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Biomedical subjects

J H Linehan

Publications and source records attributed to J H Linehan.

At least 91 records · Page 5Linked to original sources
PubMed1983

Motor function of the opossum sphincter of Oddi.

We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that originate in the proximal SO and propagate toward the duodenum; (b) these forceful SO peristaltic contractions are myogenic in origin and serve as a peristaltic pump that actively empties the SO segment; (c) CBD outflow occurs passively during SO diastole, but is interrupted transiently during each SO peristaltic contraction; and (d) a short HPZ with active as well as passive components exists in the distal SO segment and acts as a variable resistor to SO outflow.

Ampulla of Vater↗
PubMed1982

Distribution of vascular resistance and compliance in a dog lung lobe.

We have modeled the left lower dog lung lobe as three serial compartments, each containing resistance (R) and compliance (C). The intracompartmental arrangement of R and C was chosen to permit their evaluation from pressure data obtained following occlusion of the venous outflow. We found that two mathematically distinct models permitted evaluation of the distribution of R and C. The models were complementary in that when used together the R and C of the three compartments could be determined. The central compartment had 46% of the lobar vascular resistance and 75% of the lobar vascular compliance under control conditions. We found that serotonin and histamine, which increased the resistance proximal and distal to the central compartment, respectively, did not increase the central resistance. Therefore, we conclude that the central compartment includes the capillary bed. The equilibrium pressure (Pd), obtained when arterial inflow and venous outflow were simultaneously occluded, was in close agreement with the average preocclusion pressure of the central compartment, indicating that Pd is close to the pulmonary microvascular pressure.

Animals↗
PubMed1982

Influence of blood and plasma flow rate on kinetics of serotonin uptake by lungs.

Serotonin extraction following a bolus injection of serotonin and a nonpermeating indicator into the pulmonary artery can be evaluated using a model that represents the saturable uptake of serotonin by Michaelis-Menten kinetics. By use of this model Km, Vmax, and a perfusion parameter, alpha, can be determined by multiple linear regression analysis of the time-concentration data. Kinetic and perfusion parameters were obtained using data from isolated dog lung lobes in which plasma flow rate was changed by changing the pump flow rate in blood- or plasma-perfused lobes or by keeping the pump flow rate constant and removing the blood cells. The calculated Vmax was reproducible and flow independent over the range of flow rates used in the study. The calculated Km was more sensitive than Vmax to small variations in experimental data and was independent of flow at flow rates greater than about one-half the normal cardiac output per gram of lung tissue. The perfusion parameter alpha was lower in the plasma-perfused lobes, reflecting more homogeneous perfusion in the absence of cells. The results suggest that this approach will be useful for separating changes in the kinetics of serotonin uptake by endothelial cells from effects of changes in flow and perfusion heterogeneity.

Animals↗
PubMed1981

Prostaglandin E1 uptake by isolated cat lungs perfused with physiological salt solution.

The instantaneous extraction of prostaglandin E1 (PGE1) was measured after a bolus injection of PGE1 and [14C]dextran in to the pulmonary artery of isolated cat lungs perfused with a physiological salt solution [Krebs-Ringer-bicarbonate buffer (KRB)]. The extraction ratio vs. time curves exhibited characteristic shapes. For low injected doses of PGE1, the extraction ratios were constant early in time, whereas for high doses, they were concave upward. To evaluate the data, we used a model assuming homogeneous perfusion and a saturable uptake mechanism (Michaelis-Menten kinetics) for the PGE1. The model was used in a linear regression analysis to estimate Vmax and Km. The kinetic parameters were compared with our previous results for blood-perfused lungs, and it was found that the values of Km were significantly smaller than in blood-perfused lungs but that the values of Vmax were not significantly different. These results were consistent with the observation that PGE1 uptake was greater in KRB- than in blood-perfused lungs when the dose of PGE1 was low but that the difference disappeared at high doses. The absence of plasma protein binding in KRB-perfused lungs may be responsible for the lower Km.

Animals↗
PubMed1981

Kinetics of serotonin uptake in the dog lung.

A bolous containing [3H]serotonin and indocyanine green dye was rapidly introduced into the pulmonary artery on an isolated blood-perfused left lower dog lung lobe. Sequential samples of the venous effluent were collected for approximately 25 s following the injections. The lung intake of the injected [3H]serotonin was inversely proportional to the injected dose, ranging from about 70% for a 10-nmol injection to about 38% for a 100-nmol injection. Less than 2% of the injected 3H, which appeared in the venous effluent over the sampling interval, was in the form of [3H]5-hydroxyindoleacetic acid; and during the bolous transit through the lung lobe, uptake of serotonin by platelets was negligible. The serotonin extraction ratio curves exhibited dose-dependent characteristic shapes that we have interpreted using a model in which it is assumed that serotonin uptake follows Michaelis-Menten kinetics and flow through the capillary bed is heterogeneous. Using this model and a multiple regression analysis, the outflow dye and 3H concentration vs. time curves were used to estimate Km and Vmax for serotonin uptake by the lungs.

Animals↗
PubMed1980

Chronic pulmonary inflammation modulates the fate of proteins administered by the respiratory tract.

The systemic appearance of radioiodinated proteins (125I-OA and 131I-HSA) administered via the respiratory route was studied in normal rabbits and in rabbits with BCG-induced chronic granulomatous pulmonary inflammation. The proteins were administered by i.t. injection into intact rabbits and into rabbits with tracheal cannulas or as an aerosol into isolated perfused lungs. The results showed that radioactivity appeared in the circulation as two fractions, one that was precipitables with 5% TCA and therefore protein-bound and one that was soluble in TCA. In both intact and tracheostomized animals, significantly more protein-;ound radioactive iodine was detected in the circulation of BCG-treated animals than in normal animals as early as 15 min after i.t. injection, and the differences persisted from 2 to 4 hr. However, in the isolated perfused lung, in which the only route for protein uptake into the circulation was the alveolocapillary barrier, only minimal differences in blood protein levels were observed as compared to normal BCG-inflamed lungs. This study suggests that chronic pulmonary inflammation promotes the absorption of i.t.-injected protein into the circulation, and that the route of enhanced uptake into blood is not the alveolocapillary membrane.

Animals↗
PubMed1979

Hemodynamic responses of dog lung lobe to lobar venous occlusion.

We perfused the left lower lobe of the dog lung with constant flow. When the lobar venous outflow was occluded, the lobar venous pressure rose suddenly to a level somewhere below the arterial pressure, and then the arterial and venous pressures began to rise more slowly. A possible explanation for this response is that, when the outflow was occluded, flow through some downstream segment of the bed ceased. Because flow into the lung continued, the arteriovenous pressure difference after occlusion represents the pressure drop across some upstream segment through which the flow continued. We designated the arteriovenous pressure difference just after outflow occlusion as the upstream pressure drop. The arteriovenous pressure difference before occlusion minus the upstream pressure drop was designated the downstream pressure drop. In an attempt to better understand the meaning of the upstream and downstream pressure drops, we examined the influence of pulmonary vasoconstriction and flow direction on the size of the upstream and downstream pressure drops. We also compared these pressure drops with the pressure drops occurring upstream and downstream from the midpoint of the lobar vascular volume, using the low-viscosity bolus technique. The results indicate that changes in the upstream and downstream pressure drops, as evaluated by outflow occlusion, reflect changes in the lobar arterial and venous resistances.

Animals↗
PubMed1979

A kinetic model of prostaglandin metabolism in the lung.

We have measured the instantaneous extraction of prostaglandin E1 (PGE1) after a single bolus injection of PGE1 and indocyanine green dye into the pulmonary artery of isolated cat lungs. The extraction ratio versus time curves exhibited a characteristic shape; at early times they were concave upward and later in time concave downward. To evaluate this date we utilized a model in which themechanism of PGE1 uptake is saturable and follows Michaelis-Menten kinetics. The model assumes heterogeneous perfusion of the exchanging region of the lung and can be solved by regression analysis to obtain Km and Vmax from the data collected from a single bolus injection. The results indicate that the shape of the extraction ratio curve manifests the influence of nonlinear uptake and heterogeneous perfusion and that the kinetic parameters may be calculated from the data obtained after a single bolus injection ofPGE1.

Animals↗
PubMed1979

Lung inflation and longitudinal distribution of pulmonary vascular resistance during hypoxia.

Using the low-viscosity bolus method, we examined the influence of lung inflation on the longitudinal distribution of vascular resistance during hypoxia in isolated cat lungs. During hypoxia, increasing transpulmonary pressure decreased vascular resistance but did not change the volume into the lung at which the maximum local resistance was located. This was in contrast to the normoxic situation in which inflation caused an increase in resistance over much of the transpulmonary pressure range studied and moved the maximum local resistance downstream. These results indicate that during hypoxia the major increase in resistance was in extra-alveolar vessels and that distension of these vessels by lung inflation decreased the magnitude of the pressor response. The increase in resistance in alveolar vessels, which occurred on inflation, was similar during control and hypoxic conditions but was a smaller part of the total resistance during hypoxia because of the much larger extra-alveolar vessel resistance.

Animals↗
PubMed1978

Influence of hypoxia on the longitudinal distribution of pulmonary vascular resistance.

We have examined the influence of hypoxia on the longitudinal distribution of vascular resistance and intravascular pressure in isolated cat lungs using the low-viscosity bolus technique. Hypoxia increased total vascular resistance, decreased total lung blood volume, and moved the maximum local resistance downstream away from the main pulmonary artery. The circumference of the main pulmonary artery was increased and the extravascular lung water (double indicator dilution technique) was decreased by hypoxia. Thus, it would appear that distension of the large pulmonary arteries and a decrease in the amount of lung tissue perfused contributed to the change in resistance distribution brought about by hypoxia.

Animals↗
PubMed1978

Pulmonary vasomotion and the distribution of vascular resistance in a dog lung lobe.

We examined the influence of stellate ganglion stimulation, hypoxia, and the infusion of norepinephrine, PGF2alpha, serotonin, and histamine on the longitudinal distribution of vascular resistance and intravascular pressures in an isolated left lower lobe of the dog lung using the low-viscosity bolus technique. Sympathetic stimulation, norepinephrine, serotonin, PGF2alpha, and hypoxia increased total pulmonary vascular resistance by increasing the resistance, primarily on the arterial or upstream side of the volume midpoint, whereas histamine increased the resistance near the venous end of the lobar vascular bed. Hypoxia increased the volume upstream from the site of maximum resistance, suggesting that the larger lobar arteries were distended by the elevated lobar artery pressure. Sympathetic stimulation, norepinephrine, PGF2alpha, and serotonin, on the other hand, had little effect on the volume upstream from the maximum resistance, suggesting that these vasomotor stimuli prevented distension of the larger arteries.

Animals↗
PubMed1977

Effects of lung inflation on longitudinal distribution of pulmonary vascular resistance.

A low-viscosity bolus technique was employed to determine the influence of lung inflation on the distribution of pulmonary vascular resistance in isolated cat lungs. When the lungs were collapsed, the longitudinal distribution of resistance was concentrated near the proximal (arterial) part of the vascular bed. As the lungs were inflated, the resistance became more evenly distributed with the maximum located close to the midpoint of the total blood volume. The fraction of total pressure drop across the lung which occurred proximal to the midpoint of the total lung blood volume decreased from 0.69 in the collapsed lung to 0.43 at a transpulmonary pressure of 16 cmH2O.

Animals↗
PubMed1977

Longitudinal distribution of vascular resistance in the lung.

We have modified the low-viscosity bolus technique for determining the longitudinal distribution of pulmonary vascular resistance. A bolus of saline was introduced into the pulmonary artery of an isolated cat lung. As this low-viscosity bolus passed through the lung, a fall in inflow pressure was recorded which had a characteristic shape depending on the changing shape and position of the low-viscosity bolus and the longitudinal distribution of resistance. The shape and position of the bolus within the lung at a given time were calculated using the change in viscosity of the blood measured as the bolus entered the pulmonary artery and as it emerged from the left atrium. Assuming that the hemodynamic resistance of a small segment of the vasculature is proportional to the product of the viscosity and its geometric factor, we employed a sequential-pattern search technique to calculate the "best" longitudinal distribution of the geometric factor, compatible with the position and dispersion of the bolus at any time and the arterial pressure curve.

Animals↗
PubMed1977

Improved infusion system for intraluminal esophageal manometry.

An improved catheter infusion system is needed for esophageal intraluminal manometry. Using conventional syringe-pump infusion systems undesirably rapid infusion rates of 6 ml per min or more are often needed to achieve accurate recording of esophageal peristaltic pressure. These rapid base line infusion rates are necessitated by the high compliance of syringe-pump systems which causes substantial reduction in the infusion rate during dynamic pressure transients. In this study we tested a hydraulic-capillary infusion system designed to have low compliance. This minimally compliant system yields accurate recording of esophageal peristaltic pressure at infusion rates of 0.6 ml per min or less. We believe that the hydraulic-capillary infusion system is a useful tool for performing both clinical and investigative studies of esophageal motor function.

Adolescent↗