Potential influence of the pericardial space on myocardial function: Cardiac interactions of adenosine and endothelin-1

Abstract

Adenosine (ADO) and endothelin-1 (ET-1) play an important role in the regulation of myocardial functions. The pericardial fluid accumulates these regulatory agents and reflects well their levels in the myocardial interstitium. The aim was to investigate the interaction and cardiovascular effects of ADO and ET-1 evoked from the pericardial space, determine the pericardial elimination of intrapericardially applied adenosine and its first metabolite, inosine (INO) and observe their effects on the cardiovascular function compared to their intravenous administration. The present studies were performed on in situ dog heart using the closed pericardium model. Significant increase of the pericardial concentrations of adenine nucleosides (adenosine and inosine) after intrapericardial administration of ET-1 has been found. Regarding the adenine nucleosides-ET-1 interaction, we have demonstrated ET-1 liberation after intrapericardial administration of adenine nucleosides. The present study confirmed significantly slower elimination of adenine nucleosides in the pericardial space than in the systemic circulation. In conclusion, characteristic cardiovascular effect and bidirectional interaction of adenine nucleosides and ET-1 could be provoked by and detected in the pericardial space, reflecting parallel changes in the myocardial interstitium. The low pericardial turnover rate of adenine nucleosides may offer the opportunity of utilizing their multiple beneficial effects for local pharmaco-therapeutic interventions.