Potential therapeutic applications of infusions and hydroalcoholic extracts of Romanian glutinous sage (Salvia glutinosa L.).

Ethnopharmacological relevance: Salvia glutinosa, also known as the glutinous sage, has been used in Romanian folk medicine in the treatment of inflammation, injuries, and mild infections. However, there is no direct scientific evidence to demonstrate these activities. Aim of the Study: The present research was based on evaluating antioxidant, antiproliferative, and α-glucosidase inhibitory activity of S. glutinosa extracts, as well as the in vivo anti-inflammatory activity. Materials and Methods: Infusions and 70% (v:v) ethanol solution extracts of S. glutinosa stems and leaves, collected from two different locations in Romania, were prepared. Ten phenolic compounds were identified and quantified using the LC-DAD-ESI/MSn method, and total phenolic and flavonoid content, as well as in vitro antioxidant (DPPH, ABTS, and FRAP assays), antiproliferative, anti-inflammatory and alpha-glucosidase inhibitory activities were determined. A rat model of induced inflammation with turpentine oil was used for the examination of in vivo effects of the extracts, using diclofenac as an anti-inflammatory control. Results: The highest inhibitory α-glucosidase activity was determined to be IC50 = 0.546 mg/ml for the hydroalcoholic extract made with plant material collected on the road to Sighișoara. The highest cytotoxic activity against HepG2 cell line was determined to be GI50 = 131.68 ± 5.03 µg/ml, for the hydroalcoholic extract made with plant material from Sighișoara. In vivo administration of extract (200 mg lyophilized powder/ml) showed a significant reduction of NO production. Conclusion: Our findings indicate that S. glutinosa extracts exhibit antioxidant, α-glucosidase inhibitory activity, as well as a modest cytotoxic effect on HepG2 cell line. By in vivo administration, the extracts show anti-inflammatory and antioxidant activity, which correlates with the traditional use of the species. The environmental conditions seemed to induce important changes in the chemical composition and the bioactivity of the herbal preparations derived from S. glutinosa.

Transesophageal and intracardiac ultrasound in arrhythmogenic right ventricular dysplasia/cardiomyopathy: Two case reports.

RATIONALE: Two-dimensional echocardiography (2D echo) is a major tool for the diagnosis of Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However 2D echo can skip regional localized anomalies of the right ventricular wall. We aimed to determine whether transesophageal and intracardiac ultrasound can provide additional information, on the right ventricular abnormalities compared to 2D echo. PATIENT CONCERNS: Case 1 is a 30-year-old patient that presented in the Emergency Department with multiple episodes of fast monomorphic ventricular tachycardia (VT) manifested by palpitations and diziness. Case 2 is a 65-year-old patient that also presented with episodes of ventircular tachycardia associated with low blood pressure. DIAGNOSIS: Both patients had a clear diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy confirmed by cardiac magnetic resonance imaging. INTERVENTION: In both patients transesophageal and intracardiac ultrasound was performed, which brought more information on the diagnosis of ARVD/C compared to transthoracic echocardiograpy. OUTCOMES: The first patient was implanted with an internal cardiac defibrillator and treated with Sotalol for VT recurrences. He presented episodes of VT during follow-up, treated with antitachycardia pacing. The second patient was implanted with an internal cardiac defibrillator and treated with Sotalol without any VT recurrence at 18 month-follow-up. LESSONS: Transesophageal echocardiography and intracardiac echocardiography can provide additional information on small, focal structural abnormalities in patients with ARVD/C: bulges, saculations, aneurysms with or without associated thrombus, partial or complete loss of trabeculations and hypertrophy of the moderator band. These changes are particularly important in cases with "concealed" form of the disease in which no morphological abnormalities are evident in transthoracic echocardiograpy.

NT-pro-BNP during isotonic and isometric exercise in heart failure patients with preserved LV ejection fraction.

BACKGROUND: NT-pro-BNP level is increased in both systolic and diastolic heart failure (HF) and furthermore increases more during exercise. In diastolic HF, NT-pro-BNP might increase more during isometric exercise than during isotonic exercises because of increased afterload. We studied NT-pro-BNP values during isometric (hand-grip) and isotonic (cycloergometer) exercise in HF patients with preserved left ventricular ejection fraction and different degrees of diastolic dysfunction. METHODS: We studied 87 patients, aged 58 ± 7.9 years, 42.6% females, with heart failure with LVEF > 40% and diastolic dysfunction. The patients were randomly distributed in two groups: 43 patients (Group I) and 44 patients (Group II). Group I underwent ramp exercise testing on a cycloergometer. Group II performed an isometric handgrip test. Plasma NT-pro-BNP levels were measured at rest and immediately after exercise. RESULTS: An abnormal relaxation (AR) pattern was recorded in 30 patients of Group I and 31 patients of Group II. Pseudonormalisation (PSN) and restrictive (R) pattern were noted in 13 patients of each group. As concerns Group I, NT-pro-BNP levels were increased in all patients, particularly in those with PSN or R pattern (p < 0.05). During exercise NT-pro-BNP decreases significantly in AR (1033 ± 516.63 to 800.51 ± 675.89 pg/mL) but not in PSN or R patients (1656.75 ± 977.48 to 1486.38 ± 1182.51 pg/mL). For Group II, NT-pro-BNP registered a similar increase as in Group I, with maximal values in PSN or R subgroup as compared to abnormal relaxation (p < 0.05). At peak exercise, NT-pro-BNP was practically unchanged as compared to the rest values for the whole group (-6%) and for the two subgroups (AR -6.7% and PSN or R -5.21%). We compared rest and exercise NT-pro-BNP with E/E' ratio > 12 in order to identify increased diastolic filling pressure in the LV; AUC was 0.70 and 0.66 for rest and exercise NT-pro-BNP in case of isotonic testing and 0.74 and 0.72 in case of isometric exercise. CONCLUSIONS: Our data suggest that in HF patients with preserved left ventricular ejection fraction, moderate isotonic and isometric exercises do not determine a significant increase (isometric exercise) or even decrease (isotonic exercise) in the value of NT-pro-BNP.

The acute effect of Metoprolol upon NT-proBNP level in patients with congestive heart failure.

UNLABELLED: Brain natriuretic peptide (BNP) is a sensitive and specific marker of left ventricular (LV) function. The acute effect of beta blockers upon plasma BNP levels in CHF patients has been less studied but it is important because of the initial possible depressing effect upon LV function. PURPOSE: To investigate the acute effect of oral Metoprolol upon plasma proBNP levels in CHF patients. METHODS: There were included 56 patients with congestive heart failure, 38 with ischemic heart disease and 18 with idiopathic dilated cardiomyopathy, 40 males and 16 females, aged between 25 and 65 years, who were compared with 19 healthy individuals, 12 males and 7 females, of the same age. All patients were free of beta blockers treatment. Plasma Nt-proBNP was determined in fasting state using ELISA method (NV <250 fmol/mL). After this, every patient received 50 mg Metoprolol succinate and at three hours (considered as peak plasmatic concentration) venous blood samples were again obtained and Nt-proBNP determined. RESULTS: NT-pro BNP was increased (1400 +/- 130 fmol/mL) in heart failure patients and normal (187 +/- 17.2 fmol/mL) in healthy controls. After Metoprolol the plasmatic level of NT-proBNP was not significantly different in both healthy controls (162 +/- 13.3 fmol/mL) and heart failure patients (1419 +/- 133 fmol/ml) in comparison with baseline values. After Metoprolol NT-proBNP decreased (from 1266 +/- 121 to 1120 +/- 107, p>0.05) in III NYHA class patients and increased (from 1457 +/- 142 to 1530 +/- 150, p<0.05) in IV NYHA class patients. It remained unchanged in patients with LVEF >30% (1384 +/- 140 vs 1389 +/- 129 fmol/mL) and increased (from 1480 +/- 134 to 1690 +/- 161 fmol/mL, p<0.05) in patients with LVEF <30%; it was not significantly modified in patients with atrial fibrillation in comparison with those in sinus rhythm (1348 +/- 132 vs 1516 +/- 168 fmol/mL). CONCLUSION: Beta blockers do not have a severe depressant effect on left ventricular performance in all patients with systolic heart failure. A LVEF>30% suggests, but the lack of modification of NT-proBNP levels after administration of 50 mg Metoprolol confirm, that the beta blocking treatment can be initiated with higher doses than those recommended until now.

Cardiac peptides during exercise test in ischemic and non-ischemic heart failure patients.

BACKGROUND: Cardiac peptides are increased at rest in heart failure patients representing a useful diagnostic tool for this condition. Recently it has been demonstrated that cardiac peptides increase also during myocardial ischemia. Cardiac peptides increase during exercise in heart failure patients, but it has not been established yet if the increase is the same in ischemic and nonischemic patients. METHODS: There were studied 50 heart failure patients, 32 ischemic and 18 nonischemic, 35 males and 15 females aged 61.8 +/- 11.61 after the relief of congestive syndrome, which was submitted to a symptom-limited exercise stress test on a cycloergometer. Blood samples were obtained at rest and at a peak effort and the plasmatic values of NT-proBNP (NV<250 fmoles/mL) and of NT-proANP (NV<1950 fmoles/mL) were determined using the ELISA method. RESULTS: At rest, both NT-proBNP and NT-proANP were more increased in nonischemic (1104.33 +/- 730; 3275.55 +/- 3424) than in ischemic patients (685.68 +/- 452.01, 2265.0 +/- 2552.32) with significant differences only for NT-proBNP (p=0.016). During exercise NT-proBNP increase from 836.40 +/- 596.34 to 1403.92 +/- 2126.21 and NT-proANP from 2628.80 +/- 2903.41 to 3701.30 +/- 3237.76, the final values being again more increased in nonischemic patients (NT-proBNP-2945.44 +/- 3257.89; NT-proANP-3174 +/- 2905); for NT-proBNP p<0.05. The results suggest that the stretching effect during exercise is more increased at the ventricular level in comparison with the atrial level (67% increase for NT-proBNP and only 40% for NT-proANP). Surprisingly, myocardial ischemia does not increase additionally cardiac peptides either at rest or during exercise. Our data suggest that the intracardiac pressure is more important than ischemia in determining the increase of cardiac peptides in heart failure patients because the left ventricular ejection fraction was lower in nonischemic patients (40.03 +/- 5.5 vs 38.11 +/- 4.07). CONCLUSION: Cardiac peptides are increased, both at rest and during exercise, in nonischemic heart failure patients in comparison with ischemic ones, probably in relationship with the lower left ventricular systolic function.

Results of a long-term training program after acute myocardial infarction.

BACKGROUND: It is not well known what should be the benefits of a prolonged physical rehabilitation program after an acute myocardial infarction. METHODS: Our study is an open, randomized comparison of a long-term versus a standard rehabilitation program. Sixty-seven patients with acute myocardial infarction were included in an outpatient physical rehabilitation program of 6-8 weeks. Of these, 22 randomly selected patients continued the program until the 36th month (Group A). Twenty-five of the others were rechecked after 36 months, and represented the controls (Group B). For both groups, at the end of this period, a cycloergometer exercise test evaluated the exercise capacity of subjects and an echocardiogram was performed to determine left ventricular systolic and diastolic function. RESULTS: The maximal exercise capacity increased from 147 +/- 13.8 W to 178 +/- 16.4 W in Group A (p < 0.01), but it decreased from 144 +/- 13.2 to 132 +/- 12.8 W in group B. Functional aerobic impairment decreased from 29 +/- 2.7% to 22 +/- 2.1% in Group A, but it increased from 26 +/- 2.5% to 37 +/- 3.8% in Group B. The ejection fraction and diastolic function parameters were not significantly modified during the 36 months, for both groups. CONCLUSION: Long-term physical rehabilitation is useful in patients after an acute myocardial infarction to increase effort capacity, but left ventricular performance is not significantly changed.

Plasma nitric oxide metabolite levels increase during successive exercise stress testing - A link to delayed ischemic preconditioning?

BACKGROUND: Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning. OBJECTIVES: To determine whether plasma nitrates and nitrites (NO(x) (-), as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement METHODS: Twenty-two patients with ischemic heart disease each performed two effort tests at 24-h intervals. Plasma NO(x) (-) level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical endpoints and were compared between the two tests. RESULTS: Plasma NO(x) (-)increased slightly after the first exercise test compared with pretest value (17.05+/-1.6 mumol/mL versus 15.38+/-1.4 mumol/mL). In turn, after the second test there was a significant rise in NO(x) (-) level (23.65+/-2.2 mumol/mL versus 15.10+/-1.3 mumol/mL, P<0.03). The pretest values were almost identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although ischemic stress was the same, ST depression was significantly lower (P<0.01) for the second test (0.85+/-0.06 mm versus 1.73+/-0.16 mm). CONCLUSION: Our study shows an increased plasma NO(x) (-)level after the second of two consecutive exercise stress tests at 24-h intervals, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as a trigger and effector of ischemic preconditioning.

Ischemic preconditioning by repeated exercise tests involves nitric oxide up-regulation.

BACKGROUND: Animal studies show that nitric oxide is involved in delayed ischaemic preconditioning. OBJECTIVES: To determine whether plasma nitrates/nitrites (NOx-, as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement. METHODS: There were studied 22 patients with ischemic heart disease, who performed two effort tests at 24-hour interval. Plasma NOx- level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical end-points and were compared between the two tests. RESULTS: Plasma NOx- increased slightly after the first exercise test compared to pre-test value (17.05 +/- 1.6 vs. 15.38 +/- 1.4 micromol/ml). In turn, after the second test a significant rise of NOx- level (23.65 +/- 2.2 vs. 15.10 +/- 1.3 micromol/ml, p < 0.03) was noticed. The pre-test value was practically identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although the ischaemic stress was the same, ST depression was significantly lower (p < 0.01) at the second test (0.85 +/- 0.06 vs. 1.73 +/- 0.16 mm). CONCLUSION: Our study shows an increase of plasma NOx- level after the second of two consecutive exercise stress tests at 24 hour interval, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as both trigger and effector of ischaemic preconditioning.