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Biomedical subjects

P Limbourg

Publications and source records attributed to P Limbourg.

At least 19 recordsLinked to original sources

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.

Drug Synergism

[Results of embolectomy in massive pulmonary embolism (author's transl)].

In ten patients successful embolectomy after acute massive pulmonary embolism was performed. Clinical symptoms included circulatory arrest and shock as well as collaps, syncope and dyspnoe. Pulmonary angiography regularly showed massive, bilateral emboli. In 9 patients more than one half of the pulmonary artery system was involved (perfusion defect more than 50%). Right heart catheterization demonstrated pulmonary hypertension in all cases. In 8 patients the pulmonary artery mean pressure (PAm) exceeded 30 mm Hg. In 9 patients there were signs of right heart failure (RVEDP more than 11 mm Hg). At recatheterization 6 to 30 (mean 19) days after operation using cardiopulmonary bypass there was a marked improvement of pulmonary angiograms, which were normal in 3 cases. PAm decreased from 34.3 mm Hg to 14.6 mm Hg postoperatively and RVEDP from 14.4 to 5.1 mm Hg (p less than 0.001). These results confirm, that pulmonary embolectomy leads to a good functional results.

Acute Disease

[Calcification of the mitral valve ring, a cardiac manifestation of Marfan's syndrome (author's transl)].

A 29-year-old patient with calcification of the mitral valve annulus with Marfan's syndrome and severe malformation of the chest is reported. There are 8 other cases with calcification of the mitral annulus in this syndrome in the literature. It seems to be a specific but rare cardiac manifestation of Marfan's syndrome with calcification occurring also in the younger age group. These patients, in contrast to other patients with Marfan's syndrome who mostly have mitral insufficiency of minor degree mainly in late systole, present with hemodynamically severe mitral regurgitation. Our patient died 7 weeks after implantation of a prosthetic valve in low output syndrome, probably caused by a paraprosthetic leak and newly developed aortic insufficiency. It therefore seems that indication for prosthetic replacement of the mitral valve in these patients should be made with caution, particularly in regard to the technical difficulties at operation.

Adult

Left ventricular function after acute myocardial infarction.

10 patients with their first AMI were studied within the first 48 hours and again after 3 weeks. Central and peripheral haemodynamics (CI, SV, SW, TPR) were examined, including indices of contractility (dp/dtmax) and wall stiffness (deltaP/deltaV, relation deltaP/deltaV to P) of the left ventricle. In the early phase CI and SW, as well as LV dp/dtmax were depressed in accordance with symptoms of LV failure. deltaP/deltaV was increased. Elevation of LVEDP correlated well with ventricular gallop rhythm, but less consistently with LV functional disturbance. During convalescence CI increased uniformly, both in digitalized and non-digitalized individuals. In contrast heart rate, aortic pressure, LVEDP and dp/dtmax remained unchanged. The increase of CI, SV and SW was accompanied by a fall of TPR and deltaP/deltaV. LV wall stiffness was still elevated above normal after 3 weeks. The improvement of cardiac pumping during infarct convalescence may have been effected through a fall of TPR and LV wall stiffness. Recovery of depressed contractile performance was generally not observed, and does therefore not seem to contribute to recuperation.

Acute Disease

Effect of diazoxide on left ventricular performance in hypertension.

The effect of diazoxide on left ventricular performance during rest and isometric exercise (handgrip) was examined in 16 unselected hypertensive patients, 6 of whom had been pretreated with the beta-adrenergic blocking agent pindolol. Diazoxide regularly and promptly produced a fall in left ventricle systolic and end diastolic pressures, and an increase in heart rate and left ventricular dp/dtmax. Haemodynamic changes were maximal 2 minutes after injection of the drug and decreased little over the next 8 minutes. After beta-adrenergic blockade, diazoxide caused a more pronounced reduction in left ventricular systolic pressure and a less marked fall in end-diastolic pressure, whilst the diazoxide-induced rise in heart rate was partially and the increase of dp/dtmax was completly inhibited. The increase in systolic pressure during isometric exercise was not influenced by diazoxide, but the positive inotropic reaction was augmented. The findings appear to show that cardiac stimulation by diazoxide is due to a reflex mechanism transmitted by baroreceptors, and that improvement of cardiac performance is mainly due to a reduction of left ventricular after-load.

Adult

[Studies on the effect of Melixetin (Kö 1173) on AV-conduction time and sinus pulse automation in persons with healthy hearts and in patients with disorders of the impulse-conduction system].

The influence of Mexiletine on the av-conduction time and sinus node recovery time of 24 patients with and without disturbance of impulse formation and conduction was examined. There was no change of conduction time proximal to the His-bundle. Four patients developed block distal to the His-bundle, 3 of which had a conduction disturbance before application of the drug consisting in 2:1 av-block or bifascicular block. Two patients with WPW-syndrome showed no change of impulse conduction. Five out of 12 patients showed an increase of the effective recovery period. Three out of 15 patients showed an increase of threshold potential from 0.35 to 0.7 volt with suppression of escape rhythm. The sinus node recovery time was prolonged in 2 out of 9 patients, one of which had a sick sinus syndrome. As there seems to be some influence of Mexiletine on sinus node impulse formation and the impulse conduction distal to the His-bundle, this drug probably should be used with caution in patients with disturbance of automaticity and distal av-conduction.

Anti-Arrhythmia Agents