Cardiovascular & Haematological Disorders - Drug Targets - Volume 17, Issue 1, 2017

Background: Pulmonary arterial hypertension (PAH) is a rare disease characterised by a severe impairment of functional status and quality of life (QoL). Use of rehabilitative programmes may help to improve outcomes. The aim of this pre/post test case series was to evaluate the impact of a training program, including sessions of aerobic and resistance exercise, inspiratory muscle reinforcement, slow breathing, relaxation, and psychological support, on functional outcomes. Methods: Fifteen patients affected by PAH, in World Health Organization (WHO) Functional Class (FC) II or III and in stable clinical condition, were included in a 4-week cardiorespiratory training programme conducted in outpatient service. Patients were tested during a routine control visit (T0), one month later at the beginning of the training programme (T1), and at study end (T2). Between T0 and T1, patients continued their normal activities and therapies. At each step, patients underwent respiratory and functional evaluation by spirometry, 6-minute walk test (6-MWT), maximal cardiopulmonary exercise testing (CPET), echocardiography, and levels of brain natriuretic peptide (BNP). QoL was also assessed at T1 and T2 using the Hospital Anxiety and Depression Scale and the EuroQoL-5D questionnaire. The primary endpoint was the effect of training on peak oxygen consumption (peak V#135;O2). Results: There were no significant differences in BNP levels, or in any of the respiratory or echocardiographic parameters measured, between T0 and T1. Between T1 and T2, significant improvements were recorded in QoL (HADS-Anxiety mean change 3.5 ± 3.3 and HADS-Depression mean change 1.6 ± 2.0, all p < 0.01). Significant improvements were also observed in functional capacity with distance walked at 6-MWT increasing from 455 ± 115 to 487 ± 120 (+8%, p < 0.01), workload (WR) of CPET increased of 22% (from 73 ± 22 to 87 ± 21 watt, p < 0.001), peak V#135;O2 increasing from 17.3 ± 4.2 to 19.9 ± 4.5 mL/kg/min (p < 0.001) and pulse O2 increasing from 7.8 ± 1.8 to 8.8 ± 2.4 mL/beat (p < 0.01). No adverse events or deterioration in clinical status were observed during the training sessions. Conclusion: Cardiorespiratory training in a outpatient service is a suitable option for patients with PAH in WHO FC II/III thanks to improved exercise capacity and QoL, which may allow them to achieve better outcomes.

Background: Carnosol (CS) is an ortho-diphenolic diterpene in rosemary with great antioxidant potential. This study was designed to investigate the hypolipidemic, anti-oxidant, and anti-diabetic activities of CS. Methods: In our experiment, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, three CS (1, 5, 10 mg/kg/day)-treated diabetic groups. On the first day of the study, the diabetic groups were given streptozotocin (STZ) in a single intraperitoneal (i.p.) injection at a dose of 60 mg/kg for induction of diabetes. CS was injected (i.p.) to the treatment groups from 3 days after STZ administration during a period of 4 weeks. At the end of the experimental period, we assessed the serum levels of glucose, IL-6, TNF-α, malondialdehyde (MDA), glutathione–s transferase (GST), superoxide dismutase (SOD), catalase (CAT) activities, triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL-C), and high density lipoprotein (HDL-C). Results: The results indicated that STZ caused an elevation of serum glucose, IL-6, TNF-α, MDA, TG, TC, LDL-C, and it also made a reduction of serum GST, SOD, CAT, and HDL-C (p<0.001). The findings showed amelioration in the serum glucose, IL-6, TNF-α, MDA, TG, TC, LDL-C, GST, SOD, CAT, and HDL-C in the CS-treated diabetic groups versus the untreated group, in a dose dependent manner (p < 0.001). Conclusion: In conclusion, the present investigation proposes that CS may be improved diabetes and its complications by modulation of oxidative stress and inflammatory responses.

Background: The principal aim of this study was to investigate the oxidative effects of acute alcohol consumption on the functions of the heart and the liver and the possible modification of this effect by phenolic compounds from n-butanol extract of Camellia sinensis supplementation. Method: Three experimental groups of rats were used: control, ethanol-exposed (40% v/v, 5 g/kg per oral every 12 hours for 3 doses, binge model), and ethanol-exposed plus n-butanol extract of Camellia sinensis (100 mg/kg once a day for three days before and simultaneously with ethanol administration). Serum transaminases, cholesterol, triglycerides, lipid peroxidation (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were estimated to assess organs damage. Results: n-butanol extract of Camellia sinensis at a dose of 100 mg/kg body weight exhibited a significant reversal effect in all biochemical parameters measured such as extent of lipid peroxidation, GSH, lipid profile, and serum aminotransferase activities. Conclusion: These results suggest that n-butanol extract of Camellia sinensis protected the heart and the liver from binge ethanol induced injury through attenuating oxidative stress.

Aim: This study compared the hematopoietic capacities of erythropoietin (Epo) and antioxidant drug U-74389G, based on 2 preliminary studies. The provided results on hematocrit levels augmentation were co-evaluated in a hypoxia reoxygenation protocol of an animal model. Materials and Methods: Hematocrit levels were evaluated at the 60th reoxygenation min (for groups A, C and E) and at the 120th reoxygenation min (for groups B, D and F) in 60 rats. Groups A and B received no drugs, rats from groups C and D were administered with Epo; whereas rats from groups E and F were administered with U-74389G. Results: The first preliminary study of Epo non-significantly increased the hematocrit levels by 0.24%+1.38% (p-value=0.8586). The second preliminary study of U-74389G significantly raised the hematocrit levels by 3.16%+1.33% (p-value=0.0196). These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has approximately 12.66-fold higher hematopoietic potency than Epo (p-value=0.0000). Conclusion: The anti-oxidant capacities of U-74389G provide satisfactory acute hematopoietic properties; presenting approximately 12.66-fold hematocrit level rise than epo (p-value=0.0000).

Background: The macrophage polarization is proposed to be involved in initial events and remodeling of atherosclerosis plaques. Mannose receptor, C type 1 (MRC1) is a trans-membrane glycoprotein participating in phagocytosis and, is highly expressed in the M2 macrophages. Objective: The aim of this study was to investigate the effects of sdLDL (small dense LDL) on the MRC1 gene expression level and secretion of histamine in the differentiated M2 macrophages from monocytes of patients with coronary artery stenosis and healthy subjects. Method: The monocytes were isolated from healthy subjects (< 5% stenosis) and patients (>70% stenosis, SVD (Single Vessel Disease), 2VD (Two-Vessel Disease) and 3VD (Three-Vessel Disease)) by RosetteSep kit and, were differentiated into M2 macrophages by macrophage colonystimulating factor (M-CSF). The sdLDL particles were obtained by PEG-combined precipitation method. The MRC1 gene expression and histamine levels were measured by RT-qPCR and ELISA techniques, respectively. Results: The MRC1 gene expression level was significantly increased in M2 macrophages of healthy subjects (P=0.05) while it reduced in SVD (P=0.05), 2VD (P=0.01) and 3VD (P=0.9) patients after treatment with sdLDL. The histamine value secreted from M2 macrophages (7-day) was higher (>3-fold, P=0.02) in patients as compared to healthy controls. Conclusion: The results showed that the sdLDL particles reduce the MRC1 gene expression levels in the differentiated M2 macrophages from patients with coronary artery disease. Furthermore, they had high inflammatory capacity for the secretion of histamine.

Background: Some reports have suggested that arterial embolization (AE) is a good indication to manage recurrent spontaneous hemartroses (RSH) that are refractory to intensive prophylaxis (RIP) in people with hemophilia (PWH). Objective: To clarify the role of AE in RSH that are RIP in PWH. Method: A literature review of arterial embolization in patients with hemophilia was performed using MEDLINE (PubMed) and the Cochrane Library. Results: A total of 68 articles were found, of which 6 were selected and reviewed because they were deeply focused on the topic. The total number of AEs performed so far is 78 in 69 patients. Four second AEs were required (4/78), and a third AE in one (1/78). Two complications have been found so far: a pseudoaneurym (1/78) of the femoral artery at the puncture site (that eventually required surgical repair) and a patient (1/78) that had recurrence of bleeding for whom surgical exploration was required. AE seems to be a good procedure for RSH that are RIP. Conclusion: AE seems to be too aggressive to be considered the first resort. Radiosynovectomy (RS) must always be the first resort. AE should only be indicated in RSH that are RIP to 3 RSs (with 6 month intervals) followed by an arthroscopic synovectomy. AE in PWH is technically challenging and should be performed by highly skilled interventional radiologists.

Background: Immune thrombocytopenia (ITP) in adulthood is characterized by chronic relapsing course. Despite the efficacious first line treatment (corticosteroid, intravenous immunoglobulin), majority of patients will enter the chronic phase warranting another treatment approach. Until recently, splenectomy performed in ITP chronic phase represented the standard of care with longterm remissions in more than 70% of patients, but it has never been tested in clinical trials. However, with the advances of our understanding of ITP pathophysiology and the shifting focus on megakaryocyte impairment, novel drugs were introduced in the treatment paradigm, mainly trombopoietin receptor agonists (TPO-RAs); romiplostim and eltrombopag. Methods: These TPO-RAs were tested in randomized controlled trials resulting in adequate platelet response with few side effects and less need for additional therapy leading to approval of corresponding regulatory agencies and wide acceptance by hematological community, but however TPO-RAs must be taken continuously to maintain the response. With their onset, the rate of splenectomy in chronic ITP has diminished in modern era. Conclusion: The main aim behind conducting this review is to evaluate the pros and cons of splenectomy compared to TPO-RAs treatment in order to provide the critical overview which may help the practicing clinician in managing often challenging cases of chronic ITP.

Background: Cardiovascular diseases (CVD) are the number one cause of death globally compared to any other cause. CVD accounts for approximately 17.3 million deaths per year and are rising. Hypertension is the leading risk factor for cardiovascular diseases. Approximately, 80 million people suffer from hypertension in the U.S. While, majority of these individuals are on antihypertensive medications only 54% of individuals with hypertension are optimally controlled. Heart failure and stroke are some of the devastating complications of uncontrolled hypertension. Hypertensive crisis can be classified as either an urgency or emergency; difference between the two is the presence of end organ damage, which is noted in hypertensive emergency. Hypertensive crisis is usually treated by parenteral antihypertensive medications. The main drug classes of drugs for treatment are nitrates, calcium channel blockers, dopamine-1 agonists, adrenergic-blocking agents etc. Conclusion: In this review, we discuss approach to management of hypertensive crisis and each drug class with its physiology and complications.

Background: Atrial fibrillation is a well-known independent risk factor for stroke yet there is no international consensus on guidelines regarding the introduction of anticoagulation in patients deemed at intermediate risk (e.g. CHA2DS2-VASc of 1). The evolution of cardiac biomarkers such as highly sensitive troponins and B-type natriuretic peptide as well as data on D-dimers, may offer incremental enhancements for personalized thromboembolism risk assessment. These markers provide prognostic data for risk of cardiovascular morbidities associated with atrial fibrillation and offer additional specificity for assessing stroke and thromboembolic risk. These assays may therefore enhance risk prognosis in atrial fibrillation alongside conventional stroke risk stratification tool patients. We seek to explore the application of personalised risk assessment using the biomarkers to aid the clinician treating the patient with atrial fibrillation deemed to be at intermediate risk of stroke. Conclusion: The stroke risk assessment of a patient with an intermediate risk of stroke (CHA2DS2- VASc score 1) may be improved by using cardiac biomarkers such as highly sensitive troponin, BNP and D-dimers. We explore the application of these biomarkers to provide personalised risk assessment to help a patient with AF decide on whether to commence anticoagulation.

Background: Stroke is the third leading cause of death in the United States, behind only heart disease and cancer, with over 140,000 associated deaths per year. Methods: Considerable research is ongoing to examine the role of modifiable risk factors which may cause or contribute to stroke. Although age and family history are generally considered to be the major risk factors, there are several modifiable and non-modifiable risk factors that are linked to the pathogenesis of a stroke. Lipoprotein (a), or Lp(a), is a type of low-density lipoprotein containing an integral apolipoprotein B100 (apoB100) component with an attached apolipoprotein A-1 (ApoA-1) isoform via a disulfide linkage. Lp(a) metabolism is of great interest as it sheds light on its role in pathogenesis of not only cardiovascular disorders but also stroke. Although Lp(a) has been identified as an “LDL-like particle”, its metabolism differs from low density lipoprotein (LDL). Despite some ambiguity in the literature regarding the causative effect of Lp(a) on stroke, there are clear associations of high plasma Lp(a) concentration and risk of stroke. Furthermore, the small isoforms of ApoA-1-containing lipoproteins have been shown to increase atherogenicity in atherosclerotic patients. Conclusion: Currently, there is little research examining the importance of small molecule Lp(a) distribution and risk for stroke, both on a first-case and recurrent basis. Understanding the role of Lp (a) in stroke requires investigating its molecular mechanisms particularly the key microRNA (s) components that control its expression and function (s). Therefore, the main objective of this review is to discuss the broader link between Lp(a) and stroke and to identify opportunities for future investigation and potential research prospects on the role of Lp (a) in stroke.