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Biomedical subjects

R F Coburn

Publications and source records attributed to R F Coburn.

85 records · Page 5Linked to original sources
PubMed1969

Carbon monoxide-induced arterial hypoxemia.

Inhalation of carbon monoxide produces an increase in the alveolar to arterial oxygen gradient in the presence of veno-arterial shunts or ventilation-perfusion imbalance but has no such effect in normal subjects. The increase in the alveolar to arterial oxygen gradient with rising concentrations of carboxyhemoglobin results from changes induced by carbon monoxide in the shape of the oxyhemoglobin dissociation curve.

Arteries↗
PubMed1968

Maximal erythrocyte and hemoglobin catabolism.

A series of experiments were performed on anesthetized dogs in which varying quantities of normal canine erythrocytes damaged by incubation with N-ethylmaleimide were injected into the circulation. Cell sequestration and catabolism of hemoglobin to carbon monoxide remained normal after injections that contained from 0.058 to 0.154 g of hemoglobin per kg of body weight. After administration of larger quantities of these cells, from 0.154 to 0.364 g of hemoglobin per kg of body weight, sequestration remained normal but the rate of catabolism of hemoglobin to carbon monoxide reached a maximum. Large quantities of hemoglobin entered the plasma in these experiments at a time when cell sequestration in the reticuloendothelial system appeared to be virtually complete. After injection of even larger quantities of damaged erythrocytes, 0.545 and 0.552 g of hemoglobin per kg, sequestration became slightly delayed, but was complete. These data appear to indicate that (a) the maximal rate of hemoglobin catabolism in normal anesthetized dogs averages approximately 0.07 g/kg of body weight per hr; (b) hemoglobinemia can result from "overloading" the reticuloendothelial system with damaged sequestered cells and, therefore, may not always indicate "intravascular" hemolysis; and (c) the sequestering function of the reticuloendothelial system appears not to limit the maximal rate of catabolism of hemoglobin. The limiting parameter or parameters were not defined in these studies.

Animals↗
PubMed1967

The production of carbon monoxide from hemoglobin in vivo.

Dogs anesthetized with pentobarbital were shown to produce carbon monoxide at an average rate of 0.21 +/- (SD) 0.05 ml per hour. After intravenous injection of erythrocytes damaged by incubation with N-ethylmaleimide, CO was produced in excess of base-line production for 3 to 4 hours with an average yield of 0.89 +/- (SE) 0.046 mumole of carbon monoxide to 1 mumole of heme degraded. After intravenous injection of N-ethylmaleimide (NEM)-treated erythrocytes containing hemoglobin labeled with (14)carbon, (14)CO was produced. Its specific activity was approximately one-eighth that of the injected heme. It was also produced after intravenous injection of solutions of hemoglobin-(14)C and of reconstituted methemoglobin containing hemin-(14)C, but not after injections of methemoglobin containing globin-(14)C. The average yields of (14)CO from metabolized heme in the experiments with damaged erythrocytes and hemoglobin solutions were 89 +/- (SE) 4.6 and 97 +/- (SE) 17.0%, respectively. These results demonstrate that the CO produced during hemoglobin degradation arises from the heme moiety. The yield of (14)CO after injection of hemoglobin-(14)C solutions decreased significantly to values of 35 and 42% in two experiments when exogenous CO was added to the body stores, resulting in blood carboxyhemoglobin levels of 11.3 and 13.2% saturation. This finding suggests that oxidative metabolism is required during catabolism of hemoglobin to CO and that carboxy-hemoglobin levels in this range are sufficient to cause inhibition. After intravenous injection of either hemin-(14)C or protoporphyrin-(14)C, (14)CO was also produced. After injection of protoporphyrin-(14)C labeled bilirubin was isolated from gall bladder bile, and labeled hemin was isolated from the liver. It is thus very likely that protoporphyrin is converted to heme before the formation of CO. There was a large difference between the maximal rates of catabolism of hemoglobin to CO observed after injection of damaged erythrocytes and hemoglobin solutions. The limiting parameters in these processes are not yet clear.

Animals↗
PubMed1967

Carbon monoxide production associated with ineffective erythropoiesis.

The rate of endogenous carbon monoxide production ( Vco), determined by the closed rebreathing system technique, was elevated above the normal range in four of five patients studied with ineffective erythropoiesis (four patients with primary refractory anemia, one with thalassemia). The mean molar ratio of Vco to Vheme (rate of circulating heme catabolism, determined from (51)Cr red cell survival curves) was 3.0 +/- 0.6 (SE), indicating that most of the CO originated from sources other than circulating erythrocyte hemoglobin, in contrast to previous findings in patients with hemolytic anemia, where Vco paralleled Vheme closely.After administration of glycine-2-(14)C to these patients, endogenous CO was isolated by washout of body CO stores at high pO(2) or by reacting peripheral venous blood samples with ferricyanide. The CO was then oxidized to CO(2) by palladium chloride and trapped for counting in a liquid scintillation spectrometer. "Early labeled" peaks of (14)CO were demonstrated which paralleled "early labeled" peaks of stercobilin and preceded maximal labeling of circulating heme. Production of "early labeled" (14)CO in patients with ineffective erythropoiesis was greatly increased, up to 14 times that found in a normal subject. The increased Vco and "early (14)CO" production shown by these patients are presumably related mainly to heme catabolism in the marrow. The possibility exists that hepatic heme and porphyrin compounds may also contribute significantly to Vco, as suggested by the finding of a high Vco in an additional patient with porphyria cutanea tarda.

Adolescent↗
PubMedDate not supplied

Decreased PO2 and rabbit aortic smooth muscle mechanics.

Rabbit thoracic aorta was used to determine the effects of decreasing PO2 on the mechanical properties of contractions in response to norepinephrine (NE) and KCl. Aortae were aerated with 45% O2/5% CO2/50% N2 and stimulated with 10 microM NE or 50 mM KCl. At 5 min of stimulation, 5% CO2/95% N2 aeration was introduced for 15 min, defined as hypoxia. This time period was previously shown to produce similar decrease in [ATP] in either stimulation condition. Force, stiffness and isotonic shortening velocity were monitored during the initial stimulation, during hypoxia and during re-oxygenation. Hypoxia produced a substantial and rapid decrease in force and a concomitant decrease in stiffness during NE stimulation; delayed and smaller decreases in force and stiffness were observed during KCl stimulation. The force-stiffness relationship was steeper during KCl than NE stimulation, and hypoxia did not affect these relationships. Isotonic shortening velocity was significantly depressed by hypoxia during both stimulations although the decrease during KCl stimulation required a longer time. These data demonstrate that relaxation of an agonist-induced contraction in response to hypoxia results from a decrease in the number of activated crossbridges and not formation of rigor bridges.

Animals↗