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19th World Congress on Heart Disease

 

THE PIVOTAL ROLE OF L-ARGININE IN THE ISCHEMIC HEART PRECONDITIONING - A NANOMEDICAL APPROACH


Tadeusz Malinski, Ph.D., Dr.h.c.m., Ohio University, Athens, OH, USA

 

Ischemic preconditioning with a short coronary artery occlusion has been shown to protect the heart against a subsequent myocardial infarction. Although several endogenous molecules have been implicated in the heart adaptation to an ischemic event, its mechanism is not well understood. A nanomedical approach was used to study, in vivo and ex vivo, the concentration changes of small molecules in the heart during preconditioning. Catheter-protected nanosensors, with a diameter of 300nM, were implanted into the left ventricular wall of the heart of New Zealand white rabbits, in order to measure the concentration of nitric oxide (NO), peroxynitrite (ONOO-), superoxide (O2-), and carbon monoxide (CO), as well as, tetrahydrobiopterin and L-arginine. Ischemia triggered fast release of NO level, which peaked at 1.20.2 micromol/L, after 5 minutes. The release of NO was accompanied by the generation of superoxide, which reached maximum concentration after 71 minutes, and peroxynitrite which peaked after 172 minutes. At 15 minutes of ischemia, equal concentrations (0.8 micromole/L) of NO, O2-, and ONOO- were measured. After 19 minutes, the cytoprotective NO significantly decreased and the cytotoxic ONOO- increased. Therefore, the ratio of NO/ONOO- decreased to 0.050.03 from the preischemic ratio of 7:1. Ischemic preconditioning was achieved by an episode of 4-7 minutes of occlusion, followed by 15-60 minutes of reperfusion prior to the 60 minute occlusion. L-arginine content in the heart was measured during different stages of ischemic preconditioning, reperfusion and ischemia. The content of L-arginine increased significantly, from 14 nmol/L per mg protein by 10-50%, after preconditioning. The increase in L-arginine content after preconditioning correlated directly with the decrease of infarct size (256%) when compared to the control (485%). These results support the hypothesis that the cardioprotective effect of ischemic preconditioning is dependent on L-arginine availability.

 

 

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