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PubMed1988

Muscarinic receptor subtypes mediating myocardial blood flow redistribution.

Selective M1 and M2 muscarinic receptor antagonists pirenzepine and AF-DX 116, respectively, were administered to open-chest, pentobarbital-anesthetized dogs to determine the muscarinic receptor subtype responsible for the preferential vasodilation of subendocardial blood vessels during intracoronary methacholine infusion. There were no changes in systemic hemodynamics responsible for the myocardial blood flow redistribution produced by methacholine. Selective M1 receptor blockade with pirenzepine attenuated increases in transmural perfusion and prevented the redistribution of blood flow favoring the subendocardium during methacholine infusion. M2 receptor blockade with AF-DX 116 also attenuated the increase in transmural perfusion produced by methacholine but did not selectively block increases in subendocardial blood flow. These results support the hypothesis that M1 muscarinic coronary receptors are responsible for the redistribution of blood flow to the subendocardium (increased endo/epi) during cholinergic coronary vasodilation, whereas M2 receptors mediate an increase in total coronary blood flow. In additional experiments in isolated rabbit aorta, AF-DX 116 was 0.38 times less potent than pirenzepine with respect to endothelium-dependent muscarinic vasodilation but 1.47 times more potent with respect to endothelium-independent muscarinic vasoconstriction. This suggests that differences exist in the receptors found on the vascular smooth muscle and endothelium and that the preferential distribution of blood flow to the subendocardium may be due to stimulation of M1 receptors located on the vascular endothelium.

Animals↗
PubMed1979

Medical outcome in asthmatic patients: effects of airways hyperreactivity and symptom-focused anxiety.

Hypotheses about medical outcome in asthma, indexed by rates of rehospitalization within 6 months after discharge from long-term intensive care, were evaluated. Predictions for rehospitalization were based on the levels of airways hyperreactivity, indexed by inhalation challenges with histamine or methacholine, and levels of anxiety focused upon and concurrent with periods of asthmatic distress, indexed by Panic-Fear symptomatology. Results indicated that, although some prediction could be made on the basis of levels of anxiety and airways hyperreactivity alone, the best predictions resulted from the combined effects of these factors. Almost half of the patients who had highly hyperreactive airways and a tendency to disregard symptoms of breathing difficulty were rehospitalized. By comparison, none of the patients who had less hyperreactive airways and a tendency to be vigilant about their symptoms were rehospitalized. The hypotheses and results are discussed with respect to symptom-focused and general, illness-dependent types of anxiety which have different effects upon medical outcome in chronic asthma. The results have implications for the application of anxiety-reducing forms of intervention in asthma.

Adolescent↗
PubMed1987

Clinical use of methacholine bronchial challenge testing.

Whereas the research applications have been well established, the clinical utility of bronchial challenge testing is still being defined. In 19 of 22 patients referred for testing (86%), the results of a methacholine challenge test helped to confirm a clinical suspicion of asthma or to suggest that alternative diagnoses should be investigated. There was a discrepancy between the pretest suspicion of the referring physician and the results of the challenge test in six of these 19 patients (32%). Thus our experience suggests that bronchial challenge testing provides useful information to supplement clinical acumen in the diagnosis of asthma.

Adolescent↗
PubMed1980

Absence of airway hyperreactivity to methacholine in a worker sensitized to toluene diisocyanate (TDI).

A worker with occupational asthma due to toluene diisocyanate (TDI) was studied. Detailed immunologic studies, including those for p-tolyl isocyanate IgE antibodies and the presence of leukocyte inhibition factor for isocyanate antigen, were negative. Clinically, the subject noted more pronounced symptoms beginning on Monday morning, followed by weekend off work, and lessening of her symptoms over the working week. Methacholine challenges were negative when performed on three separate occasions, including the time when maximum symptoms were present, and again six months later, before and after bronchial challenge testing. A dose-related response to TDI was observed on bronchial provocation testing using nonirritating concentrations of TDI of 0.0165 and 0.030 ppm. This case provides evidence that the response of the airway to TDI may not always be accompanied by hyperreactivity to methacholine. Screening programs utilizing methacholine challenges may not always identify sensitized workers, since a negative methacholine challenge test does not exclude TDI sensitization.

Adult↗
PubMed1986

Approaches to assessing pulmonary dysfunction and susceptibility in workers.

Indices of the maximal forced expiration are the most widely adopted method of screening for occupational lung disease because of their ease of measurement, employee acceptability, and reproducibility. However, these indices may lack sensitivity, specificity, or validity in detecting cases of some occupational lung diseases at asymptomatic stages when intervention may affect outcome. In populations at increased risk for occupational asthma, pneumoconiosis, or hypersensitivity pneumonitis, three other types of screening are being evaluated in field settings: tests for bronchial hyperreactivity, barriers to diffusion, and abnormalities in gas distribution in the lung. The potential methods of screening--cold air challenge, methacholine challenge, peak flow logs, diffusing capacity, and single breath nitrogen tests--await clinical trials in industrial settings to evaluate whether early case finding of susceptible subjects can result in prevention of morbidity.

Cold Temperature↗
PubMed1988

Does seasonal employment in grain elevators increase nonspecific airways responsiveness?

Grain handling and increased airways responsiveness (AR) have been independently associated with an accelerated decline in forced expiratory volume in 1 sec. We performed methacholine inhalation bronchial challenge tests in 45 river port grain handlers during layoff and again during employment to determine whether short-term exposure increased AR. To assess bias, due to seasonal/temporal influences, AR was also measured in 56 nonexposed men of similar age and socioeconomic status. AR, slightly higher among laid-off grain handlers than the comparison group, fell more among grain handlers during employment than among the comparison group during the same time period. Our results do not support the hypothesis that seasonal exposure to grain dust increases AR.

Adult↗
PubMed1985

Cardiovascular pharmacology of nicardipine in animals.

The haemodynamic, antianginal and antihypertensive effects of nicardipine, a vascular selective calcium antagonist, were studied in experimental animals. In the canine isolated coronary artery, nicardipine relaxed potassium-induced contraction and suppressed 3,4-diaminopyridine-induced rhythmic contractions more effectively than nifedipine, verapamil or diltiazem. In anaesthetised rats, nicardipine prevented the elevation of ST segment induced by intracoronary injection of methacholine. In anaesthetised dogs, nicardipine produced a greater vasodilatation in vertebral, carotid, and coronary vessels than in mesenteric, femoral, and renal vessels and did not affect myocardial oxygen consumption. In conscious monkeys, nicardipine given intravenously lowered blood pressure and gave rise to reflex tachycardia but did not prolong the A-V conduction time. Nicardipine given orally lowered blood pressure in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), and deoxycorticosterone acetate/salt hypertensive rats (DOCA/Salt), as well as in normotensive rats. Long-term treatment with nicardipine given orally for 12 weeks effectively lowered high blood pressure in the three types of hypertensive rats, reduced cardiac hypertrophy in SHR and DOCA/Salt rats, and prevented mortality from stroke in DOCA/Salt rats. Combined treatment with nicardipine and a beta-adrenoceptor blocking agent (indenolol) showed an antihypertensive effect similar to that obtained with nicardipine alone. Conscious renal hypertensive dogs given repeated oral administration of nicardipine for 14 days did not develop tolerance to the hypotensive activity of nicardipine. Under the same conditions, tolerance to hydralazine developed within 4 days.

Animals↗
PubMed1988

Effect of a PAF antagonist, BN52063, on PAF-induced bronchoconstriction in normal subjects.

1. The effects of an oral platelet activating factor (PAF) antagonist, BN52063, or matched placebo on inhaled PAF challenge were assessed in a double-blind study in eight normal subjects. 2. PAF (24 micrograms) induced an immediate bronchoconstriction, with a maximum fall in flow at 30% of vital capacity from a partial flow volume manoeuvre (Vp30) of 47.1 +/- 7% (mean +/- s.e. mean) 5 min after inhalation following placebo treatment. Repeated PAF challenges at 15 min intervals resulted in tachyphylaxis of the bronchoconstrictor response. 3. Two hours after the ingestion of BN52063 (120 mg) the maximum bronchoconstriction induced by inhaled PAF was attenuated (35.9 +/- 9% fall at 5 min) with a significant reduction (P less than 0.05) in response after the first and second inhalations. 4. Inhaled PAF induced an immediate neutropenia (73.2 +/- 9% fall 5 min after inhalation) followed by a rebound neutrophilia, which were unaffected by pretreatment with BN52063. 5. Oral ingestion of a dose of BN52063 which is effective in reducing skin responses to PAF gave partial protection against the bronchoconstrictor effect of inhaled PAF in normal subjects.

Adult↗