[The European Federation of Internal Medicine in Edinburgh 9-12 May, 2001].
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Humans↗
Biomedical subjects
H Bitterman
Publications and source records attributed to H Bitterman.
Severe orthostatic hypotension following weight reduction surgery.
Surgical interventions for morbid obesity are common practice in many countries, especially when other treatment options have failed or when rapid weight loss is desired. The association between weight and blood pressure is well established, especially the paradigm of obesity-related hypertension. We describe a 45-year-old obese woman with a medical history of hypertension and type 2 diabetes mellitus who lost 57 kg within a few months after a weight reduction surgery. She suffered from severe orthostatic hypotension, which probably resulted from sympathetic nervous system dysfunction. Our patient's clinical status improved with pharmacological interventions, but her symptoms resolved completely after she gained weight following a surgical reversal of the gastric partitioning owing to a local complication. Autonomic nervous system activity does change with the changes in body weight, but after evaluation of this patient, we believe that rapid weight loss may impair sympathetic function and blood pressure control. Although losing weight is a known treatment option for hypertension, exaggerated reversal of obesity-related hypertension might result in orthostatic hypotension.
Combined Modality Therapy↗
Influence of hypertonic saline on bacterial translocation in controlled hemorrhagic shock.
Translocation of enteric bacteria has been described in rats following hemorrhagic shock (HS). The aim of the present study was to evaluate the effect of hypertonic saline (HTS) on bacterial translocation (BT) in the setting of controlled HS in rats. The study included 2 arms. Arm I was a qualitative assessment of translocation. Sixty-eight anesthetized animals were studied. The rats were divided into 5 groups. Group I (n = 10) was sham shock controls. In groups II-V, HS was induced by arterial bleeding to mean arterial pressure (MAP) of 35-45 mmHg, which was maintained for 30 min. The animals were then allocated into 4 groups: group II (n = 19) untreated HS; group III (n = 13) normal saline (NS) treated; group IV (n = 13) HTS-treated; and group V (n = 13) HTS and blood treated. Mesenteric lymph nodes, liver, spleen, portal, and systemic blood were sent for culture after 24 h. Translocation occurred if enteric bacteria were cultured from at least one site. Arm II was a quantitative assessment of translocation. Two groups were studied: untreated HS (n = 7) and HTS treated (n = 6). In the qualitative arm, the 24-h mortality in untreated rats (group II) was 31.5% compared to 5.1% in treated animals (groups II-V) (P = 0.01). No BT was detected in control animals (group I). BT after HS was not different between groups II, III, and IV (92.3%, 91.6%, and 100%, respectively). Group V showed fewer translocations than groups II-IV, a difference that was especially significant compared with group IV (P = 0.039). However, BT to distant sites (systemic blood and spleen) was significantly lower in group V than in groups II-IV (P < 0.05). In the quantitative arm, the mortality rate was 16.7% in the untreated group. Although no qualitative significant difference in the translocation rate was found between the two groups (67% in untreated animals vs. 50% in HTS treated), there was significant quantitative difference: in HTS-treated group a significantly lesser bacteria translocated than in untreated animals (0.4 x 10(5) cfu/g vs. 4.2 x 10(5) cfu/g, respectively [P = 0.001]). We concluded that whereas assessed qualitatively, in this model of severe HS in rats, the hemorrhagic insult itself resulted in BT in most animals and treatment with NS, HTS, and blood resulted in reduced early mortality but did not alter significantly the translocation rate. Only the combination of HTS and blood resulted in reduced BT to distant sites. However, quantitative assessment showed that HTS significantly reduced the number of translocating bacteria.
Animals↗
Divergent effects of ischemia/reperfusion and nitric oxide donor on TNFalpha mRNA accumulation in rat organs.
We previously showed that serum TNFalpha bioactivity in rats is proportional to the extent of graded tissue injury caused by laparotomy, intestinal ischemia, and reperfusion and that the spleen is an important source of TNFalpha secretion in this condition. TNFalpha production varies, depending on the type and duration of tissue injury. It is also affected by other mediators, such as nitric oxide (NO). TNFalpha is known to increase NO production, but the effect of NO on the production of TNFalpha has not yet been fully elucidated. In this study we determined the levels of TNFalpha mRNA in rat organs after graded injury caused by anesthesia, laparotomy, intestinal ischemia, and reperfusion and evaluated the effects of the NO donor S-nitroso-N-acetylpenicillamine (SNAP) on it. Samples from different organs were removed, and TNFalpha gene expression was evaluated by semiquantitative RT-PCR. TNFalpha mRNA was not detected in the intestine (the ischemic organ) and in the kidney, brain, heart, or liver after all 4 experimental protocols. In the mesenteric lymph node (draining the ischemic organ) a basal level of expression of TNFalpha mRNA was detected in the control (anesthesia alone) group, which was increased significantly after ischemia. In the spleen (a remote immune organ not directly involved in the ischemia), a significant gradual increase in TNFalpha mRNA, which correlated to the severity of the experimental protocol, was observed. In the lung (a central participant in post-injury multiple organ failure), all interventions increased TNFalpha mRNA. Infusion of SNAP exerted a differential effect on TNFalpha mRNA: diminished its accumulation in the lymph node, enhanced it in the lung, and had no effect in the spleen. The divergent organ pattern of TNFalpha transcription emphasizes the importance of its localized expression, which is critical to the understanding of its autocrine and paracrine actions in ischemia and reperfusion.
Anesthesia, General↗
Abdominal surgery reduces the ability of rat spleen cells to synthesize and secrete active tumour necrosis factor-alpha (TNF-alpha) by a multilevel regulation.
We have previously shown that abdominal surgery (explorative laparotomy) reduces the ability of lipopolysaccharide (LPS)-triggered spleen macrophages to secrete TNF-alpha. In this study we characterize possible mechanisms which could be responsible for the reduction in splenic production of TNF-alpha. Post-operative and control (unoperated) rat splenocytes or enriched splenic macrophages were cultured with LPS. Steady-state levels of TNF-alpha mRNA were determined by Northern and slot blot analyses, and validated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The amount of TNF-alpha protein was measured by Western blot analysis, and its biological activity was determined by the fibroblast L-929 cytotoxicity assay. Surgery induced a 12-fold inhibition in TNF-alpha activity (P < 0.02), caused up to two-fold reduction in the accumulation of TNF-alpha mRNA (P < 0.01), and suppressed TNF-alpha protein maturation into its 17-kD form in cellular extracts. Post-surgical spleen supernatants revealed mainly a band of a lower molecular weight (14 kD). Our data suggest a multilevel regulation of post-operative inhibition of TNF-alpha response to LPS, at the accumulation of mRNA, translational and secretory levels. We also suggest that the reduced bioactivity could be partially caused by a proteolytic cleavage of TNF-alpha. Since TNF-alpha is an important participant in immune responses, its reduced production and activity may be a central mechanism of post-operative immunosuppression.
Animals↗
Effects of exposure to low concentrations of carbon monoxide on exercise performance and myocardial perfusion in young healthy men.
OBJECTIVE: To assess the effects of exposure to low concentrations of carbon monoxide (CO), as commonly measured in atmospheric urban air pollution and certain occupational environments, on exercise performance and myocardial perfusion in young healthy men, and the possible need for tighter restrictions on ambient concentrations of CO. METHODS: 15 young, healthy non-smoking men, 18-35 years old, were exposed blindly and randomly to air or to a mixture of CO and air, followed by an exercise treadmill test with thallium heart scintigraphy. Blood was drawn for determination of carboxyhaemoglobin before and at the end of the exposure, and for lactic and pyruvic acid at the beginning and the end of the exercise test. The main outcome measures include the duration of the exercise test, the maximal effort expressed in metabolic equivalent units (METs), the mean plasma lactic to pyruvic acid ratio at the end of the ergometry, ECG changes in the exercise test, and perfusion deficits in thallium heart scintigraphy. RESULTS: At the end of exposure to CO, the mean (SD) blood carboxyhaemoglobin concentration rose from 0.59% (0.08%) to 5.12% (0.65%) (p < 0.0001). At the end of the exercise period, the mean (SD) plasma lactate/pyruvate ratio, which reflects the level of anaerobic metabolism (69.9 (5.9) after air and 75.9 (7.0) after CO), was not significantly different between the two experimental groups. Exercise induced electrocardiographic changes were noted in only one subject after exposure to CO. No arrhythmias were detected in any of the subjects. Significant differences were found in the mean duration of the exercise test (p = 0.0012) and the METs (p = 0.0001). The mean adjusted difference of exercise duration between exposure to air and CO was 1.52 minutes 95% confidence interval (95% CI) 0.73 to 2.32 minutes. The mean adjusted difference of METs between exposure to air and CO was 2.04 95% CI 1.33 to 2.76. The models for duration of exercise and METs showed no significant sequence and period effects. Thallium myocardial perfusion imaging disclosed normal perfusion in all regions of the heart, with no significant differences in perfusion between the two exercise tests (after air or CO). CONCLUSION: Acute exposure to a low concentration of CO which produces blood carboxyhaemoglobin concentrations of 4%-6% significantly decreases exercise performance in young healthy men. No ischaemic electrocardiographic changes or disturbances in myocardial perfusion were found by graded exercise with thallium scintigraphy. Our findings suggest that pollution of atmospheric air by CO at concentrations which are commonly found in urban and industrial environments may exert an adverse effect on skeletal muscles, manifesting as decreased exercise performance.
Adolescent↗
L-arginine-NO pathway and CNS oxygen toxicity.
The involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.
Animals↗
Effects of severe hemorrhage on plasma ANP and glomerular ANP receptors.
Atrial natriuretic peptide (ANP) plays an important role in blood volume and electrolyte homeostasis in normovolemia and in hypervolemic states. The currently available information on the effects of hypovolemia on plasma ANP is contradictory. Moreover, possible regulation of ANP receptors during severe hemorrhagic hypovolemia has not been investigated. This study evaluated the effects of severe hemorrhage on plasma ANP and on the regulation of glomerular ANP receptor subtypes in anesthetized rats. Constant rate bleeding of 50% of total blood volume within 2 h induced a reproducible shock state characterized by marked decreases in blood pressure, heart rate, and hematocrit and an increase in plasma renin activity and aldosterone. Hemorrhaged rats exhibited a gradual significant increase in plasma ANP from 39.3 +/- 2.9 to 114.7 +/- 20.0 pmol/l 1 h after the bleeding (P < 0.001 from the initial value and P < 0.02 from the final value of sham-shock rats). Hemorrhage induced a significant decrease in total glomerular ANP binding sites (172 +/- 25 vs. 363 +/- 39 fmol/mg protein in hemorrhaged and sham-shock rats, respectively, P < 0.05). This decrease was mainly due to a significant decrease in ANPC receptors (132 +/- 22 vs. 312 +/- 40 fmol/mg protein in hemorrhaged and sham-shock rats, respectively, P < 0.05). Hemorrhage did not change glomerular ANPA receptor density. No significant differences in the affinity of the glomerular receptor subtypes for ANP were detected. Our data indicate that plasma ANP increases after prolonged severe hemorrhage. It is suggested that downregulation of renal ANPC receptors leads to reduced clearance of ANP and contributes to elevation of its plasma level after severe hemorrhage.
Animals↗
The effect of nitric oxide synthase inhibition on hypertonic saline treatment of controlled hemorrhagic shock.
The effect of the nitric oxide (NO) donor, L-arginine, and the NO synthase inhibitor, L-NAME on hypertonic saline (HTS) infusion in controlled hemorrhagic shock was studied in anesthetized rats. Hemorrhagic shock was induced by arterial bleeding of 35% of the total blood volume in 90 min. After 110 min, the animals were divided into two groups: in Group A, 5 mL/kg NaCl 7.5% (HTS) was infused. In Group B HTS was not infused. After 135 min the animals in both groups were divided into 4 subgroups: Group 1 (n = 8) was untreated, Group 2 (n = 8) was treated after 135 min with 100 mg/kg L-arginine, in Group 3 (n = 8) 100 mg D-arginine was infused, and in Group 4 (n = 8) 50 mg/kg L-NAME was infused. Arterial bleeding in Group A1 resulted in a fall in mean arterial pressure (MAP) to 43.5 +/- 5 mmHg (p < .001)) in 90 min. A similar fall in MAP was observed in all groups. HTS infusion in Group A1 was followed by an increase in MAP to 82.3 +/- 6 (p < .01)) after 125 min followed by a gradual decrease to 61.5 +/- 8 mmHg (p < .01)) after 4 h. Infusion of L-NAME in Group A4 resulted in an increase in MAP to 87.4 +/- 5 mmHg (p < .01)) that then rapidly dropped to 61.7 +/- 11 (p < .01)) after 4 h. Infusion of L-NAME in Group B4 resulted in an increase in MAP to 96.7 +/- 9 mmHg (p < .001)) which was maintained after 4 h at 92.2 mmHg, and was significantly higher than MAP in Group A4 (p < .01). We concluded that HTS infusion leads to a significant increase in MAP in controlled hemorrhagic shock. NO synthase inhibition by L-NAME in hemorrhagic shock leads to a protracted, significant increase in MAP. Infusion of HTS prevented the significant and sustained rise in MAP induced by L-NAME.
Animals↗
[Cholesterol emboli].
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Diagnosis, Differential↗
Effects of oxygen on regional hemodynamics in hemorrhagic shock.
This study investigated mechanisms of the hemodynamic effects of oxygen in hemorrhagic shock induced by bleeding 30% of the total blood volume in anesthetized rats. An ultrasonic flowmeter was used to monitor regional blood flow. Changes in tissue perfusion were assessed by the laser-Doppler technique. The inhalation of 100% oxygen induced a significant increase in mean arterial blood pressure (MABP) and vascular resistance in the hindquarters, with a concomitant decrease in blood flow in the distal aorta and biceps femoris muscle. In contrast, oxygen did not change vascular resistance in the superior mesenteric artery (SMA) and renal beds and induced a significant increase in blood flow to the renal artery, SMA, and small bowel in hemorrhaged rats. L-Arginine (100 mg/kg iv) but not D-arginine or the vehicle (0.9% NaCl) completely abolished the effects of oxygen on blood pressure and reversed its effects on blood flow and resistance in the hindquarters and biceps femoris muscle. Administration of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (50 mg/kg iv) significantly increased MABP and the resistance in the three vascular beds. Pretreatment of hemorrhaged rats with a superoxide dismutase mimic, the NO-stable radical 2,2,6,6-tetramethylpiperidine-N-oxyl (5 mg/kg iv), resulted in significantly diminished effects of oxygen on hindquarter hemodynamics. These results demonstrate a differential effect of oxygen, which increases vascular resistance in the hindquarters without a significant effect in the splanchnic and renal beds, thus favoring an increase in splanchnic and renal perfusion. It is suggested that inactivation of NO by reactive oxygen species may underlie the effects of oxygen on hindquarter vascular tone during shock.
Animals↗
Exposure to hyperbaric oxygen induces tumour necrosis factor-alpha (TNF-alpha) secretion from rat macrophages.
We investigated the secretion of TNF-alpha by monocytes and macrophages derived from the peripheral blood, spleen, and lungs after a single exposure to a therapeutic profile of hyperbaric oxygen (HBO). Rats were exposed for 90 min to either 100% oxygen at 0.28 MPa (2.8 atmospheres absolute) or air. Immediately after exposure, mononuclear cells were isolated from blood, spleen, and lungs and cultured for 18 h. The secretion of TNF-alpha from the cultured monocytes/macrophages was determined with and without stimulation with lipopolysaccharide (LPS). Exposure to hyperbaric oxygen induced a significant increase in the spontaneous ex vivo secretion of TNF-alpha (without LPS) by mononuclear cells from the blood, spleen, and lung (P < 0.05 from air controls). Stimulation with LPS after exposure to HBO induced a significant increase in TNF-alpha secretion by lung and spleen macrophages compared with air controls (P < 0.05). However, absolute TNF-alpha levels were not significantly higher than those achieved 'spontaneously' in macrophages exposed to HBO without LPS. Stimulation with LPS induced a marked increase in secretion of TNF-alpha from blood monocytes after exposure to air, but not after exposure to HBO. These results provide evidence in support of a role played by TNF-alpha in mediating HBO effects on different tissues and their immune responses.
Animals↗
Salutary consequences of oxygen therapy on the long-term outcome of hemorrhagic shock in awake, unrestrained rats.
Decreased oxygen delivery and cellular hypoxia are major factors in the pathophysiology of shock. We studied the effects of 100% O2 at 0.1 and 0.3 MPa (1 and 3 atm abs) in severe hemorrhagic shock in awake, unrestrained rats. Shock was induced by withdrawing 50% of the total blood volume within 120 min. Blood pressure, heart rate, and the electroencephalogram (EEG) were recorded during the first 6 h of the protocol. The animals were observed for 7 days. The shock protocol resulted in 60 and 90% mortality after 1 day and at the end of 7 days, respectively. A single 90-min exposure to O2 at 0.1 and 0.3 MPa, which was started 30 min after bleeding, maintained mean arterial blood pressure at significantly higher values compared to untreated controls throughout the exposure period (P < 0.05). Oxygen therapy at both doses also improved the long-term survival rate and survival time significantly (P < 0.01). No clinical or EEG sign of CNS O2 toxicity was detected in O2-treated animals. Our results indicate that O2 given alone after severe bleeding exerts a beneficial effect on the long-term outcome of hemorrhagic shock in awake, unrestrained rats.
Animals↗
Scintigraphic evaluation of a patient with lung cavitations. Ga-67 scintigraphy is nondiagnostic.
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Adult↗
Effect of hyperbaric oxygen on tissue distribution of mononuclear cell subsets in the rat.
In a previous study we found a significant temporary decrease in the ratio of CD4/CD8 (helper, inducer/suppressor, cytotoxic) T lymphocytes in the peripheral blood of healthy human volunteers after exposure to a single commonly used profile of hyperbaric oxygen (HBO). The transient nature of the changes suggested redistribution of T-cell subsets. The purpose of the present study was to verify such a redistribution and to locate possible target organs in an animal model. A single exposure of rats to HBO (0.28 MPa) induced a highly significant rapid decrease in the CD4/CD8 ratio in peripheral blood count (P < 0.0001), confirming our previous findings in humans. HBO also induced a significant increase in the CD4/CD8 ratio in the lungs and lymph nodes (P < 0.001) and a significant decrease in the ratio in the spleen (P < 0.01). Furthermore, exposure to HBO induced a significant increase in T cells bearing surface interleukin-2 receptors in the blood, spleen, lungs, and lymph glands (P < 0.001) and a significant decrease in T cells expressing alpha beta-receptors in the lungs (P < 0.001) and lymph glands (P < 0.05). Our findings suggest rapid T-cell activation after a brief exposure to HBO, with shifts of CD4 and CD8 subsets and variations in T-cell receptor type. These rapid changes in the parameters of cell-mediated immunity may represent the activation of protective mechanisms against the toxic effect of oxygen or the early stages of pulmonary oxygen toxicity.
Animals↗
Scintigraphic evaluation of a patient with hemangiosarcoma. Labeled red blood cell imaging is nondiagnostic.
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Diagnosis, Differential↗
Effect of a single exposure to hyperbaric oxygen on blood mononuclear cells in human subjects.
We studied the effect of a single exposure to a therapeutic profile of hyperbaric oxygen on blood mononuclear cell subset. Twenty healthy volunteers were exposed to 0.28 MPa for 90 min. Thirteen breathed pure oxygen and seven were control subjects exposed to compressed air at the same pressure. Venous blood samples were drawn before HBO exposure, immediately on exit from the chamber, and 24 h later. Immediately after the exposure, a significant increase was observed in the percentage and absolute number of CD8 (suppressor/cytotoxic) T cells, with a concomitant decrease in the CD4 (helper/inducer) T cells. These changes resulted in a decreased CD4:CD8 ratio. A rise was also observed in the number of HLA-DR antigen-bearing cells, with a transient increase in monocytes. There was no change in the total count and percentage of T cells (CD3), B cells, and NK cells. Twenty-four hours after HBO exposure there was a partial reversal of the decrease in the mean CD4:CD8 ratio, but it was still significantly lower than preexposure values. The fast reversibility of the change in the CD4:CD8 ratio suggests specific HBO-induced shifts and sequestration of T-cell subpopulations.
Adult↗
Delayed hyperbaric treatment of cerebral air embolism.
Urgent exposure to hyperbaric oxygen (HBO) is currently accepted as an effective therapy for cerebral air embolism. The diagnosis of air embolism in the critically ill post-surgical patient is frequently difficult and therefore the initiation of specific therapy is often delayed. Only limited information is currently available on the effects of delayed HBO treatment in these patients. We recently used HBO to treat five patients with cerebral air embolism resulting from invasive medical procedures; hyperbaric treatment was begun 15-60 h after the embolic event. The causes of air embolism were: cardiopulmonary bypass accidents, pulmonary barotrauma induced by mechanical ventilation, and central vein catheterization. All patients received initial treatment according to U.S. Navy Compression Table 6A in a multiplace chamber, followed by subsequent treatments with 100% O2 at 2.5 to 2.8 ATA for 90 min as indicated. Significant, partial or complete recovery was observed in three patients, one patient did not respond, and one died. The salutary effects of HBO in our subgroup of patients suggest that this treatment should be used in cerebral air embolism even when referral to a hyperbaric facility is delayed.
Adult↗