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Biomedical subjects

J R Hess

Publications and source records attributed to J R Hess.

At least 55 records · Page 3Linked to original sources
PubMed1994

Increased vascular resistance with hemoglobin-based oxygen carriers.

PURPOSE: To compare the effects of resuscitation with hemoglobin-based oxygen-carriers and conventional resuscitation fluids on hemodynamics, oxygen transport, and oxygen consumption in an animal model of the use of these fluids in the treatment of hemorrhagic shock. PROTOCOL: Twenty-eight immature swine were surgically prepared, allowed to recover five days, water deprived for 48 hours, hemorrhaged of 25 ml/kg over one hour, resuscitated promptly with 1) Ringer's lactate, 75 ml/kg, 2) 7% albumin in Ringer's acetate, 25 ml/kg, 3) 9% unmodified hemoglobin in Ringer's acetate, 25 ml/kg, or 4) 9% alpha alpha-crosslinked hemoglobin in Ringer's acetate, 25 ml/kg, and observed with three hours of hemodynamic and oxygen transport measurements. RESULTS: Systemic and pulmonary vascular resistance were increased in hemoglobin-treated animals to more than twice the levels seen in crystalloid- or colloid-treated controls. Oxygen consumption and the rate of correction of lactic acidosis were not increased in hemoglobin-treated animals. CONCLUSIONS: Increased vascular resistance limits the oxygen transport benefit of cell-free-hemoglobin-based oxygen carriers. Cell-free-hemoglobin-induced increases in vascular resistance may place animals' hearts on an unfavorable portion of the Frank-Starling curve as well as complicate further medical treatment by reducing the animals' tolerance to increases in blood viscosity.

Animals↗
PubMed1994

Denatured hemoglobin increases human blood mononuclear cell procoagulant effect.

PURPOSE: To study the effects of the common contaminants of hemoglobin solutions, red cell stroma, bacterial endotoxin, and denatured hemoglobin on the causes of the thrombotic lesions which have been reported in animal experiments after hemoglobin administration. PROTOCOL: Human blood mononuclear cells were isolated on Ficoll-Hypaque gradients and incubated with hemoglobin from the LAIR production facility, red cell stroma, bacterial endotoxin (E. coli, Wittaker Bioproducts), and hemoglobin denatured by boiling. Incubations were performed separately and in combinations. Mononuclear cells were then lysed and assayed for procoagulant activity in a recalcification time assay. RESULTS: Only bacterial endotoxin and hemoglobin denatured by boiling increased the procoagulant activity of human blood mononuclear cells. Denatured hemoglobin mixed one part in eight with undenatured hemoglobin increased mononuclear cell procoagulant activity by more than ten-fold that of the undenatured hemoglobin control. CONCLUSIONS: The study suggests that denatured but not undenatured hemoglobin causes increased blood procoagulant activity which is thought to be a marker of macrophage activation. These findings suggest a possible mechanism of toxicity of cell-free hemoglobins and the need for sensitive measures of hemoglobin denaturation.

Blood Coagulation Factors↗
PubMed1994

Diaspirin cross-linked hemoglobin: tissue distribution and long-term excretion after exchange transfusion.

This report describes the tissue distribution and long-term (14-day) excretion of hemoglobin cross-linked between the alpha-chains (alpha alpha Hb) with carbon 14-labeled bis(3,5-dibromosalicyl)fumarate. Fully conscious, chronically cannulated rats (n = 40) were treated with a 50% isovolemic exchange transfusion (ET) with solutions of 14C-labeled alpha alpha Hb (8.0 gm/dl) and were then monitored for as long as 14 days. Thirteen tissue types were analyzed for radioactivity by liquid scintillation counting. The highest concentration of label was found in the kidney and in tissues of the reticuloendothelial system (i.e., spleen, bone marrow, and liver). The 14C-labeled alpha alpha Hb did not appear to cross the blood-brain barrier, because radioactivity in the brain was barely detectable. The dose of 14C-labeled alpha alpha Hb (2.4 gm Hb/kg) produced an initial plasma Hb level of 4.6 gm/dl, with a half-life in the plasma of 5.0 hours. The peak concentration in kidney, spleen, and liver occurred at 24 hours after ET, when at least 92% of the 14C-labeled alpha alpha Hb in plasma had been cleared. At 48 hours, red casts were seen in a tiny number of renal tubules in some rats. By 14 days, up to 64% of the injected radioactivity had been recovered in urine and about 10% was recovered in feces. Most excretion occurred 24 to 48 hours after ET. This study demonstrated that 2 weeks were required for the metabolic degradation and elimination of a large dose of alpha alpha Hb in rats.

Animals↗
PubMed1993

Acute changes in systemic blood pressure and urine output of conscious rats following exchange transfusion with diaspirin-crosslinked hemoglobin solution.

This report describes acute changes in systemic blood pressure and urine output observed after a 50-percent isovolemic exchange transfusion (ET) with diaspirin-crosslinked hemoglobin (alpha alpha Hb). Stroma-free Hb was crosslinked between the alpha chains by using a 14C-labeled diaspirin, bis(3,5-dibromosalicyl)fumarate. Forty conscious, chronically cannulated rats underwent ET with 14C-labeled alpha alpha Hb solution (8.0 g/dL [80 g/L]). This resulted in systemic hypertension for 3 to 4 hours after ET (mean arterial pressure rose from 120 to 145 torr at 1 to 2 hours after ET) and mild bradycardia for 2 to 3 hours (heart rate decreased from 420 to 335 beats/min [bpm] before stabilizing at 360 +/- 10 bpm). This was accompanied by significant diuresis immediately after ET (5- 6-fold increase in urine output, which normalized after 12 hours), and mild hemoglobinuria. The total amount of Hb recovered in the urine was < 5 percent of the injected dose. Reversed-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the presence of crosslinked alpha alpha Hb molecules in the urine. Renal excretion of radioactivity was significantly greater, with 20 percent of total radioactivity being eliminated within 24 hours. The plasma half-life for alpha alpha Hb was 5 hours (administered dose, 2.4 g Hb/kg body weight). Thus, infusion of alpha alpha Hb caused a transient systemic hypertension, and intramolecular crosslinking alone was not enough to exclude completely the filtration of alpha alpha Hb by the kidneys.

Animals↗
PubMed1993

In vivo viability studies of two additive solutions in the postthaw preservation of red cells held for 3 weeks at 4 degrees C.

An optimized additive solution was developed for the postthaw preservation of red cells that contained adenine, glucose, disodium phosphate, and citrate buffer. This solution, called AS-17, was compared to AS-3 solution in a clinical trial using 40 subjects (20 in each arm). Fresh-frozen red cells were thawed and deglycerolized after 1 to 18 months and subjected to a second period of storage in either solution for up to 3 weeks at refrigerator temperatures. Both solutions yielded red cells with 24-hour survivals in excess of 75 percent. Cells stored in AS-3 for 21 days had a mean survival of 77 +/- 8 percent and cells stored in AS-17 a mean survival of 79 +/- 11 percent. The AS-17 solution resulted in improved maintenance of pH, p50, and 2,3 DPG compared to that with AS-3, but both solutions appear adequate for 3 weeks of postthaw storage.

2,3-Diphosphoglycerate↗
PubMed1993

Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin.

Human hemoglobin (Hb) and Hb cross-linked between the alpha subunits with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) were used to treat hemorrhagic shock in water-deprived swine. Water was withheld for 48 h to induce a 10% loss of body mass, and 25 ml/kg of blood were removed in 1 h to produce circulatory shock. Swine were resuscitated with 1) Hb, 2) alpha alpha Hb, 3) human serum albumin, or 4) Ringer lactate. Mild high-output renal failure was observed in the non-cross-linked Hb-treated animals but not in other groups of animals. Swine treated with Hb and alpha alpha Hb had increases in plasma creatine kinase and lactate dehydrogenase activity that were resolved within 7 days. Both Hb- and alpha alpha Hb-treated swine displayed marked elevations of mean blood pressure in the systemic (39 +/- 6 Torr) and pulmonary (20 +/- 6 Torr) circulations that continued for 3 h and were associated with reduced cardiac output and a doubling of the systemic and pulmonary vascular resistances. Oxygen delivery was equivalent, and the rate of correction of the lactic acidosis was equal in all groups.

Animals↗
PubMed1992

The effects of 7.5% NaCl/6% dextran 70 on coagulation and platelet aggregation in humans.

The combination solution of 7.5% NaCl/6% dextran 70 (HSD) administered IV gives hemodynamic improvement in the treatment of hemorrhagic hypotension. Since earlier dextran solutions were reported to interfere with blood coagulation, the effects of HSD on the prothrombin time (PT), the activated partial thromboplastin time (APTT), platelet aggregation, and platelet concentration were studied. The HSD mixed with human plasma (1:5 and 1:10) slightly prolonged PT, but had no effect on the APTT, compared with saline controls. The HSD also decreased human platelet aggregation at the 1:5 dilution. In separate mixing studies, the hypertonic saline component of HSD was associated with the prolongation of PT and decreased platelet aggregation. The data from these studies indicate that at its proposed therapeutic dose, HSD is expected to have minimal effect on blood coagulation.

Adult↗
PubMed1992

Dehydration and shock: an animal model of hemorrhage and resuscitation of battlefield injury.

We have developed a porcine model of the anticipated military use of oxygen-carrying resuscitation solutions. The objective is to determine whether toxicity under adverse conditions will limit further development of hemoglobin-based products. Splenectomized immature female swine are used because of their extensive use in the evaluation of other resuscitation solutions. Five days prior to each experiment, central vascular catheters and a renal arterial flow probe are surgically placed in the animals. After recovery and weight gain has resumed, animals are placed in metabolic cages and deprived of water for 48 hours to produce hyperosmolar dehydration resulting in loss of approximately 7% of body weight. We remove 38% of estimated blood volume, 25 ml/kg, over one hour by a controlled logarithmic hemorrhage. Resuscitation is by administration of a fixed volume of test solution. Hemodynamic function is observed but not further therapy is given for three hours, a period corresponding to evacuation in the field. After this period, corresponding to arrival at a field hospital, the animals' blood is returned. Swine are then observed in metabolic cages for an additional 7 days while blood and urine are sampled daily. At the end of this period, animals are anesthetized, urinary catheters are implanted, and creatinine clearances are measured. Swine are than euthanized, and their tissues are examined. In a pilot study, resuscitation was performed with either Ringer's lactate, albumin, stroma-free hemoglobin, or cross-linked (alpha alpha Hb) hemoglobin. All animals survived.

Animals↗
PubMed1992

Pharmacokinetic studies in the rat on a o-raffinose polymerized human hemoglobin.

We have studied the plasma half-life (T 1/2), oxygen-binding affinity (P50), organ distribution, and excretion of the individual molecular weight (MW) components of human hemoglobin polymerized with periodate-oxidized, ring-opened raffinose (oR poly-Hb), following transfusion in the rat. The model was an isovolemic 50% exchange transfusion in the conscious, chronically catheterized rat. Total plasma Hb levels yielded a (T 1/2) of 10 to 11 hr for oR poly-Hb. The T 1/2 values of individual MW components of the poly-Hb as determined by size-exclusion HPLC were approximately: 4 hr for the monomeric fraction (Hb)1, 9 hr for the dimer (Hb)2, and 15 hr for the fraction representing trimers to nanomers (Hb)3-9. The P50 values of plasma samples containing oR poly-Hb (collected from 0-24 hr after exchange) remained unchanged at 28 +/- 3 mmHg. oR stabilized and polymerized Hb were not excreted via the kidneys. Hepatic and renal distribution as well as plasma and renal clearance were determined by liquid scintillation counting using individual tritium [3H] labelled MW components purified from [3H]-oR poly-Hb: (Hb)1/2, (Hb)1, (Hb)2, (Hb)3&4, and (Hb) greater than 9. In kidney, uptake (determined by the relative concentration of radioactivity) decreased with increasing MW of the labelled component. Conversely, in liver, uptake increased with increasing MW. Plasma and renal clearance results were consistent with those obtained by HPLC analysis. Hematocrit levels returned from a 20% post-transfusion level to normal pre-transfusion levels (44%) within 10 days after the exchange.

Animals↗
PubMed1991

Preparation, properties, and plasma retention of human hemoglobin derivatives: comparison of uncrosslinked carboxymethylated hemoglobin with crosslinked tetrameric hemoglobin.

Human hemoglobin A has been crosslinked by diisothiocyanatobenzenesulfonate to give a limited number of products in a yield of approximately 70%. The predominant product was crosslinked between subunits within a tetramer and had a Mr of 64,000; no higher Mr species were formed. This product had one crosslink per tetramer located between the NH2 termini of its alpha chains, as established by HPLC analysis, amino acid analysis, Edman degradation, and mass spectrometry. This crosslinked derivative had a slightly increased oxygen affinity [P50 = 9 mmHg (1 mmHg = 133 Pa); P50 for unmodified hemoglobin = 11 mmHg], and the retention time of this derivative in the circulation of rats was 2.9 and 3.3 hr at two hemoglobin concentrations (7 g/dl and 14 g/dl, respectively). The half-life of an uncrosslinked carboxymethylated derivative, which has a low oxygen affinity (P50 = 28 mmHg), was 0.6 and 0.7 hr under the same conditions. Therefore, prolongation of the plasma-retention time of infused hemoglobin is dependent on the crosslinking of the tetramer but independent of the oxygen affinity of the derivative.

Allosteric Regulation↗
PubMed1991

Filtration-assisted exchange transfusion using alpha alpha Hb, an erythrocyte substitute.

A method for improving the efficiency of exchange transfusion to evaluate hemoglobin- (Hb) based erythrocyte substitutes is described. The method uses a continuous-flow hollow-fiber plasma separation filter to remove the erythrocytes while returning 75% of the plasma. The removed volume was replaced with a 14-g/dl solution of human Hb cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb). Filtration of 2.76 blood vol in anesthetized swine resulted in a 95% reduction of hematocrit and produced a plasma Hb concentration of 7.63 g/dl. Hyperoncotic Hb solutions cause volume expansion, which reduces the efficiency of exchange but provides hemodynamic stability in the face of decreasing blood viscosity and subsequent intravascular volume loss with Hb redistribution. Filtration-assisted exchange transfusion is rapid, conserves valuable modified Hb, and ensures continuous adequate oxygen delivery.

Animals↗
PubMed1990

Liver and kidney injury after administration of hemoglobin cross-linked with bis(3,5-dibromosalicyl) fumarate.

Human hemoglobin cross-linked between the alpha chains with bis (3,5-dibromosalicyl) fumarate (DBBF-Hb) was exchange transfused in swine and the histomorphologic changes were evaluated. Following exchange, animals were euthanized and tissues were taken for light and electron microscopy at 7.5 hours and days 1, 4, 7, and 15. Consistent hepatocellular and renal epithelial cell changes were seen. Hepatic injury, evident at 7.5 hours as cellular vacuolization, progressed to necrosis and acute inflammatory cell infiltration by days 1 and 4, was resolving by 7 days and was completely resolved by day 15. Cytochemical stains for iron and hemoglobin revealed positive material in Kupffer cells, endothelial cells, and necrotic hepatocytes. Rabbit anti-human hemoglobin antibody staining revealed immunoreactive material diffusely present at days 1 and 4 and limited to solitary hepatocytes by day 15. Kidney injury began as proximal tubular epithelial vacuolization and intraluminal casts progressing to tubular necrosis by 24 hours, with resolution by day 15. Iron and hemoglobin stains demonstrated these materials in the early lesions. Immunocytochemistries demonstrated human hemoglobin that remained as late as day 15. Electron microscopy revealed degeneration and regeneration of epithelial cells. The renal lesions were consistent with hemoglobinuria. The liver lesion was less well defined but was self limited.

Animals↗
PubMed1980

Pharmacokinetics of ceforanide in patients with end stage renal disease on hemodialysis.

The pharmacokinetics of ceforanide were evaluated in 11 patients with end stage renal disease (creatinine clearance less than 5 ml/min). A single intravenous dose of 750 mg/m2 produced peak plasma concentrations of 123 +/- 29 microgram/ml. The plasma half-life (T 1/2) of the drug was 19.1 +/- 2.5 h. A 5.5 h hemodialysis session removed 53% of the drug and reduced the T 1/2 to 5 +/- 0.7 h. Plasma concentrations greater than 10 microgram/m2 were maintained without adverse effects with a 1.5-g/m2 dose administered three times a week for 2 weeks.

Adult↗
PubMed1978

Frequency of surface microprojections and coated vesicles with increased malignancy in human astrocytic neoplasms.

Surface membrane microprojections and coated vesicles of a well differentiated (Kernohan-Sayre grade I) cerebral fibrillary astrocytoma were compared with those of anaplastic astrocytic (grade IV, glioblastoma) cerebral tumors. Both phenomena increase with increased malignancy. This provides further evidence for membrane alterations with malignant change in human astrocytic cells. It is the first comparison of fibrillary astrocytoma surface phenomena with those of more malignant astrocytic tumors of the cerebrum.

Astrocytoma↗