Search for evidence of lung chemoreflexes in man: study of respiratory and circulatory effects of phenyldiguanide and lobeline.

SUMMARY 1. Respiratory and circulatory effects of phenyldiguanide (PDG), sodium cyanide and lobeline have been studied in eighteen patients. 2. PDG, when injected into the main pulmonary artery, produced stimulation of breathing together with bradycardia and hypotension. A mean injection-response time of 5-2 s was close to the pulmonary artery-ear lobe circulation time in the same patients. 3. Sodium cyanide produced respiratory and circulatory effects similar to PDG and with the same injection-response time. It was concluded that both drugs act on the carotid body. 4. Lobeline sulphate produced apnoea with or without cough in twelve of the fifteen patients studied, with a mean injection-response time of 2.1 s; this was shorter than the pulmonary artery-ear lobe circulation time. This response preceded the well-known hyperpnoea. 5. The short injection-response time of lobeline is consistent with the hypothesis that lobeline stimulates pulmonary receptors before it acts on the carotid bodies, and that there are receptors in the human lung that are depolarized by chemical agents. 6. The cough response was replaced by apnoea when the dose of lobeline was decreased. 7. Whereas PDG did not produce any abnormal sensation in the body, lobeline caused a sensation of fumes or smoke in the lower throat or burning over the manubrium sterni. Neither drug produced a sensation of breathlessness.

[1]  J. H. Comroe,et al.  Blocking Action of Tetraethylammonium on Lobelin-Induced Thoracic Pain , 1951 .

[2]  G. Dawes,et al.  Respiratory and cardiovascular reflexes from the heart and lungs , 1951, The Journal of physiology.

[3]  G. Dawes,et al.  Chemoreflexes from the heart and lungs. , 1954, Physiological reviews.

[4]  J. Widdicombe,et al.  Chemoreceptor reflexes in the dog and the action of phenyl diguanide. , 1952, Archives internationales de pharmacodynamie et de therapie.

[5]  B. A. Paintal Impulses in vagal afferent fibres from specific pulmonary deflation receptors: the response of these receptors to phenyl diguanide, potato starch, 5-hydroxytryptamine and nicotine, and their rôle in respiratory and cardiovascular reflexes. , 1955, Quarterly journal of experimental physiology and cognate medical sciences.

[6]  A. Guz,et al.  The role of vagal and glossopharyngeal afferent nerves in respiratory sensation, control of breathing and arterial pressure regulation in conscious man. , 1966, Clinical science.

[7]  Samson Wright,et al.  Action of Lobeline , 1927 .

[8]  P. Wood Diseases of the Heart and Circulation , 1902, The Hospital.

[9]  I. Bruderman,et al.  Localization of lobeline-sensitive receptors in the pulmonary circulation in man. , 1966, American Heart Journal.

[10]  J. B. Wood,et al.  The effects of bilateral removal of the carotid bodies and denervation of the carotid sinuses in two human subjects. , 1965, The Journal of physiology.

[11]  L. Goodman,et al.  The Pharmacological Basis of Therapeutics , 1941 .

[12]  G. P. Robb,et al.  The velocity of pulmonary and peripheral venous blood flow and related aspects of the circulation in cardiovascular disease , 1934 .

[13]  G. Dawes,et al.  Circulatory and respiratory reflexes caused by aromatic guanidines. , 1950, British journal of pharmacology and chemotherapy.

[14]  A. Guz,et al.  The role of non‐myelinated vagal afferent fibres from the lungs in the genesis of tachypnoea in the rabbit , 1971, Journal of Physiology.

[15]  A. Paintal,et al.  Mechanism of stimulation of type J pulmonary receptors , 1969, The Journal of physiology.

[16]  F. Fastier,et al.  Pharmacological properties of phenyldiguanide and other amidine derivatives in relation to those of 5-hydroxytryptamine. , 1959, British journal of pharmacology and chemotherapy.