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Biomedical subjects

J E Millen

Publications and source records attributed to J E Millen.

At least 37 records · Page 2Linked to original sources

The effects of ethchlorvynol on pulmonary alveolar membrane permeability.

Intravenous injection of ethchlorvynol (Placidyl) causes noncardiogenic pulmonary edema in humans and laboratory animals. We studied the effects of intravenous ethchlorvynol (15 to 25 mg per kg of body weight) on pulmonary alveolar membrane permeability to various endogenous and exogenous solutes in the in vivo saline-filled dog lung model. Baseline and postethchlorvynol times in minutes for 50 per cent equilibration between the blood and saline-filled alveoli were, respectively, for urea, 37.3 +/- 12.4 and 12 +/- 6.3; for albumin 8,160 +/- 4,400 and 267 +/- 93; for dextrans of molecular weight 10,400 daltons, 1,150 +/- 80 and 185 +/- 160; for dextrans of molecular weight 250,000 daltons, 24,000 +/- 800 and 1,120 +/- 900; for dextrans of molecular weight 500,000 daltons, 24,500 +/- 150 and 1,020 +/- 590. All of these pairs of values were significantly different (P less than 0.01). In addition, lung liquid histamine (but not blood histamine) concentrations increased significantly (P less than 0.001) after ethchlorvynol injection. Intravenous ethchlorvynol causes marked increases in alveolar membrane permeability.

Animals↗

Endotoxin-induced increased alveolar capillary membrane permeability.

In an attempt to define the effects of endotoxin on the permeability of the pulmonary alveolar capillary membrane (ACM) to a variety of substances [molecular weight (MW) varying from 60 to 69,000], we studied the movement of specific molecular species from the pulmonary capillary blood to the saline-filled "alveolus," employing an in vivo dog lung model. Following endotoxin injection (2-2.5 mg/kg) baseline T1/2 values (time, in minutes, for 50% equilibration of the specific solute between the blood and the saline-filled lung) decreased as follows (compared to baseline values): urea (MW 60) - 42.5 +/- 24 to 21.3 +/- 18; sucrose (MW 360) - 201 +/- 72 to 76 +/- 53; 3,000 MW dextran - 1,275 +/- 746 to 686 +/- 433; 10,400 MW dextran - 1,871 +/- 845 to 1,052 +/- 630 (all p less than 0.05). Neither 20,000 MW dextran nor albumin (MW 69,000) showed an increased permeability following endotoxin injection. Histamine analysis revealed a significant increase in all lung liquid samples post-endotoxin injection without a significant increase in blood histamine values. We conclude that, acutely (within 4 hr of injection), endotoxin causes an increase in permeability of the ACM for substances up to 10,400 MW. The role of histamine in this increased permeability remains controversial.

Animals↗

Continuous positive airway pressure without tracheal intubation in spontaneously breathing patients.

Indications for the use of therapy with continuous positive airway pressure (CPAP) in spontaneously breathing patients are increasing in number. The value of this technique without tracheal intubation was investigated in 14 patients with acute respiratory distress. In most patients (eight patients, or 57 percent) the technique was successful, as evidenced by avoidance of the necessity for tracheal intubation and improvements in clinical appearance, arterial oxygen pressure, and chest x-ray films. Complications were observed in three patients, but these necessitated discontinuation of therapy in only one. The use of this technique allows avoidance of endotracheal intubation and mechanical ventilation, with their attendant risks.

Acute Disease↗

Dissociation of bradycardia and arterial constriction during diving in the seal Phoca vitulina.

Bradycardia associated with diving in the harbor seal has been dissociated from the arterial constrictor response by intracardiac pacing. Development of arterial constriction does not depend upon the development of bradycardia. During pacing, arterial constriction continues in the absence of bradycardia. Increases in heart rate to values greater than 120 beats per minute during a dive produce a progressive decrease in mean aortic pressure, which suggests that one major function of bradycardia is to reduce cardiac output, thus matching left ventricular output to the restricted vascular bed and decreased venous return associated with diving.

Animals↗

Humoral agent from calf lung producing pulmonary arterial vasoconstriction.

Saline washings obtained in vivo from the lung of young calves produce pulmonary hypertension upon intrayascular (systemic or pulmonary) injection into either the dog or the calf. This pulmonary hypertension is produced by vasoconstriction of small, precapillary pulmonary vessels. The active agent, pulmonary arterial constrictor substance, differs chemically and physiologically from other substances which have been investigated with respect to vasomotor activity in the pulmonary circulation. Although the chemical nature of the active agent is not known it appears to have a relatively large molecular weight. Whether this agent plays a role in the physiological regulation of the pulmonary circulation is not known.

Angiography↗

Pulmonary mechanics during pregnancy.

Previously reported changes in static lung volumes during pregnancy have been confirmed. Measurements of lung compliance (C(L)) and total pulmonary resistance (R(L)) were made in 10 women in the last trimester of pregnancy and 2 months postpartum, employing an esophageal balloon and recording spirometer. C(L) was unaffected by pregnancy, but R(L) was 50% below normal during pregnancy. Measurements of airway conductance (C(A)) were made, employing the constant pressure body plethysmograph on 14 nonpregnant and 13 pregnant women. Specific airway conductance was increased during pregnancy. Serial measurements of C(A) indicated a progressive increase beginning at about 6 months of gestation and a return to normal by 2 months postpartum. The mechanism of the increased C(A) during pregnancy is not known. It may be related to changes in bronchial smooth muscle tone and conceivably explains the tolerance of certain patients with lung resections to pregnancy.

Adolescent↗

Arterial constrictor response in a diving mammal.

Angiograms were obtained in the harbor seal, Phoca vitulina, in air and during diving. During diving there is arterial constriction of the vascular beds of muscle, skin, kidney, liver, spleen, and presumably of all vascular beds except those perfusing the brain and heart. There is sudden constriction and narrowing of muscular arteries close to their origin from the aorta. Constriction of small arterial branches is so intense that blood flow is essentially lost in all involved organs.

Angiography↗

The effect of salicylate infusion on the alveolar epithelial membrane in the isolated perfused lung.

We observed two patients with aspirin (ASA) ingestion (blood levels of 87 and 56.5 mg/100 ml) who presented with noncardiogenic pulmonary edema (adult respiratory distress syndrome. To determine if ASA had a direct effect on the alveolar epithelial membrane, we established an in vitro isolated lung model and perfused it with platelet free plasma. T1/2 (in minutes), the time for 50% equilibration between the plasma and the saline filled lung, was determined before and after 500 mg salicylate infusion for various molecular weight dextrans. T1/2 decreased significantly (p less than 0.05) as follows: 3000 MW dextran, 2273 +/- 932 to 961 +/- 375; 40,000 MW dextran, 4059 +/- 1550 to 733 +/- 275; 70,000 MW dextran, 11,730 +/- 2750 to 7700 +/- 2230. Histamine levels in plasma and lung liquid did not change significantly with ASA infusion. We conclude that ASA directly increases alveolar epithelial permeability to dextrans less than 70,000 MW.

Aged↗