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The role of free radicals in the ischemic myocardium
1Cattedra di Cardiologia, Università di Brescia, Italy.
Insights
Reperfusion therapy effectively treats myocardial ischemia but can cause damage via oxygen free radicals. Further research is needed to understand and mitigate this damage, especially in humans, before widespread antioxidant use.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Reperfusion is crucial for treating ischemic heart muscle.
- Late reperfusion can paradoxically worsen heart damage through complex mechanisms.
- Oxygen free radicals are implicated in reperfusion injury, potentially overwhelming natural defenses.
Purpose of the Study:
- To investigate the role of oxygen free radicals in myocardial reperfusion injury.
- To explore potential therapeutic strategies targeting oxygen free radical formation.
- To highlight the need for human studies on reperfusion injury.
Main Methods:
- Review of existing literature on reperfusion injury and oxygen free radical production.
- Analysis of experimental evidence suggesting enhanced free radical formation post-ischemia/reperfusion.
- Evaluation of studies using antioxidant agents to mitigate reperfusion damage.
Main Results:
- Evidence suggests increased oxygen free radical production after ischemia and reperfusion, possibly originating from mitochondria.
- Prolonged ischemia may impair the heart's natural antioxidant defenses.
- Experimental models show potential for circumventing oxygen free radical-mediated damage.
Conclusions:
- Oxygen free radicals are likely contributors to reperfusion injury, though definitive proof is lacking.
- Further research, particularly in humans, is essential to clarify the role of free radicals and guide antioxidant therapy.
- Caution is advised when interpreting studies on antioxidant interventions due to existing controversies.
Abstract:
Reperfusion is beyond doubt the most effective way to treat the ischaemic myocardium. Late reperfusion may cause further damage, the extent of which can be modified, although the underlying mechanism is still not understood and is likely to be of multifactorial origin. Myocardial production of oxygen free radicals exceeding the neutralizing capacity of the myocytes may be important cause of reperfusion damage. This possibility, however, has by no means been proven. There is evidence that prolonged ischaemia reduces the natural defence mechanism of the heart against oxygen free radicals. Although each method has its limitations, comparison several different methods provided evidence, albeit preliminary, that the formation of these toxic species is enhanced after ischaemia and particularly after reperfusion. It seems that the presence of blood is not a prerequisite for oxygen free radical formation and that the mitochondria are likely to be an important site of production. Experimental work does indicate that the oxygen free radicals-mediated component of the reperfusion damage can be circumvented, which gives rise to optimism for the pharmacologist. However, several controversies exist regarding the meaning of studies in which agents known to interfere with oxygen free radicals have provided protection and conclusions derived from such studies should be considered with caution. Almost no data are available on the role of oxygen free radicals in reperfusion injury in man. This, in our opinion, is the goal to achieve in the very near future, before antioxidant therapy will be blindly and irrationally combined with thrombolytic therapy in the treatment of acute myocardial infarction in man.