Ventricular function in patients with silent myocardial ischemia before and following aortocoronary bypass operation

In 12 patients with silent myocardial ischemia (fall of the ejection fraction (EF) greater than or equal to 5%, without angina pectoris) and in 15 symptomatic patients with coronary heart disease (fall of the EF during exercise EF greater than or equal to 5%, with angina pectoris), the left ventricular ejection fraction and the diastolic function (Peak Filling Rate, PFR; Time to Peak Filling Rate, TPFR) were evaluated before coronary artery bypass surgery and afterwards by the aid of the Nuclear Stethoscope. Our results showed a slight insignificant improvement in the EF from 60 +/- 8.3 per cent at rest to 66 +/- 7.9 per cent vs. 57 +/- 12 per cent to 62.6 +/- 9 per cent in patients with silent ischemia and in patients with angina pectoris after surgery. In contrast to this the EF increased significantly during exercise both in patients with silent ischemia from 52.0 +/- 15.2 per cent to 70.1 +/- 7.9 per cent and in symptomatic patients after revascularisation from, 49 +/- 11.7 per cent on to 64.2 +/- 8.4 per cent (both p less than 0.0001). There was also a similar significant improvement in the diastolic function, whereby the PFR was enhanced from 2.52 +/- 0.54 EDV/sec to 3.31 +/- 0.87 EDV/sec (p less than 0.02) in patients with silent myocardial ischemia and from 2.55 +/- 0.86 EDV/sec to 3.40 +/- 0.98 EDV/sec (p less than 0.02) in symptomatic patients. The TPFR showed a similar improvement.     

Clinicopathogenetic features of coronary heart disease combined with chronic obstructive pulmonary diseases and efficiency of therapy with trimetazidin

Based on retrospective analysis of 2446 in-patient cards, autopsy protocols, outpatient medical documentation, prevalence and features of clinical manifestation of cardiorespiratory pathology (CRP): coronary heart disease (CHD) combined with chronic obstructive pulmonary disease (COPD)--1 stage of study, and also (after randomization and forming of main and control groups), efficiency of myocardial cytoprotector trimetazidin (TMZ) at its long-term use (1 year) in combined therapy (2 stage of study): 135 CHD patients (stable exertional angina functional class II-III: 92 and 43 persons respectively) with COPD of medium severe (111 persons) and severe course (24 persons), were studied. It is shown that CRP is prevailed in elder age groups (after 45 years) and noticed in 56.7% CHD patients. More sevenre course with great risk of myocardial infarction with Q wave (twice, p < 0.001), prolongation of painless ischemia (62.4+/-11.5 min/day vs. 22.8+/-11.1 min/day), inclination to complicated rhythm disturbances (38 vs. 21.9, p < 0.05) and earlier clinical manifestations of heart failure (4.3+/-0.6 years earlier, p < 0.001) is typical for CHD with COPD vs. patients without pulmonary pathology. In one year after beginning of treatment with TMZ (35 mg) number of weekly pain attacks was decreased in patients of 1st group vs. 2nd group (at the average -50.8% -29.3% vs. +12.5% +16.6% respectively); significant (p < 0.05) decrease in duration of painless myocardial ischemia was registered. Decrease in number of supraventricular and ventricular extrasystoles (42.7+/-1.48 vs. 20.5+/-1.07 cases in a day, a < 0.0001), significant (p < 0.05) increase in ejection fraction and decrease in left ventricle end-diastolic volume (12.2+/-0.4% E 12.2+/-0.3% respectively), in dimensions of left (10.9+/-0.03%) and right (8.8+/-0.9%) atrium, in risk of development of acute coronary syndrome were noticed in the patients of main group received TMZ. Thus, long-term (not less then 1 year) use of TMZ (35 mg) in combined treatment assists to normalization of cardiovascular indices, decreases cardiovascular complication occurrence, improves disease prognosis and do not has negative side-effects.     

Trimetazidine in Angina Combination Therapy--the TACT study: trimetazidine versus conventional treatment in patients with stable angina pectoris in a randomized, placebo-controlled, multicenter study

The aim of this study was to assess the efficacy and acceptability of trimetazidine (TMZ) in combination with hemodynamic agents (beta-blockers or long-acting nitrates) in 177 stable angina patients. In this randomized, placebo-controlled study (TACT: Trimetazidine in Angina Combination Therapy), stable angina patients resistant to nitrates or beta-blockers were selected. After a 1-week selection period (W0), patients who had a difference of <10% in duration between 2 positive exercise tests, defined as 1-mm ST-segment depression (STD) 80 milliseconds after J point with angina pain or 1.5 mm without pain were randomly treated with TMZ (20 mg t.i.d., n = 90) or placebo (Pbo t.i.d., n = 87) orally. A final exercise test was performed after 12 weeks of treatment (W12). The efficacy was assessed by exercise test duration, time to 1-mm STD, time to angina onset, mean number of angina attacks, mean short-acting nitrate consumption, and rate-pressure product. Differences (W12 - W0) in these parameters were analyzed using the Student t test. All statistical tests were conducted at the 5% significance level. At inclusion and during the study, 52% of patients received long-acting nitrates, and 48% were treated with a beta-blocker as monotherapy. At the beginning of the study, the TMZ and Pbo groups were statistically homogeneous with respect to all analyzed characteristics (demographic characteristics, characteristics of anamnesis, characteristics used for evaluation of antianginal therapy efficacy). For various reasons, 11 patients (7 from the Pbo group and 4 from the TMZ group) were excluded from the trial. A total of 166 patients (80 from the Pbo group and 86 from the TMZ group) completed the study in full compliance with the protocol. After 12 weeks of therapy, exercise test duration increased from 417.7 +/- 14.2 (W0) to 506.8 +/- 17.7 seconds (W12) in the TMZ group versus 435.3 +/- 14.8 (W0) to 458.9 +/- 16.2 seconds (W12) in the Pbo group (P < 0.05). Time to 1-mm STD increased from 389.0 +/- 15.3 (W0) to 479.6 +/- 18.6 seconds (W12) in the TMZ group versus 411.8 +/- 15.2 (W0) to 428.5 +/- 17.3 seconds (W12) in the Pbo group (P < 0.05). Time to onset of anginal pain increased from 417.0 +/- 16.9 (W0) to 517.3 +/- 21.0 seconds (W12) in the TMZ group versus 415.1 +/- 16.5 (W0) to 436.4 +/- 18.5 seconds (W12) in the Pbo group (P < 0.005). The mean number of anginal attacks per week decreased from 5.6 +/- 0.6 to 2.7 +/- 0.5 in the TMZ group versus 6.8 +/- 0.7 to 5.1 +/- 0.7 in the Pbo group (P < 0.05), mean consumption short-acting nitrates per week decreased from 5.2 +/- 0.9 to 2.8 +/- 0.8 in the TMZ group versus 5.5 +/- 0.8 to 4.1 +/- 0.9 in the Pbo group (NS). No change in the rate-pressure product was seen in both. The combination of trimetazidine with beta-blockers or long-acting nitrates significantly improves exercise stress test parameters and angina symptoms compared with placebo. Due to its metabolic effect, free of any hemodynamic action, trimetazidine has proven to be beneficial for combination in patients with stable angina.     

Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study

BACKGROUND: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. AIM: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. RESULTS: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. DISCUSSION: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.     

Depression in cardiological practice: pilot results from a multicenter clinico-epidemiological trial in hypertensive patients with ischemic heart disease (koordinata)

AIM: To study effects of depression on the course and prognosis of arterial hypertension (AH) and coronary heart disease (CHD), potentialities of the combined treatment in a prospective multicenter trial. MATERIAL AND METHODS: A total of 376 patients with AH and/or CHD having depression (10 scores and higher by HADS scale) were assigned to two groups: 189 (50.3%) patients received somatotropic therapy+coaxil (the study group), 187 (49.7%) patients received somatotropic therapy alone (the comparison group). Coaxil was given for 6 weeks in a dose of 37.5 mg/day, to patients over 70 years--25 mg/day. The effects were assessed by changes in HADS, CGI scale, blood pressure, heart rate; by tolerance and side effects (objective effects); complaints, well- being, stress, tolerance (subjective effects). RESULTS: The addition of coaxil to somatotropic therapy of patients with AH and/or CHD associated with depression led to improvement of the psychological status (a 36% decrease by HADS depression scale from 13.1 +/- 2.75 to 8.43 +/- 3.64, -delta4.76, p < 0.0001; by HADS anxiety scale--by 35.6% from 12.08 +/- 3.90 to 7.78 +/- 3.63, -delta4.31, p < 0.0001; by response to psychoemotional stress--by 23% from 6.65 +/- 1.94 to 4.77 +/- 1.85, -delta1.88, p < 0.05). Control patients also showed a positive trend in the above indices (a decrease in the above indices from 13.15 +/- 2.65 to 11.79 +/- 3.31, from 11.50 +/- 3.66 to 10.12 +/- 3.95, from 6.63 +/- 1.99 to 6.03 +/- 2.07, p < 0.05, respectively) but positive changes were much weaker than in the coaxil group (p < 0.001). To the end of the treatment, patients of the study group had less number of complaints, more patients achieved the target level of arterial pressure under 140/90 mm Hz (43.9 versus 29.9% in the control group; p < 0.005). CONCLUSION: Standard somatotropic treatment of AH patients with CHD and depression is not sufficiently effective. Combination of such treatment with antidepressive therapy (coaxil) significantly improves psychological status, and efficacy of therapy of basic cardiological diseases.     

Cardioselective beta-adrenoblockers in patients with stable angina pectoris. Comparison of efficacy and safety

AIM: To compare efficacy and safety of cardioselectivc beta-blockers (BB) in patients with stable angina. MATERIAL AND METHODS: An open comparative randomized trial with participation of 40 patients suffering from stable angina (NYHA FC II-III) was made. All the patients were divided into two groups. Patients of group 1 received betaxolol, those of group 2--other selective BB: metoprolol (n = 13), bisoprolol N = 6, nebivolol (n = 1). The BB dose was doubled each 2 weeks up to achievement of the maximal tolerable dose. The trial continued for 2 months during which the patients were also given aspirin, statins, ACE inhibitors, mononitrates, amlodipin and thiazide diuretics. The efficacy of the treatment was assessed by the data of the treadmill test by Brus protocol, echocardiography according to ASE recommendations, high resolution ultrasound examination of endothelium-related relaxation of the brachial artery. Lipid transport parameters were estimated with enzyme techniques. RESULTS: A mean dose of betaxolol, metoprolol and bisoprolol was 14 +/- 4.5 mg/day, 127 +/- 24 mg/ day, 10 +/- 4 mg/day. A noticeable lowering of heart rate (HR) and blood pressure (BP) was observed in both groups, but HR in group 1 decreased more (57.35 +/- 5.19 and 62.4 +/- 8.84 b/m, respectively, p = 0.033) and systolic pressure showed a trend to greater reduction. Exercise tolerance in both groups was compatible. The lowest threshold HR was achieved in betaxolol group (a fall from 133.8 +/- 23.5) to 105.0 +/- 14, 23 b/min (p+0.027). Endotheium-related relaxation of the brachial artery was improved in betaxolol group: the diameter of the artery increased from 6.38 +/- 4.32 to 9.22 +/- 4.37% (p = 0.057), the peak blood flow velocity--from 14.81 +/- 3.91 to 23.87 +/- 3.7% (p = 0.031). In group 2 a positive trend in these parameters was not observed. BB had no negative effect on left ventricular contractility, parameters of transmitral blood flow, bronchial conduction, metabolism. CONCLUSION: Compared to other BB, betaxolol had a stronger effect on hemodynamic parameters (HR and BP) at rest and exercise, improved endothelial vascular function in patients with stable angina.     

Brain natriuretic peptide in the prediction of recurrence of angina pectoris

BACKGROUND: Circulating levels of brain natriuretic peptide (BNP) provide prognostic information for patients with heart failure, but little is known about its prognostic usefulness in patients with stable angina pectoris. We investigated whether BNP could be used as a marker for the prediction of anginal recurrence after successful treatment. DESIGN: Brain natriuretic peptide levels of 77 patients with stable angina pectoris were measured at enrolment and after confirmation of successful treatment (i.e. no anginal attack for at least 6 months: chronic phase) with percutaneous transluminal coronary angioplasty and/or conventional medication. Then, we prospectively followed them up for 25.9 +/- 1.4 months, with the endpoint being a recurrence of anginal attacks. RESULTS: An anginal attack recurred in seven patients. In patients without recurrence, BNP levels in the chronic phase (21 +/- 12 [median +/- median absolute deviation] pg mL-1) were lower than those measured at enrolment (46 +/- 25 pg mL-1, P < 0.0001), whereas the levels in patients with recurrence increased during the same period (from 36 +/- 16 to 72 +/- 42 pg mL-1, P < 0.05). A univariate analysis revealed that the BNP level measured in the chronic phase was the significant predictor of future anginal recurrence. Analysis of the receiver operating characteristic curve indicated that the cutoff level of BNP in the chronic phase was 68 pg mL-1. The Kaplan-Meier method revealed that the incidence of anginal recurrence was higher in patients with higher (71.4%) than lower levels of BNP (2.9%; P < 0.0001). CONCLUSIONS: Measurement of BNP levels after successful therapy is clinically useful for the prediction of recurrence of anginal attacks in patients with angina pectoris.     

Peritoneal ultrafiltration and serum icodextrin concentration during dialysis with 7.5% icodextrin solution in Japanese patients.

OBJECTIVES: To assess the efficacy and safety of icodextrin in Japanese patients and to investigate the relationship between net ultrafiltration (UF) during the long dwell and plasma oligosaccharides. DESIGN: Open-labeled clinical trial involving patients on continuous ambulatory peritoneal dialysis (CAPD) receiving icodextrin during the 12-hour long dwell for 6 weeks, preceded by and followed by a 2-week baseline period and a follow-up period during which 1.36% glucose was used for the 8-hour long dwell. SETTING: A prospective, randomized multicenter study done in tertiary medical centers. PATIENTS: 18 stable patients on CAPD for 3 months or longer. MAIN OUTCOMES MEASURES: Net UF (in milliliters), UF rate (in milliliters per hour), plasma oligosaccharides, serum osmolarity (in milliosmoles per liter), peritoneal absorption of icodextrin, and peritoneal clearances of icodextrin, creatinine, and urea were assessed. Adverse events, laboratory findings, and vital signs were also monitored. RESULTS: Long-dwell net UF (544.4 +/- 96.7 mL at day 3, p < 0.001; 309.4 +/- 60.7 mL at week 4, p < 0.001; and 391.7 +/- 61.1 mL at week 6, p < 0.001) and UF rate (48.2 +/- 38.8 mL/ hour at day 3, p < 0.001; 26.9 +/- 22.1 mL/hr at week 4, p < 0.002; and 35.3 +/- 22.9 mL/hr at week 6, p = 0.0002) were significantly greater during the icodextrin period than at baseline (-25.9 +/- 46.0 mL and -2.2 +/- 22.1 mL/hr, respectively). Plasma oligosaccharides reached steady state within 2 weeks, remained stable during the treatment period, and returned to baseline level 2 weeks after discontinuation of icodextrin. Serum osmolarity increased during the use of icodextrin by approximately 5 mOsm/L. No statistically significant relationship was found between plasma oligosaccharides and net UF. Peritoneal absorption of icodextrin (36.3% +/- 5.1% at day 3, 42.2% +/- 5.9% at week 4, and 38.0% +/- 6.3% at week 6) and peritoneal clearance of icodextrin (10.1 mL/minute at day 3, 10.1 mL/min at week 4, and 10.3 mL/min at week 6) showed no major change over time. Serum sodium and serum chloride both decreased by 5 mEq/L with icodextrin but remained within the normal range during the treatment period and returned to baseline levels immediately after discontinuation. No serious adverse events were observed during the study. CONCLUSION: The results of this study do not support the hypothesis that an increased blood oligosaccharide level and the concomitant elevation in serum osmolarity have a negative impact on peritoneal UF. Therefore, the increase in plasma oligosaccharides appears to be too small to be of clinical significance.     

Serum albumin and other serum protein fractions in stable patients on peritoneal dialysis.

BACKGROUND: Hypoalbuminemia is common in peritoneal dialysis (PD) patients; but the reduction in serum albumin levels (SAlb) that should be expected in stable PD patients is less clear. OBJECTIVES: To determine prospectively, in a group of stable PD patients without comorbid conditions, the changes in SAlb concentration and in the concentrations of the other serum protein fractions. To investigate the best determinants of a significant decrease in SAlb levels. DESIGN: Prospective observational study. METHODS: Seventeen PD patients in stable clinical condition, with no signs of systemic inflammatory response, were included in the study. SAlb and the electrophoretic pattern of serum proteins were determined immediately before PD start, and after 6, 9, 12, 15, 18, 21, and 24 months on PD. In each study period, clinical characteristics, adequacy parameters, protein catabolic rate (PNPNA: protein equivalent of non protein nitrogen appearance), and protein losses were determined. Patients were divided into two subgroups according to whether SAlb decreased less than 10%, or 10% or more, from baseline values after 24 months on PD. The main differences between the subgroups were investigated. RESULTS: Mean SAlb did not decrease significantly after 24 months on PD (from baseline 3.99 +/- 0.46 g/dL to 3.80 +/- 0.54 g/dL), though percentage SAlb values did (58.36% +/- 5.58% vs 55.15% +/- 5.42%, p < 0.01). A weak increase in alpha2-globulin was observed after 18 months on PD (from 10.62% +/- 2.53% to 12.96% +/- 2.51%, p = 0.001). Alpha-globulin showed a sustained increase from a mean baseline value of 3.51% +/- 1.09% to 6.83% +/- 2.13% after 24 months (p < 0.0001). Seven patients had a reduction in SAlb greater than 10% after 24 months on PD. Kt/V urea and residual renal function tended to be lower in patients whose SAlb decreased. Mean PNPNA was significantly lower in patients who had a reduction in SAlb (0.76 +/- 0.12 g/kg/day vs 0.96 +/- 0.12 g/kg/day, p < 0.0001). However, total protein loss was even greater in patients who had no SAlb reduction. CONCLUSIONS: After 24 months on PD, a mean reduction in SAlb of 10%-15% from baseline values should be expected only in those stable patients whose PNPNA is low.     

Lipoprotein(a) levels in patients with unstable angina and their relationship with atherothrombosis and myocardial damage

The aim of the study was to compare lipoprotein(a) [Lp(a)] levels in patients with cTroponin-I (cTn-I)-positive or -negative unstable angina and to investigate their relationship with atherothrombosis. A total of 202 consecutive patients were enrolled in the study. Lp(a), fibrinogen, plasminogen, PAI-1 and t-PA levels were measured and C-reactive protein (CRP) assays were performed on admission for all patients, and venous blood samples were drawn 12 and 24 h later for cTn-I measurements. The patients were divided into cTn-I-negative (cTn-I < 1 ng/ml) and -positive (cTn-I > or = 1 ng/ml) unstable angina groups. Lp(a) levels of the cTn-I-positive patients were higher than those of the cTn-I-negative patients (52.9 +/- 6.0 and 15.7 +/- 2.5 mg/dl, p < 0.0001). There was a positive correlation between Lp(a) and cTn-I levels (r = 0.692; p = 0.0001). Increase in coagulation activity and impairment in fibrinolytic activity were significant in the cTn-I-positive patients. Elevated Lp(a) levels may have a role in the development of myocardial damage in patients with unstable angina.     

Effect of a new coronary vasodilator, nicorandil, on variant angina pectoris

The effect of nicorandil, a new coronary vasodilator, was evaluated in 32 patients with variant angina pectoris in a single-blind trial. The study was comprised of a pretreatment period of 2 days with a placebo, a 3-day nicorandil medication period (20 mg/day), and a 2-day posttreatment period with the placebo. Anginal attacks disappeared completely in 24 of the 32 patients. The number of attacks during the pretreatment period, 3.6 +/- 0.4 per day, became significantly reduced to 0.7 +/- 0.2 per day during nicorandil therapy (P less than 0.001) and significantly increased to 1.3 +/- 0.3 per day after withdrawal of the drug (P less than 0.05). In 17 patients with continuous ECG monitoring, the frequency of occurrence of ST-segment elevation was 8.6 +/- 2.7 per day during the preobservation period, significantly decreased to 0.4 +/- 0.2 per day during nicorandil therapy (P less than 0.01), and significantly increased to 1.9 +/- 0.7 per day after withdrawal of the drug (P less than 0.05). The results demonstrate the effectiveness of nicorandil in the treatment of variant angina pectoris.     

Transfusion of red cells after autologous bone marrow harvest in patients with acute leukemia and malignant lymphoma

Bone marrow was harvested for the purpose of autologous bone marrow transplantation (ABMT) in 21 patients previously treated with chemotherapy and in complete remission from acute leukemia or non-Hodgkin's lymphoma. The volume required to obtain 2 x 10(8) nucleated cells per kg was less than 15 mL per kg in 13 patients and more than 15 mL per kg in 8 patients. The blood admixture was proportional to the aspirated volume (p less than 0.0001). The number of granulocyte-macrophage colony-forming units (CFU-GM) harvested in the groups was 8.4 +/- 2.2 and 3.4 +/- 1.4 x 10(4) per kg, respectively (p less than 0.0001). Autologous red cells were transfused into 16 of 21 patients, who did not require further homologous transfusions. The mean drop in hemoglobin from the preoperative level was 1.0 +/- 0.2 g per dL. No adverse effects were noted. It is concluded that large single-volume bone marrow harvests are possible and may reduce the need for a second harvest, and that, through the transfusion of autologous red cells obtained during marrow harvest, homologous blood transfusion can be avoided in most patients.     

Infliximab in severe steroid-refractory ulcerative colitis: a pilot study.

Tumor necrosis factor-alpha (TNF alpha)-neutralization by infliximab has previously proven efficacious in chronic active Crohn's disease (CD). We performed an open-label pilot study of a single infusion of 5 mg/kg infliximab in six patients with severe active, steroid-refractory ulcerative colitis (UC). Clinical activity was evaluated according to Lichtiger on days -1, day 7, and day 28. Colonoscopy with biopsy was performed on day -1 and day 7. All patients showed marked clinical improvement by day 7 (Lichtiger score 16.3 +/- 0.4 [day -1] vs 4.8 +/- 0.7 [day 7], p < 0.0001). Four of six patients had long-term remission (Lichtiger score 7.7 +/- 2.2 [day 28], P < 0.01 compared to day -1), with a median follow-up of 5.5 months. Colonoscopy confirmed significant healing of endoscopic lesions. The inflammatory infiltrate disappeared on H&E stains, with a marked reduction in infiltrating neutrophils. Semiquantitative evaluation of T and B lymphocytes and macrophages by immunohistochemistry did not reveal major differences compared to pre-treatment. Apoptotic cells in the mucosa were reduced on day 7. Our data point toward a novel efficacious treatment option in severe steroid-refractory UC and raise the need for controlled trials.     

Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients

BACKGROUND: Dipeptide alanyl-glutamine is a commonly used substrate in major trauma patients. Its importance and effects are widely discussed; as yet, it has not been elucidated whether its administration influences glucose homeostasis. OBJECTIVE: We studied the effect of alanyl-glutamine administration on insulin resistance. DESIGN: Prospective, randomized, controlled trial. SETTING: Intensive care unit of a tertiary level hospital. PATIENTS: Multiple-trauma patients. INTERVENTIONS: Patients were randomized into two groups and assigned to receive parenterally an equal dose of amino acids either with alanyl-glutamine in the dose of 0.4 g x kg body weight(-1) x 24 hrs(-1) (group AG) or without alanyl-glutamine (control group C). This regimen started 24 hrs after injury and continued for 7 days. To assess insulin sensitivity, we performed an euglycemic clamp on day 4 and day 8 after injury. MEASUREMENTS AND MAIN RESULTS: We randomized 40 patients, 20 into each group. At day 4, insulin-mediated glucose disposal was higher in group AG (2.4 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference from group C (1.9 +/- 0.6 mg x kg(-1) x min(-1), p = .044). At day 8, glucose disposal was higher in group AG (2.2 +/- 0.7 mg x kg(-1) x min(-1) glucose), with significant difference in comparison with group C (1.2 +/- 0.6, p < .001). Diminution of the main glucose homeostasis variables in group C between days 4 and 8 of the study was statistically significant (p < .001); however, differences in these variables in group AG were without statistical significance. CONCLUSIONS: Parenteral supplementation of alanyl-glutamine dipeptide was associated with better insulin sensitivity in multiple-trauma patients.     

Basal asynchrony and resynchronization with biventricular pacing predict long-term improvement of LV function in heart failure patients

Biventricular pacing (BiV) is emerging for patients with dilated cardiomyopathy (DCM) and asynchrony. We measured basal asynchrony and early resynchronization by radionuclide angioscintigraphy (RNA) in order to predict long-term evolution of ventricular function after BiV. Thirty-four patients (NYHA Class III-IV,65.4 +/- 11 years) with large QRS(179 +/- 18 ms)were implanted with BiV and studied by RNA before (D0), at day 8 (D8), and during follow-up(20 +/- 7 months). We calculated left and right ejection fractions, the interventricular dyssynchrony (TRVLV), and the apicobasal dyssynchrony (Tab). LVEF improved from 20.2 +/- 8.1%(D0) to27.1%+/- 12.6%(follow-up,P < 0.003 vs D0) and RVEF from 28.6%+/- 13%(D0) to 34.3 +/- 11.5%(follow-up,P < 0.03 vs D0). Inter- (DeltaTRVLV) and intraventricular resynchronization was immediate and remained stable: TRVLV decreased from 68.3 +/- 38 ms(D0) to 13.4 +/- 48.5 ms(D8) and1.8 +/- 39.2 ms(follow-up,P < 0.0001 vs D0); and Tab from 45.8 +/- 64.1 msto-18 +/- 68(D8) and-28.3 +/- 53.6 ms(follow-up,P < 0.0001 vs D0). Early inter- and intraventricular resynchronization (DeltaTab) at D8 were related to late LVEF and RVEF improvement. Together, an LVEF > 15% and a significant interventricular dyssynchrony (TRVLV > 60 ms) at D0 have a sensitivity of 79% and a positive predictive value of 83% to predict an improvement of LVEF superior to 5% at follow-up. In DCM patients, BiV resynchronizes ventricles early and in the long-term, while RVEF and LVEF improve progressively. Patients with large electromechanical dyssynchrony benefit most from BiV.     

Enterovirus infection as a risk factor of acute coronary syndrome and its complications

Antigens of enteroviruses were detected quantitatively in the modified complement-binding reaction in blood samples from 102 of the 208 (49%) patients with ACS, in coronary artery tissues from 23 of 24 and heart from 51 of 94 (54.3%) patients with MI who died from cardiogenic shock and/or cardiac rupture. The relative level of enterovirus antigen (RLEVA) in the blood of patients with MI complicated and uncomplicated by cardiogenic shock and/or cardiac rupture was 0.42 +/- 0.04 and 0.29 +/- 0.02 arbitrary units respectively (p = 0.032) compared with 0.21 +/- 0.07 in patients with unstable angina (UA) (p = 0.0001). RLEVA in patients with UA was significantly lower than in those with uncomplicated MI (p < 0.011). RLEVA in necrotized myocardial areas after death from cardiogenic shock (0.54 +/- 0.18) and/or cardiac rupture (0.46 +/- 0.15) was higher than outside MI zones (0.30 +/- 0.14 and 0.26 +/- 0.10 respectively) (p < 0.01). RLEVA in coronary vessels feeding the necrotic zones of patients with MI complicated by cardiogenic shock (0.44 +/- 0.18) was higher (p = 0.03) than in the vessel feeding tissues outside the MI zone (0.29 +/- 0.19). It is concluded that enterovirus infection is a factor of ACS; it is directly involved in its pathogenesis and promotes the development of cardiogenic shock and/or cardiac rupture.     

Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units

OBJECTIVES: To study the effect of a parenteral nutrition solution enriched with potential precursors of glutamine, i.e., arginine and glutamate, on plasma glutamine concentrations and protein metabolism. DESIGN: Prospective, randomized, single-blind, comparative study. SETTING: Two intensive care units in two different hospitals. PATIENTS: Fifteen surgical patients. INTERVENTIONS: Patients were randomized to receive total parenteral nutrition for 5 days with the enriched glutamine precursor solution (GlnP+ group) or a conventional solution (control group), both total parenteral nutrition providing 0.25 gN/kg per day and 35 kcal/kg per day (glucose/lipids, 70%:30%). MEASUREMENTS AND MAIN RESULTS: Plasma amino acid concentrations before (T0) and after 3 hrs (T3) of perfusion, nitrogen balance (daily and cumulated), and urinary excretion of 3-methylhistidine were measured daily from day 1 to day 5. The two groups were identical for age, weight, severity score, and nitrogen and energy intakes. After a 3-hr perfusion, plasma concentrations of arginine, ornithine, and glutamine increased, and the differences (T3 - T0) were significantly higher in the GlnP+ group: arginine, 107.6+/-7.0 vs. 51.9+/-3.3 (mean over 5 days; p < .001); ornithine, 78.9+/-7.1 vs. 43.6+/-3.1 (p < .001); and glutamine, 32.4+/-8.6 vs. 6.7+/-5.0 micromol/L (p < .05), respectively. A positive correlation was found between arginine and glutamine plasma increases only in the GlnP+ group: r = .45; p < .01 (Spearman's rank-correlation test). Daily and cumulated nitrogen balances were not significantly different between the two groups but were positive (difference from 0) only in the GlnP+ group. The urinary 3-methylhistidine/creatinine ratio decreased significantly from day 1 to day 5 only in the GlnP+ group: 24.5+/-2.7 vs. 18.8+/-2.7 micromol/mmol (p < .05). CONCLUSIONS: Total parenteral nutrition enriched with arginine and glutamate promotes a better nitrogen balance, limits protein myofibrillar catabolism, and generates glutamine, with arginine (not glutamate) probably being the main contributor to the glutamine-generating effect of the solution through the formation of ornithine.     

Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial

Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p < 0.01). The serum levels of urea also declined (p < 0.01), more pronouncedly in Group I (p < 0.025). In Group I, there was a significant rise in the levels of leucine (p < 0.01), isoleucine (p < 0.01), valine (p < 0.02) and albumin (p < 0.01) and a decrease in protein-uria (p < 0.01). Analysis of the lipid spectrum revealed a mild yet significant decrease in total cholesterol and LDL-cholesterol (p < 0.02), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 4.2 +/- 0.8 down to values a low as 2.2 +/- 0.6 mmol/L; p < 0.01) whereas HDL-cholesterol levels increased (from 0.9 +/- 0.1 to 1.2 +/- 0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum concentration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD and EPO potentiates the beneficial effects on metabolism of proteins, amino acids and surprisingly, also lipids. Long-term co-administration of KA, EPO and LPD was also associated with a delay in progression of renal insufficiency and a reduction in proteinuria. Thus, concomitant administration of KA and EPO during a low-protein diet presents an effective treatment modality in the conservative management of CRF.     

Oxygen free radical generation in healthy blood donors and cardiac patients: the protective effect of allopurinol

Cardiopulmonary bypass (CPB) activates the complement system, which leads to granulocyte activation and free radical production. Free radical activity during CPB has been associated with myocardial dysfunction. However, the relationship between cardiac enzymes and granulocytes to lipid peroxidation in cardiac surgery patients is unknown. Moreover, the effect of allopurinol on lipid peroxidation during mechanical trauma has to be explored. Thirty-four patients undergoing coronary bypass surgery and 26 healthy blood donors participated in this prospective study where granulocyte counts, cardiac enzymes and malondialdehyde (MDA) were measured and related. Allopurinol was used ex vivo, as scavenger, to explore its effect on lipid peroxidation. In the patient group, the mean preoperative MDA level (2.2 +/- 0.7, nmol/ml) significantly increased after 30 min of bypass (3.3 +/- 0.9 nmol/ml; p < 0.0001), and showed a second peak at aortic declamping (4.1 +/- 0.9 nmol/ml). There were significant correlations between MDA and granulocyte counts (r = 0.59, p < 0.0001) and cardiac enzymes (r = 0.55, p < 0.0001). In an ex vivo setting, further mechanical trauma to blood significantly increased the MDA levels, both in the control (p < 0.0001) and in the patient group (p < 0.0001) and this effect could be reduced by allopurinol (p < 0.0001). CPB and mechanical trauma generate oxygen free radicals. Allopurinol was found to reduce lipid peroxidation of red cells following mechanical trauma and this has to be further investigated regarding its ability to reduce morbidity in patients undergoing open heart surgery.     

Blood pressure, volume, and sodium control in an automated peritoneal dialysis population.

OBJECTIVES: To examine the control of blood pressure and volume, and the role of sodium removal in a single, large, contemporary, automated peritoneal dialysis (APD) population where icodextrin is used liberally and there is a policy to avoid long duration glucose-based daytime dwells. DESIGN: Observational cross-sectional study. SETTING: A university hospital. PATIENTS: 56 APD patients, with a mean duration on peritoneal dialysis of 1.9 years; 50% were prescribed icodextrin. MAIN OUTCOME MEASURES: Blood pressure, extracellular water volume (ECW)-to-intracellular water volume (ICW) ratio, and total (peritoneal and urinary) sodium removal. RESULTS: Sodium Removal: Mean total sodium removal, while low at 102.9 +/- 64.6 mmol/day, showed a wide range, with 41% having a sodium removal of >120 mmol/day. Total sodium removal correlated with total body water, ECW, and ICW (p < 0.001, p < 0.001, p < 0.025, respectively), as well as with height and weight (p < 0.06, p < 0.01 respectively). On multivariate analysis, only ultrafiltration volume and urine volume were significantly associated with total sodium removal (r(2) = 0.67, p < 0.0001 for both). There was also a correlation between sodium removal and urea nitrogen appearance (r(2) = 0.31, p < 0.001), with urea nitrogen appearance in turn being closely correlated with ICW (p < 0.001). Volume Status: The ECW/ICW ratio was 0.88 +/- 0.17, which was not significantly different to that found in hemodialysis patients without clinical evidence of fluid overload, either predialysis (0.96 +/- 0.16) or postdialysis (0.92 +/- 0.16); p = 0.07 and 0.36 respectively. Blood Pressure: Mean +/- standard deviation systolic blood pressure (BP) was 111.9 +/- 18.2 mmHg and diastolic BP was 63.3 +/- 11.9 mmHg, with only 4 (7%) patients having a systolic BP > 140 mmHg and 1 (2%) having a diastolic BP > 80 mmHg. Median number of antihypertensives was 1 per day. Blood pressure control and ECW/ICW ratio were similar in those with sodium removal >120 mmol/day compared to those with sodium removal < or =120 mmol/day (p = 0.39 for SBP, p = 0.70 for diastolic BP, p = 0.24 for ECW/ICW). CONCLUSIONS: We have shown that good blood pressure and volume control is achievable in a large contemporary APD population with liberal use of icodextrin and avoidance of long daytime glucose-based dwells. Neither low nor high sodium removal was associated with more frequent hypertension or volume expansion.