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In this study, the isolated use of methylene blue (MB) in the treatment of anaphylactic shock induced by Compound 48/80 (C48/80), a potent histamine releaser, was examined, and the study of the effects of MB on the function of the aorta artery endothelium was accomplished in vitro. MB was used in a single 3.0 mg/kg dose, and C48/80 was used in a single 4.5 mg/kg dose. The study protocol included the following experimental groups, containing six animals each: group I (control), animals in the absence of any drug action; group II (MB), MB infusion; Group III (C48/80), anaphylactic shock induced by using C48/80; group IV (C48/80 + MB), anaphylactic shock treated with MB infusion at the moment of major hypotension; and group V (MB + C48/80), prevention of anaphylactic shock with MB by means of MB infusion minutes before the 4.5 mg/kg C48/80 infusion. Nitric oxide plasma levels were measured in each of the experimental groups. After the in vivo studies were performed, an in vitro study was conducted using segments of the abdominal aortas of the rabbits to determine the effect of MB on the arterial endothelium. The results obtained in the present investigation have shown that MB intravenous infusion does not change the mean arterial pressure when compared with the control group (n = 6 in each group, P < 0.05); that C48/80 is effective in producing experimental anaphylactic shock (n = 6, P < 0.05); that the attempt to prevent anaphylactic shock with MB results in a mean prolongation of animal survival ranging from 17 to 34 min (n = 6 in each group, P < 0.05); that MB is effective in reversing anaphylactic shock in all the studied rabbits (n = 6, P < 0.05); that absolute and percentage plasma nitrate values obtained with the experimental groups do not differ (n = 6, each group, P < 0.05); and that the in vitro study of segments of abdominal aorta has shown that there has not been endothelial dysfunction in any of the groups (n = 6 in each group, P < 0.05). The good results obtained in this study open a research path that may offer data to define new paradigms for treating anaphylaxis.

Background: Most prior physiological studies of the endothelium of intact saphenous veins have used organ chambers to assay abluminal release of vasoactive factors that affect smooth muscle contraction and relaxation. However, intraluminal release of vasoactive factors may have important implications in saphenous vein bypass graft patency., Methods and Results: To study the basal and stimulated intraluminal release of endothelium-dependent relaxing factor (EDRF), 5-cm segments of human saphenous veins were cannulated and perfused in vitro with physiological salt solution. Vasoactive properties of the effluent were bioassayed on canine coronary artery smooth muscle. Effluent from saphenous veins produced vasodilation of 4.0 +/- 1.8% (+/- SEM) (n = 26) under basal conditions and 36.1 +/- 6.7% when stimulated with calcium ionophore, A23187 (n = 19, P < .05). Fourteen of the 26 vein segments showed no basal release of EDRF. Vasodilation produced by the effluent could be eliminated by mechanically removing the endothelium or by treatment with NG-monomethyl-L-arginine or NG-nitro-L-arginine, two competitive inhibitors of nitric oxide synthesis from L-arginine. Vasodilation was not influenced by indomethacin., Conclusions: Previous studies of EDRF from human saphenous veins were performed in organ chambers, which could detect only extraluminal EDRF release. This is the first demonstration of intraluminal release of EDRF from human saphenous veins. The variable and relatively poor basal release of EDRF into the lumen may account for early thrombogenicity of vein grafts and may contribute to late atherosclerosis.

Background: When used to reverse the anticoagulant effect of heparin, protamine sulfate often causes vasodilation that can lead to systemic hypotension. Protamine is rich in the basic amino acid arginine, which is the precursor of endothelial cell synthesis of nitric oxide, and nitric oxide is the active component of endothelium-derived relaxing factor (EDRF)., Methods and Results: To determine whether the hypotensive effect of protamine could be due to stimulated release of EDRF, we studied rings (4-5 mm) of canine coronary, femoral, and renal artery suspended in organ chambers containing physiological salt solution (37 degrees C and 95% O2-5% CO2). Arterial rings with and without endothelium were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and exposed to increasing concentrations of protamine (final organ bath concentration, 40-400 micrograms/ml). In arterial segments without endothelium, protamine caused only a modest decrease in tension. However, protamine induced concentration-dependent relaxation in all arterial segments with endothelium, which was significantly greater than in segments without endothelium (p less than 0.05). The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10(-5) M), but L-NMMA had no effect on rings without endothelium. The action of L-NMMA could be reversed by L-arginine (10(-4) M) but not D-arginine (10(-4) M)., Conclusions: This study demonstrates that protamine stimulates the release of EDRF from arterial endothelium, and that endothelium-dependent vasodilation may be an important cause of systemic hypotension during protamine infusion.

Traumatic rupture of the interventricular septum is a rare condition usually presenting in infancy and childhood. This report describes two cases: a 3-year-old boy operated on soon after the diagnosis was made, and a 15-year-old girl operated on 12 years following the causative accident. Both patients had the diagnosis confirmed by cardiac catheterization. The typical appearance of a traumatic ventricular septal defect (VSD) was seen during surgical repair that was successfully carried out in both patients. The protracted clinical course of the second patient, eventually requiring corrective intervention, contributes to the understanding of natural history of traumatic VSD.