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Biomedical subjects

S Permutt

Publications and source records attributed to S Permutt.

At least 91 records · Page 5Linked to original sources

Hypoxic constriction of alveolar and extra-alveolar vessels in isolated pig lungs.

To examine whether hypoxia causes constriction of alveolar or extra-alveolar vessels, we determined the relationships among transpulmonary pressure, pulmonary arterial pressure (Ppa), blood flow (Q), and transvascular fluid filtration rate (W) during normoxia (PO2 = 200 Torr) and hypoxia (PO2 = 50 Torr) in isolated pig lungs perfused with autologous blood. Left atrial pressures were always subatmospheric. The effects of lung inflation and hypoxic vasoconstriction on the Ppa-Q relationship were similar; when transpulmonary pressure was greater than 5 Torr, both shifted the curve to higher pressures in a parallel fashion. When transpulmonary pressure was 0-5 Torr, however, inflation had no effect on the Ppa-Q relationship during either normoxia or hypoxia. During normoxia at a transpulmonary pressure of 3.5 Torr, the relationship between fluid filtration rate and flow was characterized by a W of zero at Q less than 1.5 l/min and a rapid increase in W with Q above this value. Both hypoxia and inflation shifted this relationship to higher filtration rates in a parallel fashion. Furthermore, the combined effects of hypoxia and inflation on filtration rate were additive. These results suggest that hypoxia caused constriction of both alveolar and extra-alveolar vessels, resulting in increased intraluminal pressure and filtration of fluid in vessels upstream from the sites of constriction.

Animals↗

The effect of alpha adrenergic blockade on non-specific airways reactivity and exercise induced asthma.

In asthmatics, alpha-adrenergic blockage with oral phentolamine partially or completely blocked bronchospasm after maximal exercise challenge. Bronchial reactivity to isocapnic hyperventilation with conditioned cold air was also reduced. However, non-specific airways reactivity to inhaled histamine did not change. Therefore, exercise and cold induced bronchospasm in asthma may be partially mediated by alpha adrenergic neural mechanisms perhaps through sensitization of alpha receptors during airway cooling.

Airway Resistance↗

Hemodynamic mechanisms in anaphylaxis.

Intravenous administration of ascaris suum antigen (1 mg) as well as histamine (5 mg) was associated with rapid and marked reductions in cardiac output (QT) and systemic arterial pressure (Pa) in anesthetized mechanically ventilated dogs. When venous return was maintained constant by an external pump reservoir system, both antigen and histamine caused rapid reductions in the reservoir blood volume consistent with peripheral pooling. In addition, interruption of the splanchnic arterial inflow by occlusion of the descending thoracic aorta restored the cardiac output to control during histamine shock, whereas QT during antigen shock was unaffected by aortic occlusion, even though the circulatory failure was of similar magnitude. Therefore, we conclude that differences in responses of antigen and histamine shock to aortic occlusion indicate that mechanisms leading to peripheral pooling of blood are different with the two agents. In addition, stability of left atrial pressure following the administration of either agent, when the venous return is maintained constant, suggests that intrinsic myocardial dysfunction is not a major initiating mechanism in the two shock states studied.

Anaphylaxis↗

Aspiration pneumonia: treatment with pulmonary vasodilators.

Experimental aspiration pneumonia induced in the isolated perfused ventilated canine pulmonary lobe by the intrabronchial instillation of hydrochloric acid is characterized by pulmonary edema, intrapulmonary shunting, and loss of lung compliance. In addition, pulmonary artery pressure increases. In an attempt to modify the injury response, we restricted the increase in pulmonary artery pressure in the isolated lobe model by administering vasodilator drugs. In control lobes perfused for 4 hours there was minimal weight gain (14 gm), pulmonary artery pressure remained stable (13 mm Hg), and intrapulmonary shunting did not occur. Following intrabronchial instillation of 0.2 ml of 0.1N HCl/gm of lobe weight, lobe weight tripled (183 gm), pulmonary artery pressure (20 mm Hg) was significantly increased, and significant intrapulmonary shunting (32%) developed. When sodium nitroprusside (2 micrograms/min/kg of dog body weight) was infused into the pulmonary artery 3 minutes after HCl instillation, the pulmonary artery pressure was significantly reduced (13 mm Hg) compared to that in untreated acid lobes. This was accompanied by a significant reduction in mean weight gain (100 gm) and intrapulmonary shunting (15%) compared to untreated acid lobes. Similarly, when isoproterenol (0.04 micrograms/min/kg dog body weight) was infused into the pulmonary artery following acid instillation, the pulmonary artery pressure (12.5 mm Hg) was significantly reduced compared to that in untreated acid lobes. This was also accompanied by a significant reduction in weight gain (60 gm) and intrapulmonary shunting (6%) compared to untreated acid lobes. These data demonstrate that the increase in pulmonary artery pressure following acid injury can be lowered pharmacologically and that a significant decrease in injury response follows. This suggests that the magnitude of the injury response is in part a function of pulmonary artery pressure.

Animals↗

Increased cardiac output following occlusion of the descending thoracic aorta in dogs.

Occlusion of the thoracic aorta (AO) in dogs with a constant volume right ventricular extracorporeal bypass increased cardiac output (Q) by 43% and mean arterial pressure by 46%, while mean systemic pressure (MSP) was unchanged. We compared AO with occlusion of the brachiocephalic and left subclavian arteries (BSO) which decreased cardiac output by 5%, increased mean arterial pressure by 32%, and increased MSP by 11%. We feel these results confirm that AO elevates preload by transferring blood volume from the splanchnic veins to the vascular system drained by the superior vena cava. If the heart is competent to keep right arterial pressure at or near zero, this increase in preload will elevate Q above control levels. Comparing our data with results of other authors who have not controlled right atrial pressure, emphasizes the importance of a competent right ventricle in allowing venous return to determine Q.

Animals↗

Diurnal variation of air and helium-oxygen flow-volume curves in asthmatic children.

In order to assess diurnal variation of flow-volume curves and to determine whether small airways are involved in the diurnal variation of pulmonary function in asthmatic children, we studied eight asthmatics who were attending an asthma summer camp. Spirometry and maximal expiratory flow-volume curves with air and a helium-oxygen mixture were obtained in the morning and afternoon over a 10-day period. We found that significant increases in maximal expiratory flows at all lung volumes occurred in the afternoon. However, the increase in flows with helium (helium response) was unchanged from morning to afternoon. These results suggest that both large and small airways are involved in the diurnal variation of pulmonary function in asthmatic children.

Adolescent↗

Effect of PEEP on left ventricular function in right-heart-bypassed dogs.

Positive-pressure ventilation with positive end-expiratory pressure (PEEP) has been associated with elevation of left ventricular filling pressure for a stable or reduced cardiac output. To exclude the possibility that right ventricular distension due to increased pulmonary vascular resistance decreases left ventricular compliance (ventricular interdependence), we studied the effect of PEEP on left ventricular function in open-chest right-heart-bypassed dogs. A rightward shift of the left ventricular function curve was caused by 15 cmH2O PEEP without a change in the aortic pressure-flow relationship. The pericardial pressure, however, was found to exceed atmospheric pressure on 15 cmH2O even with the chest widely opened. This increase in the pressure surrounding the heart accounted for the increase in left ventricular filling pressure. We postulate, therefore, that the elevation in left ventricular filling pressure found with PEEP is due in part, if not entirely, to mechanical interaction of the heart and lungs by direct compression or pericardial traction.

Animals↗

Effects of hypoxia on the closing pressure of the canine systemic arterial circulation.

We studied the relationships among closing pressure (Pc) and indices of systemic arterial resistance (Ra) and compliance (Ca) during hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) in anesthetized dogs with cardiac bypass and constant ventilation. Closing pressure was measured as the lowest level to which arterial pressure (Pa) fell after inflow to the arterial bed was reduced suddenly to zero. Since the fall of Pa to Pc could be well-described as a single exponential function of time and since Pc was always greater than outflow (venous) pressure. Ra and CA were determined by applying a "vascular waterfall" model to the arterial bed. During HH, Pc increased while Ra and Ca decreased. During COH, Pc and Ra decreased, but Ca did not change. The Pc results indicate that during HH, but not COH, a large portion of the systemic arterial bed experienced a marked increase in vasomotor tone, a qualitative difference that would have been missed if Pc had not been measured. The relationship among Pc, Ra, and Ca during hypoxia suggest these indices may have been determined largely by different portions of the arterial bed in which tone changed independently.

Animals↗

Aspiration pneumonia: treatment with osmotically active agents.

Utilizing the ex vivo perfused ventilated canine pulmonary lobe, we evaluated the effects of three osmotically active agents on pulmonary function after acid aspiration. Control lobes were stable during a 44-hour perfusion with minimal weight gain, stable pulmonary artery and end-inspiratory pressures, and no increase in intrapulmonary shunting. After acid aspiration during a 44-hour perfusion period, massive weight gain occurred (228 gm), pulmonary artery and end-inspiratory pressure increased, and marked intrapulmonary shunting (44%) developed. When mannitol (molecular weight 182) or dextran 40 (molecular weight 40,000) were added to the perfusate of the acid-instilled lobes, no significant modifications of the acid-induced response were seen during the 44-hour perfusion. The administration of albumin (molecular weight 69,000), however, markedly modified the acid-induced response. Weight gain (53 gm) was almost completely eliminated, pulmonary artery and end-inspiratory pressures were stable, and intrapulmonary shunting increased only minimally (10%). It is concluded that despite the permeability change in the capillary-alveolar membrane produced by acid aspiration, albumin is retained within the vascular space and is effective in reducing the injury response.

Airway Resistance↗

Pulmonary injury caused by free fatty acid: evaluation of steroid and albumin therapy.

Intrapulmonary free fatty acid (FFA) release has been suggested as a pathogenetic mechanism in respiratory failure caused by acute pancreatitis and fat embolism. Utilizing the isolated perfused ventilated canine pulmonary lobe, we evaluated the effects of FFA infusion and its subsequent modification by albumin and steroid therapy. In control lobes perfused for a 4-hour period, there was minimal weight gain (11 gm), intrapulmonary shunting did not occur, and compliance remained within normal limits. When 1 ml of oleic acid was infused into the pulmonary artery lobe weight tripled (188 gm), intrapulmonary shunting (20%) developed, and compliance was significantly decreased compared to controls. When 30 gm of human salt-poor albumin was added to the perfusate immediately after FFA infusion, the lobe response was similar to that of untreated oleic acid lobes. In contrast, when 400 mg of methylprednisolone succinate was added to the perfusate immediately after FFA infusion, lobe weight gain was significantly reduced (94 gm) compared to oleic acid lobes, intrapulmonary shunting did not occur, and compliance was within normal limits. This study suggests that steroids may be of benefit in the treatment of respiratory insufficiency secondary to acute pancreatitis and fat embolism.

Airway Resistance↗

Is ABH nonsecretor status a risk factor for obstructive lung disease?

In a multidisciplinary study of risk factors for chronic obstructive pulmonary disease (COPD), a significantly more impairment of forced expiration was observed in ABH nonsecretors than in ABH secretors among 1017 white adults. (ABH refers to the "A" and "B" antigens of the ABO blood group system and "H", the heterogenetic substance which is found in persons of all ABO types including type "O".) Nonsecretors had significantly lower mean values of forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC%) and a significantly larger proportion of them had aberrant values, defined as FEV1/FVC% less than 68. These differences remained when mean values or rates of aberrancy were adjusted for other factors reported to alter risk of airway obstruction. In view of the known COPD-peptic ulcer and nonsecretor-duodenal ulcer associations, these findings suggest that the ability to secrete ABH antigens into secretions of the respiratory and gastrointestinal tract may have a protective effect on epithelialized organs in general, or on the lung and portions of the gut specifically.

ABO Blood-Group System↗

Alcohol consumption and airway obstruction.

To clarify the basis of the reported association between alcohol and pulmonary disease, the relationship between intake of alcohol and pulmonary function was examined in 2,539 community-dwelling adult participants in an ongoing longitudinal study of risk factors for airway obstruction. Forced expiratory volume in 1 s, expressed as a percentage of forced vital capacity, was used as the indicator of airway obstruction, and forced vital capacity expressed as a percentage of the predicted value was used as an index of restriction. Although crude (unadjusted) mean values of the ratio of forced expiratory volume in 1 s to forced vital capacity were significantly lower for heavy than for light drinkers, the difference disappeared when adjustment was made for numerous confounding factors (including such recognized risk factors for pulmonary disease as cigarette smoking, low socioeconomic status, male sex, and age). There was also no evidence of an association between consumption of alcohol and airway restriction. Although these findings do not rule out a possible effect of alcohol on pulmonary disease, its impact, if any, is probably the result of interaction with other factors associated with alcoholism, if not derived primarily from those other factors.

Adult↗

The effects of positive end-expiratory pressure on right and left ventricular performance.

The cardiovascular effects of positive end-expiratory pressure (PEEP) were studied in mechanically ventilated, vagotomized, Beta-blocked, anesthetized dogs. To compensate for the effect of PEEP on decreasing systemic venous return, acute plasma volume expansion was accomplished returning stroke volume and cardiac output to control values. Left and right ventricular filling pressures (LVFP and RVFP) and aortic pressure were measured relative to pressure (transmural pressure). Ventricular performance was assessed by comparing the transmural ventricular filling pressures at similar stroke volumes. Studies were performed on individual dogs with increasing LVFP produced by Beta-blockade, volume expansion, and obstruction of the descending thoracic aorta. Utilizing these methods we observed that for a given cardiac output, transmural LVFP was higher on PEEP compared to a control state with both normal and elevated control LVFP. On the right side, for a given cardiac output, RVFP was elevated only when the control LVFP was elevated. Our results suggest a nonneuronal adverse effect of PEEP on both left and right ventricular performance. This effect is probably due to mechanical heart-lung interaction since left ventricular (LV) dp/dt showed no change.

Animals↗