Biomedical subjects

E R Bleecker

Publications and source records attributed to E R Bleecker.

At least 91 records · Page 5Linked to original sources

PubMed1991

Effects of carbon monoxide on myocardial ischemia.

The purpose of this study was to determine whether low doses of carbon monoxide (CO) exacerbate myocardial ischemia during a progressive exercise test. The effect of CO exposure was evaluated using the objective measure of time to development of electrocardiographic changes indicative of ischemia and the subjective measure of time to onset of angina. Sixty-three male subjects (41-75 years) with well-documented coronary artery disease, who had exertional angina pectoris and ischemic ST-segment changes in their electrocardiograms, were studied. Results from three randomized, double-blind test visits (room air, low and high CO) were compared. The effect of CO exposure was determined from the percent difference in the end points obtained on exercise tests performed before and after a 1-hr exposure to room air or CO. The exposures resulted in postexercise carboxyhemoglobin (COHb) levels of 0.6% +/- 0.3%, 2.0% +/- 0.1%, and 3.9% +/- 0.1%. The results obtained on the 2%-COHb day and 3.9%-COHb day were compared to those on the room air day. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) decreases in the time to development of ischemic ST-segment changes after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. In addition, there were 4.2% (p = 0.027) and 7.1% (p = 0.002) decreases in time to the onset of angina after exposures producing 2.0 and 3.9% COHb, respectively, compared to the control day. A significant dose-response relationship was found for the individual differences in the time to ST end point and angina for the pre- versus postexposure exercise tests at the three carboxyhemoglobin levels. These findings demonstrate that low doses of CO produce significant effects on cardiac function during exercise in subjects with coronary artery disease.

Adult↗

PubMed1990

Airways hyperreactivity, bronchial inflammation and obstructive lung disease.

Understanding the mechanisms responsible for the development of chronic airflow obstruction is very important since this disease is the fifth leading cause of death in the United States and it produces a significant economic and social burden for society. Since reversal of established airflow obstruction is not possible, it would appear that the best prognosis and therapeutic results can be obtained by early diagnosis and prevention of irreversible disease. Understanding the underlying pathophysiologic mechanisms is necessary to detect susceptible individuals and develop effective interventions.

Animals↗

PubMed1990

Clinical trials in asthma and chronic airflow obstruction.

Clinical trials are becoming increasingly important in objectively evaluating therapeutic interventions in pulmonary medicine. Although the overall methodology for clinical trials is similar for most diseases, there are specific questions and problems unique to pulmonary medicine. This review is limited to a discussion of the general design and commonly encountered "problems and pitfalls" for clinical trials in respiratory medicine. Three examples of designs for intervention in asthma and chronic obstructive airways disease are presented.

Asthma↗

PubMed1990

Peripheral lung resistance in normal and asthmatic subjects.

In obstructive lung disease, peripheral airways are a major site of pathologic abnormalities. However, resistance to airflow in small airways in the periphery of the lung accounts for only a small fraction of total airway resistance. Consequently, abnormalities of small airway function may not be readily detected using routine pulmonary function testing. In the present study, resistance of the peripheral lung was examined directly in six normal subjects and nine mildly asthmatic subjects. There were no significant differences between the normal and asthmatic groups in pulmonary function assessed by spirometry (FEV1, FVC) and body plethysmography (specific airway conductance). Direct measurements of peripheral lung function were made using a fiberoptic bronchoscope wedged into a subsegmental, right upper lobe bronchus. Using a double-lumen catheter inserted into the instrument channel of the bronchoscope, pressures (PB) produced by three or more different levels of gas flow (V) (5% CO2 in air) between 50 and 500 ml/min were measured. All pressure measurements were made at a constant lung volume (i.e., functional residual capacity) confirmed by monitoring transpulmonary pressure with an esophageal balloon. The pressure-flow relationship in both normal and asthmatic subjects could be approximated by a straight line through the origin, demonstrating these airways to be relatively nondistensible. Peripheral lung resistance (Rp) was defined by PB/V and averaged for three or more levels of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

PubMed1990

Evidence for elevated levels of histamine, prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma.

Histamine and certain cyclooxygenase products of arachidonic acid have been implicated as mediators of inflammation and are potent constrictors of human airways. Because asthma may represent manifestations of chronic inflammation of the airways, the levels of histamine and six prostanoid mediators were measured in airway fluids obtained by bronchoalveolar lavage (BAL) of 12 normal, 11 allergic rhinitic, and 15 asymptomatic, allergic asthmatic subjects. Simultaneous profiling of prostanoid mediators in individual samples was performed using gas chromatography-mass spectrometry. Levels of PGD2, 9 alpha,11 beta-PGF2 and PGF2 alpha were 12 to 22 times higher in asthmatic than in normal subjects (p less than 0.01), with concentrations in airway fluids of asthmatic subjects after correction for dilution of 3.8, 0.5, and 1.4 nanomolar, respectively. Levels of PGD2 and 9 alpha,11 beta-PGF2 were increased nearly tenfold in asthmatic subjects compared with those in rhinitic subjects (p less than 0.01), distinguishing the subjects with lower airway disease from those with another atopic condition. Histamine levels were increased fourfold in asthmatic subjects compared with those in normal subjects (p less than 0.001); however, similar increases were found in rhinitic subjects. We conclude that elevated levels of multiple mediators with potent bronchoconstricting activity are present in the airways of subjects with mild asthma, indicating that even mild disease is associated with evidence of airway inflammation. The interactions of bronchoconstricting mediators and airway inflammation may play important roles in the pathogenesis of asthma.

Adult↗

PubMed1989

Short-term effects of carbon monoxide exposure on the exercise performance of subjects with coronary artery disease.

Patients with atherosclerotic cardiovascular disease may be adversely affected by the presence of carboxyhemoglobin, even at low concentrations. We investigated the effects of carbon monoxide exposure on myocardial ischemia during exercise in 63 men with documented coronary artery disease. On each test day, subjects performed two symptom-limited incremental exercise tests on a treadmill; the tests were separated by a recovery period and 50 to 70 minutes of exposure to either room air or air containing one of two concentrations of carbon monoxide (117 +/- 4.4 ppm or 253 +/- 6.1 ppm). The order of exposure was assigned randomly. On each occasion, neither the subjects nor the study personnel knew whether the subjects had been exposed to room air or to one of the concentrations of carbon monoxide. Exposure to room air resulted in a mean carboxyhemoglobin level of 0.6 percent, exposure to the lower level of carbon monoxide resulted in a carboxyhemoglobin level of 2.0 percent, and exposure to the higher level of carbon monoxide resulted in a level of 3.9 percent. An effect of carbon monoxide on myocardial ischemia was demonstrated objectively by electrocardiographic changes during exercise. We observed a decrease of 5.1 percent (90 percent confidence interval, 1.5 to 8.7 percent; P = 0.02) and a decrease of 12.1 percent (90 percent confidence interval, 9.0 to 15.3 percent; P less than or equal to 0.0001) in the length of time to a threshold ischemic ST-segment change (ST end point) after carbon monoxide exposures that produced carboxyhemoglobin levels of 2.0 percent and 3.9 percent, respectively. The length of time to the onset of angina decreased by 4.2 percent (90 percent confidence interval, 0.7 to 7.9 percent; P = 0.054) at the 2.0 percent carboxyhemoglobin level and by 7.1 percent (90 percent confidence interval, 3.1 to 10.9 percent; P = 0.004) at the 3.9 percent carboxyhemoglobin level. Significant dose-response relations were found in both the change in the length of time to the ST end point (P less than or equal to 0.0001) and the change in the length of time to the onset of angina (P = 0.02). We conclude that low levels of carboxyhemoglobin exacerbate myocardial ischemia during graded exercise in subjects with coronary artery disease.

Adult↗

PubMed1989

Effects of body composition and exercise capacity on glucose tolerance, insulin, and lipoprotein lipids in healthy older men: a cross-sectional and longitudinal intervention study.

The relationships of age, body composition, and physical conditioning status to glucose tolerance, insulin, and lipoprotein levels were examined in 77 healthy, nonsmoking white male volunteers, aged 46 to 73 years with no evidence of coronary artery or endocrine-metabolic disease. The men had a wide range of body fat (13% to 39%), indexed as waist-to-hip ratio (WHR, 0.84 to 1.08), and maximal aerobic capacity (VO2max, 17 to 48 mL/kg.min). Multiple regression analysis with age, VO2max, WHR, and percent body fat as independent variables demonstrated that fasting plasma insulin, triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) levels were independently related to both percent body fat and WHR. In contrast, fasting plasma glucose levels and insulin responses during oral glucose tolerance tests (OGTT) correlated independently with percent body fat, and glucose responses to OGTT correlated only with WHR. Although fasting plasma TG and HDL-C correlated with glucose and insulin levels, in multiple regression analyses only percent body fat and WHR were the significant independent variables. Fasting total and low density lipoprotein cholesterol values were not related to these variables. To test the effects of weight loss and exercise training on these relationships, 20 obese men of comparable age, percent body fat, WHR, and VO2max were randomly assigned to weight loss or aerobic exercise training programs. A 12% +/- 3% loss in body weight (P less than .01, mean +/- SD) resulted in a 19% +/- 9% decline in body fat (P less than .01) with no change in fat free mass, WHR, or VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Acute effects of carbon monoxide exposure on individuals with coronary artery disease.

The purpose of this study was to determine, using more objective evidence than that reported in previous studies, whether or not exposures to carbon monoxide that produce approximately 2% or 4% blood carboxyhemoglobin levels cause an exacerbation of myocardial ischemia during a progressive exercise test. The objective measurements were based on the development of electrocardiographic evidence of ischemia. In addition, time to onset of angina pectoris was studied. Male subjects, ages 35 to 75, with stable exertional angina pectoris and positive exercise treadmill tests with reproducible ischemic ST-segment changes in their electrocardiograms, were studied. In addition, each subject fulfilled at least one of the following criteria of coronary artery disease: angiographic evidence of at least a 70% occlusion of one or more major coronary artery; prior documented myocardial infarction; or a positive exercise thallium test. Each subject was evaluated on four separate occasions, a qualifying visit and three blinded test visits, which involved exposure (in random order) to air without added carbon monoxide and to air that contained carbon monoxide concentrations calculated to produce approximately 2.2% or 4.4% carboxyhemoglobin, measured by gas chromatography, at the end of the exposure period. These immediate postexposure target levels were set 10% higher than the desired postexercise carboxyhemoglobin levels of 2.0% and 4.0% because exercise while breathing room air results in loss of carbon monoxide. The actual one-minute postexercise levels reached were 2.0% +/- 0.1% (mean +/- standard error of the mean) and 3.9% +/- 0.1%. On each test day, the subject performed a symptom-limited exercise test on a treadmill, was exposed for approximately one hour to air or to one of two levels of carbon monoxide in air, and then performed a second exercise test. Time to the onset of ischemic ST-segment changes and time to the onset of angina were determined for each exercise test. The percent difference for these endpoints on the pre- and postexposure exercise tests was determined, and then the results on the 2%-COHb-target day and the results on the 4%-COHb-target day were compared to those on the control day. Data from the 63 subjects who completed the three test visits and met all protocol criteria were analyzed. There were 5.1% (p = 0.01) and 12.1% (p less than or equal to 0.0001) (trimmed mean) decreases in the time to development of ischemic ST-segment changes after the 2%- and 4%-COHb-target exposures, respectively, compared to the control day.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1988

Profiling of bisenoic prostaglandins and thromboxane B2 in bronchoalveolar fluid from the lower respiratory tract of human subjects by combined capillary gas chromatography-mass spectrometry.

Methods for the profiling of prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 15(S),9 alpha,11 beta-trihydroxyprosta-5Z,13E-dien-1-oic acid (9 alpha,11 beta-PGF2), 6-keto-prostaglandin F1 alpha (6kPGF1 alpha), and thromboxane B2 (TxB2) in bronchoalveolar lavage (BAL) fluids from human subjects by combined capillary gas chromatography-mass spectrometry are described. Aliquots (5 ml) of BAL fluid obtained using a standardized lavage protocol were extracted on octadecylsilyl silica cartridges after addition of 0.8 to 2.0 nanograms of tetradeuterated analogs of PGE2, PGF2 alpha, and 6kPGF1 alpha as internal standards. Eluted analytes and internal standards were prepared for vapor phase analysis by sequential reactions resulting in the formation of methyloxime-pentafluorobenzyl ester-trimethylsilyl ether derivatives. The derivatized analytes were detected by simultaneous monitoring of ions at six different masses characteristic for each of the derivatized prostanoids. The samples were of adequate purity for identification and quantitation of each of the prostanoids with detection limits of 0.1 to 0.2 picograms of each analyte per milliliter of BAL fluid. The time required for analysis of each sample was approximately 30 minutes. Standard curves of unlabeled species of the six prostanoids extracted after addition to BAL fluid were linear over a range from subpicogram to nanogram quantities. The differences between the amounts of prostanoid added and the amounts of prostanoid measured were typically less than 19%, and the intra-assay coefficients of variation for repeated measurements of a single sample were less than 20%. PGE2, PGD2, PGF2 alpha, and TxB2 were detectable in BAL fluids from normal subjects with levels of each of these compounds being less than 2.6 picograms/ml. BAL fluids from patients with lung disease presented qualitative and quantitative profiles of prostanoids markedly different than those from normal subjects. These analytical methods provide a basis for in vivo comparisons of prostanoid profiles in the lower respiratory tract of man and should be readily adaptable for use in a variety of clinical studies.

Alveolitis, Extrinsic Allergic↗

PubMed1988

Effects of antihistamines on the cardiopulmonary changes due to canine anaphylaxis.

Histamine has long been considered to be an important chemical mediator in the pathogenesis of immediate hypersensitivity reactions. We evaluated the efficacy of antihistamines to determine the physiological role of histamine in canine anaphylaxis. Either a saline vehicle (control group), an H1 antihistamine (chlorpheniramine, 10 mg/kg), or this H1 antihistamine and an H2 antihistamine (cimetidine, 30 mg/kg) was administered to three separate groups of anesthetized dogs (n = 8). Cardiopulmonary responses and plasma histamine levels were measured after the separate intravenous injection of Ascaris suum antigen and histamine. Results were analyzed only from the animals demonstrating physiological responses or histamine release after antigen injection. In the control group, antigen produced a 43 +/- 15% (mean +/- SE) decrease in mean arterial blood pressure, a 34 +/- 13% fall in cardiac output, and a 19 +/- 9% decrease in lung compliance, whereas pulmonary vascular resistance increased 161 +/- 87% and airway resistance rose 114 +/- 66%. Similar physiological abnormalities were observed with histamine shock. However, peak plasma histamine levels were, in most cases, greater after histamine injection than after antigen injection. An H1 antihistamine alone or in combination with an H2 antihistamine did not alter the physiological changes associated with systemic anaphylaxis. In contrast, the combined use of H1 and H2 antihistamines prevented the cardiopulmonary responses associated with the intravenous administration of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylaxis↗

PubMed1987

Effects of airway pressure on bronchial blood flow.

We studied the effects of increased airway pressure caused by increasing levels of positive end-expiratory pressure (PEEP) on bronchial arterial pressure-flow relationships. In eight alpha-chloralose-anesthetized mechanically ventilated sheep (23-27 kg), the common bronchial artery, the bronchial branch of the bronchoesophageal artery, was cannulated and perfused with a pump. The control bronchial blood flow (avg 12 +/- 1 ml/min or 0.48 ml X min-1 X kg-1) was set to maintain mean bronchial arterial pressure equal to systemic blood pressure. Pressure-flow curves of the bronchial circulation were measured by making step changes in bronchial blood flow, and changes in these curves were analyzed with measurements of the pressure at zero flow and the slope of the linearized curve. The zero-flow pressure represents the effective downstream pressure, and the slope represents the resistance through the bronchial vasculature. At a constant bronchial arterial pressure of 100 mmHg, an 8 mmHg increase in mean airway pressure caused a 40% reduction in bronchial blood flow. Under constant flow conditions, increases in mean airway pressure with the application of PEEP caused substantial increases in bronchial arterial pressure, averaging 4.6 mmHg for every millimeters of mercury increase in mean airway pressure. However, bronchial arterial pressure at zero flow increased approximately one-for-one with increases in mean airway pressure. Thus the acute sensitivity of the bronchial artery to changes in mean airway pressure results primarily from changes in bronchovascular resistance and not downstream pressure.

Animals↗

PubMed1987

Acute upper airway injury in burn patients. Serial changes of flow-volume curves and nasopharyngoscopy.

Serial flow-volume curves and fiberoptic nasopharyngoscopy were performed in 36 patients with cutaneous burns and/or smoke inhalation. Baseline flow-volume curve patterns were abnormal in 26 (72.2%) patients, and follow-up studies demonstrated significant reductions (p less than 0.04) in inspiratory and expiratory flow rates in the 6 patients who required endotracheal intubation because of anatomic upper airway obstruction. None of the patients with stable or increased flow rate measurements required intubation. The progression of upper airway edema in 14 patients was characterized by obliteration of the aryepiglottic folds, arytenoid eminences, and interarytenoid areas by boggy, edematous tissue that prolapsed to occlude the airway. These changes correlated with an increased size of cutaneous burns (p less than 0.0001), the presence of burns of the face and neck (p less than 0.05), and more rapid intravenously administered fluid resuscitation (p less than 0.04). Anatomic and physiologic changes consistent with upper airway dysfunction occur frequently in burn victims. Progression of these abnormalities correlates with the severity and distribution of cutaneous injury and is influenced by intravenously administered fluid.

Acute Disease↗

PubMed1987

Computed chest tomography in the evaluation of hemoptysis. Impact on diagnosis and treatment.

The results of computed chest tomograms (CT) and chest roentgenograms (CR) were compared in 32 patients who presented with hemoptysis. The CT demonstrated roentgenographic abnormalities more often than CR (p less than 0.01), providing new diagnostic information in 15 patients (46.9 percent), and clarifying CR abnormalities in five (15.6 percent) others. In addition, CT correctly localized sources of bleeding in 23 (88.5 percent) of the 26 patients in whom a site was identified at bronchoscopy, while CR localization was correct in 17 (65.4 percent) (p less than 0.05). Despite this augmentation of roentgenographic yield, information derived from CT scans influenced the management of only six patients, did not obviate the need for bronchoscopy, and supplemented the combined diagnostic yield of CR and bronchoscopy in only two. Outcome was changed in one patient in whom CT had demonstrated an otherwise unrecognized malignant solitary pulmonary nodule. The chest roentgenogram and fiberoptic bronchoscopy provided all the information essential for diagnosis and therapeutic recommendations in 93.7 percent of these patients. Although the CT provided additional information in over one half of our patients, its overall impact on clinical management was small and does not support routine use of this imaging procedure in evaluation of hemoptysis. The possible role of chest CT in evaluating carefully selected patients with hemoptysis requires further study.

Bronchitis↗

PubMed1986

Comparison of the anticholinergic bronchodilator ipratropium bromide with metaproterenol in chronic obstructive pulmonary disease. A 90-day multi-center study.

The short- and long-term efficacy and safety of an inhaled quaternary ammonium anticholinergic agent, ipratropium bromide, and a beta agonist aerosol, metaproterenol, were compared in 261 nonatopic patients with chronic obstructive pulmonary disease (COPD). The study was a randomized, double-blind, 90-day, parallel-group trial. On three test days-one, 45, and 90-mean peak responses for forced expiratory volume in one second and forced vital capacity and mean area under the time-response curve were higher for ipratropium than for metaproterenol. Clinical improvement was noted in both treatment groups, especially during the first treatment month, with persistence of improvement throughout the remainder of the study. Side effects were relatively infrequent and generally mild; tremor, a complication of beta agonists, was not reported by any subject receiving ipratropium. These results support the effectiveness and safety of long-term treatment with inhaled ipratropium in COPD.

Adult↗

PubMed1986

Cholinergic and neurogenic mechanisms in obstructive airways disease.

Although primary neural control of airway function is through parasympathetic pathways, more recent evidence indicates that there are important adrenergic and non-adrenergic, non-cholinergic neural mechanisms that may also influence respiratory function. The parasympathetic nervous system component includes neural receptors in the airways as well as afferent and efferent pathways that travel in the vagus nerves. Afferent vagal sensory receptors mediate the response to irritant or rapidly adapting receptor activation, Hering-Breuer, and the unmyelinated "C" fibers or "J" receptor pathways. The motor component of the parasympathetic nervous system has several important functions that regulate tone in normal system has several important functions that regulate tone in normal and obstructed airways. These pathways affect the following respiratory structures: bronchial smooth muscle; the mucociliary system; the larynx; and the nose. Finally, the parasympathetic nervous system may play a role in some species in the control of breathing and in the hyperpneic responses associated with airflow obstruction. In addition to cholinergic neural mechanisms, bronchomotor tone may also be influenced by adrenergic mechanisms and non-adrenergic, non-cholinergic neural pathways. Although there is minimal innervation of the airways by the sympathetic nervous system, there is ample evidence that beta-adrenoreceptors are present on bronchial smooth muscle. Beta-receptor stimulation not only relaxes airway smooth muscle, but also inhibits mediator release from mast cells in the airways and may alter vascular permeability. Alpha-adrenoreceptors are found in human airways and stimulation of these receptors causes bronchoconstriction. Although the importance of alpha-adrenoreceptors has been questioned, recent evidence suggests that alpha stimulation may play a role in cold air- and exercise-induced asthma. Finally, non-adrenergic, non-cholinergic nerves have been shown to cause relaxation of human airways in in vivo studies. There is increasing evidence that vasoactive intestinal peptide and peptide histidine methanol are the mediators of these responses. More recently, other neuropeptides (substance P, neurokinin A, and calcitonin gene-related peptide) have been localized in nerves in airways. These cause bronchoconstriction in vitro and may be released from afferent nerve terminals by an axon reflex. Although the precise role of these substances in controlling airway tone and bronchial secretions in humans is not fully understood, they may have important modulatory effects on the neural control of airway function.

Animals↗

PubMed1986

Profiling of prostaglandin biosynthesis in biopsy fragments of human lung carcinomas and normal human lung by capillary gas chromatography-negative ion chemical ionization mass spectrometry.

Methods for the profiling of prostaglandin F2 alpha (PGF2 alpha), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) biosynthesis in tissue samples of clinical origin by capillary gas chromatography-negative ion chemical ionization mass spectrometry (CGC-NICIMS) are detailed. Aliquots (25 microliter 1) of incubates (1 ml volume) of human lung carcinoma and normal human lung tissue fragments (total protein content = 0.2 to 2.0 mg) were derivatized for vapor phase analysis in the presence of 0.75 to 1.60 ng of tetradeuterated analogs of PGE2, PGF2 alpha and 6KPGF1 alpha without prior extraction and/or chromatography. The derivatized analytes and internal standards were detected by simultaneous monitoring of ions at six different masses characteristic for each of the derivatized prostanoids. The inter-sample and intra-sample coefficients of variation for the assay method were typically less than 12%. The analysis of biological samples was completed with less than 2.5% of each derivatized sample per injection. The samples were of adequate purity for the identification and quantitation of each of the eicosanoids. The methods described in this report are highly selective and highly sensitive with detection limits of 0.1 to 0.2 picograms per injection. The analytical procedures provide the basis for comparisons of the qualitative and quantitative profiles of prostaglandin biosynthesis and should be adaptable for use in a variety of biological and clinical studies.

Biopsy↗

PubMed1986

Peripheral circulatory alterations in canine anaphylactic shock.

We have examined peripheral circulatory variables that might contribute to the decrease in cardiac output and arterial pressure characteristic of anaphylactic shock. In six dogs instrumented with a right heart bypass, the intravenous administration of Ascaris suum antigen caused a 53% decrease in cardiac output and a 58% decrease in arterial pressure. Resistance to venous return increased from 0.0038 +/- 0.0004 to 0.0056 +/- 0.0006 mmHg X ml-1 X min (P less than 0.05), mean systemic pressure decreased from 7.0 +/- 0.6 to 4.4 +/- mmHg (P less than 0.005), and vascular compliance did not change. Assuming a constant vascular volume, the decrease in mean systemic pressure could be explained by a rightward shift of the systemic pressure volume curve. This constant-volume assumption was tested in intact (n = 6) and splenectomized dogs (n = 7). Serial measurements of protein oncotic pressure and hematocrit were used to estimate plasma volume changes during anaphylaxis. Both methods for estimating volume showed small increases in plasma volume at the time of the largest decrease in arterial pressure in both groups of animals. These results suggest that the primary circulatory mechanisms responsible for anaphylactic shock are an increase in resistance to venous return and a shift of the systemic pressure volume curve and not an acute loss of plasma volume.

Anaphylaxis↗

PubMed1986

Prevention of canine anaphylaxis with isoproterenol.

Sympathomimetic agents are used to reverse the cardiovascular and respiratory abnormalities that are associated with anaphylactic shock. In addition, in vitro studies have demonstrated that beta-adrenergic stimulation modulates IgE-mediated release of chemical mediators. To separately evaluate the ability of isoproterenol, a beta-adrenergic agonist, to prevent mediator release and anaphylactic shock, as well as to reverse the cardiopulmonary manifestations of systemic anaphylaxis, we administered a continuous infusion of isoproterenol before and during canine anaphylactic shock. An intravenous injection of Ascaris suum antigen was used to produce shock, which was characterized by a 50 +/- 15% (mean +/- SEM) decrease in mean arterial blood pressure, a 30 +/- 8% decrease in cardiac output, and a 122 +/- 95% increase in total pulmonary resistance. These changes were associated with significant increases in plasma histamine concentrations from 1.1 +/- 0.1 to 158.4 +/- 137 ng/ml. Administration of a continuous infusion of isoproterenol during anaphylactic shock did not significantly improve any of these physiologic abnormalities. However, when isoproterenol was administered prior to the injection of antigen, these physiologic changes were prevented and histamine release was inhibited in a significant proportion of animals. In contrast, beta-adrenergic stimulation did not prevent nonimmunologic shock and mediator release induced with compound 48/80. We conclude that the administration of a beta-adrenergic agonist prevented the cardiopulmonary manifestations of anaphylactic shock by inhibiting mediator release and that the physiologic effects of isoproterenol administered during systemic anaphylaxis were minimal.

Airway Resistance↗