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Functional and reactive hyperemia are unaltered by homocysteine in conscious dogs
Authors:N. Sadick  Deborah Campano German  Ph. A. McHale  J. C. Greenfield Jr. M.D.  N. M. Kredich
Affiliation:(1) Present address: Department of Medicine, Division of Cardiology and Department of Biochemistry, and Howard Hughes Medical Institute at Duke University Medical Center, Box 3246, 27710 Durham, NC, USA;(2) Medical Service Cardiology Section, Veterans Administration Medical Center, Durham, (U.S.A.)
Abstract:
Summary The purpose of this study was to test the hypothesis that L-homocysteine thiolactone (L-HCTL), through its reaction with adenosine to formS-adenosylhomocysteine, may modulate myocardial functional and reactive hyperemic responses. Reactive hyperemic responses to 10-sec occlusions or 400-msec diastolic occlusions of the circumflex coronary artery and functional hyperemic responses to ventricular extra-activations were studied in a chronic heart-blocked dog preparation during a control period and following L-HCTL (40 mg/kg). In two additional dogs multiple venous blood samples and left ventricular myocardial biopsies were obtained following L-HCTL to measure changes in plasma homocysteine and tissueS-adenosylhomocysteine. Despite a 75-fold increase in peak plasma homocysteine and a 26-fold increase in tissueS-adenosylhomocysteine, L-HCTL did not alter myocardial functional and reactive hyperemic responses.The rapid increase in myocardialS-adenosylhomocysteine confirmed cellular entry of homocysteine and its reaction with endogenous adenosine. The failure of L-HCTL to alter functional and reactive hyperemic responses suggests that either such treatment does not affect myocardial release of adenosine or that adenosine is not an important regulator of coronary flow.Supported in part by the National Institutes of Health Grants HL 18468 and AM 12828 and the Medical Research Service of the Veterans Administration. Dr. Sadick is a recipient of an Overseas Research Fellowship from the Australian National Heart Foundation. Parts of this work were presented at the 56th Scientific Sessions, American Heart Association, Anaheim, California, November, 1983.
Keywords:coronary functional and reactive hyperemia  S-adenosylhomocysteine  adenosine  homocysteine  ventricular extra-activation
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