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Biomedical subjects

A E Baue

Publications and source records attributed to A E Baue.

At least 19 recordsLinked to original sources

The effect of shock on blood oxidation-reduction potential.

Oxidation-reduction (redox) potential measurements were made in the blood of rabbits subjected to hemorrhagic shock followed by treatment with a mild oxidizing agent (albumin). Control redox potential reading corrected for pH was -8.8 +/- 1.3 millivolts (mV) in arterial blood (A) and -18.0 +/- 2.0 mV in venous blood (V). This A-V difference indicated that hydrogen equivalents coming from muscle and other tissues were partially consumed in the lungs. A 20-mV drop on the V and a 13 mV on the A side was seen after shock. This did not fully return to control 2 h after return of the shed blood. Infusion of 2 g of albumin/kg/h raised the V redox potential to control, but it returned to untreated levels when the albumin was discontinued. The reductive load imposed on the animal by shock appeared to be large and not readily reversed by reperfusion or by the quantity of albumin given. Thus, it may be concluded that cellular respiration had not been adequately restored. This reductive load may impede recovery by suppression of cellular respiration and other cell and organ functions.

Animals

The horror autotoxicus and multiple-organ failure.

An injury or operation with tissue injury, ischemia, and sepsis provokes a neuroendocrine, immune, and inflammatory response to promote survival and heal the wound. If the injury is massive or complicated by infection, the inflammatory response may become generalized and excessive, producing organ and tissue damage and multiple-organ failure, a modern "horror autotoxicus." Many inflammatory mediators have been identified. In isolated organs, the use of blocking mediators to prevent combined ischemia-reperfusion injury is feasible. With regional ischemia, activator attenuation may be possible. It is unclear whether blockade or modulation of all or part of an excessive inflammatory response will be possible, helpful, and without hazard in patients with multisystem injuries or sepsis. Feedback loops and control mechanisms of these systems will better define such possibilities. Employment of growth factors and other protective agents to stimulate wound healing, infection control, and host resistance may be more helpful. Ultimately, prevention of multiple-organ failure requires sound surgical judgment, techniques, and organ support.

Adult

Pyrimidine-enhanced purine uptake in hepatocytes and improved survival from hypovolemic shock.

To assess the effect of pyrimidines on the incorporation of purines into rat hepatocytes, monolayer preparations of hepatocytes were incubated with radiolabeled precursors and their uptake determined. The uptake of purine precursors (inosine monophosphate, inosine, and hypoxanthine) was 27.8 +/- 1.31 nmoles per well, per 30 min. In the presence of added pyrimidines (uridine monophosphate, uridine, and orotate), this increased by 22%. Further enhancement (45%) was observed when L-dihydroxyphenylalanine (L-DOPA) plus pyridoxal-5'-phosphate was added to the purine/pyrimidine incubation medium. The effect of increased uptake of purines on survival after hypovolemic shock was also studied. Rats were bled to a blood pressure of 40 mmHg for 105 min and then treated with return of shed blood plus saline with or without purines and pyrimidines. Survival at 24 hr was 43% (15/35) in control animals, 66% (8/12) (P = 0.276) when treated with inosine monophosphate (IMP) and aspartate (60 mumoles/kg each), and 83% (10/12) (P = 0.037) for IMP with aspartate and orotate treatment (60 mumoles/kg each). Thus, the addition of orotate enhanced survival possibly by promoting salvage or by uptake of purines. Nucleotide concentrations in the livers of animals after shock which had received IMP and orotate demonstrated a return of both ATP and energy charge to normal, further indicating the value of this treatment.

Adenosine Diphosphate

Clearance and maintenance of blood nucleotide levels with adenosine triphosphate-magnesium chloride injection.

ATP-MgCl2 has been found to be helpful in experimental animals after shock and ischemia with improvement in organ function and survival. The reasons for this pharmacologic action are unclear. To evaluate the clearance and circulation of ATP and its metabolites after intravenous injection, 20 rabbits received ATP-MgCl2 as a bolus injection or a continuous intravenous infusion. Arterial blood was withdrawn, and ATP and its metabolites were measured using a high-performance liquid chromatography (HPLC) technique with ultraviolet (UV) absorption. Forty seconds following a bolus injection, only 1% of the injected dose was present in arterial blood as ATP, and at 280 sec only inosine remained. With a 60 min continuous ATP-MgCl2 infusion, the inosine level peaked at 62.9% at 30 min and was 37.6% at 60 min, whereas ATP was 4.9% and AMP was 17.4% at 60 min. Thus a single dose of ATP-MgCl2 has a half-life of less than 40 sec as ATP. With a continuous infusion, although some ATP circulates, inosine and AMP are the major remaining nucleotides. Thus, the beneficial effects of ATP-MgCl2 may be through ATP itself with magnesium or with adenine nucleotide metabolites for recycling of the nucleotides, phosphorylation of cell membrane inositides, and/or its vasoactive effects.

Adenosine Diphosphate

Preoperative chemotherapy and radiotherapy for esophageal carcinoma.

From October 1986 to January 1991, 47 patients with esophageal cancer (29 squamous, 18 adenocarcinoma) were treated with simultaneous radiotherapy (3000 or 3600 cGy) and chemotherapy (infusional 5-fluorouracil, cisplatin) delivered during a 5-week period. This treatment was well tolerated; 44 patients (94%) completed a full course of therapy, 40 (85%) had relief from dysphagia, and 21 (45%) noted either weight gain or no net weight loss. One patient (2%) died of complications (tracheoesophageal fistula, perforated ulcer) during chemotherapy and radiotherapy. The remaining 46 patients were referred for operation. Six refused because of excellent relief of their dysphagia, and one was denied operation. Thirty-nine patients went to operation, and 34 (83%) had lesions that were resectable. Eight of the 39 surgically treated patients (21%) had no evidence of residual tumor identified in the resected specimens. One of these complete responders died 7 weeks postoperatively after multiple complications (3% operative mortality rate). Three of the remaining seven have also died since the operation, one of recurrent cancer and two with no known recurrent disease. Actuarial survival in this present series was significantly better than that of our 1980 to 1985 historical control patients (p less than 0.005). There was no difference between patients with squamous carcinoma and those with adenocarcinoma with regard to the prevalence of complete response or long-term survival. Survival of the seven patients who did not undergo operation was comparable with that of the 34 patients in whom esophagectomy was performed. This study suggests that combined preoperative chemotherapy plus radiotherapy for esophageal cancer is well tolerated, provides excellent palliation of symptoms, allows for a high rate of resectability, is equally effective for squamous carcinoma and adenocarcinoma, and provides encouraging early results with regard to long-term survival. The data also call into question the role of esophagectomy, particularly in patients who have a complete response to preoperative therapy.

Actuarial Analysis

Nutrition and metabolism in sepsis and multisystem organ failure.

Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure. When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated. Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount. Organ and nutritional support to prevent complications is necessary. The gastrointestinal tract should be used for nutrition whenever possible with a blenderized regular diet with fiber, glutamine, and short-chain fatty acids to protect and preserve the gut. If parenteral nutrition is necessary, special solutions may be necessary for the liver, kidneys, or lungs. If not, protein with 45% branched-chain amino acid, medium- and short-chain triglycerides, glutamine supplementation, and carbohydrates seem best. Other substances are being evaluated that may be helpful in nutrition and organ support, including arginine, xylitol, growth hormone, and anabolic steroids. Multiple organ failure should be prevented, if at all possible, by stopping or controlling the injury, removing as much necrotic tissue as possible, improving blood flow and oxygen consumption, supporting metabolism, and preventing infection or treating it early and adequately. Nutritional support plays a key role in preventing metabolic failure.

Energy Metabolism

Surgery.

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Cardiac Surgical Procedures

Studies of peripheral glucose uptake during sepsis.

Glucose intolerance occurs in patients with sepsis, and resistance to insulin has been thought to be part of this process. To study this phenomenon, peritonitis was produced in rats by cecal ligation and puncture. One group was killed ten hours later (early sepsis). A second group of rats was killed 16 to 24 hours after ligation, just prior to their expected death (late sepsis). Insulin stimulated glucose uptake to the same extent in muscles from rats in early sepsis, late sepsis, and from control rats. Even at an insulin concentration that produced submaximal stimulation of glucose uptake, no difference in glucose uptake between the three groups of muscles was observed. Thus, there was no resistance to the stimulatory action of insulin on glucose uptake by skeletal muscle during early and late sepsis. However, basal glucose uptake by isolated soleus muscle from animals in late sepsis was significantly increased compared with controls when these muscles were incubated in an aerobic environment. Under anaerobic conditions, glucose uptake in these two groups of muscles increased to the same level. This indicates that there is some stimulus that increases glucose uptake in late peritonitis and may explain the hypoglycemia of late experimental or untreated sepsis. This stimulus could be hypoxia or some other factor resulting from decreased blood flow and increased anaerobic metabolism.

Animals

Impairment of reticuloendothelial system function with sepsis and its improvement with ATP-MgCl2 plus glucose administration.

Peritonitis in rats was produced by cecal ligation and puncture. Sixteen hours following cecal ligation and puncture, the gangrenous cecum was removed and the animals received either 4 ml saline (nontreated), 0.75 ATP-MgCl2 (100 mumoles ATP plus 50 mumoles MgCl2), and 2.0 ml of 50% glucose or 2.0 ml of 50% mannitol and 1.25 ml saline. Two hours after the removal of the cecum, RES function was evaluated by measuring the intravascular clearance of a 131 I triolein-labeled gelatinized test lipid emulsion. The intravascular half-time (t1/2) in the nontreated animals was double that of sham-operated animals, suggesting that significant depression in RES function occurred during sepsis. Administration of ATP-MgCl2 plus glucose following sepsis resulted in t1/2 values similar to those of sham-operated animals, indicating that the impairment of pagocytic activity of the RES was reversed with treatment. The beneficial effect of treatment following sepsis does not appear to be due to hypertonicity, since administration of 50% mannitol failed to decrease the t1/2. The precise mechanism of the beneficial effect of ATP-MgCl2 + glucose on restoration of RES function is not known.

Adenosine Triphosphate

Effect of sepsis on tissue adenine nucleotide levels.

Tissue adenine nucleotides were measured in rats to determine if there is depletion of energy stores associated with sepsis. Peritonitis was produced by cecal ligation and cecal puncture. At 16 to 24 hours after ligation, rats which were lethargic but still normotensive (late sepsis) and showed clinical and laboratory confirmation of peritonitis-sepsis were stunned by a blow on the head, and small pieces of tissue were removed and frozen. Adenine nucleotides were measured enzymatically. In late sepsis adenosine triphosphate (ATP) levels in liver and kidney decreased significantly; however, no significant decreases were observed in the diaphragm or gastrocnemius muscle. Hydrogen polarograph measurements of hepatic blood flow indicated that flow was decreased markedly at this stage of peritonitis. A second group of rats was prepared in the same manner, except they were studied 10 hours after ligation (early sepsis). Most rats at this stage of sepsis appeared to be only mildly ill; however, blood cultures obtained from six rats so prepared all were positive. These rats did not show any decrease in either hepatic blood flow or tissue adenine nucleotides. Thus the changes in adenine nucleotides observed in late sepsis (lpw-flow septic rats) are similar to those seen during early hemorrhagic shock and suggest inadequate perfusion associated with peritonitis as the cause.

Adenine Nucleotides

Surgery.

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Child