The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computerassisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis. Circulation 75, No. 3, 627-635, 1987. THE ADDITION of certain linear macropolymers to flow can under certain conditions greatly reduce frictional resistance by polymer drag reduction, an effect also known among hydrodynamicists as the "Toms phenomenon." Flow can thus be increased by threefold or more without alteration of the driving pressure.'-3The effect occurs only in the presence of disturbed or turbulent flow, and it is associated with a laminarization of the flow. This phenomen has also been observed in pipe blood flow with at least four different drag-reducing polymers, 7 including the anionic polyacrylamide Separan AP-30.Application of the polymer drag-reduction principle to blood flow in vivo was first attempted independently From the
The purpose of this investigation was to determine whether the calcium blocking agent, verapamil, could modify Adriamycin cardiotoxicity, and if so, whether or not such modification is mediated by a mechanism involving myocardial electrolyte distribution. The mean survival time of female New Zealand white rabbits administered Adriamycin was reduced by pretreatment with verapamil. Myocardial cellular calcium concentration, [Ca]i, in animals pretreated with verapamil before receiving Adriamycin was lower than in animals receiving Adriamycin alone (1.49 +/- 0.11 vs. 2.22 +/- 0.35 mmol/kg cell water, respectively; P = 0.05). Myocardial [Ca]i in control animals was 1.68 +/- 0.10 mmol/kg cell water. Myocardial [Mg]i in animals receiving Adriamycin alone was lower than that for animals receiving verapamil alone (15.6 +/- 1.4 vs. 19.2 +/- 0.8 mmol/kg cell water, respectively). When these drugs were combined, [Mg]i approached the control value of 17.3 +/- 0.06 mmol/kg cell water. Cellular concentrations of the monovalent electrolytes were little affected by these drugs, except for a reduction of [Cl]i by verapamil. Neither myocardial water distribution nor plasma concentrations of these electrolytes were altered by either drug. The data indicate that verapamil pretreatment increases the mortality associated with Adriamycin in rabbits despite the continued efficacy of verapamil as a Ca-blocking agent after injection of Adriamycin. Particular caution must be exercised if clinical combination of Ca-blocking agents and anthracyclines is contemplated.
Calcium, magnesium, sodium, potassium, and water distributions were determined in rat ventricular muscle during the development of myocardial hypertrophy. Hypertrophy was produced by constriction of the ascending aorta with a silver band. Sham-operated controls were treated similarly, except that the aorta was not constricted. Cation and water distributions were examined at intervals of 1 hour, 1 day, 1 week. Myocardial extracellular space was determined by distribution of [35S] sulphate. In separate experiments, extracellular space was determined in different regions of the normal rat ventricle using [3H] inulin as the extracellular marker. Although some changes were observed in tissue calcium content and the plasma concentrations of several cations, at no time were the cellular concentrations of any cation significantly altered. Myocardial water content and distribution remained nearly constant after constriction of the aorta. Results do not support hypotheses that the heart responds to increased afterload with an accumulation or loss of myocytic calcium sufficiently large to be detectable with standard quantitative methods.
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