Coadministration of Atorvastatin Prevents Nitroglycerin-Induced Endothelial Dysfunction and Nitrate Tolerance in Healthy Humans

ObjectivesWe aimed to assess whether concurrent administration of atorvastatin would modify the development of tolerance and endothelial dysfunction associated with sustained nitroglycerin (GTN) therapy in humans.BackgroundAnimal studies have demonstrated that administration of 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors can protect against GTN-induced endothelial dysfunction and tolerance, likely through an antioxidant mechanism.MethodsThirty-six healthy male volunteers were randomized to receive continuous transdermal GTN (0.6 mg/h) and placebo, atorvastatin (80 mg/day) alone, or continuous transdermal GTN (0.6 mg/h) with concurrent atorvastatin (80 mg/day), all for 7 days. On the second visit, forearm blood flow was measured with venous-occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 μg/min). Acetylcholine infusions were coinfused first with saline, and repeated during the coinfusion of vitamin C (24 mg/min). Blood pressure responses to sublingual GTN (400 μg) were assessed on both visits.ResultsAcetylcholine responses in the GTN plus placebo group were significantly attenuated versus those in the GTN plus atorvastatin and atorvastatin groups (p < 0.01). Coinfusion of vitamin C completely restored acetylcholine responses in the GTN plus placebo group (p < 0.01 vs. saline coinfusion), but caused no change in either the atorvastatin or the GTN plus atorvastatin groups. Blood pressure responses to sublingual GTN did not significantly change between visits in subjects receiving GTN plus atorvastatin and atorvastatin alone, but were significantly blunted in the GTN plus placebo group (p < 0.05).ConclusionsThe present findings demonstrate, for the first time in humans, that atorvastatin prevents both GTN-induced endothelial dysfunction and nitrate tolerance, likely by counteracting the GTN-induced increase in oxidative stress

Model Numerikal Reservoir Sistem Panasbumi Pada Daerah Topografi Relatif Datar Untuk Mencari Kondisi Natural State Dan Menganalisa Sensitivitas Panas Pada Reservoir Menggunakan Software Tough2

Telah dilakukan pemodelan reservoir menggunakan software Tough2 dengan data sintetik, berupa data permeabilitas dan pororsitas. Dimana terdiri dari 4 lapisan, yaitu lapisan overburden, lapisan clay caps, lapisan recharge area + lapisan reservoir (berada pada lapisan yang sama), dan lapisan basement dengan tujuan untuk menganalisa sensitivitas panas, serta untuk mencari kondisi natural state (natural state merupakan kondisi setimbang, yaitu dimana kondisi tekanan, temperatur dan kondisi reservoirnya tidak berubah terhadap waktu).Dari hasil pemodelan reservoir oleh Tough2 didapat bahwa kondisi natural state selama 2,20857E+4 tahun, dimana terjadi penurunan suhu dari kondisi natural state tanpa sumur produksi berbanding kondisi natural state dengan sumur produksi, dimana suhu pada saat kondisi natural state tanpa sumur produksi sebesar 245OC dan suhu pada saat kondisi natural state dengan sumur produksi sebesar 235OC pada kedalaman 1350 m. Sedangkan untuk penggunaan rate 20 kg/s, 25 kg/s, 30 kg/s dan 35 kg/s untuk melihat sensitivitas heat nya, didapatkan bahwa semakin besar nilai rate yang dipakai dalam suatu sumur produksi, maka akan menurunnya nilai temperatur di sumur produksi tersebut

The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

Integration of a palliative approach into heart failure care: a European Society of Cardiology Heart Failure Association position paper

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence-based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day-to-day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline-directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure

Palliative care: essential support for patients with heart failure in the COVID-19 pandemic

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Electrical Remodeling of Ventricular Repolarization Abnormality after Treatment in Pheochromocytoma: U Wave Finding in a Retrospective Analysis

Background. Pheochromocytoma is a rare neuroendocrine tumor, clinically characterized by high blood pressure, palpitations, and headache. It is often associated with abnormalities of the ventricular repolarization phase; the dispersion of ventricular repolarization is the basis for ventricular arrhythmias (torsion de point, ventricular tachycardia or ventricular fibrillation). Objectives. Analysis of abnormal ventricular repolarization focused on the presence and amount of U wave in patients affected by pheochromocytoma and its modification after surgery. Materials and Methods. We reviewed pathology records of 722 patients admitted for adrenal nodule or suspected chromaffin-cell tumor and identified 39 patients affected by pheochromocytoma. Metanephrine, normetanephrine, and 3-methoxytyramine have been assessed by determining concentrations in 24-hour urine collection. Standard 12-lead electrocardiogram records have been reviewed with analysis of heart rate, P wave, PR interval, QRS duration, QTc, and U wave. Then we selected and compared 22 patients of 39 affected by pheochromocytoma, with both clinical and electrocardiographic data before and after surgery. Results. In our cohort of 39 patients affected by pheochromocytoma, we found U wave in ECG, before treatment, in 82.8 percent of patients, while only 37.0 percent after treatment (p<0.001) and we observed a statistically significant correlation between this wave and the urinary metanephrine. After surgery, in the selected 22 patients, we observed a clear significant reduction in systemic blood pressure, fasting glucose, metanephrine, normetanephrine, and 3-methoxytyramine. We found a significant reduction of U wave presence and leads involved in these patients after surgery (90.9% versus 9%). We observed a linear correlation between the amount of U waves in 12-lead electrocardiogram and metanephrine (r2=0.333, p=0.015), 3-methoxytyramine levels (r2=0.458, p=0.006), and tumor size (r2=0.429, p=0.003). Conclusions. In our retrospective analysis, patients affected by pheochromocytoma presented U wave in electrocardiogram. The presence and amount of U wave were associated with the metanephrine levels and the tumor size with significant reduction after surgical removal

Phenotypic variability of a pathogenic PKP2 mutation in an Italian family affected by arrhythmogenic cardiomyopathy and juvenile sudden death : considerations from molecular autopsy to sport restriction

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder with an estimated prevalence between 1:2,000 and 1:5,000 and is characterized by the fibrofatty replacement of cardiomyocytes that predisposes to malignant arrhythmias, heart failure, and sudden cardiac death. The diagnosis is based on the 2010 Task Force Criteria including family history, electrocardiographic traits and arrhythmogenic pattern, specific gene mutations, and structural and/or histological abnormalities. Most ACMs display an autosomal dominant mode of inheritance often with incomplete penetrance and variable expressivity. Genetic screening of patients with ACM identifies pathogenic or likely pathogenic variants, prevalently in genes encoding the cardiac desmosome (PKP2, DSP, DSC2, DSG2, and JUP) or less frequently in non-desmosomal genes (CTNNA3, PLN, TMEM43, RYR2, SCN5A, CDH2, and DES). Methods: In the present study, we performed molecular autopsy in a boy who died suddenly during physical exertion. In addition to post-mortem examination, a DNA sample was analyzed with next-generation sequencing (NGS). Results: The genetic analysis revealed the presence of pathogenic heterozygous c.314del (p.Pro105Leufs(*)7) frameshift variant in the PKP2 gene. Cascade screening of family members allowed us to identify 12 mutation carriers and to intervene on subjects at risk, many of whom were athletes. Conclusions: Molecular autopsy can establish cardiogenetic diagnosis and allow appropriate preventative measures in high-risk relatives