The Effects of Orciprenaline on the Contractility of Isolated Cardiomyocytes under Septic Conditions Mediated by Lipopolysaccharide

Abstract

The septic cardiomyopathy is associated with a high morbidity and mortality. In a sepsis, the contractility of a cardiomyocyte is reduced significantly. Consecutively, the cardiac output of the heart is compromised. This so-called "low cardiac output syndrome" caused by a septic cardiomyopathy is responsible for the deaths of about one fifth of the patients. A patient suffering from sepsis needs a prolonged therapy with catecholamine under an intensive care setting. In this study, the influence of catecholamine on the contractility of isolated cardiomyocyte was observed experimentally. The hypothesis was that the reversal of the septic cardiac depression through catecholamine in vivo ("rescue effect") was based on the improvement of the contractility of the cells. The ventricular cardiomyocytes of C57BL/6 mice were isolated through Langendorff-Perfusion-Technique. Then, one group of the cells were incubated for six hours with the addition of Lipopolysaccharide (LPS) so that a bacterial sepsis could be simulated. The second group was incubated in culture medium for six hours without LPS. When the incubation was over, the cardiomyocytes of the two groups were stimulated electrically in different frequencies. The stimulation was carried out with or without the addition of orciprenaline, a none-selective β-Sympathomimetic agent, with which the catecholamine therapy in a septic cardiomyopathy could be simulated. The sarcomere shortening of each cell was recorded through light microscope. Then, the data was digitized and processed, so that the following parameters could be derived: resting sarcomere length, sarcomere shortening amplitude, sarcomere shortening speed and relaxation speed. This study proved that the above mentioned "rescue effect" of a β-stimulation was able to completely reverse the negative influence of LPS on shortening even on the level of isolated cardiomyocytes. This study was able to extend a clinically proven therapy of septic cardiomyopathy to the level of single cardiomyocyte.