Selective venous sampling for secondary hypertension.

Selective venous sampling (SVS), an invasive radiographic procedure that depends on contrast media, holds a unique role in diagnosing and guiding the treatment of certain types of secondary hypertension, particularly in patients who may be candidates for curative surgery. The adrenal venous sampling (AVS), in particular, is established as the gold standard for localizing and subtyping primary aldosteronism (PA). Throughout decades of clinical practice, AVS could be applied not only to PA but also to other endocrine diseases, such as adrenal Cushing syndrome (ACS) and Pheochromocytomas (PCCs). Notably, the application of AVS in ACS and PCCs remains less recognized compared to PA, with the low success rate of catheterization, the controversy of results interpretation, and the absence of a standardized protocol. Additionally, the AVS procedure necessitates enhancements to boost its success rate, with several helpful but imperfect methods emerging, yet continued exploration remains essential. We also observed renal venous sampling (RVS), an operation akin to AVS in principle, serves as an effective means of diagnosing renin-dependent hypertension, aiding in the identification of precise sources of renin excess and helping the selection of surgical candidates with renin angiotensin aldosterone system (RAAS) abnormal activation. Nonetheless, further basic and clinical research is needed. Selective venous sampling (SVS) can be used in identifying cases of secondary hypertension that are curable by surgical intervention. Adrenal venous sampling (AVS) and aldosterone measurement for classificatory diagnosis of primary aldosteronism (PA) are established worldwide. While its primary application is for PA, AVS also holds the potential for diagnosing other endocrine disorders, including adrenal Cushing's syndrome (ACS) and pheochromocytomas (PCCs) through the measurements of cortisol and catecholamine respectively. In addition, renal venous sampling and renin measurement can help to diagnose renovascular hypertension and reninoma.

Benefits of laboratory personalized antiplatelet therapy in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials.

BACKGROUND: The preventive effects of laboratory personalized antiplatelet therapy (PAPT) strategy in-cluding genetic detection and platelet function testing (PFT) on major adverse cardiac events (MACEs) and bleeding events in coronary artery disease (CAD) patients undergoing stenting has been extensively studied. Despite that, no clear conclusion can be drawn. In this study, a meta-analysis was performed to explore a more precise estimation of the benefits of laboratory PAPT. METHODS: Randomized controlled trials were identified by the use of search databases such as PubMed, Embase, and Cochrane Controlled Trials Register up to May 2017, and the estimates were pooled. RESULTS: Fourteen studies including 9497 patients met the inclusion criteria. The laboratory PAPT reduced MACEs risk (risk ratio [RR] 0.58, 95% confidence interval [CI] 0.42-0.80, p = 0.001), stent thrombosis (RR 0.60, 95% CI 0.41-0.87, p = 0.008) and myocardial infarctions (RR 0.43, 95% CI 0.21-0.88, p = 0.02) compared to the non-PAPT group. No statistically significant difference was observed between the two groups regarding cardiovascular death (RR 0.77, 95% CI 0.51-1.16, p = 0.21), bleeding events (RR 0.96, 95% CI 0.81-1.13, p = 0.59) and ischemic stroke (RR 0.81; 95% CI 0.39-1.66, p = 0.57). The preventive effect on MACEs was more significant in patients with high on-treatment platelet reactivity (RR 0.46; 95% CI 0.27-0.80, p = 0.006). CONCLUSIONS: Coronary artery disease patients after stenting could obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128-141).

Effects of the Sympathetic Nervous System on Regulatory T Cell and T Helper 1 Chemokine Expression in Patients with Acute Coronary Syndrome.

OBJECTIVE: To observe the effects of sympathetic overactivity on the immune system involved in the imbalance of T helper (Th) lymphocytes, we investigated the correlation between autonomic dysregulation and the generation of regulatory T (Treg) and Th1 chemokines in patients with acute coronary syndrome (ACS). METHODS: Blood samples obtained from patients with coronary artery disease and controls were analyzed for levels of Th1 and Treg cells and their associated cytokines by flow cytometry. In addition, the activity of the cyclic adenosine monophosphate (cAMP), the levels of norepinephrine (NE), epinephrine (EPI) and serum cytokines, and the activity of protein kinase A (PKA) were analyzed by Western blot, radioimmunoassay, high-performance liquid chromatography and enzyme-linked immunoassay, respectively. All subjects were evaluated for heart rate variability (HRV). RESULTS: Levels of Th1 cells and T-bet (a T-box transcription factor), NE, EPI, cAMP and PKA significantly increased (all p < 0.01) whereas HRV and levels of Treg cells and STAT5 decreased (all p < 0.01) in ACS patients compared to patients with stable angina and controls. The disorder of Th1 and Treg cells is closely related to the activation of cAMP-PKA induced by hyperactivity of the sympathetic system. CONCLUSIONS: This study showed that the abnormalities in specific subsets of CD4+ T cells are associated with sympathetic hyperactivity in ACS patients. It may provide surprising insights into the pathogenesis of arteriosclerosis, involving the regulation of the sympathetic nervous system on immune inflammation.

Effects of paroxetine-mediated inhibition of GRK2 expression on depression and cardiovascular function in patients with myocardial infarction.

BACKGROUND: Paroxetine is a selective serotonin reuptake inhibitor utilized in the treatment of depression and anxiety disorders. Recent studies have identified paroxetine as a G protein-coupled receptor kinase-2 (GRK2) inhibitor capable of reversing cardiac dysfunction and remodeling in experimental models of acute myocardial infarction (AMI). We determine the clinical importance of paroxetine on cardiac functions in patients having AMI with depression (AMID) in comparison with fluoxetine, an unrelated selective serotonin reuptake inhibitor that does not inhibit GRK2. METHODS: Diagnosis of depression was based on the 17-item Hamilton Depression Scale and Self-rating Depression Scale in AMI patients after hospital admission. AMID patients were randomly assigned to paroxetine or fluoxetine for treatment of depression. Heart rate variability and cardiac function were evaluated. GRK2 protein levels were measured using peripheral lymphocytes and Western blot. RESULTS: GRK2 expression in AMID patients was significantly higher than that in AMI patients without depression. In AMID patients, GRK2 levels were positively correlated with the 17-item Hamilton Depression Scale and the Self-rating Depression Scale scores, and negatively correlated with heart rate variability. Treatment of AMID patients with paroxetine significantly reduced the expression of GRK2, normalized the autonomic nervous system function, and improved cardiac performance. In contrast, fluoxetine normalized the autonomic nervous system but did not reduce the expression of GRK2 nor improved cardiac performance. CONCLUSION: This study suggests that paroxetine is effective for improving cardiac function in patients with AMID and such effect correlates with GRK2 reduction.

Nrf2 protects mitochondrial decay by oxidative stress.

Sublethal levels of oxidative stress are commonly associated with various pathophysiological conditions. Cardiomyocytes have the highest content of mitochondria among all cell types, allowing the study of mitochondria in cells surviving oxidative stress and address whether nuclear factor-erythroid-derived 2-related factor 2 (Nrf2) can reverse these changes. Mitochondria normally exist in elaborated networks, which were replaced by predominately individual punctuate mitochondria 24 h after exposure to a nonlethal dose of H2O2. Electron microscopy revealed that cells surviving H2O2 show swelling of mitochondria with disorganized cristae and areas of condensation. Measurements of functional mitochondria showed a H2O2 dose-dependent decrease over a course of 5 d. At the protein and mRNA levels, cells surviving H2O2 treatment show a reduction of mitochondrial components, cytochrome c, and cytochrome b. Nrf2 overexpression prevented H2O2 from inducing mitochondria morphologic changes and reduction of cytochrome b/c. Although Nrf2 is known as a transcription factor regulating antioxidant and detoxification genes, Nrf2 overexpression did not significantly reduce the level of protein oxidation. Instead, Nrf2 was found to associate with the outer mitochondrial membrane. Mitochondria prepared from the myocardium of Nrf2 knockout mice are more sensitive to permeability transition. Our data suggest that Nrf2 protects mitochondria from oxidant injury likely through direct interaction with mitochondria.

Effects of cAMP and ß-adrenergic receptor antagonists on the function of peripheral T helper lymphocytes in patients with heart failure.

OBJECTIVE: To observe the effects of cyclic adenosine monophosphate (cAMP) in peripheral lymphocytes on T helper 1 (TH1)/TH2 cytokine ratios and to investigate the potential impact and mechanism of ß-adrenergic receptor antagonists on immune function in patients with chronic heart failure (CHF). METHODS: Sixty-nine patients with New York Heart Association functional class II-IV CHF and a radionuclide left ventricular ejection fraction of less than 45% received carvedilol or metoprolol in a randomized fashion. Thirty healthy persons were studied as controls. Interferon (IFN)-γ and interleukin (IL)-10 in CD4+ T lymphocytes were quantified by three-color flow cytometry. cAMP levels in peripheral blood mononuclear cells were tested by radioimmunoassay at baseline and 6 months after treatment. RESULTS: The levels of lymphocyte cAMP in CHF patients were significantly lower than in normal controls (p < 0.01). The IFN-γ/IL-10 ratio was significantly higher in CHF patients (p < 0.01). The levels of cAMP, IFN-γ and IL-10 among CHF patients with different pathogenic factors displayed no significant differences (p > 0.05). The lymphocyte cAMP level was negatively correlated with the IFN-γ/IL-10 ratio (p < 0.01). After treatment with metoprolol and carvedilol, the IFN-γ/IL-10 ratio in the CHF patients was dramatically decreased (p < 0.01 for each drug) and lymphocyte cAMP was remarkably increased (p < 0.01 for each drug). CONCLUSION: These results suggest that the decrease of cAMP affects the TH1/TH2 phenotype in peripheral lymphocytes of CHF patients. ß-Blocking medications appear to have a beneficial effect on the TH1/TH2 balance and on the immune system through increasing production of cAMP, offering further evidence to support the use of ß-adrenergic receptor blockers to treat CHF.