Urinary leukotriene E(4) levels are not increased prior to high-altitude pulmonary edema.

STUDY OBJECTIVE: To examine whether increased urinary cysteinyl-leukotriene E(4) (LTE(4)) excretion, which has been found to be elevated in patients presenting with high-altitude pulmonary edema (HAPE), precedes edema formation. DESIGN: Prospective studies in a total of 12 subjects with susceptibility to HAPE. SETTING: In a chamber study, seven subjects susceptible to HAPE and five nonsusceptible control subjects were exposed for 24 h to an altitude of 450 m (control day), and exposed for 20 h to 4,000 m after slow decompression over 4 h. In a field study, prospective measurements at low and high altitude were performed in five subjects developing HAPE at 4,559 m. PARTICIPANTS: Mountaineers with a radiographically documented history of HAPE and control subjects who did not develop HAPE with identical high-altitude exposure. INTERVENTIONS: 24-h urine collections. MEASUREMENTS AND RESULTS: In the hypobaric chamber, none of the subjects developed HAPE. The 24-h urinary LTE(4) did not differ between HAPE susceptible and control subjects, nor between hypoxia and normoxic control day. In the field study, urinary LTE(4) was not increased in subjects with HAPE compared to values obtained prior to HAPE at high altitude and during 2 control days at low altitude. CONCLUSIONS: These data do not provide evidence that cysteinyl-leukotriene-mediated inflammatory response is associated with HAPE susceptibility or the development of HAPE within the context of our studies.

Dibutyryl cAMP effects on thromboxane and leukotriene production in decompression-induced lung injury.

Decompression-induced venous bubble formation has been linked to increased neutrophil counts, endothelial cell injury, release of vasoactive eicosanoids, and increased vascular membrane permeability. These actions may account for inflammatory responses and edema formation. Increasing the intracellular cAMP has been shown to decrease eicosanoid production and edema formation in various models of lung injury. Reduction of decompression-induced inflammatory responses was evaluated in decompressed rats pretreated with saline (controls) or dibutyryl cAMP (DBcAMP, an analog of cAMP). After pretreatment, rats were exposed to either 616 kPa for 120 min or 683 kPa for 60 min. The observed increases in extravascular lung water ratios (pulmonary edema), bronchoalveolar lavage, and pleural protein in the saline control group (683 kPa) were not evident with DBcAMP treatment. DBcAMP pretreatment effects were also seen with the white blood cell counts and the percent of neutrophils in the bronchoalveolar lavage. Urinary levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were significantly increased with the 683 kPa saline control decompression exposure. DBcAMP reduced the decompression-induced leukotriene E4 production in the urine. Plasma levels of thromboxane B2, 11-dehydrothromboxane B2, and leukotriene E4 were increased with the 683-kPa exposure groups. DBcAMP treatment did not affect these changes. The 11-dehydrothromboxane B2 and leukotriene E4 levels in the bronchoalveolar lavage were increased with the 683 kPa exposure and were reduced with the DBcAMP treatment. Our results indicate that DBcAMP has the capability to reduce eicosanoid production and limit membrane permeability and subsequent edema formation in rats experiencing decompression sickness.

Urinary leukotriene E4 levels in high-altitude pulmonary edema. A possible role for inflammation.

STUDY OBJECTIVES: Inflammation may contribute to the pathogenesis of high-altitude pulmonary edema (HAPE). This study was designed to determine whether a marker of inflammation, urinary leukotriene E4 (LTE4), is elevated in patients with HAPE. DESIGN: We conducted a case-control study to collect clinical data and urine samples from HAPE patients and healthy control subjects at moderate altitude (> or = 2727 m), and follow-up urine samples from HAPE patients following their return to low altitude (< or = 1,600 m). SETTING: Five medical clinics in Summit County, Colorado. PATIENTS: Questionnaire data were evaluated in 71 HAPE patients and 36 control subjects. Urinary LTE4 levels were determined from a random subset of 38 HAPE patients and 10 control subjects presenting at moderate altitude, and on 5 HAPE patients who had returned to low altitude. MEASUREMENTS AND RESULTS: Using an enzyme immunoassay technique, urinary LTE4 levels were found to be significantly higher in HAPE patients (123 [16 to 468] pg/mg creatinine, geometric mean [range]) than in control subjects (69 [38 to 135]), p = 0.02. Following return to low altitude, urinary LTE4 levels fell significantly from 122 (41.8 to 309) to 53.6 (27.6 to 104) pg/mg creatinine (p = 0.05). Urinary LTE4 levels were not related to age, sex, time at altitude, physical condition or habitual exercise, recent use of alcohol or nonsteroidal anti-inflammatory drugs (NSAIDs), or oxygen saturation. Clinical factors associated with HAPE included male sex, regular exercise, and recent use of NSAIDs. CONCLUSIONS: We conclude that urinary LTE4 levels are elevated in patients with HAPE, supporting the view that HAPE involves inflammatory mechanisms.

Urinary excretion of polyamines in the adult respiratory distress syndrome.

Polyamines are low molecular weight polycations that are critically important in cellular proliferation and differentiation. To investigate their potential role in acute lung injury, the polyamines spermidine, spermine, and putrescine were measured in 24-h urine collections from intubated patients with ARDS (n = 12) or congestive heart failure with cardiogenic pulmonary edema (CHF, n = 10) and in normal subjects (n = 10). Mean concentrations of putrescine were similar between groups, but spermidine concentrations in patients with ARDS (52.7 +/- 19.7 nmol/mg creatinine) were significantly higher than in normal subjects (4.9 +/- 0.7 nmol/mg), p < .05. Mean concentrations of spermine in ARDS (270.6 +/- 78.1 nmol/mg) were higher than in CHF (1.0 +/- 0.5 nmol/mg), p < .05, and normal subjects (0.3 +/- 0.1 nmol/mg), p < .05. Concentrations of putrescine increased significantly during the first 7 days of ARDS (241.5 +/- 127.1% above baseline, n = 6), p < .05. Urinary polyamine excretion did not correlate with severity of gas exchange or death. These results are the first to suggest a potential role for polyamines in the pathophysiology of ARDS.

Intravenous torsemide as adjunctive therapy in patients with acute pulmonary edema.

The safety and efficacy of intravenous (i.v.) torsemide as adjunctive therapy for acute cardiogenic pulmonary edema was evaluated. Thirteen patients were treated with i.v. torsemide and six patients, with i.v. furosemide, as a positive control. Doses of torsemide, 20 mg or 40 mg, and furosemide, 40 mg or 80 mg, were administered initially. The dose was titrated as necessary over the next 24 hours. In patients who received i.v. torsemide, median fractional sodium excretion significantly increased from 2.88% (0.04-10.1%) at baseline to 6.76% (0.71-11.6%) at peak (P = 0.0342). Hourly urine volume increased from 134 mL (25-400 mL) to 375 mL (145-790 mL) (P = 0.0034). Torsemide administration resulted in a significant improvement in both pulmonary rales and orthopnea. None of the patients experienced serious adverse events or required withdrawal from the study. These results suggest that i.v. torsemide is an effective and well-tolerated diuretic in patients with acute cardiogenic pulmonary edema.

Proteinuria in congestive heart failure.

To clarify the association between proteinuria and congestive heart failure (CHF), 24-hour urinary protein determinations were obtained from 27 patients with objectively documented CHF, before and after therapy of the CHF. The results demonstrate that modest proteinuria is a frequent feature of CHF and that this proteinuria reverses promptly with successful CHF therapy. Proteinuria exceeding 500 mg/day occurred only in patients with acute pulmonary edema. However, there was no other correlation between severity of proteinuria and type or chronicity of CHF. When proteinuria exceeds 1 g/24 h or when proteinuria does not reverse within 2 weeks of successful CHF therapy, intrinsic renal disease should be suspected.

Acute pulmonary oedema in a patient with phaeochromocytoma.

A young patient with a phaeochromocytoma who presented as an acute non cardiogenic pulmonary oedema is described. Phaeochromocytoma should be considered as a possible cause of the "adult respiratory distress syndrome."

Urinary catecholamine excretion in temporary residents of high altitude.

Urinary catecholamine excretion was estimated in 50 lowlanders temporarily staying at altitudes above 3,000 m. They were divided in subgroups according to the length of their continuous stay. For comparison, 25 highlanders who were born and brought up at high altitude and 50 lowlanders who had never been to altitudes of more than 1,000 m were also studied. High catecholamine excretion was noted in temporary residents staying at high altitude for up to 30 days as compared to that in lowlanders (P greater than 0.01). The excretion rate gradually returned to basal values thereafter. Catecholamines were essentially similar in lowlanders and highlanders. The significance of these findings is discussed regarding the possible pathogenetic role of the sympathoadrenal system in the development of ill effects in respone to high-altitude exposure.

Electrolyte changes at 3500 m in males with and without high-altitude pulmonary edema.

Ten normal healthy male subjects between 20-30 years of age were initially examined at Delhi (200 m) and thereafter air-lifted to an altitude of 3,500 m. Excretion of sodium, potassium and chloride in urine and their plasma level were determined at sea level (SL) and daily at high altitude (HA) for 4 d. At HA, four subjects developed high-altitude pulmonary edema (HAPE), four remained normal, and two suffered from acute mountain sickness. The results on normals and HAPE are presented. There was increased excretion of potassium at HA in both groups resulting in reduction of plasma level. The sodium and chloride excretion was also increased in normals at HA irrespective of urine volume. In HAPE cases, the sodium and chloride excretion was related to urine output. With the retention of fluid, the excretion of these ions in urine was diminished without a parallel change in plasma levels.

Changes in systolic time intervals in acute myocardial infarction.

After acute myocardial infarction there is a shortening of the QS2 interval and the ejection time. The pre-ejection time is either normal or prolonged. After the stage of maximum shortening of the QS2 interval and ejection time, there is a progressive improvement towards the normal. In this study there was no correlation between the shortened QS2 interval and ejection time, and the level of urinary catecholamine excretion. The physiological and clinical significance of these changes in the systolic time intervals and their relation to the altered haemodynamics and mechanics are discussed.