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Biomedical subjects

C R Valeri

Publications and source records attributed to C R Valeri.

At least 109 records · Page 6Linked to original sources

The effect of viable and nonviable autologous red blood cell transfusions on experimental bacteremia.

Nonviable red blood cells are rapidly cleared from the peripheral blood by the reticuloendothelial system. Since bacteria present in the blood stream are also cleared by the reticuloendothelial system, the possibility that nonviable red blood cells would interfere with the clearance of bacteria has been raised. Groups of dogs were studied in whom an experimental bacteremia was produced by the injection of E. coli (1 x 10(10)/kg). Bacterial clearance, endotoxin clearance, changes in mean arterial pressure, changes in oncotic pressure, and coagulation responses were monitored before and following autologous transfusion of approximately 10 cc/kg of packed red blood cells (PRBC) preserved with acid citrate dextrose or heparinized PRBC stored without preservative. In the latter blood product the majority of the red blood cells were nonviable. Clearance of E. coli over a 4-hr period was similar in the two transfused groups and in a control group without blood transfusion. Mean arterial pressure and blood pH fell significantly in all groups, but was again not significantly different among the groups studied. Endotoxin clearance, changes in oncotic pressure, blood oncotic proteins, and parameters of the blood coagulation system were also similar in all three groups. The results of this study indicate that in normal dogs made acutely bacteremic with E. coli, there were no significant differences over a 4-hr period in their hemodynamic or hematologic responses following transfusion of viable or nonviable autologous red blood cells.

Animals↗

Erythrocyte, plasma, and blood volume of healthy young men.

Insufficient data are readily available concerning the vascular fluid volumes of healthy young men. The primary purpose of this study was to develop a normative database for the erythrocyte volume, plasma volume, and blood volume of healthy young men. The secondary purposes were to relate these vascular fluid volumes to the person's body size and physical fitness level and to develop equations that enable their prediction. Fifty-one male soldiers with a mean age of 22 (range 18-35) yr and with a mean maximal aerobic power of 53 (range 42-65) ml O2.kg-1.min-1 had their lean body mass and vascular fluid volumes measured. Erythrocyte volume was measured by 51Cr, and plasma volume was measured by 125I. The findings concerning the erythrocyte volume, plasma volume, and blood volume of these young men are summarized as follows: 1) these vascular fluid volumes are accurately predicted from several indices of body size; 2) lean body mass is the anthropometric index that is most closely correlated to these vascular fluid volumes; 3) the erythrocyte volumes for a given body surface area are lower, particularly for large individuals, than values previously reported in surveys of undefined populations; 4) aerobic fitness is generally not related to vascular volumes; and 5) F-cell ratio is not related to aerobic fitness.

Adolescent↗

Electrode-derived myocardial pH measurements reflect intracellular myocardial metabolism assessed by phosphorus 31-nuclear magnetic resonance spectroscopy during normothermic ischemia.

To determine the ability of extracellular myocardial tissue pH measured with an intramural electrode to reflect myocardial intracellular metabolic status during normothermic ischemia, we studied 14 open-chest dogs with in vivo phosphorus 31-nuclear magnetic resonance spectroscopy during left anterior descending coronary artery occlusion (experimental group, group I, n = 7) or after a sham operation (control group, nonischemic, group II, n = 7). Phosphorus nuclear magnetic resonance spectra were acquired every 5 minutes at 4.7 tesla (256 averages, TR = 1000 msec, pulse width = 30 microseconds) with a 2 cm two-turn radiofrequency surface coil. Intracellular myocardial adenosine triphosphate peak area was normalized to an external phosphate standard. The change in adenosine triphosphate peak area was expressed as percent of baseline value. During 3 hours of normothermic ischemia the observed extracellular myocardial pH correlated with nuclear magnetic resonance-calculated myocardial pH in the ischemic dogs with an average r value of 0.94 (p less than 0.0001). During this same interval, the fall in extracellular myocardial pH correlated with the loss of adenosine triphosphate peak in each ischemic dog, with an average r value of 0.91 (p less than 0.0001). Thus extracellular myocardial pH, measured with an intramural electrode, correlated with nuclear magnetic resonance-derived myocardial pH and loss of myocyte adenosine triphosphate peak content and reflected the metabolic status of the myocyte during ischemia. These data validate the use of extracellular myocardial pH to assess the adequacy of myocardial preservation during aortic crossclamping for cardiac operations.

Adenosine Triphosphate↗

Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass.

Thirty-seven patients undergoing cardiopulmonary bypass operations were studied to assess the effect of skin temperature on platelet function. Differences in skin temperature between the two arms were created during bypass, at the completion of bypass, and at 2 and 24 hours after the completion of bypass. In each of 37 patients the temperature of one arm was increased with a water-filled blanket set at 40 degrees C. In 11 of these patients the other arm was allowed to equilibrate with the environment, and in the other 26 patients the arm was cooled with ice. Except for the differences in local skin temperature between the two arms, all factors known to affect the patient's bleeding time were similar. Measurements were made of bleeding times and the levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha in shed blood obtained at the template bleeding time site. In the 33 patients not treated with aspirin, local hypothermia produced an increased bleeding time and a significant reduction in the thromboxane B2 level at the bleeding time site, but no reduction in 6-keto-prostaglandin F1 alpha level. Local rewarming produced a significant increase in the shed blood thromboxane B2 level. In the four patients treated with aspirin, local hypothermia produced no differences in bleeding times or shed blood levels of thromboxane B2 or 6-keto-prostaglandin F1 alpha. These data show the benefits of rewarming patients with hypothermia who have nonsurgical blood loss to restore to normal both core and peripheral temperatures before resorting to the transfusion of homologous blood products.

6-Ketoprostaglandin F1 alpha↗

Inactivation of viruses in red cell and platelet concentrates with aluminum phthalocyanine (AIPc) sulfonates.

Aluminum phthalocyanine tetrasulfonates (AIPcS) are photoactive compounds with absorption maxima at 665-675 nm. The inactivation of viruses (vesicular stomatitis virus, VSV; human immunodeficiency virus, HIV) added to either whole blood or red blood cell concentrates (RBCC) and platelet concentrates (PC) on treatment with tetrasulfonated AIPc (AIPcS4) was evaluated. Treatment of RBCC with 10 microM AIPcS4 and 44 J/cm2 visible light resulted in the inactivation of greater than or equal to 10(5.5) infectious doses (TCID50) of cell-free VSV, greater than or equal to 10(5.6) TCID50 of cell-associated VSV, and greater than or equal to 10(4.7) TCID50 of cell-free sindbis virus. Both greater than or equal to 10(4.2) TCID50 of cell-free and greater than or equal to 10(3.6) TCID50 of cell-associated forms of HIV were also shown to be inactivated. Encephalomyocarditis virus, used as a model for nonenveloped viruses, was not inactivated. Equivalent virus kill with Photofrin II required a substantially higher concentration of dye and longer exposure to visible light. Following AIPcS4 treatment, red cell integrity was well maintained as judged by the low level (less than 2%) of hemoglobin release immediately following treatment and on subsequent storage, by measurements of erythrocyte osmotic fragility, and by the normal recovery and circulatory survival on infusion of treated, autologous red blood cells in baboons. Treatment of PC with 10 microM AIPcS4 and 44 J/cm2 visible light also resulted in effective virus kill (greater than or equal to 10(5.5) TCID50) of VSV; however, both the rate and extent of platelet aggregation in response to collagen addition declined by at least 50%. Based on these results, further characterization of AIPcS4-treated RBCC is justified.

Animals↗

Pathophysiology of ischaemia reperfusion injury: central role of the neutrophil.

Ischaemia is a common clinical event leading to local and remote injury. Evidence indicates that tissue damage is largely caused by activated neutrophils which accumulate when the tissue is reperfused. If the area of ischaemic tissue is large, neutrophils also sequester in the lungs, inducing non-cardiogenic pulmonary oedema. Ischaemia reperfusion injury is initiated by production of reactive oxygen species which initially appear responsible for the generation of chemotactic activity for neutrophils. Later, once adherent to endothelium, neutrophils mediate damage by secretion of additional reactive oxygen species as well as proteolytic enzymes, in particular elastase. Therapeutic options for limiting ischaemia reperfusion injury include inhibition of oxygen radical formation, pharmacological prevention of neutrophil activation and chemotaxis, and also the use of monoclonal antibodies which prevent neutrophil-endothelial adhesion, a prerequisite for injury.

Arachidonic Acids↗

Thromboxane A2 induces leukotriene B4 synthesis that in turn mediates neutrophil diapedesis via CD 18 activation.

Previous studies have indicated that thromboxane (Tx) and leukotriene (LT) B4 act synergistically to induce neutrophil (PMN) adhesion in the microvasculature. This study explores the ability of Tx to induce LTB4 synthesis, which then leads to activation of PMN and endothelial adhesion receptors. Tx-mimic (U46619, 1 microgram/ml) was administered into abraded skin chambers placed on the backs of rabbits (n = 6). After 3 hr LTB4 was synthesized in the blister fluid at 385 pg/ml, a value higher than levels in saline-treated blisters, 10 pg/ml (P less than 0.05). The LTB4 generation following Tx-mimic was correlated (P less than 0.05, r = 0.70) with neutrophil diapedesis. These averaged 645 PMN/mm3, values higher than saline values of 20 PMN/mm3 (P less than 0.05). Intravenous (iv) treatment of other rabbits (n = 4) with the lipoxygenase inhibitor diethylcarbamazine at 60 mg/kg, followed by 40 mg/kg/hr, prevented Tx-mimic-induced LTB4 synthesis (10 pg/ml) and diapedesis (19 PMN/mm3) (both P less than 0.05). Intravenous treatment of yet other rabbits (n = 4) with the anti-CD 18 monoclonal antibody R 15.7 at 1 mg/kg abolished Tx-induced diapedesis (3 PMN/mm3) (P less than 0.05). In contrast, local administration of 3 ng of the protein synthesis inhibitor actinomycin D, to prevent expression of endothelial adhesion proteins, limited TNF- but not Tx-induced diapedesis. The data indicate that Tx-induced diapedesis is mediated by the generation of LTB4 and the activation of neutrophil CD 18 but not endothelial adhesion proteins.

Animals↗

The estimation of whole blood viscosity by a porous bed method.

A significant impediment in determining the relative contribution of whole blood viscosity to the pathogenesis of cardiovascular and cerebrovascular disease has been the lack of an uncomplicated method to measure whole blood viscosity. To address this problem, a simplified porous bed viscometer has been developed to measure whole blood viscosity. Whole blood is passed through a porous bed of branching channels with a mean pore diameter of 69.6 +/- 20.2 microns and an estimated mean shear rate of 19.6 seconds-1. The effects of sample collection, sample storage, and temperature are described. The mean whole blood viscosity of 242 healthy persons was 22.7 +/- 5.3 seconds, which, when corrected to centipoise using Darcy's equation, corresponds to an apparent viscosity of 5.7 +/- 1.3 cp. There was a significant difference in the whole blood viscosity of normal men and women related to their different packed cell volumes. Platelets and granulocytes influenced whole blood viscosity in proportion to their contribution to the total packed cell volume. Fibrinogen levels did not significantly influence measured whole blood viscosity, which is consistent with the disaggregating conditions and the mean shear rate of the instrument. The porous bed viscometer is a convenient means to measure whole blood viscosity and it should be useful as a screening test for clinical and epidemiologic studies.

Anticoagulants↗

Intravascular chemoattractants inhibit diapedesis by selective receptor occupancy.

An extravascular chemoattractant leads to migration of polymorphonuclear neutrophils (PMN) to that site, whereas intravascular administration leads to PMN oxidative activity and sequestration in microvessels but no diapedesis. This study examines the inhibitory role of intravascular chemoattractants. Rabbits (n = 37) were pretreated with zymosan-activated plasma (ZAP), leukotriene (LT) B4, or thromboxane (Tx) mimic. These agents were given intra-arterially, topically into plastic chambers taped atop sites of dermabrasion on the back, or into a lobar bronchus (n = 35). Intra-arterial injection of each chemoattractant resulted, 10 min later, in a 29-42% increase in intracellular PMN H2O2. In saline-infused animals, topical administration of the chemoattractants into dermabrasion chambers resulted in PMN accumulation per cubic millimeter after 3 h of 600 with ZAP, 536 with LTB4, and 643 with Tx mimic; all values higher than 46 with saline and 63 with normal plasma (all P less than 0.05). In other saline-infused animals, lobar lung aspiration of chemoattractants led to diapedesis as measured in bronchoalveolar lavage (BAL) fluid (PMN x 10(4)/ml) after 3 h: 19.0 with ZAP, 11.2 with LTB4 and 14.5 with Tx mimic, all greater than aspiration with saline or normal plasma 4.0 and 4.9, respectively (all P less than 0.05). Intra-arterial chemotactic administration inhibited subsequent PMN diapedesis in response to that same chemoattractant, both in dermabrasion chambers and in BAL fluid. When different intra- and extra-vascular chemoattractants were used diapedesis was promoted. Thus Tx infused intra-arterially and ZAP applied to a blister or lobar bronchus led to rapid cell migration and increased cell numbers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neutrophil elastase and oxygen radicals: synergism in lung injury after hindlimb ischemia.

Hindlimb ischemia and reperfusion lead to lung injury dependent on activated polymorphonuclear neutrophils (PMN) adherence. This study tests whether elastase and oxygen radicals participate in PMN-induced injury once they have become sequestered in lungs. Anesthetized rats treated with saline (n = 9) or the specific elastase inhibitor methoxysuccinyl-L-Ala-L-Ala-L-Pro-L-Val-chloromethylketone (MAAPV, n = 6) underwent 4 h of bilateral hindlimb tourniquet ischemia followed by 4 h of reperfusion. At this time, in saline-treated rats, PMN were sequestered in lungs as assayed by myeloperoxidase activity [(MPO) 51 +/- 5 U/g tissue], higher than MPO in saline-treated sham rats (n = 9; 18 +/- 3 U/g MPO; P less than 0.01); bronchoalveolar lavage (BAL) fluid leukotriene (LT) B4 levels increased to 594 +/- 46 relative to 200 +/- 38 pg/ml in shams (P less than 0.01); increased permeability was documented by BAL fluid protein content of 599 +/- 91 compared with 214 +/- 35 micrograms/ml in sham animals (P less than 0.01); and edema was shown by increase in lung wet-to-dry weight ratio of 4.77 +/- 0.14 relative to 4.00 +/- 0.09 in sham rats (P less than 0.01). In MAAPV-treated animals, lung neutrophil sequestration (62 +/- 9 U/g MPO) and rise of LTB4 in BAL fluid (780 +/- 244 pg/ml) were not affected, but both BAL fluid protein (335 +/- 32 micrograms/ml) and lung wet-to-dry weight ratio (4.21 +/- 0.17) were reduced (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nitric oxide inhibition in rats improves blood pressure and renal function during hypovolemic shock.

We have examined the systemic and renal hemodynamic effects of nitric oxide (NO) inhibition with NG-monomethyl-L-arginine (L-NMMA) in normotensive rats as well as in rats with hypovolemic shock induced by hemorrhage. L-NMMA increased mean arterial blood pressure (MAP) from 114 +/- 4 to 130 +/- 6 mmHg (P less than 0.05) in the nonhemorrhaged rats and from 61 +/- 3 to 89 +/- 3 mmHg (P less than 0.05) in the hypovolemic animals. The absolute increase in MAP was greater in the hypovolemic (31 +/- 3 mmHg) than in the nonhemorrhaged (15 +/- 2 mmHg) rats (P less than 0.05). An excess of L-arginine reversed the increase in MAP induced by L-NMMA in both groups. In the normotensive rats the increase in blood pressure was associated with an elevation in renal vascular resistance (RVR; from 6.5 +/- 0.7 to 8.2 +/- 0.9 mmHg.ml-1.min-1, P less than 0.05) so that renal plasma flow (RPF) and glomerular filtration rate (GFR) were unchanged. In contrast, in the hypotensive rats, the marked increase in MAP induced by L-NMMA infusion was not associated with a significant increase in RVR. As a result L-NMMA increased both RPF (from 6.0 +/- 0.4 to 7.8 +/- 0.4 ml/min, P less than 0.05) as well as GFR (from 1.7 +/- 0.2 to 2.5 +/- 0.2 ml/min, P less than 0.05). We conclude that NO is produced and modulates peripheral resistance in normotensive rats as well as in rats with hypovolemic shock. In the hypovolemic rats NO inhibition substantially improves RPF and GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide.

Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neutrophil accumulations due to pulmonary thromboxane synthesis mediate acid aspiration injury.

Acid aspiration leads to lung injury associated with high levels of plasma thromboxane (Tx). This study tests the role of Tx synthesis by the aspirated lung segment in mediating local and remote neutrophil (PMN) sequestration, alveolar diapedesis, and permeability edema. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the installation of either 0.1 ml saline (n = 18) or the Tx synthase inhibitor OKY 046 (0.1 mg/kg in 0.1 ml, n = 18). Twenty minutes later either 0.1 ml 0.1 N HCL or 0.1 ml saline was similarly introduced (n = 18). Three hours later, in the saline-HCl group, the rise in Tx concentration in both plasma (1,340 pg/ml) and bronchoalveolar lavage (BAL) fluid (2,100 pg/ml) was higher than that in the saline-saline aspirated control group (350 and 115 pg/ml, respectively; both P less than 0.05). In the acid-aspirated lung PMN sequestration [87 PMN/10 high-power fields (HPF)] and diapedesis (96 x 10(4) PMN/ml in BAL) were higher than control values of 7 PMN/10 HPF and 3 x 10(4) PMN/ml (both P less than 0.05). Acid aspiration induced local permeability edema with a high protein concentration in BAL of 3,350 micrograms/ml and an increase in lung wet-to-dry weight ratio (W/D) of 6.6, both higher than control values of 482 micrograms/ml and 3.4, respectively (P less than 0.05). Leukosequestration in the aspirated side started at 30 min and was progressive over a 3-h monitoring period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role for tumor necrosis factor as mediator of lung injury following lower torso ischemia.

Ischemia and reperfusion of the ischemic lower torso lead to a neutrophil- (PMN) dependent lung injury characterized by PMN sequestration and permeability edema. This mimics the injury seen after infusion of tumor necrosis factor alpha (TNF), a potent activator of PMN and endothelium. This study tests whether TNF is a mediator of the lung injury after lower torso ischemia. Anesthetized rats underwent 4 h of bilateral hindlimb tourniquet ischemia, followed by reperfusion for 10 min, 30 min, 1, 2, 3, and 4 h (n = 6 for each time point). Quantitative lung histology indicated progressive sequestration of PMN in the lungs, 25 +/- 3 (SE) PMN/10 high-power fields (HPF) 10 min after reperfusion vs. 20 +/- 2 PMN/10 HPF in sham animals (NS), increasing to 53 +/- 5 PMN/10 HPF after 4 h vs. 23 +/- 3 PMN/10 HPF in sham animals (P less than 0.01). There was lung permeability, shown by increasing protein accumulation in bronchoalveolar lavage (BAL) fluid, which 4 h after reperfusion was 599 +/- 91 vs. 214 +/- 35 micrograms/ml in sham animals (P less than 0.01). Similarly, there was edema, shown by the lung wet-to-dry weight ratio, which increased by 4 h to 4.70 +/- 0.12 vs. 4.02 +/- 0.17 in sham animals (P less than 0.01). There was generation of leukotriene B4 in BAL fluid (720 +/- 140 vs. 240 +/- 40 pg/ml, P less than 0.01), and in three of six rats tested at this time TNF was detected in plasma, with a mean value of 167 pg/ml. TNF was not detectable in any sham animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Thromboxane mediates diapedesis after ischemia by activation of neutrophil adhesion receptors interacting with basally expressed intercellular adhesion molecule-1.

Ischemic injury is characterized by neutrophil (PMN)--endothelial cell adhesion and diapedesis associated with thromboxane (TX) generation. Neutrophil-endothelial cell interaction is regulated in part by the leukocyte adhesion receptor CD 18 glycoprotein complex and the endothelial intercellular adhesion molecule-1 (ICAM-1). This study tests the role of TX in ischemia-induced diapedesis and evaluates whether the diapedesis is regulated by neutrophil or endothelial adhesion receptors. Plasma derived from rabbit hind limbs made ischemic for 3 hours (n = 6) and reperfused for 10 minutes had increased levels of TXB2 3,450 pg/ml, which was higher than sham rabbit (n = 6) values of 653 pg/ml (p less than 0.05). When introduced into abraded skin chambers placed on the dorsum of other normal rabbits (n = 6), this ischemic plasma induced 1,000 pg/ml of new TX synthesis and diapedesis of 1,235 PMN/mm3. The total TX concentration and PMN accumulations in blister fluid were correlated (r = 0.88, p less than 0.05). In contrast, sham rabbit plasma induced no TX synthesis and diapedesis of only 77 PMN/mm3 (p less than 0.05). Administration of 50 ng/ml of authentic TXB2 into blisters induced an accumulation of 453 PMN/mm3, which was higher than that in saline controls (18 PMN/mm3) (p less than 0.05). Pretreatment of normal rabbits used for the diapedesis assay (n = 4) with the TX synthetase inhibitor OKY 046 (2 mg/kg/hr) limited ischemic plasma and authentic TXB2 induced diapedesis to 142 and 76 PMN/mm3, respectively (both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of the Quantitative Buffy Coat (QBC) method to detect malaria-infected red blood cells.

The conventional thin blood film method of detecting malaria is a long and tedious procedure, requiring significant technical expertise. In this study, we compared the Quantitative Buffy Coat (QBC) capillary tube method, which requires only minimal technical training, to the thin blood film method, and found it to be not only more rapid but also more sensitive than the thin blood film method in the detection of parasitized red blood cells. We do not suggest that the QBC capillary method can replace the conventional thin blood film method for the detection of malaria since it does not identify or quantitate the parasite species, only that it would serve as a valuable screening test.

Animals↗

Effect of graft material on loss of erythrocytes after aortic operations.

It has been suggested that loss of erythrocytes after abdominal aortic grafting is influenced by the type of synthetic graft used. A prospective randomized study was done to compare loss of erythrocytes in patients receiving Dacron (polyester fiber, Meadox woven double velour) and Gore-Tex (polytetrafluoroethylene [PTFE]) grafts during the perioperative period. A total of 25 patients (13 Dacron and 12 PTFE) was studied, including 21 with abdominal aortic aneurysms and four with aortoiliac occlusive disease. Erythrocyte volume (EV) was measured using 51Cr-labeled autologous erythrocytes on the day prior to the operation, one to two hours after the operation when the patients were hemodynamically stable and 24 hours postoperatively. In addition to measurements of 51Cr EV and the volume of intraoperatively salvaged washed erythrocytes, the length of storage of the units of homologous liquid preserved erythrocytes at 4 degrees C. prior to transfusion were recorded. The mean intraoperative erythrocyte loss (+/- S.D.) for the Dacron group was 892 +/- 543 milliliters and for the PTFE group, 842 +/- 403 milliliters (p = NS). Patients in the Dacron group received intraoperatively 2.2 +/- 1.6 (units +/- S.D.) milliliters with a range of zero to 4 units of homologous liquid preserved erythrocytes and patients in the PTFE group received 1.2 +/- 1.2 milliliters with a range of zero to 3 units of homologous liquid preserved erythrocytes (p = NS). The mean total loss of erythrocytes (+/- S.D.) was 1,055 +/- 649 milliliters for the Dacron group and 978 +/- 503 milliliters for the PTFE group (p = NS). Despite inherent differences in graft material, there were no significant differences in intraoperative or post-operative loss of erythrocytes or in the number of homologous units of liquid preserved erythrocytes transfused with a p value of less than 0.05 considered significant.

Aged↗

Modulation of pulmonary permeability in vivo with agents that affect the cytoskeleton.

In vitro studies show that the cytoskeleton of the microvascular barrier moderates polymorphonuclear leukocyte (PMN) diapedesis and the transport of macromolecules. This in vivo study tests indirectly whether the cytoskeleton of the pulmonary microvasculature responds similarly to agents known to reorganize the cytoskeleton to alter diapedesis and permeability in vitro. One of four agents, saline solution, cytochalasin B (which promotes actin microfilament disassembly), leukotriene (LT) B4 (PMN chemoattractant), or phalloidin (which promotes and stabilizes F-actin polymerization) was introduced into the bronchus of the anterior segment of the left lung of anesthetized rats (n = 152) through a tracheostomy and fine-bore cannula. Twenty minutes later, saline solution, cytochalasin B, LTB4, or phalloidin was similarly introduced. PMN accumulations (x 10(4) cells/ml), protein concentration in bronchoalveolar lavage fluid, and lung wet/dry weight ratios were measured 3 hours later. When the initial and secondary treatments were saline solution, PMN accumulations were 3 +/- 1 cells/ml and the protein level was 274 +/- 48 micrograms/ml. Secondary treatment of the saline-treated group with cytochalasin B or LTB4 led to increases in PMN to 18 +/- 2 and 9 +/- 2 cells/ml and protein to 960 +/- 50 and 840 +/- 40 micrograms/ml (p less than 0.05); secondary treatment with phalloidin was similar to that with saline solution. With saline solution used for both treatments, the wet/dry ratio was 3.4 +/- 0.2. Primary saline solution and secondary treatments with either cytochalasin B or LTB4 led to a similar increase in wet/dry ratios to 3.9 +/- 0.1 (p less than 0.05), whereas phalloidin was without effect (3.5 +/- 0.3). Initial cytochalasin B treatment followed by LTB4 led to increased PMN diapedesis (43 +/- 6 cells/ml and wet/dry ratio 4.3 +/- 0.2) (p less than 0.05). Secondary phalloidin treatment attenuated the cytochalasin B effect with counts of 12 +/- 2 PMN/ml, protein levels of 460 +/- 30 micrograms/ml, and a lower wet/dry ratio of 3.7 +/- 0.1 (p less than 0.05). Even more striking, phalloidin as initial treatment further reduced the cytochalasin B effect to 7 +/- 1 PMN/ml, whereas protein level was 490 +/- 60 micrograms/ml and wet/dry ratio was 3.5 +/- 0.1 (p less than 0.05). Further, phalloidin, given initially, attenuated the effect of secondary treatment with LTB4, resulting in fewer cells (4 +/- 2 PMN/ml), a lower wet/dry ratio (3.4 +/- 0.1), and protein level of 650 +/- 20 micrograms/ml (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗