Plasma adrenaline and noradrenaline in patients with acute myocardial infarction. Relationship to ventricular arrhythmias of varying severity.

Plasma adrenaline (A) and noradrenaline concentrations (NA) were determined in 41 patients admitted to the coronary care unit (CCU). Eleven with suspected acute myocardial infarction (AMI), subsequently excluded as a diagnosis, had significantly elevated A and NA compared with 20 normal resting subjects. Patients with proven infarcts but no ventricular fibrillation had even higher levels of A and NA. Nine patients with ventricular fibrillation as a complication of AMI showed the highest plasma catecholamine values on admission. Patients with AMI and congestive heart failure exhibited substantially increased A, while NA was only slightly elevated compared with that of AMI patients without congestive heart failure. High plasma catecholamines and the relationship between adrenaline and the severity of ventricular arrhythmias suggest that the sympathetic nervous system plays an important role in sustaining a vicious circle of increased myocardial damage and increased irritability during the acute phase of AMI.

Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication.

The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized treatment period. A total of 302 patients were allocated to treatment with either placebo (154 patients) or indobufen (148) 200 mg twice daily. The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial (ICD) and absolute claudication distances (ACD). The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively. After six months' treatment with active drug or placebo, this parameter reached 227.9 +/- 174.4 and 153.1 +/- 86.8 m (mean +/- SD), respectively (p < 0.01). Similar results were obtained on ACD. The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen-treated patients. There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment. Adverse events of any type were reported by 18 patients (12.2%) in the indobufen group and by 11 patients (7.2%) in the placebo group. The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects.

[Basic concepts in hemodynamic monitoring in intensive care]. / Grundbegriffe der hämodynamischen Uberwachung in der Intensivmedizin.

The interpretation of hemodynamic measurements in intensive care must be based on a knowledge of how blood flow, blood pressure and blood volume are regulated. The adrenergic nervous system plays a pivotal role in control of these circulatory functions. Blood pressure and blood flow are regulated via the variation of heart rate, cardiac contractility, peripheral vascular resistance, and redistribution and retention of volume. The assessment of quantitative measurements and of formal abnormalities of detected pressure curves, in conjunction with considerations on compensatory mechanisms, render possible a logical approach to therapy.

[Long-term prognosis of pacemaker therapy in acute myocardial infarct with arrhythmias]. / Die Langzeitprognose der Schrittmacher-therapie beim akuten Myokardinfarkt mit Konduktionsstörungen.

The short- and long-term results of provisional pacemaker therapy in fresh myocardial infarction have been investigated. In this cardiac unit in the period 1975--1977 provisional pacemakers were implanted in 48 patients due to severe conduction disturbance or sinus node syndrome with non-tolerated heart failure. 16 patients had bifascicular block (11 anterior, 3 diaphragmatic, and 2 non-localizable infarctions): in 9 (56%) of them, progression to complete AV block occurred. 27 patients exhibited AV block of 2nd to 3rd degree without evidence of fascicular blockades (21 diaphragmatic, 3 anterior, and 3 non-localizable infarctions). In 5 patients, sinus node dysfunction was the reason for pacemaker implantation. Hospital mortality in the group was 31.2% and thus was twice as high as the hospital mortality in all patients hospitalized in this unit with myocardial infarction during the same period (16.5%). The hospital mortality in patients with anterior infarction was 57.2% compared with a mortality of 16.7% in patients with diaphragmatic infarction. Late mortality (18 months after myocardial infarction) in the group was 46.8%. None of the patients with diaphragmatic infarction died during this observation period. In the patient group with anterior infarction, the mortality rose to 85.8%. Of the 14 patients who died in hospital, death in 12 was due to severe heart failure: neither bradycardic nor tachycardic arrhythmias were immediate factors in death. At autopsy, all patients exhibited severe coronary sclerosis with extensive myocardial infarction. Only 2 patients died from arrhythmia (atrial fibrillation/asystole). In 6 of the 34 survivors, a definitive pacemaker was implanted. 3 of these patients died in the first year after the myocardial infarction. Death was sudden in all three.

[Stress hemodynamics in fresh myocardial infarct]. / Belastungshämodynamik beim frischen Myokardinfarkt.

Hemodynamic measurements before and during graded leg-up tilt were performed in 20 patients on the 1st and 3rd day following myocardial infarction. In those with an elevated pulmonary capillary pressure (greater than 11 mm Hg), independent of the cardiac index, the tilt-test (i.e. an additional increase in preload) unmasked heart failure. When applied to test drug responses, furosemide (n = 7) reduced the tilt-stimulated cardiac index with an attendant fall in pulmonary capillary pressure; nitroglycerine (n = 7) did not change cardiac index but reduced the pulmonary capillary pressure.

Electrophysiologic changes after tiapamil in coronary and noncoronary patients.

26 patients who had undergone right heart catheterization were enrolled in the study. The average age was 51.7 +/- 15 years. Half the patients showed coronary artery disease at selective coronary angiography. His bundle recordings and atrial pacing were performed before and 10 min after 1 or 1.5 mg/kg i.v. tiapamil. In addition, arterial blood pressure was recorded. P-R interval increased from a mean value of 153 +/- 36 to 168 +/- 49 ms (p less than 0.05) due to an increase in the A-H time from 88 +/- 19 to 97 +/- 23 ms (p less than 0.05). Arterial blood pressure and heart rate decreased significantly. These changes were more pronounced in patients with coronary artery disease. In the groups with the higher dosage, the differences from the control values were greater than in the patient groups receiving 1.0 mg/kg. Sinus node recovery time tended to increase in all groups but the differences did not reach significance. Patients with the 'sick sinus syndrome' were not studied.

[Hemodynamic consequences of the furosemide treatment of cardiac insufficiency in recent myocardial infarct]. / Hämodynamische Konsequenzen der Herzinsuffizienzbehandlung mit Furosemid beim frischen Myokardinfarkt.

Furosemide was administered intravenously to 11 patients with cardiac failure after acute myocardial infarction. After an initial loading dose furosemide was given four-hourly if the pulmonary capillary wedge pressure (PCW) was not normalized, i.e. less than or equal to 15 mm Hg. The comparison of the hemodynamic results with the results of a previous study with nitrates was as follows: like the nitrates furosemide lowered the PCW early, i.e. within 15 minutes from 22 +/- 3 to 18 +/- 5 mm Hg, but the therapeutic objective (PCW less than or equal to 15 mm Hg) was reached later than with nitrates. During the 24-hour observation period PCW and total peripheral resistance decreased steadily. The decrease of cardiac index to critical low values in some patients after a mean of 7.5 hours of therapy, and of the mean arterial pressure from 100 +/- 13 to 91 +/- 14 mm Hg, may limit the use of furosemide alone in these patients. During nitrate therapy PCW started to rise again after 12 hours in some patients, necessitating higher doses of nitrates with a corresponding decrease of diuresis. A combination of both forms of therapy may be of value and needs further investigation.

[Accuracy of clinical findings in patients with disturbed myocardial function in acute myocardial infarction]. / Treffsicherheit der klinischen Beurteilung von Patienten mit eingeschränkter myokardialer Funktion bei akutem Myokardinfarkt.

The relationship between clinical findings and invasively measured hemodynamic data was investigated in a prospective trial of 70 patients with acute myocardial infarction. In 26 out of 27 consecutive patients without clinical signs of disturbed myocardial function, normal hemodynamic values were also found invasively. In 43 patients, depressed myocardial function was diagnosed on the basis of the clinical findings. These findings were verified in 38 patients (88%) by means of cardiac catheterization; 5 patients (12%) had normal hemodynamic values. In 26 patients with clinical signs of congestive heart failure, an attempt was made to identify non-invasively those with a low output (cardiac index less than 2/min/m2). Only 3 of the 6 patients with a low output could be identified by clinical examination alone. In one patient a low output was clinically diagnosed despite normal cardiac function measured invasively. In 16 patients, 48 subsequent clinical examinations were performed during treatment of congestive heart failure to identify either persistent elevated left ventricular filling pressure or low output; 15 (31%) were found to be incorrect when compared with the cardiac catheterization data. Patients with acute myocardial infarction and normal ventricular function can be identified with high accuracy by means of clinical examination alone. The clinical diagnosis of congestive heart failure was incorrect in 12% of the patients. A low output state in acute myocardial infarction is often overlooked in clinical examination alone. Of the clinical examinations on patients during therapy, 30% were incorrect. Invasive hemodynamic monitoring in acute myocardial infarction therefore appears to be unnecessary in patients with normal clinical findings, but in those with clinically diagnosed congestive heart failure it is mandatory for precise indication and evaluation of therapy.

[Peroral nitrate therapy in severe cardiac insufficiency following acute myocardial infarct]. / Perorale Nitrattherapie der schweren Herz-insuffizienz nach akutem Myokardinfarkt.

Ten patients with severe congestive heart failure after acute myocardial infarction were treated with 40 mg isosorbiddinitrate-retard every 4 hours and additional sublingual nitroglycerine. There was a prompt improvement of hemodynamic parameters which was maintained for 24 hours: pulmonary capillary wedge pressure (PCW) decreased within 10 min from 26 +/- 5 (X +/- SEM) to 17 +/- 2 mm Hg (p less than 0.01) and mean arterial pressure from 109 +/- 7 to 98 +/- 6 mm Hg. The heart rate remained constant, and the cardiac index improved from 2.3 +/- 0.2 to 2.5 +/- 0.21/min/m2. The fall in blood pressure was dependent on the pretreatment pressure: it was significantly greater in patients with elevated blood pressure and only slight in those with a low pretreatment blood pressure. In the presented series of patients neither adverse effects or symptoms nor a critical reduction of blood pressure were observed. Combined oral treatment with isosorbiddinitrate and nitroglycerine can therefore be carried out without invasive blood pressure monitoring.

Antiarrhythmic effects of tiapamil on exercise-induced arrhythmias in patients with coronary artery disease.

57 patients were admitted to the study, 3-6 weeks after acute myocardial infarction. They received either placebo or 1 mg/kg tiapamil intravenously according to a randomized, double-blind procedure. The study had two objectives: (a) to assess the effect of tiapamil on work tolerance and exercise-induced myocardial ischemia: (b) to demonstrate possible antiarrhythmic effects against exercise-induced arrhythmias. The duration of exercise and physical work capacity increased slightly in both groups, these effects, however, not reaching statistical significance. On the other hand, the number of exercise-induced extrasystoles did not change significantly under placebo but decreased from 30.9 to 14.8 beats/min after tiapamil (p less than 0.01). No side effects were observed. While the hemodynamic effects of tiapamil in patients with coronary artery disease are yet to be elucidated, our findings confirm the efficacy of this calcium antagonist against exercise-induced ventricular premature beats in patients with coronary artery disease.

[Iloprost in the treatment of ischemic tissue lesions in diabetics. Results of a placebo-controlled multicenter study with a stable prostacyclin derivative]. / Iloprost in der Behandlung ischämischer Gewebsläsionen bei Diabetikern. Ergebnisse einer placebokontrollierten Multizenterstudie mit einem stabilen Prostazyklinderivat.

The efficacy of iloprost, a stable prostacyclin analog, was investigated in a placebo-controlled trial in 109 diabetics with ischemic lesions. 56 patients were randomly allocated to iloprost and 53 patients to placebo. Iloprost was intravenously applied for 6 hours daily on 28 consecutive days at an individually tolerated dose up to 2 ng/kg/min. The control group received identical solvent volumes. In addition all patients had an intensive basic, mainly local, therapy. At the end of the treatment in the iloprost group 31 of 50 patients (62%) showed partial (greater than 30%) or total healing of the lesion(s). In the placebo group this was the case in 12 of 51 patients (22.5%). The difference of 38.5% was statistically significant (p less than 0.05, chi 2-test, alpha = 0.05, beta = 0.1). The percentage of patients who were free of pain increased from 23% to 42% (+19%) in the iloprost group and from 38% to 48% (+10%) in the placebo group. After dose-titration iloprost was well tolerated. Flush, headache and abdominal complaints were the most frequent side effects. Heart rate and blood pressure were not influenced and the control of diabetes was not altered.

[Iloprost, a stable prostacyclin derivative, in stage 4 arterial occlusive disease. A placebo-controlled multicenter study]. / Iloprost, ein stabiles Prostacyclinderivat, bei arterieller Verschlusskrankheit im Stadium IV. Eine placebo-kontrollierte Multizenterstudie.

The effectiveness of iloprost, a prostacyclin derivative, was assessed in a placebo-controlled multicentre trial on 101 patients with chronic arterial disease, stage IV. All patients were on a basic local treatment, 53 randomly being assigned to the iloprost group, 48 to the placebo one. Both groups received identical saline infusions, one with the other without iloprost. Infusions were given on 28 consecutive days, iloprost being added at a dose of up to 2 ng/kg.min over six hours. At the end of the treatment period, 32 of 52 patients (61.5%) of the iloprost group and eight of the 47 in the placebo group (17%) had partial or complete healing of ulcers (P less than 0.05), the treatment effect persisting in both groups for a mean duration of at least one year. Iloprost was well tolerated, once individual dosages had been appropriately adjusted. Facial flushes, headache and nausea were the most common side effects. Heart rate and blood-pressure variations did not differ between the two groups.