Solbert Permutt

Effect of Epinephrine on Pressure, Flow, and Volume Relationships in the Systemic Circulation of Dogs

The effect of epinephrine on peripheral circulation was studied in ten anesthetized open-chest dogs. Blood flow and right atrial pressure were independently controlled by a right heart bypass; changes in blood volume could be precisely determined from the changes occurring in the bypass reservoir. At constant blood flow and right atrial pressure, a constant infusion of epinephrine (5.8 μg/kg min−1) decreased blood volume by an average of 208 ml. During epinephrine infusion, the ratio of changes in blood volume to changes in blood flow measured at constant right atrial pressure, (ΔV/ΔQ˙)Pra, decreased from 0.226 minutes to 0.153 minutes and the ratio of changes in blood volume to changes in right atrial pressure at constant blood flow, the vascular compliance, decreased from 27.1 ml/cm H2O to 20.7 ml/cm H2O. Transient changes in blood volume following a step decrease in right atrial pressure at constant blood flow showed that blood was draining from two vascular compartments with different time constants: 0.059 minutes and 0.388 minutes before epinephrine infusion and 0.058 minutes and 0.486 minutes during epinephrine infusion. We analyzed the data using a mathematical model of the peripheral circulation consisting of two compartments with different time constants. The analysis showed that the primary effect of epinephrine on the systemic circulation was to redistribute blood flow away from the compartment with the longest time constant. The reduction in (ΔV/ΔQ˙)pra and the decrease in blood volume at constant flow and right atrial pressure were essentially determined by the change in flow distribution brought about by a change in arteriolar tone and not by a change in venous tone.

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.

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. Circ Res 45: 719-?28, 1979

Mechanism of decreased left ventricular stroke volume during inspiration in man.

Radionuclide ventriculography was performed in 15 healthy subjects during quiet breathing and during inspiration against a 24 cm H2O threshold load with a respiratory gating technique. Inspiratory threshold loading caused an inspiratory decrease in ejection fraction from 64% to 59% (p less than .001). Stroke counts proportional to stroke volume decreased by 9.6% (p less than .02) due to an increase in end-systolic counts of 15.9% (p less than .05). End-diastolic counts decreased in four subjects and increased in three subjects, but the mean counts did not change significantly. These findings suggest that negative pleural pressure causes an impediment to left ventricular ejection comparable to an increase in arterial pressure. Respiratory gating of radionuclide ventriculography during loaded breathing is suggested as a controlled stress on the ventricle for diagnostic purposes.

Frequency Function of Transit Times through Dog Pulmonary Circulation

The frequency function of transit times through the pulmonary vascular system in dogs was obtained by deconvolution of a pair of simultaneous tracer dilution curves. One tracer dilution curve represented transit times from pulmonary artery to aorta; the other represented transit times from left atrium to aorta. Theory of and requirements for deconvolution are presented. Two preparations were used: closed chest with recirculation, open chest with only myocardial recirculation. The frequency function of pulmonary vascular transit times was skewed markedly to the right. At constant cardiac output and left atrial pressure it was unaffected by change in heart rate or by respiratory movements. Frequency functions of transit time obtained by deconvolution of observed tracer concentration curves, including recirculation, were compared with those obtained by monoexponential extrapolation of the same tracer concentration curves to “eliminate” recirculation. If recirculation seemed to appear before the observed concentration curve (aortic sampling following pulmonary arterial injection) fell to 20% of peak, monoexponential extrapolation led to a 10% overestimate of mean transit time and to greater errors in estimate of higher moments. If recirculation did not seem to occur until the concentration fell to 10% or less of peak, there was no difference between the frequency functions of transit times calculated by the two methods. Increased coefficients of variance and skewness were associated with large mean transit times produced by hypovolemia and reduced cardiac output secondary to withdrawal of blood.

Room Air Disinfection by Ultraviolet Irradiation of Upper Air

Disinfection of air in lower part of a room by ultraviolet irradiation of upper air has been studied after artificial dissemination of test organisms (Serratia marcescens). On basis of disinfection rates in lower air with different intensities of UV in upper air, the rates at which organisms are killed in upper air and at which air mixes between upper and lower parts of the room were calculated. By performing studies under different conditions of air motion, it was possible to analyze factors affecting air mixing and upper-air disinfection. With no fans to increase air motion, a single 30-w UV tube increased the rate of disappearance of organisms from lower part of room by the equivalent of 61 air changes per hour (median value). With a large-bladed ceiling fan, the same UV tube almost doubled the rate of disappearance of organisms.

Lung Size Mismatch in Bilateral Lung Transplantation Is Associated With Allograft Function and Bronchiolitis Obliterans Syndrome

BACKGROUND Size mismatch between donor lungs and a recipient thorax could affect the major determinants of maximal expiratory airflow: airway resistance, propensity of airways to collapse, and lung elastic recoil. METHODS A retrospective review of 159 adults who received bilateral lung transplants was performed. The predicted total lung capacity (pTLC) for donors and recipients was calculated based on sex and height. Size matching was represented using the following formula: pTLC ratio = donor pTLC / recipient pTLC. Patients were grouped according to those with a pTLC ratio > 1.0 (oversized) or those with a pTLC ratio ≤ 1.0 (undersized). Allograft function was analyzed in relation to the pTLC ratio and to recipient and donor predicted function. RESULTS The 96 patients in the oversized cohort had a mean pTLC ratio of 1.16 ± 0.13 vs 0.89 ± 0.09 in the 63 patients of the undersized group. At 1 to 6 months posttransplant, the patients in the oversized cohort had higher FEV(1)/FVC ratios (0.895 ± 0.13 vs 0.821 ± 0.13, P < .01) and lower time constant estimates of lung emptying (0.38 ± 0.2 vs 0.64 ± 0.4, P < .01) than patients in the undersized cohort. Although the FVCs expressed as % predicted for the recipient were not different between cohorts, the FVCs expressed as % predicted for the donor organ were lower in the oversized cohort compared with the undersized cohort (at 1-6 months, 52.4% ± 17.1% vs 65.3% ± 18.3%, P < .001). Kaplan-Meier estimates for the occurrence of bronchiolitis obliterans syndrome (BOS) showed that patients in the oversized cohort had a lower probability of BOS (P < .001). CONCLUSIONS A pTLC ratio > 1.0, suggestive of an oversized allograft, is associated with higher expiratory airflow capacity and a less frequent occurrence of BOS.

Convection, Air Mixing, and Ultraviolet Air Disinfection in Rooms

The efficiency with which airborne test organisms were removed from the lower part of a room when the upper air was irradiated with ultraviolet light (UV) was used to evaluate convective air mixing between the upper and lower parts of the room. The temperature of air entering the room through four diffusers in the ceiling was 10 to 15 F hotter or colder than lower room air during the studies. Rates of disappearance of test organisms atomized into the air were more than twice as fast when cold air entered at the ceiling as when hot air entered. Mean vertical mixing rates were estimated to be 20 air changes per hour (AC/hr) with hot air entering at the ceiling and 150 to 300 AC/hr with cold air entering at the ceiling. These large differences resulted from the large temperature gradients which favored or inhibited vertical mixing of air.

Airways hyperresponsiveness and the effects of lung inflation

Lung inflation has a beneficial effect on the airways of healthy subjects. It acts as a bronchoprotector, that is to prevent bronchoconstriction, and as a bronchodilator, in that it reverses bronchial obstruction. The bronchoprotective effect of deep inspiration is more potent than the bronchodilatory one, and the two phenomena appear to advocte different mechanisms. Asthmatics and rhinitics with airways hyperresponsiveness show an impairment in bronchoprotection induced by deep breaths, whereas the bronchodilatory effect, although reduced, is still effective. The lack of the bronchoprotective effect of deep inspiration may contribute to the development of airways hyperresponsiveness. The mechanisms through which lung inflation exerts its beneficial role in healthy subjects, and the factors impairing such an effect in those with airways hyperresponsiveness, are currently under investigation.

Parameters of donor-recipient size mismatch and survival after bilateral lung transplantation

BACKGROUND The purpose of this study was to investigate the relationship between donor-recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival. METHODS The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio ≤1.0 or >1.0 and height ratio ≤1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models. RESULTS There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival. CONCLUSIONS A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft-thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes.