Airway structure and function in Eisenmenger's syndrome.
The responsiveness of airways from patients with Eisenmenger's syndrome (n = 5) was compared with that in airways from organ donors (n = 10). Enhanced contractile responses to cholinergic stimulation were found in airways from patients with Eisenmenger's syndrome. The maximal responses to acetylcholine, carbachol, and parasympathetic nerve stimulation in airway tissue from these patients were 221%, 139%, and 152%, respectively, of the maximal responses obtained in donor tissue. Further, relaxation responses to isoproterenol and levocromakalim were absent (n = 2) or markedly impaired (n = 3) in airways from patients with Eisenmenger's syndrome. This attenuated relaxation response was nonspecific in that it was also absent after vasoactive intestinal peptide, sodium nitroprusside, papaverine, and electrical field application. These observations can most likely be explained by a decrease in intrinsic smooth muscle tone, as precontraction of airways revealed relaxation responses that were equivalent to those obtained in donor tissues. Morphometric analysis of tissues used for the functional studies revealed no differences in the airway dimensions (internal perimeter) or airway wall components (e.g., smooth muscle, cartilage) or total area to explain these observations. Although the mechanism for this observed decrease in intrinsic airway smooth muscle tone is not certain, it may be due to alteration in the substructure of the airway wall or, alternatively, may result from the continued release of depressant factors in the vicinity of the smooth muscle which permanently alters smooth muscle responsiveness.
McKay
K O
KO
Departments of Pharmacology and Pharmacy, University of Sydney; and the Cardiopulmonary Transplant Unit, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.
Johnson
P R
PR
Black
J L
JL
Glanville
A R
AR
Armour
C L
CL
D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002356:Cartilage / Q000473:pathology / Q000503:physiopathology; D018678:Cholinergic Agents / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004541:Eisenmenger Complex / Q000473:pathology* / Q000503:physiopathology; D004558:Electric Stimulation; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D016040:Lung Transplantation / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009129:Muscle Tonus / Q000502:physiology; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009930:Organic Chemicals; D010208:Papaverine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001993:Bronchodilator Agents; D002121:Calcium Channel Blockers; D018678:Cholinergic Agents; D018679:Cholinergic Agonists; D018696:Neuroprotective Agents; D009930:Organic Chemicals; D010276:Parasympatholytics; D010277:Parasympathomimetics; D014665:Vasodilator Agents; C102234:levochromakalim; D009599:Nitroprusside; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D010208:Papaverine; D007545:Isoproterenol; D000109:Acetylcholine