Evaluation of hepatoprotective effect of Nebivolol and sodium copper Chlorophyllin on CCL4-induced hepatotoxicity in mice.

OBJECTIVE: In this study, the protective effect of sodium copper chlorophyllin and nebivolol was evaluated in a mice model of CCL4 induced hepatotoxicity. Silymarin was used as a traditional hepatoprotective drug. MATERIALS AND METHODS: Thirty (30) mice were used as they were divided into five groups: the first group was the control group which received distilled water + olive oil, the second group which received 1.5 ml/kg of CCl4 diluted in olive oil three times a week, the third group which received CCl4 + Silymarin 50 mg/kg/day, the fourth group which received CCl4 + nebivolol 4 mg/kg/day, and the fifth group which received 1.5 ml/kg of CCl4+ Cu-chlorophyllin 50 mg/kg/day. The drugs were given by intraperitoneal route for 5 weeks. The detection, quantification of CCl4 induced hepatotoxicity and possible protective effect of either silymarin, nebivolol, or sodium copper chlorophyllin were assessed using biochemical analysis of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein, lipid profile, an assay of oxidants and antioxidants, assay of interleukin 6 (IL6) and tumor necrosis factor-alpha (TNF-α), and histopathological examination. RESULTS: The administration of carbon tetrachloride (CCl4) produced pronounced liver impairment. It significantly increased ALT, AST, ALP, malondialdehyde, and serum nitric oxide levels compared to normal control group besides a decrease in total protein, serum catalase, tissue SOD, and GSH levels. IL-6 and TNF-α levels were significantly higher while total cholesterol was significantly lower in mice receiving CCL4 compared to the normal control group. CCL4 induced severe hyperemia and congestion inside the portal area with leukocytic infiltration, hepatic degeneration, and bridge fibrosis. CONCLUSIONS: Co-administration of either silymarin, nebivolol, or sodium copper chlorophyllin with CCl4 was able to ameliorate up to almost contradict CCl4 induced hepatic injury through their anti-inflammatory and antioxidant activities.

Author Correction: Assessment of the cardioprotective effect of liraglutide on methotrexate induced cardiac dysfunction through suppression of inflammation and enhancement of angiogenesis in rats.

Correction to: European Review for Medical and Pharmacological Sciences 2021; 25 (19): 6013-6024-DOI: 10.26355/eurrev_202110_26879-PMID: 34661261, published online on 15 October 2021. After publication, the authors applied to add some corrections to the paper. They wanted to change the second affiliation of one co-author Dr. Eman Said. The second affiliation will be "Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, Saudi Arabia", instead of "College of Pharmacy, Qassim University, Al-Qassim, Saudi Arabia". There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause.  https://www.europeanreview.org/article/26879.

Assessment of the cardioprotective effect of liraglutide on methotrexate induced cardiac dysfunction through suppression of inflammation and enhancement of angiogenesis in rats.

OBJECTIVE: Methotrexate (MTX) is one of the most commonly used anti-cancer drugs for various types of neoplasms. It is associated with multiple cytotoxic effects including nephrotoxicity, hepatotoxicity and cardiotoxicity. Liraglutide (LIR) is a potent anti-diabetic drug and also has antioxidant and anti-inflammatory properties. In this study, we tried to investigate the protective effect of LIR on MTX induced cardiotoxicity and to identify the molecular mechanisms for this protection. MATERIALS AND METHODS:  Rats were divided into 4 groups, including control group, LIR group, MTX group and LIR + MTX group. ECG was measured then blood samples were taken, and hearts were excised for biochemical and histological investigations. RESULTS: MTX group exhibited a mild non-significant irregular bradycardia, an increase of CK-MB besides a decrease of total antioxidant capacity. MTX administration also resulted in downregulation of vascular endothelial growth factor (VEGF), while caused upregulation of interleukin 1 beta (IL-1B) and interleukin 6 (IL-6) in comparison to the control group. Also, MTX group showed histological abnormalities besides negative VEGF and positive iNOS as detected by immunohistochemical staining compared to the control group. LIR administration could reverse these results. CONCLUSIONS: LIR prevented MTX induced cardiotoxicity through its antioxidant and anti-inflammatory properties.

Abnormal left ventricular early diastolic filling during dobutamine stress Doppler echocardiography is a sensitive indicator of significant coronary artery disease.

OBJECTIVES: This study was designed to assess changes in Doppler indexes of left ventricular ejection and filling in response to high dose (40 micrograms/kg body weight per min) dobutamine stress and their utility in detection of coronary artery disease compared with that of new wall motion abnormalities. METHODS: Ten patients with a low likelihood of coronary artery disease served as a control group, and 23 patients with documented single-vessel coronary artery disease underwent baseline and peak dobutamine echocardiographic and Doppler studies. RESULTS: In both groups dobutamine induced similar increases in heart rate and systolic blood pressure. During the test, 14 patients had new wall motion abnormalities, 13 had angina, and 7 had electrocardiographic ST segment changes. No markers of ischemia occurred in the control subjects. Dobutamine induced qualitatively similar changes from baseline to peak dobutamine stress in control subjects and patients in peak aortic velocity (46% vs. 42%, p = NS), average aortic acceleration (61% vs. 43%, p = 0.03) and systolic time-velocity integral (7% vs. 2%, p = NS). Dobutamine caused marked increases in control subjects and decreases in patients in peak early filling velocity (E) (33% vs. -22%, p < 0.0001) and average E acceleration (76% vs. -28%, p < 0.0001). The response of Doppler early filling indexes to dobutamine stress was abnormal in all patients. There was no overlap in the percent change from baseline to peak dobutamine stress between control subjects and patients for E and E acceleration. CONCLUSIONS: During dobutamine stress testing, an abnormal response of Doppler indexes of left ventricular early filling is a more sensitive marker of significant single-vessel coronary disease than are new wall motion abnormalities, and it is far superior to the response of Doppler ejection variables as a predictor of coronary artery disease.

Prognostic value of dipyridamole sestamibi single-photon emission computed tomography and dipyridamole stress echocardiography for new cardiac events after an uncomplicated myocardial infarction.

A high-dose dipyridamole stress test (0.84 mg/kg in 6 minutes) with simultaneous sestamibi single-photon emission computed tomographic (SPECT) and echocardiographic imaging was performed in 89 patients before hospital discharge after an uncomplicated myocardial infarction. The aim of this study was to determine the prognostic value of these tests for new cardiac events and to compare the relative values of SPECT and echocardiography in a postinfarction dipyridamole stress test. Two years after infarction, nine patients (10%) had died, five patients (6%) had suffered a nonfatal reinfarction, and 14 patients (16%) had been readmitted to the hospital for a revascularization procedure. Cardiac death had occurred in 5 (10%) of 48 patients with a positive SPECT versus 4 (10%) of 41 with a negative SPECT (difference not significant) and in 6 (19%) of 31 with a positive echocardiogram versus 3 (5%) of 56 with a negative echocardiogram (p = 0.05). Cardiac death or reinfarction had occurred in 8 (17%) of 48 patients with a positive SPECT versus 6 (15%) of 41 with a negative SPECT (difference not significant) and in 6 (19%) of 31 with a positive echocardiogram versus 8 (14%) of 56 with a negative echocardiogram (difference not significant). Thus the predictive value of the dipyridamole stress test for new cardiac events after an uncomplicated myocardial infarction was limited, irrespective of the method used to detect ischemia. Reversible perfusion defects were identified more frequently than new wall motion abnormalities but did not predict late events. A positive dipyridamole echocardiogram was associated with a higher late mortality rate but did not predict other cardiac events.

[Stress echocardiography: 4 years of experience at the Thoraxcenter]. / Ecocardiografia da stress: quattro anni di esperienza al Thoraxcenter.

In this article, we report the experience on stress echocardiography at the Thoraxcenter of Erasmus University of Rotterdam in the years 1990-1994. Different types of stress have been used in conjunction with ultrasound techniques. The results have been compared with other non-invasive methods (exercise ECG testing, myocardial perfusion scintigraphy with single photon emission computed tomography) and with coronary arteriography. Both the diagnostic and prognostic value of stress echocardiography have been assessed in different clinical situations, as in patients with chest pain and suspected or proven coronary artery disease, patients referred for percutaneous transluminal coronary angioplasty, patients referred for major non cardiac vascular surgery. After this period of validation, stress echocardiography has now a definite role in the clinical decision making for the evaluation of myocardial ischemia. The assessment of viable myocardium, especially in patients with advanced left ventricular dysfunction, is one of the major topic currently under investigation. Practical aspects of the interpretation of the tests, costs and organization of the stress echo laboratory, indications and newest research applications are also discussed.

Atropine increases the accuracy of dobutamine stress echocardiography in patients taking beta-blockers.

Dobutamine-atropine stress echocardiography is used for the non-invasive diagnosis of coronary artery disease, but stress test results may be influenced by beta-blockers. The aim of this study was to assess if the addition of atropine can compensate for the presence of beta-blockers in dobutamine stress echocardiography. Twenty-six patients referred for evaluation of chest pain were studied twice, on and off metoprolol 100 mg b.i.d. (in random order sequence) with a wash-out period of at least 48 h. Dobutamine stress echocardiography was performed using up to 40 micrograms.kg-1.min-1, followed, if necessary, by the addition of atropine to achieve 85% of the age-predicted maximal heart rate, unless symptoms or markers of ischaemia appeared. Atropine was given to patients on beta-blockers more often [(22/26) vs (6/26)] than to those off beta-blockers (P < 0.001). Heart rate at every stage of the test was lower on beta-blockers. Chest pain occurred in patients on beta-blockers significantly less than in those off beta-blockers (8% vs 46%), and the addition of atropine made no significant difference (31% vs 46%). During dobutamine stress, new wall motion abnormalities occurred in three patients on beta-blockers (12%); this number increased to 15 after the addition of atropine (57%). New or worsened wall motion abnormalities occurred in 12 patients (46%) off beta-blockers with dobutamine alone and in 14 patients after adding atropine (53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine stress--Doppler echocardiography before and after coronary angioplasty.

To determine if dobutamine-induced myocardial ischaemia causes abnormalities in Doppler parameters of left ventricular ejection and filling and to assess early effects of successful coronary angioplasty (PTCA) on these parameters, dobutamine stress echocardiography and Doppler studies were performed once in 11 normal volunteers and twice in 17 patients (within 1 day pre- and post-PTCA). Dobutamine induced wall motion abnormalities, ST changes and angina in 11, five and five patients, respectively, before and three, two and one patients, respectively, after PTCA. Doppler indices of both systolic and diastolic function were comparable at rest, before and after PTCA. Dobutamine induced similar increases in peak aortic velocity and average acceleration in healthy individuals (39% and 53%) and in patients with one-vessel disease both before (38% and 39%) and after PTCA (39% and 40%). In the three patients with multivessel disease, peak aortic velocity showed a blunted response (-0.3%) before PTCA but increased by 17% after PTCA, while acceleration decreased both before (12%) and after PTCA (14%). There were significant differences (P < 0.0001) between healthy individuals and pre-PTCA patients in the effect of dobutamine on peak early (E) filling velocity (+34% vs -19%), E-acceleration (+35% vs -26%), peak early to atrial filling velocity ratio (E/A) (-0.7% vs -37%) and diastolic time velocity integral (TVI) (+34% vs -22%). After PTCA, the response of Doppler diastolic indices improved during dobutamine, as shown by the increase in E and E-acceleration (+8%, +24%), respectively) and by the decline in the reduction of E/A and TVI (-17% and -10%, respectively). Thus, the response of Doppler diastolic parameters to dobutamine stress is a sensitive indicator of significant coronary disease and is superior to changes in ejection indices. Successful PTCA resulted in an improved diastolic filling response to dobutamine stress.

Simultaneous dobutamine stress echocardiography and technetium-99m isonitrile single-photon emission computed tomography in patients with suspected coronary artery disease.

OBJECTIVES: The purpose of this study was to determine the relative value of dobutamine stress echocardiography and technetium-99m isonitrile single-photon emission computed tomography (mibi SPECT) in the detection of myocardial ischemia. BACKGROUND: Stress-induced new wall motion abnormalities and transient perfusion defects are both used for the diagnosis of myocardial ischemia. METHODS: One hundred five consecutive patients with either proved or suspected coronary artery disease, who were referred for perfusion scintigraphy, were studied by a combination of the two techniques. Both echocardiographic and mibi SPECT images were visually analyzed. Three patients were excluded from the final analysis because of unsatisfactory examinations: two with noninterpretable stress echocardiograms and one with noninterpretable mibi SPECT images. The response to stress was concordantly classified by both techniques in 68% of patients (kappa = 0.51). RESULTS: Dobutamine stress echocardiography revealed the presence of ischemia in 38 and mibi SPECT in 45 patients (overall agreement = 74%, kappa = 0.46). The agreement was higher in patients without previous myocardial infarction (84%, kappa = 0.62). When regional analysis was performed, concordance of stress echocardiography and mibi SPECT occurred in 84% of the 306 regions (kappa = 0.45). Regional agreement was also slightly higher in patients without previous infarction (88%, kappa = 0.50). In 21 patients without previous myocardial infarction who underwent coronary angiography, the overall sensitivity of dobutamine stress echocardiography and mibi SPECT for the diagnosis of coronary artery disease (diameter stenosis > 50%) was 75% and 83%, respectively, with a specificity of 89% (eight of nine patients) for both tests. CONCLUSIONS: Dobutamine stress echocardiography represents a reasonable alternative to dobutamine mibi SPECT for the functional assessment of patients with suspected myocardial ischemia and without previous myocardial infarction.