[Fibrinolytic therapy in acute myocardial infarction].
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Biomedical subjects
Publications and source records attributed to A Eldor.
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The effect of diet-induced hypercholesterolemia on the recovery of prostacyclin (PGI2) synthetic capacity was assessed at the luminal surface of previously injured rabbit aorta. Prostacyclin synthesis and release were measured by radioimmunoassay following arachidonic acid stimulation of deendothelialized and reendothelialized aortas of hypercholesterolemic rabbits. Assay of PGI2 production by aorta was performed at 15, 35, and 70 days following removal of endothelium with a balloon catheter. Prostacyclin production by both deendothelialized and reendothelialized areas of aorta from normocholesterolemic rabbits was initially low following injury and increased with time, reaching levels at 70 days equal to uninjured aortas. Prostacyclin production by both deendothelialized and reendothelialized areas of aorta from rabbits with moderately elevated serum cholesterol concentrations (203 to 350 mg/dl) was also initially low, but in contrast to normocholesterolemic rabbits, it did not increase with time. Results indicate that hypercholesterolemia like that seen in humans inhibits the recovery of PGI2 production in deendothelialized and reendothelialized areas of previously injured rabbit aorta.
Arteries are capable of producing significantly larger quantities of prostacyclin than are veins. To test the hypothesis, whether prostacyclin production by the vessel wall is related to blood pressure and flow, we measured the amounts of PGI2 released and synthesized by venous segments transplanted for 6 weeks into the arterial circulation. These results were compared with the production of prostacyclin by normal veins and arteries. In 20 dogs a segment of jugular vein was interposed into the carotid system; a sham dissection was done on the opposite side. "Arterialized" vein grafts showed prominent intima lined by endothelium, medial smooth muscle cell proliferation and fibrotic proliferation in adventitia. Spontaneous and arachidonic acid-stimulated prostacyclin production (measured by radioimmunoassay for 6-keto-PGF1 alpha) was not significantly different between arterialized venous autografts and jugular veins. Significantly larger amounts of prostacyclin were synthesized by the carotid artery. Thus, histologic changes and rheologic effects occurring in vein grafts transposed to the arterial site do not affect prostacyclin production.
1 The effect of the surfactant, Cetomacrogol 1000, on the absorption of insulin across the rectal mucosa has been studied. 2 Rectal administration of microenemata containing Cetomacrogal 1000 and insulin causes a rise in the plasma concentration of insulin and a consequent fall in the blood glucose concentration in diabetic and non-diabetic rats. 3 The hypoglycaemic response is dependent on both the concentration of surfactant and the dose of insulin administered. 4 The results suggest that the transport of insulin across the rectal mucosa is facilitated by Cetomacrogal 1000.
Prostacyclin (PGI2) synthetic capacity was assayed at the surface of aortas at various intervals after removal of endothelium with a balloon catheter. Results were correlated with morphologic changes in the vessel wall seen by light microscopy, scanning and transmission electron microscopy. To assay PGI2 synthetic capacity, we applied an incubation chamber to the luminal surface of the aortas; after arachidonic acid stimulation we assayed the PGI2 synthesized with a bioassay and radioimmunoassay. PGI2 synthesis in de-endothelialized aortas was determined immediately after balloon-catheter injury and at intervals of 1 h and 2, 4, 15, 35, and 70 d. PGI2 synthesis was low at 1 h and increased over time with levels at 35 and 70 d reaching that of normal artery. Scanning and transmission electron microscopy of de-endothelialized areas showed persistent absence of endothelium with formation of a neointima composed of smooth muscle cells. De-endothelialized aorta was covered with adherent platelets shortly after injury, however several days later only a few platelets adhered to the denuded surface. Results indicated that (a) endothelium is responsible for nearly all PGI2 production at the luminal surface of the normal aorta, (b) de-endothelialized muscular neointima synthesized increasing quantities of PGI2 with time after injury, and (c) increase of PGI2 production at the luminal surface of de-endothelialized aorta correlates with formation of a neointima and with the acquired thromboresistance of the aorta.
Efforts to improve myocardial preservation during aortocoronary bypass procedures have led to the perfusion of saphenous vein segments with potassium cardioplegic (KCP) solutions after completion of the distal anastomosis. Recent reports show that the procurement of veins leads to varying degrees of damage, particularly to the endothelial surface, as a result of the dissection itself, the hydrostatic pressure required to distend the veins in obtaining hemostasis and the composition of the solutions used to irrigate the harvested segments. The biologic activity of arterialized vein segments is largely unknown. We tested the hypothesis that the degree of venous injury inherent in vein harvesting may be compounded by perfusion with a potassium-rich solution, a known vascular irritant. The external jugular vein was removed from 18 dogs. Half of the vein was perfused with 300 ml of a KCP solution at 4 degrees C (40 mEq/l KCl, 10 ml sodium bicarbonate, pH 7.6, osmolarity 340 mosmol) and the other half with lactated Ringer's solution (LR). The treated vein was reversed and interposed into the excluded internal carotid circulation. A sham dissection was done on the opposite jugular vein. The veins were harvested after 6 weeks and assayed for spontaneous and arachidonate-stimulated (AS) prostacyclin activity as well as light microscopic analysis of morphologic changes. Spontaneous and AS production of prostacyclin did not differ significantly in the sham, LR and KCP groups: 1539 +/- 709 and 4166 +/- 1802, 1569 +/- 763 and 3767 +/- 2706, 1860 +/- 1233 and 3947 +/- 3347 pg/ml). Light microscopic analysis revealed an intense adventitial fibrotic reaction in the KCP group and the appearance of fibroblast-like cells in the outer layer of the vein wall. The intima was intact in all three groups. We conclude that intimal damage sustained during harvesting is repaired within 6 weeks, and there is no impairment to surface production of prostacyclin. The intense adventitial fibrotic reaction observed in the KCP-treated group has not been previously reported, and its significance remains unexplained.
In their study of prostaglandin E1 (PGE1)-sensitive adenylate cyclase (AC) in rat brain homogenates, Collier and Roy claimed that the activity of this enzyme is inhibited by opiates. They also proposed that opiates exert their analgesic and allied effects by inhibiting AC of neurones that are normally stimulated by E prostaglandins. Studies using neuroblastoma x glioma hybrid cells supported this hypothesis. However, subsequent studies with mammalian brain and rat brain tissue slices yielded conflicting results. PGE1 also inhibits platelet aggregation, probably through activation of platelet AC. Gryglewski et al. showed that morphine inhibits the anti-aggregating effect of PGE1 on ADP- and adrenaline-induced platelet aggregation, and suggested that the inhibition by morphine is mediated through platelet AC activity. We report here our attempts to reproduce the results of Gryglewski et al. and our examination of the effect of morphine on PGE1-sensitive AC activity in platelet lysates and on PGE1-induced accumulation of cyclic AMP in intact platelets. The possible existence of opiate receptors in platelets was also assessed by direct binding studies with 3H-etorphine. In contrast to Gryglewski et al., we could not detect any effect of opiates on the aggregation of human platelets, nor did we find any other evidence supporting the presence of opiate receptors in these cells. Thus we conclude that the presence of opiate receptors in human platelets is unlikely.
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The quantity of myosin, actin, and actin-binding protein (ABP) in platelets and platelet fractions of 5 patients with Glanzmann's thrombasthenia were compared to those of normal individuals. No significant differences were observed between the average amounts of these contractile proteins in unfractionated platelets or platelet membrane obtained after osmotic shock. However, the amount of myosin was significantly decreased in the KCl extract of thrombasthenic platelets ruptured by freezing and thawing,while its specific ATPase activity was increased.
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The effect of magnesium sulfate on thrombus formation in vivo was studied by scanning electron microscopy utilizing the model of endothelial damage by temporary arterial occlusion with a Heifetz clip. Examination of arterial segments compressed by the surgical clip for 30 minutes, followed by 2 hours of reflow, revealed marked attachment of platelets and deposition of erythrocytes, with very few leukocytes, to exposed subendothelial tissues. This thrombotic deposition protruded as much as 150 mu into the vascular lumen (15% of luminal diameter). By contrast, in animals pretreated with magnesium sulfate, this deposition was limited to isolated areas of single or very few platelets with few erythrocytes or leukocytes. The difference in overall quantity of thrombus formation between nontreated and magnesium sulfate-treated groups was much less obvious after 24 hours; however, fewer leukocytes and erythrocytes were seen to be attached to the platelet carpet in the treated group as compared with the nontreated group. The effect of magnesium sulfate on the overall quantity of thrombus formation corresponded inversely to the measured levels of serum magnesium in these groups.
A three-year-old white girl from a haemophiliac A family was a symptomatic carrier. The clinical and laboratory data concur with the form of a heterozygous symptomatic carrier state.
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