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Biomedical subjects

J L Ferguson

Publications and source records attributed to J L Ferguson.

At least 73 records · Page 4Linked to original sources

Dramatic changes in blood gases that are unrelated to arterial pH or cerebral oxygen delivery during endotoxin shock in conscious rats.

In preliminary studies we demonstrated an effect of endotoxin on arterial blood gases that appeared to be related to the dose of endotoxin used and unrelated to changes in arterial pH. In the present study we tested the hypothesis that these changes in blood gases result from decreased oxygen delivery to central respiratory control areas. PO2 significantly rose from a pre-endotoxin value of 91.4 +/- 1.5 (mean +/- SEM) to 97.5 +/- 1.7, 104.0 +/- 0.8, and 108.4 +/- 0.9 at 10, 30, and 60 minutes, respectively, after administration of 6 mg/kg endotoxin and from 93.8 +/- 3.1 to 105.2 +/- 2.6, 118.7 +/- 1.4, and 121.0 +/- 2.8, respectively, after administration of 10 mg/kg endotoxin. PCO2 fell significantly from a pre-endotoxin value of 38.3 +/- 1.2 to 28.6 +/- 0.6 and 24.5 +/- 1.9 at 30 and 60 minutes post-endotoxin, respectively, in 6-mg/kg-treated rats, and from 40.5 +/- 2.1 to 30.7 +/- 4.5, 20.1 +/- 3.9, and 19.3 +/- 1.0, respectively, at 10, 30, and 60 minutes post-10 mg/kg endotoxin. The only significant change (decrease) in pH occurred at 60 minutes after 10 mg/kg treatment. In 10-mg/kg-treated rats, serum lactate rose significantly over time, while HCO-3 decreased. Heart rate was increased significantly (472 +/- 9.6) from a pre-10 mg/kg endotoxin value of 373 +/- 11.8 by 10 minutes post-endotoxin and remained elevated throughout the experiment. Cerebral medullary/pontine blood flow, mean arterial blood pressure, and respiratory rate were not significantly altered by endotoxin administration. Hemoglobin concentration and arterial oxygen content were significantly increased after 10 mg/kg endotoxin. These findings indicate that decreased oxygen delivery to central respiratory control areas is not a cause of the observed dramatic changes in blood gases.

Acid-Base Equilibrium↗

Binding of chloroform to the cysteine of hemoglobin.

The products of the covalent binding of chloroform to rat hemoglobin during microsomal metabolism were isolated and identified by gas chromatography (GC) and mass spectroscopy (MS). After isolation by Proteinase K hydrolysis, amino acid analysis and cellulose thin-layer chromatography (TLC), the major product was identified by GC/MS as N-hydroxymethyl cysteine and a minor product as 2-hydroxythiazolidine-4-carboxylic acid. N-Hydroxymethyl cysteine is proposed to be formed during isolation from the 2-oxothiazolidine-4-carboxylic acid present in the intact hemoglobin.

Amino Acids↗

Vasoactive drugs in acute pancreatitis.

Experimental evidence has shown that pancreatic blood flow is severely diminished during acute pancreatitis, but it is unclear whether a decrease in blood flow is a critical event in the evolution of complications of this disease. When an episode of edematous pancreatitis is complicated by necrosis of part of the gland, there is a risk of both acute and chronic complications, including sepsis, hemorrhage, and abscess. One of the questions that remains is whether the decreases in blood flow alluded to are primary or secondary causes. If primary, treatments that preserve pancreatic blood flow during pancreatitis might have a salutary effect on observed morbidity and mortality. This study determined whether two vasoactive drugs, oxidopamine (6-hydroxydopamine) and dihydroergotamine tartrate, given prior to experimentally induced pancreatitis in rats, affected observed mortality. After oxidopamine treatment, rats had a higher survival rate and greater pancreatic blood flow than untreated controls. The association of greater pancreatic blood flow and reduced mortality did not exclude other possible effects of oxidopamine treatment but was consistent with the hypothesis that vasoactive therapy may have a role in this disease.

Acute Disease↗

Characteristics of smooth eye movements with stabilized targets.

Eye movements of two subjects were recorded with a Double Purkinje Image Tracker while they pursued horizontal triangle or ramp stimuli (1, 2, 4 or 8 degrees/sec, p--p 8 degrees). Subjects then attempted to imitate their smooth pursuit eye movement patterns with an electronically-stabilized target or with an afterimage. Next, they attempted to reset the velocity of the stimulus to their memory of the velocity they had previously pursued. The smooth pursuit eye movements of both subjects were very similar. Their attempts to imitate this pattern of eye movements with a stabilized target were only partially successful and subject to large, qualitative individual differences. These differences did not arise from faulty memories of the nature of the pursuit stimuli. Similar results were obtained on the vertical meridian, with a lighted background, and with the stabilized target in eccentric retinal positions. We conclude that stabilization techniques are of dubious value in elucidating properties of the human smooth pursuit subsystem.

Afterimage↗

Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis.

Cardiac output (CO) and the distribution of blood flow were studied in chronically catheterized conscious rats during sustained (4 days) sepsis. Septicemia was induced by intraperitoneal administration of a pooled fecal inoculum, and tissue blood flow and CO were determined daily with 15-micron radioactive microspheres. Mean arterial blood pressure (MABP, 113 +/- 2 mmHg), CO (244.5 +/- 11.4 ml X min-1 X kg-1), and total peripheral resistance (TPR, 1.36 +/- 0.07 mmHg X ml-1 X min) were stable in control rats over the 4 days postinoculation. Septic animals showed a consistent tachycardia with MABP significantly reduced only on days 3 and 4 (86 +/- 4 mmHg). A hyperdynamic response to sepsis was indicated by an elevated CO (27%) and similarly reduced TPR on day 2. The calculated stroke volume averaged 0.22 +/- 0.01 ml/beat and did not vary over time or between the two groups. There was a 40-70% increase in blood flow to the heart, spleen, adrenal glands, and small intestine, and a greater than sixfold increase in hepatic arterial blood flow. The sustained elevation of coronary blood flow, observed in septic animals, was independent of myocardial work and is consistent with impaired myocardial function. Pancreas, stomach, and skeletal muscle blood flow was consistently compromised (24, 39, and 52%, respectively) during sepsis. Blood flow in other organs remained unchanged over time. Sepsis-induced changes in the fractional distribution of blood flow to various organs were similar to those described for absolute flow. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of cortisone treatment and burn injury on plasma and lung lavage cortisol concentrations and alveolar macrophage activity.

Thermal injury often results in the development of compromised host defense mechanisms against infections (eg, increased incidence of pulmonary sepsis in postburn animals has been attributed to impaired cellular defenses in the lung). Recent reports have demonstrated that high dose glucocorticoid therapy used in the treatment of inflammatory diseases and shock also results in an increased susceptibility of the host to pulmonary sepsis. Although several defense mechanisms are available to the respiratory tract combating bacterial challenges, the major cellular defense is the alveolar macrophage, which phagocytizes infectious agents and potentially toxic particulate matter that infiltrate the lower respiratory tract. Recent evidence has demonstrated that high doses of cortisol in vivo impair both functional and metabolic activities of the alveolar macrophage. However, there is little information regarding whether alterations in endogenous levels of glucocorticoids following systemic injury can mediate similar defects on the cellular defenses of the lung. The present study demonstrated that both high dose glucocorticoid treatment and burn injury severely impaired the functional activity of the resident lung macrophage. The phagocytic cell population in the lower respiratory tract was reduced by more than 50%, 24 hr following either burn injury or a 7 day cortisone regimen. Furthermore, the remaining alveolar macrophages lavaged from either experimental group demonstrated a marked impairment in phagocytic activity. The combination of a reduced macrophage population in the lung and a decreased phagocytic activity of the residual cells indicated a severe deficiency in the total lung phagocytic capacity. The 7 day cortisone treatment markedly elevated plasma (greater than 400%) and lung lavage (greater than 200%) levels of cortisol. Although plasma levels of cortisol were also significantly increased (greater than 50%) 24 hr post burn injury, lung lavage cortisol levels were not higher than saline-treated sham burn control values. However, lung lavage concentration of cortisol was increased over threefold following cortisone treatment and burn injury.

Animals↗

Resting blood flow and oxygen consumption in soleus and gracilis muscles of cats.

In contrast to previous reports, the results of the present study indicate that vascular responses of isolated soleus muscles of cats are functionally similar to those of gracilis muscles. Vascularly isolated muscles were perfused under free-flow conditions. Venous outflow was measured by a drop counter. Resting blood flows were similar in soleus (n = 16) and gracilis (n = 12) muscles, 6.6 +/- 1.2 and 3.8 +/- 0.6 ml . min-1 . 100 g-1, respectivley (P > 0.05). Resting oxygen consumption averaged 0.26 +/- 0.06 and 0.33 +/- 0.10 ml O2 . min-1 . 100 g-1 for soleus (n = 10) and gracilis muscles (n = 5), respectively (P > 0.05). In four animals, blood flow to soleus muscles measured by the microsphere technique was 2.0 +/- 0.3 ml . min-1 . 100 g-1 before and 4.6 +/- 2.1 ml . min-1 . 100 g-1 after isolation of its circulation. Before isolation, blood flow to gracilis muscle was 2.0 +/- 0.1 ml . min-1 . 100 g-1 after isolation of its circulation. Before isolation, blood flow to gracilis muscle was 2.0 +/- 0.1 ml . min-1 . 100 g-1. Both soleus and gracilis muscles exhibited active hyperemia. Autoregulation of blood flow in both muscles was weak. However, oxygen supply exceeded demand because oxygen consumption was maintained as blood flow decreased in response to reductions in perfusion pressure. There was no evidence of blood flow-limited oxygen consumption. Thus, the soleus muscles of the present study not only have low-resting blood flows and oxygen consumptions, but their responses to physiological stimuli are similar to those of gracilis muscles.

Animals↗

Effects of E coli endotoxin on pancreatic hormones and blood flow.

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.

Animals↗

Body fluid compartment changes during burn shock in the guinea pig.

The alterations in body fluid compartments 1, 4, and 8 hours after a 70% full-skin thickness burn were studied in conscious guinea pigs. Concurrently, we measured hemodynamic changes associated with the burn. Cardiac output and heart rate were depressed one hour postburn, and mean arterial blood pressure was depressed eight hours postburn. A hemoconcentration one-hour postburn, as evidence by an increase in hematocrit, was due exclusively to a loss of plasma volume. Red blood cell (RBC) volume remained constant after the burn. As a consequence of decreased plasma volume, total blood volume was also depressed. Extracellular fluid was decreased on hour after the burn; how ever, four and eight hours postburn, extracellular fluid space was comparable to that in the control group. Total body water and body weights of burned animals did not differ from control values. This study has demonstrated the very rapid redistribution of fluids in burn shock without a loss of fluids from the body.

Animals↗

Total and regional cerebral blood flow during perfusion from the lateral ventricle to the cisterna magna in the conscious dog: effect of hemorrhagic hypotension and retransfusion on cerebral blood flow.

This study was performed to determine if autoregulation of regional cerebral blood flow (rCBF) occurs in conscious dogs with ventriculocisternal perfusion (VCP) during moderate hypotension. Six dogs were perfused for 360 minutes using mock cerebrospinal fluid (CSF). A 120-minute control period was followed by 180 minutes of moderate hemorrhagic hypotension (mean arterial pressure (SAP) 60-80 mm Hg). The lost blood (approximately 40% of the calculated blood volume) was retransfused after 300 minutes of perfusion, and an additional 60 minutes of observation concluded the study. The rCBF was measured at 120, 240, and 360 minutes of perfusion using labeled microspheres of 15 mu diameter. Cardiac output (CO) was 2.8 +/- 0.41 liters/min at 120 minutes, decreased to 1.4 +/- 0.10 liters/min after hemorrhage, and rose after retransfusion to 2.2 +/- 0.13 liters/min. The percentage of cardiac output (%CO) received by the brain was 1.8 +/- 0.37% at 120 minutes, 3.8 +/- 0.44% at 240 minutes, and 2.2 +/- 0.22% after retransfusion (P < 0.05). There was no significant change in rCBF during hypotension. The regional cerebral blood flow was, however, significantly elevated in the thalamus, mesencephalon, pons, and medulla after retransfusion indicated a local alteration of set point in the plateau of the autoregulatory curve. Cerebral venous pH (measured in internal maxillary venous blood) decreased significantly during hemorrhage to 7.25, while cerebral arteriovenous difference of oxygen and A-VpH increased significantly during hemorrhage. Thus, autoregulation of total cerebral blood flow (CBF) during acute moderate hypotension remains intact during VCP at a rate of 0.2 ml/min using a perfusate of a constant pH and, hence, CSF-pH appears not to be of major significance for the autoregulation of CBF in moderate hypotension.

Animals↗

Role of the paleostriatum in species-typical display behavior of the lizard (Anolis carolinensis).

In a comparative study of forebrain mechanisms of species-typical behavior, unilateral lesions were placed in the subpallial telencephalon of male green anolis lizards (Anolis carolinsis), in which there is an almost complete decussation of the optic nerve. Responses to a conspecific male antagonist in a territorial confrontation were then tested when the subject's vision was limited to an eye leading to either the normal or lesioned hemisphere. In lizards with lesions involving the paleostriatum and lateral forebrain bundle, there was an elimination of or marked deficit in the performance of the challenge display while signature displays and measures of general activity were not significantly affected. Lesions predominantly in anterior or posterior dorsal ventricular ridge resulted in no significant deficit in any behavioral measure.

Animals↗

Increased free fatty acid turnover in CSF during hypotension in dogs.

Cerebrospinal fluid turnover rates of FFA were investigated using ventriculocisternal perfusion techniques. Seven conscious dogs were perfused over a 6-h period from the lateral ventricle to the cisterna magna with mock cerebrospinal fluid (CSF) containing [14C]palmitate and 100 mumol/l of FFA. One hundred and twenty minutes of perfusion were allowed to establish equilibrium of the FFA concentration in the ventricular space. Moderate hemorrhage hypotension was then induced (MABP greater than 60 mmHg) for 3 h, followed by rapid retransfusion and a final hour of perfusion. Cerebral blood flow did not change significantly (45 +/- 6 before, 53 +/- 6 after hemorrhage, and 47 +/- 5 ml.min-1. 100 g-1 after retransfusion). Cerebral arteriovenous difference of O2, glucose, and pH increased significantly during hemorrhage. Hypotension was accompanied by an increased turnover of FFA from 60 to 120 nmol/min (P less than 0.01) in the CSF. FFA turnover was directly correlated with the fatty acid concentration of the CSF (r = 0.77). It is speculated that the increased fatty acid turnover during hypotension may indicate increased phospholipid turnover and/or increased oxidation by tissues lining the ventricular space.

Animals↗

Prosencephalic pathways related to the paleostriatum of the pigeon (Columba livia).

Afferent connections of the avian paleostriatal complex were traced by means of anterograde and retrograde transport of horseradish peroxidase (HRP). The paleostriatum augmentatum (PA), a cell field comparable to mammalian caudate nucleus and putamen, was found to receive projections from a distinct population of elencephalic neurons in the temporal-parietal-occipital (TPO) and lateral cortical (CDL) areas of the neostriatum. TPO neurons, in turn, were found to receive projections from the contralateral ventral archistriatum (Av) and from neurons in the ipsilateral frontal neostriatum adjacent to the rostral portion of the ectostriatum (e). the paleostriatum primitivum (PP), comparable to globus pallidus, receives projections from the small cells of PA, and from neutrons in the anterior nucleus of the ansa lenticularis (ALa). ALa appears similar to the mammalian subthalamic nucleus on the basis of its afferent and efferent connections. In addition, PA was also found to receive extensive projections from the nucleus tegmenti pedunculopontinus of the midbrain, a dopamine-containing cell group. Evidence of projections from the nucleus dorointermedius posterior (DIP), a cell group receiving both cerebellar and paleostriatal afferents, to the rostral telencephalon was also found.

Animals↗

Metabolic and hemodynamic aspects of the hypothermia of early burn shock.

Guinea pigs briefly anesthetized with Halothane were burned over 70% of their body surface area. Core temperature progressively decreased over an 8 hour period reaching its lowest level just before death. Heart rate, cardiac output, and oxygen consumption also diminished over this period. The fractional distribution of the cardiac output to the pancreas, adipose tissue, burned and unburned skin and muscles fell sharply. Actual volume flow to the heart and brain also decreased while plasma FFA concentration exhibited little change. However, hyperglycemia was noted due in part to peripheral insulin resistance. Although plasma catecholamines increased during this trauma, their effect was muted by a low plasma pH and a rising lactic acid concentration. It is postulated that the destroyed peripheral temperature receptors, hypoxic areas of the brain, decreased blood flow through high metabolic areas and low oxygen and substrate utilization in the periphery brought about the hypometabolism.

Animals↗

Distribution of neurons projecting to the retina of Caiman crocodilus.

Horseradish peroxidase (HRP) was injected into the vitreous of the eye, the orbital cavity, or the optic tectum of Caiman crocodilus. Following intravitreal injections, retrograde transport of the enzyme was observed bilaterally, but predominantly contralaterally, in a large oblong field of cells at the isthmic level of the midbrain, bounded medially by the trochlear nucleus and laterally by the nucleus isthmi. Control injections of HRP into the orbital cavity and eye muscles labelled motoneurons of the extraocular muscles but not cells of this isthmic field. The field is therefore the source of a projection efferent to the retina in Caiman. Injections of HRP into the dorsal optic tectum produced a fine pattern of anterograde labelling in fibers projecting to the region in which retinopetal cells were identified, but no retrograde labelling of cells in this area. In contrast, the nucleus isthmi showed dense anterograde labelling of fibers and terminals as well as retrograde labelling of cells following tectal injections. These results extend recent evidence for a close evolutionary relationship between the order Crocodilia and modern birds, since birds also possess a well-developed retinopetal system derived from a cell group in the isthmic midbrain.

Alligators and Crocodiles↗

Effect of moderate hemorrhagic hypotension on cerebral metabolism during ventriculocisternal perfusion in the conscious dog.

Early changes in cerebral metabolism during hemorrhagic hypotension in conscious dogs have been studied with a chronic ventriculocisternal perfusion system. The mean arterial blood pressure was held above the lower limit of the cerebral autoregulatory curve. There was a rise of free fatty acids (FFA) in cerebrospinal fluid at 30 minutes after the onset of hemorrhage. The cerebral arteriovenous difference of oxygen (AVDO2), AVD-glucose, and AVD-pH increased significantly after 60 minutes of hemorrhage, while AVD-TCO2 (tissue culture oxygen) rose only slightly. These changes may reflect some of the metabolic alterations that occur in moderate hypotension.

Animals↗

Dexamethasone treatment during hemorrhagic shock: blood pressure, tissue perfusion, and plasma enzymes.

In a study to determine beneficial effects of dexamethazone (5 mg/kg) during hemorrhagic shock, perfusion (as measured by radioactive microspheres) and plasma enzymes were measured. Hemorrhagic shock (mean arterial blood pressure, MABP, of 50 mm of Hg) was induced in dogs and then the dogs were isolated from the shed-blood reservoir and were allowed to compensate their MABP. Hemodynamic changes, tissue perfusion, and plasma enzymes were measured at different intervals of time in nontreated and dexamethasone-treated dogs. Beneficial effects were increased MABP, improved blood flow to the lungs, gastrointestinal tract, and kidneys, and less cell damage as indicated by amounts of plasma enzymes released from damaged tissues. These effects favor the maintenance of the homeostatic state and, in turn, a greater chance for survival of the dog.

Alanine Transaminase↗