New preclinical evidence is promising with H2S; rapamicin; sildenafil; ticagrelor, LCZ696; etc

Dear Francisco,

thanks a lot for your answer.

Hydrogen sulfide prodrugs now only under study, and I do not find data about cardioprotective property H2S. Good data about cardioprotective effects of rapamycin in ischaemia-reperfusion injury. Protective Effects of Ticagrelor on Myocardial Injury After Infarction - first publications in 2016. Very good result. LCZ696. Just returned from HF congress in Paris, many presentations and posters but nobody talk about cardioprotective effect LCZ696. President of HF Association said - I do not known what kind of mechanism of action of this drug...

Thanks again.

Dear Sergey, I´m performing research in a lab where my boss is diving deeply into mechanistic cardioprotective effects of H2S. This are some of his previous publications.

In my case, I´m performing preclinical research in rabbit animal model to assess cardioprotective effect of LCZ696 after ischemia rep. Anything I can help you just ask me.

Article Beetroot juice reduces infarct size and improves cardiac fun...

Article Hydrogen sulfide and cardioprotection — Mechanistic insights...

Article Hydrogen sulfide mediates the cardioprotective effects of ge...

Thank you sou much Francisco! I need time to read those article.

Sergey.

Effect of Erythropoietin in patients with acute myocardial infarction: five-year results of the REVIVAL-3 trial

Erythropoietin (EPO) has been suggested to promote cardiac repair after MI. However, the randomized, double-blind, placebo controlled REVIVAL-3 trial showed that short term high dose EPO in timely reperfused myocardium does not improve left ventricular ejection fraction after 6 months. Moreover, the study raised safety concerns due to a trend towards a higher incidence of adverse clinical events as well as a increase in neointima formation after treatment with EPO. The present study therefore aimed to assess the 5-year clinical outcomes.

These 5 years follow-up data show that short-term use of 3 IV doses epoetin beta in PCI-treated STEMI patients does not improve clinical long-term prognosis. Our results further support the erythropoietin paradox and advise caution regarding the application of erythropoetin in patients with STEMI.

Does this mean that the direction for studying EPO in patients with AMI is closed?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5251242/pdf/12872_2016_Article_464.pdf

Is cardioprotection dead?

In 2011 the National Heart, Lung, and Blood Institute established a network called the Consortium for Preclinical Assessment of Cardioprotective Therapies (CAESAR) that was based on the principles of clinical trials (ie, randomization, investigator blinding, exclusion criteria, and appropriate statistical analyses).

Table 1. For the outcome of all agents, there was no effect on infarct size. *Experimental Biology Abstract. April 26-30, 2014. San Diego, CA.

Results (part of table) Table 2.

Similarly dispiriting results.

But my opinion - сardioprotection is alive.

New direction of cardioprotection:

- stem cells...

- cardioprotective and regenerative microRNAs... 

By David J. Lefer and Eduardo Marbán.