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.

Pilot scale production of pyrogen-free human hemoglobin for research.

A pilot scale production facility for the preparation of 20 to 30 liters of stroma-free hemoglobin is described. The system is capable of producing pyrogen-free solutions for research purposes. It is not certified for production of parenteral solutions for human use, but the plan could be implemented to meet standards for such materials.

Dextran-coupled deferoxamine improves outcome in a murine model of head injury.

Tissue damage involving oxygen-derived free radicals may be greatly exacerbated by free, reactive iron, which acts as a catalyst in oxidative reactions. The effects of free iron can be attenuated by the administration of deferoxamine (DFO), an iron chelator. However, DFO has limited therapeutic utility because it has a short plasma half-life (approximately 5.

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.

Influences of traumatic brain injury on the outcomes of delayed and repeated hemorrhages.

Effects of traumatic brain injury (fluid percussion) on outcomes of hemorrhage, either delayed (70.5 min after the injury) or repeated (0.5 min after injury, then followed by a delayed hemorrhage), were examined in 4 groups of 10 anesthetized rats.

Blood Substitutes.

Although the need for an alternative to red cells for transfusion has been recognised since the initial description of the circulation of the blood by William Harvey in 1628, there is still no approved product available to clinicians. Recent concern over the safety of human blood has stimulated a renewed interest in finding alternatives to transfusion of red cells. Two types of solutions, those based on perfluorocarbons and those based on haemoglobin are currently being aggressively developed.

Influence of nicotine on tissue trace element concentrations and tissue antioxidant defense.

Both altered trace element metabolism and cigarette smoking have been proposed to be risk factors for cardiovascular disease (CVD). Thus, it is important to identify the mechanisms by which cigarette smoke alters trace element metabolism. In the present study, serum trace element concentrations were measured in 19 smokers and 13 nonsmokers.

Cardiovascular and pulmonary effects of morphine in conscious pigs.

Cardiovascular and pulmonary effects of morphine (1 mg/kg bolus iv) were investigated in conscious chronically instrumented pigs, a species exhibiting an excitable response. Control animals received an equivalent volume (less than 2 ml) of normal saline. Morphine induced an immediate but small increase in cardiac output and substantial increases in heart rate, mean systemic and pulmonary arterial pressure, left and right ventricular work, hematocrit, and hemoglobin concentration, but did not change stroke volume or systemic vascular resistance.

Determination of the rate and equilibrium constants for oxygen and carbon monoxide binding to R-state human hemoglobin cross-linked between the alpha subunits at lysine 99.

The kinetics of O2 and CO binding to R-state human hemoglobin A0 and human hemoglobin cross-linked between the alpha chains at Lys99 residues were examined using ligand displacement and partial photolysis techniques. Oxygen equilibrium curves were measured by Imai's continuous recording method (Imai, K. (1981) Methods Enzymol.

Neuroendocrine responses to hypertonic saline/dextran resuscitation following hemorrhage.

The neuroendocrine responses to resuscitation with 7.5% hypertonic saline/6% Dextran-70 (HSD) following hemorrhagic hypotension were evaluated in conscious swine. Following hemorrhage (37.

The detrimental effects of intravenous crystalloid after aortotomy in swine.

We tested the hypothesis that, after aortotomy, rapidly replacing three times the blood volume deficit with intravenous crystalloid will increase hemorrhage and decrease survival. Sixteen anesthetized Yorkshire swine underwent splenectomy and stainless steel wire placement in the infrarenal aorta and were instrumented with pulmonary artery and carotid artery catheters. The wire was pulled, producing a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage.

Suppression by traumatic brain injury of spontaneous hemodynamic recovery from hemorrhagic shock in rats.

The effects of brain trauma on cardiovascular and endocrine responses to hemorrhage were investigated. Forty anesthetized rats were randomly assigned to one of four groups of 10 rats each: a control group (Group C): a group with induction of hemorrhage at 16.2 ml/kg/10 min (Group H); a group with fluid-percussion brain injury at a peak pressure of 1.

Modification of pituitary-adrenal axis responses to hemorrhage by handling techniques in conscious swine.

Responses of the pituitary-adrenal axis to hemorrhagic hypotension were compared in chronically instrumented swine that were allowed to move freely in a holding cage (n = 11) and swine trained to accept physical restraint in a Pavlov sling (n = 14). Seven to ten days after surgical preparation, each animal was hemorrhaged (37.5 ml/kg over 60 min) while confined to its environment.

Percutaneous penetration and skin retention of topically applied compounds: an in vitro-in vivo study.

Radiolabeled compounds with varying partition coefficients (paraoxon, benzoic acid, parathion, and DDT) were chosen to study the percutaneous penetration and extent of dermal retention in pig skin both in vitro and in vivo. Radiolabel distributions within the skin were determined from 1 min to 24 h after application in ethanol. The distribution of radioactivity in the skin during the first 4 h was comparable between in vitro and in vivo experiments.

Metabolic actions of morphine in conscious chronically instrumented pigs.

Effects of a modest dose of morphine sulfate (1 mg/kg) on total body energy metabolism, body thermal status, and the plasma concentrations of certain electrolytes and metabolites were investigated in conscious chronically instrumented pigs (n = 8). Control pigs (n = 8) received an equivalent volume of normal saline. Intravenous morphine injection led to an excitatory state associated with significant (P less than or equal to 0.

Simultaneous determination of inosine, hypoxanthine, xanthine, and uric acid and the effect of metal chelators.

We describe a sensitive, reproducible method for the simultaneous determination of the ATP catabolites inosine, hypoxanthine, xanthine, and uric acid in biological samples and organ perfusate using reverse-phase chromatography and multiwavelength detection at 254, 270, and 292 nm. Sample preparation includes precipitating proteins with perchloric acid, neutralizing the sample, passing the supernatant over a polyethyleneimine column, and analyzing the collected fractions by high-performance liquid chromatography. Addition of metal chelators to the perchloric acid resulted in increased values for xanthine, hypoxanthine, and uric acid.

Metabolic changes in the mouse kidney after subcutaneous injection of butyl 2-chloroethyl sulfide.

Subcutaneous exposure to vesicants such as butyl 2-chloroethyl sulfide (butyl mustard, BCS) produces local tissue injury (vesication) primarily by alkylation and cross-linking of the purine nucleotides and rapidly binding to proteins. We recently reported that administering BCS can cause other biochemical and morphological alterations, not only in tissues at the injection site but in other areas as well. In this study, we have examined the metabolic effects of BCS administration on the mouse kidney.

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).

Noninvasive infrared thermometry for application in skin biology--I: Model measurements and local measurements on the dorsal surface of the rabbit.

Understanding thermal energy distribution is essential to interpret skin temperature for diagnosing various pathological and experimental conditions. The present paper investigates temperature data measurements acquired with an infrared thermometer system and in vivo temperature measurements on the backs of New Zealand rabbits. Local differences in skin temperature are significant around bony structures and in visceral areas.

Carbon dioxide binding to human hemoglobin cross-linked between the alpha chains.

The binding of carbon dioxide to human hemoglobin cross-linked between Lys alpha 99 residues with bis(3,5-di-bromosalicyl) fumarate was measured using manometric techniques. The binding of CO2 to unmodified hemoglobin can be described by two classes of sites with high and low affinities corresponding to the amino-terminal valines of the beta and alpha chains, respectively (Perrella, M., Kilmartin, J.

Theodor Kocher and the Scientific Foundation of Wound Ballistics.

The systemic and rational approach used by Kocher, coupled with his interest in research of wound ballistics for more than 40 years, resulted in a clear elucidation of the principles that form the basic scientific foundation of modern wound ballistics. The validity of his work has been proved repeatedly on the battlefields of the world for more than a century. Presently, more than ever before, the sound scientific precepts revealed by Kocher are essential to keep technologic investigation within the framework of good judgment.

Neuroendocrine abnormalities in patients with traumatic brain injury.

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians.

Immediate hypertensive response to fluid percussion brain injury may be related to intracerebral hemorrhage and hypothalamic damage.

Fluid percussion brain injury is associated with an immediate rise in mean arterial pressure (MAP). However, the cerebral morphologic basis for this response is still not clear. Thirty-four anesthetized rats were injured using a lateral craniotomy preparation.