Yusuke Sata

Short- and long-term outcomes of intracoronary and endogenously mobilized bone marrow stem cells in the treatment of ST-segment elevation myocardial infarction: A meta-analysis of randomized control trials

Bone marrow stem cell (BMSC) treatment of ST‐segment elevation myocardial infarction (STEMI) has been primarily via the intracoronary route or via endogenous mobilization using granulocyte colony‐stimulating factor (G‐CSF). Studies have provided conflicting results. We therefore performed a meta‐analysis of these treatments, examining short‐ and long‐term efficacy and safety.

Impact of heart failure and changes to volume status on liver stiffness: non‐invasive assessment using transient elastography

The impact of cardiac dysfunction on the liver is known as cardiac hepatopathy. In certain instances this can result in significant hepatic fibrosis or cirrhosis. The validity of non‐invasive tools to assess hepatic fibrosis, such as FibroScan® which measures liver stiffness (LSM), has not been established in this setting. We examined the impact of cardiac dysfunction on LSM using FibroScan® and the influence of volume changes on LSM.

Reverse cardiac remodeling after renal denervation: Atrial electrophysiologic and structural changes associated with blood pressure lowering

BACKGROUND Hypertension is the most common modifiable risk factor associated with atrial fibrillation. OBJECTIVE The purpose of this study was to determine the effects of blood pressure (BP) lowering after renal denervation on atrial electrophysiologic and structural remodeling in humans. METHODS Fourteen patients (mean age 64 ± 9 years, duration of hypertension 16 ± 11 years, on 5 ± 2 antihypertensive medications) with treatment-resistant hypertension underwent baseline 24-hour ambulatory BP monitoring, echocardiography, cardiac magnetic resonance imaging, and electrophysiologic study. Electrophysiologic study included measurements of P-wave duration, effective refractory periods, and conduction times. Electroanatomic mapping of the right atrium was completed using CARTO3 to determine local and regional conduction velocity and tissue voltage. Bilateral renal denervation was performed, and all measurements repeated after 6 months. RESULTS After renal denervation, mean 24-hour BP reduced from 152/84 mm Hg to 141/80 mm Hg at 6-month follow-up (P < .01). Global conduction velocity increased significantly (0.98 ± 0.13 m/s to 1.2 ± 0.16 m/s at 6 months, P < .01), conduction time shortened (32 ± 5 ms to 27 ± 6 ms, P < .01), and complex fractionated activity was reduced (37% ± 14% to 19% ± 12%, P = .02). Changes in conduction velocity correlated positively with changes in 24-hour mean systolic BP (R(2) = 0.55, P = .01). There was a significant reduction in left ventricular mass (139 ± 37 g to 120 ± 29 g, P < .01) and diffuse ventricular fibrosis (T1 partition coefficient 0.39 ± 0.07 to 0.31 ± 0.09, P = .01) on cardiac magnetic resonance imaging. CONCLUSION BP reduction after renal denervation is associated with improvements in regional and global atrial conduction and reductions in ventricular mass and fibrosis. Whether changes in electrical and structural remodeling are solely due to BP lowering or are due in part to intrinsic effects of renal denervation remains to be determined.

Dynamic characteristics of baroreflex neural and peripheral arcs are preserved in spontaneously hypertensive rats

Although baroreceptors are known to reset to operate in a higher pressure range in spontaneously hypertensive rats (SHR), the total profile of dynamic arterial pressure (AP) regulation remains to be clarified. We estimated open-loop transfer functions of the carotid sinus baroreflex in SHR and Wistar Kyoto (WKY) rats. Mean input pressures were set at 120 (WKY₁₂₀ and SHR₁₂₀) and 160 mmHg (SHR₁₆₀). The neural arc transfer function from carotid sinus pressure to efferent splanchnic sympathetic nerve activity (SNA) revealed derivative characteristics in both WKY and SHR. The slope of dynamic gain (in decibels per decade) between 0.1 and 1 Hz was not different between WKY₁₂₀ (10.1 ± 1.0) and SHR₁₂₀ (10.4 ± 1.1) but was significantly greater in SHR₁₆₀ (13.2 ± 0.8, P < 0.05 with Bonferroni correction) than in SHR₁₂₀. The peripheral arc transfer function from SNA to AP showed low-pass characteristics. The slope of dynamic gain (in decibels per decade) did not differ between WKY₁₂₀ (-34.0 ± 1.2) and SHR₁₂₀ (-31.4 ± 1.0) or between SHR₁₂₀ and SHR₁₆₀ (-32.8 ± 1.3). The total baroreflex showed low-pass characteristics and the dynamic gain at 0.01 Hz did not differ between WKY₁₂₀ (0.91 ± 0.08) and SHR₁₂₀ (0.84 ± 0.13) or between SHR₁₂₀ and SHR₁₆₀ (0.83 ± 0.11). In both WKY and SHR, the declining slope of dynamic gain was significantly gentler for the total baroreflex than for the peripheral arc, suggesting improved dynamic AP response in the total baroreflex. In conclusion, the dynamic characteristics of AP regulation by the carotid sinus baroreflex were well preserved in SHR despite significantly higher mean AP.

Predominant Role of Neural Arc in Sympathetic Baroreflex Resetting of Spontaneously Hypertensive Rats:– Analysis of an Open-Loop Baroreflex Equilibrium Diagram –

BACKGROUND There is ongoing controversy over whether neural or peripheral factors are the predominant cause of hypertension. The closed-loop negative feedback operation of the arterial baroreflex hampers understanding of how arterial pressure (AP) is determined through the interaction between neural and peripheral factors. METHODS AND RESULTS: A novel analysis of an isolated open-loop baroreceptor preparation to examine sympathetic nervous activity (SNA) and AP responses to changes in carotid sinus pressure (CSP) in adult spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was conducted. In the neural arc (CSP-SNA relationship), the midpoint pressure (128.9±3.8 vs. 157.9±8.1 mmHg, P<0.001) and the response range of SNA to CSP (90.5±3.7 vs. 115.4±7.6%/mmHg, P=0.011) were higher in SHR. In the peripheral arc (SNA-AP relationship), slope and intercept did not differ. A baroreflex equilibrium diagram was obtained by depicting neural and peripheral arcs in a pressure-SNA plane with rescaled SNA (% in WKY). The operating-point AP (111.3±4.4 vs. 145.9±5.2 mmHg, P<0.001) and SNA (90.8±3.2 vs. 125.1±6.9% in WKY, P<0.001) were shifted towards a higher level in SHR. CONCLUSIONS The shift of the neural arc towards a higher SNA range indicated a predominant contribution to baroreflex resetting in SHR. Notwithstanding the resetting, the carotid sinus baroreflex in SHR preserved an ability to reduce AP if activated with a high enough pressure.

Renal artery anatomy affects the blood pressure response to renal denervation in patients with resistant hypertension

BACKGROUND Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. METHODS We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. RESULTS RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (P<0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P<0.05). There was no deterioration in kidney function in any group. CONCLUSION While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences.

Renal denervation: current implications and future perspectives

SNS (sympathetic nervous system) activation is a common feature of arterial hypertension and has been demonstrated to contribute to the development and progression of the hypertensive state. Persuasive evidence suggests a strong association between SNS overactivity and variety of disease states, including chronic renal failure, insulin resistance, congestive heart failure, sleep apnoea, ventricular arrhythmias and others. Although sympatholytic agents are available to target SNS overactivity pharmacologically, they are not widely used in clinical practice, leaving the SNS unopposed in many patients. The recent introduction of catheter-based renal denervation as an alternative approach to target the SNS therapeutically has been demonstrated to result in a clinically relevant blood pressure reduction in patients with resistant hypertension, presumably through its effects on both efferent and afferent renal nerve traffic. Available data on this interventional procedure demonstrate a favourable vascular and renal safety profile. Preliminary data obtained primarily from small and mostly uncontrolled studies in related disease states often characterized by overactivity of the SNS are promising, but require confirmation in appropriately designed clinical trials. In the present paper, we briefly review the physiology of the renal nerves and their role in hypertension and other relevant disease states, summarize the data currently available from clinical studies pertaining to the safety and efficacy of renal denervation in resistant hypertension, discuss potential future implications and the available data supporting such a role for renal denervation, and describe some of the newer devices currently under investigation to achieve improved blood pressure control via renal denervation.

Contrasting effects of moderate vagal stimulation on heart rate and carotid sinus baroreflex-mediated sympathetic arterial pressure regulation in rats

AIMS To examine whether moderate efferent vagal nerve stimulation (VNS) attenuates the carotid sinus baroreflex-mediated arterial pressure (AP) regulation via its antagonism to the sympathetic system. MAIN METHODS Carotid sinus baroreceptor regions were isolated from the systemic circulation in eight anesthetized and vagotomized rats. A staircase-wise input was imposed on carotid sinus pressure (CSP) with or without efferent VNS (20Hz, 2ms, 1-4V), while the responses in AP, heart rate (HR), and splanchnic sympathetic nerve activity (SNA) were measured. KEY FINDINGS A multiple linear regression analysis indicated that VNS decreased the minimum HR in the CSP-HR relationship by 58.2±4.9 beats/min (P<0.01) from its reference value of 387.0±5.8 beats/min. Although VNS significantly decreased an intercept of the SNA-AP relationship, it did not affect parameters of the CSP-AP relationship or the CSP-SNA relationship significantly. The operating-point AP of the baroreflex was decreased by 2.8±1.0mmHg (P<0.01) during VNS, which was less than 3% of the reference value of 117.7±1.2mmHg. SIGNIFICANCE VNS, at an intensity of decreasing HR by approximately 13%, does not acutely attenuate the baroreflex-mediated sympathetic AP regulation.

Effect of renal denervation on kidney function in patients with chronic kidney disease

AIMS Renal denervation (RDN) can reduce blood pressure (BP) and slow the decline of renal function in chronic kidney disease (CKD) up to one year. Whether this effect is maintained beyond 12months and whether the magnitude of BP reduction affects estimated glomerular filtration rate (eGFR) is unknown. METHODS AND RESULTS We examined eGFR in 46 CKD patients (baseline eGFR ≤60mL/min/1.73m2) on a yearly basis from 60months before to 3, 6, 12 and 24months after RDN. Ambulatory BP was measured before and after RDN. Linear mixed models analysis demonstrated a significant progressive decline in eGFR from months 60 to 12months (-15.47±1.98mL/min/1.73m2, P<0.0001) and from 12months to baseline prior to RDN (-3.41±1.64mL/min/1.73m2, P=0.038). Compared to baseline, RDN was associated with improved eGFR at 3months (+3.73±1.64mL/min/1.73m2, P=0.02) and no significant changes at 6 (+2.54±1.66mL/min/1.73m2, P=0.13), 12 (+1.78±1.64mL/min/1.73m2, P=0.28), and 24 (-0.24±2.24mL/min/1.73m2, P=0.91) months post procedure were observed. RDN significantly reduced daytime SBP from baseline to 24months post procedure (148±19 vs 136±17mmHg, P=0.03) for the entire cohort. Changes in SBP were unrelated to the eGFR changes at 6 (r=0.033, P=0.84), 12 (r=0.01, P=0.93) and 24months (r=-0.42, P=0.17) follow-up. CONCLUSION RDN can slow further deterioration of renal function irrespective of BP lowering effects in CKD. RDN-induced inhibition of sympathetic outflow to the renal vascular bed may account for improved eGFR via alterations of intrarenal and glomerular hemodynamics.

Central vagal activation by alpha2-adrenergic stimulation is impaired in spontaneously hypertensive rats

To elucidate the abnormality of vagal control in spontaneously hypertensive rats (SHR) by measuring left ventricular myocardial interstitial acetylcholine (ACh) release in response to α2‐adrenergic stimulation as an index of in vivo vagal nerve activity.