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Biomedical subjects

C R Valeri

Publications and source records attributed to C R Valeri.

425 records · Page 24Linked to original sources

Ischemia in the isolated erythrocyte-perfused rat kidney. Protective effect of hypothermia.

We have examined the effects of 25 min of ischemia in the isolated erythrocyte-perfused rat kidney (IEPK). We have previously shown that, in this model, perfusate flow rate is close to blood flow rates in vivo and morphology is normal. The functional and morphological consequences of both warm ischemia (at 37 degrees C) and ischemia induced during mild hypothermia (27 degrees C) were compared. (1) Warm ischemia resulted in a 51% increase in renal vascular resistance (RVR) during the reflow period, while glomerular filtration rate (GFR) was reduced to 24% of control levels. (2) Kidneys subjected to warm ischemia showed marked morphological damage localized to the proximal tubule. There was dilatation of the proximal segments and widespread loss of the proximal brush border due both to shedding into the lumen and interiorization into the cell. In contrast to the proximal tubular damage, the cells of the medullary thick ascending limb segments were intact. However, the lumena of many of these segments were filled with cytoplasmic blebs and necrotic cell debris. There was also pronounced vascular congestion of the capillary plexus in the inner stripe of the outer medulla. (3) Hypothermia to 27 degrees C resulted in almost complete protection against ischemic injury: RVR and GFR were not different from control values. Also, kidneys subjected to cold ischemia showed only isolated areas of mild brush border damage; no evidence of tubular obstruction or vascular congestion was present. (4) Thus, warm ischemia in the IEPK results in functional and morphological effects comparable to those found in vivo. Post-ischemic vasoconstriction as well as medullary congestion occur in the absence of systemic hormones and renal nerves. These consequences of ischemia are prevented by modest hypothermia.

Animals↗

Effect of flow split on separation and stagnation in a model vascular bifurcation.

This is a study of the flow disturbance in a plastic model of an asymmetric vascular bifurcation. A sidearm was attached to the mainlimb at an angle of 15 degrees to the inlet flow axis. Water at steady flow was used and flow patterns were demonstrated by a dye injection technique. The proportion of inlet flow (Qi) exiting from the sidearm (Qs) was varied and flow patterns were recorded photographically. A laser Doppler anemometer (LDA) was used to measure near-wall velocity. At a physiologic Reynolds' number of 500, no flow disturbance occurred in the mainlimb when the sidearm was completely occluded. When the fraction of flow exiting from the sidearm (Qs/Qi) reached 0.19, a region of boundary layer separation developed along the wall of the mainlimb opposite the flow divider. This region of nearly static fluid spread circumferentially around the mainlimb as Qs/Qi increased. Near-wall velocity within the separation decreased and became negative when Qs/Qi = 0.31. When Qs/Qi reached 0.38, the separation enveloped the wall of the entire bifurcation with a shell of slowly moving fluid. At the same time, the rapidly moving mainstream impinged directly on the flow divider. There is a similarity between the region of separation seen in this model and the site of formation of atherosclerotic plaque at the carotid bifurcation. Separation may contribute to atherogenesis by creating a region of low wall shear at bifurcations.

Biomechanical Phenomena↗

Blood components in the treatment of acute blood loss: use of freeze-preserved red cells, platelets, and plasma proteins.

To avoid untoward reactions from blood transfusions and to make best use of the limited supply of blood, anesthesiologists and surgeons have many newly developed means at their disposal. Blood components should be separated from whole blood at the time of collection and prepared for either liquid or freeze-preservation. Citrate-phosphate-dextrose (CPD) blood should be separated into its components at room temperature within 4 hours of collection for greatest service from each collected unit. Red cell concentrates with hematocrits of 70 volumes percent can be prepared from the whole blood at the time of collection and frozen either shortly thereafter or after storage at 4 degrees C. for up to 3 weeks. Red-cell levels of 2, 3-diphosphoglycerate (2, 3-DPG) and adenosine triphosphate (ATP) can be increased by a rejuvenation process prior to freeze-preservation with either 40 percent W/V glycerol and storage at minus 80 degrees C. or with 20 percent W/V glycerol and storage at minus 150 degrees C. While hemorrhagic shock can best be managed with fresh whole blood, such blood is often not available; liquid- and freeze-preserved products serve as best substitutes. When previously-frozen washed red cells are used, crystalloid, colloid, coagulation factors, and platelets may also be required. Platelet concentrates stored at 4 degrees C. provide platelets that are hemostatically effective immediately upon infusion but have poor circulation. Platelet concentrates stored at 22 degrees C. provide platelets that have good circulation but upon transfusion have impaired hemostatic effectiveness. The coagulation factors and oncotic properties of plasma protein necessary for proper treatment of patients in hemorrhagic shock can be met by an adequate supply of fresh-frozen plasma and albumin. When liquid-stored red-cell concentrates or whole blood is given, filters must be used to remove the accumulated amorphous material, although the actual effects of the infused microaggregates are not yet known.

Blood Platelets↗

Whole blood viscosity in beta thalassemia minor.

Patients with heterozygous beta-thalassemia minor have a decreased hematocrit (HCT). Since the HCT is a primary determinant of whole blood viscosity, the known reduction in HCT in beta-thalassemia minor should lead to a measurable reduction of whole blood viscosity. The influence of the relatively lower mean corpuscular volume and consequent higher red blood cell count and beta-thalassemia minor on whole blood viscosity using a microporous viscometer has not previously been the subject of investigation. Accordingly, the blood of a group of normal and beta-thalassemia minor subjects was examined with a microporous viscometer to elucidate further the relations between whole blood viscosity, HCT, and red blood cell count. The data show that for normal and beta-thalassemia minor subjects a significant positive correlation (r = 0.65, p less than 0.01) exists between HCT and whole blood viscosity. However, the slope of the regression of whole blood viscosity and HCT of beta-thalassemia minor subjects was significantly higher z = 3.14, p less than 0.001) than that of normals. Thus, for any given HCT their whole blood viscosity was higher than that of normals. Studies of the relation of red blood cell counts to whole blood viscosity indicate the higher whole blood viscosity at a given HCT was related to the increased red blood cell counts in beta-thalassemia minor subjects. Because of the opposing interactions of HCT and red blood cell counts, the mean whole blood viscosity of the group of beta-thalassemia minor subjects examined was not significantly lower than the normal whole blood viscosity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Viscosity↗

Hemoglobin and 2,3-diphosphoglycerate levels in transfused dialysis patients with myocardial infarction.

Thirty frequently transfused patients on long term hemodialysis were studied and a similar number of age and sex-matched patients who were infrequently transfused were used as a control group to ascertain the influence of a previous myocardial infarction (MI) on transfusion requirements. The frequency of previous MI on electrocardiogram (ECG) in the transfused and control groups was similar (40 percent and 37 percent, respectively). In frequently transfused dialysis patients with MI, the hemoglobin level (transfusion trigger) at which these patients were transfused was higher than that of frequently transfused patients without MI (8.3 +/- 1.5 g per dl vs. 6.9 +/- 1 g per dl, p less than 0.01) which indicated that patients without MI tolerated a greater degree of anemia than those with MI. The 2,3-diphosphoglycerate (2,3-DPG) levels were significantly elevated in all transfused patients when compared to matched controls. However, levels of 2,3-DPG were significantly higher in MI patients receiving frequent transfusions than in other transfused patients, suggesting oxygen demands may not have been fully met despite the frequent transfusions. The results suggest levels of 2,3-DPG deserve further study in relation to the adequacy of tissue oxygenation in anemic dialysis patients.

2,3-Diphosphoglycerate↗

Assessment of blood interactions with the Therapore Apheresis System.

Biocompatibility evaluations are a complex issue involving not only classical toxicity and animal testing but also the interactions of biological systems. The evaluations of the Therapore Primary System are reported for three model systems: (1) in vitro human blood, (2) a baboon (Papio anubis) animal model, and (3) normal human volunteer apheresis. Measurements of both complement (C3a) and platelet (BTG and TXB2) activation products during the apheresis procedures are given as a sensitive indicator of biocompatibility. No statistically significant elevations of these activation products were observed. Thus, the Therapore System was found to have negligible perturbations of the interacting biological systems evaluated even with the highly sensitive RIA procedures employed. These observations and methods establish a solid foundation for comprehensive biocompatibility evaluations of future extracorporeal devices.

Animals↗

A solid phase urease-linked cellular immunosorbent assay for circulating polymorphonuclear binding immunoglobulin.

A cellular enzyme linked immunosorbent assay (CELISA) is reported for the detection of circulating polymorphonuclear granulocyte binding immunoglobulin (PBG) in patients' sera. The assay features a solid phase microtiter method in which the enzyme urease is fixed to the antihuman globulin conjugate reagent and uses 0.25 percent glutaraldehyde fixed normal human polymorphonuclear neutrophils (PMNs) as target cells. The assay gave positive results in four of 13 (31 percent) cases of idiopathic neutropenia in which an autoimmune etiology was suspected and one typical case of isoimmune neonatal neutropenia. In a group of 15 patients receiving multiple blood transfusions for chronic anemia, five (33 percent) showed significantly higher levels (p less than 0.001) of PBG than non-transfused normal donors. The PBG-CELISA appears potentially useful for the detection of autoimmune and isoimmune PMN antibodies and PMN binding IgG immune complexes.

Antigen-Antibody Complex↗

Low density lipoprotein cholesterol and whole blood viscosity.

Whole blood viscosity (WBV) was measured in a normal population and was analyzed in relation to packed cell volume, (hematocrit, PCV), fibrinogen, white blood cell count (WBC), platelet count, and plasma lipids, including total cholesterol, triglycerides, high density lipoprotein cholesterol (HDLc) and low density lipoprotein cholesterol (LDLc). Conventional assays were used for all blood and lipid measurements. Whole blood viscosity was measured under disaggregating conditions with a disposable, porous bed viscometer. As expected, the strongest correlation was seen between WBV and PCV (r = 0.78, p < 0.001). Significant positive correlations also were demonstrated between WBV and cholesterol (r = 0.22, p < 0.001), triglycerides (r = 0.14, p < 0.001) and LDLc (r = 0.21, p < 0.001). A significant negative correlation was found between HDLc and WBV (r = -0.20, p < 0.001). Correlation analysis by sex showed only the correlation of LDLc was significant for both men and women. A stepwise multiple regression analysis of WBV indicated that LDLc, fibrinogen (Fbg) and platelet (Plt) counts correlated independently of PCV to WBV. The equation derived from multiple regression and partial correlation analysis was: WBV (mPa.sec) = -9.317 + 0.0047 (LDLc) + 0.381 (PCV) + 0.00152 (Plt) + 0.0021 (Fbg). The calculated mean specific contribution of PCV was 90.8 percent, LDLc 3.5 percent, and fibrinogen 3.3 percent to observed mean WBV. This study shows that LDLc is the principal lipoprotein independently influencing whole blood viscosity and its effect is similar in magnitude to fibrinogen. Further studies to elucidate the mechanism and clinical significance of the effects of LDLc on WBV are indicated.

Adult↗

Blood rheology and 2,3-diphosphoglycerate levels after erythropoietin treatment.

Twenty-seven transfusion dependent patients with end-stage renal disease on long-term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3-diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p < 0.03). There were no major side effects or vascular complications.

2,3-Diphosphoglycerate↗