cardiovascular-agents and Hypertrophy--Right-Ventricular

There now is strong evidence to recognize the pivotal role of the right ventricle (RV) in heart disease and to establish it as a unique and separate entity than the left ventricle (LV). Here, we summarize the differences between the two ventricles, the diagnosis of RV failure, and the management of acute and chronic RV failure. We review the indices derived by echocardiography used to measure RV function, and novel biomarkers that may play a role diagnosing and prognosticating in RV-specific disease. There are new novel therapies that specifically target the RV in disease. For example, phosphodiesterase type 5 inhibitors improve contractility of the hypertrophied RV while sparing the normal LV in pulmonary arterial hypertension. The metabolism of the hypertrophied RV is another area for therapeutic exploitation by metabolic modulation. We also suggest future potential molecular targets that may be unique to the RV because they are upregulated in RV hypertrophy greater than in LV hypertrophy.

Topics: Biomarkers; Cardiovascular Agents; Case Management; Chronic Disease; Diagnosis, Differential; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Molecular Targeted Therapy; Phosphodiesterase 5 Inhibitors; Ultrasonography; Ventricular Dysfunction, Right; Ventricular Function, Right

There is an increase in oxidative stress and apoptosis signaling during the transition from hypertrophy to right ventricular (RV) failure caused by pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). In this study, it was evaluated the action of copaiba oil on the modulation of proteins involved in RV apoptosis signaling in rats with PAH. Male Wistar rats (±170 g, n = 7/group) were divided into 4 groups: control, MCT, copaiba oil, and MCT + copaiba oil. PAH was induced by MCT (60 mg/kg intraperitoneally) and, 7 days later, treatment with copaiba oil (400 mg/kg by gavage) was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and the RV was collected for morphometric evaluations, oxidative stress, apoptosis, and cell survival signaling, and eNOS protein expression. Copaiba oil reduced RV hypertrophy (24%), improved RV systolic function, and reduced RV end-diastolic pressure, increased total sulfhydryl levels and eNOS protein expression, reduced lipid and protein oxidation, and the expression of proteins involved in apoptosis signaling in the RV of MCT + copaiba oil as compared to MCT group. In conclusion, copaiba oil reduced oxidative stress, and apoptosis signaling in RV of rats with PAH, which may be associated with an improvement in cardiac function caused by this compound.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cardiovascular Agents; Disease Models, Animal; Fabaceae; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; JNK Mitogen-Activated Protein Kinases; Male; Monocrotaline; Myocardium; Nitric Oxide Synthase Type III; Oxidative Stress; Plant Oils; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Signal Transduction; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling

Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

Topics: Animals; Arterial Pressure; Cardiovascular Agents; Disease Models, Animal; Fibrosis; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Macrophages, Alveolar; Male; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Osteopontin; Pioglitazone; PPAR gamma; Pulmonary Artery; Rats, Sprague-Dawley; Thiazolidinediones; Vascular Remodeling; Ventricular Function, Right; Ventricular Remodeling

Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right-heart failure and death. A dys-regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH.. A single s.c. injection of MCT (50 mg·kg(-1) ) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg(-1) C21, 3 mg·kg(-1) PD-123319 or 0.5 mg·kg(-1) A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses.. Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, PD-123319, or the Mas antagonist, A779, abolished the protective actions of C21.. Taken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH.

Topics: Angiotensin II; Angiotensin II Type 2 Receptor Blockers; Animals; Cardiovascular Agents; Disease Models, Animal; Fibrosis; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Imidazoles; Lung; Male; Monocrotaline; Myocardium; Peptide Fragments; Proto-Oncogene Mas; Proto-Oncogene Proteins; Pulmonary Fibrosis; Pyridines; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 2; Receptors, G-Protein-Coupled; Signal Transduction; Vascular Remodeling; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling

Topics: Adrenal Cortex Hormones; Biopsy; Cardiomyopathies; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Cyclophosphamide; Defibrillators, Implantable; Electrocardiography; Heart Septum; Humans; Hypertrophy, Right Ventricular; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Sarcoidosis; Sarcoidosis, Pulmonary; Syncope; Tachycardia, Ventricular; Ultrasonography

Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation.Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients.In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10.We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding.

Topics: Adult; Cardiac Surgical Procedures; Cardiovascular Agents; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Pulmonary Valve; Pulmonary Valve Insufficiency; Recovery of Function; Reoperation; Retrospective Studies; Stroke Volume; Texas; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Young Adult