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Biomedical subjects

G H Parsons

Publications and source records attributed to G H Parsons.

17 recordsLinked to original sources

Pulmonary C-fiber stimulation by capsaicin evokes reflex cholinergic bronchial vasodilation in sheep.

We investigated changes in bronchial blood flow (Qbr) associated with capsaicin-induced stimulation of pulmonary C-fibers in seven anesthetized and two unanesthetized sheep. A Doppler flow probe chronically implanted around the common bronchial artery provided a signal (delta F, kHz) linearly related to bronchial arterial blood velocity (Vbr, cm/s), which was proportional to Qbr. An index of bronchial vascular conductance (Cbr, in arbitrary units) was calculated as the ratio of Vbr to systemic arterial pressure (Pa). Right atrial injection of capsaicin evoked a prompt pulmonary chemoreflex (apnea, bradycardia, and hypotension), with immediate increases in Vbr (average +34%) and Cbr (+63%) that reached a maximum approximately 7 s after the injection. A second increase in Vbr, but not in Cbr, occurred approximately 12 s later, coinciding with an increase in Pa. Vagal cooling (0 degrees C) prevented the pulmonary chemoreflex; it also abolished the immediate increases in Vbr and Cbr in four of six sheep and substantially reduced them in two sheep; it did not affect the late increases in Vbr and Pa. Results after atropine indicated that the immediate increases in Vbr and Cbr were mainly cholinergic. In two sheep a small residual vasodilation survived combined cholinergic and adrenergic blockade and may have been due to peripheral release of neurokinins.

Animals

Peptide mediator effects on bronchial blood velocity and lung resistance in conscious sheep.

Peptide mediators or neuropeptides released from sensory nerves may induce inflammatory effects in airways, but their effects on airway blood velocity and lung resistance have not been previously studied simultaneously in awake animals. Nine adult sheep were chronically prepared for continuous measurement of blood flow velocity to the distal trachea and bronchi by surgical implantation of a 20-MHz pulsed Doppler flow probe on the common bronchial branch of the bronchoesophageal artery. Awake restrained animals were intubated and connected to a pneumotachograph to measure resistance to airflow across the lung (RL). Doubling doses of bradykinin (BK, 0.02-1.51 nmol/kg), calcitonin gene-related peptide (CGRP, 0.004-0.26 nmol/kg), or substance P (SP, 0.02-1.19 nmol/kg) were injected as a bolus into the right atrium while mean arterial pressure (MAP), bronchial blood velocity (Vbr), and RL were measured. BK at 0.76 nmol/kg caused a transient dose-related increase in Vbr from a baseline of 19.3 +/- 2.5 to 41.4 +/- 4.1 (SE) cm/s (P less than 0.05) despite a decrease in MAP from 118 +/- 6 to 80 +/- 6 mmHg. CGRP at 0.26 nmol/kg caused a transient dose-related increase in Vbr from 16.8 +/- 2.7 to 25.3 +/- 4.7 cm/s (P less than 0.05) despite a decrease in MAP from 113 +/- 5 to 87 +/- 8 mmHg. Neither BK nor CGRP affected RL. SP at 1.19 nmol/kg transiently increased Vbr from 18.3 +/- 2.3 to 45.1 +/- 8.3 cm/s (P less than 0.05), MAP from 138 +/- 9 to 162 +/- 15 mmHg, and RL from 4.5 +/- 1.0 to 106.6 +/- 62.1 cmH2O.l-1.s.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

Bronchial vasodilation by histamine in sheep: characterization of receptor subtype.

Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols

Treatment of proximal deep-vein thrombosis using subcutaneously administered calcium heparin: comparison with intravenous sodium heparin.

In a prospective, randomized clinical trial we compared the efficacy of subcutaneously (SC) administered (every 8 h) calcium heparin to intravenous (IV) sodium heparin in the treatment of proximal deep-vein thrombosis (DVT). A secondary objective was to give enough heparin to achieve a therapeutic anticoagulant effect by the end of the first 24 h. Five of 36 patients (14%) in the SC heparin group failed to achieve a therapeutic anticoagulant effect by the end of the first 24 h compared to 2 of 23 patients (9%) in the IV group (p = NS; 95% CI for true difference = -11.7% to 22.1%). Two of 31 patients (6.5%) in the SC group had venographic evidence of clot propagation compared to 1 of 19 patients (5.3%) in the IV group (p = NS; 95% CI for true difference = -12.4% to 14.8%). The rate of major hemorrhagic complications was similar in each group (approximately 15%). We conclude: (1) using a large initial dose of SC heparin, a therapeutic anticoagulant effect can be readily achieved within 24 h, and (2) combining the results of this trial with previous studies, the efficacy of SC administered calcium appears to be comparable to IV sodium heparin.

Adult

Laser Doppler velocimetry of tracheal blood flow in sheep.

A laser-Doppler velocimetry (LDV) apparatus was adapted to assess sheep airway blood flow. The LDV signal obtained was compared to microsphere determinations of blood flow to tracheal tissues utilizing 15 microns radioactive microspheres injected before and after intubation and anesthesia, during hemorrhagic hypotension, and after reinfusion-resuscitation. During hemorrhagic hypotension, airway wall blood flow decreased to 16% of control by the microsphere method and to 30% by LDV. After reinfusion-resuscitation, airway wall blood flow increased over control values 40% and 33% by the two methods, respectively. Although at low flows LDV values were greater than microsphere determinations, the overall LDV recordings correlated with airway microsphere flow determinations of tracheal wall blood flow (R = 0.85) and tracheal mucosa flow (R = 0.81), but not with tracheal muscularis flow (R = 0.32). With certain but significant limitations, such as calibration in absolute units, stability of position placement, motion artifacts, and the effects of mechanical irritation-induced hyperemia, LDV represents a relatively noninvasive means for qualitatively evaluating changes in the microcirculatory blood flow of airway mucosa.

Animals

Acute ozone exposure increases bronchial blood flow in conscious sheep.

This study was initiated to determine the effects of ozone (O3) on sheep airway blood flow. Twenty-three nasally intubated sheep were exposed to filtered air (n = 5), 1 ppm O3 (n = 4), 2 ppm O3 (n = 5), 3 ppm O3 (n = 5), and 4 ppm O3 (n = 4) for 3 h. Bronchial artery flow (Qbr) was measured using a chronically implanted 20 MHz pulsed Doppler flow probe. Qbr, mean aortic pressure, cardiac output, pulmonary artery pressure, arterial blood gases, and core temperature were monitored during the period of the exposures. Exposure to 3 and 4 ppm O3 resulted in a significant increase in Qbr (103 and 204% change, respectively) without affecting any of the other cardiopulmonary parameters measured. These results indicate that O3 induces a dose dependent increase in Qbr which is the result of a vasodilation of the bronchial vasculature which is not dependent upon changes in blood gases or upstream driving pressure.

Administration, Intranasal

Tracheal blood flow during spontaneous and mechanical ventilation of dry gases in sheep.

Tracheal blood flow increases greater than twofold in response to eucapnic hyperventilation of dry gas in anesthetized sheep. To determine whether this occurs at normal minute ventilation, we studied sheep in which tracheal blood flow was measured in response to humid and dry gas ventilation while 1) awake and spontaneously breathing and 2) anesthetized and intubated during isocapnic mechanical ventilation. In additional sheep, three tracheal mucosal temperatures were measured during humid and dry gas mechanical ventilation to measure airway tissue cooling. Tracheal blood flow was determined by use of a left atrial injection of 15-microns-diam radiolabeled microspheres. Previously implanted flow probes on the pulmonary artery and the common bronchial artery allowed continuous recording of cardiac output and bronchial blood flow. Tracheal blood flow in awake spontaneously breathing sheep was 10.8 +/- 5.6 (SD) ml.min-1.100 g wet wt-1 while humid gas was breathed, and it was unchanged with dry gas. In contrast, isocapnic ventilation of intubated animals with dry gas resulted in a 10-fold increase in blood flow to the most proximal two-ring tracheal segment compared with that seen while humid gases were spontaneously ventilated [101 +/- 75 vs. 11 +/- 6 (SD) ml.min-1.100 g-1, P less than 0.05]. Despite a 10-fold increase in proximal tracheal blood flow, there was no response in distal tracheal and bronchial blood flow, as indicated by no change in the common bronchial artery blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

Airway blood flow response to eucapnic dry air hyperventilation in sheep.

Eucapnic hyperventilation, breathing dry air, produces a two- to fivefold increase in airway blood flow in the dog. To determine whether airway blood flow responds similarly in the sheep we studied 16 anesthetized sheep. Seven sheep (1-7) were subjected to two 30-min periods of eucapnic hyperventilation breathing 1) warm humid air [100% relative humidity (rh)] followed by 2) warm dry air [0% rh] at 40 breaths/min. To determine whether there was a dose-response effect on blood flow of increasing levels of hyperventilation of dry air, another nine sheep (8-16) were subjected to four 30-min periods of eucapnic hyperventilation breathing warm humid O2 followed by warm dry O2 at 20 or 40 breaths/min in random sequence. Five minutes before the end of each period of hyperventilation, hemodynamics, blood gases, and tracheal mucosal temperature were measured, and tracheal and bronchial blood flows were determined by injection of 15- or 50-micron-diam radiolabeled microspheres. After the last measurements had been made, all sheep were killed, and the lungs and trachea were removed for determination of blood flow to trachea, bronchi, and parenchyma. In sheep 1-7, warm dry air hyperventilation at 40 breaths/min produced an increase in blood flow to trachea (7.6 +/- 3.5 to 17.0 +/- 6.2 ml/min, P less than 0.05) and bronchi (9.0 +/- 5.4 to 18.2 +/- 8.2 ml/min, P less than 0.05) but not to the parenchyma. When blood flow was compared with the two ventilatory rates (sheep 8-16), tracheal blood flow increased (9.1 +/- 3.3 to 18.2 +/- 6.1 ml/min, P less than 0.05) at a rate of 40 breaths/min but not at 20 breaths/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Bronchial blood flow measured by video dilution technique in sheep.

Bronchial blood flow was studied with the video dilution technique (VDT) in seven sheep. All animals were anesthetized (thiamylal and halothane) and ventilated. A videodensitometer and a videotape replay of the fluoroscopic image of dye moving through the common bronchial artery were used to construct dye mass vs. time curves. The areas under the curves were inversely proportional to flow in the bronchoesophageal artery, the site of dye injection. At thoracotomy, an electromagnetic flow probe (EMFP) was placed on the common bronchial artery (the major branch of the bronchoesophageal artery) to measure blood flow changes simultaneously by EMFP and by VDT. These two methods of measurement of blood flow to the airways were compared to validate the use of VDT in this circulation. Common bronchial artery blood flow was increased by injection of radiocontrast dye into the fluoroscopically positioned bronchoesophageal artery catheter causing hyperosmotically induced hyperemia. In 160 simultaneous measurements in five sheep, the percent change in flow as measured by EMFP and VDT correlated closely (r = 0.96). When flow changed because of spontaneous aortic pressure changes or pharmacologic intervention (28 simultaneous measurements in five sheep), the percent change in flow by EMFP and VDT also correlated well (r = 0.98). Bronchial blood flow changes in sheep can be measured accurately using the video dilution technique.

Animals

Effect of cold and warm dry air hyperventilation on canine airway blood flow.

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.

Animals

Mechanisms of pulsus paradoxus in upper airway obstruction.

Pulsus paradoxus, a greater than 10 Torr systolic pressure fluctuation during the respiratory cycle, is seen in upper airway obstruction. To test the hypotheses 1) that blood is pooled in the pulmonary circulation with reduced return to the left heart during inspiration and 2) that inspiration increases left ventricular afterload, the following was done. Esophageal pressure (Pes), pericardial pressure (Pp), left atrial transmural pressure (Platm), and left ventricular transmural pressure at end-isovolumic systole (Plvtm) were recorded during partially obstructed inspirations in spontaneously breathing dogs anesthetized with pentobarbital (25 mg/kg). Changes in Pes and Pp were nearly identical (r = 0.9883) confirming that changes in Pes adequately reflect changes in Pp. During inspiration Platm and Plvtm increased 0.5 and 0.4 Torr, respectively, per Torr decrease in Pes suggesting that increased blood return to left atrium and increased left ventricular afterload occur. Similar changes were observed during near constant thoracic volume (total airway block) and cardiac reflex blockade (atropine 0.05 mg/kg and propranolol 0.5 mg/kg). Thus mechanical factors including left ventricular afterload appear of major importance in producing pulsus paradoxus in upper airway obstruction.

Airway Obstruction

Hemoptysis.

Hemoptysis is an alarming symptom that should not be dismissed lightly. A thorough evaluation will lead to the correct diagnosis in 80 to 90 percent of cases. Surgery is occasionally necessary where life-threatening hemorrhage is present but, more commonly, appropriate therapy can only be determined when the etiology is discovered, thus mandating a careful, thorough diagnostic search.

Adult