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Updated: Aug 6, 2026
Induction and Assessment of Ischemia-reperfusion Injury in Langendorff-perfused Rat Hearts
Published on: July 27, 2015
Historical account of reperfusion therapy and the development of cardioprotection beyond reperfusion
Gerd Heusch1, Petra Kleinbongard2, Bernard J Gersh3
1Cardioprotection Unit, Institute for Pathophysiology, West German Heart and Vascular Center, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. Gerd.heusch@uk-essen.de.
Insights
Timely reperfusion of blocked arteries is crucial for saving heart muscle after infarction, reducing damage and death. Research also explores cardioprotection strategies beyond reperfusion, like ischemic conditioning, though clinical application is pending.
Area of Science:
- Cardiovascular Medicine
- Interventional Cardiology
- Experimental Cardiology
Background:
- Myocardial infarction necessitates prompt restoration of blood flow to salvage heart tissue.
- Reperfusion therapy has evolved significantly, improving outcomes in acute myocardial infarction.
- Cardioprotective strategies beyond reperfusion are under investigation.
Purpose of the Study:
- To review the historical development of reperfusion therapy for acute myocardial infarction.
- To examine the evolution of treatments from thrombolysis to percutaneous coronary intervention.
- To discuss the progress and challenges in establishing cardioprotection beyond reperfusion.
Main Methods:
- Historical review of key clinical trials and experimental studies in reperfusion therapy.
- Analysis of the progression of treatment modalities, including pharmacological and mechanical approaches.
- Examination of research into cardioprotective strategies such as ischemic conditioning.
Main Results:
- Timely reperfusion significantly reduces infarct size and mortality.
- Therapeutic advancements include streptokinase, tissue plasminogen activator, platelet inhibition, and percutaneous coronary intervention with stenting.
- Experimental evidence supports cardioprotection via ischemic conditioning, but clinical translation remains limited.
Conclusions:
- Timely reperfusion remains the cornerstone of acute myocardial infarction management.
- Percutaneous coronary intervention with stenting represents the current standard for mechanical recanalization.
- Further research and clinical trials are needed to establish novel cardioprotective strategies in clinical practice.
Abstract:
The only way to salvage myocardium from infarction is timely reperfusion of the occluded coronary artery. Timely reperfusion reduces infarct size and mortality. The history of reperfusion therapy from the first clinical use of intravenous streptokinase in patients with acute myocardial infarction by Sherry et al. in the late 1950s, over seminal experimental dog studies by Ross Jr. et al., demonstrating infarct size reduction by timely reperfusion in the early 1970s, to a more systematic use of initially streptokinase and a later tissue plasminogen activator in clinical trials (GISSI, TIMI), the addition of platelet inhibition (ISIS) and ultimately mechanical recanalization by percutaneous coronary intervention with stenting, is reviewed in detail. Cardioprotection beyond timely reperfusion was first demonstrated in the seminal experimental dog studies of ischemic conditioning by Murry, Reimer, and Jennings in the 1980s and initiated a tsunami of experimental studies in various experimental models to identify the underlying signal transduction, but has not yet been established in clinical practice. Clinical trials on various forms of ischemic conditioning, potentially cardioprotective drugs and transcutaneous vagal nerve stimulation, are still underway.
