[PP.20.04] CARDIOPROTECTIVE MODULATION OF T-CELL IMMUNITY BY ANTIHYPERTENSIVE SS-BLOCKER NEBIVOLOL DURING EXPERIMENTAL ISCHEMIA IN HUMAN MYOCARDIAL TISSUE

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Objective: Recent experimental evidence suggests a crucial role of T-lymphocytes in the pathophysiology of myocardial injury. It has been indicated that a pro-inflammatory imbalance resulting from T-cell activation could be responsible for activating the inflammatory cascade ultimately responsible for cellular injury, left ventricular dysfunction, remodelling and outcome. In the present study nebivolol is compared to another standard ß-blocker, atenolol, commonly used in the treatment of myocardial ischemia. Design and method: Myocardial tissue probes derive from the right auricle of patients undergoing cardiac surgery. A small part of the right auricle is removed when the heart is put on extra-corporal circulation. This sample is then be placed in cooled Tyrode solution and hypoxia is brought about by switching 100% oxygen to 100% nitrogen (hypoxia) in one of the two chambers. By doing so, we are able to compare ischemic and non-ischemic tissue of the same patient. Snap frozen samples are stored at -70°C until RNA isolation. Quality of isolated RNA is analysed by Agilent's Bioanalyzer 2100 system. Arrays are scanned with the AB1700 Chemiluminescence Array Reader and images, data are processed by PANTHER software. Results: After 30 minutes of myocardial hypoxia we find that gene expression related to T-cell immunity is more than two-fold up-regulated compared to normoxic controls (25 of 185, 10,4 expected; P < 0.00008). In contrast, when 22,47 μmol nebivolol has been added to the solution, gene expression related to T-cell mediated immunity is significantly down-regulated (21 down of 249, 7.3 expected; P < 0.0001). Conversely, 15 of 21 genes down-regulated by nebivolol during experimental hypoxia have been neither up- nor down-regulated in the presence of an equipotent dose of atenolol during experimental hypoxia. Our observations are in accordance with published data indicating that nebivolol reduced the expression of pro-inflammatory genes in endothelial and vascular smooth muscle cells. Conclusions: Nebivolol, not atenolol inhibits the expression of T-cell immunity related genes during experimental hypoxia. In the light of recent publications on modulating inflammation by pleiotropic effects of cardiovascular drugs, the specific property of T-cell modulation by the antihypertensive drug nebivolol in myocardial ischemia may warrant further attention.

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