Search PubMed⌕ Search

Biomedical subjects

M A Barradas

Publications and source records attributed to M A Barradas.

At least 73 records · Page 4Linked to original sources
PubMed1987

Platelet activation following intravenous injection of a conventional heparin: absence of effect with a low molecular weight heparinoid (Org 10172).

1. The effects of an intravenous injection of a conventional high molecular weight heparin (HMWH) were compared with those of a low molecular weight heparinoid (Org 10172). A bolus injection of HMWH (5000 iu) was associated with: (a) a small but significant prolongation of bleeding time (BT); (b) a significant fall in PRP platelet count; (c) significantly enhanced platelet aggregation; and (d) significantly increased platelet thromboxane A2 (TXA2) release. These changes were not observed following the intravenous injection of Org 10172 (3200 anti Xa U). 2. These experiments were repeated following the oral administration of acetylsalicylic acid (ASA). HMWH again caused some enhancement of platelet aggregation despite the ASA-mediated inhibition of platelet aggregation and TXA2 release. Administration of Org 10172 to subjects taking ASA did not alter any of the platelet function indices. 3. In additional control experiments the injection of 5000 iu of HMWH was associated with a significant fall in PRP but not whole blood platelet counts. This finding suggests that the fall in PRP platelet count is a methodological artefact. 4. The HMWH also induced a significantly greater increase in serum non-esterified fatty acid (NEFA) concentrations than Org 10172. 5. The present findings indicate that Org 10172 is a less potent stimulator of platelet aggregation and lipolysis than HMWH. 6. The minor prolongation of the BT after HMWH is not compatible with enhanced aggregation but may be a consequence of alterations in the activity of coagulation factors and vascular-platelet interactions or of ongoing platelet activation accompanied by granule depletion. 7. The different effects of the two anticoagulants assessed suggests a therapeutic advantage in favour of Org 10172, especially in patients with hyperactive platelets.

Adult↗
PubMed1987

Comparison of the platelet pro-aggregatory effect of conventional unfractionated heparins and a low molecular weight heparin fraction (CY 222).

Two unfractionated heparins (UH), a porcine intestinal mucosal heparin (PIM), a bovine lung heparin (BLH) and a low molecular weight heparin (LMWH), CY 222, were assessed for their capacity to enhance platelet aggregation in vitro. Their potential proaggregatory effect was investigated in four systems: (a) enhancement of submaximal platelet aggregation induced by conventional agonists in platelet rich plasma and (b) in whole blood; (c) reversal of inhibition of platelet aggregation induced by iloprost, a stable analogue of prostacyclin; (d) the direct aggregatory effect of these anticoagulants on hyperactive platelets prepared from patients with severe peripheral vascular disease or anorexia nervosa. Whereas BLH and PIM, at therapeutic concentrations, had a proaggregatory effect in all four systems, CY 222 had no significant effect when compared with the controls. BLH was more potent than PIM in three of the four systems studied. These observations confirm that conventional UH are more proaggregatory than LMWH, and thus the latter may be potentially safer. These observations are also consistent with the fact that BLH administration causes thrombocytopenia more frequently than PIM. The direct activation by UH of platelets from patients not previously exposed to heparin also challenges the hypothesis that heparin-induced platelet activation and thrombocytopenia is solely mediated by classical heparin-dependent immune mechanisms.

Adult↗
PubMed1987

Platelet function in patients admitted with a diagnosis of myocardial infarction.

Platelet function and thromboxane A2 release were measured in 71 patients admitted to a coronary care unit with a provisional diagnosis of acute myocardial infarction (AMI). All measurements were carried out within twenty-four hours of admission. Of these, 35 patients had the diagnosis of AMI confirmed. The remainder (n = 36), who did not have AMI (NMI), were divided into two groups: those (n = 18) with an unequivocal history of previous vascular disease and those without vascular disease (n = 18). Platelet aggregation and thromboxane A2 (TXA2) release were significantly increased in the AMI group when compared with those in the NMI without vascular disease group or a healthy control group with similar age and sex distribution. Aggregation and TXA2 release in the NMI patients with vascular disease were greater than those in controls and did not differ significantly from those in the AMI group. Patients in the AMI or NMI with vascular disease groups who were taking beta-blockers or calcium channel antagonists at the time of admission showed significantly less platelet aggregation than those who were not taking these drugs. Heparin, added in vitro at therapeutic concentrations, induced significantly more aggregation in patients in the AMI and NMI with vascular disease groups than in the NMI without vascular disease group. We conclude that: platelets obtained from patients with AMI are hyperaggregable and release more TXA2; platelets from patients with significant vascular disease are hyperaggregable, even in the absence of AMI, although they are not as hyperaggregable as those from AMI; treatment with nifedipine and beta-blockers protects these patients from platelet hyperaggregability; heparin induces significant aggregation of platelets from patients with AMI and NMI with vascular disease. These observations are of importance in considering the pathogenesis and treatment of AMI and ischemic heart disease.

Adrenergic beta-Antagonists↗
PubMed1986

Platelet function defects in chronic alcoholism.

Platelet function in alcoholic patients was assessed on admission and during abstinence in hospital. On admission platelets from these patients were significantly less responsive (percentage aggregation and thromboxane A2 release) to conventional in vitro aggregating agents (adrenaline, adenosine diphosphate, and collagen) than platelets from healthy, moderate drinkers. Initially, platelet counts in platelet rich plasma tended to be low and the Simplate II bleeding times frequently prolonged. Platelet aggregation and thromboxane A2 release, however, were inhibited even in patients with normal platelet counts on admission. Platelet aggregation and thromboxane A2 release returned to normal or became hyper-responsive during two to three weeks of abstinence. Platelet counts rose during this period, the largest responses occurring in those patients with the lowest counts on admission. Bleeding times reverted to normal during abstinence and correlated significantly with changes in platelet aggregation, thromboxane A2 release, and platelet count and with the estimated ethanol consumption during the week before admission. Chronic, heavy alcohol ingestion evidently exerts an inhibitory effect on platelet function even in the absence of alcohol in the blood, and this phenomenon is reversible on abstaining. The impaired platelet function, together with the reduced platelet count, may contribute to the bleeding diathesis associated with chronic alcoholism and to the increased incidence and recurrence of gastrointestinal haemorrhage associated with excessive alcohol intake.

Adult↗
PubMed1986

The effect of cimetidine on platelet function: a study involving gastric fluid measurements.

Gastric fluid samples were aspirated 30 and 60 minutes after the ingestion of two 200 mg tablets of cimetidine. The concentration of cimetidine in these samples was measured and their effect on platelet aggregation assessed in vitro. Gastric fluid samples significantly inhibited adrenaline- and ADP-induced platelet aggregation in vitro. In a further series of experiments, cimetidine solutions, at concentrations found in gastric fluid, inhibited platelet aggregation and thromboxane A2 (TXA2) release, in vitro. Ranitidine, another H2-receptor antagonist, was a more potent inhibitor of platelet aggregation than cimetidine. Since ranitidine is also the more potent H2-receptor antagonist which, unlike cimetidine, does not include an imidazole group (which is known to inhibit TXA2 synthesis) in its structure, we conclude that H2 blockade mediates the observed inhibition of aggregation. This platelet anti-aggregatory effect may be relevant to haemostatic mechanisms involved in bleeding peptic ulcers or gastric erosions exposed to high local concentrations of H2-receptor antagonists.

Blood Platelets↗
PubMed1986

Adrenaline-induced hyperaggregability of platelets and enhanced thromboxane release in anorexia nervosa.

Platelet aggregation and thromboxane A2 release in response to adrenaline and the relationship of this response to body weight was investigated in female patients with anorexia nervosa. Platelets obtained from patients with body weights below 75% of the expected average weight (Group I) showed significantly greater aggregation and TXA2 release in response to adrenaline when compared with controls matched for sex and age. Patients with body weights 75-95% of the expected average weight (Group II) did not show enhancement of platelet aggregation or TXA2 release. In Group I patients, platelet hyperaggregability and enhanced TXA2 release induced by adrenaline tended to normalise following inpatient treatment and weight gain: with 0.5 mumol/l adrenaline, the pre-weight gain median aggregation was 65%, whereas the post-weight gain value was 37% - P less than 0.01. Markedly underweight patients also had hyperaggregability following stimulation with ADP and collagen. This hyperaggregability also tended to normalise after weight gain but these changes were not statistically significant. Platelet hyperaggregability (especially in response to adrenaline) in anorexia nervosa is therefore secondary to weight loss and reverts to normal with normalisation of weight. These changes may reflect the previously documented increase in platelet alpha-adrenoceptors in thin patients with anorexia nervosa and their normalisation following weight gain. However, the hyperaggregability in response to agonists other than adrenaline suggests that an additional post-receptor mechanism may be involved.

Adenosine Diphosphate↗
PubMed1986

The effect of dihomogammalinolenic acid on platelet aggregation and prostaglandin release, erythrocyte membrane fatty acids and serum lipids: evidence for defects in PGE1 synthesis and delta 5-desaturase activity in insulin-dependent diabetics.

The effect of dihomogammalinolenic acid (DHLA) administration on platelet aggregation and prostaglandin production, erythrocyte fatty acid composition and serum lipids was compared in healthy subjects and insulin-dependent diabetics (IDDs). In healthy subjects, DHLA caused a significant inhibition of ADP-induced platelet aggregation and an increase in platelet PGE1 release; IDDs did not show these changes. There were no differences, however, in platelet thromboxane A2 (TXA2) or PGE2 release between healthy subjects and IDDs before and after DHLA. Following DHLA, the arachidonic acid content of erythrocytes increased in healthy subjects; this increase was not observed in IDDs. DHLA induced a significant fall in serum non-esterified fatty acid concentrations in both groups without altering either cholesterol or triglyceride concentrations. These data show for the first time that IDD platelets may have a specific defect of PGE1 synthesis quite distinct from the delta 5- and delta 6-desaturase defects known to be associated with experimental diabetes; this defect may contribute to platelet hyper-aggregability in diabetes; and DHLA has a potent antilipolytic effect in vivo; and erythrocytes from IDDs may have a delta 6-desaturase defect.

8,11,14-Eicosatrienoic Acid↗
PubMed1986

An investigation of maternal and neonatal platelet function.

We have previously shown that the human placenta possesses a potent platelet antiaggregatory activity which is probably due to an ADPase. This led us to investigate platelet aggregation (in response to: adenosine diphosphate; adrenaline; collagen) in maternal blood samples obtained pre- and post-delivery and in cord blood at the time of delivery. Platelet aggregation in maternal samples did not differ significantly pre- and post-delivery, nor did it differ significantly from platelet aggregation observed in age-matched, non-pregnant women. On the other hand, platelets obtained from cord blood samples were insensitive to adrenaline even when very high concentrations (100 mumol/l) of this agonist were used. This lack of response to adrenaline could be overcome by incubation of cord platelet rich plasma (PRP) with sub-aggregatory doses of collagen or ADP or by standing PRP at room temperature for 2-3 h. ADP-induced aggregation was also diminished in cord PRP samples but this was only significant at the lowest ADP concentrations. The physiological significance of these findings is unclear but it may be of relevance that plasma catecholamine levels are high in neonates. Some adults show a defect of aggregation with absence of response to adrenaline, suggesting that neonatal platelet function patterns may persist in some adults.

Adenosine Diphosphate↗