The relationship of acute pulmonary effects of organic materials to chronic pulmonary effects.
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Effective pulmonary capillary pressure and extravascular lung water were investigated in dogs (n = 9) with normal heart function and after development of acute myocardial ischaemia. During control, no impairment of cardiopulmonary performance was observed. Extravascular lung water was in the normal range (8.1 +/- 2.8 ml.kg-1) and the effective pulmonary capillary pressure accounted for 1.36 +/- 0.53 kPa (10.2 +/- 4 mmHg). No correlation between extravascular lung water and effective pulmonary capillary pressure was observed (r2 = 0.347, P = 0.06). Arterial (RPA) and venous pulmonary resistance (RPV) were 70 +/- 15% and 30 +/- 6%, respectively. Acute myocardial ischaemia was induced by one stage occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, heart rate and left ventricular end-diastolic pressure. Oxygenation deteriorated, but no hypoxaemia occurred in any animal and CO2 elimination remained unchanged. Extravascular lung water was elevated (16.5 +/- 7.9 ml.kg-1, P < or = 0.01), and effective pulmonary capillary pressure was higher when compared with the control state (2.32 +/- 1.05 kPa (17.4 +/- 7.9 mmHg), P < or = 0.01). There was a significant correlation between both parameters (r2 = 0.528, P < or = 0.05). Longitudinal distribution of pulmonary vascular resistance was altered, and RPA decreased to 60 +/- 13% (P < or = 0.05), while RPV increased to 40 +/- 8% (P < or = 0.05). It is concluded that development of lung oedema is related to elevated effective pulmonary capillary pressure in dogs with acute myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
The hemodynamic and pulmonary effects of fluid resuscitation with crystalloid and colloid solutions in the presence of mild pulmonary edema were investigated. Anesthetized dogs received oleic acid to increase pulmonary capillary permeability, and one hour later bled to produce hemorrhagic shock. One hour after the shock, resuscitation was performed with Ringer's lactate, 6% hydroxyethyl starch (HES) solution, or dog's plasma. Resuscitation from hemorrhagic shock restored hemodynamics to pre-hemorrhagic levels with all of the above solutions. Ringer's lactate resuscitation resulted in increases in extravascular lung water volume (EVLWV) and oxygen consumption, and decreases in colloid osmotic pressure and oxygen delivery. Resuscitation with HES solution and plasma did not result in increases in EVLWV, but with HES solution resulted in decreases in colloid osmotic pressure to pre-hemorrhagic levels in two hours. This suggests that the resuscitation with HES solution can not maintain colloid osmotic pressure for more than two hours. The author concludes that the hemodynamic and pulmonary effects of HES solution and plasma are similar in mild lung injury cases.
This paper describes a rebreathing method for the simultaneous measurement of oxygen consumption (VO2) and effective pulmonary blood flow (QP. eff) at rest and during exercise. Subjects rebreathed a test gas consisting of 35% oxygen, 3.5% chlorodifluoromethane (freon-22), and 10% argon in nitrogen for 30 seconds or until the respired oxygen tension fell to below 13.3 kPa. Sixty normal subjects were studied on a motorized treadmill, the Bruce protocol being used. The rebreathing manoeuvre was performed at three minute intervals, and was initially practised sitting down. Measurements were then made with the subjects standing at rest, and subsequently during the last minute of each stage of the Bruce exercise protocol until the subjects were exhausted. Heart rate was recorded from the electrocardiogram. Oxygen uptake plotted against calculated power (watts) showed a discontinuity between resting and exercise values, probably because power output during treadmill exercise is underestimated. The arbitrary addition of 30 watts to the exercise power output abolished this discontinuity. There was good agreement between rebreathing estimates of oxygen consumption and values measured during a second exercise test by the conventional open circuit argon dilution method. Coefficients of variation of oxygen consumption and effective pulmonary blood flow measured by rebreathing were usually less than 10% even during maximal exertion. At rest mean (SD) effective pulmonary blood flow corrected for body surface area was 2.2 (0.46) l/min/m2. Effective pulmonary blood flow rose linearly with oxygen consumption. At rest the arteriovenous oxygen content difference for pulmonary blood (VO2/QP eff) was 9.1 (1.6) ml/dl, rising to a maximum of 16.4 (1.8) ml/dl. The stroke volume index was 27.5 (6.8) ml/m2, rising to a maximum of 46.5 (7.1) ml/m2 during exertion.
Effective pulmonary blood flow was measured with a soluble inert gas uptake method (10% argon, 3.5% freon-22, 35% oxygen, balance nitrogen) in 98 apparently healthy children aged 5-14 years. None had any evidence of cardiorespiratory disease and all had normal values for absolute and dynamic lung volumes and transfer factor for carbon monoxide. Values of blood flow measured by a rebreathing method correlated reasonably closely with height, weight, body surface area, and lung volumes, and to a lesser extent with hand and foot size. The mean (SD) effective pulmonary blood flow index was 2.7 (0.31) 1 min-1 m-2. Small children found a single breath method of measuring flow more difficult to perform and the results were more variable.
Effective pulmonary capillary blood flow was measured on the first day of life in twenty term infants with birth asphyxia and twenty-five normal term infants. The infants studied showed no clinical or laboratory evidence of respiratory distress. The mean effective pulmonary capillary blood flow of 121 ml/kg/min in the birth asphyxia group was significantly lower than the mean of 162 ml/kg/min in the normal group. The possible relationship of birth asphyxia and pulmonary hypoperfusion in the aetiology of the idiopathic respiratory distress syndrome is discussed.
Serial pulmonary function tests including single-breath carbon monoxide-diffusing capacity (DLCO), forced vital capacity (FVC), and forced expiratory volume in 1 sec were performed in a relatively homogeneous group of male patients with germ cell tumors treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum. Of the pulmonary function tests used, the DLCO was shown to be the most sensitive indicator of subclinical bleomycin pulmonary effects. Decreases in DLCO were both total dose and schedule dependent. Patients receiving their total dose of bleomycin at a rate of 25 +/- 2 (S.D.) units/week developed a linear decrease in DLCO with increasing total doses of bleomycin. Changes in FVC did not correlate with bleomycin total dose. Although both the mean DLCO and FVC decreased after completion of bleomycin therapy, the mean FVC returned to base-line levels rapidly, whereas the decrease in mean DLCO was persistent for several months. When routine volumetric tests (FVC and forced expiratory volume in 1 sec) and DLCO are used in a systematic manner, DLCO is the most sensitive indicator of the subclinical pulmonary effects of bleomycin in germ cell tumor patients treated with vinblastine, bleomycin, and cis-diamminedichloroplatinum.
A cost-effective pulmonary rehabilitation program can be created by using strategic planning, a thorough budgetary process, and then promotion of the program. Strategic planning assesses the need for such a program, develops its overall direction, establishes priorities, assesses economic factors and the presence or absence of similar services already in existence, and identifies the proposed scope of the program. The budgetary process identifies the specific services to be offered and estimates the volume of services, their costs, and revenues. Promotion of the program serves to acquaint potential referring physicians and patients with the services to be offered. If preliminary investigation indicates that a pulmonary rehabilitation program is needed in the community, then strategic planning, careful budgeting, and creative promotion can help assure that the program is financially viable.
This study evaluated the cardiac and pulmonary effects of administering multiple inhaled doses of albuterol, isoproterenol sulfate, and placebo in ten patients with reversible obstructive disease of the airways. The pulmonary effects of therapy with albuterol were similar in magnitude to those of isoproterenol but lasted longer. The inotropic and chronotropic effects of therapy with isoproterenol were greater than those of albuterol. It appears that albuterol has beta2-adrenergic selectivity over a wide range of dosages and is an effective bronchodilator drug.
In animals pulmonary hypertension, a decrease in total body O2 consumption and metabolic acidosis occur after transfusion of blood with an elevated screen filtration pressure (SFP) through standard blood transfusion filters. The purpose of this study was to define in detail the pulmonary abnormalities that develop following transfusion of blood with an elevated SFP through standard blood transfusion filters. Exchange transfusions of approximately twice blood volume were administered through standard commercially available blood transfusion filters (measured pore size--200 microns) to 6 animals. SFP measurements verified the presence of large numbers of aggregates in the transfusions. Although filters reduced SFP of the stored blood somewhat, numerous microaggregates passed the filters, and post-filtration SFP remained high. After transfusion average O2 consumption decreased to 77% of normal and metabolic acidosis developed. Pulmonary arterial hypertension was associated with an increase in pulmonary shunting of blood and a decrease in pulmonary diffusing capacity. The presence of extensive numbers of microemboli in the pulmonary arteriolar and capillary bed was confirmed by microscopic examination of lung tissue.
To clarify the beta-1 selectivity of beta-adrenergic receptor blocking agents (beta-blocking agents) after typical oral doses, the relationships between the effects on exercise heart rate or FEV1 and beta-1 or beta-2 receptor occupancies (phi 1, phi 2) of seven beta-blocking agents, acebutolol, atenolol, metoprolol, oxprenolol, timolol, propranolol, and pindolol were analyzed retrospectively. Nonlinear relationships between the pharmacologic effect and phi 1 and between the pulmonary adverse effect and phi 2 were obtained. Based on these findings, a new index of cardiovascular selectivity is proposed, given by the ratio of beta-1 receptor occupancy to beta-2 receptor occupancy (phi 1/phi 2). Using this new index, there was a little difference in beta-1 selectivity between acebutolol and pindolol (3.1:1.0), in contrast to a marked difference in beta-1 selectivity (320:1) as a conventional index between these two drugs. This finding indicates that even beta-1 selective drugs must be administered carefully to patients with pulmonary disease. Furthermore, the relationship between the pharmacologic or pulmonary effects and phi 1 or phi 2 has been analyzed quantitatively with a ternary complex model and used to develop rational dosage regimens for beta-1 selective beta-blocking agents, such as atenolol, to obtain the desired pharmacologic effects with minimum adverse pulmonary effects.
1. Epoprostenol (prostacyclin) has been widely used as a vasodilator, but its effects on cardiac output are controversial and the time course of its effects little studied. 2. We report its cardiovascular effects in doses of 5 and 10 ng kg-1 min-1 in six healthy volunteers. 3. Each of the two doses caused a mean 20% rise in effective pulmonary blood flow and a 15% rise in heart rate. These effects appeared to reach a maximum within 10 min of starting or increasing the rate of infusion, with no evidence of a rebound effect. 4. When the dose was reduced, heart rate and effective pulmonary blood flow appeared to reach a new steady state within 5 min of reducing or stopping the infusion. Only minor side-effects were encountered, and they were rapidly reversed on stopping the drug. 5. These results should be applied to the therapeutic use of epoprostenol as a vasodilator, particularly when titrating the optimum dose for a given individual.
Radiation-induced pulmonary injury is common following treatment for a variety of tumors in and around the thorax. While symptomatic injury is unusual, subclinical injury identified by formal pulmonary function tests and/or radiographs is very common. In this article, the radiologic, symptomatic, and physiologic pulmonary effects of whole and partial thoracic irradiation are summarized from the animal and human data available. The risk of developing significant lung injury appears to be most dependent upon the radiation dose and volume of lung irradiated. Additional studies are needed to develop algorithms to predict the physiologic consequences of a proposed radiation treatment program such that reasonable risk-benefit assessments can be made. This may lead to improvements in the therapeutic ratios that facilitate dose escalation and improve local tumor control and cure rates.
PRIMARY OBJECTIVE: To evaluate a new technical approach to measuring effective pulmonary blood flow (PBF) in mechanically ventilated patients. RESEARCH DESIGN: Prospective clinical study; evaluation of accuracy and reproducibility. METHODS: Effective pulmonary blood flow was determined non-invasively in 32 mechanically ventilated patients by using a new rebreathing system (PBF(rb)). Cardiac output corrected for intrapulmonary shunt was taken as reference value (PBF(thd)). Bias, precision and reproducibility of the rebreathing method were calculated from duplicate measurements in each patient. MAIN RESULTS: The mean difference between PBF(rb) and PBF(thd) was - 0.67 +/- 0.83 l min(-1). The mean difference between duplicate measurements with the rebreathing system was 0.16 +/- 0.36 l min(-1). However, the accuracy of the rebreathing system tended to decrease in patients with PBF levels greater than 6 l min(-1). CONCLUSIONS: The new device appears to be reliable for determination of PBF values below 6 l min(-1). With this limitation, the present method may be used as a trend-indicator of PBF in mechanically ventilated patients.
Because minimal data are available regarding the pulmonary effects of ozone (O3) at levels less than 0.27 ppm, six groups of healthy young males were exposed for 2.5 h to one of the following O3 concentrations: 0.0, 0.12, 0.18, 0.24, 0.30, or 0.40 ppm. Fifteen-minute periods of rest and exercise (65 l/min minute ventilation) were alternated during the first 2 h of exposure. Coughing was observed at all levels of O3 exposure. Small changes in forced-expiratory spirometric variables [forced vital capacity (FVC), forced expiratory volume in 1 s, and mean expiratory flow rate between 25 and 75% FVC] were observed at 0.12 and 0.18 ppm O3, and larger changes were found at O3 levels greater than or equal to 0.24 ppm. Changes in tidal volume and respiratory frequency during exercise, specific airway resistance, the presence of pain on deep inspiration, and shortness of breath occurred at O3 levels greater than or equal to 0.24 ppm. In conclusion, pulmonary effects of O3 were observed at levels much lower than that for which these effects have been previously described. Stimulation of airway receptors is probably the mechanism responsible for the majority of observed changes; however, the existence of a second mechanism of action is postulated.
The pulmonary effects of the cocaine pyrolysis product, methylecgonidine (MEG; anhydroecgonine methyl ester), were assessed in guinea pigs. Specific airway conductance (SGaw), which decreases during bronchoconstriction, was measured in guinea pigs exposed to atmospheres containing a condensation aerosol of MEG free base (13 +/- 1 mg/liter of air), nebulized MEG fumarate (3 and 12% in phosphate buffered saline) or nebulized acetylcholine chloride (0.2 and 0.4% in phosphate buffered saline). A decrease in SGaw to 24.0 +/- 4.2% (mean +/- 2 S.E.M.) of baseline levels was observed in guinea pigs breathing MEG free base. A decrease to 28.4 +/- 4.5% of baseline was observed following administration of 0.4% acetylcholine. No change in SGaw was measured in guinea pigs exposed to 3% MEG fumarate but SGaw was reduced to 69.3 +/- 5.3% of baseline after exposure to 12% MEG fumarate. MEG free base poses an alkaline challenge to the lung, 3% MEG fumarate is neutral (pH approximately 7.4) and 12% MEG fumarate is acidic (pH approximately 4.3); thus, MEG free-base and 12% MEG fumarate might provoke a reflex bronchoconstriction due to direct pulmonary irritant effects. These results suggest that MEG free base produced during crack pyrolysis may play a role in bronchoconstriction observed in crack smokers.
Cardiovascular and pulmonary effects of morphine (1 mg/kg bolus iv) were investigated in conscious chronically instrumented pigs, a species exhibiting an excitable response. Control animals received an equivalent volume (less than 2 ml) of normal saline. Morphine induced an immediate but small increase in cardiac output and substantial increases in heart rate, mean systemic and pulmonary arterial pressure, left and right ventricular work, hematocrit, and hemoglobin concentration, but did not change stroke volume or systemic vascular resistance. Morphine administration also led to a gradual increase in ventilatory rate and rapid increases in tidal volume, expired and alveolar ventilation, ventilation-perfusion ratio, and shunt fraction. In addition, morphine administration produced substantial decrements in arterial and mixed venous PO2, hemoglobin saturation and mixed venous O2 content; no change in arterial O2 content; and a widening of the arteriovenous O2 difference. Arterial O2 transport was increased slightly. Finally, it produced substantial increments in arterial and mixed venous PCO2 and substantial decrements in arterial and mixed venous pH. It was concluded that arterial O2 delivery did not adequately rise to meet tissue O2 demand, in part because an appropriate increase in cardiac output was attenuated by morphine, and in part because morphine impaired pulmonary gas exchange.
The number of people smoking free-base cocaine, or "crack," has increased dramatically in recent years. Concomitantly, the literature describing complications of such use has grown as well. Adverse pulmonary effects are being increasingly noted, such as respiratory symptoms, pulmonary hemorrhage, pulmonary edema, asthma, and pulmonary barotrauma. These and other pulmonary effects are reviewed.