The calcium messenger system and the kinetics of elastase release from human neutrophils in patients with abdominal aortic aneurysms.
Aortic elastase and neutrophil elastase is higher in patients with abdominal aortic aneurysms. The purpose of this study was to determine if these proteolytic elevations occur after abdominal aortic aneurysms have been repaired. Specifically, we studied the stimulation and inhibition of elastase degranulation from neutrophils in postoperative abdominal aortic aneurysm patients compared to aortic occlusive disease patients. Neutrophil elastase was determined in postoperative abdominal aortic aneurysm and aortic occlusive disease patients in response to calcium and the ionophore A23187. Inhibition of elastase release was determined with the calcium channel blocking agent Verapamil. Neutrophil elastase secretion was significantly higher in the abdominal aortic aneurysm patients (47%) versus aortic occlusive disease (20%) (p less than .05), while the effect of Verapamil in blocking this response was significantly lower in the abdominal aortic aneurysm patients (14%) compared to aortic occlusive disease patients (27%) (p less than .02). The time for degranulation to occur was longer in the abdominal aortic aneurysm patients (14.7 minutes) versus aortic occlusive disease patients (3.5 minutes), but the rate of secretion was not different between the two groups. These data indicate that, (1) neutrophils secrete more elastase in response to a calcium stimulus in abdominal aortic aneurysm patients; (2) it takes longer to secrete the increased amount of elastase in abdominal aortic aneurysm patients since the rate of secretion is similar between the two groups; and (3) Verapamil blocks elastase secretion ineffectively in abdominal aortic aneurysm patients. We conclude that the proteolytic alterations in abdominal aortic aneurysm patients are more likely a primary event and not a response to the abdominal aortic aneurysm and that Verapamil is a poor drug to use to medically manipulate the protease system in abdominal aortic aneurysm patients.
Cohen
J R
JR
Department of Surgery, Long Island Jewish Medical Center, New Hyde Park, New York 11042.
Faust
G
G
Tenenbaum
N
N
Sarfati
I
I
Rogowsky
P
P
Wise
L
L
D001012:Aorta, Abdominal; D001014:Aortic Aneurysm / Q000188:drug therapy / Q000201:enzymology*; D001157:Arterial Occlusive Diseases / Q000201:enzymology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D015220:Calcium Channels; D014700:Verapamil; D010196:Pancreatic Elastase; D002118:Calcium