Deficient t-PA release and elevated PA inhibitor levels in patients with spontaneous or recurrent deep venous thrombosis.

The fibrinolytic system was investigated in 120 patients with spontaneous or recurrent deep vein thrombosis (DVT) without any known organic disease able to explain by itself the occurrence of a thrombosis and without any known defect of antithrombin III, Heparin Cofactor II, Protein C, or Protein S. The assays included: Euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator related antigen (t-PA-Ag) and plasminogen activator inhibitor activity (PA inhibitor), which were measured before and after 10 min of venous occlusion (V.O.). On the basis of the results, the patients could be classified in 3 groups: good responders with an at least two-fold increase of EFA after venous occlusion (n = 76), poor responders with a lesser increase of EFA due to deficient release of t-PA (n = 12), and poor responders with a normal t-PA release but an increased level of PA-Inhibitor (n = 32). The poor responders due to deficient t-PA release (10% of total) had a higher incidence of recurrence of deep vein thrombosis, than the other groups (p less than 0.01). An overall correlation was found between the level of PA-Inhibitor activity and the triglyceride level (r = 0.40, p less than 0.01), suggesting that these elevations may be due to a common cause, at least in some of the patients. It is concluded that a poor fibrinolytic response to venous occlusion occurs in 35 percent of DVT patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of 99mTc plasminogen on fibrin.

Binding of plasminogen to fibrin was studied in vitro and in vivo using 99mTc Glu- and Lys-plasminogen. Binding of Glu-plasminogen on the clot was not observed in vitro, and in vivo in the dog. Conversely, the binding of Lys-plasminogen to fibrin displays a linear relationship to the concentration of Lys-plasminogen, up to doses exceeding equimolarity; thus suggesting the existence of several Lys-plasminogen binding sites on fibrin. Binding levels were identical, regardless of whether plasminogen was incubated in normal plasma or in plasma devoid of antiplasmin. In the dog, Lys-plasminogen bound specifically to the clot, however, clot sites could not be localized by scintigraphy in the dog or in man.

Methergin testing with angiographically normal coronary arteries.

To evaluate the incidence of spasm in patients with angiographically normal coronary arteries or with stenosis less than or equal to 50%, methergin testing was done consecutively in 1,200 patients (742 men and 458 women). The methergin test was performed 850 times during coronary angiography and 350 times after it. The test was globally positive in 11% (127 of 1,200 patients), positive in 7% among 921 patients presenting with atypical chest pain, 13% of 31 patients with effort angina, 54% of 54 with angina at rest, 57% of 53 with Prinzmetal's angina, 3% of 59 with acute myocardial infarction and 1% of 82 miscellaneous patients without chest pain. Another test was done in 291 patients after blockade of the cardiac autonomous nervous system with 0.04 mg/kg of atropine and 2 mg/kg of labetolol. The frequency of positive results in the methergin test increased after blockade from 8 to 19% (p less than 0.01). The increase of positive results was especially obvious among patients with atypical chest pain (from 6 to 14%). Thus, frequency of spasm in these patients with normal coronary arteries or without significative lesions was 11%. This incidence was influenced by the composition of the patient population and increased with blockade of the cardiac autonomous nervous system.

Molsidomine prevents post-ischaemic ventricular fibrillation in dogs.

Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 micrograms kg-1 as an i.v. bolus - 15 min prior to coronary occlusion - followed by an infusion of 0.05 micrograms kg-1 min-1. Standard electrocardiographic leads 2 and 3 were continuously recorded to measure ST segment and delta R% changes and to document both the number of ventricular premature beats and the onset of ventricular fibrillation; aortic pressure and cardiac output were measured; thromboxane B2 plasma levels, platelet aggregation produced by ADP, and molsidomine plasma levels were determined before and at 10, 30 and 75 min after the start of the drug protocol. Molsidomine protected the treated animals from early (10 min) post-ischaemic ventricular fibrillation (0 of 20 vs 6 of 20, P = 0.0202), reduced the incidence of overall post-occlusion ventricular fibrillation (3 of 20 vs 10 of 20, P = 0.0407) and improved the total survival rate (P = 0.0067). In molsidomine treated dogs: mean aortic pressure and the rate-pressure product were lowered 10 min after the start of the drug; immediate post-occlusion (3 min) ST segment changes (0.82 +/- 0.52 vs 1.52 +/- 0.78 mV, P less than 0.025) and delta R% changes (37 +/- 50 vs 90 +/- 84%, P less than 0.025) were less marked; the number of ventricular premature beats was lowered and finally, a progressive decline of platelet aggregation produced by ADP was achieved after 75 min of drug infusion. These results were obtained in the presence of mean plasma levels of molsidomine ranging from 20 to 28 ng ml-1. The time-action curve of the antifibrillatory effect of molsidomine parallels those at the level of post-ischaemic electrocardiographic changes.

Lisinopril versus slow-release nifedipine in the treatment of mild to moderate hypertension: a multicentre study. The Cooperative Study Group.

The antihypertensive effects of lisinopril 20 mg once daily and slow-release nifedipine 20 mg twice daily were compared in a double-blind, parallel group, 10-week study involving 274 patients with mild to moderate hypertension. During the first 6 weeks of treatment, slow-release nifedipine and lisinopril produced similar reductions in lying and standing blood pressure (BP), except for lying systolic BP (SBP) which was reduced to a greater extent by lisinopril. After 6 weeks of double-blind treatment, hydrochlorothiazide 25 mg once daily was added if BP remained uncontrolled (lying DBP greater than or equal to 95 mmHg); a significantly greater proportion of patients in the nifedipine group than in the lisinopril group required additional diuretic treatment (29% versus 14%, respectively; P = 0.005). Moreover, after a further 4 weeks of treatment BP was adequately controlled (lying DBP less than 95 mmHg) in significantly more lisinopril-treated patients than in the nifedipine group (91.4% versus 78.3%, respectively; P = 0.006). Lisinopril was better tolerated than slow-release nifedipine. The frequency of drug-related events was significantly lower (threefold) for lisinopril than for nifedipine (P = 0.001) and the number of withdrawals from treatment with nifedipine was more than three times that in the lisinopril treatment group (P = 0.009). Lisinopril appears to provide an effective once-daily antihypertensive treatment which is at least as effective as, and better tolerated than, slow-release nifedipine.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.

Value of phlebography for diagnosis and treatment of pulmonary embolism.

The frequency of recurrencies and of post-phlebitic syndrome after PE lead the Authors to perform phlebography of the legs before and after treatment of PE. A venous thrombosis was found in 124 cases out of 144 recent PE proven by angiopneumography. The thrombosis affected the ilio-caval veins 43 times, in 27/103 severe PE cases (24%), in 16/33 moderate PE cases (40%). Patients were treated: by H. in 67 cases; 33 (group I) with moderate PE, (4 (group II) with severe PE; by Streptokinase (SK) 24 times: 5 cases with moderate PE, 19 (group III) with severe PE; but U.K., high dose (UKf) 19 times; by U.K., moderate dose (UKm) 40 times, 3 cases with moderate PE, 37 cases (group V) with severe PE. After treatment, the mean volume of the venous clot, measured by the Marder's index, decreased in all groups. However, S.K. lysed 7 out of 17 proximal thrombosis, whereas the other treatments were unefficient. Failures were less frequent with S.K. (3/16) than with U.K. f (11/15), U.K.m (12/28) and H. (29/65). Recurrency was noticed 8 times: in 7 cases, it was seen in patients affected with proximal V.T. and not treated by I.V.C. interruption. Such facts warrant the systematic search for V.T. when PE is suspected. They justify the use of thrombolytic drugs not only for severe PE, but also for moderate PE which are associated to a proximal V.T.

The contribution of echocardiography in the management of thrombo-embolic disease.

To evaluate the contribution of echocardiography on the management of acute pulmonary embolism (A.P.E.) a study was carried out on 84 patients. For each of them echocardiography was performed: (a) the M mode shows an increase in RVDD/LVDD quotient correlated with the gravity of the A.P.E.; (b) the two dimensional mode allows 9 times the discovery of a thrombus which could be: static and broad based 6 cases or mobile, large sized 3 cases. So echocardiography can be systematically and initially be proposed for any patient suspected of having A.P.E.; (c) the absence of increase in RVDD/LVDD ratio 0.33 exclude the possibility of a serious A.P.E. and it is possible to postpone the pulmonary angiogram. On the contrary the increase of the RVDD/LVDD ratio must lead to the angiographic exploration due to the seriousness of A.P.E.: (d) the discovery of a mobile, large sized thrombus with hight embolic potential makes the catheterism of the right cavities dangerous and lead to an emergency embolectomy because of the high risks of a new A.P.E.

Value of real time B mode ultrasound imaging in the diagnosis of deep vein thrombosis of the lower limbs.

In order to determine the value and the role of real time B mode ultrasound imaging (USI) in the diagnosis of deep vein thrombosis (DVT) of the lower limbs, it was compared to bilateral contrast ascending venography used as a standard of reference, prospectively and systematically on 430 patients suspected of having DVT or pulmonary embolism. A total of 854 limbs were thus studied double blindly both by the two methods. The results corresponded in 95% of the legs with a sensitivity of 98% and a specificity of 95% for USI. Isolated thrombosis of the calf were detected in 91% of the legs and proximal thrombosis were in 100% in this series whatever their topography and extent should be and whatever be the degree of obstruction of the vein. The discrepancies between the two methods are related to: (a) Vein thrombosis especially located in the calf, in the soleal sinuses and the gastrocnemius with in most cases the direct image of the thrombus detected by U.S.I. more often than by venography, provided that the technique and the equipment are appropriate. (b) The absence of visualisation of venous segments with venography which is not specific of venous thrombosis. These veins when non affected by the thrombosis are not filled by the contrast medium if located above an occluded ilio-femoral or ilio-caval junction or when they are the site of extrinsic compression. The direct imaging of the vein and the surrounding structures obtained with USI enhances the diagnostic sensitivity and specificity and provides precision of the exact extension of the thrombosis. Venous study by USI is always coupled with the Doppler.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of venous thrombosis and pulmonary embolism by streptokinase.

We applied the standard treatment with streptokinase to 52 cases of deep venous thrombosis and 35 cases pulmonary embolism. Angiography demonstrated total lysis of the clot 22 times, partial lysis 42 times, and no lysis 23 times. The absence of lysis was more frequent in venous clots than in pulmonary clots. Early treatment was more effective, achieving complete lysis in 21 of 22 cases. Nevertheless, in deep venous thrombosis, late treatment can result in partial lysis and set an important venous junction free. With the standard treatment, the biologic controls showed good lysis in 75% of the cases, insufficient lysis in 15%, and no lysis in 10%. The extent of the thrombosis is an important point. The clot was totally lysed in 9 of 10 cases of localized deep venous thrombosis. In patients with pulmonary embolism, about 30% of the obstructed surface is cleared. Nevertheless, in such cases we must take into consideration not only the nonperfused pulmonary area, but also the venous starting point of the clot.

Comparison of two-dimensional echocardiography with scanography and indium-111 platelet scintigraphy in detection of intracardiac thrombi.

The authors compare three diagnostic-imaging methods (two-dimensional-echography, heart scans and indium-111 platelet scintigraphy) used in the detection of intracardiac thrombi in 82 patients. They attempt to define their respective diagnostic values in the presence of left ventricular and atrial thrombi.

[Thrombolysis in the pre-hospitalization phase of myocardial infarction]. / La thrombolyse à la phase préhospitalière de l'infarctus du myocarde.

In myocardial infarction (MI), the sooner thrombolysis is performed, the greater the chances of it being effective. We report a 19-month experience (July 1, 1986 to December 31, 1987) of thrombolysis performed at home prior to hospitalization by an organization called SOS Myocardial Infarction (SOS MI). Method. Throughout 24 hours, any patient may call by telephone a doctor attached to SAMU 13. If the doctor suspects a coronary emergency, he sends to the patient's home the SOS MI team (1 doctor and 1 nurse) in a medically-equipped ambulance. The diagnosis of MI is made on the finding of a nitroglycerin-resistant chest pain of more than 30 minutes duration associated with a more than 2 mm elevation of the ST segment on at least two electrocardiographic leads. Patients aged under 70 and in whom thrombolytic drugs are not contra-indicated are then treated intravenously with either streptokinase (1.5 million units over 30 min) or the tissue plasmogen activator (10 mg followed by a 90 mg infusion over 90 min). Results. During the 19-month period, 648 coronary emergencies were suspected from data given by telephone. The diagnosis made by the SOS MI doctor was non-coronary chest pain in 119 cases (18.4 p. 100), angina pectoris in 211 cases (32.6 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ergometrine test in 1200 consecutive patients presenting with normal coronary vessels]. / Le test à l'ergométrine chez 1,200 malades consécutifs présentant des coronaires normales.

An ergonovine test (ET) was performed in 1,200 patients-742 men, 458 women aged from 34 to 73 years (mean: 49.5 years)-either during (850 cases) or after (350 cases) coronary arteriography. Another ET made more sensitive by blocking the cardiac autonomous nervous system (CANS) with labetalol 0.04 and 2 mg/kg was performed in 291 of these patients. The ET test was positive in 10.7 p. 100 (127) of all patients and in 11.2 p. 100 (127/1125) of patients presenting with retrosternal pain. In the group where spontaneous angina could be confirmed by ECG recordings during the attack, the percentage of positive responses rose significantly to 53.7 p. 100 patients with ST depression and 56.6 p. 100 of patients with ST elevation. When the anginal nature of the retrosternal pain was not confirmed before the test, the proportion of positive responses was 6.6 p. 100. In patients who had the sensitized test the positive response rate increased in all groups and globally rose significantly from 7.9 p. 100 to 18.6 p. 100 (p less than 0.01). Thus, the usually low frequency of positive ergonovine tests differs according to the population selected and increases after CANS blockade.

[Pure coronary spasm: autonomic disease or form of onset of atheroma? Contribution of repeat coronarography in 23 patients]. / Angor spastique pur: maladie autonome ou forme de début de l'athérome? Apport de la coronarographie répétée chez 23 malades.

Coronary spasm has often been blamed for facilitating the development of atheroma, but some authors regard it as a separate disease. In order to form an opinion on these two theories, we performed repeat coronary arteriography at an interval of 4 years on average in 23 patients: 19 men and 4 women aged from 38 to 62 years (mean: 49,4 years). At the initial examination the coronary vessels were normal in 11 patients and showed irregular arterial walls without significant stenosis in 12 patients. Coronary spasm was demonstrated directly in 17 cases (6 spontaneous spasms during arteriography and 11 induced spasms) and indirectly in 6 cases (ECG signs of ischaemia during the anginal attack). At the second coronary arteriography we found that the spasms persisted, with positive response to a challenge test in 17 out of the 19 patients tested. The challenge test was not performed in 4 patients who had developed significant lesions. The vessels themselves were altered in 6 patients, with images of occlusion (2 cases), stenosis (2 cases), parietal irregularities (1 case) and aneurysm (1 case) appearing on spastic arteries, and images of stenosis in 2 patients with apparently non-spastic arteries. There was no difference in age, sex, risk factors, initial coronary status and time interval between arteriographies between these 6 patients and the 17 patients whose coronary arteries had remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of continous electrocardiography (Holter monitoring) in mitral valve prolapse]. / Intérêt de l'enregistrement continu de l'électrocardiogramme (procédé Holter) dans le prolapsus de la valve mitrale.

Twenty three patients with mitral valve prolapse underwent ambulatory 20 to 24 hour electrocardiography to study the incidence and severity of ventricular arrhythmias. These arrhythmias were found in 20 cases (87 p. 100). Ventricular extrasystoles were usually grouped (14 cases) causing doublets in 8 cases and bursts of ventricular tachycardia in the 6 others. The importance of the information obtained by Holter monitoring should not detract from the value of the standard resting electrocardiogramme. In fact, there appears to be a good correlation between the severity of the ventricular arrhythmia and the presence of ST changes over the postero-inferior zones. These abnormalities were never present in patients without ventricular extrasystoles but on the other hand they were observed in 5 of the 6 patients with ventricular tachycardia. From a practical point of view this may represent a simple means of identifying patients at high risk of dangerous arrhythmias.

[Disappearance of coronary collateral circulation during a crisis of spontaneous angina. The role of spasm]. / Disparition de la circulation collatérale coronarienne au cours d'une crise d'angor spontané. Rôle du spasme.

Disappearance of the collateral coronary circulation was observed during an attack of spontaneous angina. During coronary angiography, the patient developed precordial pain, ST depression in Leads I, II, III, AVL, AVF, and V2 to V6. The two coronary arteries were opacified: there was no change in the left coronary tree but the collateral circulation arising from the right coronary artery and revascularising the obstructed left anterior descending artery the ECG reverted to its previous state and the collateral circulation reappeared. This case suggests that coronary artery spasm may lead to disappearance of the collateral circulation. It raises problems of methodology in the demonstration of spastic phenomena and emphasises the role of the collateral circulation in the genesis of ischaemia. It is another illustration of coronary artery spasm accompanied by ST depression.

[Block of the autonomic nervous system in the study of sinus function]. / Blocage du système nerveux autonome dans l'exploration de la fonction sinusale.

Blockade of the autonomic nervous system by injection of propranolol (0,2 mg/Kg) and atropine (0,04 mg/Kg) was carried out in a series of 48 patients classified in 3 groups:--Group I:sinus bradycardia (22 cases)--Group II:suspected tachycardia-bradycardia syndrome (14 cases)--Group III:suspected sinus node dysfunction (12 cases). Two parameters were studied after autonomic blockade: observed intrinsic sinus node frequency (OIF) and corrected "adjusted" sinus node recovery time (CASRT). The results were compared with those obtained during basal electrophysiological investigation. The OIF was abnormal in 26 cases (54%) and junctional rhythm was observed 9 times (19%). Prolongation of the post-stimulation pause occurred in 32 cases (67%), transformation from a normal to a pathological pause in 15 cases and normalisation of a pathological pause in 4 cases (8%). Sinus node recovery time did not change significantly in the other cases. There was a good correlation between OIF and CASRT when the OIF was abnormal and mediocre (48%), when the OIF was normal. The following conclusions were made:--CASRT improves diagnosis of organic sinus node dysfunction which may escape detection by basal electrophysiological investigation and excludes functional abnormalities.--OIF is of good diagnostic value when pathological. However, the integrity of sinus node function cannot be affirmed when this parameter is normal.

[Medical treatment of ilio-caval venous thrombosis]. / Traitement médical des thromboses veineuses ilio-caves.

120 patients with ilio-caval thrombosis were managed medically. 55 patients were given heparin (5 mg/Kg/day for 15 days), 50 patients received streptokinase (loading dose 250,000 u; maintenance dose 100,000 m/h for 48 hours) and 15 patients had urokinase (112,500 u/h for 44 hours). Thrombolytic therapy was prescribed, in the absence of contraindications, for patients below 70 year of age: other patients were treated with heparin. The results were assessed by venography performed before and after treatment: success was defined as the complete disappearance of the thrombus of disobliteration of the ilio-caval axis. The overall success rate was 32%, with 68% failures. Success was higher with streptokinase (50%) than with heparin (20%) or urokinase (13%). The site, extension ans aetiology of the thrombosis did not affect the results. On the other hand, two other factors seemed to play an important role: - the duration of thrombosis: this only affected the streptokinase group; 23 of the 25 successes were obtained in patients treated before the tenth day. The results were unaffected by the duration of the thrombosis in the heparin group; - the biological effectiveness of therapy: 7 out of the 11 successes in the heparin group had been constantly well anticoagulated; there were only 4 successes out of 38 patients in whom the biological effectiveness had been intermittent. There were 21 successes out of 32 patients treated by streptokinase with serum fibrin levels of less than 1 g. There were only 4 successes in the 18 other cases. The incidence of haemorrhage was identical in the 3 groups. Embolism was slightly commoner in the streptokinase (3) than in the heparin group (2).

[Chemical blockade of the cardiac autonomic nervous system. Effects on the coronary arterial vasomotor activity]. / Blocage chimique du systéme nerveux autonome cardiaque. Effets sur la vasomotricité artérielle coronaire.

The results of cardiac plexectomy in spastic angina are controversial. This study was undertaken to evaluate the effects of blocking the cardiac autonomic nervous system (CANS) in this syndrome in 61 patients presenting with chest pain and angiographically normal coronary arteries. All patients underwent a methyl-ergometrine provocation test with a sequential protocol. They were then divided into two groups: Group 1 (13 patients): positive response to ergometrine. Group 2 (48 patients): negative response to ergometrine. Three sub-groups were identified: 2: 1: 9 patients with coronary spasm demonstrated by another method: 2: 2: 6 patients with myocardial infarction: 2: 3: 33 patients with chest pain alone. The results of these tests were compared with those obtained after blocking the CANS by intravenous injection over 3 minutes of an alpha and beta-blocker (labetalol 2 mg/kg) and a parasympathetic blocker (Atropine. 0.04 mg/kg). The CANS blockade was confirmed by two facts: the basal heart rate of 66.38 +/- 9.91 rose to ots intrinsic rate of 89.76 +/- 10.5 (p less than 0.01) and remained at that rate after ergometrine and trinitrate administration and myocardial ischaemia; changes in blood pressure were greater after CANS blockade: + 30.62 +/- 16.13 mmHg instead of + 8.62 +/- 0.33 mmHg after ergometrine (p less than 0.01) and -43.16 +/- 16.32 mmHg instead of -25.16 +/- 3.64 mmHg after trinitrate (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Antihypertensive effect of a new form of nifedipine compared to a beta-blocker during chronic administration]. / Etude de l'effet antihypertenseur d'une nouvelle forme de nifédipine comparée à un bêtabloqueur en administration chronique.

The aim of this study was to test the efficacy of a 20 mg tablet preparation of nifedipine alone in twice daily dosage, in the treatment of moderate hypertension (95 greater than or equal to DBP less than or equal to 115 mmHg). Efficacy was defined as the ability to maintain treatment for 6 months with a fall in DBP of a least 5 mmHg after the first month, and with a DBP 100 mmHg from the second month. One hundred and seventy seven patients were recruited from november 1981 to december 1982, 55% during the first three months of the trial. There were 95 men (54%) and 82 women, with a mean age of 55.6 +/- 10 years. The DBP ranged from 96 to 111 mmHg in 80% of cases. The patients were randomly allocated in lots of 6, to three groups: placebo (58 patients), nifedipine (57 patients) and acebutolol (61 patients). The comparability of 21 parameters amongst these 3 groups was verified. After 1 month of placebo, 25 patients did not meet the criteria of inclusion and were excluded from the study. During this phase, 19 patients (10.5%) complained of at least one side effect. Of the 152 patients who received active treatment, 34 (22.4%) were "wrongly included", 17 did not complete the test period for undefined reasons and were considered to have been "lost to follow-up", and 6 patients "deviated" from the protocol. These 3 groups were taken into account in the statistical analysis of the graphs of non-failure.