Dynamic changes in synovitis activity after intra-articular administration of xefocam in patients with rheumatoid arthritis (according to clinical and device examinations)

AIM: To assess efficacy of intraarticular administration of lornoxicam (xefocam) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Xefocam was injected into the knee joints of 58 patients with RA once a week for 3 weeks in a dose 8 mg. The treatment efficacy was evaluated by changes in the severity of arthralgias, pain in the joints at palpation, circumference of the knee joints at the level of the upper edge of the patella, ultrasound and thermography of the knee joints. RESULTS: Xefocam relieved arthralgia (in 44 patients at least by 30%), pain in the joints at palpation and joint circumference. Ultrasound investigation registered a significant thinning of the synovial membrane and amount of exudates. CONCLUSION: If local steroid therapy is not definitely indicated, intraarticular administration of xefocam can be effectively used for suppression of moderate inflammation in the joints in RA patients.     

Clinico-functional evaluation of hypotensive effect of carvedilol in elderly patients with mild and moderate arterial hypertension

AIM: To study a hypotensive activity of carvedilol (dilatrend, Beringer Mannheim GMBH), its influence on 24-h profile of arterial pressure (AP), baroreceptor control of BP and vegetative regulation of the heart in elderly patients with mild and moderate arterial hypertension (AH). MATERIAL AND METHODS: A 3-week monotherapy with carvedilol in a single dose 25 mg/day was conducted in 47 elderly patients with mild or moderate isolated systolic or essential hypertension. The effect of the treatment was assessed by the data of synchronous 24-h monitoring of blood pressure (BP), ECG, by variability of the cardiac rhythm (Cardio Tens, Cardio Tens 01, Meditech, Hungary), baroreceptor regulation of BP (the study of synocarotid areas by the method of "cervical" camera). RESULTS: Carvedilol produced a positive trend in the clinicofunctional indices of the circulation. The hypotensive effect lasted 24 hours in 78.8% of the examinees. The drug had no negative effect on the circadian rhythm of AP, is active early in the morning, did not induce a rise in the hypotonic load or diagnostically significant deviation of ST segment, reduced AP variability, improved vegetative and baroreceptor regulation of blood circulation. CONCLUSION: Carvedilol in a dose 25 mg/day is an effective monotherapy of mild and moderate AH in elderly patients.     

Assessment of the efficacy and tolerance of delayed-action nifedipine as the monotherapy or in combination with metoprolol in patients with arterial hypertension

AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis, Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis, Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3 years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in combination with metoprolol which was administered 50 mg twice a day (a daily dose 100 mg/day). The control examination consisted of a physical examination, measurement of arterial pressure (AP) by Korotkov, registration of heart rate, ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4-week treatment with nifedipin-retard alone resulted in lowering of systolic arterial pressure. The combined treatment produced a more pronounced fall both in systolic and diastolic pressure. Diastolic left-ventricular function improved in combined therapy. Side effects observed in nifedipin-retard monotherapy got much more weaker when this drug combined with metoprolol. CONCLUSION: Combination of nifedipin-retard with metoprolol provides better clinical response and tolerance than monotherapy with nifedipin-retard.     

Chronological structure of arterial pressure in hypertensive patients on enalapril

34 male patients with hypertension stage I and II aged 29-52 years (mean age 40.9 +/- 6.00) having mean 24-h arterial pressure (AP) above 135/85 mm Hg in mean daytime AP above 140/90 mm Hg and heart rate maximum 80 b/m entered the study of AP chronostructure in conditions of pure background and on enalapril treatment week 4, 8 and 12. The initial dose of the drug was 5 mg. Dose selection was controlled by 24-h AP monitoring. Enalapril was shown to significantly reduce mean daytime and 24-h AP as well as hyperbaric index, chronobiological time index, variability of systolic AP. The above dose selection brought more balanced AP lowering at daytime and at night. After 11 weeks of treatment no night-peakers were registered, the number of over-dippers decreased. Circadian rhythm of some hemodynamic parameters was characterized by a significant fall of rhythm average in unchanged acrophase and circadian AP amplitude indicating physiological action of enalapril.     

Effect of atenolol and trimetazidine on dispersion of cardiac rhythm in patients with moderately expressed postinfarction left ventricular dysfunction

AIM: To study effects of atenolol and trimetazidine on heart rhythm variability in postmyocardial infarction patients with moderate left ventricular dysfunction. MATERIAL AND METHODS: Fifty postmyocardial infarction (PMI) patients participated in a 3-week randomized blind trial. They were divided into two groups given atenolol or trimetazidine. Time and spectral analyses of heart rhythm dispersion on short ECG parts (5 min) were done before and after treatment with atenolol (76.9 +/- 6.6 mg/day) or trimetazidine (60 mg/day). RESULTS: Only course therapy with atenolol raised heart rhythm variability registered both by time and spectral analysis. CONCLUSION: Studying heart rhythm variability enables efficient non-invasive control over effectiveness of neurohumoral heart unloading in the course of pharmacotherapy of ischemic left ventricular dysfunction.     

Combined therapy with amlodipin and lisinopril in arterial hypertension: efficacy of a low-dose combination

AIM: To assess antihypertensive efficacy of a low-dose combination of amlodipin with lisinopril in the treatment of patients with arterial hypertension (AH) of the second degree. MATERIAL AND METHODS: A total of 42 patients with the second degree of AH (16 males, 26 females, mean age 55-9 +/- 1.9 years) entered an open, comparative and controlled trial. They were divided into three groups by the treatment. Group 1 (n = 14) received amlodipin (normodipin, Gedeon Richter) monotherapy in a mean dose 8.9 +/- 0.6 mg/day, group 2 (n = 12) - lisinopril (diroton, Gedeon Richter) in a mean dose 17.5 +/- 1.4 mg/day, group 3 (n = 16) was given combined therapy with amlodipin+lisinopril in a dose 6.8 +/- 0.7 and 8.7 +/- 0.6 mg/day, respectively. The drugs were given for 12 weeks. The efficacy of the treatment was assessed by the results of 24-h monitoring of blood pressure, echocardiography, endothelium-related vasodilatation of the brachial artery (ERVD), dopplerographic investigation of circulation in the middle cerebral artery (MCA), heart rate and cost-effect estimation. RESULTS: Combined low-dose treatment with amlodipin and lisinopril for 12 weeks allowed achievement of target blood pressure in more patients and lower systolic and diastolic blood pressure than monotherapy with each of the drugs. There was also a positive effect on E/A index, ERVD, MCA circulation. CONCLUSION: Low-dose combined treatment with lisinopril and amlodipin is more effective and cost-efficient. Moreover, lisinopril addition to amlodipin corrects side effects of amlodipin on central nervous system.     

The efficacy of lysinopril (and/or its combination with hydrochlorothiazide) in patients with essential hypertension

The aim of the study was to estimate the efficacy of lysinopril (and/or its combination with hydrochlorothiazide) in terms of alteration of the diurnal AP profile and heart rhythm in patients with essential hypertension (EH). The study included 47 patients (18 men. 29 women) with grade 1-3 EN (I-II stages). They were given lysinopril at a single dose of 3-5 mg/day after the initial non-treatment period of 1-2 weeks. The dose was increased up to 20 mg in the absence of effect within the first 3-5 days and supplemented with 12.5 hydrochlorothiazide if the response was still absent after 4 weeks. The follow up period was 4 and 12 weeks. Lysinopril was shown to effectively reduce AP in 72.3% of the patients within 4 weeks and in 87.2% if given in combination with hydrochlorothiazide for 12 weeks. It is concluded that long-term monotherapy or combined therapy with lysinopril stabilizes the disturbed diurnal AP profile, decreases variability and morning rises of AP, normalizes vegetative regulation of heart rhythms, and promotes regression of myocardial hypertrophy.     

Cardiorenal pathology in diabetes mellitus type 1: mechanisms of development and medical correction

AIM: To elicit the role of endothelial dysfunction in development of cardiorenal syndrome in patients with diabetes mellitus type 1 (DM1) with diabetic nephropathy (DN) and to evaluate the efficacy of endotheliotropic drugs: nebivolol (a selective beta-blocker) and enalapril (ACE inhibitor). MATERIAL AND METHODS: The trial enrolled 60 patients with DM1: 15 patients with normoalbuminuria (NAU), 15 patients with microalbuminuria (MAU), 15 patients with proteinuria (PU) and 15 with chronic renal failure (CRF). The control group consisted of 15 healthy volunteers matched by sex and age. All the patients were examined for endothelium-dependent dilation of the brachial artery (by duplex scanning in the test with reactive hyperemia), serum markers of endothelial dysfunction (endothelin-1--ET-1), Willebrand factor (WF), inflammation markers (C-reactive protein-CRP), incidence rate of ischemic heart disease (IHD). 24-h arterial pressure monitoring and echocardiography were also made. For 12 weeks the patients were given nebivolol monotherapy in a dose 5 mg/day or enalapril monotherapy in a dose 10 mg/day. The effects of these drugs on urinary excretion of albumin and protein, arterial pressure, circadial rhythm of arterial pressure and endothelial dysfunction were studied. RESULTS: In DM1 patients DN advances with an increase in development of IHD: in MAU--by 13%, PU--by 33%, CRF--53%. Concentric hypertrophy and left ventricular remodeling were registered in 33, 40 and 60% of cases, respectively. A circadian rhythm disturbance correlated with DN severity. DN progression was associated with increasing endothelial dysfunction. It is shown that nebivolol and enalapril correct endothelial dysfunction, have comparable antiproteinuric and antihypertensive actions at different stages of nephropathy. CONCLUSION: A close correlation was found between DN progression and development of cardiovascular pathology in DM1 patients. This serves the basis of cardiorenal syndrome. These two pathologies are associated with vascular endothelial dysfunction which leads to disorders in vascular tonicity regulation.     

Lipid and non-lipid effects of enduracin in patients with arterial hypertension]

AIM: To analyze lipid and non-lipid effects of 6-month administration of enduracine in patients with marked dislipoproteinemia suffering from arterial hypertension with ischemic heart disease or without it. MATERIALS AND METHODS: 40 hypertensive patients (27 males and 13 females, mean age 52.43 +/- 1.68 years) entered the study of enduracine effects. Most of them received enduracine for 6 months in a dose 1500 mg/day. Lipids levels were measured in all the patients. Blood flow along major brain arteries was determined at transcranial dopplerography in 23 patients. RESULTS: A 6-month course of enduracine in a dose 1500 mg/day promoted normalization of serum lipid spectrum, vascular tonicity and reactivity of cerebral arteries, produced a mild hypotensive effect. CONCLUSION: Endurance (a long-acting form of nicotinic acid) has favourable lipid and non-lipid effects in patients with dislipoproteinemias and arterial hypertension in the presence or absence of ischemic heart disease.     

Osmo-adalat in the treatment of isolated systolic and systolic-diastolic arterial hypertension in aged patients

AIM: To examine efficiency and tolerance of osmo-adalat in monotherapy of mild and moderate arterial hypertension (AH) in the elderly. MATERIAL AND METHODS: 60 AH patients were randomized into two groups. Group 1 received osmo-adalat monotherapy in daily dose 30 mg for 3 weeks. These were 14 patients with isolated systolic AH (ISAH) and 16 patients with essential hypertension (EH). Of group 2 patients, 15 with ISAH and 15 with EH received cordipin in a dose 10 mg three times a day. All the patients underwent 24-h monitoring of arterial pressure, in 18 patients arterial pressure and ECG were registered in parallel for 24 hours. RESULTS: AH treatment with osmo-adalat is rather effective. This is proved by its positive effect on shifted profile of arterial pressure in patients with ISAH and EH. A fall of arterial pressure on the peak of osmo-adalat antihypertensive action is not associated with hypotonic overloading of target organs, myocardial ischemia and increased heart rate. A single intake of osmo-adalat provides a smooth circadian control of arterial pressure in elderly hypertensive patients, the end effect being 50% of the peak one. The drug is well tolerated. Side effects do not require osmo-adalat discontinuation. CONCLUSION: Osmo-adalat in a single daily dose 30 mg is effective and safe in the treatment of mild and moderate AH in elderly patients.     

A 24-hour profile of arterial pressure: vegetative regulation in persons with isolated systolic arterial hypertension

A total of 117 persons were studied: 60 patients with isolated systolic arterial hypertension (ISAH) (22 males, 38 females; mean age 68.7 +/- 4.2 years), 22 males with ISAH (mean age 20.1 +/- 2.7 years), 15 healthy elderly subjects and 20 healthy young males. The analysis of heart rhythm variability and the results of 24-h arterial pressure monitoring specified an individual 24-h profile of arterial pressure and effects of vegetative regulation on this profile.     

24-hour arterial hypertension profile and heart rhythm variability in patients with arterial hypertension and NIDDM

The study covered 72 patients with non-insulin-dependent diabetes mellitus (NIDDM) whose mean age was 54.2 +/- 0.8 years, duration of the disease 8.6 +/- 3.6 years. They had also mild or moderate arterial hypertension mean duration of which was 12.4 +/- 4.3 years. The examination of the patients consisted of 24-h arterial pressure (AP) monitoring, Holter ECG monitoring, cardiointervalography. For eight weeks 19 patients received enalapril (5-20 mg/day), 14 patients were given felodipin (5-10 mg/day) and 15 patients were treated with valsartan (80-160 mg/day). Enhanced activity of the sympathetic nervous system in hypertensive subjects with NIDDM raises daily average values of systolic and diastolic AP, variability and speed of AP morning rise. In NIDDM patients with moderate arterial hypertension vegetative regulation of AP was more stressed than in mild hypertension. Optimal medication of NIDDM patients' arterial hypertension may consist of ACE inhibitors and antagonists of angiotensin II receptors. These drug lower stress of the sympathetic nervous system and thus promote normalization of daily profile of AP.     

Comparative anti-hypertensive effectiveness and tolerance of drugs in patients with mild and moderate arterial hypertension

120 patients with mild and moderate arterial hypertension were treated outpatiently for 6 weeks with dilren (group 1), norvask (group 2), invoril (group 3) and caposide (group 4). Each group consisted of 30 patients. The drugs were given in doses: 300 mg/day, 5-10 mg/day, 10-20 mg/day and 1 tablet a day (50 mg capoten + 25 mg hydrochlortiaside), respectively. Arterial pressure was measured by patients in the morning and in the evening. A complete hypotensive response (AP < 140/90 mm Hg) to dilren was achieved in 25(83.3) patients, norvask in 22(73.3%), invoril in 18(60%), caposide in 13(43.3%) patients. The other 45(37.5%) patients responded partially. Side effects occurred in 31(25.8%) of 120 patients. In caposide, norvask, invoril and dilren treatment they were recorded in 9(30.3%), 8(26.7%), 8(26.7%) and 6(20%) patients, respectively. 11 patients withdrew because of side effects. Thus, dilren (300 mg/day), norvask (5-10 mg/day) and invoril (10-20 mg/day) are effective and safe in mild and moderate arterial hypertension. Caposide (1 tablet a day) failed to provide an adequate fall in arterial pressure throughout 24 hours.     

Pharmacokinetics,safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension

BACKGROUND: Bosentan, a dual endothelin-receptor antagonist, is registered for the treatment of pulmonary arterial hypertension. Little is known about the effects of bosentan in children. This study was conducted to investigate the pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. METHODS: In this 2-center, open-label study, 19 pediatric patients with pulmonary arterial hypertension were enrolled and stratified for body weight and epoprostenol use. Patients weighing between 10 and 20 kg, between 20 and 40 kg, or greater than 40 kg received a single dose of 31.25, 62.5, or 125 mg, respectively, on day 1, followed by 4 weeks of treatment with the initial dose. The dose was then up-titrated to the target dose (31.25, 62.5, or 125 mg twice daily). Pharmacokinetic and hemodynamic parameters were obtained at baseline and after 12 weeks of treatment. Six-minute walk distance and cardiopulmonary exercise testing results were measured at baseline and at week 12 in children aged 8 years or older. RESULTS: The variability in exposure among the 3 groups was less than 2-fold after single- and multiple-dose administration. The exposure to bosentan decreased over time in all groups. The covariates body weight, gender, age, and the use of epoprostenol had no significant effect on the pharmacokinetics of bosentan. Bosentan produced hemodynamic improvement and was well tolerated. The mean change from baseline in mean pulmonary artery pressure was -8.0 mm Hg (95% confidence interval, -12.2 to -3.7 mm Hg), and that in pulmonary vascular resistance index was -300 dyne x s x m(2)/cm(5) (95% confidence interval, -576 to -24 dyne x s x m(2)/cm(5)). CONCLUSIONS: The pharmacokinetics of bosentan in pediatric patients with pulmonary arterial hypertension and healthy adults are similar, and treatment with bosentan resulted in hemodynamic improvement. These results suggest that the applied dosing regimens may be appropriate to treat pediatric patients.     

Lornoxicam (xefocam) as an agent for the prevention and treatment of postoperative pain among other nonsteroidal anti-inflammatory drugs

Lornoxicam (xefocam) as an agent of perioperative antinociceptive defense was studied and compared with other nonsteroidal anti-inflammatory drugs (NSAIDs) (ketorolac, ketoprofen). A comparative study was performed in 140 cancer surgical patients who were mainly middle-aged and elderly (51 +/- 10.9 years) and who had various concomitant diseases (ASA II-III). Extensive oncological operations under multicomponent general anesthesia were performed in these patients on the abdomen (n=60), small pelvis (n=46), and head and neck (n=34). All NSAIDs were used on the principle of preemptive analgesia, by intramuscularly injecting the therapeutic dose of an analgesic 40-60 min before surgery and by further continuing this basic therapy in combination with an opioid after surgery. Thirty patients received lornoxicam (xefocam, 16 mg/day), 30 had ketorolac (ketanov, 60-90 mg/day), 30, ketoprofen/ketonal (200 mg/day), and 20 patients, ketoprofen/artrozilene (320 mg/day). A control group comprised 30 patients who did not receive NSAIDs. In the patients of all the groups, the anesthesia scheme included one more antinociceptive agent--the kininogenesis inhibitor contrical (the total dose was 50,000-60,000 ATrU) (beginning from the stage of induction) and its administration (30,000 ATrU/day) was continued within 2 days after surgery. The studies performed have established that lornoxicam (xefocam) used in therapeutic doses shows a 50% reduction (versus 30% when ketorolac or ketoprofen is used) in a need for the potent opioid bepronorfine after extensive operations for cancer is one of the most effective NSAIDs. It has been noted that a short-term course of perioperative therapy with NDAIDs does not cause complications or side effects if individual contraindications to and limitations on their use are followed.     

The influence of antihypertensive agents on circadian rhythms of blood pressure and heart rate in patients with essential hypertension.

The effects of once-daily administration of calcium (Ca) channel blockers, beta-blockers and and angiotensin-converting enzyme (ACE) inhibitors on circadian rhythms of blood pressure (BP) and heart rate (HR) were studied using the cosinor method. Sixty-two recruited patients with essential hypertension (WHO stage I or II) were divided into three groups based on the class of administered drugs. In the Ca channel blocker group (n = 37, age 54 +/- 9.0 years), 18 patients were given YM 730 at a mean dose of 11 +/- 4.0 mg/day (mean +/- S.D.), 8 were given nitrendipine (11 +/- 6.7 mg/day), and 11 were given nisoldipine (8 +/- 6.4 mg/day). In the beta-blocker group (n = 15, age 42 +/- 13.5 years), 13 patients were given atenolol (44 +/- 11.0 mg/day), 1 was given nadolol (30 mg/day), and 1 was given sustained-release propranolol (60 mg/day). In the ACE inhibitor group (n = 10, age 56 +/- 8.7 years), 7 patients were given enalapril (6 +/- 2.8 mg/day), and 3 were given lisinopril (20 mg/day). Ambulatory BP monitoring (ABPM) was performed before and during treatment. Mean arterial pressure (MAP) and HR were monitored under ambulatory conditions every five minutes for 24 hr with a finger volume oscillometric device. In all three groups, the mesor of MAP decreased significantly, while the amplitude and acrophase did not change during treatment. beta-Blockers reduced the amplitude as well as the mesor of HR. Ca channel blockers increased the amplitude of HR without influencing the mesor. ACE inhibitors had no effect on the circadian rhythm parameters of HR. These results suggest that Ca channel blockers, beta-blockers and ACE inhibitors lowered BP throughout the day without changing the circadian BP rhythm. However, the three drug classes may have different influences on the autonomic nervous system that regulates circadian cardiac rhythm.     

Effect of diroton on characteristics of 24-hours arterial pressure monitoring in hypertensive patients with polycythemia vera

AIM: To study the data of 24-h monitoring of blood pressure (MBP) and effects of an ACE inhibitor lisinopril (diroton) in hypertensive patients with polycythemia vera (PV). MATERIAL AND METHODS: 20 patients with arterial hypertension of degree II and III with PV aged 41 to 77 years. Mean duration of AH and PV was 11.8 +/- 2.2 and 2.0 +/- 0.2 years, respectively. Diroton was given as monotherapy in a single morning dose 10-40 mg for 4 weeks. 24-h MBP was made before the treatment and on the 4th week of the treatment. In addition to standard estimations, hour-to-hour double product (DP) was estimated. RESULTS: After 4 weeks of diroton therapy there was a 12.2%, 9.5%, 25% and 15.4% fall in mean 24-h systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), DP, respectively. A positive effect was registered on variability and 24-h profile of BP. A response was achieved in 85% patients. The target level of mean 24-h blood pressure < 135/85 mm Hg was achieved in 65%, and 10% fall in SBD and/or DBP in 20% patients. ACE inhibitors' side effect--severe dry cough--was not encountered. CONCLUSION: PV aggravates arterial hypertension. Monotherapy with diroton effectively controls BP in hypertensive patients with PV in a 4-week course intake in a single morning dose and is well tolerated.     

Experience in application of various antidepressants in gerontology

The article presents data on the effectiveness of comorbide therapy with amlodipine and antidepressants of various groups in patients more than 65 years old suffering from coronary artery disease (CAD), arterial hypertension (AH), and comorbide depression. Eighty-eight patients with stable FC I-III stenocardia, accompanied by AH and comorbide depression, were examined. The patients were divided into three groups. Patients in group I (n = 21) received amlodipine therapy in a dose of 2.5 to 5 mg/day with amitriptyline in a dose of 25 mg/day. Group II patients (n = 25) received tianeptine in a dose of 25 mg/day in addition to amlodipine in a dose of 2.5 to 5 mg/day. Group III patients (n = 20) were treated with a combination of amlodipine 2.5 to 5 mg/day with sertraline in a dose of 50 mg/day. The comparison group consisted of 22 patients who received monotherapy in a dose of 2.5 to 5 mg/day. The study revealed that all these combinations with different antidepressants significantly lowered the average depression score and significantly improved the quality of life, unlike amlodipine monotherapy. The best combination was amlodipine plus tianeptine, which did not only demonstrate antidepressive and anxiolytic effects, but also led to improvement in prognostically significant parameters of cardiac rhythm variability in elderly patients with comorbide depressive disorders underlied by stable stenocardia and arterial hypertension.     

Immediate and long-term hemodynamic and clinical effects of sildenafil in patients with pulmonary arterial hypertension receiving vasodilator therapy

OBJECTIVE: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Thirteen patients with PAH received empirical adjunctive sildenafil treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. RESULTS: Sildenafil significantly increased cardiac output (CO) (P = .04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P < or = .01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose), sildenafil significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P = .01). Ten patients discharged from the hospital were taking the highest-tolerated dose of sildenafil every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117 +/- 70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. CONCLUSION: Sildenafil has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects of sildenafil on PAH, both in untreated and concurrently treated patients.     

Autonomic nervous system function and effects of beta-adrenoblockers on heart rhythm variability in patients with myocardial infarction

Heart rhythm variability on myocardial infarction (MI) day 1, 3, 7 and 11 was assessed mathematically to study function of the autonomic nervous system in 101 MI patients. The initial autonomic tonicity (IAT), autonomic reactivity (AR) and autonomic maintenance (AM) were studied. Depending on the site of the infarction in the myocardium, different type of autonomic homeostasis were identified. Moderate sympathicotonia, sympathicotonic type of AR and adequate AM irrespective of IM location were found most favourable in relation to the MI course and prognosis. The spectral analysis of the heart rhythm showed a significant shift of the frequency spectrum in the inferior MI to high frequencies and in anterior MI--to low frequencies. Autonomic dysfunction score is higher in the anterior MI. Psychoemotional state of the patients was determined by Spilberg-Khanin test evaluating reactive and personality anxieties. These characteristics were moderate and high in patients with MI and effort angina, respectively. The study of selective beta-adrenoblockers effect on heart rhythm variability proved that lokren (betaxolol) in a dose of 10 mg/day significantly and positively influences heart rhythm and objective status of the patients. Less effective is betacard (atenolol). Nebivolol is not indicated in acute MI. Significant correlations are found between the findings of IAT mathematical analysis, psychoemotional features of the patients and complications of MI. Parameters of an unfavourable course and outcome of MI are described.