title: Heparin as a therapy for atherosclerosis: preliminary observations on the intrapulmonary administration of low-dose heparin in the morning versus evening gauged by its effect on blood variables.
abstract: Reports on clinical trials with subcutaneous and intrapulmonary administration of low-dose heparin suggest that it may be an attractive therapeutic modality for the treatment of coronary artery disease because of unprecedented reduction in mortality of treated subjects. As a preliminary to a clinical trial with low-dose intrapulmonary heparin, a pilot study was conducted on three subjects. It compares overall circadian responses of 37 blood variables following intrapulmonary administration of heparin (10,500-18,800 U) in the morning (0800 h) and in the evening (2000 h). After each of these times, blood samples, mostly at 3 h intervals for the ensuing 27 h, were analyzed for heparin, APTT, TT, functional fibrinogen, CBC, enzymes, lipids, electrolytes, and hormones. Each time series was analyzed for circadian rhythm by the least-squares fit of a 24 h cosine and circadian mesors were compared by the Bingham test of rhythm parameters. Following heparin in the evening, but not in the morning, a statistically significant increase in circulating heparin levels, as well as directional increases in APTT and TT and decreases in fibrinogen, were observed in all three subjects. Same direction changes in several other variables were also observed. It is concluded that inhalation of heparin in low-dose levels results in variable circadian effects on blood parameters measured, ranging from no changes in their levels to minimal within normal range changes, and that these effects are dependent upon the timing of dose administration. It is suggested that the timed self-administration of low-dose heparin by inhalation be seriously considered for long-term clinical trials in the treatment and prevention of atherosclerosis.
authors.affiliation: Department of Internal Medicine, Edward J. Hines Jr., V.A. Hospital, IL 60141.
authors.forename: E L
authors.initials: EL
authors.lastname: Kanabrocki
authors.forename: R B
authors.initials: RB
authors.lastname: Sothern
authors.forename: W F
authors.initials: WF
authors.lastname: Bremner
authors.forename: S A
authors.initials: SA
authors.lastname: Gruber
authors.forename: L E
authors.initials: LE
authors.lastname: Scheving
authors.forename: D L
authors.initials: DL
authors.lastname: Bushnell
authors.forename: M
authors.initials: M
authors.lastname: Ryan
authors.forename: M E
authors.initials: ME
authors.lastname: Rubnitz
authors.forename: N
authors.initials: N
authors.lastname: Fabbrini
authors.forename: S
authors.initials: S
authors.lastname: Lampo
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D001772:Blood Cell Count; D001777:Blood Coagulation; D002940:Circadian Rhythm; D004573:Electrolytes / Q000097:blood; D004798:Enzymes / Q000097:blood; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006728:Hormones / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011863:Radioimmunoassay
chemical_list: D004573:Electrolytes; D004798:Enzymes; D006728:Hormones; D008055:Lipids; D006493:Heparin