Key result
A bicyclic FXIIa inhibitor did not significantly reduce infarct size compared to an inactive control peptide in a porcine model of myocardial ischemia/reperfusion injury (p > 0.05).
Why the study?
Does a bicyclic FXIIa inhibitor reduce infarct size in a porcine model of myocardial ischemia/reperfusion injury?
Does a bicyclic FXIIa inhibitor reduce infarct size in a porcine model of myocardial ischemia/reperfusion injury?
In a standardized closed-chest porcine model of myocardial ischemia/reperfusion injury, a novel bicyclic FXIIa inhibitor did not significantly reduce infarct size, though this may be due to unoptimized dosing.
Answers are grounded in this paper and cite their sources.
Null result in porcine IRI model does not support FXIIa inhibition; leaves open dosing optimization and translation.
Myocardial ischemia reperfusion (I/R) injury contributes to almost half of the necrotic area after myocardial infarction. To date there is no approved drug to prevent or reduce myocardial I/R injury. The study and understanding of the pathophysiological mechanisms of myocardial I/R injury is essential to develop successful treatments. Large animal experiments are an important step in translational methods. The porcine model of acute myocardial infarction has been established and described by ourselves and others. We aimed to further improve the value of the model by focusing in detail on the sampling techniques for use in future experiments. Furthermore, we emphasize small but important steps that can affect the quality of the final results. To mimic the clinical situation of myocardial I/R injury, a percutaneous coronary intervention (PCI) catheter was inserted into the left anterior descending coronary artery (LAD) of an anesthetized pig. °°°This model mimics acute myocardial infarction and PCI treatment in humans with the possibility of accurately determining the area at risk as well as the necrotic- and viable ischemic tissue. Here the model was used to investigate the effect of a bicyclic peptide inhibitor of FXIIa. The model can also be modified to allow longer reperfusion times to study later effects of myocardial infarction.
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Abdelhafez et al. (2018) studied Myocardial ischemia/reperfusion injury (n=5). Bicyclic FXIIa inhibitor vs. Inactive bicyclic control peptide was evaluated on Infarct size (necrotic ischemic tissue as a percentage of the area at risk) (p=>0.05). A bicyclic FXIIa inhibitor did not significantly reduce infarct size compared to an inactive control peptide in a porcine model of myocardial ischemia/reperfusion injury (p > 0.05).
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