Effects of vasoactive and inflammatory mediators on endothelin-1 expression in pulmonary endothelial cells.

Endothelin-1 (ET-1) is known to be involved in a variety of pathophysiologic conditions, especially of the pulmonary vasculature. The aim of this study was to investigate physiologic mediators potentially involved in the pathogenesis of pulmonary hypertension, for their effects on ET-1 gene expression at both the transcriptional and translational level. Rat microvascular and pulmonary artery endothelial cells grown in culture were exposed to vasoactive mediators (thrombin or an anoxic gas mixture) and inflammatory mediators (lipopolysaccharide, interleukin 1 alpha, interleukin 1 beta, or tumor necrosis factor alpha) for various time periods. The change in prepro-ET-1 (ppET-1) mRNA levels in these cells in response to stimuli was a time-dependent phenomenon. The inflammatory mediators caused an acute rise in ppET-1 mRNA levels whereby peak induction occurred after 1 h with a rapid decline to control levels by 4 h. The vasoactive mediators elicited a more sustained response whereby a significant elevation in ppET-1 mRNA expression occurred quickly and remained elevated through 4 h. The pattern of induction was more rapid for thrombin than for anoxic gas exposure. Radioimmunoassay analysis demonstrated a similar response for thrombin and the inflammatory mediators in ET-1 mature peptide release, whereas the effect of anoxic gas exposure was divergent. Significant elevations were noted after 6 h for thrombin as well as each of the inflammatory mediators except IL-1 alpha. In response to the anoxic gas exposure, however, a significant rise in ET-1 peptide release was not evident until after 24 h. To determine the level at which ppET-1 mRNA induction is regulated, cells were cotreated with each of the stimuli and actinomycin D or cycloheximide. Results indicate that the induction of ppET-1 mRNA levels is likely due to de novo transcription, as well as mRNA stabilization. In summary, inflammatory and vasoactive agents are important regulators of ET-1 gene expression in rat pulmonary endothelial cells; most important, we observed a differential response at the mRNA or peptide level depending on the mediator involved.

Gonococcal endocarditis during pregnancy: simultaneous cesarean section and aortic valve surgery.

Gonococcal endocarditis is a rare and potentially fatal consequence of disseminated gonococcal infection. Presented is the first known case of culture-proved gonococcal and serratia endocarditis in pregnancy. The case was further complicated by fetal distress at 30 weeks' gestation as a result of maternal decompensation from worsening congestive heart failure secondary to rapid destruction of her aortic valve. Consequently, cardiopulmonary bypass with subsequent aortic valve replacement and implantation of a left ventriculoaortic shunt was initiated immediately after an emergency cesarean section.

Alveolar pressure in fluid-filled occluded lung segments during permeability edema.

In a model of increased hydrostatic pressure pulmonary edema Parker et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 267-276, 1978) demonstrated that alveolar pressure in occluded fluid-filled lung segments was determined primarily by interstitial fluid pressure. Alveolar pressure was subatmospheric at base line and rose with time as hydrostatic pressure was increased and pulmonary edema developed. To further test the hypothesis that fluid-filled alveolar pressure is determined by interstitial pressure we produced permeability pulmonary edema-constant hydrostatic pressure. After intravenous injection of oleic acid in dogs (0.01 mg/kg) the alveolar pressure rose from -6.85 +/- 0.8 to +4.60 +/- 2.28 Torr (P less than 0.001) after 1 h and +6.68 +/- 2.67 Torr (P less than 0.01) after 3 h. This rise in alveolar fluid pressure coincided with the onset of pulmonary edema. Our experiments demonstrate that during permeability pulmonary edema with constant capillary hydrostatic pressures, as with hemodynamic edema, alveolar pressure of fluid-filled segments seems to be determined by interstitial pressures.

Angiotensin-converting enzyme (ACE) in sepsis.

Angiotensin-converting enzyme (ACE) is localized to the luminal surface of pulmonary endothelial cells, where it converts angiotensin I and activates bradykinin. Sepsis may result in endothelial cell dysfunction. We have previously reported that the marked decrease in serum ACE in patients with the Adult Respiratory Distress Syndrome (ARDS) is present only in septic patients. Serum was evaluated in seven baboons made septic by the infusion of live E coli. There was a significant decline in serum ACE from a control value of 41.5 +/- 4.2 to 25.8 +/- 2.2 at 8 h (P less than 0.05), which correlated with the 65 +/- 11 torr decline in mean arterial pressure. There was no change in PaO2. We conclude that sepsis results in marked depletion of serum ACE activity, which corresponds to the decrease in mean arterial pressure, and may reflect reduced bradykinin inactivation.

Does reduced colloid oncotic pressure increase pulmonary dysfunction in sepsis?

Starling's hypothesis of forces governing fluid movement across capillary membranes suggests that any unopposed decrease in intracapillary colloid oncotic pressure (COP) or increase in capillary permeability should result in increased interstitial fluid. Iso-oncotic increase in pulmonary artery wedge (PAW) causes pulmonary dysfunction. Isobaric reduction of COP with normal capillary permeability does not result in pulmonary interstitial edema. Because sepsis is a frequent antecedent of clinical pulmonary dysfunction, the question was asked: does reduction in the COP-PAW gradient in the presence of sepsis result in increased pulmonary dysfunction? Twenty baboons were studied: group 1--control, group 2--4-h constant infusion of E. coli, group 3--plasmapheresis alone, group 4--plasmapheresis followed by sepsis. Ringer's lactate was infused to keep PAW constant. Arterial and mixed venous blood gases were drawn and the intrapulmonary shunt (QS/QT) was calculated. The data were compared using Tukey's HSD test and one way analysis of variance. Plasmapheresis alone resulted in a 68% reduction in COP (15 +/- 2.9 (SD) torr to 4.6 +/- 0.6 in group 3 and 16.5 +/- 4.3 to 5.7 +/- 0.9 in group 4, p less than 0.05). Sepsis resulted in an increase in QS/QT in all septic animals. There was no increased QS/QT in those animals that had sepsis added to plasmapheresis, group 4 (p less than 0.05). These data indicate that sepsis leads to pulmonary dysfunction but that this dysfunction appears to be independent of colloid oncotic forces.

Preoperative CEA level: a prognostic test in patients with colorectal carcinoma.

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were evaluated in 42 patients with colorectal carcinoma. Preoperative CEA values correlated inversely with survival at a statistically significant level and provided prognostic information not available by pathologic staging. Postoperative plasma CEA can accurately predict recurrent disease and may, when serial values are elevated, serve as an indication for a second-look procedure.

Reassessment of circle tube nephrostomy in advanced pelvic malignancy.

The dilemma created for and presented to the urologist by the combination of a patient with increasing uremia from advanced pelvic malignancy and a referring physician frustrated by the situation is solved best by individual decisions appropriate for each case. Urinary diversion should be reserved for the occasional circumstance when reasonable life expectancy approaches 6 months or more. Drainage by circle tube nephrostomy provides minimal trouble for patient and physician, while providing excellent relief from the obstructive uropathy. In this series of 20 patients the average survival was 5.3 months. An attempt to assess the quality of life after diversion by circle tube nephrostomy is made.