Distinguishing different surface interactions for nucleotides adsorbed onto hematite and goethite particle surfaces through ATR-FTIR spectroscopy and DFT calculations.

Geochemical interfaces can impact the fate and transport of aqueous species in the environment including biomolecules. In this study, we investigate the surface chemistry of adsorbed nucleotides on two different minerals, hematite and goethite, using infrared spectroscopy and density functional theory (DFT) calculations. Attenuated total reflectance-Fourier transform infrared spectroscopy is used to probe the adsorption of deoxyadenosine monophosphate (dAMP), deoxyguanosine monophosphate (dGMP), deoxycytidine monophosphate (dCMP), and deoxythymidine monophosphate (dTMP) onto either hematite or goethite particle surfaces. The results show preferential adsorption of the phosphate group to either surface. Remarkably, surface adsorption of the four nucleotides onto either hematite or goethite have nearly identical experimental spectra in the phosphate region (900 to 1200 cm-1) for each mineral surface yet are distinctly different between the two minerals, suggesting differences in binding of these nucleotides to the two mineral surfaces. The experimental absorption frequencies in the phosphate region were compared to DFT calculations for nucleotides adsorbed through the phosphate group to binuclear clusters in either a monodentate or bidentate bridging coordination. Although the quality of the fits suggests that both binding modes may be present, the relative amounts differ on the two surfaces with preferential bonding suggested to be monodentate coordination on hematite and bidentate bridging on goethite. Possible reasons for these differences are discussed.

FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

Obeticholic acid (OCA) is a selective farnesoid X receptor (FXR) agonist that regulates bile acid and lipid metabolism. FXR activation induces distinct changes in circulating cholesterol among animal models and humans. The mechanistic basis of these effects has been elusive because of difficulties in studying lipoprotein homeostasis in mice, which predominantly package circulating cholesterol in HDLs. Here, we tested the effects of OCA in chimeric mice whose livers are mostly composed (≥80%) of human hepatocytes. Chimeric mice exhibited a human-like ratio of serum LDL cholesterol (LDL-C) to HDL cholesterol (HDL-C) at baseline. OCA treatment in chimeric mice increased circulating LDL-C and decreased circulating HDL-C levels, demonstrating that these mice closely model the cholesterol effects of FXR activation in humans. Mechanistically, OCA treatment increased hepatic cholesterol in chimeric mice but not in control mice. This increase correlated with decreased SREBP-2 activity and target gene expression, including a significant reduction in LDL receptor protein. Cotreatment with atorvastatin reduced total cholesterol, rescued LDL receptor protein levels, and normalized serum LDL-C. Treatment with two clinically relevant nonsteroidal FXR agonists elicited similar lipoprotein and hepatic changes in chimeric mice, suggesting that the increase in circulating LDL-C is a class effect of FXR activation.

Optical and Physicochemical Properties of Brown Carbon Aerosol: Light Scattering, FTIR Extinction Spectroscopy, and Hygroscopic Growth.

A great deal of attention has been paid to brown carbon aerosol in the troposphere because it can both scatter and absorb solar radiation, thus affecting the Earth's climate. However, knowledge of the optical and chemical properties of brown carbon aerosol is still limited. In this study, we have investigated different aspects of the optical properties of brown carbon aerosol that have not been previously explored. These properties include extinction spectroscopy in the mid-infrared region and light scattering at two different visible wavelengths, 532 and 402 nm. A proxy for atmospheric brown carbon aerosol was formed from the aqueous reaction of ammonium sulfate with methylglyoxal. The different optical properties were measured as a function of reaction time for a period of up to 19 days. UV/vis absorption experiments of bulk solutions showed that the optical absorption of aqueous brown carbon solution significantly increases as a function of reaction time in the spectral range from 200 to 700 nm. The analysis of the light scattering data, however, showed no significant differences between ammonium sulfate and brown carbon aerosol particles in the measured scattering phase functions, linear polarization profiles, or the derived real parts of the refractive indices at either 532 or 402 nm, even for the longest reaction times with greatest visible extinction. The light scattering experiments are relatively insensitive to the imaginary part of the refractive index, and it was only possible to place an upper limit of k ≤ 0.01 on the imaginary index values. These results suggest that after the reaction with methylglyoxal the single scattering albedo of ammonium sulfate aerosol is significantly reduced but that the light scattering properties including the scattering asymmetry parameter, which is a measure of the relative amount of forward-to-backward scattering, remain essentially unchanged from that of unprocessed ammonium sulfate. The optical extinction properties in the mid-IR range (800 to 7000 cm(-1)) also showed no significant changes in either the real or the imaginary parts of the refractive indices for brown carbon aerosol particles when compared to ammonium sulfate. Therefore, changes in the optical properties of ammonium sulfate in the mid-IR spectral range due to reaction with methylglyoxal appear to be insignificant. In addition to these measurements, we have characterized additional physicochemical properties of the brown carbon aerosol particles including hygroscopic growth using a tandem-differential mobility analyzer. Compared to ammonium sulfate, brown carbon aerosol particles are found to have lower deliquescence relative humidity (DRH), efflorescence relative humidity (ERH), and hygroscopic growth at the same relative humidities. Overall, our study provides new details of the optical and physicochemical properties of a class of secondary organic aerosol which may have important implications for atmospheric chemistry and climate.

Impact of acellular hemoglobin-based oxygen carriers on brain apoptosis in rats.

BACKGROUND: Extracellular hemoglobin (Hb)-based oxygen carriers (HBOCs) are under extensive consideration as oxygen therapeutics. Their effects on cellular mechanisms related to apoptosis are of particular interest, because the onset of proapoptotic pathways may give rise to tissue damage. STUDY DESIGN AND METHODS: The objective was to assess whether the properties of the Hb that replaces blood during an isovolemic hemodilution would modulate apoptotic-response mechanisms in rat brain and whether such signaling favors cytoprotection or damage. We exposed rats to exchange transfusion (ET; 50% blood volume and isovolemic replacement with Hextend [negative colloid control], MP4OX [PEGylated HBOC with high oxygen affinity], and ααHb [αα-cross-linked HBOC with low oxygen affinity; n=4-6/group]). Sham rats acted as control. Animals were euthanized at 2, 6, and 12 hours after ET; brain tissue was harvested and processed for analysis. RESULTS: In MP4OX animals, the number of neurons that overexpressed the hypoxia-inducible factor (HIF)-1α was higher than in ααHb, particularly at the early time points. In addition, MP4OX was associated with greater phosphorylation of protein kinase B (Akt), a well-known cytoprotective factor. Indeed, the degree of apoptosis, measured as terminal deoxynucleotidyl transferase-positive neurons and caspase-3 cleavage, ranked in order of MP4OX < Hextend < ααHb. CONCLUSION: Even though both HBOCs showed increased levels of HIF-1α compared to shams or Hextend-treated animals, differences in signaling events resulted in very different outcomes for the two HBOCs. ααHb-treated brain tissue showed significant neuronal damage, measured as apoptosis. This was in stark contrast to the protection seen with MP4OX, apparently due to recruitment of Akt and neuronal specific HIF-1α pathways.

Heterogeneous photochemistry of trace atmospheric gases with components of mineral dust aerosol.

Mineral dust aerosol is known to provide a reactive surface in the troposphere for heterogeneous chemistry to occur. Certain components of mineral dust aerosol, such as semiconductor metal oxides, can act as chromophores that initiate chemical reactions, while adsorbed organic and inorganic species may also be photoactive. However, relatively little is known about the impact of heterogeneous photochemistry of mineral dust aerosol in the atmosphere. In this study, we investigate the heterogeneous photochemistry of trace atmospheric gases including HNO(3) and O(3) with components of mineral dust aerosol using an environmental aerosol chamber that incorporates a solar simulator. For reaction of HNO(3) with aluminum oxide, broadband irradiation initiates photoreactions to form gaseous NO and NO(2). A complex dynamic balance between surface adsorbed nitrate and gaseous nitrogen oxide products including NO and NO(2) is observed. For heterogeneous photoreactions of O(3), iron oxide shows catalytic decompositions toward O(3) while aluminum oxide is deactivated by ozone exposure. Furthermore, the role of relative humidity, and, thus, adsorbed water, on heterogeneous photochemistry has been explored. The atmospheric implications of these results are discussed.

A kinetic study of ozone decomposition on illuminated oxide surfaces.

The heterogeneous chemistry and photochemistry of ozone on oxide components of mineral dust aerosol, including α-Fe(2)O(3), TiO(2), and α-Al(2)O(3), at different relative humidities have been investigated using an environmental aerosol chamber. The rate and extent of ozone decomposition on these oxide surfaces are found to be a function of the nature of the surface as well as the presence of light and relative humidity. Under dark and dry conditions, only α-Fe(2)O(3) exhibits catalytic decomposition toward ozone, whereas the reactivity of TiO(2) and α-Al(2)O(3) is rapidly quenched upon ozone exposure. However, upon irradiation, TiO(2) is active toward O(3) decomposition and α-Al(2)O(3) remains inactive. In the presence of relative humidity, ozone decay on α-Fe(2)O(3) subject to irradiation or under dark conditions is found to decrease. In contrast, ozone decomposition is enhanced for irradiated TiO(2) as relative humidity initially increases but then begins to decrease at higher relative humidity levels. A kinetic model was used to obtain heterogeneous reaction rates for different homogeneous and heterogeneous reaction pathways taking place in the environmental aerosol chamber. The atmospheric implications of these results are discussed.

Assessing the Validity and Reliability of the Pharmacist Interprofessional Competencies Tool.

Objective. To determine the validity and reliability of the Pharmacist Interprofessional Competencies Tool (PICT). Methods. Faculty members at Ferris State University, College of Pharmacy developed the PICT, which has five interprofessional criterion (collaboration, ownership, respect, engagement, and application) and four competency levels (unacceptable, novice, competent, and proficient) to assess the interprofessional competencies of pharmacy students. Fourteen pharmacy faculty members were trained in how to use the PICT and then used it to assess students' behaviors in four to six video-recorded interprofessional education (IPE) learning activities. A subset of these faculty members evaluated the video-recorded IPE learning activities using two other previously validated interprofessional assessment tools. Psychometric analysis of the PICT, including internal consistency and inter-rater reliability, was conducted, along with a correlation analysis and factor analysis, and the results were compared to those from the other validated assessment tools. Results. The overall rating of the internal consistency of the PICT was excellent and item-total correlations of the individual criterion were fair to good, with the exception of the respect criterion. The PICT demonstrated excellent overall inter-rater reliability, and individual criterion rated as fair to excellent with the exception of the respect criterion. Specific dimensions of the PICT showed high convergence with previously validated interprofessional assessment tools. Conclusion. The PICT exhibited overall validity and reliability as an assessment tool for measuring the interprofessional competencies of pharmacy students. In establishing the overall validity and reliability of the assessment tool, the respect criterion was not proved to be reliable or valid. Additional training and slight modifications to the PICT and associated IPE learning activities are planned to assist with longitudinal assessment of student performance across the curriculum.

Effect of ozone and relative humidity on the heterogeneous uptake of octamethylcyclotetrasiloxane and decamethylcyclopentasiloxane on model mineral dust aerosol components.

We have carried out kinetic and reaction yield studies to determine the effect of O(3) on the heterogeneous reaction of two cyclic volatile methylsiloxanes (cVMS), octamethylcyclotetrasiloxane (D(4)) and decamethylcyclopentasiloxane (D(5)), with model mineral dust aerosol in order to obtain a better understanding of the atmospheric fate of cVMS. The heterogeneous chemistry was studied in an environmental reaction chamber using FT-IR spectroscopy to monitor the reaction progress. The uptake kinetics and the reaction extent for D(4) and D(5) in the presence of O(3) were quantified for two components of mineral dust aerosol, hematite and kaolinite. Some experiments with a carbonaceous particulate, carbon black, were also performed for D(5). The relative humidity (RH) inside the chamber was varied to investigate the influence of surface adsorbed water on the heterogeneous chemistry of the dust samples. With the dust samples, but not carbon black, the coadsorption of O(3) introduced a new reaction pathway, characterized by a linear, zero-order, decay of both gas phase cVMS and ozone. The new pathway does not saturate on the time scale of our experiments. Elevated RH was observed to decrease the total uptake of cVMS and ozone by the end of the experiment, but the characteristic linear decay was still present. The atmospheric loss of cVMS due to heterogeneous uptake is enhanced due to O(3), even at higher RH values, but the overall loss rate is reduced at RH values typical of the troposphere.

Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch.

OBJECTIVES: Hemospan (Sangart Inc, San Diego, CA) (MP4) is a hemoglobin-based oxygen carrier consisting of human hemoglobin modified with polyethylene glycol. This study evaluated the effects of MP4 on blood volume, hemodynamics, and metabolic stability in a rat model of hemodilution and hemorrhage. MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4). DESIGN: An open-label, randomized comparison of treatments. SETTING: Pharmaceutical industry. PARTICIPANTS: Sprague Dawley rats. INTERVENTIONS: Rats underwent 50% hemodilution with one of the solutions. Control rats were not hemodiluted. Blood volume was determined at baseline and 0, 60, and 120 minutes after exchange. In separate groups, hemodilution and subsequent 60% hemorrhage were examined to determine effectiveness of hemodilution. MEASUREMENTS AND MAIN RESULTS: Endpoints were blood volume after hemodilution and survival, hemodynamics, and acid-base status during hemorrhage. Volume expansion was similar with MP4 (159% of infused volume) and HES 260/0.45 (145%) and less with HES 130/0.4 (104%). The duration of expansion was longest with MP4 (1-2 hours). In the hemorrhage studies, 2-hour survival was 90% with MP4, 50% with controls, and 10% and 0% with HES 260/0.45 and HES 130/0.4, respectively. The severity of hemodynamic and acid-base changes paralleled the survival, with the least disturbance observed in MP4-treated animals. CONCLUSIONS: Hemodilution with MP4 was more effective in maintaining hemodynamic and metabolic stability than starch solutions or no hemodilution before simulated intraoperative hemorrhage. The benefit of MP4 is not ascribed solely to volume expansion. The results suggest that perioperative administration of MP4 may improve outcomes in surgical settings.

Impact of chronic plantar heel pain on health-related quality of life.

BACKGROUND: Chronic plantar heel pain (CPHP) is common and is thought to have a detrimental impact on health-related quality of life. However, no study has used normative data or a control data set for comparison of scores. Therefore, we describe the impact of CPHP on foot-specific and general health-related quality of life by comparing CPHP subjects with controls. METHODS: Foot Health Status Questionnaire scores were compared in 80 subjects with CPHP and 80 sex- and age-matched controls without CPHP. RESULTS: The CPHP group demonstrated significantly poorer foot-specific quality of life, as evidenced by lower scores on the foot pain, foot function, footwear, and general foot health domains of the Foot Health Status Questionnaire. The group also demonstrated significantly poorer general health-related quality of life, with lower scores on the physical activity, social capacity, and vigor domains. In multivariate analysis, CPHP remained significantly and independently associated with Foot Health Status Questionnaire scores after adjustment for differences in body mass index. Age, sex, body mass index, and whether symptoms were unilateral or bilateral had no association with the degree of impairment in people with CPHP. CONCLUSION: Chronic plantar heel pain has a significant negative impact on foot-specific and general health-related quality of life. The degree of negative impact does not seem to be associated with age, sex, or body mass index.

Oxidation and haem loss kinetics of poly(ethylene glycol)-conjugated haemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates.

Haemoglobin-based oxygen carriers can undergo oxidation of ferrous haemoglobin into a non-functional ferric form with enhanced rates of haem loss. A recently developed human haemoglobin conjugated to maleimide-activated poly(ethylene glycol), termed MP4, has unique physicochemical properties (increased molecular radius, high oxygen affinity and low cooperativity) and lacks the typical hypertensive response observed with most cell-free haemoglobin solutions. The rate of in vitro MP4 autoxidation is higher compared with the rate for unmodified SFHb (stroma-free haemoglobin), both at room temperature (20-22 degrees C) and at 37 degrees C (P<0.001). This appears to be attributable to residual catalase activity in SFHb but not MP4. In contrast, MP4 and SFHb showed the same susceptibility to oxidation by reactive oxygen species generated by a xanthine-xanthine oxidase system. Once fully oxidized to methaemoglobin, the rate of in vitro haem loss was five times higher in MP4 compared with SFHb in the fast phase, which we assign to the beta subunits, whereas the slow phase (i.e. haem loss from alpha chains) showed similar rates for the two haemoglobins. Formation of MP4 methaemoglobin in vivo following transfusion in rats and humans was slower than predicted by its first-order in vitro autoxidation rate, and there was no appreciable accumulation of MP4 methaemoglobin in plasma before disappearing from the circulation. These results show that MP4 oxidation and haem loss characteristics observed in vitro provide information regarding the effect of poly(ethylene glycol) conjugation on the stability of the haemoglobin molecule, but do not correspond to the oxidation behaviour of MP4 in vivo.

Effect of maleimide-polyethylene glycol hemoglobin (MP4) on hemodynamics and acid-base status after uncontrolled hemorrhage in anesthetized swine: comparison with crystalloid and blood.

BACKGROUND: Maleimide-polyethylene glycol hemoglobin, 4.3 g/dL (MP4), is a hemoglobin-based oxygen carrier consisting of native human hemoglobin modified with maleimide polyethylene glycol. This study evaluated resuscitation with MP4 after uncontrolled hemorrhage in anesthetized swine, and compared the effects of MP4 alone with those of standard-of-care crystalloid or crystalloid + blood. METHODS: Pigs were anesthetized with isoflurane and hemorrhaged 250 mL by controlled withdrawal, which was followed by a 5-mm tear in the abdominal aorta. Three groups of pigs (n = 7 each) were randomized after aortic tear to receive 500 mL of MP4, unlimited Ringer's acetate (RA), or 2 L of RA + 250 mL of autologous blood. Measurements included arterial and pulmonary artery pressures, central venous and pulmonary capillary wedge pressures, cardiac output, renal blood flow, urine output, arterial and venous blood gases, lactate concentration, and hemoglobin. Animals were monitored for 150 minutes after hemorrhage. RESULTS: Average body weight (22-24 kg) and hemorrhage volume (28-34 mL/kg) were similar in the three groups. The nadir of mean arterial pressure (23-25 mm Hg) and base excess (-3 to -4 mEq/L) after hemorrhage were similar in all groups, indicating equivalent shock in the three groups. Two hours after administration of MP4, arterial pressure and base excess were significantly improved compared with those of animals administered RA or RA + blood, despite a significantly lower volume of infused fluids (MP4 = 36 +/- 2 mL/kg; RA = 224 +/- 28 mL/kg; RA + blood = 110 +/- 10 mL/kg), and a significantly lower total hemoglobin than achieved with RA + blood. Arterial pressure did not rise above baseline values, cardiac output was not diminished, and systemic vascular resistance was unchanged after administration of MP4, indicating the lack of cardiac effects or peripheral vasoconstriction. CONCLUSIONS: These data demonstrate that resuscitation with a small volume of MP4 induces recovery from hemorrhage without vasoconstriction. Overall, the effects of MP4 alone on hemodynamic and acid-base indices appear to be of greater benefit than those observed with a large volume of RA alone or RA + blood.

Obesity and pronated foot type may increase the risk of chronic plantar heel pain: a matched case-control study.

BACKGROUND: Chronic plantar heel pain (CPHP) is one of the most common musculoskeletal disorders of the foot, yet its aetiology is poorly understood. The purpose of this study was to examine the association between CPHP and a number of commonly hypothesised causative factors. METHODS: Eighty participants with CPHP (33 males, 47 females, mean age 52.3 years, S.D. 11.7) were matched by age (+/- 2 years) and sex to 80 control participants (33 males, 47 females, mean age 51.9 years, S.D. 11.8). The two groups were then compared on body mass index (BMI), foot posture as measured by the Foot Posture Index (FPI), ankle dorsiflexion range of motion (ROM) as measured by the Dorsiflexion Lunge Test, occupational lower limb stress using the Occupational Rating Scale and calf endurance using the Standing Heel Rise Test. RESULTS: Univariate analysis demonstrated that the CPHP group had significantly greater BMI (29.8 +/- 5.4 kg/m2 vs. 27.5 +/- 4.9 kg/m2; P < 0.01), a more pronated foot posture (FPI score 2.4 +/- 3.3 vs. 1.1 +/- 2.3; P < 0.01) and greater ankle dorsiflexion ROM (45.1 +/- 7.1 degrees vs. 40.5 +/- 6.6 degrees; P < 0.01) than the control group. No difference was identified between the groups for calf endurance or time spent sitting, standing, walking on uneven ground, squatting, climbing or lifting. Multivariate logistic regression revealed that those with CPHP were more likely to be obese (BMI > or = 30 kg/m2) (OR 2.9, 95% CI 1.4 - 6.1, P < 0.01) and to have a pronated foot posture (FPI > or = 4) (OR 3.7, 95% CI 1.6 - 8.7, P < 0.01). CONCLUSION: Obesity and pronated foot posture are associated with CPHP and may be risk factors for the development of the condition. Decreased ankle dorsiflexion, calf endurance and occupational lower limb stress may not play a role in CPHP.

The effect of topical wheatgrass cream on chronic plantar fasciitis: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To investigate the efficacy of a topical wheatgrass cream for improving pain and function in patients with chronic plantar fasciitis. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Eighty participants with chronic plantar fasciitis were randomly assigned to a treatment group (wheatgrass cream) or a control group (placebo cream). All participants applied a cream twice daily for 6 weeks. Follow up was conducted at 6 and 12 weeks. MAIN OUTCOME MEASURES: Visual Analogue Scale (VAS) for daily first-step pain and the Foot Health Status Questionnaire (FHSQ) for overall foot function. Secondary measures of foot posture, calf muscle strength and range of ankle dorsiflexion were also assessed. RESULTS: No significant differences were found between groups with respect to main outcomes of first-step pain or foot function at any time. Both groups improved significantly from baseline to 6 weeks, and these improvements were maintained at 12 weeks. CONCLUSIONS: The topical application of wheatgrass cream is no more effective than a placebo cream for the treatment of chronic plantar fasciitis.

B-Flow Imaging in Lower Limb Peripheral Arterial Disease and Bypass Graft Ultrasonography.

Doppler ultrasonography plays a key role in the diagnosis of peripheral arterial disease, but is often limited by pitfalls that may be overcome by B-flow imaging. Thus far, there is little information on B-flow imaging for the assessment of peripheral arterial disease and bypass grafts in lower limbs. This article describes the authors' early experience with B-flow in the lower extremities. Sixty patients were included among a large cohort of patients routinely referred to the vascular laboratory for peripheral arterial disease and bypass graft assessments. Two experienced vascular sonographers performed all scans, comparing color Doppler ultrasonography with B-flow imaging. All scans were performed using a combination of the 9 L linear and C2-9 curvilinear transducers with the LOGIQ E9 system (GE Healthcare, Waukesha, WI, USA). Our experience indicates that this relatively unexplored technology has the potential to significantly improve peripheral blood flow evaluation. Nevertheless, B-flow imaging is not exempt from limitations and should be considered complementary to color Doppler ultrasonography.

Effect of oxygenated polyethylene glycol decorated hemoglobin on microvascular diameter and functional capillary density in the transgenic mouse model of sickle cell anemia.

Malemide polyethylene glycol-conjugated Hb (MP4OX, Sangart Inc.), a high-affinity low-concentration acellular hemoglobin (P50 = 5 mmHg, 4.3 g/dl) solution, has been shown to optimize microvascular perfusion and target oxygen delivery to anoxic tissue. Microvascular perfusion during an acute hypoxic challenge in a transgenic anemic sickle cell disease mouse model was studied with MP4OX and saline. Arterioles were dilated in both groups. Functional capillary density (FCD) was maintained at a higher level with MP4OX. In conclusion, MP4OX treatment reduced the hypoxia-mediated decline in FCD, an effect in part due to higher arterial pressure resulting in increased microvascular perfusion pressures.

Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4).

Cell-free Hb increases systemic and pulmonary pressure and resistance and reduces cardiac output and heart rate in animals and humans, effects that have limited their clinical development as "blood substitutes." The primary aim of this study was to evaluate the hemodynamic response to infusion of several formulations of a new polyethylene glycol (PEG)-modified human Hb [maleimide PEG Hb (MalPEGHb)] in swine, an animal known to be sensitive to Hb-induced vasoconstriction. Anesthetized animals underwent controlled hemorrhage (50% of blood volume), followed by resuscitation (70% of shed volume) with 10% pentastarch (PS), 4% MalPEG-Hb in lactated Ringer (MP4), 4% MalPEG-Hb in pentastarch (HS4), 2% MalPEG-Hb in pentastarch (HS2), or 4% stroma-free Hb in lactated Ringer solution (SFH). Compared with baseline, restoration of blood volume after resuscitation was similar and not significantly different for the PS (103%), HS2 (99%), HS4 (106%), and MP4 (87%) animals but significantly less for the SFH animals (66%) (P < 0.05). All solutions that contained MalPEG-Hb restored mean arterial and pulmonary pressure and cardiac output. Systemic vascular resistance was unchanged, and pulmonary arterial pressure and resistance were increased slightly. Both systemic and pulmonary vascular resistance increased significantly in animals that received SFH, despite less adequate blood volume restoration. Oxygen consumption was maintained in all animals that received MalPEG-Hb, but not PS. Base excess improved only with MalPEG-Hb and PS, but not SFH. Red blood cell O2 extraction was significantly increased in animals that received Hb, regardless of formulation. These data demonstrate resuscitation with MalPEG-human Hb without increasing systemic vascular resistance and support our previous observations in animals suggesting that the efficacy of low concentrations of PEG-Hb in the plasma results from reduced vasoconstriction.