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Canine coronavirus (CCV) and canine parvovirus type 2 (CPV-2) are the causative agents of gastroenteritis in dogs. Seventy fecal samples from dogs with signs of gastroenteritis (vomiting and diarrhea), twenty-five fecal samples from healthy dogs and one CPV-2 vaccine strain were amplified by semi-nested polymerase chain reaction (PCR) and semi-nested reverse transcriptase polymerase chain reaction (RT-PCR), aimed at specifically studying the gene encoding the most abundant capsid protein VP2 of CPV-2 and spike protein of CCV. The specificity of the CCV RT-PCR product was evaluated by sequencing. Positive specimens comprised 44 samples (62.8%) and 9 samples (12.8%) for CPV-2 and CCV, respectively. In nine CCV positive samples, seven displayed co-infection between CCV and CPV-2. Our CCV sequence (AF482001) showed a 94.9% nucleotide identity to CCV reported in GenBank accession number D13096. High prevalence of CCV and CPV-2 infections was found in 1-2 month- and 3-6 month-old dogs, respectively. Molecular biology of these viruses is important primarily for epidemic control and preventive measures.

Giving the right information to the right person at the right time is one of the main factors contributing to the success of e-commerce applications. Existing applications of active views to e-commerce mostly generate application views based on user roles such as customers and vendors, so they cannot completely serve one-to-one marketing. Furthermore, the data controlled by the existing applications is limited to those retrieved from databases, but does not include other web contents such as pictures, descriptive information and hyperlinks. In addition, the integration of active views to existing e-commerce applications still presents some difficulties in tackling heterogenity. This work presents a model of the Active View Agents System (AVAS), based on a co-performance model of multi-agents, to resolve these problems.

Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by 2-16% gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (FER and MER) of cholesterol in plasma and HDL were also determined. As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes (boys: r = -0.694, 0.708 and 0.701, girls: r = -0.579, 0.551 and 0.539, P < 0.001). However, a closer association was found between FER in HDL (FER(HDL)) and LDL-size (boys: r= -0.874, girls: r= -0.642, P < 0.001). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 76% and 41% of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4% and 19% in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FER(HDL) is useful to predict the particle size of LDL in children.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) benefits patients with cardiogenic shock (CS) but can increase left ventricular afterload and exacerbate pulmonary edema. Adding a percutaneous left ventricular assist device (LVAD) to VA-ECMO can optimize the hemodynamics. Because managing VA-ECMO and LVAD simultaneously is complex and labor-intensive, we developed a closed-loop automated control system for VA-ECMO and LVAD. Based on the circulatory equilibrium framework, this system automatically adjusts VA-ECMO and LVAD flows and cardiovascular drug and fluid dosages to achieve target arterial pressure (AP, 70 mm Hg), left atrial pressure (PLA, 14 mm Hg), and total systemic flow (Ftotal, 120-140 ml/min/kg). In seven anesthetized dogs with CS, VA-ECMO significantly increased AP and PLA from 24 (23-27) to 71 (63-77) mm Hg and 20.1 (16.3-22.1) to 43.0 (25.7-51.4) mm Hg, respectively. Upon system activation, PLA was promptly reduced. At 60 min postactivation, the system-controlled AP to 69 (65-74) mm Hg, PLA to 12.5 (12.0-13.4) mm Hg, and Ftotal to 117 (114-132) ml/min/kg while adjusting VA-ECMO flow to 59 (12-60) ml/min/kg, LVAD flow to 68 (54-78) ml/min/kg, and cardiovascular drug and fluid dosages. This system automatically optimizes VA-ECMO and LVAD hemodynamics, making it an attractive tool for rescuing patients with CS., Competing Interests: Disclosure: K.S. received research funding from NTT Research, Inc., Abiomed Japan K.K., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals Inc., and Zeon Medical Inc., and honoraria from Abiomed Japan K.K., Mallinckrodt Pharma K.K., and Ono Pharmaceutical Co., Ltd. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Background: Retrohepatic inferior vena cava (IVC) injuries remain among the most lethal and serious liver injuries. Gauze packing is currently the first choice for IVC injuries; however, laparotomy itself poses the risk of circulatory collapse. Thus, less invasive treatment strategies are needed., Methods: In this study, we conducted an animal experiment to replicate and validate successful treatments for an actual case of retrohepatic IVC injury that we had encountered., Results: A woman in her 80s presented to our hospital due to cardiac arrest caused by a pulmonary artery embolism. Venoarterial extracorporeal membrane oxygenation (ECMO) was introduced, and the patient was resuscitated. After resuscitation, contrast-enhanced CT revealed liver and retrohepatic IVC injuries, possibly caused by chest compressions. Liver injury was treated using transarterial embolization of the left hepatic artery. To treat the retrohepatic IVC injury, ECMO flow was increased to enhance the negative drainage pressure. The extravasation of the contrast medium had resolved in IVC angiography, and we opted for nonoperative management. The patient's hemodynamic status gradually stabilized, and ECMO was withdrawn on day 6. We confirmed these findings in a dog model of retrohepatic IVC injury., Conclusions: Our findings from the patient and the animal model suggest that the flow diversion effect of ECMO can effectively manage active bleeding from the IVC by inserting a drainage cannula across the injured lesion. We think this procedure represents a novel treatment option for retrohepatic IVC injuries., Competing Interests: KS received research funding from Abiomed Japan KK, NTT Research, Inc, Asahi Kasei ZOLL Medical Corporation, Neuroceuticals, Inc, and Zeon Medical, Inc. He also received honoraria from Abiomed Japan KK and Mallinckrodt Pharmaceuticals, Inc., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Bilateral renal denervation (RDN) decreases arterial pressure (AP) or delays the development of hypertension in spontaneously hypertensive rats (SHR), but whether bilateral RDN significantly modifies urine output function during baroreflex-mediated acute AP changes remains unknown. We quantified the relationship between AP and normalized urine flow (nUF) in SHR that underwent bilateral RDN (n = 9) and compared the results with those in sham-operated SHR (n = 9). Moreover, we examined the acute effect of an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) on the AP-nUF relationship. Bilateral RDN significantly decreased AP by narrowing the response range of the total arc of the carotid sinus baroreflex. The slopes of nUF versus the mean AP (in μL·min -1 ·kg -1 ·mmHg -1 ) in the sham and RDN groups under baseline conditions were 0.076 ± 0.045 and 0.188 ± 0.039, respectively; and those after telmisartan administration were 0.285 ± 0.034 and 0.416 ± 0.078, respectively. The effect of RDN on the nUF slope was marginally significant (P = 0.059), which may have improved the controllability of urine output in the RDN group. The effect of telmisartan on the nUF slope was significant (P < 0.001) in the sham and RDN groups, signifying the contribution of circulating or locally produced angiotensin II to determining urine output function regardless of ongoing renal sympathetic nerve activity., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Although sympathetic suppression is considered one of the mechanisms for cardioprotection afforded by sodium-glucose cotransporter 2 (SGLT2) inhibitors, whether SGLT2 inhibition acutely modifies sympathetic arterial pressure (AP) regulation remains unclear. We examined the acute effect of an SGLT2 inhibitor, empagliflozin (10 mg/kg), on open-loop baroreflex static characteristics in streptozotocin (STZ)-induced type 1 diabetic and control (CNT) rats (n = 9 each). Empagliflozin significantly increased urine flow [CNT: 25.5 (21.7-31.2) vs. 55.9 (51.0-64.5), STZ: 83.4 (53.7-91.7) vs. 121.2 (57.0-136.0) μL·min -1 ·kg -1 , median (1st-3rd quartiles), P < 0.001 for empagliflozin and STZ]. Empagliflozin decreased the minimum sympathetic nerve activity (SNA) [CNT: 15.7 (6.8-18.4) vs. 10.5 (2.9-19.0), STZ: 36.9 (25.7-54.9) vs. 32.8 (15.1-37.5) %, P = 0.021 for empagliflozin and P = 0.003 for STZ], but did not significantly affect the peripheral arc characteristics assessed by the SNA-AP relationship. Despite the significant increase in urine flow and changes in several baroreflex parameters, empagliflozin preserved the overall sympathetic AP regulation in STZ-induced diabetic rats. The lack of a significant change in the peripheral arc may minimize reflex sympathetic activation, thereby enhancing a cardioprotective benefit of empagliflozin., (© 2024. The Author(s).)

Background: Left ventricular (LV) unloading by Impella, an intravascular microaxial pump, has been shown to exert dramatic cardioprotective effects in acute clinical settings of cardiovascular diseases. Total Impella support (no native LV ejection) is far more efficient in reducing LV energetic demand than partial Impella support, but the manual control of pump speed to maintain stable LV unloading is difficult and impractical. We aimed to develop an Automatic IMpella Optimal Unloading System (AIMOUS), which controls Impella pump speed to maintain LV unloading degree using closed-feedback control. We validated the AIMOUS performance in an animal model., Methods: In dogs, we identified the transfer function from pump speed to LV systolic pressure (LVSP) under total support conditions (n = 5). Using the transfer function, we designed the feedback controller of AIMOUS to keep LVSP at 40 mmHg and examined its performance by volume perturbations (n = 9). Lastly, AIMOUS was applied in the acute phase of ischemia-reperfusion in dogs. Four weeks after ischemia-reperfusion, we assessed LV function and infarct size (n = 10)., Results: AIMOUS maintained constant LVSP, thereby ensuring a stable LV unloading condition regardless of volume withdrawal or infusion (±8 ml/kg from baseline). AIMOUS in the acute phase of ischemia-reperfusion markedly improved LV function and reduced infarct size (No Impella support: 13.9 ± 1.3 vs. AIMOUS: 5.7 ± 1.9%, P < 0.05)., Conclusions: AIMOUS is capable of maintaining optimal LV unloading during periods of unstable hemodynamics. Automated control of Impella pump speed in the acute phase of ischemia-reperfusion significantly reduced infarct size and prevented subsequent worsening of LV function., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high-resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure ( P r ) and blood flow ( F r ) during random ventricular pacing to induce pressure fluctuation at three different mean P r (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from F r to P r . The RA impedance was found to align with a three-element Windkessel model consisting of proximal ( R p ) and distal ( R d ) resistance and compliance ( C ). Our study showed R d reflected the composite characteristics of afferent and efferent arterioles. R d increased with increasing P r under the baseline condition with a slope of 1.03 ± 0.21 (× 10 -1 ) min·mL -1 . ANG II significantly increased the slope by 0.72 ± 0.29 (× 10 -1 ) min·mL -1 ( P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10 -1 ) mmHg·min·mL -1 ( P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10 -1 ) mmHg·min·mL -1 , whereas it did not affect the slope. In contrast, R p was less sensitive than R d to ANG II or TELM, suggesting R p may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature. NEW & NOTEWORTHY This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II.

Objective: To assess the occurrence, predictors, and outcomes of hypo-attenuated leaflet thickening (HALT) and thrombus outside the prosthetic valve following surgical aortic valve replacement., Methods: A total of 118 patients underwent surgical aortic valve replacement with bioprosthetic valves between July 2020 and June 2022. Sixty-two (52.5%) patients, which is a fairly high number of patients, underwent cardiac computed tomography and transthoracic echocardiography one week after surgery. Patients were divided into two groups, those with HALT (n = 14) and those without HALT (n = 48)., Results: Of the 62 patients who underwent cardiac computed tomography, HALT was observed in 14 (22.5%) patients during the very early postoperative phase. Reduced leaflet motion was observed in two of the 14 patients. The low-attenuation areas were located outside the prosthetic valve in 10 cases (71.4%) in the HALT group and in 14 cases (29.2%) in the non-HALT group. More than 50% of patients (57.1%) with HALT and 79.2% without HALT were administered warfarin. Neither in-hospital deaths nor postoperative thromboembolic events were observed during hospitalization. No patient had a mean pressure gradient > 20 mmHg in either group., Conclusion: HALT was observed in one-fifth of the cases after surgical aortic valve replacement during the very early postoperative phase in an institution wherein administration of continuous heparin infusion after surgery is a standard practice. HALT did not affect the early prognosis or incidence of cerebral infarction., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Background: Impella (Abiomed, Danvers, MA, USA) is a percutaneous ventricular assist device commonly used in cardiogenic shock, providing robust hemodynamic support, improving the systemic circulation, and relieving pulmonary congestion. Maintaining adequate left ventricular (LV) filling is essential for optimal hemodynamic support by Impella. This study aimed to investigate the impact of pulmonary vascular resistance (PVR) and right ventricular (RV) function on Impella-supported hemodynamics in severe biventricular failure using cardiovascular simulation., Methods: We used Simulink® (Mathworks, Inc., Natick, MA, USA) for the simulation, incorporating pump performance of Impella CP determined using a mock circulatory loop. Both systemic and pulmonary circulation were modeled using a 5-element resistance-capacitance network. The four cardiac chambers were represented by time-varying elastance with unidirectional valves. In the scenario of severe LV dysfunction (LV end-systolic elastance set at a low level of 0.4 mmHg/mL), we compared the changes in right (RAP) and left atrial pressures (LAP), total systemic flow, and pressure-volume loop relationship at varying degrees of RV function, PVR, and Impella flow rate., Results: The simulation results showed that under low PVR conditions, an increase in Impella flow rate slightly reduced RAP and LAP and increased total systemic flow, regardless of RV function. Under moderate RV dysfunction and high PVR conditions, an increase in Impella flow rate elevated RAP and excessively reduced LAP to induce LV suction, which limited the increase in total systemic flow., Conclusions: PVR is the primary determinant of stable and effective Impella hemodynamic support in patients with severe biventricular failure., Competing Interests: Declaration of competing interest Matsushita H, Nishikawa T, Unoki T, Yokota S, Sato K, Morita H, Yoshida Y, Fukumitsu M, Nishiura A, Uemura K, Kawada T, Kikuchi A, and Yamaura K, declare no conflicts of interest. Saku K received research funding from Abiomed Japan K.K., NTT Research, Inc., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals Inc., and Zeon Medical Inc. and honoraria from Abiomed Japan K.K., Mallinckrodt Pharma K.K., and Ono Pharmaceutical Co., Ltd., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The IMPELLA 5.5 (Abiomed Inc., Danvers, Massachusetts, United States) is a catheter-based, micro-axial blood pump designed to enhance organ perfusion in patients with cardiogenic shock. Despite its superior hemodynamic support, vascular complications are a significant concern, with many patients needing to discontinue IMPELLA therapy due to these issues. Patients may even require surgical intervention to address device-related vascular injuries. The IMPELLA 5.5 implantation in vessels with severe calcification is particularly associated with complications such as vascular calcification, stenosis, vascular tortuosity, and the use of larger sheaths are risk factors following endovascular therapy and IMPELLA implantation. In this report, we present a case of severe calcification in the right subclavian artery, in which the IMPELLA 5.5 was lodged. The calcifications protruded into the vascular lumen, becoming lodged between the IMPELLA motor and the cannula, complicating extraction despite the vessel having sufficient diameter. We successfully removed the device using a balloon dilation technique, ensuring safe extraction. No vascular complications such as pseudoaneurysm or dissection were observed in the right subclavian artery one month after extraction. This case highlights a potential approach for managing similar complications and vascular access for IMPELLA insertion., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Kurume University issued approval 21001. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Takagi et al.)

Objective: Total artificial heart (TAH) using dual rotary blood pumps (RBPs) is a potential treatment for end-stage heart failure. A well-noted challenge with RBPs is their low sensitivity to preload, which can lead to venous congestion and ventricular suction. To address this issue, we have developed an innovative closed-loop control system of dual RBPs in TAH. This system emulates the Frank-Starling law of the heart in controlling RBPs while monitoring stressed blood volume (V) based on the circulatory equilibrium framework. We validated the system in in-vivo experiments., Methods: In 9 anesthetized dogs, we prepared a TAH circuit using 2 centrifugal-type RBPs. We first investigated whether the flow and inlet atrial pressure in each RBP adhered to a logarithmic Frank-Starling curve. We then examined whether the RBP flows and atrial pressures were maintained stably during aortic occlusion (AO) and pulmonary cannula stenosis (PS), whether averaged flow of dual RBPs and bilateral atrial pressures were controlled to their predefined target values for a specific V, and whether this system could maintain the atrial pressures within predefined control ranges under significant changes in V., Results: This system effectively emulated the logarithmic Frank-Starling curve. It robustly stabilized the flow and atrial pressures during AO and PS without venous congestion or ventricular suction, accurately achieved target values in averaged flow and atrial pressures, and efficaciously maintained these pressures within the control ranges., Conclusion: This system controls dual RBPs in TAH accurately and stably., Significance: This system may accelerate clinical application of TAH with dual RBPs.

Nitric oxide (NO) inhalation improves pulmonary hemodynamics in participants with pulmonary arterial hypertension (PAH). Although it can reduce pulmonary vascular resistance (PVR) in PAH, its impact on the dynamic mechanics of pulmonary arteries and its potential difference between control and participants with PAH remain unclear. PA impedance provides a comprehensive description of PA mechanics. With an arterial model, PA impedance can be parameterized into peripheral pulmonary resistance ( R p ), arterial compliance ( C p ), characteristic impedance of the proximal arteries ( Z c ), and transmission time from the main PA to the reflection site. This study investigated the effects of inhaled NO on PA impedance and its associated parameters in control and monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) male rats (6/group). Measurements were obtained at baseline and during NO inhalation at 40 and 80 ppm. In both groups, NO inhalation decreased PVR and increased the left atrial pressure. Notably, its impact on PA impedance was frequency dependent, as revealed by reduced PA impedance modulus in the low-frequency range below 10 Hz, with little effect on the high-frequency range. Furthermore, NO inhalation attenuated R p , increased C p , and prolonged transmission time without affecting Z c . It reduced R p more pronouncedly in MCT-PAH rats, whereas it increased C p and delayed transmission time more effectively in control rats. In conclusion, the therapeutic effects of inhaled NO on PA impedance were frequency dependent and may differ between the control and MCT-PAH groups, suggesting that the effect on the mechanics differs depending on the pathological state. NEW & NOTEWORTHY Nitric oxide inhalation decreased pulmonary arterial impedance in the low-frequency range (<10 Hz) with little impact on the high-frequency range. It reduced peripheral pulmonary resistance more pronouncedly in pulmonary hypertension rats, whereas it increased arterial compliance and transmission time in control rats. Its effect on the mechanics of the pulmonary arteries may differ depending on the pathological status.

Introduction: Intra-operative hypotension is a common complication of surgery under general anesthesia in dogs and humans. Computer-controlled closed-loop infusion systems of norepinephrine (NE) have been developed and clinically applied for automated optimization of arterial pressure (AP) and prevention of intra-operative hypotension in humans. This study aimed to develop a simple computer-controlled closed-loop infusion system of NE for the automated control of the mean arterial pressure (MAP) in dogs with isoflurane-induced hypotension and to validate the control of MAP by the developed system., Methods: NE was administered via the cephalic vein, whereas MAP was measured invasively by placing a catheter in the dorsal pedal artery. The proportional-integral-derivative (PID) controller in the negative feedback loop of the developed system titrated the infusion rate of NE to maintain the MAP at the target value of 60 mmHg. The titration was updated every 2 s. The performance of the developed system was evaluated in six laboratory Beagle dogs under general anesthesia with isoflurane., Results: In the six dogs, when the concentration [median (interquartile range)] of inhaled isoflurane was increased from 1.5 (1.5-1.5)% to 4 (4-4)% without activating the system, the MAP was lowered from 95 (91-99) to 41 (37-42) mmHg. In contrast, when the concentration was increased from 1.5 (1.0-1.5)% to 4 (4-4.8)% for a 30-min period and the system was simultaneously activated, the MAP was temporarily lowered from 92 (89-95) to 47 (43-49) mmHg but recovered to 58 (57-58) mmHg owing to the system-controlled infusion of NE. If the acceptable target range for MAP was defined as target MAP ±5 mmHg (55 ≤ MAP ≤65 mmHg), the percentage of time wherein the MAP was maintained within the acceptable range was 96 (89-100)% in the six dogs during the second half of the 30-min period (from 15 to 30 min after system activation). The median performance error, median absolute performance error, wobble, and divergence were - 2.9 (-4.7 to 1.9)%, 2.9 (2.0-4.7)%, 1.3 (0.8-1.8)%, and - 0.24 (-0.34 to -0.11)%·min -1 , respectively. No adverse events were observed during the study period, and all dogs were extubated uneventfully., Conclusion: This system was able to titrate the NE infusion rates in an accurate and stable manner to maintain the MAP within the predetermined target range in dogs with isoflurane-induced hypotension. This system can be a potential tool in daily clinical practice for the care of companion dogs., Competing Interests: JA and YK are employees of NTT Res. Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sasaki, Kawada, Matsushita, Yokota, Kakuuchi, Yokoi, Yoshida, Morita, Sato, Nishikawa, Kutter, Kataoka, Alexander, Saku, Ishikawa and Uemura.)

Purpose: Mechanical circulatory support (MCS) using a venoarterial extracorporeal membrane oxygenation (VA-ECMO) device or a catheter-type heart pump (Impella) is critical for the rescue of patients with severe cardiogenic shock. However, these MCS devices require large-bore cannula access (14-Fr and larger) at the femoral artery or vein, which often requires surgical decannulation., Methods: In this retrospective study, we evaluated post-closure method using a percutaneous suture-mediated vascular closure system, Perclose ProGlide/ProStyle (Abbott Vascular, Lake Bluff, IL, Perclose), as an alternative procedure for MCS decannulation. Closure of 83 Impella access sites and 68 VA-ECMO access sites performed using Perclose or surgical method between January 2018 and March 2023 were evaluated., Results: MCS decannulation using Perclose was successfully completed in all access sites without surgical hemostasis. The procedure time of ProGlide was shorter than surgical decannulation for both Impella and VA-ECMO (13 min vs. 50 min; p < 0.001, 21 min vs. 65 min; p < 0.001, respectively). There were no significant differences in the 30-day survival rate and major adverse events by decannulation including arterial dissection requiring endovascular treatment, hemorrhage requiring a large amount of red blood cell transfusion, and access site infection., Conclusion: Our results suggest that the post-closure technique using the percutaneous suture-mediated closure system appears to be a safe and effective method for large-bore MCS decannulation., Competing Interests: Declaration of competing interest Keita Saku received research funding from Omron Healthcare Co., Abiomed Japan K.K., NTT Research, Inc., Asahi Kasei ZOLL Medical Corporation, Neuroceuticals Inc., and Zeon Medical Inc., and honoraria from Abiomed Japan K.K., Ono Pharmaceutical Co., Ltd., and Mallinckrodt Japan Co. Ltd. The other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The acetylcholinesterase inhibitor donepezil restores autonomic balance, reduces inflammation, and improves long-term survival in rats with chronic heart failure (CHF) following myocardial infarction (MI). As arterial hypertension is associated with a significant risk of cardiovascular death, we investigated the effectiveness of donepezil in treating CHF in spontaneously hypertensive rats (SHR). CHF was induced in SHR by inducing permanent MI. After 2 weeks, the surviving SHR were randomly assigned to sham-operated (SO), untreated (UT), or oral donepezil-treated (DT, 5 mg/kg/day) groups, and various vitals and parameters were monitored. After 7 weeks of treatment, heart rate and arterial hypertension reduced significantly in DT rats than in UT rats. Donepezil treatment improved 50-day survival (41% to 80%, P = 0.004); suppressed progression of cardiac hypertrophy, cardiac dysfunction (cardiac index: 133 ± 5 vs. 112 ± 5 ml/min/kg, P < 0.05; left ventricular end-diastolic pressure: 12 ± 3 vs. 22 ± 2 mmHg, P < 0.05; left ventricular +dp/dt max : 5348 ± 338 vs. 4267 ± 114 mmHg/s, P < 0.05), systemic inflammation, and coronary artery remodeling (wall thickness: 26.3 ± 1.4 vs. 34.7 ± 0.7 μm, P < 0.01; media-to-lumen ratio: 3.70 ± 0.73 vs. 8.59 ± 0.84, P < 0.001); increased capillary density; and decreased plasma catecholamine, B-type natriuretic peptide, arginine vasopressin, and angiotensin II levels. Donepezil treatment attenuated cardiac and coronary artery remodeling, mitigated cardiac dysfunction, and significantly improved the prognosis of SHR with CHF., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Although body fluid volume control by the kidneys may be classified as a long-term arterial pressure (AP) control system, it does not necessarily follow that the urine flow (UF) response to changes in AP is slow. We quantified the dynamic characteristics of the UF response to short-term AP changes by changing mean AP between 60 mmHg and 100 mmHg every 10 s according to a binary white noise sequence in anesthetized rats ( n = 8 animals). In a baro-on trial (the carotid sinus baroreflex was enabled), the UF response represented the combined synergistic effects of pressure diuresis (PD) and neurally mediated antidiuresis (NMA). In a baro-fix trial (the carotid sinus pressure was fixed at 100 mmHg), the UF response mainly reflected the effect of PD. The UF step response was quantified using the sum of two exponential decay functions. The fast and slow components had time constants of 6.5 ± 3.6 s and 102 ± 85 s (means ± SD), respectively, in the baro-on trial. Although the gain of the fast component did not differ between the two trials (0.49 ± 0.21 vs. 0.66 ± 0.22 µL·min -1 ·kg -1 ·mmHg -1 ), the gain of the slow component was greater in the baro-on than in the baro-fix trial (0.51 ± 0.14 vs. 0.09 ± 0.39 µL·min -1 ·kg -1 ·mmHg -1 , P = 0.023). The magnitude of NMA relative to PD was calculated to be 32.2 ± 29.8%. In conclusion, NMA contributed to the slow component, and its magnitude was approximately one-third of that of the effect of PD. NEW & NOTEWORTHY We quantified short-term dynamic characteristics of the urine flow (UF) response to arterial pressure (AP) changes using white noise analysis. The UF step response approximated the sum of two exponential decay functions with time constants of ∼6.5 s and 102 s. The neurally mediated antidiuretic (NMA) effect contributed to the slow component of the UF step response, with the magnitude of approximately one-third of that of the pressure diuresis (PD) effect.

Background: ECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO 2 ) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO 2 into our developed cardiovascular simulation., Methods and Results: Both the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure-volume relationship (PV loop), and global DO 2 under different VA-ECMO flows and Impella support levels., Results: In the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure-volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV-PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO 2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO 2 increment under ECPELLA total support conditions., Conclusions: The optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO 2 in total ECPELLA support conditions., (© 2024. The Author(s).)

Although Gaussian white noise (GWN) inputs offer a theoretical framework for identifying higher-order nonlinearity, an actual application to the data of the neural arc of the carotid sinus baroreflex did not succeed in fully predicting the well-known sigmoidal nonlinearity. In the present study, we assumed that the neural arc can be approximated by a cascade of a linear dynamic (LD) component and a nonlinear static (NS) component. We analyzed the data obtained using GWN inputs with a mean of 120 mmHg and standard deviations (SDs) of 10, 20, and 30 mmHg for 15 min each in anesthetized rats ( n = 7). We first estimated the linear transfer function from carotid sinus pressure to sympathetic nerve activity (SNA) and then plotted the measured SNA against the linearly predicted SNA. The predicted and measured data pairs exhibited an inverse sigmoidal distribution when grouped into 10 bins based on the size of the linearly predicted SNA. The sigmoidal nonlinearity estimated via the LD-NS model showed a midpoint pressure (104.1 ± 4.4 mmHg for SD of 30 mmHg) lower than that estimated by a conventional stepwise input (135.8 ± 3.9 mmHg, P < 0.001). This suggests that the NS component is more likely to reflect the nonlinearity observed during pulsatile inputs that are physiological to baroreceptors. Furthermore, the LD-NS model yielded higher R 2 values compared with the linear model and the previously suggested second-order Uryson model in the testing dataset. NEW & NOTEWORTHY We examined the input-size dependence of the baroreflex neural arc transfer characteristics during Gaussian white noise inputs. A linear dynamic-static nonlinear model yielded higher R 2 values compared with a linear model and captured the well-known sigmoidal nonlinearity of the neural arc, indicating that the nonlinear dynamics contributed to determining sympathetic nerve activity. Ignoring such nonlinear dynamics might reduce our ability to explain underlying physiology and significantly limit the interpretation of experimental data.

Background: Mitral valve repair (MVr) is an established procedure for patients who require surgery for primary mitral regurgitation (PMR). The Colvin-Galloway Future Band (CGFB) is a semi-rigid posterior band expected to improve the clinical outcomes of MVr. However, information on the hemodynamic and functional performance and long-term outcomes of CGFB is limited. We evaluated the quality, durability, and clinical performance after MVr using CGFB for PMR as the cohort study., Methods: A total of 244 patients who underwent MVr with CGFB were enrolled. Clinical and echocardiographic assessments were performed (mean follow-up period, 4.0±2.4 years)., Results: Posterior mitral leaflet resection was the most common MVr procedure. CGFBs measuring 28 mm (35.2%) and 30 mm (36.5%) were used. The incidence of systolic anterior motion (SAM) was 1.6%. A total of 93.4% of the patients had no or trace MR at discharge. Over 90% of patients had no or mild MR at the last follow-up. The mean pressure gradient and mitral valve orifice area one year after MVr ranged between 2.6 and 3.6 mmHg and 2.3 and 3.4 cm 2 , respectively. At follow-up, 85.4% of the patients were New York Heart Association class I. Three patients underwent repeat mitral valve surgery., Conclusions: The CGFB demonstrates satisfactory quality and durability in MVr for PMR. Other advantages include a low occurrence of SAM and acceptable hemodynamic outcomes, particularly in patients requiring a smaller annuloplasty device., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1486/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Acute aortic dissection (AAD) with impaired perfusion of the left coronary artery has a poor prognosis, even after urgent radical aortic surgery, due to extensive myocardial damage. Although Impella, a microaxial-flow catheter pump, is useful in managing acute myocardial infarction, it is generally contraindicated in patients with AAD because it is an intra-aortic device and the aortic structure is compromised in these cases. Here, we introduce a novel intervention that allowed a planned aortic repair after managing circulation using Impella and venoarterial extracorporeal membrane oxygenation in a case of AAD with left main trunk malperfusion., Case Presentation: A 40-year-old man presented with cardiogenic shock. Percutaneous coronary intervention was performed to address left main trunk obstruction using an intra-aortic balloon pump; however, circulatory instability persisted. The patient was transferred to our hospital after venoarterial extracorporeal membrane oxygenation. Impella CP™ was used to improve his circulatory status. However, a subsequent CT scan confirmed an AAD diagnosis. After 5 days of stable circulatory support, the patient underwent aortic root replacement and coronary artery bypass grafting., Conclusions: In patients with AAD and coronary malperfusion, adjunctive circulatory management with Impella may be a valuable therapeutic option., (© 2024. The Author(s).)

Cardiogenic shock is a complex and diverse pathological condition characterized by reduced myocardial contractility. The goal of treatment of cardiogenic shock is to improve abnormal hemodynamics and maintain adequate tissue perfusion in organs. If hypotension and insufficient tissue perfusion persist despite initial therapy, temporary mechanical circulatory support (t-MCS) should be initiated. This decade sees the beginning of a new era of cardiogenic shock management using t-MCS through the accumulated experience with use of intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO), as well as new revolutionary devices or systems such as transvalvular axial flow pump (Impella) and a combination of VA-ECMO and Impella (ECPELLA) based on the knowledge of circulatory physiology. In this transitional period, we outline the approach to the management of cardiogenic shock by t-MCS. The management strategy involves carefully selecting one or a combination of the t-MCS devices, taking into account the characteristics of each device and the specific pathological condition. This selection is guided by monitoring of hemodynamics, classification of shock stage, risk stratification, and coordinated management by the multidisciplinary shock team., (© 2023. The Author(s).)

Background: Hyogo Prefecture has managed smoking ban legislation with partial restrictions in public places (Hyogo-L) since 2013. Previous studies have reported a significant decrease in admissions for acute coronary syndrome (ACS) in Kobe-city, but not in other districts of Hyogo Prefecture in the 2 years after Hyogo-L. The aim of the present study was to define the long-term effect of Hyogo-L., Methods and results: The JROAD-DPC dataset was used to collect information on the number of hospitalizations for ACS in Hyogo Prefecture, and in Osaka-city without smoking ban legislation, from April 2013 to March 2020. Poisson regression analysis was performed to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). ACS records of 3,101 in Kobe-city, 11,375 in areas of Hyogo Prefecture other than Kobe-city and 11,079 in Osaka-city were collected for admissions. The incidence of ACS reduced significantly over time in Kobe-city [IRR (95% CI); 0.96 (0.94-0.97)], but did not reduce in the others. The decrease in Kobe-city was observed in ACS patients without smoking, hypertension, and hyperlipidemia, but not in those with such risk factors., Conclusions: The long-term ACS reduction or non-reduction under Hyogo-L was determined at the initial period and the same scenario continued, supporting the importance of legislation and compliance with the smoking ban. The lowering effect was remarkable in ACS patients without risk factors such as non-smoking.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have exerted cardioprotective effects in clinical trials, but underlying mechanisms are not fully understood. As mitigating sympathetic overactivity is of major clinical concern in the mechanisms of heart failure treatments, we examined the effects of modulation of glucose handling on baroreflex-mediated sympathetic nerve activity and arterial pressure regulations in rats with chronic myocardial infarction (n = 9). Repeated 11-min step input sequences were used for an open-loop analysis of the carotid sinus baroreflex. An SGLT2 inhibitor, empagliflozin, was intravenously administered (10 mg/kg) after the second sequence. Neither the baroreflex neural nor peripheral arc significantly changed during the last observation period (seventh and eighth sequences) compared with the baseline period although urinary glucose excretion increased from near 0 (0.0089 ± 0.0011 mg min -1  kg -1 ) to 1.91 ± 0.25 mg min -1  kg -1 . Hence, empagliflozin does not acutely modulate the baroreflex regulations of sympathetic nerve activity and arterial pressure in this rat model of chronic myocardial infarction., (© 2023. The Physiological Society of Japan.)

Aims: To quantify in vivo the effects of the soluble guanylate cyclase (sGC) stimulator, vericiguat, on autonomic cardiovascular regulation in comparison with the nitric oxide (NO) donor, sodium nitroprusside., Methods: In anesthetized Wistar-Kyoto rats, baroreflex-mediated changes in sympathetic nerve activity (SNA), arterial pressure (AP), central venous pressure (CVP), and aortic flow (AoF) were examined before and during the intravenous continuous administration (10 μg·kg-1·min-1) of vericiguat or sodium nitroprusside (n = 8 each). Systemic vascular resistance (SVR) was calculated as SVR = (AP-CVP) / AoF., Results: Neither vericiguat nor sodium nitroprusside affected fitted parameters of the baroreflex-mediated SNA response. Both vericiguat and sodium nitroprusside decreased the AP mainly through their peripheral effects. Vericiguat halved the slope of the SNA-SVR relationship from 0.012 ± 0.002 to 0.006 ± 0.002 mmHg·min·mL-1·%-1 (P = 0.008), whereas sodium nitroprusside caused a near parallel downward shift in the SNA-SVR relationship with a reduction of the SVR intercept from 1.235 ± 0.187 to 0.851 ± 0.123 mmHg·min/mL (P = 0.008)., Conclusion: Neither vericiguat nor sodium nitroprusside significantly affected the baroreflex-mediated SNA response. The vasodilative effect of vericiguat became greater toward high levels of SNA and AP, possibly reflecting the increased sGC sensitivity to endogenous NO. By contrast, the effect of sodium nitroprusside was more uniform over the range of SNA. These results help better understand cardiovascular effects of vericiguat., Competing Interests: The authors declare no conflict of interest regarding this study., (Copyright: © 2023 Yokoi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adaptation of the right ventricle (RV) to a progressively increasing afterload is one of the hallmarks of pulmonary arterial hypertension (PAH). Pressure-volume loop analysis provides measures of load-independent RV contractility, i.e., end-systolic elastance, and pulmonary vascular properties, i.e., effective arterial elastance (E a ). However, PAH-induced RV overload potentially results in tricuspid regurgitation (TR). TR makes RV eject to both PA and right atrium; thereby, a ratio of RV end-systolic pressure (P es ) to RV stroke volume (SV) could not correctly define E a . To overcome this limitation, we introduced a two-parallel compliance model, i.e., E a = 1/(1/E pa + 1/E TR ), while effective pulmonary arterial elastance (E pa = P es /PASV) represents pulmonary vascular properties and effective tricuspid regurgitant elastance (E TR ) represents TR. We conducted animal experiments to validate this framework. First, we performed SV analysis with a pressure-volume catheter in the RV and a flow probe at the aorta in rats with and without pressure-overloaded RV to determine the effect of inferior vena cava (IVC) occlusion on TR. A discordance between the two techniques was found in rats with pressure-overloaded RV, not in sham. This discordance diminished after IVC occlusion, suggesting that TR in pressure-overloaded RV was diminished by IVC occlusion. Next, we performed pressure-volume loop analysis in rats with pressure-overloaded RVs, calibrating RV volume by cardiac magnetic resonance. We found that IVC occlusion increased E a , suggesting that a reduction of TR increased E a . Using the proposed framework, E pa was indistinguishable to E a post-IVC occlusion. We conclude that the proposed framework helps better understanding of the pathophysiology of PAH and associated right heart failure. NEW & NOTEWORTHY This study reveals the impact of tricuspid regurgitation on pressure-volume loop analysis in right ventricle pressure overload. By introducing a novel concept of parallel compliances in the pressure-volume loop analysis, a better description is provided for the right ventricular forward afterload in the presence of tricuspid regurgitation.