TY - JOUR
T1 - Coronary constriction by leukotriene C4, D4, and E4 in the intact pig heart
AU - Ezra, David
AU - Boyd, Lillie M.
AU - Feuerstein, Giora
AU - Goldstein, Robert E.
N1 - Funding Information:
From the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology; Division of Cardiology, Department of Medicine; and Neurobiology Research Unit, Uniformed Services University of the Health Sciences, Bethesda, Maryland. This study was supported by Protocol R08329 of the Uniformed Services University of-the Health Sciences, Bethesda, Maryland. Dr. Boyd is a Postdoctoral Fellow supported by Grant IF 34 GM08713-01 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences. The experiments reported herein were conducted according to the principles set forth in the “Guide for the Care and Use of Laboratory Animals,” Institute of Laboratory Animal Resources, National Research Council DHEWP ublication (NIH)7 4-23. Manuscript received October 28, 1982; revised manuscript received January 1, 1983, accepted January 4, 1983.
PY - 1983/5/1
Y1 - 1983/5/1
N2 - Leukotrienes are naturally occurring vasoactive metabolites of arachidonic acid that increase during inflammatory reactions and anaphylaxis. Coronary constriction and reduced myocardial contractility after leukotriene C4 and D4 administration were demonstrated in the isolated guinea pig heart. To explore the effects of leukotrienes in the in situ, blood-perfused heart, we administered leukotrienes C4, D4, and E4 into the coronary artery of the domestic pig. Increasing doses (0.1, 0.3, 1.0, and 3.0 μg) of leukotrienes C4, D4, and E4 were injected into the left anterior descending coronary artery of 8 openchest domestic pigs. Significant dose-related reduction in coronary blood flow was observed after each leukotriene administration. Three micrograms of each leukotriene produced the following maximal decreases (mean ± standard error): C4 = 80 ± 9%, p < 0.001; D4 = 81 ± 3%, p < 0.001; E4 = 64 ± 12%, p < 0.005. In several instances, surface electrograms recorded from the myocardial region exposed to leukotrienes showed signs of focal myocardial ischemia, sometimes accompanied by ventricular arrhythmia. Significant elevation of left ventricular end-diastolic pressure was observed after large doses (1 or 3 μg) of leukotrienes C4 and D4. Minimal (5 to 10%) decreases in mean arterial pressure and no change in heart rate were observed after leukotriene injection. We conclude that leukotrienes C4, D4, and E4 are extremely potent coronary constrictors in the in situ heart. The intensity of response and associated electrocardiographic signs of ischemia suggest that constriction is mainly due to a primary effect on vascular smooth muscle. However, coronary flow reduction may also reflect consequences of a primary negative inotropic action. Leukotrienes may play a significant role in the pathogenesis of a variety of cardiac disorders, particularly those associated with extensive inflammatory charges.
AB - Leukotrienes are naturally occurring vasoactive metabolites of arachidonic acid that increase during inflammatory reactions and anaphylaxis. Coronary constriction and reduced myocardial contractility after leukotriene C4 and D4 administration were demonstrated in the isolated guinea pig heart. To explore the effects of leukotrienes in the in situ, blood-perfused heart, we administered leukotrienes C4, D4, and E4 into the coronary artery of the domestic pig. Increasing doses (0.1, 0.3, 1.0, and 3.0 μg) of leukotrienes C4, D4, and E4 were injected into the left anterior descending coronary artery of 8 openchest domestic pigs. Significant dose-related reduction in coronary blood flow was observed after each leukotriene administration. Three micrograms of each leukotriene produced the following maximal decreases (mean ± standard error): C4 = 80 ± 9%, p < 0.001; D4 = 81 ± 3%, p < 0.001; E4 = 64 ± 12%, p < 0.005. In several instances, surface electrograms recorded from the myocardial region exposed to leukotrienes showed signs of focal myocardial ischemia, sometimes accompanied by ventricular arrhythmia. Significant elevation of left ventricular end-diastolic pressure was observed after large doses (1 or 3 μg) of leukotrienes C4 and D4. Minimal (5 to 10%) decreases in mean arterial pressure and no change in heart rate were observed after leukotriene injection. We conclude that leukotrienes C4, D4, and E4 are extremely potent coronary constrictors in the in situ heart. The intensity of response and associated electrocardiographic signs of ischemia suggest that constriction is mainly due to a primary effect on vascular smooth muscle. However, coronary flow reduction may also reflect consequences of a primary negative inotropic action. Leukotrienes may play a significant role in the pathogenesis of a variety of cardiac disorders, particularly those associated with extensive inflammatory charges.
UR - http://www.scopus.com/inward/record.url?scp=0020628671&partnerID=8YFLogxK
U2 - 10.1016/0002-9149(83)90328-4
DO - 10.1016/0002-9149(83)90328-4
M3 - Article
C2 - 6303103
AN - SCOPUS:0020628671
SN - 0002-9149
VL - 51
SP - 1451
EP - 1454
JO - The American Journal of Cardiology
JF - The American Journal of Cardiology
IS - 8
ER -