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F DeVenuto

Publications and source records attributed to F DeVenuto.

At least 19 recordsLinked to original sources
PubMed1983

Preparation and evaluation of pyridoxalated-polymerized human hemoglobin.

A solution of hemoglobin has several potential applications as a blood substitute. However, because of high oxygen affinity (P50 approximately 14 mm Hg) and short vascular retention time of hemoglobin (plasma half-disappearance time approximately 3.5 hr), a solution of hemoglobin presents limitations for its general use in blood replacement therapy. To overcome these limitations crystalline hemoglobin was modified by pyridoxalation and subsequent polymerization. Pyridoxalation yielded a product with a P50 ranging from 23 to 26 mm Hg. The pyridoxalated hemoglobin was then polymerized with glutaraldehyde and the final modified hemoglobin showed a P50 of 19 to 22 mm Hg. The modified hemoglobin was tested in vitro for coagulation activities. The results indicated that no adverse coagulant activity was demonstrated by the modified products. In vivo studies in the rat have shown that pyridoxalated-polymerized hemoglobin has a plasma half-disappearance time of about 25 hr. The data demonstrated that a solution of pyridoxalated-polymerized hemoglobin, because of its lower oxygen affinity and longer vascular retention than unmodified hemoglobin, has significant potential as a basis for an efficient resuscitation solution.

Animals↗
PubMed1983

Modified hemoglobin solution as a resuscitation fluid.

Hemoglobin solution, as a potential oxygen-carrying resuscitation fluid in blood volume replacement therapy, has two limitations: higher oxygen affinity (P50 approximately 12-16 mm Hg) and shorter vascular retention time (plasma half-disappearance time approximately 2-4 h) of free hemoglobin as compared to hemoglobin in the red cells. To overcome these two limitations, several investigators have used a variety of reactions and procedures for the modification of the hemoglobin molecule. This article presents a review of the modifications of the hemoglobin, including reactions with different agents for the intra- or intermolecular cross-linking of hemoglobin, reactions with pyridoxal phosphate with or without subsequent polymerization, and manipulations for the encapsulation of hemoglobin to obtain artificial cells. The P50 and the vascular retention time of the products obtained are indicated whenever they have been reported in the literature. The oxygen transport characteristics of a resuscitation fluid, in general, and of modified hemoglobin solution, in particular, have been correlated to the oxygen dissociation curve and to the hemoglobin concentration.

Animals↗
PubMed1983

Morphologic effects on the retina of massive exchange transfusion with stroma-free hemoglobin solution.

Retinal morphology serves as an extremely sensitive end point to hypoxic and ischemic conditions manifested by circulatory perturbations. Therefore, the effect of massive transfusion of stroma-free hemoglobin solution (SFHS) on retinal morphology of rats was evaluated. Seventy-three rats were divided into three groups. Two groups were transfused to 75% blood volume replacement--one (n = 30) with 7% SFHS one (n = 26) with 7% albumin solution and the third group (n = 17) was cannulated, not transfused (controls). Animals in each group were killed at 1, 5, 12, and 24 hours and 2 months after the procedure. In the transfused rats, focal and perivascular regions of edema, axonal swelling, and vacuoles were observed by light and transmission electron microscopy in the nerve fiber layer of the central retina. These conditions progressively decreased from 1 to 12 hours in the albumin-treated group. The retinas of SFHS-treated rats killed at 12 and 24 hours had similar but more severe morphologic changes than any of the albumin-treated animals; swelling was more severe in those obtained at 24 than at 12 hours, whereas vacuoles were larger in animals obtained at 12 hours. Abnormalities were observed in the prelaminar portion of the optic disc of the SFHS-treated groups killed at 12 and 24 hours. Subretinal hemorrhaging occurred in about 50% of the SFHS-treated animals killed at both 12 and 24 hours and was associated with swelling, vacuolization, and disruption of the photoreceptor outer segments and retinal pigment epithelium. Below normal levels of glycogen were present in the Müller cells of the retinas of albumin-treated rats killed at 5, 12, and 24 hours. At 12 hours after transfusion the Müller cells in lesions of the retinas obtained from the SFHS-treated rats were devoid of glycogen. High glycogen levels, however, appeared in a zone peripheral to the lesions. The latter effect was not apparent in the specimens obtained at 24 hours. The damage observed was probably due to hypoxic and ischemic effects secondary to urinary hemoglobin excretion and concomitant blood volume loss. No abnormalities were seen in the controls. The retinas of SFHS-treated rats killed at 1 and 5 hours showed normal retinal morphology and glycogen levels. Presumably, SFHS exerted a protective effect during this time period. If the current formulation of SFHS is to be used clinically, it will have to be administered continuously until blood is available for transfusion, and the patient's intravascular volume should be monitored carefully to prevent hypovolemia.

Animals↗
PubMed1983

Hemoglobin solutions as a blood substitute.

The ultimate objective for a Hb-derived oxygen-transporting solution is human use. There are four basic issues that must be addressed before this objective can be reached. 1) Assessment of the physiologic criteria for an oxygen-transporting Hb is needed to select those products with the best properties for tissue oxygenation. 2) Since modification requires chemical changes to the Hb molecule or its environment, these changes must be characterized. 3) The efficacy of the product(s) must be evaluated in animal models that simulate clinical situations where they will be used. 4) The safety of their use must be established.

2,3-Diphosphoglycerate↗
PubMed1983

Hematologic effects of hemoglobin solutions in animals.

Hb could cause abnormalities in coagulation if stromal lipid contaminated the solution. We prepared Hb by two procedures; it was lipid-free by the assays employed. These solutions were given to three species of animals (dogs, pigs, primates) at the dose of 15 ml/kg and then observations were made for hematologic changes. Only dogs demonstrated significant alterations. A consistent transient thrombocytopenia (60% drop) was seen five minutes after infusion and returned to baseline by one hour. Control dogs, receiving albumin, also showed a transient thrombocytopenia but not as pronounced (15% drop). Two Hb-treated dogs had signs of subclinical DIC (positive FDF, protamine sulfate precipitation, and a 70% drop in Factor VIII). There were no differences in any hematologic parameters between Hb and albumin treated pigs and monkeys. These results show that species-specific hematologic responses to lipid-poor Hb can be demonstrated.

Animals↗
PubMed1983

Distinctive characteristics of pyridoxalated-polymerized hemoglobin.

The development and evaluation of an effective Hb solution as a blood substitute are important not only for the care of casualties resulting from mass disasters, but also for eventual use in other special clinical situations. Substantial improvements have been made in recent years in the quality of Hb solutions. Solutions of unmodified Hb, although with certain limitations as indicated, potentially could be useful in several applications. The limitations presented by unmodified Hb can be overcome by a modification of the Hb molecule. In oxygen transport, not only the flow of the vascular fluid but also the vascular retention time, the oxygen affinity, and the concentration of free circulating Hb are important. A solution of Pyr-Poly Hb possesses positive characteristics in regard to the last three of these factors and, if the possibility of using bovine Pyr-Poly Hb is considered, the problem of supply for the material needed for the stockpiling of large quantities of this resuscitating solution can be eliminated. Products obtained by such modification must be evaluated also for their safety so that no potential adverse clinical effects would develop when administered to human patients.

Animals↗
PubMed1982

Hemoglobin solutions as oxygen-delivering resuscitation fluids.

Human hemoglobin (Hb) solution is being developed for use as an oxygen-delivering resuscitation fluid. Substantial improvements in the general purity and quality of experimental Hb solutions have been achieved by recent research efforts. Hb solutions now appear to be free of the undesirable biological effects that were reported in earlier studies. The present product, furthermore, is suitable for prolonged storage and can be dehydrated for greater efficiency in shipping and stockpiling during emergencies. Such improvements have enabled investigators to study the potential resuscitative properties of hemoglobin solutions in vivo, in experimental animals. From recent investigations, a reasonable picture of the limitations as well as a knowledge for potential improvements has evolved. Limitations are insufficient intravascular hemoglobin retention and increased oxygen affinity of free Hb, as compared to intraerythrocytic Hb. Potential improvements that could overcome these limitations may be achieved by modifying Hb to maintain the tetrameric molecule, thus providing a stable Hb compound having longer intravascular life as well as lower oxygen affinity.

Animals↗
PubMed1982

Effectiveness of stroma-free hemoglobin solution as seen in a right heart bypass swine model.

To determine if tolerance to severe anemia (Hct less than or equal to 10%) might be improved with stroma-free hemoglobin solution (SFH), 15 swine were placed on normothermic right heart bypass (RHBP) for evaluation of stroke volume (SV), coronary blood flow (CBF), arterial-coronary sinus oxygen content difference S(a-cs)O2, and myocardial oxygen consumption (MVO2) during a control period at a hematocrit (Hct) level of 30%. These 15 animals, divided into three equal groups, subsequently underwent exchange transfusion either to a Hct of 5% using 7% SFH (group 1), or to a Hct of 5% (group 2) or 10% (group 3) using 7% bovine albumin solution. All tests were repeated during these experimental conditions. Myocardial performance after albumin solution exchange was sustained on RHBP in only 1 of 10 animals. SFH animals (group 1) had a significant drop in SV at 14 torr after exchange (20 +/- 3 ml vs 10 +/- 4 ml, p less than 0.025), but this 50% performance level could be sustained. CBF rose and MVO2 fell in all groups, although the statistically nonsignificant mean differences were less with SFH. S(a-c)O2 fell significantly (p less than 0.05) with albumin solution (group 2 7.3 +/- 1.4 vs 2.2 +/- 0.2, group 3 8.9 +/- 2.0 vs 3.8 +/- 1.0), and nonsignificantly with SFH (5.6 +/- 0.7 vs 4.1 +/- 1.4). Although myocardial performance decreased with SFH, the authors believe these comparative results support the use of SFH at an Hct of 5%.

Animals↗
PubMed1982

Morphological effects of transfusions with hemoglobin solutions.

The current investigation describes the morphological and pathophysiological effects of stroma-free hemoglobin solution (SFH) on the liver and kidney. One h after a 75% blood volume exchange in animals receiving 7% SFH, hepatic morphology was normal. Animals whose blood was similarly exchanged with 7% albumin demonstrated evidence of cellular hypoxia. These findings suggested that SFH initially transported and offloaded sufficient oxygen to prevent hypoxic alterations. Twelve and 24 h after exchange with albumin, the livers were normal, whereas those of SFH-transfused rats exhibited centrolobular necrosis. Studies of intravascular volume, free circulating hemoglobin distribution, and urinary volumes revealed that the hemoglobin tetramer was degraded rapidly into monomers which traversed the glomerular basement membrane, causing a diuresis. The latter resulted in a 40% loss of intravascular volume, 6 h after SFH administration. When intravascular volume and hemoglobin concentration were maintained by bolus infusions of SFH, hepatic necrosis did not occur. Free hemoglobin was incorporated into the cytoplasm of proximal renal tubular cells and also appeared in the lumens of the distal tubules. However, 24 h after exchange transfusion, almost all of the hemoglobin had left the kidneys and there was no morphological evidence of renal dysfunction. Serum creatinines were normal after SFH administration. The slight rise in BUN was attributed to the dehydration caused by hemoglobin diuresis.

Albumins↗
PubMed1982

Blood exchange with pyridoxalated and polymerized hemoglobin solution.

A solution of pyridoxalated and polymerized hemoglobin has been used for total blood exchange in the rat to test its effectiveness in vivo. Two groups of eight rats each were transfused to 93 to 95 per cent blood replacement with hemoglobin, control group, or with modified hemoglobin, experimental group, solution. All of the rats in the experimental group survived and became hematologically and physiologically normal at eight days after transfusion, whereas the rats in the control group died at approximately five hours after transfusion. Immediately after transfusion, the circulating fluid in the two groups of rats showed the same oxygen carrying capacity. At three and five hours after transfusion, differences in the oxygen capacity were observed with values in the experimental group of 34 and 103 per cent higher, respectively, than in the control group. The P50 of the vascular fluid in the experimental rats was 47 to 49 per cent greater than the corresponding value in the control group at zero, three and five hours after transfusion. The disappearance of hemoglobin from plasma was faster in the control than in the experimental group with a plasma half-disappearance time of 3.5 and 25 hours, respectively. The differences observed in the rate of disappearance of plasma hemoglobin were reflected in the rate of accumulation of hemoglobin in the urine. A solution of pyridoxalated and polymerized hemoglobin appears to be beneficial in blood replacement, since it promotes survival after massive transfusions.

Animals↗
PubMed1981

Oxygen transport after hemodilution of human blood with crystalline hemoglobin solution.

Fresh human blood and hemoglobin solution were mixed in different proportions to simulate hemodilution volumes occurring when blood is replaced by hemoglobin solution. Oxygen dissociation curves, P50 and hematocrit value of blood, hemoglobin solution and mixtures of blood and hemoglobin solution were determined. Total hemoglobin and oxygen content of the samples and the contribution to the total content by the two components in the mixtures were also measured. From these data, calculations were made of the oxygen release, at different pO2, by blood, hemoglobin solution and mixtures of blood and hemoglobin solution with contribution by each of two components. An in vitro analysis of static equilibrium between hemoglobin and oxygen demonstrates that the contribution of hemoglobin to the total oxygen released is affected by three factors, the left shift of the oxygen dissociation curve, the pO2 at the tissue level and the concentration of the hemoglobin in the solution used for hemodilution.

Biological Transport↗
PubMed1980

Massive exchange transfusions with crystalline hemoglobin solution and subsequent replacement of hemoglobin and blood volume.

Crystalline hemoglobin solution was used to exchange transfuse rats to 75 per cent blood replacement. At three hour intervals after transfusion, the rats received bolus injections of hemoglobin solution to replace plasma hemoglobin and intravascular volume lost during each time interval. At 12 and 24 hours after termination of exchange transfusion, the livers of five of six rats exhibited normal hepatic structure. One rat had centrilobular hepatic neurosis similar to that reported for rats given a single transfusion. Plasma hemoglobin, packed cell volume, plasma oncotic pressure and oxygen-carrying capacity of the intravascular fluid were monitored; the data demonstrate that changes observed in these parameters are rectified by the bolus injection which brought their values to the levels observed after transfusion. No hepatic lesions or other abnormalities were observed in the rats in the control group exchange transfused isovolemically with pooled rat blood or subjected to surgical procedures only. Serial bolus injections of hemoglobin solution, by rapidly restoring blood volume and hemoglobin concentration, appear to prevent the hepatic necrosis observed in rats a few hours after a single transfusion, as reported in previous studies.

Animals↗
PubMed1979

Morphologic effects following massive exchange transfusions with a stroma-free hemoglobin solution. II. Kidney.

The effects on renal morphology of exchange transfusion with stroma-free hemoglobin solutions (SFHS) were compared in rats to the results obtained using an asanguineous resuscitative fluid containing albumin. Animals underwent 75 per cent blood volume replacement, and tissue collected at intervals after the exchange transfusion was examined by light and electron microscopy. Urine volumes, osmolarity, and pH also were determined, and serum creatinine and blood urea nitrogen were measured both before and after exchange transfusion. Hemoglobin was filtered through the renal glomerular basement membrane, and a portion was reabsorbed into the proximal tubular cells in the form of absorption droplets. Unabsorbed hemoglobin was excreted in the urine. Despite a distention of proximal and distal tubules 5 hours after exchange transfusion with SFHS, there was no ultrastructural evidence of renal parenchymal damage. Proximal tubular cells of albumin-exchanged animals contained fewer protein absorption droplets and no intraluminal material. The apparent higher rate of glomerular filtration of hemoglobin over albumin probably reflected the dissociation of hemoglobin into dimers, resulting in a diuresis. Urine volumes were 3 times greater in SFHS-exchanged animals than in albumin-treated rats, and the urine was relatively hypoosmolar in the former. The greater urine volumes in SFHS-treated animals also were associated with a large reduction in intravascular fluid volume. There was no alteration of serum creatinine or blood urea nitrogen after exchange transfusion with albumin and only a mild elevation in blood urea nitrogen in SFHS-treated rats. The latter most likely was a result of prerenal hypovolemia. SFHS, even when exchange-transfused in massive quantities, does not appear to affect renal function or ultrastructural morphology adversely. However, the rapid disappearance of hemoglobin from the intravascular space, the consequent loss of intravascular fluid volume, and the diuresis induced by its administration are complications which must be overcome before the product can be a useful adjunct in the treatment of hemorrhagic shock.

Animals↗
PubMed1978

Morphologic effects following massive exchange transfusions with a stroma-free hemoglobin solution. I. Liver.

Hepatic morphology was studied in rats that were exchange transfused with either a stroma-free hemoglobin solution (SFHS) or with various asanguineous resuscitative fluids. The animals under-went 75 per cent blood volume replacement and tissues were collected and fixed at timed intervals after the exchange transfusion. In addition, blood volumes were determined, using chromium labeled red blood cells, in both albumin and SFHS-treated rats at varying time periods after exchange transfusion. One hour following exchange transfusion, livers of animals infused with asanguineous fluids demonstrated marked centrolobular hepatocellular vacuolization and mitochondrial shape alterations consistent with the effects of hypoxia. SFHS appeared to protect the liver from these early abnormalities. However, at later time intervals livers of albumin-treated animals appeared normal, whereas those of SFHS-transfused rats exhibited centrolobular necrosis. Blood volume was reduced approximately 10 per cent during the first 18 hours after exchange transfusion with albumin, while SFHS-treated rats experienced a 42 per cent blood volume decrement in only 6 hours. Blood volumes were near normal in all animals by 48 hours. These findings suggest that SFHS protects the liver from hypoxia immediately after exchange transfusion, presumably by its ability to transport and release oxygen. However, the eventual disappearance of hemoglobin from the intravascular space is associated with a marked reduction in blood volume which is accompanied by hepatic ischemia and centrolobular necrosis.

Animals↗