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In acute myocardial infarction a third up to half of death registered within the first month occur in the first hour of the onset of attack most frequently because of ventricular fibrillation. Immediate self administration of drugs stabilizing electrically the heart may prevent it. On the basis of experiments in dogs and in rats flunitrazepam (Rohypnol tabl. 1 mg), tramadol (Tramal caps. 50 mg) and the beta blocker metipranolol (Trimepranol tabl. 10 mg) were selected for clinical trial on high risk patients. As the chosen combinations of drugs were not yet tested in view of possible interactions, we studied their effect on circulation and cardiovascular reflexes in eight healthy volunteers. When the drugs were absorbed from the mouth mucosa, the decrease in the heart rate during deep breathing was observed already 15 minutes after the intake of drugs. The subjects started to feel relaxed; later on they had pleasant feelings and felt sleepy. There were no undesirable changes in the heart rate or blood pressure. In the three drug combination with metripranolol, the decrease in the heart rate was more marked. The tests in volunteers were without any undesirable effects and both combinations may, therefore, be given to selected high risk subjects, e g. convalescents from myocardial infarction. Randomized trial to prove the preventive effect already started.

Functional disorders of the circulation imply an inadequate circulatory response to repeated, in particular mental strain, associated with typical complaints and manifestations. Instead of the formerly used term of neurocirculatory asthenia nowadays neurotic conditions with manifestations in the circulation are described more frequently as hyperventilation syndrome, syndrome of chronic fatigue or panic anxiety syndrome. The paper deals with the pathogenesis, diagnosis, prognosis and therapy where a talk with the patient, elucidating the relationship between the stressing situation and circulatory manifestations is most important.

Acute local myocardial ischaemia is associated with a decrease in baroreflex sensitivity while electrical instability (vulnerability) of ventricles increases. Co-administration of a benzodiazepine and a potent analgesic (analgosedation) has been found to raise both baroreflex sensitivity and ventricular fibrillation threshold. Pharmacological modulation of neurovegetative ionization of the heart in the early phase of ischaemia is a promising method for preventing sudden coronary death.

In acute local myocardial ischaemia produced in mongrel dogs, the sensitivity of baroreflex decreased as electrical instability (vulnerability) of cardiac ventricles increased. Simultaneous administration of a benzodiazepine and a powerful analgesic (analgosedation) augmented both baroreflex sensitivity and ventricular fibrillation threshold. Modulation of neurovegetative activation of the heart by drugs in the early stage of ischaemia holds promise as a potential technique of sudden coronary death prevention.

The following results were obtained in an experimental study in the dogs in general pentobarbital anaesthesia: Lidocaine type antiarrhythmics (lidocaine, Xylocaine ASTRA, Ethmozin USSR) administered shortly before artery ligation have a pro-fibrillation effect. This effect is indirectly proportional to the ischaemic focus development. A 3rd-generation beta blocker with intrinsic sympathetic activity (celiprolol, Selectol Chemie-Linz) had the same electrostabilizing effect on the ventricles in the acute phase of ischaemia as a 1st-generation beta blocker (metipranolol, Trimepranol SPOFA). The 3rd-generation blocker, however, stopped short of provoking a drop in the heart rate invariably associated with the 1st-generation beta blocker. The analgesic fentanyl (G. Richter) in combination with benzodiazepine (m,idazolam, Dormicum Hoffmann-La Roche) inducs analgosedation. In this way the dose of the analgetic can be reduced and yet the analgesia and electrostability of the heart remain the same. Due to the lower dose of the analgesic there is a lesser decrease in the heart rate and blood pressure. Analgosedation can be discontinued by administering an antagonist-agonist of benzodiazepines (flumazenil, Anexate Hoffmann-La Roche) or an antagonist of potent analgesics (butorphanol, Beforal SPOFA) without the risk of eliminating, at the same time, the electrostabilizing effect of analgosedation on the ischaemically damaged ventricles of the heart. For the prevention of sudden coronary death due to ventricular fibrillation in the acute phase of local myocardial ischaemia we can, on the basis of our experimental results, recommend analgosedation and the use of beta blockers with intristic sympathetic action. The use of lidocaine antiarrhythmics may lead to a reduction in the electric stability of the heart ventricles the ischaemic focus is developing under a certain "critical" blood level of the antiarrhythmics.

To determine the effect of strong analgesics on electrical instability (vulnerability to ventricular fibrillation), we examined the action of fentanyl (60 micrograms/kg), sufentanil (10 micrograms/kg) and carfentanil (3 micrograms/kg) on the ventricular fibrillation threshold (VFT) in a dog model of coronary artery occlusion. The effect of strong analgesics was compared with that of the first-generation beta-blocker propranolol (1.2 mg/kg) and the third-generation beta-blocker celiprolol (3 mg/kg). In the 5th minute of ischaemia, VFT declines in all groups of dogs. VFT values rise significantly from the 23rd to the 60th minute of ischaemia after opiate analgesic administration. The mean increase in VFT after opiate analgesics is less pronounced than after beta-blockers. Administration of opioid analgesics is followed by strong prevalence of vagal drive to the heart. Sympathetic drive to the heart after propranolol administration disappears and is depressed after the administration of celiprolol only. Blockers of the beta-receptors apparently intervene directly in the ischaemic focus and affect the "substrate" of electrical instability. The opioid analgesics probably exert their effect through a change in "substrate" modulation. There is an ongoing search for drugs that would stabilize the heart electrically in acute myocardial infarction, thus preventing sudden death. Our experimental results favour a combination of strong analgesics with other electrostabilizing drugs.

A health educational film on the psychosocial problems of their illness and recovery was viewed by 51 male patients with myocardial infarction. The attractiveness of the topic was tested and found to be high. Reactions elicited by separate messages of the film during the performance were recorded: their rate rose significantly after statements concerning mostly psychosocial aspects of recovery. On behalf of 13 criteria the film was evaluated by the patients medium positively with differences depending on their education. Viewing of the film changed the kind and structure of expressed demands for more health information and made them more concrete.

The fall in the ventricular fibrillation threshold during the first half an hour following ligation of the descending branch of the left coronary artery in dog was not influenced by the i.v. injection of trimecain (Mesokain Spofa). On the other hand, an i.v. injection of methypranol (Trimepranol Spofa) given prior to ligation increased the level of ventricular fibrillation threshold 3 to 4 times compared to control value before occlusion in all 10 studied dogs. Depression of the beta-blocking adrenergic activity may thus prevent the occurrence of ventricular fibrillation in acute myocardial ischaemia.

The pathogenesis of electrical instability of tissue in the earliest phase of ischaemia is well known. Convincing results in the prevention of ventricular fibrillation at this stage have been obtained only by agents inhibiting sympathetic activation of the heart, or by agents significantly prolonging the refractory period of heart cells. On the other hand, it was documented that sodium channel inhibitors are not suitable for prevention of electrical instability in the early phase of ischaemia and can, on the contrary, aggravate it. A question which is still unresolved and deserves further research is the effect of calcium channel inhibitors and of agents acting directly on the metabolism of ischaemic tissue.

Using a model of local myocardial ischaemia in the dog, the authors studied the electrostabilizing effect of a combination of the benzodiazepine midazolam (Dormicum Hoffman--La Roche) and the strong narcotic analgesic drug Fentanyl (Richter). The electrostabilizing effect was assessed using the method of ventricular fibrillation threshold (VFT) measurement. The same increase in the fibrillation threshold as that induced by the administration of midazolam or fentanyl alone was achieved by a combination of both drugs given, however, in reduced doses. The electrostabilizing effect of benzodiazepines and potent analgesics is enhanced by their simultaneous administration. At the same time, the adverse side effects observed on the administration of fentanyl alone (bradycardias, hypotension, cardiac blockade) due to the prevalence of parasympathetic drive, are reduced. Simultaneous administration of a benzodiazepine and an analgesic has become a modern technique, in anaesthesiology, so-called analgosedation. Experiments have shown the technique, in addition to the generally recognized analgesia, sedation and anxiolysis, exerts electrostabilizing effects on the myocardium damaged by ischaemia. The authors therefore recommend analgosedation in the drug treatment of acute myocardial infarction.

1. Benzodiazepines and strong analgesics raise considerably the ventricular fibrillation threshold and thus electrically stabilize the heart in the early stage of myocardial ischaemia. 2. Benzodiazepines markedly potentiate the electrostabilizing effect of the beta-blocker metipranolol. 3. Trimecaine per se does not electrically stabilize the heart in the first hour of ischaemia. When combined with a benzodiazepine, trimecaine stabilizes the heart also in this early stage of myocardial ischaemia. 4. Infusion of a benzodiazepine (midazolam) combined with fractionated administration of a potent analgesic (fentanyl) does not produce pronounced changes in the haemodynamics and ventilation of healthy subjects. 5. Benzodiazepines and strong analgesics exert a favourable effect on the neurovegetative stress response in the early stage of acute myocardial ischaemia. They can be therefore recommended as a component in the treatment of patients with acute myocardial infarction.