Minocycline inhibits apoptosis and inflammation in a rat model of ischemic renal injury.

Tetracyclines exhibit significant anti-inflammatory properties in a variety of rheumatologic and dermatologic conditions. They have also been shown to inhibit apoptosis in certain neurodegenerative disorders. Because ischemic renal injury is characterized by both apoptosis and inflammation, we investigated the therapeutic potential of tetracyclines in a rat model of renal ischemia-reperfusion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion and received either minocycline or saline for 36 h before ischemia. Minocycline reduced tubular cell apoptosis 24 h after ischemia as determined by terminal transferase-mediated dUTP nick end-labeling staining and nuclear morphology. It also decreased cytochrome c release into the cytoplasm and reduced upregulation of p53 and Bax after ischemia. The minocycline-treated group showed a significant reduction in tubular injury and cast formation. In addition, minocycline reduced the number of infiltrating leukocytes, decreased leukocyte chemotaxis both in vitro and ex vivo, and downregulated the expression of ICAM-1. Serum creatinine 24-h postischemia was significantly reduced in the minocycline-treated group. We conclude that minocycline has potent antiapoptotic and anti-inflammatory properties and protects renal function in this model of ischemia-reperfusion. Tetracyclines are among the safest and best-studied antibiotics. They are thus attractive candidates for the therapy of human ischemic acute renal failure.

Frequency and prognostic significance of pericardial effusion in primary pulmonary hypertension. PPH Study Group. Primary pulmonary hypertension.

Pericardial effusion was noted in 43 of 79 patients (54%) with severe primary pulmonary hypertension. Larger effusion was associated with hemodynamic and echocardiographic evidence of right heart failure, impaired exercise tolerance, and a poor 1-year prognosis.

Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin.

OBJECTIVE: To evaluate the effects of long-term-intravenous infusion of prostacyclin on exercise capacity, hemodynamics, and survival in patients with primary pulmonary hypertension. DESIGN: Open, multicenter, uncontrolled trial. SETTING: Four referral centers. PATIENTS: 18 patients with primary pulmonary hypertension: 1 New York Heart Association (NYHA) class II patient, 13 NYHA class III patients, and 4 NYHA class IV patients. INTERVENTIONS: Continuous intravenous prostacyclin administered by portable infusion pumps. All patients were treated with anticoagulant agents. MEASUREMENTS AND MAIN RESULTS: With the 6-minute walk used to evaluate exercise capacity, patients could walk on average more than 100 meters farther after prostacyclin therapy was initiated (distance at 6 months, 370 +/- 119 meters compared with 264 +/- 160 meters at baseline; P < 0.001; distance at 18 months, 408 +/- 138 meters; P = 0.02 compared with baseline). Hemodynamics were improved at 6 months: The cardiac index increased 18% (95% CI, 0.1% to 36.7%; P = 0.02), and mean pulmonary artery pressure and total pulmonary resistance decreased 9% (CI, 1.4% to 15.7%; P = 0.03) and 26% (CI, 6.1% to 46.3%; P = 0.02), respectively, compared with baseline. The improvements in cardiac index and total pulmonary resistance were maintained at 12 months (27% increase [CI, 1.3% to 51.9%; P = 0.05] and 32% decrease [CI, 9.7% to 53.6%; P = 0.02] compared with baseline, respectively). Survival was improved in NYHA class III and IV patients who received continuous prostacyclin (n = 17; follow-up, 37 to 69 months) when compared with historical controls who received standard therapy (National Institutes of Health Primary Pulmonary Hypertension Registry, n = 31, P = 0.045). Kaplan-Meier estimates of 1-, 2-, and 3-year survival rates for the patients treated with prostacyclin were 86.9%, 72.4%, and 63.3%, respectively, compared with 77.4%, 51.6%, and 40.6% for the historical control group (hazard ratio, 2.9 [CI, 1.0 to 8.0; P = 0.045]). Serious complications attributable to the drug and delivery system included two deaths and seven episodes of nonfatal sepsis in three patients. CONCLUSIONS: Continuous intravenous prostacyclin resulted in sustained clinical and hemodynamic improvement and probably in improved survival in patients with severe primary pulmonary hypertension. Despite potentially serious complications, long-term prostacyclin may be especially helpful in seriously ill patients awaiting transplantation.

Effects of dense, high-volume, artificial surfactant aerosol on a heated exhalation filter system.

OBJECTIVE: To evaluate a supplemental heated filter system during mechanical ventilation with continuous nebulization of an artificial surfactant by a new, high-volume nebulizer. DESIGN AND METHODS: A new nebulizer system, containing artificial surfactant, provided half of a 20-L minute ventilation and the remainder of this minute ventilation was provided by a commonly used mechanical ventilator. Ventilation sources were joined in the inspiratory limb of the breathing circuit, which was connected to a test lung system. A supplemental filter system was placed upstream of the ventilator's heated filter in the expiratory limb of the circuit. Circuit pressures at the inlet of the supplemental filter (P1), between the filters (P2), and after the ventilator expiratory filter (P3) were monitored and recorded. Nebulizer canisters containing artificial surfactant were replaced every 4 hrs. The performance of four supplemental filters in continuous use was examined. Another four filters were each used over 4 hrs, steam autoclaved, and reused. SETTINGS: The ventilator was set at a rate of 20 breaths/min, with a tidal volume of 0.5 L, a flow rate of 40 L/min, and positive end-expiratory pressure of 10 cm H2O. The nebulizer provided an equal volume and flow rate so that the delivered tidal volume was 1.0 L with a flow rate of 80 L/min. RESULTS: Ventilator failure and/or excessive airway pressure caused by increased filter resistance occurred at a mean of 7.3 +/- 1.3 (SD) hrs of continuous ventilation. Mean P1-peak increased from 67.5 +/- 8.2 to 94.0 +/- 10.7 cm H2O (p < .001) and P1-baseline increased from 9.3 +/- 1.0 to 53.5 +/- 17.1 cm H2O (p = .014). Filters that were autoclaved after 4 hrs of ventilation and reused lasted a total of 7.0 +/- 1.3 hrs. Mean P1-peak increased from 68.9 +/- 4.9 to 84.8 +/- 19.1 cm H2O and P1-baseline increased from 9.5 +/- 1.7 to 30.8 +/- 14.2 cm H2O (p < .05). CONCLUSIONS: The supplemental filter system was able to protect the ventilatory exhalation sensors for approximately 7 hrs at a minute ventilation of 20 L/min. Steam sterilization did not extend the supplemental filter life.

Histamine and ascorbic acid: a survey of women in labor at term and significantly before term.

In ascorbic acid-requiring species (human, guinea pig), elevations of circulating histamine occur as the result of marginal ascorbic acid status. Marginal ascorbic acid status during pregnancy is associated with preeclampsia, abruption, and prematurity. Furthermore, circulating histamine is known to be elevated in these complications perhaps as a result of placental dysfunction which diminishes normal placental histaminase. We hypothesized that women with preeclampsia and premature labor would have elevated histamine and the lowest concentrations of ascorbic acid. Plasma total whole blood histamine and ascorbic acid were surveyed in women in term (T) and preterm (PT) labor. Blood histamine was elevated in PT compared to T labor but so was plasma ascorbate, indicating that marginal ascorbate status does not cause the elevated circulating histamine observed in PT. However, marginal ascorbate status concomitant with reduced placental histaminase may contribute to further increases in circulating histamine and to any pathology which might result from elevated histamine. Regression analysis of histamine on ascorbate for T and PT labor revealed a significant inverse relationship between ascorbate and histamine only in PT labor (p less than 0.027). An unexpected finding was that a history of maternal cigarette smoking, to a degree which resulted in marginal ascorbic acid status, confounded the relationship between ascorbate and circulating histamine in T labor.

Traumatic pneumocephalus: a hazard of resuscitators.

A patient with traumatic pneumocephalus following use of an oxygen-powered resuscitator with a face mask is presented. Pressures of 50 cm H2O delivered by the device apparently were sufficient to force air into the cranium through a fracture communicating with the nasal cavity. The authors feel that manual-powered resuscitators should be used on patients suspected of skull fracture.