Lowering asymmetric dimethylarginine levels as a possible therapeutic strategy in myocardial ischemia / reperfusion

A groundbreaking project led by TU Dresden and British partners is exploring the reduction of asymmetric dimethylarginine (ADMA) as a therapeutic strategy for myocardial ischemia/reperfusion injury (MIRI), a common complication following a heart attack. MIRI exacerbates heart damage despite restored blood flow and can account for up to 50% of the final infarct size, posing a significant challenge with no specific treatment currently available.

Key highlights of the project include the development of an innovative extracorporeal device that uses immobilized DDAH1 enzyme to lower ADMA levels. Ex vivo tests demonstrated an impressive 90% reduction of ADMA in blood samples from patients at Uniklinikum Dresden’s apheresis unit. The project aims to achieve a 30% reduction in infarct size – the primary endpoint – using a pig model with a 60-minute occlusion of the left anterior descending coronary artery followed by 24 hours of reperfusion. Additionally, researchers will investigate whether lowering ADMA reduces the time to defibrillation and the number of shocks required during surgery. The study involves 20 pigs, split evenly between an ADMA-lowering group and a sham group, with further analysis focusing on apoptosis rates, inflammatory cell infiltration, and proinflammatory cytokine levels in heart tissue.

The experimental phase is scheduled to conclude by August 31, 2025, with histological analysis completed by October 31, 2025, statistical evaluation by November 30, 2025, and a final manuscript prepared by December 31, 2025. If successful, these findings could pave the way for clinical trials, offering a transformative approach to improving heart health post-infarction.

Dr. Sergey Tselmin, a clinician-scientist with over 20 years of apheresis expertise, and Prof. Mahmoud Barbir, a leading cardiologist specializing in lipoprotein apheresis, combine their skills to drive this promising therapy forward. Their collaboration holds the potential to revolutionize treatment for heart attack patients.