Sanguinate's effect on pial arterioles in healthy rats and cerebral oxygen tension after controlled cortical impact.

Sanguinate, a polyethylene glycol-conjugated carboxyhemoglobin, was investigated for cerebral vasoactivity in healthy male Sprague-Dawley rats (Study 1) and for its ability to increase brain tissue oxygen pressure (PbtO2) after controlled cortical impact (CCI) - traumatic brain injury (TBI) (Study 2). In both studies ketamine-acepromazine anesthetized rats were ventilated with 40% O2. In Study 1, a cranial window was used to measure the diameters of medium - (50-100µm) and small-sized (<50µm) pial arterioles before and after four serial infusions of Sanguinate (8mL/kg/h, cumulative 16mL/kg IV), volume-matched Hextend, or normal saline. In Study 2, PbtO2 was measured using a phosphorescence quenching method before TBI, 15min after TBI (T15) and then every 10min thereafter for 155min. At T15, rats received either 8mL/kg IV Sanguinate (40mL/kg/h) or no treatment (saline, 4mL/kg/h). Results showed: 1) in healthy rats, percentage changes in pial arteriole diameter were the same among the groups, 2) in TBI rats, PbtO2 decreased from 36.5±3.9mmHg to 19.8±3.0mmHg at T15 in both groups after TBI and did not recover in either group for the rest of the study, and 3) MAP increased 16±4mmHg and 36±5mmHg after Sanguinate in healthy and TBI rats, respectively, while MAP was unchanged in control groups. In conclusion, Sanguinate did not cause vasoconstriction in the cerebral pial arterioles of healthy rats but it also did not acutely increase PbtO2 when administered after TBI. Sanguinate was associated with an increase in MAP in both studies.

Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with altered oxygen affinity and viscosity on systemic and microcirculatory variables in a top-load rat model.

The effects of a polymerized bovine hemoglobin-based oxygen carrier (HBOC) and two derivatives on arteriolar vasoactivity and tissue oxygen tension were explored by administering HBOC in a dose-response fashion to normovolemic rats. The effect of oxygen affinity (P50) and viscosity was also explored, where the P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50 and LP50A) were as follows: 40mmHg and 3.0cP (HBOC-20l); 18mmHg and 4.4cP (MP50); and 17mmHg and 12.1cP (LP50A). Anesthetized male Sprague-Dawley rats (N=32) were randomized to receive one of the HBOC solutions, and were administered four infusions that increased in concentration for each dose (2, 22, 230 and 780mg/kg, IV). Data were compared to rats receiving an equivalent volume for each of the four infusions (0.4, 0.4, 3.8, 13.1ml/kg, IV) of iso-oncotic 5.9% human serum albumin (HSA). Increasing doses of either HBOC solutions or HSA were associated with increasing MAP. Doses 3 and 4 of HBOC-201, MP50 and HSA produced significant increases in MAP, whereas similar increases began at a lower dose (Dose 2) with LP50A. There were no significant changes in arteriolar diameters at any dose for any group. Interstitial partial pressure of oxygen (ISF PO2) remained unchanged for HBOC-201, MP50 and HSA, but LP50A caused a significant decrease in ISF PO2 compared to baseline after Doses 3 and 4. In conclusion, there was no evidence that HBOC-201 would perform better with increased oxygen affinity (40 to 18mmHg) or viscosity (3.0 to 4.4cP).

Pre-hospital resuscitation with HBOC-201 and rFVIIa compared to HBOC-201 alone in uncontrolled hemorrhagic shock in swine.

In a previous dose escalation study our group found that combining 90µg/kg rFVIIa with HBOC-201 reduced blood loss and improved physiologic parameters compared to HBOC alone. In this follow-up study in a swine liver injury model, we found that while there were no adverse hematology effects and trends observed in the previous study were confirmed, statistical significance could not be reached. Additional pre-clinical studies are indicated to identify optimal components of a multifunctional blood substitute for clinical use in trauma.

When blood is not an option: factors affecting survival after the use of a hemoglobin-based oxygen carrier in 54 patients with life-threatening anemia.

BACKGROUND: In consenting Jehovah's Witness patients and others for whom blood is contraindicated or not available, hemoglobin-based oxygen carrier (HBOC)-201 may enable survival in acutely anemic patients while underlying conditions are treated. METHODS: Survival factors were identified in a multicenter, unblinded series of severely anemic "compassionate use" patients receiving available standard treatment plus consultant-supported HBOC-201 administration by novice users. Predictors of outcome were sought and compared between survivors and nonsurvivors. A compound variable, hemoglobin-duration deficit product was used to describe the interactive clinical effects of severity and duration of anemia. Mortality,correlations between patient characteristics, and survival to hospital discharge were determined from patient records. RESULTS: Fifty-four patients (median age 50 years) with life-threatening anemia (median hemoglobin concentration at time of request = 4 g/dL) received 60 to 300 g HBOC-201.Twenty-three patients (41.8%) were discharged. Intraoperative blood loss (45%), malignancy(18%), and acute hemolysis (13%) were the prevailing reasons for anemia. Time from onset of anemia (< or = 8 g/dL) to HBOC-201 infusion was shorter for survivors than nonsurvivors (3.2 vs 4.4 days, P = 0.027). Mean hemoglobin levels before HBOC-201 infusion in survivors and nonsurvivors were 4.5 and 3.8 g/dL, respectively (P = 0.120). No serious adverse event was attributed to HBOC-201. The hemoglobin-duration deficit product separated survivors from nonsurvivors. Cancer and renal disease were associated with nonsurvival. CONCLUSION: Earlier, compared with later, administration by inexperienced users of HBOC-201 to patients with anemia was associated with improved chances of survival of acutely bleeding and hemolyzing patients. Survival was more likely if the duration and magnitude of low hemoglobin was minimized before treatment with HBOC-201.

Regional blood flow after serial normovolemic exchange transfusion with HBOC-201 (Hemopure) in anesthetized swine.

BACKGROUND: This study determined individual organ blood flows and global hemodynamic, oxygen delivery and consumption parameters after normovolemic exchange transfusions with the hemoglobin based oxygen carrier (HBOC)-201 in a lightly anesthetized swine model. METHODS: The exchange transfusions were performed as a stepped reduction in blood volume to attain volume exchanges of 10%, 30%, and 50% with a 1:1 replacement with HBOC-201 (n = 8) or oncotically matched 5.9% human serum albumin (HSA, n = 8). Four additional animals served as time controls. RESULTS: There was no change in the regional blood flows in 8 of 9 organs (brain, heart, kidney, liver, pancreas, gall bladder, small intestines, large intestines, and skeletal muscle) after HBOC-201 compared with controls; only skeletal muscle blood flow decreased. In contrast, with HSA, blood flow increased 150% to 200% of baseline in all organs except muscle where blood flow was unchanged. HBOC-201 effectively restored oxygen delivery after these exchanges. The mean arterial pressure increases in the HBOC-201 group were within 15% to 20% of baseline during the initial 10% exchange and similar to controls during subsequent exchanges. Although peak pulmonary arterial pressure increases in the HBOC-201 group were 10 mm Hg to 15 mm Hg above baseline, cardiac index was unchanged. There were no differences in global oxygen consumption, consistent with unchanged regional blood flow and suggests intact physiologic coupling of oxygen delivery and consumption that was unimpaired by local vasoconstriction. This is in contrast to significant changes of increased cardiac index, decreased arterial pressure, decreased oxygen content, and increased oxygen extraction ratio to maintain normal oxygen consumption in the HSA group. CONCLUSION: Although the use of HBOC-201 caused alterations in systemic (minimal) and pulmonary (modest) pressures, these changes had no consequence on regional organ blood flow.

Dodecafluoropentane Emulsion (DDFPE) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.

Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, whereas anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This minireview summarizes our progress in developing a battlefield-ready product to prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies, for both indications, show promising effects of DDFPe as a resuscitation fluid. DDFPe may become a part of the toolkit for tactical healthcare professionals in battlefield and domestic emergency medicine.

Hypobaria during long-range flight resulted in significantly increased histopathological evidence of lung and brain damage in a swine model.

BACKGROUND: Aeromedical evacuation to definitive care is standard in current military conflicts. However, there is minimal knowledge on the effects of hypobaria (HYPO) on either the flight crew or patients. The effects of HYPO were investigated using healthy swine. METHODS: Anesthetized Yorkshire swine underwent a simulated 4 h "transport" to an altitude of 2,441 m (8,000 feet.; HYPO, N = 6) or at normobaric conditions (NORMO, N = 6). Physiologic and biochemical data were collected. Organ damage was assessed for hemorrhage, inflammation, edema, necrosis, and for lungs only, microatelectasis. RESULTS: All parameters were similar prior to and after "transport" with no significant effects of HYPO on hemodynamic, neurologic, or oxygen transport parameters, nor on blood gas, chemistry, or complete blood count data. However, the overall Lung Injury Score was significantly worse in the HYPO than the NORMO group (10.78 ± 1.22 vs. 2.31 ± 0.71, respectively) with more edema/fibrin/hemorrhage in the subpleural, interlobular and alveolar space, more congestion in alveolar septa, and evidence of microatelectasis (vs. no microatelectasis in the NORMO group). There was also increased severity of pulmonary neutrophilic (1.69 ± 0.20 vs. 0.19 ± 0.13) and histiocytic inflammation (1.83 ± 0.23 vs. 0.47 ± 0.17) for HYPO versus NORMO, respectively. On the other hand, there was increased renal inflammation in NORMO compared with HYPO (1.00 ± 0.13 vs. 0.33 ± 0.17, respectively). There were no histopathological differences in brain (whole or individual regions), liver, pancreas, or adrenals. CONCLUSION: Hypobaria, itself, may have an adverse effect on the respiratory system, even in healthy individuals, and this may be superimposed on combat casualties where there may be preexisting lung injury. The additional effects of anesthesia and controlled ventilation on these results are unknown, and further studies are indicated using awake models to better characterize the mechanisms for this pathology and the factors that influence its severity.

Hitachi Hemolytic Index correlates with HBOC-201 concentrations: impact on suppression of analyte results.

OBJECTIVES: To determine the feasibility of laboratories to use an instrument's Hemolytic Index (HI) to determine if a test result would be accurate in the presence of hemoglobin-based oxygen carrier HBOC-201. DESIGN AND METHODS: HI values from the Roche Hitachi Modular P800 for samples containing HBOC-201 were determined. HI limits for 24 tests determined by addition of RBC lysate hemoglobin to serum and the instrument manufacturer's HI limits were compared to HI limits for reporting the same tests determined by adding HBOC-201 to plasma. RESULTS: There is a linear relationship (R(2)=0.99) between the HI value on the Modular P800 and HBOC-201 concentrations. Twenty-one of 24 HI limits for reporting results as determined by the manufacturer or adding RBC lysate to serum were more conservative or equal to the limit determined by HBOC-201 interference testing. HBOC-201 interference testing was more conservative for albumin, creatinine, and uric acid. CONCLUSION: For most analytes, the Modular P800 HI provides an accurate, conservative and automated method to determine whether laboratory results should be reported or suppressed when samples contain HBOC-201.

Determination of methemoglobin and hemoglobin levels in small volume samples.

Background/aims Hemoglobin-based oxygen carriers (HBOCs) have been previously studied as resuscitation fluids. Due to HBOCs specific molecular conformation, hemoglobin (Hb) and methemoglobin (MetHb) determination is not always possible with automated apparatus. A practical technique was designed that allows simultaneous reading of MetHb and Hb in small volume samples. Methods A spectrophotometric method for measuring low levels of MetHb and Hb from limited volume samples was developed using a 96-well-plate by downsizing the Evelyn-Malloy and Drabkin methods. Either blood or buffer samples were spiked with one of five HBOCs (HBOC-201, M101, MP4CO-NP, Sanguinate and Oxyvita C). After treatment with cyanides, the samples were read at 540, 630, and 680 nm, and Hb and MetHb results were compared to certificate-of-analysis. Results Hb levels ranging from 0.2 to 2.8 g/dl were detected accurately with the 96-well-plate method with HBOC-201. Similarly, this method accurately measured Hb from either plasma or buffer samples containing any of the HBOCs. The MetHb plasma samples with HBOC-201 were also in agreement with ABL results (R = 0.99719). MetHb from all HBOCs in buffer measured with this method was comparable to reference but the accuracy was compromised for HBOCs in blood. Conclusions A useful 96-well-plate method of measuring HBOCs' Hb was designed for small-volume plasma samples. It was accurate for measuring MetHb from samples, that contained M101, MP4CO-NP, Sanguinate, and Oxyvita C diluted in buffer. This well-plate method allows reading of batch samples, multiple replicates, and using small volumes to accommodate limited animal blood collection which would not be otherwise detected by automated instrumentation.

Normalization of hemoglobin-based oxygen carrier-201 induced vasoconstriction: targeting nitric oxide and endothelin.

Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore, we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with either adenosine (ADO) or nitroglycerin (NTG); 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS), and endothelin (ET) in mediating the observed vasoconstriction; and 3) compare these effects in resting and exercising swine. Chronically instrumented swine were studied at rest and during exercise after administration of HBOC-201 alone or in combination with ADO. The role of NO was assessed by supplementation with NTG or administration of the eNOS inhibitor Nω-nitro-l-arginine. Alternative vasoactive pathways were investigated via intravenous administration of the ETA/ETB receptor blocker tezosentan or a mixture of ROS scavengers. The systemic and to a lesser extent the pulmonary pressor effects of HBOC-201 could be counteracted by ADO; however, dosage titration was very important to avoid systemic hypotension. Similarly, supplementation of NO with NTG negated the pressor effects but also required titration of the dose. The pressor response to HBOC-201 was reduced after eNOS inhibition and abolished by simultaneous ETA/ETB receptor blockade, while ROS scavenging had no effect. In conclusion, the pressor response to HBOC-201 is mediated by vasoconstriction due to NO scavenging and production of ET. Further research should explore the effect of longer-acting ET receptor blockers to counteract the side effect of hemoglobin-based oxygen carriers.NEW & NOTEWORTHY Hemoglobin-based oxygen carrier (HBOC)-201 can disrupt hemodynamic homeostasis, mimicking some aspects of endothelial dysfunction, resulting in elevated systemic and pulmonary blood pressures. HBOC-201-induced vasoconstriction is mediated by scavenging nitric oxide (NO) and by upregulating endothelin (ET) production. Pressor effects can be prevented by adjuvant treatment with NO donors or direct vasodilators, such as nitroglycerin or adenosine, but dosages must be carefully monitored to avoid hypotension. However, hemodynamic normalization is more easily achieved via administration of an ET receptor blocker.

Cerebral Microvascular and Systemic Effects Following Intravenous Administration of the Perfluorocarbon Emulsion Perftoran.

Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase tissue oxygenation during hypoxic states and to reduce ischemic cell death. Regulatory approval of oxygen therapeutics was halted due to concerns over vasoconstrictive side effects. The goal of this study was to assess the potential vasoactive properties of Perftoran by measuring brain pial arteriolar diameters in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend) solutions were administered as four sequential 30 min intravenous (IV) infusions, thus allowing an evaluation of cumulative dose-dependent effects. There were no overall changes in diameters of small-sized (<50 µm) pial arterioles within the Perftoran group, while both saline and Hextend groups exhibited vasoconstriction. Medium-sized arterioles (50-100 µm) showed minor (~8-9%) vasoconstriction within saline and Hextend groups and only ~5% vasoconstriction within the Perftoran group. For small- and medium-sized pial arterioles, the mean percent change in vessel diameters was not different among the groups. Although there was a tendency for arterial blood pressures to increase with Perftoran, pressures were not different from the other two groups. These data show that Perftoran, when administered to healthy anesthetized rats, does not cause additional vasoconstriction in cerebral pial arterioles or increase systemic blood pressure compared with saline or Hextend.

Polymerized bovine hemoglobin (Oxyglobin Solution) administration in two river otters (Lutra canadensis).

Polymerized bovine hemoglobin (Oxyglobin Solution®) was successfully administered to two river otters (Lutra canadensis) that required general anesthesia and surgery for trap-related injuries. In both animals, blood oxygen content was maintained at presurgical levels despite a 47-70% decrease in their hematocrit. Otter 1 received a dose of 19 mL kg-1, given at a rate of 29 mL kg-1 h-1. Otter 2 received a dose of 20 mL kg-1, given at a rate of 5 mL kg-1 h-1. For many of the uncommon species, there are limited resources in the form of blood products to treat anemia, blood loss or hypovolemia. Successful use of polymerized bovine hemoglobin in these two otters suggests that it is useful for acute treatment of anemia and blood loss in such species.

Effects of perfluorocarbon dodecafluoropentane (NVX-108) on cerebral microvasculature in the healthy rat.

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.25 ml/kg (low dose [L]) NVX-108 compared to 2.0 ml/kg Saline (control) in healthy anesthetized rats (N = 6/group). Results showed that post-infusion vessel diameters for small (< 50 µm) and medium (50-100 µm)-sized pial arterioles were significantly (p < 0.05) narrower after only the NVX- 108 H infusion although this vasoconstriction was not statistically significant when analyzed as a percentage change in these vessels. Pial arteriolar vessel diameters were not significantly different for mean value or percentage change after either NVX-108 L or Saline infusions. There were no significant post-infusion changes from baseline in systolic, mean or diastolic blood pressures after any of the treatments although post-infusion blood pressure was statistically higher in the NVX-108 L group compared to NVX-108 H and Saline groups. Arterial blood gases, methemoglob in and lactate were not different from baseline or among groups. No adverse events were observed at either dose of NVX-108. In conclusion, neither 0.25 nor 1.0 ml/kg NVX-108 caused vasoconstriction in cerebral pial arterioles of healthy rats nor resulted in blood pressure changes; the compound should be considered for further investigation for TBI therapy.

Effects of N-acetyl-L-cysteine and hyaluronic acid on HBOC-201-induced systemic and cerebral vasoconstriction in the rat.

Hemoglobin-based oxygen carrier-201 (HBOC) was developed as a resuscitative fluid but concerns exist over potentially adverse vasoconstriction. This study evaluated whether concurrent IV (intra venous) N-acetyl-L-cysteine (NAC) or hyaluronic acid (HA) would attenuate HBOC-associated vasoconstriction, assessed by systemic blood pressures and cerebral pial microvasculature, when administered to healthy, anesthetized rats. Rats (8-9/group) received a 30 min infusion of 3 ml/kg HBOC, HBOC plus 600 mg/kg NAC (HBOC/NAC), HBOC plus 1.5 mg/kg HA (HBOC/HA) or 3 ml/kg Albumin. Mean (MAP) and systolic (SBP) blood pressures, blood chemistries and cerebral pial vessel diameters were measured at baseline, end of infusion, and intermittently for an additional 90 min. HBOC caused immediate and sustained increases in SBP and MAP (35.3 ± 3.6 and 29.1 ± 2.5 mm Hg peak increases above baseline, respectively; mean ± SEM) and immediate but progressive vasoconstriction (11 µm maximum reduction) in medium-sized (50-100 µm) pial arterioles. When NAC was co-administered, blood pressure changes were attenuated and vessel changes were abolished. Similar trends were noted with co-administration of HA but were not statistically different from HBOC-alone. Small-sized (< 50 µm) pial vessels and blood parameters showed no differences from baseline or among groups. No adverse clinical signs were observed. We demonstrated that it is possible for adjuvant drugs to reduce the vasoconstriction associated with HBOC-201. Coinfusion of the anti-oxidant NAC mitigated HBOC-201-associated increases in blood pressures and vasoconstriction in medium-sized cerebral pial vessels. The drag-reducing polymer HA may be more effective at a higher dose as a similar but non-significant trend was observed.

Fluid resuscitation of uncontrolled hemorrhage using a hemoglobin-based oxygen carrier: effect of traumatic brain injury.

Animal models of combined traumatic brain injury (TBI) and hemorrhagic shock (HS) suggest a benefit of hemoglobin-based oxygen carrier (HBOC)-based resuscitation, but their use remains controversial, and little is known of the specific effects of TBI and high-pressure (large arterial injury) bleeding on resuscitation. We examine the effect of TBI and aortic tear injury on low-volume HBOC resuscitation in a swine polytrauma model and hypothesize that HBOC-based resuscitation will improve survival in the setting of aortic tear regardless of the presence of TBI. Anesthetized swine subjected to HS with aortic tear with or without fluid percussion TBI underwent equivalent limited resuscitation with HBOC, lactated Ringer's solution, or HBOC + nitroglycerine (vasoattenuated HBOC) and were observed for 6 h. There was no independent effect of TBI on survival time after adjustment for fluid type, and there was no interaction between TBI and resuscitation fluid type. However, total catheter hemorrhage volume required to reach target shock blood pressure was less with TBI (14.0 mL · kg(-1) [confidence interval, 12.4-15.6 mL · kg(-1)]) versus HS only (21.0 mL · kg(-1) [confidence interval, 19.5-22.5 mL · kg(-1)]), with equivalent lactate accumulation. Traumatic brain injury did not affect survival in this polytrauma model, but less hemorrhage was required in the presence of TBI to achieve an equivalent degree of shock suggesting globally impaired cardiovascular response to hemorrhage in the presence of TBI. There was also no benefit of HBOC-based fluid resuscitation over lactated Ringer's solution, contrary to models using liver injury as the source of hemorrhage, considering wound location is of paramount importance when choosing resuscitation strategy.

Effects of top-loading a zero-link bovine hemoglobin, OxyVita, on systemic and microcirculatory variables.

This study was designed to test the effect of top-load infusions of increasing doses of two versions of the novel, high molecular weight hemoglobin-based oxygen carrier, OxyVita and OxyVita C solution ([Hb] = 6 g/dL), on mean arterial pressure (MAP), arteriolar diameter, and tissue oxygenation. Experiments were carried out on 18 anesthetized male Sprague-Dawley rats in which microcirculatory observations were made on the spinotrapezius muscle. Intravenous infusions of four increasing doses of the OxyVita solutions (2, 22, 230, and 780 mg/kg) were made for each group, and a separate group of animals was used for volume control. Tissue oxygenation was measured as interstitial fluid (ISF) PO2 using phosphorescence quenching microscopy. Increasing doses of either OxyVita solution or Lactated Ringer's solution (LRS, volume control) were associated with increasing MAP. For LRS infusions, MAP returned to baseline between each incremental dose injected, whereas there was an incomplete return for either of the OxyVita solutions. ISF PO2 for OxyVita was significantly lower than that for either LRS or OxyVita C, whereas ISF PO2 for OxyVita C was never statistically different from LRS. There were no significant changes in arteriolar diameters for LRS and either of the OxyVita solutions.

Vital organ tissue oxygenation after serial normovolemic exchange transfusion with HBOC-201 in anesthetized swine.

This study determined the effects of serial, normovolemic, stepwise exchange transfusions with either 6% human serum albumin (HSA) or the hemoglobin-based oxygen carrier, HBOC-201, on tissue oxygenation of the heart, brain, and kidney in intact anaesthetized pigs. Exchange transfusions to 10%, 30%, and 50% of the pigs' total blood volume were completed at a withdrawal rate of 1.0 mL·kg(-1)·min(-1) followed by an infusion rate of 0.5 mL·kg(-1)·min(-1) of HBOC-201 or iso-oncotically matched 6% HSA. Measurements included invasive systemic hemodynamic (blood pressures, left ventricular end-diastolic pressure), hematolic (hemoglobin, hematocrit, methemoglobin), acid-base (pH, PCO2), and biochemistry (serum lactate) measurements. Brain and kidney tissue oxygenation (tPO2) was determined by electron paramagnetic resonance and heart tPO2 by O2 sensitive fiberoptic probe. The main results demonstrated that tPO2 after HBOC-201 remained stable despite significant decreases in hematocrit and changing hemodynamics. In vivo tPO2 measurements (heart tPO2 average ≥22 mmHg, brain tPO2 average ≥8 mmHg, and kidney tPO2 average ≥10 mmHg) were maintained in all groups at all times. Blood pressures were 20 to 30 mmHg higher after HBOC-201 compared with HSA controls. Heart rate and left ventricular end-diastolic pressure were not different among treatment groups. In conclusion, the administration of HBOC-201 maintained tPO2 in three vital organs after profound hemodilution.

Perioperative factors associated with puppy vigor after delivery by cesarean section.

This prospective study examined the perioperative factors associated with puppy vigor in a clinical population of 807 litters containing 3,410 cesarean-derived puppies. Information was obtained from 109 private and institutional practices in the United States and Canada. Puppy vigor was determined by assessing three spontaneous conditions within 2 minutes after delivery: breathing, moving, and vocalizing. The percentages of live-born puppies with these characteristics were 85%, 73%, and 60%, respectively. After screening tests, logistic-regression models were run on all remaining factors using the litter as the unit of analysis, and odds ratios [OR] were determined. An OR <1.0 means that the odds are decreased for that puppy vigor condition when the factor is present, compared with a litter in which the factor is not present. Conversely, when the OR is >1.0, the odds are increased for that puppy vigor condition when that factor is present. The following factors were associated with the litter having all puppies breathing at birth: using an inhalant anesthetic (0.36 OR) or ketamine (0.43 OR), surgery at one particular private practice (3.52 OR), and surgery at a teaching institute rather than a private practice (0.36 OR). The following factors were associated with the litter having any spontaneously moving puppies at birth: all puppies breathing spontaneously (2.72 OR), any puppy vocalizing spontaneously (117 OR), using inhalant anesthesia (0.26 OR), and using thiopental or thiamylal (0.37 OR). The following factors were associated with the litter having any spontaneously vocalizing puppies at birth: all puppies breathing spontaneously (2.58 OR), any puppy moving spontaneously (152 OR), brachycephalic dam (0.62 OR), the dam was a Labrador retriever (7.23 OR), and using isoflurane (2.51 OR). In conclusion, the anesthetic factors associated with increased puppy vigor included the use of isoflurane and the avoidance of ketamine, thiamylal, and thiopental.

Effects of oxypolygelatin and dextran 70 on hemostatic variables in dogs.

OBJECTIVE: To evaluate and compare coagulation variables following the administration of oxypolygelatin and dextran 70 to clinically healthy dogs. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: A total of eight healthy adult female Beagles aged 2-4 years old and weighing 11.8 +/- 2.7 kg. METHODS: The dogs received a 15-minute intravenous (IV) infusion of 5 mL kg-1 oxypolygelatin or 10 mL kg-1 6% dextran 70. Before (PRE) and at 2, 5, and 24 hours after administration, packed cell volume (PCV), total solids concentration (TS), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), platelet numbers (Plat), factor VIII coagulant activity (VIII:C), von Willebrand factor antigen concentration (vWf:Ag) and platelet function and buccal mucosal bleeding time (BMBT) were measured. Platelet function was assessed using aggregation and by measuring ATP release from aggregating platelets over 6 minutes, with 20, 10, and 5 micro m ADP and 5 and 10 micro g of collagen mL-1 as platelet activation agonists. RESULTS: All baseline values were within our normal ranges, except for one dog that had low vWf:Ag PRE values prior to both dextran and oxypolygelatin administration. Following dextran and oxypolygelatin administration, the PCV and TP were significantly (p < 0.05) decreased. Plat, FIB, and vWf:Ag decreased, while BMBT and VIII:C increased following dextran administration. Dextran also caused a significant decrease in platelet aggregation in response to ADP. Oxypolygelatin caused a significant decrease in vWf:Ag, Plat, and FIB compared to PRE values. The total amount of ATP released, standardized to platelet number, did not vary significantly for either group at any sampling time from PRE values. No significant changes from PRE values were noted at any time in either group for PT or APTT. CONCLUSION: At the doses administered, both dextran and oxypolygelatin can interfere with hemostatic variables in healthy dogs, but dextran's effect is more profound and prolonged when compared to oxypolygelatin. CLINICAL RELEVANCE: Oxypolygelatin causes fewer hemostatic abnormalities when compared to dextran, making it a superior colloid for administration at the doses tested.