Biomedical subjects
C L Rice
Publications and source records attributed to C L Rice.
Fluosol-DA as a red-cell substitute in acute anemia.
We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (+/- SE) of 7.2 +/- 0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0 +/- 0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7 +/- 0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3 +/- 4.3 hours), and the limited total dose. Six of the eight patients receiving Fluosol-DA died. One of the survivors received red-cell transfusions against his wishes, under a court order, after his total Fluosol-DA dose. Fourteen of the 15 moderately anemic patients survived. The data in this select group of patients refusing blood products suggest that, after blood loss, Fluosol-DA is unnecessary in moderate anemia and ineffective in severe anemia.
Experimental pulmonary inflammatory injury in the monkey.
Inflammatory pulmonary injury was induced in Macaca mulatta rhesus monkeys by the intrabronchial instillation of the formylated peptide norleu-leu-phe (FNLP) or phorbol myristate acetate (PMA). Indicators of pulmonary injury included an increase in mean protein content of bronchoalveolar lavage (BAL) fluid from 0.51 mg/ml in untreated animals to 3.74 mg/ml and 6.64 mg/ml in FNLP- and PMA-treated animals, respectively, the appearance of a diffuse pulmonary infiltrate in chest roentgenograms, and histologic evidence of a predominantly neutrophilic leukocytic infiltration. Concomitant with the appearance of pulmonary injury was the generation of proteases and oxidants in the BAL fluids. Neutrophil elastase, bound to alpha 1-protease inhibitor (alpha 1-PI), was found to increase from 0.47 micrograms/ml in untreated monkeys to 0.99 micrograms/ml in FNLP-treated animals and 1.23 micrograms/ml in monkeys receiving PMA. Radioiodinated human prekallikrein, instilled for 2 min into the inflammatory site and retrieved by lavaging, was found to have undergone proteolytic cleavage; this cleavage was not consistently inhibitable with the inclusion of antibody to elastase. BAL fluids were shown to contain an amidolytic activity when tested on the synthetic substrate H-D-pro-phe-arg-pNA. This activity was partially inhibitable with known inhibitors of active Hageman factor and kallikrein. beta-Glucuronidase levels in the BAL fluids increased from 0.85 U/ml to 4.36 U/ml and 8.25 U/ml in FNLP- and PMA-treated animals, respectively. Myeloperoxidase (MPO) levels also increased from 1.37 OD U/ml X min to 16.59 and 30.47 OD U/ml X min in the same groups of animals. Oxidant generation was also assessed in several different ways. The specific activity of the oxidant-sensitive inhibitor alpha 1-PI recovered in the BAL fluid decreased from 0.80 in control samples to 0.57 and 0.65 in FNLP- and PMA-treated animals. That this inactivation was due to oxidant injury of the molecule was confirmed by the return to full activity of four out of five BAL samples after their incubation with the reducing agent dithiothreitol in the presence of methionine sulfoxide peptide reductase. The specific activity of catalase in the BAL fluids of animals given 3-amino, 1,2,4 triazole (AT) 1 h before lavaging showed drops from 0.97 in untreated monkeys to 0.04 in FNLP-treated and 0.49 in PMA-treated monkeys. MPO levels also fell in the AT-treated injured animals from 16.59 to 0.85 delta OD/min X ml in FNLP animals in the absence and presence of AT, and 30.47 to 0.60 delta OD/min X ml in PMA-treated animals. Inhibition of MPO by AT was shown in vitro to be H2O2 dependent. Total glutathione levels in the BAL fluids did not change appreciably after FNLP or PMA treatment. These studies present substantial evidence of the generation of both proteases and oxidants during the establishment of acute pulmonary inflammatory injury in an experimental primate model.
High frequency ventilation and the accumulation of extravascular lung water.
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Fluid resuscitation in shock.
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The physiologic basis of the use of blood and blood products.
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Does interstitial pressure oppose lung water formation?
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Alveolar pressure in fluid-filled occluded lung segments during permeability edema.
In a model of increased hydrostatic pressure pulmonary edema Parker et al. (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 44: 267-276, 1978) demonstrated that alveolar pressure in occluded fluid-filled lung segments was determined primarily by interstitial fluid pressure. Alveolar pressure was subatmospheric at base line and rose with time as hydrostatic pressure was increased and pulmonary edema developed. To further test the hypothesis that fluid-filled alveolar pressure is determined by interstitial pressure we produced permeability pulmonary edema-constant hydrostatic pressure. After intravenous injection of oleic acid in dogs (0.01 mg/kg) the alveolar pressure rose from -6.85 +/- 0.8 to +4.60 +/- 2.28 Torr (P less than 0.001) after 1 h and +6.68 +/- 2.67 Torr (P less than 0.01) after 3 h. This rise in alveolar fluid pressure coincided with the onset of pulmonary edema. Our experiments demonstrate that during permeability pulmonary edema with constant capillary hydrostatic pressures, as with hemodynamic edema, alveolar pressure of fluid-filled segments seems to be determined by interstitial pressures.
Angiotensin-converting enzyme (ACE) in sepsis.
Angiotensin-converting enzyme (ACE) is localized to the luminal surface of pulmonary endothelial cells, where it converts angiotensin I and activates bradykinin. Sepsis may result in endothelial cell dysfunction. We have previously reported that the marked decrease in serum ACE in patients with the Adult Respiratory Distress Syndrome (ARDS) is present only in septic patients. Serum was evaluated in seven baboons made septic by the infusion of live E coli. There was a significant decline in serum ACE from a control value of 41.5 +/- 4.2 to 25.8 +/- 2.2 at 8 h (P less than 0.05), which correlated with the 65 +/- 11 torr decline in mean arterial pressure. There was no change in PaO2. We conclude that sepsis results in marked depletion of serum ACE activity, which corresponds to the decrease in mean arterial pressure, and may reflect reduced bradykinin inactivation.
Hemoglobin solution: is a normal [Hb] or P50 more important?
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Albumin therapy in permeability pulmonary edema.
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Extravascular lung water as a function of the magnitude of pulmonary artery pressure in the septic pig.
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Fluorocarbon emulsions: methodology to assess efficacy.
The fluorocarbon emulsion Fluosol-DA (20%) is an acellular O2 carrier that has potential as a red cell substitute. Clinical evaluation of efficacy requires knowledge of the ability of the perfluorochemical (pfc) phase to both load and unload O2. A method is described to measure the oxygen dissolved in the pfc and aqueous phases, and the oxygen chemically bound to hemoglobin, during use of this drug. These O2 contents are used to calculate the contribution of the pfc phase to total O2 delivery and O2 consumption (VO2) and the fractional extraction of O2 in the pfc phase. The technique requires a blood gas analyzer, a microhematocrit centrifuge, and a standard co-oximeter found in many blood gas laboratories. This technique appears to be simple and reliable, and should facilitate the evaluation of efficacy of fluorocarbon emulsions.
Hemoglobin solutions as red cell substitutes.
Hemoglobin solutions have potential as temporary red cell substitutes. Their efficacy has been demonstrated by their ability to maintain life-supporting levels of O2 consumption and CO2 production in animals virtually free of red cells. They do not exhibit major toxic effects, but transient alterations in renal function remain a concern. Cardiac output does not increase in the face of acute anemia associated with isovolemic exchange transfusion with hemoglobin solution. However, cardiac reserve does not diminish significantly after infusion of hemoglobin solution. Alterations in production techniques may lead to a polymerized hemoglobin solution that has a hemoglobin concentration and P50 close to fresh whole blood. Though this development is encouraging, it is clear that no perfect red cell substitute currently is available.
Accuracy of pfc emulsion measurements.
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Pulmonary dysfunction in sepsis: is pulmonary edema the culprit?
Pulmonary dysfunction is a well-recognized sequela of sepsis, which has been quantitated by calculation of intrapulmonary shunt (Qs/Qt) and, more recently, by measurement of extravascular lung water (EVLW). We sought to demonstrate the relationship between Qs/Qt and EVLW in sepsis. Nine pigs were given live E. coli infusions and five control pigs received only crystalloid. Pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), arterial blood gases (ABG), and mixed venous blood gas levels were measured serially and Qs/QT calculated. EVLW was measured simultaneously using the thermal-green dye technique. The septic group showed increases from baseline in PAP (2.4 X), EVLW (2x), and Qs/Qt (1.6x). Regression analysis of Qs/Qt or EVLW yielded a correlation coefficient of r = 0.48. We concluded that while sepsis can result in both increased EVLW and Qs/Qt, the correlation is not sufficiently strong to account for the increased Qs/Qt on the basis of elevated EVLW alone. The possible relationships of arterial hypoxemia and pulmonary edema, ventilation-perfusion mismatch, and alterations in the normal hypoxic vasoconstrictive response in sepsis are considered.
Occult duodenal perforation complicating cerebral infarction: new problems in diagnosis of Cushing's ulcer.
Cushing's ulcers of the duodenum are well known complications of neurosurgery, head trauma, and other causes of increased intracranial pressure. Perforation of Cushing's ulcer of the duodenum is infrequently described. That the use of high-dose corticosteroids for cerebrovascular infarct in an aphasic patient may obscure the symptomatology and physical findings of a perforated Cushing's ulcer has not been described to our knowledge. We report a patient with a large left hemispherical infarct and resultant aphasia who developed a perforated duodenal ulcer and extensive chemical peritonitis while receiving high dose corticosteroids for increased intracranial pressure. She was unable to register any complaints and the typical physical findings of perforated duodenal ulcer with chemical peritonitis were virtually absent. A high index of suspicion must be maintained for a perforated Cushing's duodenal ulcer in the patient receiving high dose dexamethasone despite the presence of nonspecific symptomatology and abdominal findings. Elevated serum gastrin levels, as in this patient, may also indicate the patients with increased intracranial pressure who are at greater risk for developing Cushing's ulcer.
Red cell substitutes: hemoglobin solution or fluorocarbon?
Stroma-free hemoglobin (SFH) and Fluosol-DA (FL-DA) are the two acellular oxygen carriers that represent potential red cell substitutes. Although both can support life at zero hematocrit, their effectiveness as O2 carriers at intermediate hematocrits has been unclear. In the presence of red cells, the efficacy of an acellular O2 carrier can be assessed by its contribution to O2 delivery and O2 consumption. This study evaluated the efficacy of SFH and FL-DA in the presence of red cells at hematocrits less than or equal to 10%. The results illustrate that SFH and FL-DA do contribute to O2 delivery and O2 consumption in the presence of red cells. The data indicate that SFH and FL-DA are both effective acellular O2 carriers.