In porcine heart, embolization of small coronary arteries with microspheres in 25 microns in diameter induces collateral capillary vessel growth by angiogenesis in and around focal necrosis. By histological analysis the inflammatory infiltrates in this porcine tissue were characterized by numerous monocytes/macrophages and fibroblasts as well as neutrophils and numerous capillaries, some in mitosis. The aim of the present study, therefore, was to clarify the role of monocytes/macrophages and fibroblasts in angiogenesis and in repair in ischemic porcine myocardium. Using a human acidic fibroblast growth factor (aFGF) cDNA probe for in situ hybridisation labeling for aFGF mRNA was seen in monocytes and macrophages only, beginning at day 1, with a maximum at 3 and 7 days, and minimal labeling at 4 weeks. We have also shown, with a specific antibody and fluorescence microscopy, that tumur necrosis factor alpha (TNF alpha) follows the same time sequence and that it is produced by monocytes/macrophages. The number of capillaries in infiltrates at 3 and 7 days as revealed by the lectin Dolichus Biflorus Agglutinin was high and declined at 4 weeks. In situ hybridisation using a rat cDNA probe for fibronectin showed the increased production of fibronectin mRNA in fibroblasts. To describe the expression of fibronectin and the collagens I, III, VI immunohistochemistry was used. A comparison showed that fibroblasts produced fibronectin mRNA starting at day 3, but the protein was only maximally expressed at day 7 and 4 weeks. Collagen I, III, VI expression was highest at 1-4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Angiotensin converting enzyme inhibitors, left ventricular hypertrophy and fibrosis.

From pharmacological investigations and clinical studies, it is known that angiotensin converting enzyme (ACE) inhibitors exhibit additional local actions, which are not related to hemodynamic changes and which cannot be explained only by interference with the renin angiotensin system (RAS) by means of an inhibition of angiotensin II (ANG II) formation. Since ACE is identical to kininase II, which inactivates the nonapeptide bradykinin (BK) and related kinins, potentiation of kinins might be responsible for these additional effects of ACE inhibitors. a) In rats made hypertensive by aortic banding, the effect of ramipril in left ventricular hypertrophy (LVH) was investigated. Ramipril in the antihypertensive dose of 1 mg/kg/day for 6 weeks prevented the increase in blood pressure and the development of LVH. The low dose of ramipril (10 micrograms/kg/day for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity but also prevented LVH after aortic banding. The antihypertrophic effect of the higher and lower doses of ramipril, as well as the antihypertensive action of the higher dose of ramipril, was abolished by coadministration of the kinin receptor antagonist icatibant. In the regression study the antihypertrophic actions of ramipril were not blocked by the kinin receptor antagonist. Chronic administration of BK had similar beneficial effects in a prevention study which were abolished by icatibant and NG-nitro-L-arginine (L-NNA). In a one year study the high and low dose of ramipril prevented LVH and fibrosis. Ramipril had an early direct effect in hypertensive rats on the mRNA expression for myocardial collagen I and III, unrelated to its blood pressure lowering effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Fibrinopeptide A (FPA) radioimmunoassay influence of the affinity of the second antibody for FPA antiserum.

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Animals↗

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Blood coagulation changes during effective thrombolysis using urokinase and heparin.

The efficacy and the safety of a new urokinase dosage regimen (loading dose 250,000 IU, initial maintenance dosage 2,000 IU/kg/h in combination with heparin) was studied in ten cases of deep vein thrombosis with regard to the changes of the blood coagulation and fibrinolytic enzyme system. The coagulation analyses demonstrated a pronounced activation of the fibrinolytic system with a statistically significant (p less than 0.05) shortening of the euglobulin clot lysis time and increase of the FDP. The fibrinogen concentration ranged from 50-100 mg/dl already after 12-36 hours. Plasminogen was reduced by 63%, alpha 2-macroglobulin by 32% and factor VIII:C by 42% (p less than 0.05 each). The decrease of fibrinogen (Clauss method) related well to the method of Ratnoff and Menzie, the reduction of plasminogen and the shortening of the euglobulin clot lysis time. According to our data, a sufficient plasma fibrinogenolytic activity may permit on its own an assessment of an adequate therapy with urokinase and the requirements of dose adjustment. The dosage regimen applied here proved effective and readily controllable. Relevant side reactions were not observed.

Blood Coagulation↗