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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Imprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15.

Parental origin-specific alterations of chromosome 11p15 in human cancer suggest the involvement of one or more maternally expressed imprinted genes involved in embryonal tumor suppression and the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). The gene encoding cyclin-dependent kinase inhibitor p57KIP2, whose overexpression causes G1 phase arrest, was recently cloned and mapped to this band. We find that the p57KIP2 gene is imprinted, with preferential expression of the maternal allele. However, the imprint is not absolute, as the paternal allele is also expressed at low levels in most tissues, and at levels comparable to the maternal allele in fetal brain and some embryonal tumors. The biochemical function, chromosomal location, and imprinting of the p57KIP2 gene match the properties predicted for a tumor suppressor gene at 11p15.5. However, as the p57KIP2 gene is 500 kb centromeric to the gene encoding insulin-like growth factor 2, it is likely to be part of a large domain containing other imprinted genes. Thus, loss of heterozygosity or loss of imprinting might simultaneously affect several genes at this locus that together contribute to tumor and/or growth- suppressing functions that are disrupted in BWS and embryonal tumors.

Base Sequence↗
PubMed1996

The pharmacokinetics of a microemulsion formulation of cyclosporine in primary renal allograft recipients. The Neoral Study Group.

This study was a randomized, double-blind, 12-week comparison of the pharmacokinetics, safety, and tolerability of two cyclosporine (CsA) formulations, cyclosporine emulsion capsules and oral solution for microemulsion and cyclosporine, in the postoperative management of renal transplant patients. Of the 101 patients, aged 18 to 65, who entered the study, 89 were evaluable for pharmacokinetics. Initial dosage was 10 mg/kg per day, administered twice daily in two equal doses. Dosages were adjusted to achieve target CsA concentrations. The pharmacokinetic (PK) parameters (dose-normalized) of greatest interest were maximum blood concentration (C(max)/dose), time to reach maximum concentration (t(max), area under the blood concentration-vs.-time curve (AUC/dose), and trough blood concentrations (Co h/dose). The relative CsA bioavailabilty was found to be significantly enhanced with cyclosporine emulsion compared with cyclosporine with a 16% to 31% increase in AUC and a 32% to 42% increase in C(max). Intrapatient variability of PK parameters was significantly lower with cyclosporine emulsion than with cyclosporine for AUC, C(oh), t(max), and C(max) in many instances. This indicates a more consistent, rapid, and more complete total absorption of CsA. Despite higher CsA C(max) levels and AUCs with cyclosporine emulsion, safety and tolerability (detailed in a parallel report) were comparable to those of cyclosporine. The PK advantages of cyclosporine emulsion over cyclosporine are either independent of food conditions or possibly reflective of more consistent absorption of CsA with cyclosporine emulsion. The findings suggest that de novo use of cyclosporine emulsion may simplify and improve management of organ transplant recipients and that the PK advantages of cyclosporine emulsion may translate into clinical benefits.

Adolescent↗
PubMed1996

The safety and tolerability of cyclosporine emulsion versus cyclosporine in a randomized, double-blind comparison in primary renal allograft recipients. The Neoral Study Group.

A 12-week, randomized, double-blind, multicenter pharmacokinetics study was conducted to compare the clinical safety and tolerability of cyclosporine capsules and oral solution for microemulsion and cyclosporine in 101 primary renal transplant recipients Cyclosporine emulsion has more complete absorption and improved bioavailability compared with cyclosporine, and dosing of both cyclosporine formulations was adjusted to achieve comparable whole-blood trough levels. Mean serum creatinine values were higher in the cyclosporine emulsion group at baseline, 8, and 12 weeks (P<0.05). The incidence of acute rejection was similar in both treatment groups although fewer patients required monoclonal antibody therapy in the cyclosporine group (31% vs. 82%, respectively). Despite the increased bioavailability of cyclosporine emulsion, no significant differences in the incidence of adverse events were observed; the safety, tolerability, and efficacy of cyclosporine emulsion and cyclosporine were comparable.

Administration, Oral↗
PubMed1996

Combined in vitro and in vivo T lymphocyte depletion for the control of graft-versus-host disease following haploidentical marrow transplant.

Most patients requiring allogeneic bone marrow transplantation (BMT) lack a human leukocyte antigen genotypically identical sibling and require an alternative donor. This carries an increased risk of graft failure and acute graft-versus-host disease (GVHD). We sought to overcome these problems with transplants by using grafts obtained from the most readily available source: the haploidentical, partially mismatched, related donor. This study of 40 patients used a novel approach combining in vitro and in vivo T cell depletion with T lymphocyte targeted monoclonal antibodies (mAb) and intensified conditioning therapy, including fractionated total body irradiation before etoposide, cytoside arabinoside, cyclophosphamide, and methylprednisolone. Grafts were treated with T10B9.1A-31 mAb, directed against the alpha-beta heterodimer of the T cell receptor, and rabbit complement. In vivo depletion was attempted with an anti-CD5 mAb-Ricin A-chain (H65-RTA) immunotoxin (IT). Study patients were compared with a historical control group of 17 patients not given H65-RTA. Rates of engraftment were not significantly different (93% vs. 100%, P=0.12), although patients receiving IT engrafted more rapidly. The incidence of > grade I GVHD was significantly lower in the study group (36% vs. 100%, P=0.0001), as well as for severe grade III-IV GVHD (19% vs. 92%, P=0.0001). Five-year survival tended to be improved in the study group (40% vs. 18%, P=0.21). Transplant from haploidentical family members is indicated for patients without a matched sibling in whom allogeneic BMT offers the best opportunity to achieve cure.

Adolescent↗
PubMed1996

Effect of extent of resection on intestinal muscle adaptation.

The response of intestinal muscle to resection has received less attention than mucosal adaptation but may be important in relation to altered motility and improved intestinal absorption. Our aim was to determine the effect of extent of resection on intestinal muscle adaptation. Distal resections of 25% (n = 5), 50% (n = 5), and 75% (n = 5) of the intestine were performed. Transverse intestinal sections were taken at resection and 12 weeks later to evaluate changes in mucosa and circular and longitudinal muscle thickness. Muscle cell number and size and muscle length were also measured. Mucosal thickness increased (P < 0.05) after all resections, (1007 +/- 253 microns vs 1259 +/- 181 microns, 25%; 1019 +/- 191 microns vs 1366 +/- 293 microns, 50%; and 927 +/- 88 microns vs 1432 +/- 213 microns, 75%). Longitudinal muscle thickness (169 +/- 35 microns vs 254 +/- 45 microns, 50%; 207 +/- 71 microns vs 353 +/- 103 microns, 75%) and length (180 +/- 10 cm vs 203 +/- 16 cm, 50%; 90 +/- 16 cm vs 110 +/- 21 cm, 75%) increased (P < 0.05) following 50% and 75% resections but not after a 25% resection. Circular muscle length increased after 75% resection alone (4.4 +/- 0.2 cm vs 5.8 +/- 0.4 cm, P < 0.05). There was no significant change in circular muscle thickness after any resection. Muscle cell size and number per unit area were unchanged in all groups. We concluded that: (1) Intestinal muscle adapts after intestinal resection and this response is related to the extent of resection; in contrast, mucosal adaptation was evident following even the least extensive resection. (2) Increased thickness and length of the longitudinal muscle layer are the most prominent changes. (3) This increased muscle thickness results from hyperplasia rather than hypertrophy.

Adaptation, Physiological↗
PubMed1996

Smooth muscle contractility after intestinal resection.

Intestinal resection is followed by structural and functional adaptation of the remnant, including motor adaptation. Since changes also occur in intestinal smooth muscle, our aim was to determine whether changes in motor function are related to changes in smooth muscle contractility. Eighteen dogs underwent transection alone (GPI, n=6), 50% distal resection (GP II, n = 6) and 50% distal resection with jejunocolostomy (GP III, n = 6). Histologic measurements and length-tension studies with response to carbachol were made at 12 weeks. Longitudinal muscle (LM) length tended to increase in the resected animals but not significantly (174 +/- 23 and 180 +/- 23 vs 156 +/- 16 cm, GP II, GP III, and GP I, respectively). Circular muscle (CM) length was similar in all three groups (8.2 +/- 0.9 and 7.9 +/- 0.6 vs 7.5 +/- 0.6 cm). Both CM and LM tended to be thicker in the resected groups (CM: 660 +/- 163 and 733 +/- 139 vs 569 +/- 199 micron; LM: 213 +/- 77 and 246 +/- 76 vs 220 +/- 104 micron, GP II, GP III, and GP I, respectively, NS). Length-tension relationships for both CM and LM were similar in all three groups. The length (Lo) at which maximal active tension (To) was achieved was 130-140% initially in both LM and CM. Passive tension at Lo and the response to cholinergic stimulation were similar in all three groups. There were no significant differences in absolute active and total tension generated or force/cm2. The carbachol dose responses were similar with the maximal active tension occurring at 10(-4) M carbachol. The ED50 was greater in CM than in LM (P < 0.05 for transection animals). The ED50 was lower after resection and bypass (P < 0.05 GP III vs Gp I). There were no significant differences in in vitro smooth muscle length tension relationships or the response to cholinergic stimuli of jejunum 12 weeks after resection with or without bypass of the ICJ. Thus, any changes in motor adaptation during this period are related to earlier transient effects or other factors.

Adaptation, Physiological↗
PubMed1996

The role of prophylactic cholecystectomy in the short-bowel syndrome.

OBJECTIVES: To determine the factors associated with cholelithiasis and define the role of prophylactic cholecystectomy in the short-bowel syndrome. DESIGN: Retrospective clinical review of cohort of consecutive patients. SETTING: Tertiary care, academic medical center. PATIENTS: Fifty adult (age, > 16 years) patients with intestinal remnants less than 180 cm were evaluated over a 15-year period. MAIN OUTCOME MEASURES: Incidence and natural history of cholelithiasis, postoperative morbidity, and mortality rates. RESULTS: Prophylactic cholecystectomy was performed in 5 patients (10%). Ten patients (20%) died within 20 days without evidence of gallstones. Eleven (31%) of the other 35 patients at risk developed biliary disease; 6 of these patients had inflammatory complications or common bile duct stones. Biliary disease was more likely (P < .05) in patients with intestinal remnant length less than 120 cm (47% vs 13%), an absent ileocecal junction (41% vs 0%), long-term total parenteral nutrition (45% vs 13%), and Crohn's disease (67% vs 24%). Patients with mesenteric vascular disease had high initial mortality (50%) and a 38% incidence of biliary disease. Patients with cancer and/or irradiation had a lower initial mortality (7%) and no biliary disease. Patients with benign conditions had a significant incidence of cholelithiasis (57%). CONCLUSIONS: Patients with the short-bowel syndrome have a significant risk for cholelithiasis if the intestinal remnant length is less than 120 cm, total parenteral nutrition is required, and the terminal ileum is resected. Prophylactic cholecystectomy is indicated in patients with benign conditions and anticipated long-term survival. It should also be considered in patients with mesenteric vascular disease who, despite significantly shortened survival, may have a high incidence of early biliary problems.

Adolescent↗
PubMed1996

Differential effect of growth factors on intestinal wall components.

Both the mucosal and muscle layers respond to surgical manipulation of the small intestine. Various growth factors influence the mucosal response but less is known about changes in the muscle layers. Our aim was to evaluate the effect of epidermal growth factor (EGF) and octreotide (OCT) on changes in the intestinal wall induced by serosal patching. Twenty-four New Zealand white rabbits (3-4 kg) were studied. Group I (n=6) were unoperated controls. Group II (n=6) underwent creation of a 2 X 5-cm serosal patch in the ileum. Group III (n=6) and Group IV (n=6) received EGF (1.5 micrometer/kg/hr SQ) or OCT (1000 microgram/d SQ) after serosal patching. Wall composition, collagen content, and mucosal proliferation and enzyme activity of normal adjacent ileum were studied after 7 days. Serosal patching resulted in thickening of the mucosa and muscle layers (circular muscle: 189 +/- 54 vs 86 +/- 33 microns longitudinal muscle: 105 +/- 17 vs 55 +/- 12 microns P < 0.05) with increased proliferation and collagen content. EGF augmented the mucosal thickening (705 +/- 66 vs 573 +/- 94 microns, P < 0.05) and stimulated mucosal proliferation but inhibited the changes in muscle and collagen content. OCT inhibited the mucosal thickening and proliferation, but had less affect on the muscle. Disaccharidase activity was similar in all of the patched groups. We conclude the following. (1) Growth factors have differential effects on the intestinal wall components. (2) EGF stimulates the mucosa but has inhibitory effects on induced muscle changes. (3) Octreotide inhibits mucosal proliferation with less effect on muscle. (4) These observations have important implications for the therapeutic applications of these agents.

Animals↗
PubMed1996

Time course of adaptive regulatory peptide changes following massive small bowel resection in the dog.

Basal and postprandial concentrations of gastrointestinal hormones were measured in 12 dogs before and at one and three months after a 75% small bowel resection. Five animals were studied again at six months. Concentrations of enteric hormones and neuropeptides, measured in the proximal jejunum and distal ileum adjacent to the anastomotic site at the time of euthanasia, were compared with concentrations in control tissues taken from each animal at the time of resection. Increased basal and postprandial levels of gastrin (P < 0.05), cholecystokinin (CCK, P < 0.05), glucose-dependent insulinotropic peptide (GIP, P < 0.01), peptide YY (PYY, P < 0.001), and enteroglucagon (P < 0.001), were seen at one month after small bowel resection. In contrast, no significant changes were seen in concentrations of secretin, motilin, neurotensin, somatostatin, PP, or glucagon. Concentrations of enteroglucagon, GIP, and PYY remained high throughout the six-month study period. In contrast, gastrin and CCK had normalized by three months. Thus, only enteroglucagon, PYY, and GIP showed sustained elevations following enterectomy; the gastrin and CCK changes were transient. Following enterectomy, concentrations of vasoactive intestinal polypeptide (VIP) were reduced by about 50% in mucosal (P < 0.001) and muscle (P < 0.05) layers of proximal and distal gut. In contrast, calcitonin gene-related peptide (CGRP) was increased by about twofold in jejunal and ileal mucosa (P < 0.05), and CGRP elevations were even more marked in the muscle layers (P < 0.001). Somatostatin and neuropeptide Y (NPY) concentrations were similar to controls in all areas except for a small decrease in NPY in ileal mucosa (P < 0.05). These findings suggest that the increased motilin and PP concentrations previously reported after bowel resection in man are more likely to reflect underlying inflammatory bowel disease rather than enterectomy. The normalization of hypergastrinemia explains why the increased acid secretion after small bowel resection is transient. These results provide evidence for independent secretory control of enteroglucagon and PYY, which are both products of intestinal L cells. In addition, these studies reveal marked changes in enteric neuropeptide concentrations following bowel resection. VIP, which is thought to be a major inhibitory transmitter in the gut, is markedly reduced, while CGRP, which is mainly localized in sensory afferent fibers, is increased. These major neuropeptide changes are likely to be of importance in the adaptive responses to massive small bowel resection.

Adaptation, Physiological↗
PubMed1996

Smooth muscle adaptation after intestinal transection and resection.

Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.

Adaptation, Physiological↗
PubMed1996

Neutral endopeptidase inhibitors and the pulmonary circulation.

1. Neutral endopeptidase (NEP) EC 3.4.24.11 is a zinc-metallopeptidase which is partly responsible for the degradation of atrial natriuretic peptide (ANP) in vivo. 2. ANP inhibits vascular smooth muscle cell proliferation, and elicits vasorelaxation of the systemic and, more potently, the pulmonary vasculature. Plasma ANP levels are elevated in human disease states characterized by pulmonary hypertension, and in animal models of these diseases. 3. However, the short in vivo half-life of ANP suggests that it has limited therapeutic potential. Therefore, it has been hypothesized that inhibition of the metabolism of ANP may prove successful in the treatment of pulmonary hypertension. 4. Several inhibitors of NEP have been shown to reduce the development of pulmonary hypertension secondary to chronic hypoxia in rats. In addition, the inhibitor SCH 42495, partially reversed the established cardio-pulmonary remodelling associated with this disease model, without elevating plasma ANP levels. 5. The physiological actions of ANP are many of the properties desirable in a treatment for pulmonary hypertension. Thus, attenuating the metabolism of this peptide using NEP inhibitors, should potentially enhance the effects of ANP, either by maintaining plasma levels or at a local, tissue level.

Animals↗
PubMed1996

Laparoscopic gastrostomy and jejunostomy are safe and effective for obtaining enteral access.

BACKGROUND: Laparoscopic gastrostomy (lap g-tube) and jejunostomy (lap j-tube) are relatively new procedures that do not require laparotomy. Our aim was to determine the role of laparoscopic feeding tube placement for enteral access and the safety of these techniques. METHODS: We reviewed our experience with attempted laparoscopic placement of 93 enteral tubes in 81 patients over a 3-year period. Patients received either a lap g-tube (n = 64), lap j-tube (n = 5), or both lap g/j-tube (n = 12). When enteral access was needed for nutritional support, the choice of lap g-tube or lap j-tube was based on risk of gastroesophageal reflux. RESULTS: The most common underlying conditions requiring tube placement were head and neck cancer (49%), neurologic disorders (19%), and trauma (11%). Mean operative times (minutes) were as follows (mean +/- SD): lap g-tube (39 +/- 7), lap j-tube (63 +/- 10), and lap g/j-tube (85 +/- 13). Lap g-tube placement was successful in 73 (96%) of 76 patients and lap j-tube in all 17 patients. The major complication rate for all tubes was 8% (7 of 93) and included gastrointestinal bleeding, wound infection, and failed placement. Five patients died in the 30-day period following surgery, but none of the deaths was procedure related. CONCLUSIONS: Laparoscopic tube placement should be considered for patients in whom endoscopy is not feasible or undesirable or who are undergoing other operative procedures. Lap g-tube and lap j-tube are safe procedures that avoid the potential risk of a laparotomy, and they can be done with a high success rate. This is a valuable approach for patients with head and neck cancer or neurologic disorders and for trauma patients with multiple disease processes.

Female↗
PubMed1996

Use of antioxidant supplements in the treatment of human oral leukoplakia.

An increasing public awareness of antioxidants may prompt a patient's request to be treated without surgery if a leukoplakic lesion is discovered. However, surgical excision remains the treatment of choice for oral leukoplakia. The use of antioxidant supplements has shown some promise, but the predictability of success remains uncertain and long-term results are unavailable. Before the decision to use any antioxidant is made, it is critical to obtain a histopathologic diagnosis of the lesion. When dealing with a lesion diagnosed as hyperkeratosis, it may be appropriate to choose an antioxidant that may take some time for clinical improvement to occur. However, as the grade of epithelial dysplasia becomes more severe, consideration must be given to the possibility of malignant transformation during antioxidant treatment. We do not recommend the use of antioxidant supplements in the treatment of any carcinoma. The therapeutic use of antioxidant supplements outside of clinical trials conducted at academic medical centers should be done with considerable caution by practitioners in private practice. It should be emphasized that in these clinical trial patients were seen at frequent intervals to monitor their progress and to intervene if there was a noticeable deterioration in the clinical appearance of the lesion. In spite of the uncertainty with respect to antioxidant treatment, there are circumstances in which it should be considered. Recurrence after surgical excision when there is little reason to believe that a second surgical excision would be any more successful is an ideal candidate. Also, patients with widespread leukoplakia that involves a large area of the oral mucosa might be suitable for treatment with antioxidants, as well as patients who have extensive medical problems that make them surgical risks. The choice of which antioxidant(s) to use is complex because thus far there is no combination that is superior to the others. Beta-carotene with ascorbic acid or alpha-tocopherol is attractive because of a lack of side effects, but the range in reported values for lesion improvement has been broad and the clinical improvement typically takes several months. Clinical response with 13-cRA is faster but requires baseline and periodic serologic testing, as well as close monitoring for side effects. In those circumstances in which time is an important consideration, 13-cRA might be useful because clinical improvement can be evaluated within a matter of weeks as compared with beta-carotene. The group from M.D. Anderson Hospital has shown the value of an induction dose of 13-cRA that is followed by a lower maintenance dose. Unfortunately, the problem of recurrence after discontinuation of 13-cRA is quite common. One aspect that has not been evaluated is the combination of conventional surgical excision and the administration of postoperative antioxidants. This would have the obvious advantage of conventional treatment of surgery together with the possible protective effect of the antioxidants. Although this is an attractive hypothesis, we do not know of any studies that have proven this to be beneficial.

Animals↗
PubMed1996

Inhibition of endogenous nitric oxide synthase potentiates nitrovasodilators in experimental pulmonary hypertension.

BACKGROUND: The role of endogenous nitric oxide (NO) in the regulation of pulmonary vascular tone is complex. Inhibition of endogenous NO synthase, potentially through upregulation of guanylyl cyclase, results in an increase in potency of nitrovasodilators in the systemic circulation. This study considered whether inhibition of endogenous NO synthase would increase the potency of nitrovasodilators, but not of cyclic adenosine monophosphate-dependent vasodilators, in the pulmonary vasculature. METHODS: We used the isolated buffer-perfused rabbit lung. Preparations were randomized to receive either pretreatment with NG-nitro-L-arginine methyl ester (or L-NAME, an inhibitor of endogenous NO synthase) or no pretreatment. Stable pulmonary hypertension was then produced by infusing the thromboxane A2 analog U46619. The dose-response characteristics of two nitrovasodilators, sodium nitroprusside and nitroglycerin, and two nonnitrovasodilators, prostaglandin E2 and 5'-N-ethylcarboxamidoadenosine, were studied. RESULTS: Inhibition of endogenous NO synthase caused no significant changes in baseline pulmonary artery pressure but did significantly reduce the U46619 infusion rate required to produce pulmonary hypertension. Pretreatment with L-NAME (vs. no L-NAME) resulted in significantly lower values of the log median effective dose with sodium nitroprusside and nitroglycerin. In contrast, pretreatment with L-NAME resulted in no changes in the dose-response characteristics of the cyclic adenosine monophosphate-mediated, NO-independent vasodilators prostaglandin E1 and 5'-N-ethylcarboxamidoadenosine. CONCLUSIONS: These data suggest that endogenous NO synthase is not an important regulator of basal pulmonary tone in this model but is an important modulator of pulmonary vascular responses to vasoconstriction and to nitrovasodilators. The pulmonary vasodilator effects of nitrovasodilators, but not of nonnitrovasodilators, may depend on the level of activity of NO synthase.

Adenosine↗
PubMed1996

Laparoscopic gastrostomy versus open gastrostomy in head and neck cancer patients.

Alimentation in the surgically treated head and neck cancer patient frequently requires bypassing the upper aerodigestive tract. The laparoscopic gastrostomy fulfills this criterion. The authors compared 25 laparoscopic gastrostomies (group 1) with 18 open gastrostomies (group 2) performed on head and neck cancer patients. The length of operation, morbidity, mortality, and cost were evaluated. Operative time was significantly shorter in group 1 (40 +/- 2 minutes) than in group 2 (56 +/- 4 minutes), with P=.003. The major complication rate was 9% for group 1 and 11% for group 2. There was no procedure-related mortality in group 1, but 1 patient died in the immediate postoperative period in group 2. The cost was not significantly different. It is concluded that the laparoscopic gastrostomy is a safe and cost-effective alternative to open gastrostomy in this patient group.

Anesthesia, General↗
PubMed1996

A comparison of pathophysiological changes during hypobaric and normobaric hypoxia in rats.

Littermate male Wistar specific pathogen-free rats were divided into three groups at 28 days of age. The pathophysiological effects seen in rats exposed to normobaric hypoxia (NB) at 10% O2 were compared with those seen in animals exposed to hypobaric hypoxia (HB) at 500 mbar, equivalent to an inspired O2 concentration of 10%, and controls after periods of 5, 10 and 14 days. 5 days' exposure to a low oxygen environment resulted in less weight gain, the development of right ventricular hypertrophy and double elastic laminae in the pulmonary arterioles and an increase in haematocrit and plasma levels of atrial natriuretic peptide (ANP) in both the HB and NB animals compared to controls. There was no significant difference in these values between the two hypoxic groups. After 10 days' exposure to a low oxygen environment, body weight, ventricular ratio, plasma ANP levels and double elastic laminae were higher than the levels seen after 5 days in both NB and HB groups of rats. At day 14 only body weight and haematocrit were greater when compared to day 10 values in NB and HB groups. In conclusion the stress of this hypobaric environment caused no additional changes in the pathophysiological variables studied, compared with the changes seen in NB.

Animals↗