Cardiorenal Syndrome

To date, the complex pathological interactions between renal and cardiovascular systems represent a real global epidemic in both developed and developing countries. In this context, renovascular hypertension (RVH) remains among the most prevalent, but also potentially reversible, risk factor for numerous reno-cardiac diseases in humans and pets. Here, we investigated the anti-inflammatory and reno-cardiac protective effects of a polyphenol-rich fraction of bergamot (BPF) in an experimental model of hypertension induced by unilateral renal artery ligation. Adult male Wistar rats underwent unilateral renal artery ligation and treatment with deoxycorticosterone acetate (DOCA) (20 mg/kg, s.c.), twice a week for a period of 4 weeks, and 1% sodium chloride (NaCl) water (n = 10). A subgroup of hypertensive rats received BPF (100 mg/kg/day for 28 consecutive days, n = 10) by gavage. Another group of animals was treated with a sub-cutaneous injection of vehicle (that served as control, n = 8). Unilateral renal artery ligation followed by treatment with DOCA and 1% NaCl water resulted in a significant increase in mean arterial blood pressure (MAP; p< 0.05. vs CTRL) which strongly increased the resistive index (RI; p<0.05 vs CTRL) of contralateral renal artery flow and kidney volume after 4 weeks (p<0.001 vs CTRL). Renal dysfunction also led to a dysfunction of cardiac tissue strain associated with overt dyssynchrony in cardiac wall motion when compared to CTRL group, as shown by the increased time-to-peak (T2P; p<0.05) and the decreased whole peak capacity (Pk; p<0.01) in displacement and strain rate (p<0.05, respectively) in longitudinal motion. Consequently, the hearts of RAL DOCA-Salt rats showed a larger time delay between the fastest and the lowest region (Maximum Opposite Wall Delay-MOWD) when compared to CTRL group (p<0.05 in displacement and p <0.01 in strain rate). Furthermore, a significant increase in the levels of the circulating pro-inflammatory cytokines and chemokines (p< 0.05 for IL-12(40), p< 0.01 for GM-CSF, KC, IL-13, and TNF- α) and in the NGAL expression of the ligated kidney (p< 0.001) was observed compared to CTRL group. Interestingly, this pathological condition is prevented by BPF treatment. In particular, BPF treatment prevents the increase of blood pressure in RAL DOCA-Salt rats (p< 0.05) and exerts a protective effect on the volume of the contralateral kidney (p <0.01). Moreover, BPF ameliorates cardiac tissue strain dysfunction by increasing Pk in displacement (p <0.01) and reducing the T2P in strain rate motion (p<0.05). These latter effects significantly improve MOWD (p <0.05) preventing the overt dyssynchrony in cardiac wall motion. Finally, the reno-cardiac protective effect of BPF was associated with a significant reduction in serum level of some pro-inflammatory cytokines and chemokines (p<0.05 for KC and IL-12(40), p<0.01 for GM-CSF, IL-13, and TNF- α) restoring physiological levels of renal neutrophil gelatinase-associated lipocalin (NGAL, p<0.05) protein of the tethered kidney. In conclusion, the present results show, for the first time, that BPF promotes an efficient renovascular protection preventing the progression of inflammation and reno-cardiac damage. Overall, these data point to a potential clinical and veterinary role of dietary supplementation with the polyphenol-rich fraction of citrus bergamot in counteracting hypertension-induced reno-cardiac syndrome.

Chronic heart failure (CHF) is the terminal stage of a variety of heart diseases with higher morbidity and mortality. Although CHF has been studied for decades, the comprehensive analysis by bibliometrics has not been done. So, we analyzed the scientific outputs of global chronic heart failureresearches, explored the current research status and hotpots from 2009 to 2019. Web of Science Core Collection was the data source, and the data was retrieved on June 25, 2020, according to the set search strategy. Bibliometrics tools— CiteSpace V (Drexel university, Chaomei Chen) and VOS viewer (Leiden University, van Eck NJ)–were used for analyzing published literature and exploring research hotspots and frontier directions. A total of 21,484 articles were included, and the rate of published articles increased from 2009 to 2019 annually. United States of America was the leading country, Duke University was the leading institution, and Stefan D Anker was the most productive researcher in this field. The analysis of keywords showed that mortality, risk, outcomes, association, and dysfunction were the main hotpots and frontier directions of CHF. Bibliometric analysis of the outputs on CHF shows an overall view about the current status of the research on CHF. Clinical treatment and the associations among organs in the patients with CHF are the major research frontiers. However, further research and collaboration are still required worldwide. Our findings can help researchers grasp the research status of CHF and determine new directions for future researches as soon as possible.

Atrial fibrillation (AF) is a common arrhythmia in patients with hypertrophic cardiomyopathy (HCM) and is associated with renal function deterioration. The protective effects of catheter ablation (CA) of AF on renal function in patients with HCM remain unsolved. From 2009 to 2020, a total of 169 consecutive patients with HCM and AF (age 70 ± 12, 87 males) were retrospectively evaluated. The estimated glomerular filtration rate (eGFR) was evaluated at the study enrollment or 1 month before the CA and reevaluated 3 and 12 months later. In the 169 patients, 63 underwent CA of AF (ablation group), and the remaining 106 did not (control group). After propensity score matching, 45 pairs were matched. The baseline eGFR was similar between the 2 groups (p = 0.83). During a mean follow-up period of 34 ± 27 months, sinus rhythm was maintained in 36 patients (80%) after 1.7 ± 0.8 ablation procedures. The eGFR significantly decreased from baseline to 3 months (p <0.01) and from baseline to 1 year (p <0.01) in the control group, whereas the eGFR in the ablation group was maintained both from baseline to 3 months (p = 0.94) and from baseline to 1 year (p = 1.00) after the CA. The change in the eGFR between baseline and 12 months was significantly smaller in the ablation group than in the control group (p <0.01). After logistic regression analysis, CA of AF was the independent predictor of an improvement of eGFR (odds ratio 2.81, 95% confidence interval 1.08 to 7.36, p = 0.04). In conclusion, CA of AF had a protective effect on renal function in patients with HCM.

Acute kidney injury (AKI) is a syndrome affecting most patients hospitalized due to kidney disease; it accounts for 15 % of patients hospitalized in intensive care units worldwide. AKI is mainly caused by ischemia and reperfusion (IR) injury, which temporarily obstructs the blood flow, increases inflammation processes and induces oxidative stress. AKI treatments available nowadays present notable disadvantages, mostly for patients with other comorbidities. Thus, it is important to investigate different approaches to help minimizing side effects such as the ones observed in patients subjected to the aforementioned treatments. Therefore, the aim of the current review is to highlight the potential of two endogenous gasotransmitters - hydrogen sulfide (H₂S) and nitric oxide (NO) - and their crosstalk in AKI treatment. Both H₂S and NO are endogenous signalling molecules involved in several physiological and pathophysiological processes, such as the ones taking place in the renal system. Overall, these molecules act by decreasing inflammation, controlling reactive oxygen species (ROS) concentrations, activating/inactivating pro-inflammatory cytokines, as well as promoting vasodilation and decreasing apoptosis, hypertrophy and autophagy. Since these gasotransmitters are found in gaseous state at environmental conditions, they can be directly applied by inhalation, or in combination with H₂S and NO donors, which are compounds capable of releasing these molecules at biological conditions, thus enabling higher stability and slow release of NO and H₂S. Moreover, the combination between these donor compounds and nanomaterials has the potential to enable targeted treatments, reduce side effects and increase the potential of H₂S and NO. Finally, it is essential highlighting challenges to, and perspectives in, pharmacological applications of H₂S and NO to treat AKI, mainly in combination with nanoparticulated delivery platforms.