 13.00% of left ventricular area; <i>P</i><0.001) and improved myocardial salvage index (MSI, 64.76% versus 43.11%; <i>P</i>=0.03). MBF was significantly higher in the SSO<sub>2</sub> group compared with controls at the end of therapy (1.1 versus 0.59; <i>P</i>=0.03). In the controls, following initial hyperemia, flow decreased significantly at 165, 195, and 225 minutes (<i>P</i>=0.01). Conversely, the SSO<sub>2</sub> group showed no significant decrease in MBF in the same interval (<i>P</i>=0.38). Median angiography-derived index of microcirculatory resistance values showed a nonsignificant trend of reduced final microvascular resistance in the SSO<sub>2</sub> group only.</p><p><strong>Conclusions: </strong>In a translational ST-segment-elevation myocardial infarction model, SSO<sub>2</sub> prevented a reduction in MBF during the 120-minute reperfusion period, with significantly increased MBF at the end of the experiment. 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引用次数: 0
摘要
背景:st段抬高型心肌梗死后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。我们假设过饱和氧(SSO2)治疗可以通过减轻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SSO2对MBF和MVO时间过程的影响。方法:12头存活90分钟的球囊性st段抬高型心肌梗死和15分钟的自动再灌注的猪,被分配到120分钟的SSO2 (n=6)或进一步的120分钟的自动再灌注(n=6)。在多个时间点将微球注射到左心室以评估MBF,计算为危险区域内的总血流归一化到偏远区域内的总血流。分析了血管造影衍生的微循环阻力指数。采用硫黄素- s和2,3,5-三苯基氯化四氮唑染色确定MVO和梗死区,并用ImageJ软件定量。结果:与对照组相比,SSO2治疗显著降低了MVO(左心室面积4.64% vs 13.00%;页= 0.03)。治疗结束时,SSO2组MBF显著高于对照组(1.1比0.59;P = 0.03)。在对照组中,初始充血后,血流在165、195和225分钟显著下降(P=0.01)。相反,SSO2组在同一时间段内MBF无显著降低(P=0.38)。血管造影中微循环阻力指数显示,仅SSO2组微血管最终阻力降低趋势不显著。结论:在平移性st段抬高型心肌梗死模型中,SSO2阻止了120分钟再灌注期间MBF的降低,实验结束时MBF显著增加。MBF改善转化为MVO范围相对减少64%,心肌挽救指数相对增加50%。
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.
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 (SSO2) Therapy may reduce infarct size by alleviating MVO, so we evaluated the effects of SSO2 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 SSO2 (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: SSO2 Therapy significantly reduced MVO compared with controls (4.64% versus 13.00% of left ventricular area; P<0.001) and improved myocardial salvage index (MSI, 64.76% versus 43.11%; P=0.03). MBF was significantly higher in the SSO2 group compared with controls at the end of therapy (1.1 versus 0.59; P=0.03). In the controls, following initial hyperemia, flow decreased significantly at 165, 195, and 225 minutes (P=0.01). Conversely, the SSO2 group showed no significant decrease in MBF in the same interval (P=0.38). Median angiography-derived index of microcirculatory resistance values showed a nonsignificant trend of reduced final microvascular resistance in the SSO2 group only.
Conclusions: In a translational ST-segment-elevation myocardial infarction model, SSO2 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.
期刊介绍:
As an Open Access journal, JAHA - Journal of the American Heart Association is rapidly and freely available, accelerating the translation of strong science into effective practice.
JAHA is an authoritative, peer-reviewed Open Access journal focusing on cardiovascular and cerebrovascular disease. JAHA provides a global forum for basic and clinical research and timely reviews on cardiovascular disease and stroke. As an Open Access journal, its content is free on publication to read, download, and share, accelerating the translation of strong science into effective practice.