Faculty Bibliography

Human endothelium obtained from both the aorta and the pulmonary artery has been evaluated for the presence of the messenger RNA coding for the expression of sterol 27-hydroxylase. Unique oligomers were designed to detect the mRNA by reverse transcription followed by the polymerase chain reaction. The amplified product was sequenced and was found to be identical to the published sequence for nucleotides 491 to 802 of the human sterol 27-hydroxylase cDNA. Northern blot analysis confirmed the presence of 27-hydroxylase mRNA in pulmonary artery and aortic endothelium. As part of these studies, enzymatic activity was assayed in cultured arterial endothelium using cholesterol as a substrate and isotope ratio gas-liquid chromatography-mass spectrometry to identify the metabolites, 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, in the medium. Localization of sterol 27-hydroxylase to vascular endothelium indicates intracellular production of the biologically active metabolite 27-hydroxycholesterol

Platelet activating factor (PAF) enhances polymorphonuclear leukocyte (PMN) superoxide (.O2-) production, CD11b expression, and elastase release, all essential components in the pathophysiology of multiple-organ failure. This study was designed to determine the effects of Lexipafant, a PAF receptor antagonist, on PAF-mediated PMN functions. PMNs from 10 healthy volunteers were isolated and pretreated with various concentrations of Lexipafant (0-100 microM). PMNs were then incubated for 5 min with 200 nM PAF for .O2- detection or 2000 nM PAF for elastase measurement and activated with 1 microM N-formylmethionylleucylphenylalanine. The mean rate of .O2- production was determined by a cytochrome c reduction assay (nmole .O2-/min/1.33 x 10(5) PMN +/- SEM). Elastase release was measured by the cleavage of the synthetic elastase substrate Meo-Suc-Ala-Ala-Pro-Val-pNA (mean elastolytic activity +/- SEM). In parallel experiments, PMNs were incubated with 200 nM PAF for 30 min following pre-treatment with Lexipafant and CD11b expression was determined by flow cytometry (mean fluorescence intensity +/- SEM). Statistical analysis was performed using repeated-measures ANOVA (P < 0.05). Lexipafant inhibited PAF-enhanced PMN .O2- generation, CD11b expression and elastase release in a dose dependent fashion. The IC50 of Lexipafant for .O2- production, CD11b expression, and elastase release was 0.046, 0.285, and 0.05 microM, respectively. Lexipafant attenuated the PAF-mediated upregulation of PMN .O2- production, CD11b expression, and elastase release in a dose dependent fashion. These data support the hypothesis that Lexipafant may reduce the severity of the inflammatory response to injury produced by PAF-enhanced activation of PMNs

BACKGROUND: A variety of surgical techniques has been developed to attempt to minimize the risk of paraplegia after descending thoracic aortic aneurysm repair. This study reviews our institutional experience with several basic techniques over a period of 10 years. METHODS: Seventy-eight consecutive patients underwent repair of descending thoracic aortic aneurysm between 1983 and 1993. Two basic repair strategies were used: (1) distal perfusion with somatosensory evoked potential monitoring (n = 54) and (2) cross-clamping (n = 24), alone (n = 6) or with controlled distal exsanguination (n = 18). RESULTS: The operative mortality rate was 6.5% for elective repair (n = 62), 25.0% for emergent repair (n = 16), and 10.3% overall. Univariate predictors of increased operative risk were emergent operation, rupture, and shock. Neither death nor paraplegia was related to the operative technique used. The incidence of paraplegia was 3.7% in perfused patients and 4.2% in cross-clamping patients (p > 0.05). Paraplegia did not occur after any elective operation (zero of 62) but occurred in 18.6% of emergent cases (p < 0.01). In perfused patients, paraplegia did not occur when the distal pressure was maintained above 55 mm Hg and somatosensory evoked potentials remained intact. When somatosensory evoked potentials were lost (n = 7) in perfused patients, the operative technique was altered successfully in 5 patients, whereas in 2 patients (28.6%), paraplegia developed. CONCLUSIONS: The risks associated with elective descending thoracic aortic aneurysm repair were extremely low using an operative strategy that was flexible but skewed toward perfusion with somatosensory evoked potential monitoring. In perfused patients, paraplegia did not occur when distal pressure was greater than 55 mm Hg and somatosensory evoked potentials remained intact. However, the risks of death and paraplegia were primarily related to emergent presentation, not to technique, and the technique of cross clamping with controlled distal exsanguination was found to be valuable in unstable or in anatomically complicated subsets of patients

Thoracoscopic cardiac surgery is presently under intense investigation. This study examined the feasibility and efficacy of closed chest cardiopulmonary bypass and cardioplegic arrest in comparison with standard open chest methods in a dog model. The minimally invasive closed chest group (n = 6) underwent percutaneous cardiopulmonary bypass and cardiac venting, as well as antegrade cardioplegic arrest through use of a specially designed percutaneous endovascular aortic occluder and cardioplegic solution delivery system. The control group (n = 6) underwent standard sternotomy and conventional open chest cardiopulmonary bypass, aortic crossclamping, and antegrade cardioplegia. Ischemic arrest time was 1 hour in each group. Ventricular pressures and sonomicrometer segment lengths were recorded before bypass and at 30 and 60 minutes after bypass. Left ventricular function did not differ significantly between the two groups, as demonstrated by measurements of elastance and end-diastolic stroke work. Also, the preload recruitable work area was 69% and 60% of baseline at 30 and 60 minutes after bypass in the minimally invasive group versus 65% and 62% in the conventional control group (p = not significant); the stroke work end-diastolic length relationship was 78% and 71% of baseline in the minimally invasive group at these intervals versus 77% and 74% in the conventional control group (p = not significant). Myocardial temperatures were similar throughout bypass in the two groups, and ultrastructural examination of prebypass and postbypass biopsy specimens showed no differences between groups. These results demonstrate that minimally invasive cardiopulmonary bypass with cardioplegic arrest is as feasible, safe, and effective as conventional open chest cardiopulmonary bypass. Thus current technology may allow wider clinical application of closed chest cardiac surgery