Antiplatelet effects of prostacyclin and nitric oxide in patients with type I diabetes and ischemic or edematous retinopathy.

The aim of this study was investigate prostacyclin and nitric oxide (NO) and their platelet second messengers cAMP and cGMP, in patients with type I diabetes with or without retinopathy. We compared 20 healthy volunteers and 97 patients with type I diabetes: 24 with no signs of diabetic retinopathy (DR), 43 with ischemicproliferative DR, and 30 with edematous DR. The following parameters were recorded: platelet aggregometry, nitrites/nitrates, 6-keto-prostaglandin-F(1alpha), and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients with edematous DR. The platelets in patients with diabetes were more resistant to inhibition by prostaglandin E(1) or sodium nitropruside. Nitrite concentration in patients with ischemic-proliferative DR was 80% lower than the value in healthy controls, but there was no significant difference between the control group and patients with edematous DR. In the latter group, stimulation of neutrophils with L-arginine increased nitrite + nitrate production by 44 +/- 3.6%, whereas in patients with ischemic-proliferative DR, the increase was 9.8 +/- 0.8%. We conclude that NO production is higher in patients with type I diabetes and edematous retinopathy than in those with ischemic-proliferative retinopathy. This finding, together with the possibly greater production of free radicals, may explain the greater impairment of platelet function in the former patients.

Antithrombotic potential of olive oil administration in rabbits with elevated cholesterol.

Olive oil is the main source of dietary fatty acids in the Mediterranean region. The objective of this study was to evaluate the effect of dietary supplementation with virgin olive oil in an experimental model with rabbits fed an atherogenic diet (saturated fat 48% of total fat). Four different groups of 10 animals each were studied: (1) normolipemic diet (NLD), (2) atherogenic diet or saturated fatty acid-enriched diet (SFAED), (3) NLD with 15% olive oil (NLD+OLIV), and (4) SFAED with 15% virgin olive oil (SFAED+OLIV). The animals were fed the experimental diets for 6 weeks, after which we determined serum lipid profile (total cholesterol, HDL-cholesterol, and triglycerides), platelet aggregation, platelet thromboxane B(2), aortic prostacyclin, and platelet and vascular lipid peroxidation. Scanning electron microscopic images of the vascular endothelium were studied, as were morphometric parameters in the arterial wall and thrombogenicity of the subendothelium (annular perfusion chamber). Animals fed the SFAED showed platelet hyperactivity and increased subendothelial thrombogenicity. Animals fed the SFAED+OLIV showed, compared with the SFAED group, an improved lipid profile with decreased platelet hyperactivity and subendothelial thrombogenicity and less severe morphological lesions of the endothelium and vascular wall. We conclude that supplementation of the SFAED with 15% olive oil reduced vascular thrombogenicity and platelet activation in rabbits. Although the percentage of olive oil in the diet was higher than the amount in the human diet, these results may be helpful in determining the effect of olive oil in the human thrombogenic system.

The effect of a single intravenous dose of metamizol 2 g, ketorolac 30 mg and propacetamol 1 g on haemodynamic parameters and postoperative pain after heart surgery.

Although nonopiate analgesics may be particularly useful in the immediate postoperative period after major surgery, their use has been associated with haemodynamic adverse effects during postoperative pain treatment and in critically ill patients in intensive care. The effect of a single intravenous dose of metamizol (dipyrone) 2 g, ketorolac 30 mg and propacetamol 1 g on haemodynamic variables and pain control in the immediate postoperative period after heart surgery is compared. Seventy-two patients undergoing elective coronary and/or heart valve surgery, were included in a cohort study of 1-years duration (1998). After weaning from mechanical ventilation and extubation, haemodynamic variables and a 4-point verbal rating pain scale were asseseed at base-line and 60 min after the administration of a single doses of metamizol, ketorolac or propacetamol. The Student's t-test for paired samples was used to compare changes produced by the study medications. A significant, but small, decrease in radial artery blood pressure was observed in all treatment groups which had little clinical relevance; no vasodilator effects were observed and ventricular function showed only minor changes: propacetamol decreased cardiac index by 10% and a 15% decrease in right ventricular work was also observed. Metamizol and ketorolac produced a 10% decrease in the left ventricular work index. Pain scores showed a statistically significant decrease in all treatment groups. The analgesic effects of metamizol, ketorolac and propacetamol were not associated with a clinically significant impairment in haemodynamic function when administered to haemodynamically stable patients.

Antiplatelet effect of the anaesthetic drug propofol: influence of red blood cells and leucocytes.

1. The present study was designed to investigate the mechanism of the antiplatelet action of the anaesthetic propofol in vitro. 2. Human whole blood was incubated with different concentrations of propofol and its solvent Intralipid(R). We determined, platelet aggregometry in whole blood, platelet-enriched plasma (PRP), PRP plus red blood cells (RBC), and PRP plus leucocytes (LC); platelet production of thromboxane B2 (TxB2), ATP release by platelet dense granules, adenosine uptake by RBC, intraplatelet levels of cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), and LC production of nitric oxide (NO). 3. Propofol-induced inhibition of platelet aggregation was greater in whole blood (IC50 80 - 136 microM) than in PRP (IC50>600 microM), except when aggregation was induced by arachidonic acid, in which case the antiaggregatory effect of the anaesthetic was similar in both media (IC50 72 - 85 microM). Inhibition of platelet aggregation correlated significantly with inhibition of TxB2 synthesis (r2=0.83). Propofol also inhibited granular ATP release; this effect was greatest in whole blood. 4. The presence of RBC or LC increased the antiaggregatory effect of propofol, mainly when collagen was used as aggregating agent. Intralipid inhibited the uptake of adenosine by RBC, however this effect probably does not contribute significantly to its antiaggregatory effect. 5. The anaesthetic potentiated the NO-cyclic GMP pathway, mainly by increasing the synthesis of NO by LC. Intralipid had no effect on the NO-cyclic GMP pathway in the LC-platelet interaction. 6. Propofol inhibited platelet aggregation in human whole blood, possibly through the sum of the effects of Intralipid on the platelet-RBC interaction and the increased synthesis of NO by LC in the platelet-LC interaction.

The effect of propofol on oxidative stress in platelets from surgical patients.

UNLABELLED: We investigated the changes in oxidative stress in platelets from surgical patients anesthetized with propofol. We studied 60 surgical patients (ASA physical status I and II) and 12 healthy volunteers. The patients were divided into three groups: anesthesia induced with an IV bolus dose of 4 mg/kg thiopental; anesthesia induced with an IV bolus dose of 2 mg/kg propofol; and total IV anesthesia (induction with propofol 2 mg/kg, infusion with propofol 10 mg/kg during the first 10 min, then 8 mg/kg for 10 min, and 6 mg/kg during the rest of the operation). Healthy volunteers were given an IV bolus dose of 10% fat emulsion (Intralipid). We measured the following variables in platelets: thiobarbituric acid reactive substances content, glutathione content, and glutathione peroxidase, reductase, and transferase activities. Thiopental did not modify any of the variables. Propofol decreased thiobarbituric acid reactive substances production by 25.7% and increased total glutathione content by 24.6%. The percentage of glutathione in oxidized form was 29.5% smaller in patients anesthetized with propofol. Glutathione peroxidase activity was 28.3% less, glutathione transferase was 44.5% more, and glutathione reductase was not significantly different. Intralipid had no effect on any of the variables. After infusion of propofol for 1 h, the effects were, in qualitative terms, the same as those seen after an initial bolus dose. In conclusion, our findings show that propofol has an antioxidant effect in humans. This effect may be beneficial in patients who have diseases in which free radicals play an important role. IMPLICATIONS: This study demonstrates that propofol inhibits cellular oxidative damage, measured in platelets from surgical patients. Neither thiopental nor the fat emulsion (Intralipid) showed any effect. Moreover, propofol increased the antioxidant defense of glutathione. This could be applied in the protection of tissues from ischemic damage.

Effect of S-adenosyl methionine on muscarinic receptors in young rats.

In the present study we have investigated the effect of a chronic administration of S-Adenosyl Methionine (SAM) on muscarinic receptor subtypes in young rat forebrain, cerebellum, heart and lacrimal gland. Saturation binding experiments were performed using 3H-N-methylscopolamine (3H-NMS) to label the total population of muscarinic receptors in plasma membranes from forebrain, cerebellum, heart and lacrimal gland. 3H-Pirenzepine (3H-Pz) was used to label the M1 subtype in plasma membranes from forebrain. The results obtained in cerebellum, heart and lacrimal gland show no changes in the affinity (Kd) nor in the number of receptors (Bmax) of the treated versus control groups. Saturation experiments in forebrain show an increase in the number of receptors of the treated versus control groups when using 3H-NMS (Bmax 2117 +/- 63 versus 1643 +/- 104 fmol/mg protein) without changes in the affinity. Saturation experiments with 3H-Pz, show an increase in the number of M1 receptors in the treated group with no changes in the affinity (Bmax 421 +/- 16 versus 225 +/- 19 fmol/mg protein). From our results, we conclude that SAM increase the number of receptors in forebrain and this increase is mainly due to changes in the number of M1 receptor subtypes.

Endogenous digoxin-like substance in liver failure.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin. We therefore studied the sensitivity of EMIT Convenience Pack Digoxin immunoassay to interference by DLIS in patients with liver failure. Serum digoxin was measured in cirrhotic patients with moderate to severe liver failure (Child-Pugh B or C grade), patients with mild liver disease (chronic hepatitis) and matched control patients without liver disease. Excluded were patients taking or who had ever received any cardiac glycoside in the past. Blood samples were obtained by venipuncture and assayed in duplicate. Twenty-two out of 30 cirrhotic patients (73%) showed false-positive results, vs. one of 6 patients (16.7%) with mild liver disease, and 1 of 10 (10%) controls. The serum DLIS level was negatively correlated with prothrombin activity (r = -0.55, p < 0.00011). Digoxin levels must be interpreted carefully in patients with moderate to severe liver failure.