Histamine is released into the systemic circulation during anaphylaxis, by drugs and surgical procedures. Studies in animal models have shown that released histamine is one of the major mediators of arrhythmia occurring during anaphylaxis or the administration of histamine-releasing drugs. The variations in plasma histamine levels in dogs with a subacute coronary thrombosis were investigated and the effects of dimaprit and cimetidine on the electrocardiographic consequence of this thrombosis and on histamine release were assessed. During the first day after the myocardial infarction a ventricular arrhythmia developed and plasma histamine levels were found significantly increased, returning to the basal values when the sinusal rhythm was restored. Dimaprit was able to decrease the number of ventricular extrasystoles and to modulate plasma histamine levels. The action of dimaprit on ECG was not reversed by pretreatment with cimetidine, which on the contrary was able to antagonize the decrease in plasma histamine concentrations induced by dimaprit perfusion.

Histamine inhibits superoxide anion (O-2) production from human neutrophils stimulated by N-formylmethionyl-leucyl-phenylalanine (FMLP). The effects of histamine are dose-dependent and competitively antagonized by cimetidine. When passively sensitized rat serosal mast cells and human neutrophils are mixed together, O-2 production from FMLP-activated granulocytes is significantly reduced, following mast cell degranulation by acetylcholine. These inhibitory effects can be counteracted by cimetidine. Exposure of non-sensitized rat mast cells to FMLP-stimulated human neutrophils causes histamine release. These results suggest bidirectional control mechanisms between mast cells and neutrophils, that further stress the role of histamine in regulating inflammatory processes.

Superoxide (O^––₂) and nitric oxide (NO) production by polymorphonuclear leukocyte (PMNs) and monocytes in patients with liver cirrhosis were evaluated. PMNs obtained from cirrhotic patients were less effective than those from controls in producing O^––₂ after stimulation with opsonized zymosan, while they were more effective in producing NO, as shown by the inhibition of platelet aggregation and by the increase in cGMP content. NO synthase activity was higher in leukocytes from cirrhotic patients than in controls. A correlation was found between the cardiac index and the observed changes in the inflammatory cells.

Mast cell heterogeneity in response to acetylcholine has been evidentiated by the virtual lack of sensitivity or by the full reaction to nanomolar concentrations of acetylcholine, observed in samples of serosal mast cells isolated from the same animal species. The incubation with IgE of isolated rat mast cells renders the originally heterogeneous response homogeneous, the release of histamine evoked by acetylcholine being proportional to the IgE concentration. The histamine release induced by acetylcholine is due to the activation of muscarinic receptors, since it is blocked by atropine, not reproduced by acetylthiocholine and potentiated by exposure of the cells to the specific antigen.

1 Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2 In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration-dependent fashion. At the highest concentration studied (10-6 M), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3 The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NG-monomethyl-L-arginine (L-NMMA, 10-4 M), an inhibitor of nitric oxide synthase (NOS). 4 The endothelium-dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10-4 M). 5In guinea-pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6 Reperfusion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7 The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed.