Intramyocardial Hemorrhage and the “Wave Front” of Reperfusion Injury Compromising Myocardial Salvage

Ting Liu; Andrew G. Howarth; Yinyin Chen; Anand R. Nair; Hsin-Jung Yang; Daoyuan Ren; Richard Tang; Jane Sykes; Michael S. Kovacs; Damini Dey; Piotr Slomka; John C. Wood; Robert Finney; Mengsu Zeng; Frank S. Prato; Joseph Francis; Daniel S. Berman; Prediman K. Shah; Andreas Kumar; Rohan Dharmakumar

doi:10.1016/j.jacc.2021.10.034

An Introduction to Cardioprotection

10.1093/med/9780199544769.003.0001 ◽

2011 ◽

Keyword(s):

Reperfusion Injury ◽

Myocardial Injury ◽

Artery Bypass ◽

Bypass Graft ◽

Myocardial Damage ◽

Myocardial Salvage ◽

Ischaemia Reperfusion Injury ◽

Acute Ischaemia ◽

Ischaemia Reperfusion ◽

Considerable Morbidity

• In its broadest sense, the term ‘cardioprotection’ encompasses ‘all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage’• However, for the purposes of this book, the term ‘cardioprotection’ will refer to the endogenous mechanisms and therapeutic strategies that reduce or prevent myocardial damage induced by acute ischaemia-reperfusion injury• In this context, cardioprotection begins with the primary prevention of coronary heart disease and includes the reduction of myocardial injury sustained during coronary artery bypass graft surgery, and an acute myocardial infarction, conditions with considerable morbidity and mortality• An understanding of the pathophysiology of acute myocardial ischaemia-reperfusion injury is essential when designing new cardioprotective strategies• Several methods exist for both quantifying myocardial damage induced by acute ischaemia-reperfusion injury and for assessing myocardial salvage following the application of cardioprotective strategies• Importantly, novel cardioprotective strategies must be capable of preventing and reducing myocardial damage over and above that provided by current optimal therapy.

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Myocardial Salvage by Chimyl Alcohol: Possible Role of Peroxisomal Dysfunction in Reperfusion Injury

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1994.tb36752.x ◽

1994 ◽

Vol 723 (1) ◽

pp. 380-384 ◽

Cited By ~ 5

Author(s):

NILANJANA MAULIK ◽

ARPAD TOSAKI ◽

RICHARD M. ENGELMAN ◽

GERALD A. CORDIS ◽

DIPAK K. DAS

Keyword(s):

Reperfusion Injury ◽

Myocardial Salvage

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LO076: Remote ischemic conditioning to reduce reperfusion injury during acute STEMI: a systematic review and meta-analysis

CJEM ◽

10.1017/cem.2016.113 ◽

2016 ◽

Vol 18 (S1) ◽

pp. S56-S56

Author(s):

S.L. McLeod ◽

A. Iansavitchene ◽

S. Cheskes

Keyword(s):

Heart Failure ◽

Systematic Review ◽

Infarct Size ◽

Reperfusion Injury ◽

Mean Difference ◽

Controlled Trials ◽

Myocardial Salvage ◽

Cochrane Central Register ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning

Introduction: Remote ischemic conditioning (RIC) is a non-invasive therapeutic strategy that uses brief cycles of inflation and deflation of a blood pressure cuff to reduce ischemia-reperfusion injury during acute ST-elevation myocardial infarction (STEMI). The primary objective of this systematic review was to determine if RIC initiated prior to catheterization increases myocardial salvage index, defined as the proportion of area at risk of the left ventricle salvaged by treatment following emergent percutaneous coronary intervention (PCI) for STEMI. Secondary outcomes included infarct size and major adverse cardiovascular events. Methods: Electronic searches of PubMed, Ovid MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were conducted and reference lists were hand-searched. Randomized controlled trials comparing PCI with and without RIC for patients with STEMI published in English were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random-effects models and reported as risk ratios (RR) with 95% confidence intervals (CIs). Results: Nine RCTs were included with a combined total of 999 patients (RIC+PCI = 534, PCI = 465). The myocardial salvage index was higher in the RIC+PCI group at 3 and 30 days; mean difference 0.09 (95% CI: 0.04, 0.15) and 0.12 (95% CI: 0.03, 0.21), respectively. Infarct size was reduced in the RIC+PCI group at 3 and 30 days; mean difference -3.82 (95% CI: -8.15, 0.51) and -4.00 (95% CI: -7.07, -0.93), respectively. There was no statistical difference with respect to death and re-infarction, however there was a reduction in heart failure with RIC+PCI at 6 months; RR: 0.43 (95% CI: 0.19, 0.99). Conclusion: RIC is emerging as a promising adjunctive treatment to PCI for the prevention of reperfusion injury in STEMI patients. Ongoing, multicenter clinical trials will help elucidate the effect of RIC on clinical outcomes such a hospitalization, heart failure and mortality.

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Hypothermia for Reduction of Myocardial Reperfusion Injury in Acute Myocardial Infarction: Closing the Translational Gap

Circulation Cardiovascular Interventions ◽

10.1161/circinterventions.120.010326 ◽

2021 ◽

Author(s):

Mohamed El Farissi ◽

Danielle C.J. Keulards ◽

Jo M. Zelis ◽

Marcel van ’t Veer ◽

Frederik M. Zimmermann ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Infarct Size ◽

Reperfusion Injury ◽

Myocardial Reperfusion ◽

Myocardial Reperfusion Injury ◽

Current Status ◽

Myocardial Salvage ◽

Nonlinear Phenomena ◽

Comprehensive Overview

Myocardial reperfusion injury—triggered by an inevitable inflammatory response after reperfusion—may undo a considerable part of the myocardial salvage achieved through timely percutaneous coronary intervention in patients with acute myocardial infarction. Because infarct size is strongly correlated to mortality and risk of heart failure, the importance of endeavors for cardioprotective therapies to attenuate myocardial reperfusion injury and decrease infarct size remains undisputed. Myocardial reperfusion injury is the result of several complex nonlinear phenomena, and for a therapy to be effective, it should act on multiple targets involved in this injury. In this regard, hypothermia remains a promising treatment despite a number of negative randomized controlled trials in humans with acute myocardial infarction so far. To turn the tide for hypothermia in patients with acute myocardial infarction, sophisticated solutions for important limitations of systemic hypothermia should continue to be developed. In this review, we provide a comprehensive overview of the pathophysiology and clinical expression of myocardial reperfusion injury and discuss the current status and possible future of hypothermia for cardioprotection in patients with acute myocardial infarction.

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Abstract 2666: Randomized Controlled Trial to Compare High-Dose N-Acetylcystein Versus Placebo to Prevent Contrast-Induced Nephropathy and Myocardial Reperfusion Injury in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Circulation ◽

10.1161/circ.118.suppl_18.s_764 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Holger Thiele ◽

Ingo Eitel ◽

Lysann Hildebrand ◽

Carmen Schirdewahn ◽

Volker Adams ◽

...

Keyword(s):

Oxidative Stress ◽

Placebo Group ◽

Reperfusion Injury ◽

Microvascular Obstruction ◽

Myocardial Reperfusion ◽

High Dose ◽

Myocardial Salvage ◽

Primary Pci ◽

Contrast Induced Nephropathy ◽

Randomized Controlled

STEMI patients undergoing PCI are at high risk for contrast-induced nephropathy (CIN) because of hemodynamic instability and lack of effective prophylaxis. High-dose N-Acetylcystein (N-ACC) reduced the incidence of CIN in patients with high contrast volumes. In addition, previous animal trials showed that the antioxidant effects of N-ACC reduce reperfusion injury. Aim of this randomized, controlled, single-blinded trial was to assess the effects of N-ACC on CIN and reperfusion injury in patients undergoing primary PCI with moderate contrast volumes. Two hundred-fifty patients undergoing primary PCI were randomized to either high-dose N-ACC (2x1200 mg/d for 48 hours) or placebo plus optimal hydratation. The two primary endpoints were: 1) occurrence of CIN defined as an increase in the serum creatinine concentration of >25% from the baseline value within 72 h; 2) Myocardial salvage measured by T2-weighted STIR-images and delayed enhancement MRI at day 2– 4 after primary PCI. Secondary endpoints were infarct size and microvascular obstruction, ST-resolution at 90 minutes and occurrence of MACE at 30 day follow-up. The median volume of an isoosmolar contrast agent during PCI was 190 ml (IQR 130, 250 ml) in the N-ACC and 180 (IQR 143; 228 ml) in the placebo group (p=n.s.). Baseline creatinine and creatinine clearance were 88 vs 86 μmol/l and 90 vs 95 ml/min, respectively. The primary endpoint CIN occurred in 14% in the N-ACC group and in 18% in the placebo group (p=n.s.). The primary endpoint reperfusion injury measured by myocardial salvage was also not different between both treatment groups (25.4%; IQR 14.1; 38.1 versus 22.5%; IQR 16.8; 36.5; p=n.s.). In addition, no differences in infarct size and microvascular obstruction as well as in ST-segment resolution were observed. The MACE rate after N-ACC was similar to placebo (19.4% versus 19.4%, p=n.s.). Lipid peroxidation as a marker for oxidative stress was reduced by 20% in the N-ACC group (p<0.05), whereas no change was evident in placebo. High-dose N-ACC reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and prevention of myocardial reperfusion injury in patients undergoing PCI with moderate doses of contrast medium and optimal hydratation.

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