European Heart Journal Advance Access originally published online on November 30, 2004
European Heart Journal 2005 26(1):99; doi:10.1093/eurheartj/ehi029
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Letter to the Editor
What is ‘reperfusion injury’?
Department of Cardiology
2nd Faculty of Medicine
Charles University
University Hospital Motol
V Uvalu 84
150 18 - Prague 5
Czech Republic
E-mail address: ostadal{at}yahoo.com
I read with great interest the article by Turschner et al.1 describing the echocardiographic observation of experimentally induced myocardial infarction and subsequent reperfusion in the pig model. They have demonstrated an increase in regional wall thickness in the reperfused infarct zone due to ‘oedema associated with reperfusion injury’.
The phenomenon of ‘reperfusion injury’ (first described by Tennant and Wiggers2) comes entirely from experimental laboratories; there are a number of experimental observations showing the deleter-ious effects of reperfusion leading to further progression of already existing ischaemic damage. Data from human studies are, however, in discrepancy with experimental models. Large clinical trials concerned with reperfusion therapy and acute myocardial infarction have shown a clearly positive effect of early reperfusion in thousands of patients. Based on these observations, early reperfusion therapy became the first-choice therapeutic option to reduce mortality, limit infarct size, and improve functional parameters in patients suffering from acute myocardial infarction. What is the reason for this discrepancy?
At least a partial explanation offers the different timing of experimental and clinical studies: the deleterious effect of experimental ‘reperfusion injury’ is shown in minutes or at most hours after restoration of perfusion; clinical trials showing a protective effect of reperfusion were designed as a long-term follow-up of patients after myocardial infarction in days, months, and even years. Short-term experimental settings are unable, however, to distinguish whether observed changes represent newly developed injury or just an acceleration of healing, associated with destroying the already severely damaged, non-viable cells (even if these cells have some signs of viability at the time of reperfusion).3 Until now, there has been no clear evidence that reperfusion may be harmful for the fully viable cardiomyocyte.4
Another fact requires our attention: ‘reperfusion injury’ does not occur without preceding ischaemic injury. After a short period of ischaemia, restoration of coronary flow does not induce any signs of ‘reperfusion injury’ and therefore ischaemic injury is a conditio sine qua non for the development of subsequent ‘reperfusion injury’. This observation is clear evidence that ‘reperfusion injury’ is at least tightly connected with preceding ischaemia but very probably a part of ‘ischaemia–reperfusion injury’.3,5
With some exaggeration, I would provide one indubitable example of deleterious effect of ‘reperfusion injury’: 3 years ago, there was admitted to the CCU with acute myocardial infarction a general practitioner, who was refusing reperfusion therapy because of being afraid of ‘reperfusion injury’. It took at least 10 min to convince him about the beneficial effect of reperfusion; in these 10 min he could have already profited from reperfusion.
To conclude, I would emphasize that until now, there has been no clear evidence that reperfusion causes an additional injury to the ischaemic myocardium. Based on the literature data I would fully support the suggestion presented by Bolli6 that the term ‘reperfusion injury’ is actually a misnomer and that the appropriate term should be ‘ischaemia–reperfusion injury’.
References
- Turschner O, D'hooge J, Dommke C, Claus P, Verbeken E, De Scheerder I, Bijnens B, Sutherland GR. The sequential changes in myocardial thickness and thickening which occur during acute transmural infarction, infarct reperfusion and the resultant expression of reperfusion injury. Eur Heart J 2004;25:794–803.
[Abstract/Free Full Text] - Tennant R, Wiggers C. The effect of coronary occlusion on myocardial contraction. Am J Physiol 1935;112:351–361.
[Free Full Text] - Ostadal P, Zdobnicka I, Dhalla NS. Does reperfusion cause any injury to the myocardium? In: Dhalla NS, Chockalingam A, Berkowitz HI, Singal PK, eds. Frontiers in Cardiovascular Health. Boston: Kluwer Academic Publishers; 2003, p145–159.
- Ferrari R, Hearse DJ. Reperfusion injury: does it exist and does it have clinical relevance? J Thromb Thrombolysis 1997;4:25–34.[CrossRef][Medline]
- Bolli R, Marban E. Molecular and cellular mechanisms of myocardial stunning. Physiol Rev 1999;79:609–634.
[Abstract/Free Full Text] - Bolli R. Postischemic myocardial "stunning": pathogenesis, pathophysiology, and clinical relevance. In: Yellon DM, Jennings RB, eds. Myocardial Protection: The Pathophysiology of Reperfusion and Reperfusion Injury. New York: Raven Press; 1992, p105–149.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||