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We studied the effects of alpha- and beta-adrenergic antagonists on lung fluid and protein exchange in anesthetized sheep. alpha-Adrenergic blockade with 2 mg/kg phentolamine caused a transient and small decrease in lung lymph flow (Qlym), which was associated with a decrease in mean pulmonary arterial pressure (Ppa); but the steady-state Qlym and mean left atrial pressure were not different from base-line values. In contrast, beta-adrenergic blockade with propranolol (2 mg/kg) caused an increase in Qlym from a base-line value of 7.7 +/- 2.2 ml/h to a steady-state value of 10.6 +/-2.3 ml/h within 2 h (P less than 0.05), which was not associated with a change in Ppa. The increase in Qlym persisted for the 4-h duration of the study. The 39% increase in Qlym after propranolol was associated with a 50% increase in transvascular protein clearance (CL), whereas in control animals the 100% increase in Qlym after left atrial hypertension was associated with only a 36% increase in CL, indicating increased transvascular transport of proteins after propranolol. The transient decrease in Qlym after phentolamine may be due to the short-lasting decreased in pulmonary microvascular pressure and vascular surface area. However, the long-lasting increases in Qlym and CL after propranolol may be due to an increase in vascular surface area and to an increase in endothelial permeability of proteins. The results suggests that beta-adrenergic receptors regulate the transendothelial transport of fluid and proteins.

We determined the effect of pulmonary hypoperfusion on extravascular water accumulation in anesthetized dogs by occluding the left pulmonary artery for 3 h and then reperfusing it for 24 h. The lung was reperfused either at normal left atrial pressure (Pla) or during increased Pla induced by a left atrial balloon. In each case the extravascular water content-to-bloodless dry weight ratio (W/D) of the left lung was compared with that of the right lung. The W/D of the left lung of 3.26 +/- 0.49 ml/g was not significantly different from the value of 2.87 +/- 0.37 for the right lung after the reperfusion at normal Pla. However, the W/D of the left lung of 5.10 +/- 0.38 ml/g was greater (P less than 0.05) than the value of 4.42 +/- 0.34 for the right lung after reperfusion at Pla of 25 Torr. This difference could not be prevented by pretreatment with heparin, suggesting that the increase in lung water content was not due to activation of intravascular coagulation secondary to stasis occurring during the occlusion. Because the left lung was more edematous than the right one, even though both lungs had been subjected to the same increase in Pla, the results suggest that a period of pulmonary hypoperfusion causes an increase in the interstitial protein concentration.

Ischemia of extremities is responsible for considerable morbidity and mortality and the pathophysiology of this condition warrants further study. The purpose of this review is to discuss techniques used in the evaluation of limb ischemia and reperfusion. It is of critical importance to study limb blood flow distribution to the microcirculation where nutritive exchange occurs. Skeletal muscle ischemia progresses to infarction when critical deficits of cellular metabolites develop, which mandates that studies be focused at the cellular level. It is clear that the adverse effects of ischemia can be exacerbated by a reperfusion injury to the endothelium of the microvasculature. Investigators wishing to study limb ischemia have a wide spectrum of methodology and established models available to use in improving the understanding of the complex events of ischemic injury.

We examined the effect of left atrial hypertension on lung fluid and protein exchange in acutely prepared anesthetized sheep. The results were compared with those reported by Erdmann jet al. (Circ. Res. 37:271-284, 1975) in chronically instrumented conscious sheep. Animals were anesthetized with halothane and efferent duct of the caudal mediastinal node was cannulated. Pulmonary microvascular pressure (Pmv) was elevated by raising left atrial pressure with a left atrial balloon. For every elevation in Pmv of 1 cmH2O pulmonary lymph flow (Qlym) increased by 0.5 ml/h. Increasing the Pmv resulted in a linear decrease (p less than 0.05) in the ratio of lymph to plasma protein concentration as a result of a significant reduction in lymph protein concentration. Transvascular clearance of lymph proteins increased by 39% with a doubling of Qlym. The steady-state changes in pulmonary fluid and protein exchange induced by an increase in Pmv in acutely prepared anesthetized sheep were the same as those observed by Erdmann et al. in chronically instrumented unanesthetized sheep, indicating that the acute preparation is equally reactive to increase in Pmv and that the lung endothelial permeability is not increased.

The records of 6,452 consecutive patients who underwent cardiopulmonary bypass procedures were examined for intra-abdominal complications. There were 60 complications in 51 patients for an incidence of 0.94 per cent. The mortality rate was 59 per cent. Complications included bleeding in the gastrointestinal tract in 20, intestinal ischemia in 16, acute cholecystitis in 11, pancreatitis in five, small intestinal obstruction in three, perforated ulcer in two, hepatic necrosis in two and splenic laceration in one instance. Clinical risk factors included advanced age, emergency operation, valvular surgical treatment, hypotension, intra-aortic balloon pump, pressors and reoperation. Patients with a prolonged pump time had an increased risk of intraabdominal complications (p less than 0.001).

To address the significance of clostridial bacteremia in surgical patients, the bacteriologic records of the New York Hospital from an eight year period were reviewed. Of 1,708 patients who underwent surgical treatment with positive blood cultures, 23 (1.3 per cent) with clostridial bacteremia were identified. Twenty-one of the 23 patients manifested clinical signs of sepsis at the time of clostridial bacteremia consisting of fever, leukocytosis or hypotension. Fourteen patients had intra-abdominal sources of bacteremia and eight of these had either a diverticular abscess or colorectal perforation. The over-all mortality rate was 43 per cent, with all deaths resulting from uncontrolled sepsis. An association between clostridial bacteremias and malignant disease has been described. Thirteen malignant diseases were identified in 12 of the 23 patients reported herein. Carcinoma of the colon and rectum was the most frequently associated malignant condition, but a wide variety of other malignant diseases were also identified. The diagnosis of underlying malignant disease was known prior to the clostridial bacteremia in ten patients and unknown in two. None of the patients were receiving chemotherapy or radiation therapy at the time of bacteremia. Three different Clostridium species were isolated in patients with underlying malignant disease, supporting an association between malignant conditions and other Clostridium species as well as Clostridium septicum. The identification of clostridial bacteremia in surgical patients warrants both aggressive treatment of the septic state and a thorough search for associated malignant lesions.

The effects of a transient increase in pulmonary microvascular pressure (Pmv) on pulmonary fluid and protein exchange were studied in anesthetized sheep in which pulmonary lymph was collected. Pmv was increased to 30-40 mmHg for 15-30 min in 18 sheep by either an intra-aortic injection of norepinephrine (NE) or a rapid inflation of a left atrial balloon. NE injection produced sustained two- to threefold increases in pulmonary lymph flow and protein flux, whereas rapid balloon inflation transiently elevated lymph flow even though Pmv increased to similar levels with both methods. The sustained increases with NE were not due to an increase in vascular permeability but probably the result of a persistent increase in vascular surface area. In three additional animals, Pmv was increased to over 50 mmHg for 15-30 min. In these animals, lymph flow increased only by 49%, but airway edema fluid was present. The ratio of extravascular lung water to bloodless dry lung weight was 5.77 +/- 0.13 as compared with 4.30 +/- 0.11 in sheep subjected to Pmv less than 50 mmHg and to 4.08 +/- 0.19 for controls. These findings indicate that high pressure-induced pulmonary edema depends on a threshold Pmv around 50 mmHg. A combination of high capillary pressure and impaired lymphatic flow may be the bases for the development of neurogenic and catecholamine-induced pulmonary edema.

A retrospective study was undertaken to examine the incidence and clinical significance of enterococcal bacteremia in burned patients with enterococcal burn-wound infections. During a 26-month period from 1983 to 1985, 38 patients were found to have enterococcal burn-wound infections. Twenty of these patients developed positive blood cultures for enterococcus with no other identifiable source for the bacteremia. Cases occurred sporadically during the study period without evidence of a specific epidemic. Ten patients died within ten days of the bacteremia, while nine others eventually died from other complications. Only one patient survived to discharge. Prior antibiotic therapy did not appear to increase the risk for enterococcal infection, and specific therapy against the enterococcus after the bacteremia was identified appeared to have no effect on mortality. Mortality was significantly greater for bacteremic patients than for patients with enterococcal wound infection alone or for burned patients without enterococcal infections. Although previously not considered pathogenic, enterococcal burn-wound infections should prompt aggressive therapy to prevent the development of enterococcal sepsis with its associated high mortality.

We examined the role of granulocytes in the development of increased pulmonary vascular permeability during acute pancreatitis in acute sheep lung lymph preparation. One group of animals was depleted of 95% of circulating granulocytes by injection of hydroxyurea. In this group and in a second group of control animals, acute hemorrhagic pancreatitis was produced by injection of trypsin and sodium taurocholate acid into the pancreas. Pulmonary lymph flow and transvascular protein clearance increased without changes in pulmonary vascular pressures, indicating that acute pancreatitis h ad produced a pulmonary vascular injury. These changes occurred with a decrease in circulating granulocytes. Prior granulocyte depletion prevented the increases in lymph flow and protein clearance produced by pancreatitis, whereas the changes in platelet count, fibrinogen, and peritoneal fluid amylase concentrations were similar in both groups. These findings indicate that circulating granulocytes are necessary for the development of pulmonary vascular injury after acute pancreatitis.

Post-trauma patients have an oxygen consumption which is proportional to oxygen delivery, suggesting that tissue oxygen consumption is limited by diffusion. Transfusion of packed red blood cells (RBC), which increases the oxygen-carrying capacity of blood, would be expected to increase mixed venous PO2, thereby improving tissue oxygenation. However, the low P50 of stored blood may increase the affinity of hemoglobin for oxygen and reduce oxygen consumption. To evaluate the net effect of these mechanisms, we studied hemodynamic and oxygen transport parameters before and after RBC transfusion in eight critically ill patients. Mixed venous O2 content was measured directly by fuel cell O2 analyzer, and standard P50 was calculated. Following transfusion of one unit of packed RBC which increased mean hemoglobin from 9.2 +/- 0.3 gm/dl to 10.1 +/- 0.3 gm/dl (p less than 0.01), there were no changes in oxygen delivery (490 +/- 80 ml/min/m2), oxygen consumption (210 +/- 30 ml/min/m2), or mixed venous PO/ (37 +/- 2 Torr). Cardiac index (4.1 +/- 0.71 L/min) decreased by 0.4 L/min/m2 (p less than 0.05). Standard P50 decreased by 4.2 +/- 2.4 Torr following transfusion of two units of RBC (p less than 0.05). Red blood cell transfusion thus failed to increase oxygen consumption in these patients, despite an increase in oxygen content. Thus, RBC transfusion may not improve tissue oxygenation.

We examined the effects of left pulmonary arterial occlusion and reperfusion on pulmonary transvascular fluid and protein exchange in the sheep lung lymph fistula preparation. Pulmonary lymph flow (Qlym) increased from the base-line value of 5.0 +/- 0.8 to 10.0 +/- 2.1 ml/h after occlusion (P less than 0.05); the steady-state value of 11.9 +/- 2.2 ml/h during reperfusion was not significantly different from the value during occlusion. The lymph-to-plasma protein concentration ratio (L/P) did not change significantly during either occlusion or reperfusion. Transvascular protein clearance (Qlym X L/P) increased from 3.7 +/- 0.6 to 8.4 +/- 2.1 ml/h during occlusion (P less than 0.05) and remained elevated at 8.6 +/- 1.7 ml/h during reperfusion. The sustained increases in Qlym and protein clearance could not be explained by the 3-Torr increase in mean pulmonary arterial pressure during the occlusion period or by an increase in the interstitial protein concentration caused by a period of decreased filtration during occlusion. The increases in protein clearance that occurred with increased Qlym during occlusion and reperfusion were greater than the increases in protein clearance with comparably increased Qlym during left atrial hypertension. The results suggest that occlusion of a pulmonary artery increases vascular permeability to plasma proteins in the lung.

We used the anesthetized sheep lung lymph preparation to examine the effects of acute hemorrhagic pancreatitis on pulmonary transvascular fluid and protein exchange. Induction of acute pancreatitis by injection of trypsin and sodium taurocholate into the pancreatic duct caused significant increases (p less than 0.05) in lung lymph flow, ratio of lymph to plasma protein concentration (L/P ratio), and transvascular protein clearance. Pulmonary arterial and pulmonary arterial wedge pressures did not change significantly, but pulmonary blood flow decreased (p less than 0.05) and pulmonary vascular resistance increased (p less than 0.05). In contrast to the effects of acute pancreatitis, left atrial hypertension caused increases in lung lymph flow that were associated with decreases in the L/P ratio. Extravascular lung water content was increased after acute pancreatitis by 25% from the value obtained in sham-operated animals in which saline was injected into the pancreatic duct. These findings indicate that acute hemorrhagic pancreatitis causes an increase in pulmonary vascular permeability to proteins. Because pulmonary vascular pressures did not change, the increased permeability may be due to the cellular and humoral factors rather than hemodynamic mechanisms.

The diagnosis of appendicitis may be difficult to establish even for the experienced surgeon. Considerable variability in presenting symptoms and signs, resulting in part from the numerous locations in which the appendix may be found, contributes to diagnostic insecurity. Appendicitis that mimics acute disorders of the genitourinary tract is a rare cause of diagnostic confusion. The association of appendicitis with abnormal urinary sediment or ureteral obstruction has been reported previously. We report 3 cases of proved appendicitis that presented with other symptoms suggestive of acute urological disorders (gross hematuria, acute prostatis and acute pyelonephritis). While gross hematuria caused by appendicitis has been reported previously, cases of appendicitis mimicking acute prostatitis or rupture of a renal calix with extravasation of urine following ureteral obstruction have not been described. Recognition of unusual manifestations of appendicitis is essential in current surgical practice. Appendicitis should be included in the differential diagnosis of acute urological disorders.

We investigated the cause of the reduced leukotriene B4 (LTB4) production seen in neutrophils from patients with established adult respiratory distress syndrome compared with control neutrophils. Lymphocytes/monocytes from controls were found to synergistically enhance the amount of LTB4 produced when incubated with neutrophils. This synergistic effect was not seen in cells from patients with adult respiratory distress syndrome. Fatty-acid analysis of neutrophils from patients with adult respiratory distress syndrome and controls showed remarkable similarity in all quantities of fatty acids measured except for arachidonic acid, where there was a 22% reduction in patients' cells compared with controls. Assay of the rate of generation of LTB4 and its degradation product, 20-hydroxy LTB4, revealed that reduced LTB4 generation in patients' neutrophils was not due to increased degradation of LTB4 by hydroxylase enzymes. When the amount of LTB4 being generated per milliliter of whole blood was analyzed in the patients with adult respiratory distress syndrome and compared with controls, it was determined that the potential to generate LTB4 in patients in the intensive care unit was three to five times greater than in controls.

Clinical observations indicate that gas exchange during high-frequency ventilation can be improved by decreasing the inspiratory to expiratory time ratio (I/E). Decreasing I/E at a fixed frequency may therefore allow a reduction of tidal volume (VT) without affecting gas exchange. This decreased VT may result in lower airway pressures, and thereby reduce the incidence of barotrauma. In order to quantify the effects of I/E on gas exchange, the relationship between carbon dioxide elimination and VT was studied in 6 mongrel dogs at I/E of 1/2, 1/1, and 2/1. Ventilation was provided by a jet-type high-frequency ventilator using a frequency of 5 Hz and VT of 17 to 100% of the anatomic dead space. Carbon dioxide elimination was found to vary inversely with (I/E)0.9, corroborating the clinical observations. These data add further evidence that I/E may be a useful parameter in optimizing high-frequency ventilation and provide a quantitative relationship that can be used to predict the effect that altering I/E will have on gas exchange.