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Published on: March 12, 2018
Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion
Insights
Cobra venom factor reduces myocardial infarct size after coronary occlusion by inhibiting complement-dependent inflammation. This treatment protects ischemic heart tissue from necrosis, offering a novel therapeutic approach.
Area of Science:
- Cardiovascular Research
- Immunology
- Complement System
Background:
- The complement system plays a role in inflammation and tissue damage.
- Cobra venom factor activates the alternative complement pathway, cleaving C3.
- C3 involvement in ischemic injury suggests potential therapeutic targets.
Purpose of the Study:
- To investigate if cobra venom factor can reduce tissue damage after acute coronary occlusion.
- To assess the effect of cobra venom factor on myocardial necrosis and creatine phosphokinase (CPK) activity.
Main Methods:
- Coronary artery occlusion was induced in dogs for 24 hours.
- Cobra venom factor was administered intravenously 30 minutes post-occlusion in experimental groups.
- Epicardial electrograms, CPK activity, and histological analysis were performed.
Main Results:
- Cobra venom factor significantly reduced myocardial necrosis (54% vs 97% in controls).
- A weaker correlation between ST-segment elevation and CPK activity was observed in the treatment group.
- Reduced polymorphonuclear leukocyte infiltration into the myocardium was noted.
Conclusions:
- Cobra venom factor protects ischemic myocardium from necrosis, likely by inhibiting complement-mediated inflammation.
- This study demonstrates a novel approach to limit myocardial infarct size by targeting complement pathways.
Abstract:
Components of the complement system are known to play an important role in the cytolytic process and in chemotaxis of leukocytes. Cobra venom factor specifically cleaves C3 activity via activation of the alternative (properdin) complement pathway. It does not act directly on C3. If C3 is involved in tissue necrosis after ischemic injury, cobra venom factor might reduce tissue damage after acute coronary occlusion. Accordingly, in 14 control dogs occlusion of the left anterior descending artery was carried out for 24 h. Epicardial electrograms were recorded 15 min after occlusion, and 24 h later transmural specimens for creatine phosphokinase activity (CPK) and for histological analysis were obtained from the same sites. In another 14 experimental dogs, 20 U/kg cobra venom factor was given intravenously 30 min after occlusion. Serum complement levels fell within 2-4 h to <20% of normal. In the control dogs, the relationship between ST-segment elevation and CPK activity 24 h later was: log CPK = -0.06 ST + 1.48 (n = 111 specimens, 14 dogs, r = 0.77). In the experimental dogs, log CPK = -0.024 ST + 1.46 (n = 111 specimens, 14 dogs, r = 0.60), showing significantly different slopes (P < 0.001), i.e., less CPK depression for any level of ST-segment elevation. Histologically, 69 of 71 sites (97%) with ST-segment elevation exceeding 2 mV in the control dogs showed signs of necrosis 24 h later, whereas in the experimental group only 43 of 79 sites (54%) with abnormal ST-segment elevations showed signs of necrosis (P < 0.0005). At the same time, it was shown that the administration of cobra venom factor did not alter cardiac performance, collateral blood flow to the ischemic myocardium or the clotting system, but infiltration of polymorphonuclear leukocytes into the myocardium was decreased. It is concluded that cobra venom factor, by reducing the amount of C3 and C5 substrate available for chemotactic factor generation, or other as yet undefined mechanisms, protects the ischemic myocardium from undergoing necrosis, as judged by histology and local CPK activity. Hence, a new approach to limiting the extent of myocardial infarcts after experimental coronary occlusion, based upon inhibition of complement-dependent inflammatory processes, is demonstrated.
