Intravenous clonidine in acute myocardial infarction in men.

We studied the effects of intravenous clonidine treatment in a group of 24 patients with acute myocardial transmural anterior and/or lateral wall infarction. Clonidine, known as an antihypertonic agent, was administered as a bolus of 1-2 micrograms/kg body weight and repeated every 2-3 hr. However, maximal range of the time interval was 20 min to 4 hr, maximal range of doses 37 to 150 micrograms, depending on the hemodynamic status. The effects were measured by precordial electrocardiographic mapping as well as serial creatine phosphokinase determinations. A big decrease in ST-segment elevation was observed: sigma ST reduction after 24 hr was 37% of initial value (140% in control group), after 48 hr - 30% (120% - control); NST fall after 24 hr - 45% (145% - control), after 48 hr - 41% (142% - control). NQ increased after 24 hr to 135% of initial value (156% - control), after 72 hr to 137% (167% - control). Detailed analysis revealed undoubted correlation between the dosage and favourable dynamics of precordial mapping parameters. Hemodynamic, antiarrhythmic and above all adrenolytic activity were noted. The treatment caused a distinct deterioration in daily adrenalinuria mean values to 5.99 micrograms in the first day (14.20 - control) and lower in the following days. No side effects were observed but sudden discontinuation of the therapy caused an unfavorable reaction. A temporal association between diminished adrenalinuria and both clinical improvement and limitation of infarct size was observed. Therapy with intravenous clonidine requires meticulous individualization of clonidine dosage depending on the patient's initial hemodynamic status.

[Ventricular arrhythmias and the ATc index in patients with ischemic heart disease]. / Komorowe zaburzenia rytmu serca a wskaznik QTc u chorych z choroba niedokrwienna serca.

In this multicenter study a group of 1,011 patients (233 females and 778 males, aged 23-68 years, mean 53) with ischaemic heart disease was included. Only nitrates, nifedipine and diuretics were administered during the investigation. Presence of other chronic disease excluded the patients from study group. In all patients a standard 12-lead electrocardiogram was obtained, from which the QT interval was measured, and its corrected value according to the Bazett's formula calculated [formula: see text] values greater than 440 ms were regarded to be abnormal. A 24-hour ecg ambulatory monitoring was also performed in each patient, and the detected ventricular ectopic activity was classified using the Lown's criteria. Mean QTc values were compared between each class of ventricular arrhythmia. No significant differences were disclosed. All the means were below 440 ms. Also the percentages of patients with a prolonged QTc were similar for all Lown classes of arrhythmia. The patients were then divided into two larger groups: Those with low grade (class 0-2) and high grade (class 3-5) arrhythmia. The portion of patients with the pathologic QTc was not significantly different (21% vs. 28%, NS). Such incidence of QTc prolongation was described for clinically healthy population. Since a 24-hour ecg fails to disclose the entire spectrum of arrhythmia in each individual, the fraction of patients with documented VT/VF in the past was analyzed separately. This subgroup was characterized by more frequent occurrence of QTc prolongation than other patients (35% vs. 20%, p = 0.043). Thus, no firm relationship was found between QTc prolongation and ventricular arrhythmias, but increased QTc favoured the occurrence of VT/VF.

[Pro-arrhythmic effects of antiarrhythmic drugs in patients with ischemic heart disease]. / Proarytmiczne dzialanie leków Przeciwarytmicznych u chorych z choroba niedokrwienna serca.

The incidence of proarrhythmic effect of antiarrhythmic drugs (AADs) in not well documented. The aim of the study was to assess the frequency od proarrhythmia in patients with ischemic heart disease (IHD) and ventricular premature beats (VPBs) in whom various class I, II and III AADs were tested by 24-h Holter ecg. All data were collected in a prospective manner. Our material consisted of 639 patients with IHD and VPBs (Lown's grade 2-5). The mean age was 53 years. 63% of patients had previously myocardial infarction. 15% and 3% had documented ventricular tachycardia (VT) or ventricular fibrillation (VF), (VF), respectively. Baseline Holter monitoring revealed repetitive VPBs or R on T phenomenon in 64% of cases. Plasma electrolytes level, renal and hepatic function were normal. Antiarrhythmic therapy was guided by repeated 24-h Holter ecg on a maintenance dosage of the drug. Propranolol was a drug of first choice. Disopyramide or mexiletine was added if propranolol alone was found to be ineffective in control Holter ecg. Amiodarone was a drug of a next choice. It was allowed modify the treatment in patients with contraindication to propranolol, clinical VT/VF or high grade VPBs. 794 drug tests were conducted. Number of tests/patient ranged 1-4. The following AADs were assessed: propranolol (352 tests), disopyramide (280 tests), mexiletine (73 tests), amiodarone (89 tests). Aggravation of arrhythmia was defined by modified criteria proposed by Velebit: 1) greater than or equal to 4-fold increase in VPBs, 2) greater than or equal to 10-fold increase in couplets or salvoes, 3) occurrence of VT. Proarrhythmia was recognized when at least one criterion was present.(ABSTRACT TRUNCATED AT 250 WORDS)

[Imidazoline receptors and use of drug blocking receptors I1]. / Receptory imidazolinowe i stosowanie leków blokujacych receptory l1.

Imidazoline-preferring receptors are important in the pathophysiology of hypertension. The selective l1-receptor agonists are moxonidine, cimetidine and rilmenidine. Some clinical studies indicate the usefulness of moxonidine therapy in hypertension, arrhythmias and acute myocardial infarction.

[Influence of nitrates on red blood cell deformability and clinical parameters in patients with silent ischemia]. / Wplyw azotanów na odksztalcalnosc krwinek czerwonych i parametry kliniczne chorych z niemym niedokrwieniem.

In 30 patients after myocardial infarctum with actual silent ischemia (no pain during last 12 months) mononitrate (Olicard 40) was administered and red blood cell deformability was determined. Clinical improvement and decrease of aforementioned deformability were observed after mononitrate therapy.

[Clinical effect of nitrates (Olicard 40) and their influence on deforming of erythrocytes against the background of 24-hour catecholaminuria]. / Kliniczne efekty nitratów (Olicard 40) i ich wplyw na odksztalcalnosc krwinek czerwonych na tle dobowej katecholaminurii.

Progress in the investigations upon factors influencing the course of the ischemic heart disease focused our attention on the deformability of erythrocytes. That attribute of the red blood cells (RBC) is described by their susceptibility to changes in shape without changing volume. Because of that feature, RBC can reach the smallest capillaries of the circulatory system. The aim of the study was to determine the influence of mononitrates (Olicard Ret.) on the deformability of RBC (EDI) in correlation to the clinical course of the ischemic heart disease and to evaluate the role of catecholamines in the course of the disease and their influence upon EDI. 30 patients (pts) treated with mononitrates for 4 weeks were enrolled into the study. In 27 pts clinical improvement was recorded, as evaluated by the results of repeated exercise tests and changes in the number of anginal attacks. Mean weekly number of anginal attacks decreased from 6.2 to 2.1 (p < 0.05), and parameters of exercise tests improved: DP/Wmac decreased from 0.694 to 0.479 (p < 0.001) and maximal workload attained increased from 6.8 to 9.0 METS (p < 0.001). Correspondingly to the clinical improvement, beneficial changes in RBC deformability were seen: 0.033 vs 0.040 (p < 0.01). Correlation factor for changes in EDI (r = 0.628) was higher than that for the number of anginal attacks (r = 0.589), but lower than the correlation factor for exercise test parameters (r = 0.969 for DP/Wmax and r = 0.858 for METS). There were no significant changes in the urinary output of catecholamines and no correlations were seen between urinary output of adrenaline, noradrenaline and EDI.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis of microspheres of triuranium octaoxide by simultaneous water and nitrate extraction from ascorbate-uranyl sols.

A new method for synthesis of uranium oxide microspheres (diameter <100 µm) has been developed. It is a variant of our patented Complex Sol-Gel Process, which has been used to synthesize high-quality powders of a wide variety of complex oxides. Starting uranyl-nitrate-ascorbate sols were prepared by addition of ascorbic acid to uranyl nitrate hexahydrate solution and alkalizing by aqueous ammonium hydroxide and then emulsified in 2-ethylhexanol-1 containing 1v/o SPAN-80. Drops of emulsion were firstly gelled by extraction of water by the solvent. Destruction of the microspheres during thermal treatment, owing to highly reactive components in the gels, requires modification of the gelation step by Double Extraction Process-simultaneously extraction of water and nitrates using Primene JMT, which completely eliminates these problem. Final step was calcination in air of obtained microspheres of gels to triuranium octaoxide.

Intravenous clonidine treatment in acute myocardial infarction (with comparison to a nitroglycerin-treated and control group).

This study describes the effects of intravenous clonidine treatment in a group of 24 patients with acute myocardial transmural anterior and/or lateral wall infarction. Clonidine was administered as a bolus injection of 1-2 micrograms/kg body weight and repeated every 1-3 h. The range of the time of administration varied from 20 min to 4 h, with the maximal range of doses from 37 to 150 micrograms, depending on the hemodynamic status. The effects were measured by precordial electrocardiographic mapping and compared with similar effects obtained in the nitroglycerin-treated group (30 patients) and a control group (12 patients). A large decrease in ST segment elevation was observed. The ST reduction after 24 h was 37% of initial value (compared with 52% in the nitroglycerin group, 140% in the control group); after 48 h there was a 30% reduction (compared with 55% in the nitroglycerin group and 120% in the control group). After 24 h there was a fall in NST of 45% (71% with nitroglycerin and 145% in the control group); after 48 h there was a 41% decrease (compared with 65% in the nitroglycerin group and 142% in the control group). New Q waves increased after 24 h to 135% of the initial value (compared with 122% in the nitroglycerin group and 156% in the control group); after 72 h this increased to 137% (128% in the nitroglycerin group and 167% in the control group). Detailed analysis revealed a correlation between the dosage and favorable dynamics of mapping parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Regeneration of the renal brush border after renal ischemia in rats.

An early change following mild renal ischemia is the loss of the renal microvilli, which then regenerate morphologically within 6 h. We studied microvillar regeneration in rats with 25 min of renal artery occlusion and subsequent reflow. At subsequent intervals the rats were injected intraperitoneally with [14C]choline and [3H]leucine; 25 min later they were killed and their renal brush border membranes isolated. At 30 min of reflow of blood there was a 77% reduction in the incorporation of [3H]leucine into microvillar protein compared with that of the opposite control kidney (P less than 0.02). The incorporation rose to normal within 60 min. At 30 min of reflow, the incorporation of [14C]choline into phospholipids increased twofold (P less than 0.005), then returned toward normal values after 2 h. The altered incorporation of tracers was not due to change in membrane turnover or substrate pools. The activities of alkaline phosphatase, gamma-glutamyl transpeptidase, and alpha-glucosidase decreased 50% following ischemia (P less than 0.02) and returned to control values within 2 h. Thus, renal damage severe enough to partly efface microvilli is repaired metabolically within several hours.

Clonidine effect in chronic angina pectoris. Double-blind, crossover trial on 60 patients.

Increased adrenergic activity, often manifested in chronic angina, is likely to influence adversely the course of the disease. In view of the inhibitory effect of clonidine (CL) upon the adrenergic nervous system, the effectiveness of small doses of CL in chronic angina was evaluated in a double-blind crossover study on 60 patients suffering at least 5 coronary pains per week in spite of routine medication. CL was given orally in a dose of 2 x 75 microgram/day for a 2 wk. Reduction in frequency of coronary pains by at least 50% was observed in 53.7% of patients, total nitroglycerin consumption decreased from 322 to 174 tablets/week, and ergometric performance increased from 168 to 283 W x min/patient. Urinary excretion of adrenaline and noradrenaline diminished. Blood pressure and heart rate were not considerably changed. Mild and transient side effects occurred in 10 patients, 9 of them completed the trial. It is concluded that CL in low doses is effective and safe in patients with chronic angina, presumably by alleviating adrenergic strain.

Patients with intractable angina: free thyroxine index, immunoreactive insulin and free fatty acids in blood, free adrenaline and noradrenaline in urine.

The activity of adrenergic system, thyroid gland and blood levels of insulin and FFA were studied in 120 patients with intractable angina. Noradrenaline excretion was normal but that of adrenaline was augmented in a vast majority of patients and even doubled in 27% of cases. Free thyroxine index values were abnormally high in 22% of cases and inversely correlated with ergometric performance. A diabetic-like insulin response after 50.0 g oral glucose intake was found in 10 out of 26 examined patients. Abnormally high values of FFA were observed in 66%. The mechanisms likely to account for these alterations and their suspected influence on clinical course of intractable angina are discussed.

Suppression of catecholamine excretion by low doses of clonidine in healthy subjects and feasibility study on clonidine application in angina pectoris.

The effect of low doses of clonidine (CL) (150 microgram/day p.o.) on catecholamine (CA) excretion, blood pressure (BP) and heart rate (HR) was investigated in a double-blind way on 9 healthy volunteers. CL administration for two consecutive days led to marked diminution of urinary CA, mainly of epinephrine, with only slight decrease in systolic BP and HR. The results show that this dose of CL is effective in suppressing adrenergic tone as reflected by the magnitude of CA excretion, without marked influence upon systemic BP. Subsequently, the same dose of the drug was administered for two weeks to 30 unselected patients with intractable angina known to be often associated with adrenergic overactivity. Clinical improvement manifested by complete disappearance of coronary pains or marked decrease in the incidence of anginal attacks was achieved in the majority (over 60%) of patients. Although best results were seen in patients with borderline hypertension, the drug was also effective in normotensive patients and no untoward hypotensive symptoms were noted throughout the trial. Blood CA and free fatty acids (FFA) measurements performed in 5 patients showed that favourable clinical effect of CL therapy coincides with lowering of CA and FFA levels. This study indicates that CL administered in a dose which does suppress adrenergic activity might be of value in the treatment of coronary patients. Favourable results of this preliminary trial incline to undertake well controlled clinical study.