Efficiency and mechanisms of the antioxidant effect of standard therapy and refracterin in the treatment of chronic heart failure in elderly patients with postinfarction cardiosclerosis.

Refracterin therapy of patients with chronic heart failure caused by coronary heart disease and postinfarction cardiosclerosis markedly promoted improvement in the pulmonary and systemic circulation in comparison with patients receiving traditional therapy. The mean functional class of chronic cardiac failure decreased by 43% under the effect of refracterin vs. 27% decrease in the group receiving traditional therapy. After 1-month refracterin course the end-systolic and end-diastolic sizes of the left ventricle decreased by 12 and 7%, respectively, ejection fraction increased by 7.2% in comparison with the initial level, total oxidant activity and MDA content in the plasma decreased significantly, while total antioxidant activity, catalase and SOD activities, cytochrome C, NADH, and NADPH levels increased. The prooxidant-antioxidant system was shifted towards antioxidants, which attests to activation of the defense and adaptive mechanisms after administration of refracterin, which is especially important in elderly patients with initially decreased reserve potentialities of the antioxidant defense system.

[Ageusia as the aftereffect of oxyfedrine use]. / Ageusia jako nastepstwo ubocznego dzialania oksyfedryny.

Out of oxyfedrine++ side effects known up to the present (mild agitation, stupor, heat sensation, pains in the epigastrium++, skin allergy) 24 cases of ageusia appearing usually after 4 weeks of treatment with oxyfedrine++ were presented. Disturbances of taste are found to be unpleasant for patients, and result in remarkable exacerbation of their general feeling. The complaints subside completely after finishing treatment, and the time of taste disorder withdrawal is prolonged according to the time of oxyfedrine++ treatment.

Effect of intravenous oxyfedrine on exercise in patients with ischaemic heart disease.

In a double blind crossover trial, acute effects of 8 mg intravenous oxyfedrine were compared with those of placebo in 18 patients with stable effort angina assessed by treadmill exercise testing. In the resting state, oxyfedrine caused an increase in heart rate (84 +/- 23 to 103 +/- 19 bpm, p less than 0.01), systolic blood pressure (123 +/- 16 to 133 +/- 20 mmHg, p less than 0.01) and double product (11 x 10(3) +/- 2 x 10(3) to 13.7 x 10(3) +/- 3.1 x 10(3), p less than 0.01) as compared to placebo. However, these parameters were not significantly different at the end of first or second stage of the treadmill test (p = NS). Time to one mm ST segment depression was increased with oxyfedrine as compared to placebo (1.5 +/- 1.5 to 1.9 +/- 1.5 minutes, p less than 0.05). Oxyfedrine did not increase the total duration of exercise (4.1 +/- 1.0 to 4.7 +/- 2.2 minutes, p = NS) or time to ischaemic symptoms (2.7 +/- 1.3 to 2.9 +/- 1.9 minutes, p = NS). The total work done was significantly more on oxyfedrine 312 +/- 189 joules/kg to 370 +/- 209 joules/kg, p less than 0.01) as also the double product achieved (20.6 x 10(3) +/- 6.1 x 10(3) to 22.5 x 10(3) +/- 6.4 x 10(3), p less than 0.01). It is concluded that intravenous oxyfedrine improves exercise capacity in patients with stable effort angina presumably by reducing myocardial ischaemia.

Haemodynamic effects of intravenous and oral alifedrine in patients with cardiac failure.

A randomized, double-blind, double-crossover, placebo-controlled haemodynamic study was undertaken in patients with Grade II/III (NYHA) cardiac failure to examine the acute effects of intravenous alifedrine, 20 mg and 40 mg (17 patients), and oral 40 mg alifedrine (8 of these patients). Patients received single doses of alifedrine and placebo on separate days, with invasive monitoring. Alifedrine resulted in a significant (p less than 0.001), dose-dependent increase in cardiac output. The peak effect (+23% with 20 mg i.v., +42% with 40 mg i.v. and +29% with 40 mg orally) was seen approximately 1 hour after intravenous administration (with about half of these increases still apparent at 3 hours) but developed progressively over 3 hours after oral administration. There were significant reductions (p less than 0.001) in peripheral resistance (peak mean changes -21% with 20 mg i.v., -31% with 40 mg i.v. and -23% with 40 mg orally), but little (less than +/- 6%) observed change in arterial pressure. With intravenous alifedrine, there were significant increases in stroke volume (+19% with 20 mg, +35% with 40 mg, p less than 0.001) with little (5%) change in heart rate (+3% and +7%, respectively, N.S.). With the 40 mg oral dose, there was a small increase in heart rate (+12%, p less than 0.005) associated with a 19% (N.S.) increase in stroke volume. Peak haemodynamic responses to 40 mg alifedrine orally were 50% to 75% of those seen after administration of the same dose intravenously. When assessed 3 hours after administration, responses to the two routes of administration were similar. There were no clinically or statistically significant changes in arterial (non-invasive), pulmonary artery, pulmonary capillary or right atrial pressures with any dose of alifedrine. No significant arrhythmias were noted clinically with the doses studied. Alifedrine, therefore, is an interesting agent, available both orally and intravenously, which is well tolerated and appears to produce marked acute increases in cardiac output with little change in heart rate or blood pressure. Further studies should determine whether these effects are maintained during longer-term therapy and clarify the relative contributions of positive inotropic and peripheral vasodilator activity to the effects observed.

[Enhanced cytotoxic effect of Adriamycin and vincristine against PC-6 (human lung cancer cell line) and Hattori (human breast cancer cell line)].

Enhancements of cytotoxic effects of adriamycin (ADM) and vincristine (VCR) on PC-6 (lung cancer cell line) and Hattori (breast cancer cell line) were investigated by concomitant use of a calmodulin inhibitor: nicardipine, antiplatelet agents: oxyfedrine and trimethazidine and an antihypertensive agent: trichlormethiazide. Nicardipine increased the cytotoxic activity of both drugs but other agents did not produce any significant increase. Nicardipine increased the cytocidal effect of VCR on PC-6 about 2-fold and on Hattori about 3-fold. Furthermore, it also increased the effect of ADM on Hattori about 2-fold. Thus, nicardipine enhanced the cytocidal activity of VCR more remarkably than that of ADM.

[Experimental myocardial infarct in computerized tomography]. / Der experimentelle Myokardinfarkt im Computertomogramm.

The findings on computer tomography after ligation of the coronary artery of a dogs heart are described. The ischaemic area can be differentiated from normal myocardium by its hypo-dense appearance. The localisation and size of the ischaemic area correlates with the scintigraphic findings. The known morphological and functional changes after intravenous oxyfedrin (positively inotropic, increased myocardial blood-flow) can also be seen on the computer tomogram (after oxyfedrin: myocardial thickening, reduction in cross-sectional area of the left ventricle, improved contraction, increased density of the ischaemic area). This confirms the possible diagnostic role of CT in the elucidation of changes in the left ventricle in the course of coronary disease.

[Effect of nonachlazine and oxyfedrine on central processes regulating vasomotor tone]. / Vliianie nonakhlazina i oksifedrina na protsessy tsentral'noi reguliatsii vazomotornogo tonusa.

Effect of the antianginal drugs nonachlazin and oxyfedrin on tonic and evoked activity in sympathetic renal nerves and on vasomotor reflexes induced by stimulation of the tibial nerve was studied and compared in anesthetized cats with intact brain. Low doses of nonachlizin facilitated somatosympathetic reflexes. High doses of the drug induced a selective inhibition of somatosympathetic reflexes evoked by stimulation of high-threshold afferent A-fibers. The inhibition of somatosympathetic reflexes induced by oxyfedrin had no such a selectivity and was less prolonged. The effects of nonachlazin and oxyfedrin attained after the administration of reserpine and propranolol allow a conclusion that the central effects of nonachlazin and oxyfedrin are related to the fact that they modulate the adrenergic brain structures.

[Effect of nonachlazine and oxyphedrin on a focus of myocardial ischemia]. / Vliianie nonakhlazina i oksifedrina na ochag ishemii miokarda.

In experimental angina pectoris of dogs developed by Sze-keres et al, 1976, and modified by the authors it was shown that nonachlazine in doses of 3 and 5 mg/kg decreased or even completely prevented the ST segment elevation on the epicardial electrogram from the focus of myocardial ischemia. Oxyphedrine in doses of 0.05, 0.1, and 0,3 mg/kg had no such effect. In doses of 0.1 and 0.3 mg/kg the drug aggravated the epicardial electrogram.

The bio-availability of beta-acetyldigoxine (Novodigal) alone and combined with oxyfedrine (Ildamen-Novodigal).

The bio-availability of various galenic preparations of beta-acetyldigoxine was tested in six healthy probands after a single oral dose (1 mg). The availability parameters were calculated from the areas under the plasma concentration curves and from the cumulative urinal excretion. There was no significant difference between the bio-availabilities of Novodigal (beta-acetyledigoxine tablets), Ildamen-Novodigal (beta-acetyldigoxine and oxyfedrine) and an alcoholic solution of beta-acetyldigoxine. Correlation calculations showed that the determination of the plasma concentration courses up to six hours after substance application are most favourite in regard to judging the absorption processes of digoxine preparations. For the assessment of the bio-availability, the methods of comparing the areas under the blood level curves of 0 to 6 hrs and of comparing the cumulative urinal excretion over a period of 24 hrs were of equal validity.

Excretion of norephedrine by man after oral administration of oxyfedrine.

After oral administration of oxyfedrine to healthy volunteers, norephedrine was identified in the urine by thin layer chromatography and gas liquid chromatography and mass spectrography. 30 hours after single oral doses of 8, 16 or 24 mg of oxyfedrine, about 4, 8 and 9 mg, respectively, of norephedrine were found in the urine, i.e. on a molar base 75-100% of the dose was excreted as norephedrine. The peak of excretion occurred within 2-4 hours after administration of the drug. No accumulation of oxyfedrine and/or its metabolite was observed after administration of 16 mg of oxyfedrine t.i.d. for three days. It could not be decided whether oxyfedrine was metabolized to norephedrine by liver enzymes, as in rats, or was spontaneously degraded to norephedrine, e.g. in duodenal fluid before absorption. 30-150 min after oral oxyfedrine (24 mg) norephedrine was demonstrable in duodenal fluid. Thus, in addition to the direct beta-sympathomimetic effects of oxyfedrine, it may also have indirect sympathomimetic effects because of the noradrenaline-releasing properties of its metabolite norephedrine.

[Influence of coronary-effective substances on the concentration of nonesterified fatty acids in the serum of patients with angina pectoris]. / Der Einfluss koronarwirksamer Substanzen auf die Konzentration der unveresterten Fettsäuren im Serum bei Patienten mit Angina pectoris

In a study of patients with angina pectoris the influence of coronary-effective medicaments on the concentration of non-esterified fatty acids was investigated. Supplementary establishments were carried out experimentally on pigs. Compared with normal persons patients with angina pectoris had a significantly higher level of non-esterified fatty acids. In an oral dose of 150 mg a day propranolol decreased the non-esterified fatty acids to normal values. Dipyridamol decreased the concentration of non-esterified fatty acids in the serum in an average dose of 450 mg a day also significantly. The combination of propranolol and dipyridamol did not evoke a particular additive effect on the decrease of non-esterified fatty acids. In a dosage of 300 mg a day orally trapymin had no clear influence on the non-esterified fatty acids. D,L-oxyfedrin (64 mg orally a day) increased the concentration of the non-esterified fatty acids in the serum. The decrease of the level of non-esterified fatty acids seems important for the prophylaxis of the infarction. The antilipolytic effect is a desirable therapeutic mechanism among others in the coronary therapy.