[Effect of an eicosapentaenoic acid-rich diet on the arterial pressure and lipid level in the blood of hypertension patients].
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Biomedical subjects
Publications and source records attributed to C Taube.
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The aim of the study was to test whether there are typical changes in haemodynamics and humoral regulation in untreated hypertensives compared to normotensives with acute lowering of blood pressure (and venous return) induced by nitroglycerin (NTG). 23 hypertensives were investigated by radiocardiography and microcatheterization of the pulmonary artery as well as by means of humoral analyses in comparison to 10 normotensives. After performing the studies at rest and during exercise, 0.8 mg NTG was given and the investigations were repeated. There were only insignificant differences in cardiac output and left ventricular filling pressure (PAEDP) at rest and during exercise between both groups. The pressure reductions due to NTG were also similar. Plasma renin activity and plasma kallikrein did not differ in hypertensives and normotensives either at rest and during exercise or after NTG. The prostaglandins (PgE, PgF2-alpha, PgI) were extremely variable. In hypertensives, only PgI was decreased, with increase after NTG, at rest. Thus, PgI is the only humoral indicator participating in blood pressure lowering induced by NTG.
The experiments were carried out in order to examine whether the hypotensive effect of dihydralazine can be augmented by concomitant ingestion of a diet enriched with linoleic acid. After prefeeding with a linoleic acid rich diet (13.3 J%) an augmented hypotensive dihydralazine effect (11-24 mm Hg) could be observed in acute experiments in conscious (1 mg/kg i.v.) and pentobarbital-anaesthetised (4 mg/kg i.v.) normotensive rats with different duration of the feeding period as well as in conscious (1 mg/kg i.v.) spontaneously hypertensive rats relative to linoleic acid poor (0.5 J%) fed animals. This effect was abolished by pretreatment with the cyclooxygenase inhibitors indomethacin (10 mg/kg i.v.) or acetylsalicylic acid (100 mg/kg i.v.). The chronotropic dihydralazine response was with one exception not different between the two dietary groups. In chronic experiments with spontaneously hypertensive rats the augmentation of the hypotensive dihydralazine effect (1 mg/kg X d, s.c.) after linoleic acid rich diet did not attain statistical significance after a 6-weak prefeeding period. The renovasodilatory action of dihydralazine (3 mg) was increased in isolated kidney preparations of linoleic acid rich fed rats. This effect was accompanied by a shift of the prostaglandin formation toward vasodepressive PGE. We conclude that the altered cardiovascular effects of dihydralazine after linoleic acid rich diet are primarily caused by changes in the formation of prostaglandins and the activity of the sympathetic nervous system.
Prostanoids are important for the pathogenesis of chronic inflammatory bowel diseases as mediators of inflammatory, immune and allergic reactions. The levels of thromboxane B2(TXB2), the stable hydrolysis product of thromboxane A2(TXA2) were determined in blood plasma of patients with chronic inflammatory bowel diseases. The platelet malondialdehyde (MDA) formation was determined as an indicator of the TXA2 synthetase activity. The TXB2 concentrations were measured radioimmunologically. The platelet MDA formation induced by N-ethylmaleimide was investigated with the thiobarbituric acid reaction. The investigated patients (n = 10) suffering from ulcerative colitis had a significant increasing (p less than 0.02) of the platelet MDA formation (mean = 4.39 nmol/10(9) platelets) in comparison to the normal group (n = 20; mean = 2.87; nmol/10(9) platelets). The increasing of TXB2 levels was not significantly different than in normal control subjects. The plasma concentrations of 6-keto-PGF1 were situated on the limit of detection.
Fourteen male patients with mild essential hypertension were put on a mackerel and herring diet within a prescribed isocaloric regimen in a cross-over design for 2 weeks. After mackerel diet eicosapentaenoic acid (EPA-C20:5, n-3) appeared more in cholesterol esters (1.7-11.0%), whereas docosahexaenoic acid (DHA-C22:6, n-3) was predominantly incorporated into serum triglycerides (1.0-8.3%). After herring diet, which contained half as much EPA and DHA, their increase was of minor degree. After mackerel diet serum triglycerides, total cholesterol, LDL cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased (by 28%, 9%, 14% and 14%, respectively), returning to the initial levels 3 months later. On the contrary, HDL cholesterol appeared significantly increased (by 12%). After herring diet the differences were not significant. Serum sodium was significantly lower (by 2%) at the end of the mackerel diet as compared to the initial values. On the other hand, uric acid in serum appeared transiently increased (by 24%) at the end of both dietary periods. A significant decrease (by 8%) in casual systolic blood pressure, measured in recumbent position, could be observed only at the end of the mackerel period. Moreover, the level of systolic and diastolic blood pressure before and during a standardized psychophysiological stress test was significantly lower after mackerel diet. Nevertheless, the increments after stress were similar. Plasma renin activity was increased (by 64%) after mackerel diet.(ABSTRACT TRUNCATED AT 250 WORDS)
The influence of low density lipoproteins (LDL)-cholesterol (1.69 +/- 0.08 mg/ml) and of high density lipoproteins (HDL)-cholesterol (0.62 +/- 0.09 mg/ml), respectively, on the levels of 6-oxo-PGF1 alpha and TXB2 in the perfusates of rat aortas perfused under pulsatile pressure was studied. After passage through the aortas the concentration of LDL-cholesterol was significantly decreased in the perfusates, whereas the HDL-cholesterol level was unchanged. In comparison to controls, perfused with lipoprotein free solution, the concentration of 6-oxo-PGF1 alpha was significantly decreased more than 50% by LDL and the TXB2 level was enhanced significantly by approximately 50%. This results in a significant rise of the TXB2/6-oxo-PGF1 alpha ratio in the perfusates. HDL did not significantly change the ratio of these eicosanoids in the perfusates. These results suggest that this concentration of LDL enhanced the formation of the proaggregatory TXA2 and decreased the formation of the antiaggregatory PGI2 in rat aortas perfused under pulsatile pressure. The proaggregatory action of an elevated level of LDL during the development of atherosclerosis in men may be also mediated by changes in the metabolism of eicosanoids of the vessel wall.
The experiments were carried out in order to clarify the mechanisms of attenuation of hypertension development by means of diets enriched with polyunsaturated fatty acids (PUFA) in spontaneously hypertensive rats (SHR). Female SHR were fed a linoleic acid rich (LAr) diet (13.3 cal % LA, sunflower oil), a linolenic acid rich (LNAr) diet (18.8 cal % LNA, 3.9 cal % LA; linseed oil) and a PUFA deficient diet (0.5 cal % LA, hydrogenated palm kernel fat), respectively, during the last week of pregnancy and during the suckling period. Corresponding diets were given to the male offspring up to an age of 16 weeks. Our results demonstrate that the attenuation of hypertension development in LAr and LNAr fed male SHR was paralleled by an increased in-vitro uptake of 14C-norepinephrine into cardiac and aortic tissues as well as an increased degradation rate of 14C-norepinephrine in cardiac tissue. Ex vivo prostaglandin (PG) formation was reduced after LNAr diet in the aorta (PGF2 alpha, PGI2-like material) and in the kidney medulla (PGE, PGF2 alpha). It is concluded that an increased catecholamine inactivation may play a role in the attenuation of hypertension development in LAr and LNAr diet fed SHR.
On October 1, 1983, Medicare began paying general hospitals by a prospective payment system based on DRGs. Psychiatric settings are exempted automatically or by request. By January 1985, however, a decision is required on how to integrate psychiatric settings into this system. This article provides an empirical analysis of the current DHHS DRGs categories for mental disorders. Current mental disorder DRGs and alternate DRGs examined here explain less than 3-12% of the variation in psychiatric length of stay. This is in contrast to 30-50% explained variation for other disorders. Alternatives and policy implications are discussed.
Under the new federal prospective payment system, 15 of the 467 diagnosis-related groups (DRGs) cover mental disorders, including alcohol and substance abuse. The authors compare these 15 DRGs with some criteria of an ideal patient classification system. According to their assessment, the DRGs for mental disorders pose no administrative problems, but are not sufficiently homogeneous within categories or heterogeneous between categories. The authors conclude by discussing their own attempt to develop alternative DRGs, based on such variables as age, marital status, and type of treatment as well as on diagnosis.
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Isolated perfused and electrically driven heart preparations of guinea pigs and tissue from different parts of the rabbit hearts have the capacity to rapidly synthesize prostacyclin (PGI2) and thromboxane (TXB2). Auricles showed a higher PGI2 formation than ventricles. Addition of arachidonic acid or PGH2 markedly enhanced the myocardial PGI2 biosynthesis. After acute pressure overload by a graduated aortic stenosis the PGI2 and TXB2 formation of the myocardium is decreased possibly caused by a diminished availability of substrate, an alteration of enzyme activities or changes in the functional state of the cardiac tissue. Pretreatment with dipyridamole or propranolol again induced an increase of this diminished PGI2 and TXB2 synthesis. The PGI2 formation of electrically driven ventricular strips enhanced with an increased stimulation rate. Ouabain, antianginal drugs (dipyridamole, oxyfedrine, propranolol) and endogenous mediators (norepinephrine, histamine, adenosine) induced a significant rise of the cardiac PGI2 formation. The results suggest that the cardiac prostaglandin biosynthesis is involved in the action of the myocardium indicating heart sufficiency and an adaptability to mechanical loading or drug influence.
Polyunsaturate-rich vegetable oils (sunflower oil, linseed oil, primrose oil) augment the hypotensive effect of dihydralazine, clonidine and captopril in rats under different experimental conditions. Evidence has accumulated that these effects are mediated via changes in prostanoid formation and sympathetic activity.
In a secondary prevention study 867 male and female patients with myocardial infarction (MI) were divided 3 weeks after onset of MI into 4 treatment groups: I - 273 patients received additionally to their common medication 1000 mg ASA/d; II - 313 patients got 60 mg ASA/d; III - 208 patients 30 mg ASA/d resp.; IV - 73 patients received no ASA administration due to ASA contraindications. One year after onset of MI the following parameters were checked: mortality, malignant arrhythmia, exercise tolerance, gastrointestinal symptoms and hemorrhage as typical side effects of ASA, formation of thromboxane B2 and PGF2 alpha in clotting whole blood. The low dose of 30 mg ASA/d reśultes in a clear reduction of ASA side effects (6,4% of patients with symptoms) in comparison to group I (15,9% of patients with symptoms), in a tendency to decreased mortality, and in unchanged frequency of malignant arrhythmias resp. Concerning the maximum exercise tolerance no significant difference could be observed in all 4 groups investigated. Estimations of serum thromboxane B2 by radioimmunoassay and gas chromatography revealed strong inhibitions of the thromboxane formation in all patients with ASA administrations; even the low dose of 30 mg ASA/d decreased thromboxane B2 by more than 95%.
The effects of (i) the exogenous arachidonic acid (AA), (ii) stable PG endoperoxide analogue U46619, and (iii) cyclooxygenase inhibitor aspirin on the interaction of platelets with a surface coated with commercial fibrillar calf skin collagen (CSC) were studied using scanning electron microscopy. AA and U46619 stimulate massive spreading of platelets on the CSC substrate and formation of the surface-bound multilayer (thrombi-like) aggregates. The stimulation of spreading and formation of thrombi-like aggregates induced by AA correlate with the TXA2 synthesis in platelets. Unlike AA, U46619 induces these processes without transformation into TXA2 and stimulation of its synthesis in platelets. Aspirin prevents the AA-induced platelet spreading, formation of the surface-bound thrombi-like aggregates, and TXA2 synthesis. In the absence of soluble platelet inducers, aspirin decreases the CSC substrate-induced disc - sphere transformation and spreading of platelets, but doesn't affect the initial attachment of platelets to the CSC substrate.
The influence of a modified endogenous prostanoid synthesis on circadian rhythmicity at different functional levels (prostanoid formation, behavioural parameters, circulatory indices, hematological parameters, energy metabolism) was investigated. The daily rhythmic changes observed for all parameters were partly modified by the variation of dietary linoleate intake.
Blood pressure reduction induced by antihypertensive drugs with different mode of action approximated the pathological altered synthesis of TXB2 in spontaneously hypertensive rats to values of normotensive rats: in the kidney medulla by all drugs used, in the aorta only by the most efficient drugs (clonidine, dihydralazine) and in plasma and serum only in connection with a reduction in heart rate (clonidine, propranolol). The pathologically increased synthesis of 6-keto-PGF1 alpha was unchanged by drugs, therefore the ratio PGI2/TXA2 was directed towards the vasodilatory prostanoid. Unlike SHR in NTR an equieffective blood pressure reduction induced by the same drugs was without influence on TXB2 synthesis. From these results we can conclude, that the influence of antihypertensive drugs on TXB2 synthesis depends on the normotensive or hypertensive state of the animals and not on the drug per se. In hypertensive patients a blood pressure reduction by linseed oil was connected with a reduced TXB2 plasma level, too.
Effects of an antianginal drug trapidil (Rocornal) on platelet interaction with a surface coated with fibrillar calf skin collagen (CSC) have been studied by scanning electron microscopy. Gel filtered human platelets were incubated with the CSC substrate in the absence or in the presence of soluble inducers of platelet activity: arachidonic acid (AA), stable analogue of prostaglandin (PG) endoperoxides, U46619, and thrombin. In the absence of soluble inducers, trapidil does not alter the total number of adherent platelets. At the same time, trapidil inhibits the shape change of adherent platelets, induced by the CSC substrate, increasing the percentage of discoid and decreasing the percentage of spread platelets. It was demonstrated earlier (1) and in the present study that soluble inducers of platelet activity stimulate massive spreading of platelets and formation of surface-bound thrombi-like aggregates on the CSC substrate. Trapidil completely prevents the effects of the exogenous AA and U46619 on platelet-substrate interactions, but inhibits the AA-stimulated synthesis of thromboxane A2 (TXA2) in platelets by 40-50% only. Trapidil also blocks platelet aggregation in suspension, spreading and formation of surface-bound aggregates induced by low, but not high, concentrations of thrombin. Possible sites of trapidil action are discussed.
1 The relationship between the blood pressure fall, induced by antihypertensive drugs or bleeding, and the formation of prostacyclin (PGI2)-like activity in the thoracic aorta of spontaneously hypertensive rats has been investigated. Inhibition of ADP-induced platelet aggregation was used to assess PGI2-like activity. 2 The decreases in blood pressure produced by clonidine, dihydralazine and prazosin were associated with increases of PGI2-like activity of 50-80%. The increase in PGI2-like activity correlated well with the blood pressure decrease, independently of the mechanism of the fall in blood pressure.