A critical review on the translational journey of cardioprotective therapies!

Abstract

The failure to translate novel cardioprotective therapies tested in pre-clinical studies into the clinical setting for patient benefit can be attributed to a number of factors at different stages of the research process. This review focuses on the evidences and the gaps with regard to the translational journey of cardioprotective interventions. Gaps are classified into 3 main groups: 1) those related to pre-clinical studies, 2) those associated with the validation of infarct size as a good surrogate and 3) those based on design and interpretation of randomized clinical trials on cardioprotection. Addressing these gaps might increase the chances to successfully translate cardioprotective therapies into improving both post-STEMI heart failure and cardiovascular death rates.

Ammonium tetrathiomolybdate following ischemia/reperfusion injury: Chemistry, pharmacology, and impact of a new class of sulfide donor in preclinical injury models

“…Indeed, of noncommunicable diseases, the most recent Global Burden of Disease Study cites cardiovascular disease as the leading cause of mortality worldwide [2]. Multiple strategies to prevent or minimize reperfusion injury have to date proved unsuccessful in clinical trials [3,4]. …”

Controlled Reperfusion Strategies Improve Cardiac Hemodynamic Recovery after Warm Global Ischemia in an Isolated, Working Rat Heart Model of Donation after Circulatory Death (DCD)

“…In addition, these results were obtained in an isolated rat heart model and are as such not fully representative of a clinical scenario. Indeed, extrapolation of results obtained in animal experiments to clinical scenarios certainly depends on the species being evaluated (Rossello and Yellon, 2016) and differences in animal physiology, including species-specific sensitivity to myocardial ischemia reperfusion (Lecour et al, 2014). As a consequence, additional preclinical testing is required, including evaluations in a larger animal model.…”

“…Finally, mechanical postconditioning (MPC), brief, intermittent periods of ischemia applied at the onset of reperfusion, has also been demonstrated as cardioprotective (Ferrera et al, 2015; Bartkevics et al, 2016). However, the majority of studies performed to evaluate reperfusion strategies have used models of regional ischemia induced by temporary occlusion of a coronary artery, with analysis of the infarcted area as the typical endpoint (Rossello and Yellon, 2016), and the contractile function of the heart is rarely assessed. As such, findings from these studies cannot be easily extrapolated to situations with clinically relevant DCD conditions, including high pre-ischemic fatty acids levels, warm, global ischemia and hemodynamic evaluation.…”

A Bioactive Chemical Markers Based Strategy for Quality Assessment of Botanical Drugs: Xuesaitong Injection as a Case Study

“…In this study, the anti-CCVD effects of the constituents in XST were divided into seven aspects, including myocardial protection 34, 35 , vascular protection 36, 37 , anticoagulation 29, 38 , antihypertension 38–41 , anti-inflammation 29, 42–44 , anti-oxidation 45–47 , and improvement of carbohydrate and lipid metabolism 38–40 . By manually text-mining the published literatures in Pubmed, the anti-CCVD effects of these constituents in XST were summarized.…”