I have been reading about various drugs inducing anti-remodeling effects in animal models (rats) of myocardial infarction. Can someone suggest why ischemia-reperfusion is not preferred in this regards and permanent ligation of the coronary artery is preferred? Is it because of the influence of reperfusion on infarct size, thus "reperfusion" itself may mask the true effect of therapeutic drug?
Collaterals development and cardiac remodeling (dilation, hypertrophy, fibrosis), is it more important in the long-term, after a permanent ligation of the coronary, than in a temporary ischemia / reperfusion? Maybe it explains why in remodeling studies, permanent ligature is preferred? However permanent ligation necessarily discards reperfusion lesions which would be severe and this model seams to be further from human clinical study...
I think,
The main interest here in attenuating remodeling are the effects of the drug/treatment in question on the scar and on the remaining "healthy" tissue. In order to acheive, in an animal model, the extreme clinical scenario one would prefer the ischemia protocol rather than the ischemia-reperfusion protocol. in extreme scenarios one would expect a better results or effect on remodeling, than minute damage.
In the isechenia protocol you would get a rather big scar, and affected remaining tissue "healthy muscle". both can be a potenital substrates for reverse-remodeling by various treatemtns or drugs.
Yes there is a limitation of drug delivery, as the ligation is permanent, but, I think that due to the large extent of the scar, drug can affect it through collateral or previously present coranaries that were not affect during the ligation (CRA etc) or even directly from the left ventricle itself.
Thank you all for your answers.
Thanks Dr. Ertacht for your comprehensive reply. I was reading sometimes drugs or therapies improve remodeling independent of their influence on infarct size. Thus, they improve post-infarct ventricular functions like dilation and hypertrophy. Certainly, infarct size is the direct determinant of ventricular remodeling but often therapies are meant to target post-infarct events taking place in the healthy myocardium. Moreover, I came across that 120 min of ligation produces a similar infarct as that of permanent ligation. Which model is more close to the clinical setting? I mean therapeutic targets can be hit little before or say a day after reperfusion. But how can permanent ligation be justified? Is it like for patients which cannot undergo reperfusion, they can be helped with alternative drug therapies without reperfusion.
My sincere apologies for this weird kinda question but you can guess that I don't have any clinical background.
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