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Influence of the terminal complement-complex on reperfusion injury, no-reflow and arrhythmias: a comparison between
1Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany.
Insights
The complement system
Area of Science:
- Cardiovascular Research
- Immunology
- Pathophysiology
Background:
- Reperfusion injury following myocardial infarction is a significant clinical concern.
- The complement system, particularly the C5b-9 complex, has been implicated in myocardial reperfusion injury.
- Understanding the role of complement activation in infarct size, reflow, and arrhythmias is crucial.
Purpose of the Study:
- To investigate the impact of the C5b-9 complement complex on myocardial infarct size.
- To assess the influence of C5b-9 on myocardial reflow after ischemia.
- To evaluate the role of C5b-9 in the development of post-reperfusion arrhythmias.
Main Methods:
- Utilized C6-competent and C6-deficient rabbits subjected to coronary artery occlusion and reperfusion.
- Quantified infarct size using triphenyl tetrazolium chloride staining.
- Assessed myocardial reflow via histological analysis with propidium iodide and monitored arrhythmias using continuous ECG.
Main Results:
- In early ischemia (30 min), C6-deficient rabbits showed significantly smaller infarct sizes compared to C6-competent rabbits.
- Reflow was similar in both groups at 30 min but significantly impaired in C6-competent rabbits after 2 h of ischemia.
- C6-competent rabbits experienced more fatal ventricular arrhythmias than C6-deficient rabbits.
Conclusions:
- The lytic C5b-9 complement complex contributes to reperfusion injury and larger infarcts in early ischemia.
- Complement activation exacerbates the no-reflow phenomenon after 2 h of ischemia without affecting infarct size.
- C6 status influences susceptibility to ventricular arrhythmias post-coronary artery occlusion, independent of reperfusion.
Objective:
The complement system has been suggested to play a role in reperfusion injury which may result from an enhanced destruction of myocardial tissue or from an impairment of reflow. We investigated the influence of the C5b-9 complement complex on infarct size, reflow and arrhythmogenesis.
Methods:
Twenty-eight C6-competent rabbits and 18 rabbits with congenital C6 deficiency were subjected to either 30 min or 2 h of coronary artery occlusion followed by reperfusion. C6 deficiency was confirmed by the complement titration test and immunohistology. The triphenyl tetrazolium chloride method was used to delineate infarct size. Reflow into infarcted areas was evaluated histologically after an in vivo injection of propidium iodide which served as an early fluorescence microscopic marker of damaged myocardium subjected to reflow. Continuous ECG monitoring allowed the recording of arrhythmias.
Results:
After 30 min of coronary artery occlusion infarct size was significantly smaller in C6-deficient rabbits (5.0 +/- 2% of the risk region) as compared to C6-competent rabbits (28.4 +/- 8.5%, P = 0.0371). The extent of reflow into damaged myocardium was nearly the same in both animal groups at this time (38 +/- 9 vs. 39 +/- 7% of the risk region). After 2 h of coronary artery occlusion, infarct size was not different between both animal groups, but the extent of reflow into damaged myocardium was significantly smaller in C6-competent rabbits than in C6-deficient rabbits (25 +/- 4 vs. 40 +/- 4%; P = 0.0185). Two of the 18 C6-deficient rabbits had ventricular arrhythmias (Lown II-IV), none of which was fatal. Eleven of the 28 C6-competent animals had major ventricular arrhythmias which were fatal in 6 rabbits.
Conclusions:
These results suggest that the lytic C5b-9 complement complex leads to reperfusion injury in the early phase (30 min) of ischaemia, resulting in a larger infarct. After 2 h of ischaemia, complement activation enhances the no-reflow phenomenon but does not affect infarct size. Finally, the C6 status seems to influence the susceptibility to ventricular arrhythmias after coronary artery occlusion, independent of reperfusion.