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Biomedical subjects

C Deby

Publications and source records attributed to C Deby.

At least 91 records · Page 5Linked to original sources

Prostaglandin E2, prostacyclin, and thromboxane changes during nonpulsatile cardiopulmonary bypass in humans.

To study the effect of lung bypass on the production of prostaglandin E2, prostacyclin, and thromboxane A2, we measured simultaneously arterial and venous plasma concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha (stable metabolite of prostacyclin), and thromboxane B2 (stable metabolite of thromboxane A2) before, during, and after cardiopulmonary bypass. Seventeen patients (age range 46 to 69 years) undergoing aorta-coronary bypass grafts were investigated. The prostaglandin E2 production rose sharply immediately after the onset of bypass (baseline: 9.7 +/- 2.9 pg/ml to 85 +/- 16.6 pg/ml in venous and 87 +/- 12 pg/ml in arterial plasma, p less than 0.03) and rapidly decreased after pulmonary reperfusion (53 +/- 6.4 and 57 +/- 20 pg/ml, respectively, in venous and arterial plasma at the end of bypass). The increase in prostaglandin E2 was influenced by the heart-lung machine itself (as demonstrated by a closed "bypass" circuit) and by lung bypass. Pulmonary metabolism of prostaglandin E2 was maintained after bypass. The prostacyclin production rose significantly at the beginning of bypass (154 +/- 26 pg/ml venous prebypass level to 361 +/- 94 pg/ml after aortic clamping, p less than 0.03). Prostacyclin decreased progressively during rewarming of the patient, pulmonary reperfusion, and discontinuation of bypass. When prostacyclin decreased, thromboxane B2 production rose significantly and reached peak arterial levels when the lungs were reperfused (112 +/- 33 pg/ml prebypass levels to 402 +/- 101 pg/ml, p less than 0.01). Except for prostaglandin E2, there were no significant differences between arterial and venous plasma levels of these substances. The same prostanoids were also measured in five patients undergoing major orthopedic operations, and no significant changes in prostanoids were observed. Our data demonstrate significant production of prostaglandin E2 in the systemic circulation during cardiopulmonary bypass in humans. They further indicate that lung bypass disturbs the plasma prostaglandin/thromboxane balance.

6-Ketoprostaglandin F1 alpha↗

The tachyphylactic effect of arachidonic acid on in-vivo ADP induced arterial platelet thrombosis.

The continuous superfusion of arachidonic acid over a branch of the mesenteric artery in an animal in-vivo model results in an initial increase followed by a decrease to control values of ADP induced platelet thrombogenesis. This phenomenon is observed in normal rats as well as in rats submitted to the intravenous administration of ASA three hours prior to the investigation. In the latter group the cyclooxygenase of the platelets is permanently affected while the cyclooxygenase of the endothelial cells is regenerated at the time the investigation is started. The tachyphylactic-like phenomenon observed with arachidonic acid is probably related to the dynamics of the enzymatic reactions of the arachidonate cascade involving the platelets and the endothelial cells surrounding the local de-endothelialized area.

Adenosine Diphosphate↗

The effect of inhibition of endothelial cell cyclooxygenase on arterial thrombosis.

Arterial platelet thrombosis was induced in vivo in a branch of the mesenteric artery of the white Wistar rat by topical superfusion by adenosine diphosphate following local de-endothelialization of the dissected segment by means of a small electrical current. Detection of the thrombotic phenomena was performed by projection of the arterial segment onto a set of light sensitive elements, which allows the registration of several discriminating parameters. The addition of arachidonic acid to the superfusing mixture results in an increase in thromboformation; this increasing effect can be blocked completely by prior inhibition of the vessel wall cyclooxygenase activity by inhibitors such as flurbiprofen or indomethacin. We therefore concluded that the arachidonate cascade, triggered within the endothelial cells, is involved in platelet-vessel wall interaction leading ultimately to local thrombosis.

Adenosine Diphosphate↗

The effect of free radical scavengers on "in vivo" induced arterial thrombosis in relation to the arachidonate cascade.

Arterial platelet thrombosis induced by topical superfusion with adenosine diphosphate (ADP) is enhanced by tranylcypromine, an inhibitor of prostacyclin-synthetase. This effect is evanescent; indeed continuous superfusion with tranylcypromine results in a decrease of the thrombotic parameter to normal control values within forty minutes. This tachyphylactic-like phenomenon is attributed to the deactivation of cyclooxygenase by free radicals, probably oxygen species generated during the arachidonate cascade. In the presence of free radical scavengers such as uric acid, mannitol or formate the tachyphylactic phenomenon disappears suggesting that cyclooxygenase is no longer deactivated. The regression over time induced by tranylcypromine is computed as a measure for the inactivation of cyclooxygenase.

Animals↗

Immunoreactive trypsin in the adult respiratory distress syndrome.

With the purpose of studying the role of proteinases in the development of ARDS, plasma levels of immunoreactive trypsin (IRT) and amylase were measured in 43 intensive care patients at risk of developing ARDS (22 polytrauma, seven abdominal surgery, four burns, two DIC and eight pancreatitis). Twenty four of these 43 patients developed ARDS and 31 presented abnormal IRT values (above 70 micrograms/L). Twenty-one of these 31 patients had ARDS; a significant correlation thus appeared between ARDS and abnormal IRT values. In nine patients, IRT values were higher than 800 micrograms/L and remained high for 3 to 4 days. A statistically significant correlation also appeared between abnormal IRT and septic phenomena: 20 patients with high IRT values presented septic problems. When IRT values were high, amylase values were often also abnormal: 12 of 23 patients with high IRT had abnormal amylase levels (the eight patients with documented pancreatitis were excluded); no other clinical signs or symptoms of pancreatitis were present in these patients. IRT could be one of the mediators of ARDS in septic patients. It is not clear that the pancreas is the origin of IRT in all cases.

Abdomen↗

Stimulation of cyclo-oxygenase by lidocaine, a pro-lipoperoxidant.

Lidocaine, which was recently demonstrated to be a good pro-lipoperoxidant, was tested on in vitro PGs biosynthesis, and on arachidonate-induced arterial hypotension, in the rabbit. In the in vitro experiments, lidocaine alone was a poor stimulant of cyclo-oxygenase, but it enhanced significantly the cyclo-oxygenase activation of uric acid. In the rabbit, lidocaine lowered the i.v. arachidonate dose necessary to obtain a significant drop of blood pressure.

Animals↗

Intense rises of unesterified arachidonate plasma levels in stressed humans.

Intense rises of plasma arachidonate have been observed in men in various physiopathological circumstances: in old patients who suffered from hypertension, in patients before and after various surgical procedures, in patients submitted to cardiopulmonary bypass with extracorporeal circulation or to abdominal aortic prosthesis, and in young volunteers or patients submitted to a strain test on bicycle ergometer. The plasmatic arachidonate concentration sometimes reached values ten times higher than the maximal normal value of 5 micrograms/ml plasma registered in 157 controls. These important arachidonate releases have been related to stress (pain, operative or anticipation stress).

Adult↗

[The relation between polyunsaturated fatty acids and cardio-vascular accidents. I. Study of fatty acid components phospholipids].

Blood plasma lipids of women about seventy years old who had suffered from cardiovascular diseases (AVC) were studied and compared with the plasma lipids of women of about the same age without cardiac troubles. A great difference appears in the unesterified fatty acids of the phospholipids from cardiac women: we have observed a decreasing level of polyunsaturated fatty acids with a carbon chain of more than 18 carbons, and a decreasing ratio between the total concentration of the two precursors (linoleic acid omega and alpha-linolenic acid omega 3) and the total concentration of their long chain polyunsaturated derived fatty acids. On the contrary, we did not observe any significant variation of the unesterified fatty acid level in the plasma. The triglyceride and cholesterol levels also were not different between the two groups of patients. The hypothesis of a lack of elongation and of desaturation of linoleic and alpha-linolenic acids by competitive inhibition with oleic acid seems improbable, since the plasmatic concentration of oleic acid was not statistically different.

Aged↗