Several phiysical factors, including shear stress and cyclic load, modulate the ability of endothelial cells to respond to injury. The objective of these experiments was to test the hypothesis that ...cyclic mechanical load stimulates endothelial cell DNA synthesis and division in vitro. Rabbit aortic endothelial cells were cultured on Flex I® flexible-bottomed culture plates, and subjected to load amplitudes of increasing magnitude (0, 0.18, 0.24 and 0.27 load at 1 Hz) using a Flexercell® strain unit. Cells were harvested enzymatically and cell numbers determined on days 1, 3 and 5 after initiating the load regimen. DNA synthesis was quantified after trichloroacetic acid precipitation of 3Hthymidine-labeled cells from: (1) whole culture wells and (2) areas of minimum and maximum strain in culture cells. Data were analyzed using analysis of variance and a Tukey's test (n = 6 observations/strain regimen per day in triplicate). Results from analysis of endothelial cells in whole, subconfluent cultures showed that cells subjected to strains of 0.18 had a decreased rate of cell division (76% of control) and DNA synthesis (63% of control), while cells subjected to strains of 0.24 and 0.27 had an increased rate of cell division (108 and 83% increase, respectively, compared with control; p < 0.001) and DNA synthesis (39 and 172% increase, respectively, compared with control; p < 0.001 for 0.27) on day 3 when compared with control cells. The results indicate that endothelial cells respond to various physiologic levels of cyclic load in a biphasic manner to initiate DNA synthesis and cell division. These data suggest that endothelial cell mitogenesis may be modulated by specific levels of cyclic load.
HYPOTHESIS Operative mortality rates for esophageal resection vary across hospital volume groups in a nationally representative sample of hospitals. DESIGN Cross-sectional study of all adult patients ...in the Nationwide Inpatient Sample who underwent esophageal resection from 1995 through 1999 (N = 3023). Operative mortality was determined for hospital volume quartiles (low, <3 per year; medium, 3-5 per year; high, 6-16 per year; very high, >16 per year). Multiple logistic regression of in-hospital mortality was used for case-mix adjusted analyses. SETTING Hospitals performing at least 1 esophageal resection from 1995 through 1999 in the Nationwide Inpatient Sample. PATIENTS Patients having esophageal resection from 1995 through 1999 in the Nationwide Inpatient Sample. RESULTS Overall mortality was 8.2% and varied 3-fold from 11.8% to 3.7% across hospital volume groups (P<.001). In the case-mix–adjusted multivariate analysis, having surgery at a low-volume hospital (odds ratio, 2.9; 95% confidence interval, 1.7-4.9; P<.001) or medium-volume hospital (odds ratio, 2.4; 95% confidence interval, 1.4-4.3; P = .002) was associated with an increased risk of mortality compared with the reference group of very high–volume hospitals. The effect of volume on mortality was significant for both malignant and benign disease. Given the absolute risk difference of 8.1% between very high– and low-volume hospitals, only 12 patients would need to be referred to prevent 1 death after esophageal resection. CONCLUSIONS The operative mortality rate for esophageal resection varies across hospitals in the United States. To improve the quality of care and reduce operative mortality rates for patients in need of esophageal surgery, patients should either be referred to higher-volume hospitals, or quality improvement should be directed at lower-volume hospitals.Arch Surg. 2003;138:1305-1309-->
Acute chest syndrome (ACS) is the most common form of acute pulmonary disease associated with sickle cell disease. To investigate the possibility that alterations in endothelial cell (EC) production ...and metabolism of nitric oxide (NO) products might be contributory, we measured NO products from cultured pulmonary EC exposed to red blood cells and/or plasma from sickle cell patients during crisis. Exposure to plasma from patients with ACS caused a 5- to 10-fold increase in S-nitrosothiol (RSNO) and a 7- to 14-fold increase in total nitrogen oxide (NO
) production by both pulmonary arterial and microvascular EC. Increases occurred within 2 h of exposure to plasma in a concentration-dependent manner and were associated with increases in endothelial nitric oxide synthase (eNOS) protein and eNOS enzymatic activity, but not with changes in nitric oxide synthase (NOS) III or NOS II transcripts, inducible NOS (iNOS) protein nor iNOS enzymatic activity. RSNO and NO
increased whether plasma was obtained from patients with ACS or other forms of vasoocclusive crisis. Furthermore, an oxidative state occurred and oxidative metabolites of NO, particularly peroxynitrite, were produced. These findings suggest that altered NO production and metabolism to damaging oxidative molecules contribute to the pathogenesis of ACS.
Abdominal aortic aneurysm (AAA) repair is a complex surgical procedure and is commonly performed in a variety of practice settings across the United States. The quality of surgical care is neither ...ideal nor uniform across medical centers with documented variation in both utilization and outcomes. Recent data document that screening, though effective in reducing AAA-related deaths, may have only small contributions to population mortality. Large randomized trials have provided evidence regarding the timing of AAA repair and provide strong evidence for the development of appropriateness criteria. In general, lower mortality rates have been consistently associated with higher provider volume (surgeon and hospital) and specialization in vascular surgery. Current health policy initiatives suggest referral of several complex procedures to high volume centers based on minimum volume standards. Processes of care of high-volume providers and vascular surgeons should be studied and used to guide quality improvement efforts for lower volume providers and surgeons of other specialties performing AAA repair.
There is increasing clinical interest in improving blood rheology to optimize organ function, but studies correlating the two are scarce. To study this, rat kidneys were perfused in vitro at 37 ...degrees C at a constant mean renal arterial pressure of 160 mm Hg. The perfusate consisted of an oxygenated Krebs HCO3 buffer containing 1 mg/ml glucose, 0.5 mg/ml creatinine, amino acids, 3Hinulin (marker for GFR), 2.5 g/dl albumin, and 10 or 20% hematocrit. In some experiments, RBC were made nondeformable by heating at 50 degrees C for 20 min. Deformability was measured by an ektacytometer. In other experiments, 0.001% of an anionic polyacrylamide (Separan), a drag-reducing agent, was added to the perfusate. Viscosity was measured with a cone and plate viscometer, Na+ with a flame spectrophotometer, and perfusate flow with a Brooks in-line flowmeter. Other functional parameters, GFR, urine flow, RPF, and reabsorption of sodium and water, were also measured. The results indicate that (1) making RBC nondeformable or increasing viscosity by increasing hematocrit reduces renal function, and (2) addition of a drag-reducing agent improves renal function at 20% hematocrit. We conclude that rheologic manipulation of a perfusate solution can alter flow and renal function.
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