RESUMO
PURPOSE: Vein grafts undergo morphologic and functional changes after insertion into the arterial circulation with the development of intimal hyperplasia, as well as significant alterations in endothelial and smooth muscle cell physiologic responses. METHODS: Forty New Zealand white rabbits underwent jugular vein interposition grafting of the common carotid artery. Ten animals were controls, 10 animals received 2.25% L-arginine supplementation in their drinking water (200 ml/day; 2 gm/kg) 7 days before surgery and continued thereafter until harvest, in 10 animals the veins were immersed in deferoxamine manganese (DFMn; 10(-3) mol/L in heparinized Ringer's lactate for 15 minutes) before implantation, and 10 received both L-arginine supplementation and either histologic (n=6) or isometric tension studies (n=4). The function of the vein grafts was compared with that of jugular veins. RESULTS: Treatment with DFMn, l-arginine, amd DFMn L-arginine produce increases in mean intimal thickness of 39% (51 +/ -7 microm; p<0.05), 51% (41 +/- 7 microm; p<0.05), and 65% (29 +/- 6 microm; p< 0.01), respectively, compared with control vein grafts (83 +/- 12 microm). Compared with the control group, the intimal ratio ([intima]/[intima + media]) decreased by 16% (difference not significant), 8% (difference not significant), and 47% (p<0.01) in the DFMn-, L-arginine- and and DFMn/L-arginine-treated vein grafts, respectively. Jugular veins relaxed to acetylcholine (53% +/- 12% maximal relaxation), whereas control vein grafts did not relax. In contrast, vein grafts from each of the experimental groups relaxed to acetylcholine with maximal relaxations of 26% +/- 7% (p<0.05 compared with the jugular vein), 22% +/- 8% (p<0.05), and 44% +/- 14% (difference not significant) in the DFMn, L-arginine, DFMn/L-arginine groups, respectively. Neither DFMn nor l-arginine had a significant effect on the alterations in smooth muscle contractility that occur in control vein grafts. CONCLUSION: This study demonstrates that an agent that modulates free radical production combined with a precursor of nitric oxide formation will lead to a significant decrease in the formation of intimal hyperplasia in arterial vein grafts with the preservation of endothelial-derived relaxation.
Assuntos
Arginina/administração & dosagem , Desferroxamina/administração & dosagem , Veias Jugulares/efeitos dos fármacos , Túnica Íntima/efeitos dos fármacos , Administração Oral , Aminoácidos/administração & dosagem , Animais , Artéria Carótida Primitiva/cirurgia , Hiperplasia/patologia , Hiperplasia/prevenção & controle , Veias Jugulares/patologia , Veias Jugulares/fisiopatologia , Veias Jugulares/transplante , Coelhos , Sideróforos/administração & dosagem , Túnica Íntima/patologiaRESUMO
Diabetic patients may experience fluctuations in whole blood glucose (WBG) levels while receiving hyperbaric oxygen therapy (HBO) resulting in seizure-like activity. Therefore, hyperbaric medical attendants must accurately monitor the WBG levels of these patients during HBO. In addressing this concern, this study evaluated the accuracy and reliability of commercially available glucometers (Glucometer M+, Companion 2, HemoCue, One Touch II, and ExacTech Pen) in the hyperbaric environment. WBG samples were prepared, ranging from 25 to 250 mg/dl, for testing glucometers at ground level and at 2.36 atmospheres absolute (ATA). It was noted that at 2.36 ATA, glucose values increased using the Glucometer M+, but decreased with the Companion 2 and HemoCue. The One Touch II values decreased in the hyperglycemic ranges (> 150 mg/dl), whereas the ExacTech Pen monitor readings increased in the hypoglycemic ranges (< 100 mg/dl). The accuracy of WBG monitors is significantly affected by changes in atmospheric pressure.
Assuntos
Glicemia/análise , Oxigenoterapia Hiperbárica , Monitorização Fisiológica/normas , Pressão Atmosférica , Automonitorização da Glicemia/instrumentação , Automonitorização da Glicemia/normas , Humanos , Monitorização Fisiológica/instrumentação , Reprodutibilidade dos TestesRESUMO
Pharmacologic and molecular evidence conflicts in regard to the existence of tissue-specific subtypes of thromboxane A2 receptors (TXR). The full length TXR complementary DNA (cDNA) was cloned from a platelet-like cell line. It was expressed and its pharmacology was characterized. Northern analysis of TXR transcripts in multiple tissues showed strong hybridization to K562 chronic myelogenous leukemia messenger RNA. Therefore, a K562 cDNA library was screened and a full-length TXR cDNA (K562TXR) was isolated. K562TXR encodes a protein identical to the previously characterized placenta TXR cDNA, except for a single amino acid substitution (Glu21-->Lys). Similar to thromboxane receptors on K562 cells, K562TXR transiently expressed in HEK 293 cells (K562TXR/293) bound the thromboxane agonist 125I-labeled [1S-(1 alpha,2 beta(5Z),3 alpha-(1E,3S),4 alpha]-7-[3-(3-hydroxy-4-(p- iodophenoxy)-1-butenyl)-7-oxabicyclo-[2.2.1]heptane-2-yl]-5- heptenoic acid ([125I]BOP) with a Kd of 5.5 +/- 1.1 nM, a Bmax of 289,056 +/- 60,220 sites/cell and a Hill coefficient of -0.94 +/- 0.01 (n = 6). K562TXR/293 cells also demonstrated concentration-dependent increases in intracellular calcium in response to the thromboxane agonist (15S-hydroxy-11 alpha,9 alpha(epoxymethano)-prosta-5Z,13E-dienoic acid. In contrast to the single [125I]BOP binding site observed in K562TXR/293, [125I]BOP binding to placental membranes resulted in a Hill coefficient significantly less than unity with a statistically superior two-site model for binding [KdH 0.63 +/- 0.18 nM and KdL of 12.5 +/- 5.0 nM, with Bmaxs of 29 +/- 9 and 212 +/- 41 fmol/mg of protein, respectively (n = 7)].(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , DNA Complementar/isolamento & purificação , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Receptores de Tromboxanos/genética , Sequência de Bases , Compostos Bicíclicos com Pontes/metabolismo , Cálcio/metabolismo , Clonagem Molecular , Ácidos Graxos Insaturados/metabolismo , Proteínas de Ligação ao GTP/análise , Humanos , Dados de Sequência Molecular , RNA Mensageiro/análise , Receptores de Tromboxanos/metabolismo , Transfecção , Células Tumorais CultivadasRESUMO
Necrotizing invasive pseudomonal infection of the external auditory canal (malignant external otitis) is an uncommon but important disorder in the elderly. The high morbidity, and even mortality, of this disorder has been reduced by the early and intensive use of combination antipseudomonal antibiotics. However, in severely immunocompromised patients or in infection involving the base of the skull, multiple cranial nerves, or the meninges, conventional therapy has been prolonged, intensive, and relatively ineffective. We treated 16 patients with malignant external otitis with adjuvant hyperbaric oxygen therapy. In six patients, infection was in advanced stages, infections were recurrences after previous treatment, and repeated treatment with antipseudomonal antibiotics had failed. All 16 cases responded promptly when a 30-day course of hyperbaric oxygen was added to the antibiotic regimen, and all patients remained free of infection or neurologic deficit during 1 to 4 years of follow-up. No complications of this treatment modality were noted. Hyperbaric oxygen therapy reverses tissue hypoxia, which enhances phagocytic killing of aerobic microorganisms, and stimulates neomicroangiogenesis. In addition, hyperbaric oxygen augments the action of aminoglycoside antibiotics. Adjuvant hyperbaric oxygen therapy should be considered in advanced or recurrent cases of malignant external otitis.