calcimycin and Constriction--Pathologic

Experiments were designed to determine effects of dietary supplementation with L -arginine on structure and function of flow-restricted vein grafts.. Saphenous veins were placed as bilateral interposition grafts in femoral arteries of two groups of adult male mongrel dogs; one group was maintained on a normal diet (control), the other group supplemented with L -arginine (200 mg/kg per day) beginning 1 week before surgery. In each dog, flow was reduced by 50% in one graft by placing an adjustable clamp on the artery distal to the distal anastomosis. Plasma amino acids and oxidized products of nitric oxide (NO(x )) were measured before and after L -arginine feeding. At postoperative week 4, grafts were removed and prepared for organ chamber studies to determine functions of the endothelium or smooth muscle and for histology.. Plasma L -arginine increased within 3 hours after feeding and increased from 141 +/- 8 nmol/mL to 169 +/- 11 nmol/mL (n = 6) after 5 weeks of supplementation. Plasma ornithine and citrulline paralleled arginine, whereas circulating NO(x ) was unchanged. Maximal contractions to 60 mmol/L KCl were reduced in grafts from L -arginine-fed dogs. Endothelium-dependent relaxations to the calcium ionophore A23187 and relaxations of the smooth muscle NO were reduced in grafts from L -arginine-fed dogs. Neointimal hyperplasia was increased in grafts with reduced flow and not affected by arginine feeding.. Dietary supplementation with L -arginine did not increase plasma NO in dogs with peripheral vein grafts or increase endothelium-dependent relaxations in control or flow-restricted grafts. Therefore, dietary supplementation with L -arginine may not improve long-term functions of flow-restricted peripheral bypass grafts.

Topics: Adrenergic alpha-Agonists; Amino Acids; Animals; Arginine; Blood Flow Velocity; Brimonidine Tartrate; Calcimycin; Constriction, Pathologic; Dietary Supplements; Dogs; Dose-Response Relationship, Drug; Endothelium, Vascular; Femoral Artery; In Vitro Techniques; Male; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Nitric Oxide; Quinoxalines; Saphenous Vein; Vascular Patency

The effect of antigen (ovalbumin) challenge on pulmonary hemodynamics, bronchoconstriction, and fluid filtration was investigated in Ringer's-perfused (non-recirculating) lungs that had been passively sensitized in vitro. Bolus ovalbumin injection (30 micrograms) produced immediate increases in pulmonary arterial pressure, peak intratracheal pressure, and lung weight within 1 min and secondary marked increases in intratracheal pressure and lung weight from 120 to 200 min. Electron microscopy of antigen-challenged isolated lungs showed evidence of both septal and intraalveolar edema. Ionophore A23187 (100 micrograms) challenge of nonsensitized lungs produced immediate pulmonary responses similar to antigen, whereas secondary increases in lung weight were smaller. Arachidonic acid pretreatment (1 microM) potentiated immediate antigen-induced increases in intratracheal pressure but did not affect pulmonary responses to ionophore challenge. Putative mediators of anaphylaxis including histamine, leukotrienes B4, C4, D4, and E4, platelet-activating factor, and substance P produced immediate changes in pulmonary arterial and/or intratracheal pressure similar to antigen challenge. Only platelet-activating factor and substance P partially mimicked the secondary edema formation noted following antigen challenge. Thus, antigen challenge in in vitro sensitized guinea pig lungs produced both immediate and secondary responses characterized by increases in vascular pressure, airway pressure, and edema formation. This occurred in the absence of circulating blood-formed elements and without a massive influx of cells. Synergism between mediators such as histamine, the leukotrienes, platelet-activating factor, and substance P released following antigen challenge may be necessary to produce the complete pathophysiological sequelae associated with antigen challenge in the perfused guinea pig lung.

Topics: Anaphylaxis; Animals; Antigens; Bronchi; Calcimycin; Constriction, Pathologic; Guinea Pigs; Hemodynamics; Immunization; In Vitro Techniques; Lung; Microscopy, Electron; Ovalbumin; Pulmonary Artery; Pulmonary Edema; Spasm