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Biomedical subjects

J A Will

Publications and source records attributed to J A Will.

At least 19 recordsLinked to original sources
PubMed1991

Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Animals↗
PubMed1990

An examination of the influence of the epithelium on contractile responses to peptidoleukotrienes and blockade by ICI 204,219 in isolated guinea pig trachea and human intralobar airways.

The influence of the epithelium on antagonism by ICI 204,219 of contractile responses to peptide leukotriene (LT) agonists was examined in guinea pig tracheal and human bronchial rings. The -log molar KB values for ICI 204,219 were found to be independent of the epithelium in both tissues. Even though uninfluenced by the epithelium, the -log molar KB values for ICI 204,219 were about 10-fold smaller in human airways than in guinea pig trachea. Removal of the epithelium from guinea pig trachea resulted in small leftward shifts of the concentration-response curves to LTC4 and LTD4 and rightward shifts of the concentration-response curves to LTE4 when examined in the presence of indomethacin. The potentiation of LTC4 and LTD4 by epithelium removal was not seen in the presence of inhibitors of the transformation of LTC4 to LTD4 and LTD4 to LTE4. The influence of the epithelium on responses to LTE4 remained in the presence of these metabolic inhibitors. The lipoxygenase inhibitors nordihydroguaiaretic acid, B755C, Rev 5901 and AA861 antagonized responses to LTE4 in the presence, but not in the absence of epithelium. In human airways, epithelium removal resulted in a small leftward shift of the concentration-response curve to LTD4 whereas responses to LTC4 and LTE4 were unaltered. This effect was not observed in the presence of indomethacin, relating it to reduced release of cyclooxygenase products. These data suggest that contractile responses of guinea pig trachea to LTE4 are modulated by LTE4-induced release of 5-lipoxygenase product(s) only when the epithelium is present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Differential effect of ketamine on cholinergic- and noncholinergic-induced contractions of isolated guinea-pig bronchi.

Ketamine, 3 X 10(-4) M, was found to inhibit transmural electrical stimulation-induced contractile responses of the mainstem and hilar bronchi isolated from reserpine-pretreated guinea-pigs. This concentration of ketamine did not cause direct smooth muscle relaxation in these preparations and a smaller concentration (3 X 10(-5) M) was ineffective in blocking contractions. The pattern of inhibition produced by ketamine was similar to that produced by atropine, 1 X 10(-6) M, in both preparations and was observed at the larger stimulation frequencies employed. When studied in the presence of atropine to optimize noncholinergic-induced contractions, ketamine did not antagonize contractile responses to transmural electrical stimulation. After pretreatment of the isolated tissues with capsaicin, 1 X 10(-6) M, to optimize cholinergic-induced contractions, ketamine produced inhibition of responses to electrical stimulation. Ketamine, 3 X 10(-4) M, produced a shift to the right of the dose-response curve without altering the maximum contractile responses to carbachol, but had no effect on dose-response curves to substance P, the putative noncholinergic transmitter in these bronchial segments. The data suggest that ketamine exerts a selective inhibitory effect on cholinergically mediated contractions in guinea-pig bronchi and that this antagonism is largely exerted post-junctionally, at the level of the smooth muscle muscarinic receptors.

Animals↗
PubMed1979

Pulmonary microvascular response to hemorrhagic shock, resuscitation, and recovery.

We studied the effect of hemorrhagic shock, resuscitation, and recovery on the pulmonary microcirculation. We used lung lymph flow (QL) and lymph-to-plasma protein ratio as sensitive indices of transvascular fluid filtration rate and protein permeability. We measured pulmonary vascular pressures, cardiac output, blood gases, lymph flow, and lymph and plasma proteins before and during a 2-h period of shock, a 3-h period of resuscitation, and a 72-h period of recovery, in nine unanesthetized sheep with chronic lung lymph fistula. We found a 30% decrease in QL during early shock as animals were bled into bags containing an acetate citrate dextrose solution until aortic pressure was 50 Torr. QL gradually increased to or exceeded base line in five of nine animals during late shock as pulmonary vascula resistance increased by 250%. During the 3-h resuscitation period, mean QL increased by 110%, with the lymph-to-plasma protein ratio being significantly decreased, indicating no protein permeability change. In five of nine studies, lymph became visible bloody. The increased QL and lymph RBCs were felt to be secondary to an elevation in microvascular pressure. During the recovery period, pressures and QL returned to base line.

Animals↗
PubMed1979

Pathophysiology of dehydromonocrotaline-induced pulmonary fibrosis in the beagle.

The purpose of this study was to characterize the sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascualr resistance of the experimental animals were significantly greater than the controls (p less than 0.01). Right ventricular work increased from a baseline mean of 0.58 to 1.40 kg . m/min. Morphological and morphometrical analyses revealed alveolar edema, increased numbers of alveolar macrophages, cellular hyperplasia in the alveolar septa, and a progressive interstitial fibrosis. The precise mechansims by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification; however, our data indicate that the fraction of air space is reduced relative to the fraction of tissue space, and this change occurs with concurrent fibrosis in the alveolar septa and an increased pulmonary arterial pressure although hypoxia was not clinically detectable.

Animals↗
PubMed1979

Relation between pulmonary transvascular fluid filtration rate and measured Starling's forces after major burn.

Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.

Animals↗
PubMed1979

The effect of plasma oncotic pressure on the pulmonary microcirculation after hemorrhagic shock.

Plasma oncotic pressure is considered to be an important factor in controlling lung water after hemorrhagic shock. However, it is the gradient between plasma and interstitial oncotic pressure which affects the pulmonary transvascular fluid filtration rate, Qf. Our objective was to determine the effect of decreasing plasma oncotic pressure, pip, on Qf, on interstitial oncotic pressure pii, and on the oncotic gradient. Chronic lung lymph fistulas were created in 16 sheep. Lymph flow, a reliable index of Qf, plasma and lymph (equal to interstitial) oncotic pressures, and vascular pressures were monitored in unanesthetized sheep, before and during hemorrhagic shock (50% blood volume), during resuscitation (3 hours), and during recovery (24 hours). Resuscitation was either with shed blood or lactated Ringer's solution in sufficient quantity to return left atrial pressure and cardiac output to baseline levels. During resuscitation with blood, lymph flow increased by 115%. The pip remained constant, while pii decreased, increasing the oncotic gradient. Crystalloid resuscitation produced on increase in lymph flow equal to that in the blood group at 120% over baseline; however, pip decreased by 50%, producing an oncotic gradient 4 mm Hg less than that of blood group. This was not reflected by a difference in Qf between the groups. During recovery Qf returned to baseline in the blood group and in most of the crystalloid group, as the oncotic gradient returned to baseline, despite a significant decrease in pip due to a compensatory decrease in pii. We conclude that during resuscitation Qf does not appear to be increased by a decrease in the oncotic gradient. During recovery a major decrease in pip can be compensated for rapidly by a decrease in pii, leading to no change in interstitial fluid content.

Animals↗
PubMed1979

Lactic dehydrogenase activity in lung lymph during hemorrhagic shock, resuscitation and recovery.

Lactic dehydrogenase activity was determined in lung lymph before, during and after hemorrhagic shock to determine if this insult produced pulmonary cellular damage. Lung lymph flow and lymph protein content, reliable indices of fluids filtration rate and microvascular protein permeability were also monitored. The experiment was performed in unanesthetized sheep with a chronic lung lymph fistula. Lymph flow, lymph LDH and protein content did not change during the period of shock. Lymph flow increased significantly during resuscitation but lymph LDH and protein content decreased in relation to plasma values indicating the sieving effect of the microvascular membrane for protein to be intact. The increased flow was most likely caused by an increase in microvascular hydrostatic pressure. Plasma LDH was significantly increased during the 72 hour recovery period with lymph flow, lymph protein and lymph LDH being normal. We therefore found that hemorrhagic shock produced a systemic cellular injury reflected in an increased plasma LDH activity. No pulmonary cellular damage was noted.

Animals↗
PubMed1978

Quantitative characteristics of the Feyrter cells and neuroepithelial bodies of the fetal rabbit lung in normoxia and short term chronic hypoxia.

We report here quantitative data on the Feyrter (single) cells (APUD cells) and neuroepithelial bodies (grouped Feyrter cells), in the lungs of rabbit fetuses at 26, 27.5 and 29 days gestational age, during normoxia and short term chronic hypoxia. The apparent number of these cells declines during this period; we suggest that this might be due to increased hypoxemia. Moreover, the number of cells in the lungs of fetuses from short term chronically hypoxic mothers is lower than in the normoxic animals. These findings are in agreement with our previous studies in short term chronically hypoxic neonatal rabbits, and suggest that the increased hypoxemia in the fetus, caused by the induction of hypoxia in the mother, constitutes a stimulus for secretory activity of the Feyrter cells and neuroepithelial bodies (NEBs). This in turn could be part of the mechanism responsible for maintaining the pulmonary vasoconstriction due to hypoxemia. Our results from fetuses of normoxic does provide base line data on the chronological importance of the Feyrter cells and NEBs.

APUD Cells↗
PubMed1978

A radioautographic study of the neuroepithelial bodies of the lungs in fetal and neonatal rabbits.

The neuroepithelial bodies (NEB's) of the lung of 29-day-old fetuses and 1-day-old rabbits, under the conditions of this study, neither take up 3H-thymidine nor undergo mitosis. Also the NEB's are not derived at these times from proliferations of other kinds of epithelial cells in the intrapulmonary airways. It is, therefore, suggested that the difference in numbers of NEB's previously observed by us, between the 29-day fetus and the 1-day-old rabbit, is due either to regranulation or acquisition of argyrophilic material by the NEB's or differentiation of other epithelial types. It is concluded that the NEB's are composed of well differentiated cells, which have a greatly reduced capacity to undergo mitosis.

APUD Cells↗
PubMed1978

Pulmonary artery catheterization in the rat.

A method of pulmonary artery (PA) catheterization in the closed-chest rat is described. This catheterization is best accomplished with teflon catheters having a "shepherd's crook" tip. Catheter preparation is detailed. The functional advantages of such a PA catheter are: 1) the tip can remain free within the right ventricle (RV) without becoming occluded by contact with the ventricular wall, and 2) entry into the PA is simple and reproducible. Dual catheterization of the RVand PA produced only a small systolic gradient (3 mmHg) across the pulmonic valve. We concluded that the PA catheter does not unduly obstruct blood flow through this valve.

Animals↗
PubMed1978

Myocardial perfusion and function during acute right ventricular systolic hypertension.

Hemodynamics, myocardial function, and regional myocardial blood flow (MBF) were measured in 6 closed-chest ponies anesthetized with ketamine hydrochloride before (control) and after creation of acute right ventricular systolic hypertension (RVSH) during normoxia and isocapnic hypoxia. The right ventricular (RV) systolic pressure during each RVSH approached 90 mmHg. There were significant alterations in the pattern of total ventricular MBG distribution in favor of the RV. Because RV myocardium received proportionate increments to its endocardium as well as epicardium, it is concluded that autoregulation in the RV coronary vascular bed had not been abolished even during hypoxia + RVSH. Marked increase in MBF to the right side of the septum during each RVSH with little change in perfusion to other regions suggests that RV contraction is supported by the right side of the septum. Because these increments occurred with decreased RV coronary driving pressure they were the consequence of compensatory coronary vasodilatation. The slow heart rate of the pony in the presence of a large coronary vasodilatory reserve may have been the major factor in allowing large increments in MBF to the stressed regions despite decreased coronary driving pressure.

Acid-Base Equilibrium↗
PubMed1977

Quantitative characteristics of the Feyrter (APUD) cells of the neonatal rabbit lung in normoxia and chronic hypoxia.

Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.

APUD Cells↗