Cardiovascular & Haematological Disorders - Drug Targets - Volume 20, Issue 1, 2020

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI). Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary. Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post- PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications. Conclusion: Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.

Background: A mathematical model of blood flow is a way to study the blood flow behavior. In this research work, a mathematical model of non-Newtonian blood flow through different stenosis, namely bell shape and cosine shape, is considered. The physiologically important flow quantities of blood flow behavior to describe the blood flow phenomena are obtained such as resistance to flow, skin friction and blood flow rate. Methods: Mathematical methods are used to analyze a mathematical model of blood flow through stenosed artery. The resistance to flow, skin friction and blood flow rate were obtained to describe the blood flow in stenosis. The resistance to flow is a relation between pressure and blood flow rate while the skin friction is the friction at the artery membrane. Resutls: The blood flow in cosine geometry exhibits higher resistance to flow and flow rate than in the bell geometry, while the blood flow in bell geometry gives a higher skin friction than in cosine geometry. Not only the effect of stenotic geometry was studied but also the effect of stenosis depth and stenosis height on the flow quantities Moreover, the power law index was adjusted to explore the non-Newtonian behavior. When blood exhibits Newtonian behavior, the resistance to flow and skin friction decrease but the blood flow rate increases. Conclusion: The stenosed artery geometry, the stenosis length, stenosis depth and the power law index (non-Newtonian behavior) are important factors affecting the blood flow through the stenosed artery. This work provides some potential aspects to further study the causes and development of cardiovascular diseases.

Background: Terebinthus atlanticus (Anacardiaceae) is an important source of essential oil and phenolic compounds justifying its use in traditional medicine. Objective: The present work aimed to evaluate the antidiabetic and the antioxidant activities of the aqueous extract of the leaves of Terebinthus atlanticus (T. atlanticus). Methods: The current study evaluated the effect of a single and repeated (15 days of treatment) oral administration of the aqueous extract of the leaves of T. atlanticus (PALAE) on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rats. Furthermore, the effect of PALAE on glucose tolerance and histopathological examination of the liver was carried out. Results: A single oral administration of PALAE reduced blood glucose levels in normal (p<0.05), and STZ diabetic rats (p<0.0001), 6 and 4 hours after administration, respectively. Furthermore, this extract had an optimal effect (p<0.0001) in both normal and STZ diabetic rats at the 15th and 7th day of treatment. This extract was also shown to prevent significantly the increase on blood glucose levels 120 min after glucose administration, in both normal (p<0.05), and diabetic (p<0.01) treated rats when compared to the control group. In addition, the histopathological analysis highlighted the positive effect of T. atlanticus on pancreas and liver. Conclusion: The study demonstrates the antihyperglycemic effect of the aqueous T. atlanticus extracts in diabetic rats which should be mediated through the amelioration of the oxidative stress as well as an improvement in liver histology.

Background & Objective: Acute renal failure (AKI) is one of the most important complications of PCI. Due to delay in creatinine increase, we need specific factors to detect AKI earlier. The aim of this study is to evaluate the valuable factors by focusing on HFAB-P that can be predictive for AKI after Percutaneous Coronary Intervention (PCI). Methods: This prospective study was performed on 95 patients (55 males and 44 females aged between 49-78 years) under PCI in Golestan and Imam Khomeini hospitals in Ahvaz. Patients were divided into three groups based on the development of AKI after the procedure: no AKI, severe AKI (doubling of serum creatinine or needing dialysis) and any type of AKI (increased creatinine ≥ 0/3 mg/dl or a 50% increase in the means of 1/5 times serum creatinine). The demographic and clinical characteristics of the patients, the medical history and the results of the HFABP marker, GFR, and creatinine before and after PCI were evaluated for all patients. Results: The progenies showed 6 patients with severe AKI, 17 patients with any type of AKI, and 72 patients without AKI. Diabetes (P = 0.003), hypertension (P = 0.027), gender of patients (P = 0.025) and hospital admission days (P <0.001) were significantly different among the groups. Patients' age and positive troponin were significantly higher in patients with AKI. HFABP was the only factor that had significant changes before and after PCI (P <0.001). The cut-off value of HFABP was 4.69 with 95.6% sensitivity and 84.7% specificity. It has a good negative predictive value of 98.39% which suggests it to be a good test for the AKI prediction. Glomerular Filtration Rate (GFR) and creatinine (Cr) were significantly different after PCI (P <0.001). Conclusion: HFABP can be considered as a predictor for AKI after PCI. Moreover, our study suggests that evaluating several parameters such as Cr and GFR before and after PCI can predict the AKI development after PCI.

Background: Chrysin (CH) is one of the main flavonoids of vegetables, fruits, and plants, the neuroprotective effect of which has been demonstrated in this study. Objective: The aim of the current investigation is the evaluation of the impact of chrysin (CH) on serum corticosterone level. Additionally, depression due to chronic stress was studied in animal models. Methods: The rats were restrained for 1 hour daily for 3 weeks. During these weeks, all animals were daily injected with either vehicle or CH (10, 20, 30 μg/kg). Results: Present data indicated that the serum corticosterone levels markedly elevated in the stressed group versus the non-stressed group (p<0.001). The serum corticosterone levels were significantly lower in the stress-exposed rats administered with CH versus the stress-exposed non- CH-treated rats (p<0.05). In addition, immobility time significantly increased in the rats submitted to restraint stress versus the non-stressed group (p<0.001). Also, the number of crossing significantly decreased in the rats submitted to restraint stress versus non-stressed rats (p<0.001). The immobility time and the number of crossing were also reduced in the CH-administrated stressed rats (30 mg/kg) versus non-treated stressed group (p<0.001, p<0.05, respectively). CH also ameliorated the MDA and GSH content as well as antioxidant enzymes activities in stressed rats (p<0.05). Conclusion: The present study suggested that CH might be useful for the management of depressant-like effects induced by chronic stress via decreasing oxidative damage in the brain.

Background: Diabetes mellitus is associated with high blood glucose levels due to insulin shortcoming (insulinopenia) or defective insulin action. The objective of the study was to investigate the antidiabetic and antioxidant effects of Foeniculum vulgare in streptozotocin-induced diabetic rat. Methods: The effects of the leaves aqueous extract (LAE) of Foeniculum vulgare (F. vulgare) at a dose of 10 mg/kg on blood glucose levels were evaluated in normal and streptozotocin (STZ)- induced diabetic rats. Histopathological changes were also evaluated in liver in STZ-induced rats. Results: Single oral administration of F. vulgare LAE reduced blood glucose levels 6 h after administration in STZ diabetic rats (p<0.0001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after the fifteenth day of treatment. During this test, both groups did not show any significant change in their body weight. Moreover, this aqueous extract improved oral glucose tolerance in diabetic rats and revealed a positive effect on liver histology. On the other hand, the extract used in this experiment showed an inhibitory concentration (IC50) of 50% of free radicals with a concentration of 43±1.19 μg/ml. While the synthetic antioxidant (BHT) had an IC50 equal to 22.67±2.17μg /ml. Conclusion: This study demonstrates the antihyperglycemic, hypoglycemic and antioxidant effects of the leaves of F. vulgare in normal and diabetic rats.

Background: Several cardiac biomarkers are being studied to explore their potential in the prognostication of Acute Coronary Syndrome (ACS). However, there are limited studies exploring the relationship between these biomarkers and clinical, laboratory and demographic characteristics. Objective: We sought to determine the factors which influence the concentration of novel cardiac biomarkers such as Galectin-3, suppression of tumorigenicity-2 (ST-2) and Matrix Metallopeptidase-9 (MMP-9) in patients with ACS. Methods: A total of 122 patients with ACS were enrolled in the study. The study patients were categorized into two groups namely: STEMI (n=58) and NSTEMI/UA (n=64). Plasma samples were used to determine the level of biomarkers, Galectin-3 and ST-2, and serum samples were used to determine the levels of MMP-9 using the Enzyme-linked immunosorbent assay (ELISA). The association between the plasma and serum levels of biomarkers and, demographic, clinical and laboratory variables were determined. Statistical analyses for the study were performed using SPSS 16.0 software (SPSS Inc., Chicago, IL, USA). Results: Elderly aged [0.107 (0.012-0.969); p=0.047] patients had higher ST-2. Galectin-3 was higher among female patients [3.693(1.253-10.887); p=0.018] and patients with low left ventricular ejection fraction [2.882 (1.041-7.978); p=0.042]. Patients with lower body mass index [3.385 (1.241-9.231); p=0.017], diabetes [3.650 (1.302-10.237); p=0.014] and high total leukocyte count [2.900 (1.114-7.551; p=0.029] had higher MMP-9 levels. Conclusion: The concentration of galectin-3, ST-2 and MMP-9 are independently influenced by demographic, clinical and laboratory characteristics. It is estimated that these factors should be accounted for when interpreting the results of the biomarker assays.

Background: Anthracyclines, a widely used chemotherapy agent with a definite survival improvement, can result in cardiac toxicity presenting with HF (heart failure). Objective: We aim to assess the predictive value of cardiac biomarkers assessment in combination with myocardial two-dimensional strain echocardiography for early detection of cardiac toxicity in patients who underwent Anthracycline-based chemotherapy. Methods: Fifty-two consecutive adult patients scheduled to undergo the first course of Anthracycline-based chemotherapy were subjected to the study. All the patients underwent highly sensitive 2D echocardiographic evaluation before the treatment, 4 and 12 weeks after completion of first-course chemotherapy. Longitudinal and segmental strains were measured. Serum levels of High-sensitive cardiac troponin I (hscTn-I) and N-terminal-pro-BNP (NT-proBNP) were also assessed before the initiation and 3 weeks after completion of first-course chemotherapy. Results: Fifteen patients (28.8%) revealed a decrease in LVEF (Left Ventricular Ejection Fraction) throughout the evaluations, while just 5 patients met the criteria of cardiac toxicity (9.6%). AUC for Global Longitudinal Strain (GLS) ROC curve at 4 weeks of follow-up was calculated to be 0.968. Inferoseptal Systolic Longitudinal Strain (SLS) had the highest AUC value (AUC: 0.934) among different wall SLS. LVESD (Left Ventricular End-Systolic Diameter) at first and second evaluation could predict the risk of cardiac toxicity among LVESD, LVEDD (Left Ventricular End Diastolic Diameter) and LVEDV (Left Ventricular End-Diastolic Volume). Among cardiac biomarkers, hscTnI had higher sensitivity, while NT-proBNP had higher specificity for cardiac toxicity. Conclusion: This study has shown that hs-cTnI with good sensitivity can predict cardiac toxicity in Anthracycline-based chemotherapy receiver. The use of strain with speckle echocardiography method has a prognostic value; however, both longitudinal and segmental strain should be assessed. Lateral and inferoseptal SLS (Segmental Longitudinal Strain) are specific markers of cardiac toxicity in the course of anthracycline-related cardiac toxicity.

Background: Multicentric Castleman Disease (MCD) presents with enlarged lymph nodes in multiple regions and systemic inflammatory symptoms, due to the dysregulation of cytokines, most commonly interleukin-6 (IL-6). Human herpes virus-8 (HHV-8) is strongly related to MCD (HHV-8-associated MCD) and is being implicated in cytokine dysregulation in patients, the majority of whom are HIV positive or immunosuppressed. Preferred treatment of HHV-8- associated MCD depends on the presence or not of concurrent Kaposi sarcoma and on whether the patient has life-threatening organ failure or poor performance status thought to be related to HHV- 8-associated MCD. Case Presentation: Herein, we describe a female patient with HHV-8 positive, HIV negative MCD, who responded well to the administration of rituximab once weekly for four weeks alone for three cycles. Conclusion: HHV-8 positive, HIV negative MCD treatment modalities are only anecdotal due to the rarity of this form of MCD. Administration of rituximab alone seems to be beneficial among patients with good performance status and the absence of life-threatening organ failure in cases of HHV-8 positive, HIV negative MCD.