ABSTRACT
Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.
Subject(s)
Dinucleoside Phosphates/pharmacology , Myocardial Contraction/drug effects , Platelet Aggregation Inhibitors/pharmacology , Animals , Calcium/metabolism , Calcium/physiology , Calcium Channels/drug effects , Calcium Channels/physiology , Cells, Cultured , Drug Interactions , Guinea Pigs , Heart/drug effects , Heart Atria/drug effects , Heart Ventricles/cytology , Heart Ventricles/drug effects , Humans , In Vitro Techniques , Male , Myocardium/metabolism , Xanthines/pharmacologyABSTRACT
Disruption of the middle lobe broncus as a result of blunt chest trauma is described. Patient underwent emergency reconstructive operation. Follow-up examination revealed normal postoperative chest radiogram but bronchoscopy showed decreased patency of bronchial anastomosis. Perfusion lung scintigraphy showed severely decreased perfusion of the entire right lung. Concomitant fracture of right clavicle resulted in false joint which required surgical intervention 4 weeks after the chest trauma.
