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Biomedical subjects

S Permutt

Publications and source records attributed to S Permutt.

At least 109 records · Page 6Linked to original sources
PubMed1980

Physiologic manifestations of human anaphylaxis.

In the course of a controlled study to evaluate different forms of immunotherapy for subjects with insect-sting hypersensitivity, we observed 11 subjects who had systemic cutaneous urticarial reactions and 3 subjects who experienced systemic anaphylaxis. With the exception of tachycardia, there were no cardiopulmonary changes in the subjects with urticaria, whereas the major manifestation of anaphylactic shock in the other three subjects was severe hypotension that was probably secondary to peripheral vasodilation. Significant abnormalities in gas exchange developed in two subjects. In one, bronchospasm precipitated a respiratory arrest followed by endotracheal intubation with mechanical ventilation. Although plasma histamine levels were not related to the development of cutaneous reactions, the plasma histamine levels correlated with the severity and duration of the cardiopulmonary changes observed during anaphylactic shock. The two subjects with the most severe shock showed evidence of intravascular coagulation characterized by a diminution of Factor V, Factor VIII, fibrinogen, and high molecular weight kininogen, as well as changes in components of the complement system. Standard therapy with epinephrine and fluids, usually recommended for the treatment of systemic anaphylaxis, did not immediately reverse either the hemodynamic or the respiratory abnormalities in the two subjects with the most severe anaphylactic shock. Hemodynamic recovery was gradual and did not seem directly related to any specific therapeutic intervention.

Anaphylaxis↗
PubMed1980

Patterns of forced expiratory flows in groups at risk for chronic obstructive pulmonary disease.

In a modified case-control study of obstructive pulmonary disease (COPD), airways obstruction has been found to be associated with age, sex, protease inhibitor type, socioeconomic status (SES) and smoking. In this paper patterns of forced expiratory flows are examined in persons demonstrating various risk factors. Two broad patterns of flow limitation emerge. The first pattern, characterized by lower flows at high lung volumes, is found in first-degree relatives of patients with COPD and subjects with a low SES. This pattern, consistent dysfunction of large airways, may reflect reversible decreases of airway caliber. The second pattern, characterized by lower flows at low lung volumes, is found in older subjects. This pattern, consistent with nonhomogeneously emptying lungs or dysfunction of small airways, may reflect more chronic irreversible changes. Smokers and male subjects exhibit both patterns of flow limitation when compared with subjects who had never smoked and female subjects. It is possible that the combination of the patterns reflects a particularly high risk for the development of COPD in male smokers.

Adult↗
PubMed1979

Left ventricular hemodynamics during respiration.

We have investigated the mechanisms involved in the inspiratory fall in left ventricular stroke volume (LVSV), utilizing a spontaneously breathing dog on right-heart bypass (RHBP). We have been able to control lung volume, pulmonary artery inflow, and right-heart volume (RHV). During Mueller maneuvers in one series, RHV was allowed to increase as pleural pressure (Ppl) fell; in a second series, changes in RHV were excluded. In both series LVSV fell significantly, associated with a significant rise in the transmural (relative to Ppl) aortic diastolic pressure, reflecting an increase in the effective LV afterload. The transmural left ventricular filling pressure did not fall, a fact inconsistent with decreased pulmonary venous return, causing the fall in LVSV. The LVSV fell significantly more when RHV was allowed to increase as when it was held constant with all other variables showing no statistical change. Thus, increases in both RHV and effective LV afterload are created by the inspiratory fall in Ppl and summate to decrease LVSV.

Airway Obstruction↗
PubMed1979

Effects of spontaneous respiration on canine left ventricular function.

The purpose of this study was to determine the mechanism of the decrease in left ventricular stroke volume during spontaneous inspiration. We determined the transmural pressures of the left heart by measuring left atrial and diastolic left ventricular pressures relative to esophageal pressure. We estimated the directional changes in end-systolic and end-diastolic volumes of the left ventricle by determining the transit time of sound transmission between two ultrasonic crystals facing each other across the minor axis of the left ventricle. Left ventricular stroke volume decreased with spontaneous inspiratory effort as pleural pressure fell, regardless of whether lung volume increased or remained constant. The stroke volume was decreased during the fall in pleural pressure because of an increase in end-systolic volume with an essentially unchanged diastolic volume. Thus, the decrease in stroke volume was due to a decrease in ejection, rather than a decrease in filling of the left ventricle. We believe that left ventricular ejection was impeded by the fall in pressure around the heart relative to the pressure in the aorta. In spite of the essentially constant diastolic volume, diastolic left ventricular transmural pressure rose, suggesting that spontaneous inspiration decreases the diastolic compliance of the left ventricle. The change in diastolic compliance contributed to the decrease in stroke volume but was not the primary cause.

Animals↗
PubMed1979

Respiratory failure in acute pancreatitis: a possible role for triglycerides.

Respiratory failure is a frequent complication of acute pancreatitis. Two clinical studies of this association have demonstrated a high incidence of concomitant hypertriglyceridemia. Experimental studies were carried out using an ex vivo, isolated, perfused, ventilated, canine pulmonary lobe to evaluate the effects of triglyceride elevations on pulmonary mechanics and gas exchange. Control lobes perfused for a four hour period remained stable. When 5g and 10g of triglyceride were added to the perfusate, the lobes became grossly edematous and hemorrhagic. Intrapulmonary shunting developed (23 and 46%), weight gain occurred (130 and 189g), effective compliance decreased, and the pressure-volume deflation curves became abnormal. Free fatty acid (FFA) levels increased markedly during the perfusion periods. When small quantities of FFA were infused directly into the pulmonary artery, similar changes, but less severe, occurred. These studies demonstrate that triglyceride elevations are capable of adversely affecting pulmonary gas exchange and mechanics. Such changes probably occur secondary to FFA release. These data thus add support to the concept that the respiratory insufficiency that is seen in acute pancreatitis could be mediated through triglyceride elevations.

Acute Disease↗
PubMed1978

Pulmonary function in young smokers: male-female differences.

To delineate the pattern of pulmonary function abnormalities and associated pathophysiologic mechanisms in young smokers, 205 volunteers between the ages of 18 and 25 were studied with a variety of pulmonary function tests. Differences between male and female smokers were observed. Pulmonary function abnormalities consistent with small airway dysfunction were noted in male smokers, but not in female smokers. Decreased forced expiratory flows at high lung volumes suggesting large airway dysfunction were noted in both male and female smokers. Decreases in diffusing capacity for CO consistent with abnormalities of the pulmonary vascular system were seen in smokers of both sexes, but were more prominent in females. Because men develop chronic obstruction pulmonary disease more frequently than do women even when adjustments for smoking are made, and because women develop primary pulmonary hypertension more frequently than do men, these chronic diseases may reflect distinct pathophysiologic response of the 2 sexes to agents such as cigarettes.

Adolescent↗
PubMed1978

The beneficial and harmful effects of positive end expiratory pressure.

The effects of increasing levels of positive end expiratory pressure on gas exchange and pulmonary mechanics were determined utilizing an ex vivo ventilated perfused canine pulmonary lobe. When zero positive end expiratory pressure was used, shunting, weight gain and a decrease in compliance occurred over the four and one-half hour experiment. Shunting was eliminated when 5, 10 or 15 centimeters of water of positive end expiratory pressure were used. However, increasing extravascular fluid sequestration and decreasing pulmonary compliance occurred progressively with increasing levels of positive end expiratory pressure above 5 centimeters of water. Pulmonary artery pressure increased immediately along with end inspiratory pressure, an amount approximately equal to the increase in positive end expiratory pressure, and this is thought to be the primary cause of the increased rate of fluid sequestration. These experiments suggest that an optimal level of positive end expiratory pressure exists when the shunt can be reduced and oxygenation improved without increasing the rate of extravascular fluid accumulation to the point where long time deleterious effects could outweigh immediate benefits.

Animals↗
PubMed1977

A common familial component in lung cancer and chronic obstructive pulmonary disease.

First-degree relatives of lung-cancer patients and of patients with chronic obstructive pulmonary disease had significantly higher age-sex-race-smoking-adjusted rates of impaired forced expiration than first-degree relatives of patients with non-pulmonary disease or community-derived comparison series (neighbourhood controls and teachers). Subclassification of the data and multiple adjustment for smoking, race, sex, and other confounding factors emphasised the consistency of the pattern. These findings strongly suggest that lung cancer and chronic obstructive pulmonary disease share a common familial component other than smoking. The clinical manifestation may depend on the presence of one or more other cofactors as yet undefined.

Adult↗
PubMed1977

Risk factors in chronic obstructive pulmonary disease (COPD).

In a genetic-epidemiologic study of chronic obstructive pulmonary disease (COPD) observations adjusted for age, sex, race, and smoking indicate certain factors to be associated with increased pulmonary function aberrancy, and suggest that they are risk factors for COPD. These presumptive "risk factors" include not only cigarette smoking, but also alpha1-antitrypsin (Pi system) variation, one or more other familial components, low socioeconomic status (SES), and, in whites, ABO blood type (either absence of "B" or presence of "A").

ABO Blood-Group System↗
PubMed1977

Role of the parasympathetic system in antigen-induced bronchospasm.

Human subjects, sensitive to ragweed, inhaled aerosols of increasing concentrations of ragweed pollen extract in the presence and absence of pretreatment with inhaled atropine. The cumulative dose of antigen required for a 35% decrease in airways conductance was termed PD35. Atropine, 1.2 or 5 mg, increased airways conductance before antigenic challenge but did not alter signigicantly the PD35 for ragweed extract, although these doses of atropine inhibited airways responses to inhaled methacholine chloride and citric acid. We conclude that the cholinergic nervous system plays a modulating role in bronchomotor tone and responses to irritants, but that parasympathetic reflexes are not invariably a major component of human bronchial responses to inhaled allergen.

Airway Resistance↗
PubMed1977

The effect of atropine on acute antigen-mediated airway constriction in subjects with allergic asthma.

Exposure to antigen by inhalation challenge may produce airway constriction in patients with allergic asthma. To examine the role of reflex bronchoconstriction mediated by the vagus nerve in the antigen-induced airway response, we compared the responses of 6 asthmatic volunteers to inhaled ragweed antigen alone and to antigen given after pretreatment with atropine sulfate, a parasympathetic blocking agent. We found significant increases in airway resistance, limitation of parasympathetic blocking agent. We found significant increases in airway resistance, limitation of forced expiratory flow, increases in lung volumes, and alterations in the distribution of inspired gas after antigen was given. When subjects were pretreated with atropine, we found a mean increase in the 1-sec forced expired volume of 0.380 liter (P less than 0.025) and a mean increase in specific airway conductance of 0.067 sec-1-cm H2O-1 (P less than 0.005). Atropine pretreatment did not prevent the responses to antigen in our subjects. After atropine pretreatment subjects began the antigen challenge with better pulmonary function and at a given antigen dose maintained a better level of function compared to when antigen was given alone. Differences in the absolute level of pulmonary function between the two challenges became smaller with the administration of larger antigen doses. We conclude that reflex bronchospasm involving postganglionic efferent parasympathetic nerve pathways is not a major component of the response to inhaled antigen in human allergic asthma.

Adult↗