Search PubMed⌕ Search

Biomedical subjects

J Mahadoo

Publications and source records attributed to J Mahadoo.

14 recordsLinked to original sources
PubMed1981

Effect of intrapulmonary heparin on plasma diamine oxidase (histaminase) activity in mice.

Heparin releases diamine oxidase (DAO, histaminase) from binding sites in the intestinal vasculature. Histamine is involved in a number of pathological lesions. In this study we have examined the effect of intrapulmonary administration of heparin on plasma DAO activity in mice. For comparative purposes the same parameter was measured following the administration of an intravenous heparin regimen. The time course and dose-response were examined with the two heparin regimens. The doses of heparin were based on appropriate clinical equivalents. Both heparin regimens showed a dose dependent response (correlation coefficient r = 0.9). The dose of intrapulmonary heparin (10 mg/kg) was 12 times greater than the dose injected intravenously but the DAO response lasted 48 times longer that that obtained from the intravenous heparin regimen.

Amine Oxidase (Copper-Containing)↗
PubMed1981

Effects of long-term treatment of mice with intrapulmonary heparin.

Intrapulmonary heparin calls for the administration of a single large dose of heparin. This results in a prolonged but low grade heparinemia lasting for many days. These features are quite different the response obtained from any of the currently used heparin regimens. A toxicity study was therefore conducted on mice exposed to heparin aerosol(7ppm) for 20 min, one a week for ten weeks. No deleterious effects were observed on physical and macroscopic examinations of the internal organs as well as on histological examination of tissues from most organs of the body.

Aerosols↗
PubMed1981

Reversal of protamine of the prolonged response to intrapulmonary heparin.

A single large dose of heparin (2000 units/kg) was administered to dogs by intratracheal instillation. Whole blood clotting times and plasma heparin concentrations were measured at intervals. At each interval the calculated dose of protamine required to neutralize the circulation heparin was given intravenously and the measurement of plasma heparin concentration repeated. The authors found that the whole blood clotting time was prolonged for 24 to 48 hours and there was a detectable concentration of heparin in the plasma for 96 hours. On each occasion the protamine eliminated the circulation heparin, but more heparin continued to enter the circulation. It is hypothesized that after rapid absorption from the lung, heparin is stored temporarily in a cellular pool throughout the body and then released into the circulation. At any given time the anticoagulant effect can be reversed by intravenously administered protamine sulfate if this should become necessary, but repeated administration would be required. Intrapulmonary heparin may have useful clinical applications but further clinical and laboratory investigations are required.

Animals↗
PubMed1979

Anticoagulant activity and operative blood loss after intrapulmonary heparin.

The safety and efficacy of heparin given by the intrapulmonary route are further assessed in this study. A single dose of heparin (2000 units/kg) was given by intratracheal instillation in dogs and measurements of plasma heparin concentration, whole blood clotting time and partial thromboplastin time made at intervals for 48 h. These values rose progressively and in parallel for 7 h and remained elevated for 48 h. A series of operations was performed on dogs within 3 h of a single dose of intrapulmonary heparin (1500 units/kg). Operations involving minimal dissection (small bowel resection) and extensive dissection (resection of muscle) were performed in two separate groups. Within each group the animals were randomly given heparin or saline. In the limited dissection group there were no differences in operative blood loss, wound healing, or sequential haemoglobin and haematocrit measurements. In the group subjected to muscle resection there was increased postoperative wound drainage and a slightly greater fall in haemoglobin and haematocrit in those given heparin. It is concluded that heparin is absorbed from the lung causing significant changes in coagulation parameters. Even with the relatively high dose of 1500 units/kg, operations were performed with minimal hazard. Intrapulmonary heparin may have important clinical applications after further investigation.

Animals↗
PubMed1979

Cellular control of heparin in blood.

Many investigators have observed the uptake of exogenous heparin by cells of the reticuloendothelial system (R.E.S.). When heparin is administered by the intravenous, intramuscular, subcutaneous, intraperitoneal and intratracheal routes the anticoagulant response observed is of varying magnitude. This has led us to examine the literature for evidence of a distribution of heparin between the cellular and blood compartments. A re-evaluation of such evidence has provided a new perspective on the pharmacokinetics of heparin. This is presented here in the cellular pool concept which is based on the premise that there exists in the body a pool of cells which takes up a portion of the administered heparin, stores it and later releases it to the circulation. This concept provides a rational explanation for the different types of anticoagulant response obtained with different modes of administration.

Biopharmaceutics↗
PubMed1977

The mast cell/heparin paradox.

Purified heparin extracted from tissues rich in mast cells remains the ideal rapid anticoagulant in clinical practice. Nevertheless, there are grounds for doubting that an injection of commercial heparin corresponds to the release of heparin-containing granules from the mast cells. The metachromatic granule contains much more than heparin--chondroitins, heparitins, histamine (in some species 5-hydroxytryptamine also), and a variety of enzymes. Shed granules, released by trauma of any kind, are ingested by connective-tissue phagocytes and are digested. Commercial heparin, on the other hand, is taken up by cells of the reticuloendothelial system and is stored there. This apparent paradox can be resolved by conceding that the mast cell is primarily concerned with the connective tissue, as Ehrlich saw it a century ago, and that, within these broad limits, it can express itself in a variety of ways.

Animals↗
PubMed1976

Intrapulmonary heparin. A new procedure for anticoagulant therapy.

Heparin was administered by the intrapulmonary route to dogs, mice, and human volunteers. In all species, a single administration of a large quantity of heparin via the lung resulted in a prolonged state of moderate hypocoagulability (3 days in dogs, 14 days in man) due to the production of a sustained low concentration of heparin in plasma. The lengthening of clotting-time and duration of this response increased with dosage. Effective doses are above 8 mg (1300 units) per kg body-weight. Examination of the lungs, body-fluids, and tissues shows that the heparin is cleared rapidly from the lung and enters a body cellular compartment (probably the macrophages) from which it is slowly released to plasma. No evidence was found (symptomatic or on gross or histological postmortem examination) of haemorrhage or any heparin-related pathological change indicating either immediate or long-term toxic effects in the lung or other tissues. Suggestions are made for the clinical use of the unique features of anticoagulant treatment by intrapulmonary heparin.

Aerosols↗
PubMedDate not supplied

Effect of intrapulmonary heparin on lipoprotein lipase activity in mice.

The lipoprotein lipase (LPL) activity obtained from the intrapulmonary administration of 2-10 mg of heparin in mice was compared with the same parameter measured for intravenously administered heparin. The doses administered were based on appropriate clinical equivalents. A relatively large dose of intrapulmonary heparin produced a peak LPL activity which was a third of the maximum response obtained from a small dose of i.v. heparin. This was followed by a moderate LPL activity (twice the control level) which persisted for the next 4 days while the response obtained from i.v. administered heparin lasted only 2 h. Both the intrapulmonary and the i.v. administration of heparin produced dose-dependent increases in plasma LPL activity (correlation coefficient r = 0.9). This study indicates that intrapulmonary heparin causes a prolonged antilipemic effect.

Animals↗