Biomedical subjects
D Trunkey
Publications and source records attributed to D Trunkey.
Initial treatment of patients with extensive trauma.
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Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes.
Reactive oxygen species contribute to the tissue injury seen after reperfusion of ischemic myocardium. We propose that toxicity originates from the effect that mitochondrial peroxide metabolism has on substrate entry into oxidative pathways. To support our contention, cultured adult rat cardiomyocytes were incubated with physiological concentrations of peroxide. The cellular extract and incubation medium were analyzed for adenine nucleotides and purines by reverse-phase high-pressure liquid chromatography. Cellular glutathione efflux was determined by enzymatic analysis of the incubation medium. Pyruvate dehydrogenase (PDH) activity was determined in the cultured myocytes as well as in freshly isolated cardiac mitochondria using [1-C14]pyruvate. Extracellular glutathione rose 3.3-fold in response to small doses of peroxide (approximately 108 nmol/mg protein). Likewise, small quantities of peroxide reduced total cellular adenine nucleotides to 50-60% of control values with only a modest (0.95-0.91) reduction in energy charge [ATP + 1/2 ADP)/(ATP + ADP + AMP]. Peroxide-treated myocytes selectively release inosine and adenosine, as only these two purine degradation products were detected in the incubation medium. The most dramatic response was a peroxide dose-dependent inhibition of PDH activity in cultured myocytes as well as freshly isolated mitochondria; just 65 and 30 nmol peroxide/mg protein induced a 50% reduction in cellular and mitochondrial PDH activity, respectively. In conclusion, physiological quantities of peroxide potently inhibit PDH in cultured cardiomyocytes and isolated cardiac mitochondria. PDH inhibition blocks the aerobic oxidation of glucose and inhibits the oxidative phosphorylation of ADP, which in turn leads to cellular adenine nucleotide degradation.
Importance of spontaneous alpha-ketoacid decarboxylation in experiments involving peroxide.
The potential role of spontaneous alpha-ketoacid decarboxylation as a source of interference in experiments involving peroxide was investigated. The assay of pyruvate dehydrogenase activity in isolated renal mitochondria was employed as an example. Spontaneous peroxide-induced pyruvate decarboxylation competed significantly with enzymatic decarboxylation at peroxide concentrations greater than 50 microM. Corrected values for enzymatic decarboxylation could be obtained by subtracting spontaneous decarboxylation rates from rates obtained in the presence of mitochondria. At higher peroxide concentrations (greater than 200 microM), reaction product accumulates (acetoacetate) to levels which may have regulatory effects on mitochondrial metabolism. The divalent cations, Ca2+ and Mg2+, both accelerate spontaneous peroxide-induced pyruvate decarboxylation while other components of the assay medium had an inhibitory effect on the reaction. The results are discussed in relation to the currently accepted reaction mechanism. Investigators who perform experiments involving reactive oxygen species should be familiar with this often overlooked reaction.
Ionized calcium: the effect of septic shock in the human.
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Evaluation of management of the emergency right hemicolectomy.
To evaluate the morbidity and mortality attending emergency resection of the right colon, we studied retrospectively 119 consecutive patients from two major centers, particularly examining the role of delayed anastomosis (initial ileostomy with subsequent ileocolic anastomosis). Emergency right colectomy was defined as an operative procedure in which partial resection of the terminal ileum and total or partial resection of the cecum and/or ascending colon were necessary before the colon could be evacuated and prepared as might be the case in elective resection. Ninety patients underwent primary anastomosis; hospital mortality and morbidity were 26 and 11%, respectively. Among 29 patients who underwent ileostomy, hospital mortality was 38%; hospital morbidity was 10%. In general, the patients selected for ileostomy were somewhat more ill or had more severe injury. only 17% of all deaths and 8% of all serious complications could be attributed to the anastomosis, leaving little statistical opportunity for improvement by deleting it. The data indicate that a very high mortality (29%) attends emergency right hemicolectomy. Our study indicates that ileostomy in lieu of anastomosis does not reduce this high mortality.
Hospital care of the trauma patient.
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Visceral vessel erosion associated with pancreatitis. Case reports and a review of the literature.
Visceral artery erosion is an uncommon but disasterous complication of pancreatitis. When gastrointestinal bleeding or severe intra-abdominal hemorrhage is associated with pancreatitis and the usual sources of bleeding are not detected by endoscopy or barium studies, erosion of a visceral vessel should be suspected. We present nine cases and an additional 44 cases from previous reports are reviewed. A palpable abdominal mass was present in 59% of the patients; however, a pseudocyst was present in 78%. Arteriography was performed in 15 patients and the source of bleeding was evident in 14. The splenic artery was the most common site of bleeding, although the other branches of the celiac axis and the middle colic artery have been involved. Successful treatment consisted of ligation of the bleeding vessel and, if present, drainage of the pseudocyst. Depending on the location of the vessel and the pseudocyst, major resections may be necessary. When bleeding and the pancreatic inflammatory process involved the colon, ligation of the bleeding site, drainage of the area, and colostomy was the most successful form of treatment.
Ionized calcium and magnesium: the effect of septic shock in the baboon.
Ionized calcium (Ca2+) and ionized magnesium (Mg2+) are important intracellular "second messengers" and control exictation-contraction coupling, excitation-secretion, oxidative phosphorylation, and mitochondrial acid-base balance. The present study examines the effect of septic shock on serum (Ca2+) and (Mg2+). Five adult female baboons were subjected to live E. coli septic shock and then resuscitated. Three baboons served as controls. Ca2+ was measured by the Orion SS-20 flow-through calcium electrode and Mg2+ calculated by the method of Killen. Other measurements included: total calcium, bound calcium, total magnesium, bound magnesium, phosphate, albumin, globulin, hemotocrit, and total protein. This study shows that there are significant disturbances of Ca2+ and Mg2+ during septic shock in the baboon. These disturbances may in part explain cellular dysfunction during shock including: decreased myocardial contractility, inappropriate secretion of endocrine cells, decrease in oxidative phosphorylation, and mitochondrial acidosis.
Better definition of the usefulness of burn units.
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An experience with a LeVeen ascites shunt.
A patient with intractable ascites was treated by placement of the LeVeen peritoneovenous shunt. Shunt failure was caused by malpositioning of the venous limb in the inferior vena cava. This was demonstrated by injection of water-soluble contrast material into the venous limb. Revision of the shunt led to diuresis, weight loss, and reduction of ascites. The physiologic process of the LeVeen shunt is reviewed and we suggest placement of a radiopaque marker into the tubing.
Monitoring resuscitation of primates from hemorrhagic and septic shock.
Monitoring data in 16 primates subjected to septic or hemorrhagic shock and resuscitated with various solutions is presented. From a paractical standpoint, central venous pressure and urine output appear to be the best indices to use in the emergency department for resuscitation of the shock victim. The sophisticated measurements such as cardiac output, thermodye volumes, pulmonary artery wedge pressure and oxygen consumption should be reserved for the individual with depressed cardiovascular reserves and who needs "fine tuning" of his volume status.
Calcium flux during hemorrhagic shock in baboons.
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Rural trauma: the Oregon experiment.
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