Abstract
RationaleAcute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries.ObjectiveOf relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study.Methods and ResultsAMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG.ConclusionsThese data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI.
Highlights
Even though advancements in pharmaceutical and interventional treatment have significantly reduced early mortality following acute myocardial infarction (AMI), ischemic cardiomyopathy developing after AMI still remains widely prevalent and represents an increasing economic burden in countries of the western world [1]
These data indicate that anti-thymocyte globulin (ATG), a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53
The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI
Summary
Even though advancements in pharmaceutical and interventional treatment have significantly reduced early mortality following acute myocardial infarction (AMI), ischemic cardiomyopathy developing after AMI still remains widely prevalent and represents an increasing economic burden in countries of the western world [1]. Studies confirmed that only a small proportion of transplanted cells remained in the ischemic myocardium and so the concept of stem cells forming new viable myocardium has been shattered by unsatisfactory results in large clinical trials Viewed in this light, new mechanistic concepts were proposed such as the ‘‘The Dying Stem Cell Hypothesis’’ by Thum et al [5], namely, that a large proportion of stem cells are already undergoing apoptosis at the time point of transfusion. New mechanistic concepts were proposed such as the ‘‘The Dying Stem Cell Hypothesis’’ by Thum et al [5], namely, that a large proportion of stem cells are already undergoing apoptosis at the time point of transfusion The authors of this hypothesis argued that apoptotic cells are conferring immunomodulatory signals and thereby attenuating immunoactivation and excessive inflammation in the infarcted myocardium and by doing so circumventing ventricular remodeling. This promising therapeutic concept has not been further addressed until now
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
