Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

BACKGROUND: Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass. METHODS AND RESULTS: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). CONCLUSIONS: Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

Safety and Effectiveness of Acceleration Training as Cardiac Rehabilitation Immediately After Open Heart Surgery　- A Pilot Study.

BACKGROUND: We examined the safety and efficacy of acceleration training (AT) in patients immediately after cardiac surgery. METHODS AND RESULTS: This randomized controlled study included patients who underwent open-heart surgery using cardiopulmonary bypass. Of these patients, 31 received regular cardiac rehabilitation (CR) and 39 received AT in addition to regular CR (AT group). AT was provided using a vibration platform (Power Plate®Pro7TMand Power plate®personal; Performance Health System, Chicago, IL, USA). The AT group performed 5 static resistance training sessions: squats, wide stance squats, toe stands, banded squats, and front lunges. Each vibration session lasted 30 s. We evaluated the short physical performance battery, anterior mid-thigh thickness, maximum voluntary isometric contraction of the knee extensors, and serum intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) concentrations as indicators of endothelial function. The observation period was during hospitalization and lasted approximately 20 days. No adverse events occurred during AT. Ultrasound revealed a significantly lower reduction in muscle mass at discharge in the AT group. No significant differences were observed in ICAM-1 and VCAM-1 concentrations between the 2 groups preoperatively, postoperatively, or at discharge. CONCLUSIONS: AT is considered safe and effective for patients immediately after open-heart surgery. AT, along with regular CR, may prevent skeletal muscle mass loss, muscle weakness, and physical function loss immediately after open-heart surgery.

Impact of augmented renal clearance on anticoagulant therapy in critically ill patients with coronavirus disease 2019: A retrospective cohort study.

INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

Simulation to determine the approach of transcatheter aortic valve implantation in patients undergoing hemodialysis.

PURPOSE: The present study investigated potential access vessels in patients receiving hemodialysis who underwent surgical aortic valve replacement and determined which approaches were most suitable for performing transcatheter aortic valve implantation. METHODS: Consecutive patients undergoing hemodialysis with aortic valve stenosis who underwent surgical aortic valve replacement were included. Preoperative computed tomography data were analyzed to assess the vessel diameter and calcification. Simulations were conducted to determine the feasibility of inserting the 14-F eSheath of Sapien 3 via transfemoral, trans-cervical, trans-subclavian, and direct aorta approaches. RESULTS: A total of 72 patients were included in this study. The access route was characterized by severe calcification of the common iliac artery. The transfemoral approach was feasible in 77.8% of the cases, but the rate decreased to 33% when the calculations were based on the maximum sheath extension diameter. The trans-cervical, trans-subclavian, and direct aortic approaches were suitable for many patients. Lower extremity artery disease was identified as a risk factor for the unsuitability of the transfemoral approach. CONCLUSIONS: Common iliac artery calcification in patients undergoing hemodialysis restricts the use of the transfemoral approach. Therefore, some patients require alternative approaches.

Decreased neutrophil counts prolong inflammation in acute pancreatitis and cause inflammation spillover to distant organs.

BACKGROUND/OBJECTIVE: Acute pancreatitis is an aseptic inflammation caused by pathologically activated pancreatic enzymes and inflammatory mediators produced secondarily by neutrophils and other inflammatory cells and is one of the most difficult diseases to treat. This study aimed to investigate the role of neutrophils in pancreatitis by examining tissue dynamics. METHODS: We created a model of caerulein-induced pancreatitis in 12-week-old male granulocyte colony-stimulating factor knockout mice (G-CSF-KO) and wild-type littermate control mice (six intraperitoneal injections of caerulein [80 µg/kg body weight] at hourly intervals for 2 days). Mice were sacrificed 0, 3, 6, 12, 24, 36, 48, 72, and 168 h after caerulein administration and examined histologically. RESULTS: The survival rate after one week of caerulein administration was 100 % in the control mice, whereas it was significantly lower (10 %) in the G-CSF-KO mice. Histological examination revealed significant hemorrhage and inflammatory cell migration in the G-CSF-KO mice, indicating prolonged inflammation. CONCLUSION: Prolonged inflammation was observed in the G-CSF-KO mice. Tissue cleanup by neutrophils during the acute phase of inflammation may influence healing through the chronic phase.

Delayed diagnosis of Lemierre's syndrome in a patient with severe coronavirus disease 2019: importance of comprehensive oral and neck examination - a case report.

BACKGROUND: Given the widespread prevalence of the coronavirus disease 2019 (COVID-19), oral and neck examinations tend to be avoided in patients with suspected or confirmed COVID-19. This might delay the diagnosis of conditions such as Lemierre's syndrome, which involves symptoms resembling COVID-19-related throat manifestations. CASE PRESENTATION: A 24-year-old man without any underlying conditions was diagnosed with COVID-19 7 days before presentation. He was admitted to another hospital 1 day before presentation with severe COVID-19 and suspected bacterial pneumonia; accordingly, he was started on treatment with remdesivir and meropenem. Owing to bacteremic complications, the patient was transferred to our hospital for intensive care. On the sixth day, the patient experienced hemoptysis; further, a computed tomography (CT) scan revealed new pulmonary artery pseudoaneurysms. Successful embolization was performed to achieve hemostasis. In blood cultures conducted at the previous hospital, Fusobacterium nucleatum was isolated, suggesting a cervical origin of the infection. A neck CT scan confirmed a peritonsillar abscess and left internal jugular vein thrombus; accordingly, he was diagnosed with Lemierre's syndrome. The treatment was switched to ampicillin/sulbactam, based on the drug susceptibility results. After 6 weeks of treatment, the patient completely recovered without complications. CONCLUSION: This case highlights the significance of thorough oral and neck examinations in patients with suspected or diagnosed COVID-19 for the detection of throat and neck symptoms caused by other conditions.

A protocol-based treatment for ruptured abdominal aortic aneurysm contributed to improving aorta-related mortality: a retrospective cohort study.

BACKGROUND: Recent guidelines state that improving the survival rate of patients with ruptured abdominal aortic aneurysm (rAAA) requires a protocol or algorithm for the emergency management of these patients. We aimed to investigate whether introducing a protocol treatment for rAAA improves clinical outcomes compared with the pre-protocol strategy. METHODS: At our institution, 92 patients treated for rAAA between June 2008 and August 2022 were retrospectively analyzed. In 2014, the protocol-based treatment was introduced comprising a transfer algorithm to shorten the time to proximal control, use of an endovascular occlusion balloon, strict indications for endovascular aortic aneurysm repair (EVAR) or open surgical repair, and perioperative care, including for abdominal compartment syndrome (ACS). Clinical outcomes were compared between the protocol and pre-protocol group, including operative status, all-cause mortality, and rAAA-related death at 30-day, in-hospital, and 1-year postoperative follow-ups. RESULTS: Overall, 52 and 40 patients received the protocol-based and pre-protocol treatments, respectively. EVAR was more frequently performed in the protocol group. The rate of achieving time to proximal control was significantly faster, and the transfusion volume was lower in the protocol group. ACS occurred more frequently in the protocol group with a higher EVAR. No difference was found in all-cause mortality between the two groups. The protocol group exhibited fewer rAAA-related deaths than the pre-protocol group during the following time points: 30 days (9.6% vs. 22.5%), during the hospital stay (11.5% vs. 30.0%), and 1 year (14.5% vs. 31.5%). CONCLUSIONS: The protocol-based treatment improved the survival rate of patients with rAAA.

Comparison of hemodynamics and root configurations between remodeling and reimplantation methods for valve-sparing aortic root replacement: a pulsatile flow study.

PURPOSE: To compare the characteristics of reimplantation (RI) using grafts with sinuses and remodeling (RM) with/without external suture annuloplasty using a pulsatile flow simulator. METHODS: Porcine aortic roots were obtained from an abattoir, and six models of RM and RI with sinuses were prepared. External suture annuloplasty (ESA) was performed in the RM models to decrease the root diameter to 22 mm (RM-AP22) and 18 mm (RM-AP18). Valve models were tested at mean pulsatile flow and aortic pressure of 5.0 L/min and 120/80 (100) mmHg, respectively, at 70 beats/min. The forward flow, regurgitation, leakage, backflow rates, valve-closing time, and mean and peak pressure gradient (p-PG) were evaluated. Root configurations were examined using micro-computed tomography (micro-CT). RESULTS: The backflow rate was larger in the RM models than in the RI models (RI: 8.56% ± 0.38% vs. RM: 12.64% ± 0.79%; p < 0.01). The RM-AP and RI models were comparable in terms of the forward flow, regurgitation, backflow rates, p-PG, and valve-closing time. The analysis using a micro-CT showed a larger dilatation of the sinus of the Valsalva in the RM groups than in the RI group (Valsalva: RI, 26.55 ± 0.40 mm vs. RM-AP22, 31.22 ± 0.55 mm [p < 0.05]; RM-AP18, 31.05 ± 0.85 mm [p < 0.05]). CONCLUSIONS: RM with ESA and RI with neo-sinuses showed comparable hemodynamics. ESA to RM reduced regurgitation.

Recombinant Antithrombin Attenuates Acute Respiratory Distress Syndrome in Experimental Endotoxemia.

Sepsis-induced endothelial acute respiratory distress syndrome is related to microvascular endothelial dysfunction caused by endothelial glycocalyx disruption. Recently, recombinant antithrombin (rAT) was reported to protect the endothelial glycocalyx from septic vasculitis; however, the underlying mechanism remains unknown. Here, we investigated the effect of rAT administration on vascular endothelial injury under endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 10-week-old male C57BL/6 mice, and saline or rAT was administered intraperitoneally at 3 and 24 hours after LPS administration. Subsequently, serum and/or pulmonary tissues were examined for inflammation and cell proliferation and differentiation by histologic, ultrastructural, and microarray analyses. The survival rate was significantly higher in rAT-treated mice than in control mice 48 hours after LPS injection (75% versus 20%; P < 0.05). Serum interleukin-1ß was increased but to a lesser extent in response to LPS injection in rAT-treated mice than in control mice. Lectin staining and ultrastructural studies showed a notable attenuation of injury to the endothelial glycocalyx after rAT treatment. Microarray analysis further showed an up-regulation of gene sets corresponding to DNA repair, such as genes involved in DNA helicase activity, regulation of telomere maintenance, DNA-dependent ATPase activity, and ciliary plasm, after rAT treatment. Thus, rAT treatment may promote DNA repair, attenuate inflammation, and promote ciliogenesis, thereby attenuating the acute respiratory distress syndrome caused by endothelial injury.

A modified surgical technique for the Jarvik 2000 using a postauricular approach.

The Jarvik 2000, with a postauricular cable, is a left ventricular assistance device with a driveline that is passed to the postauricular region subcutaneously. A titanium pedestal base that holds a 3-pin connector is fixed to the parietal bone, posterior to the auricle. Essentially, the device is fixed in the same position as a cochlear implant; however, the disadvantages include continuous mechanical stress on the cable by neck rotations, and the visibility of the apparatus. To improve such concerns, we adjusted the location of the pedestal of the lower parietal bone to just above the transverse sinus and closer to the mastoid process. To reach this point, the internal cable was passed through the retromastoid pathway commonly used in ventriculoperitoneal shunting. The thickness of the skull at this location is sufficient for safe fixation; however, preoperative evaluation by a neurosurgeon using CT is necessary.

[Right Coronary Ostial Aneurysm after Modified Bentall Procedure with Carrel Patch Technique in a Patient with Marfan Syndrome:Report of a Case].

A 58-year-old man with Marfan syndrome visited our clinic for a routine examination. He had undergone a modified Bentall procedure with Carrel patch technique for annuloaortic ectasia 15 years previously. Computed tomography revealed an aneurysm of 43×57 mm in diameter at the right coronary ostium. He underwent resection of the aneurysm and coronary reconstruction using Piehler technique. He was discharged on the 37th postoperative day when his renal function recovered. Although the modified Bentall procedure may improve the surgical outcome, long-term follow-up is important because of various postoperative anastomotic complications in patients with Marfan syndrome.

Surgical Results for Infective Endocarditis Complicated With Cardiogenic Shock.

BACKGROUND: Infective endocarditis remains associated with substantial mortality and morbidity rates, and the presence of acute heart failure (AHF) compromises clinical results after valve surgery; however, little is known in cardiogenic shock (CGS) patients. This study evaluated the clinical results and risk of mortality in CGS patients after valve surgery.Methods and Results:This study enrolled 585 patients who underwent valve surgery for active endocarditis at 14 institutions between 2009 and 2017. Of these patients, 69 (12%) were in CGS, which was defined as systolic blood pressure <80 mmHg and severe pulmonary congestion, requiring mechanical ventilation and/or mechanical circulatory support, preoperatively. The predictors of CGS were analyzed, and clinical results of patients with non-CGS AHF (n=215) were evaluated and compared.Staphylococcus aureusinfection (odds ratio [OR] 2.19; P=0.044), double valve involvement (OR 3.37; P=0.003), and larger vegetation (OR 1.05; P=0.036) were risk factors for CGS. Hospital mortality occurred in 27 (13%) non-CGS AHF patients and in 15 (22%) CGS patients (P=0.079). Overall survival at 1 and 5 years in CGS patients was 76% and 69%, respectively, and there were no significant differences in overall survival compared with non-CGS AHF patients (P=1.000). CONCLUSIONS: Clinical results after valve surgery in CGS patients remain challenging; however, mid-term results were equivalent to those of non-CGS AHF patients.

Clinically feasible method for assessing leukocyte rheology in whole blood.

This study reports a novel method for assessment of leukocyte rheological activation with a new designed microchannel array chip to mimic the human microvascular network for microchannel array flow analysis (MCFAN). Study subjects were 79 healthy volunteers and 42 patients with type 2 diabetes mellitus (DM) and 36 patients with acute coronary syndrome (ACS). Using the anticoagulants heparin and ethylene-diamine-tetraacetic acid (EDTA)-2Na which inhibits platelets and leukocytes by chelating Ca2+, we were able to quantify leukocyte rheological activation by the subtraction of passage time of blood treated with both heparin and EDTA-2Na from that of blood treated with heparin only. We confirmed that passage times of whole blood with heparin + EDTA-2Na were always shorter than those of whole blood with only heparin in healthy subjects and patients with DM or ACS under suction pressures of - 30 cmH2O. There was a significant correlation between delta whole blood passage time {(heparin tube) - (EDTA-2Na + heparin)} and serum levels of myeloperoxidase and adhesive leukocyte number, respectively, even in blood from patients with DM or ACS, who suffered from inflammation. In conclusion we have developed a clinically feasible method for assessing leukocyte rheological activation in whole blood in ex vivo.

Sarcopenia assessed by the quantity and quality of skeletal muscle is a prognostic factor for patients undergoing cardiac surgery.

PURPOSE: Sarcopenia was assessed as a prognostic factor for patients undergoing cardiac surgery by evaluating the quantity and quality of skeletal muscle. METHODS: Sarcopenia was assessed by perioperative abdominal computed tomography using the total psoas muscle index (TPI) and intra-muscular adipose tissue content (IMAC). Patients were classified into high- (HT, n = 143) and low- (LT, n = 63) TPI groups and low- (LI, n = 122) and high- (HI, n = 84) IMAC groups. RESULTS: There were significantly more complications in the LT and HI groups than in the HT and LI groups. (HT 15.4% vs. LT 30.2%, P = 0.014) (LI 11.5% vs. HI 31.1%, P < 0.001). There were more respiratory complications in the LT group (HT 0% vs. LT 6.3%, P = 0.002) and more surgical site infections in the HI group than in the LI group (LI 0.8% vs. HI 7.1%, P = 0.014). A multivariable analysis showed that low TPI and high IMAC significantly predicted more major complications than other combinations (odds ratio [OR] 2.375; 95% confidence interval [CI] 1.152-5.783; P = 0.036, OR 3.973; 95% CI 1.737-9.088; P = 0.001). CONCLUSIONS: Sarcopenia is a risk factor for complications. The quantity and quality of muscle must be assessed to predict operative outcomes. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000027077.

Lung-diffusing capacity for carbon monoxide predicts early complications after cardiac surgery.

PURPOSE: Preoperative pulmonary dysfunction has been associated with increased operative mortality and morbidity after cardiac surgery. This study aimed to determine whether values for the diffusing capacity of the lung for carbon monoxide (DLCO) could predict postoperative complications after cardiac surgery. METHODS: This study included 408 consecutive patients who underwent cardiac surgery between June 2008 and December 2015. DLCO was routinely determined in all patients. A reduced DLCO was clinically defined as %DLCO < 70%. %DLCO was calculated as DLCO divided by the predicted DLCO. The association between %DLCO and in-hospital mortality was assessed, and independent predictors of complications were identified by a logistic regression analysis. RESULTS: Among the 408 patients, 338 and 70 had %DLCO values of ≥ 70% and < 70%, respectively. Complications were associated with in-hospital mortality (P < 0.001), but not %DLCO (P = 0.275). A multivariate logistic regression analysis with propensity score matching identified reduced DLCO as an independent predictor of complications (OR, 3.270; 95%CI, 1.356-7.882; P = 0.008). CONCLUSIONS: %DLCO is a powerful predictor of postoperative complications. The preoperative DLCO values might provide information that can be used to accurately predict the prognosis after cardiac surgery. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000029985.

[Median Sternotomy( Re-do and Closure)].

Median sternotomy is a basic procedure in the cardiovascular surgery. Minimally invasive surgery (MICS) develops and becomes able to accomplish various operation on the cardiovascular surgery, but it cannot carry out all maneuvers. Medline incision is inferior at beauty and infection control than MICS. But medianstenotomy is still used widely. It's provided good field of vision and the incision method that evade the complexity of the operation. It is vital to carry it out surely and carefully so that there are not later complications by mediansternotomy. It is necessary to be careful about the right ventricle injury the case of the redo-sternotomy.

Effect of the Initial Strategy for Active Endocarditis Complicated With Acute Heart Failure.

BACKGROUND: Early surgery for infective endocarditis (IE) with acute heart failure (AHF) is recommended, despite clinical results being unclear. We investigated the effect of initial treatment in such patients. Methods and Results: Outcomes for 470 patients with active IE who underwent valvular surgery during 2009-2016 were reviewed. Of them, 177 had symptomatic AHF when diagnosed with IE (excluding those with cardiogenic shock or intubated for AHF). They were divided into 2 groups based on initial treatment: Group S (underwent valvular surgery immediately; n=74) and Group M (received initial medical treatment for infection and HF; n=103). The median (interquartile range) waiting period from diagnosis to surgery in Groups S and M was 1 (1-3) and 15 (8-33) days, respectively (P<0.001). The 5-year survival rate was higher in Group S than Group M (80% vs. 64%; P=0.108). Group M was divided into Group P (initial medical treatment was effective and elective surgery was performed; n=62) and Group E (emergency surgery was necessary during medical treatment; n=41); overall 5-year survival was significantly worse in Group E than Group P (42% vs. 79%; P<0.012). In Group M, multivariate analysis indicated that Staphylococcus aureus infection (odds ratio 3.82; 95% confidence interval 1.19-13.3; P=0.024) was a significant risk factor for conversion to emergency surgery. CONCLUSIONS: Considering poor outcomes of emergency surgery for medically refractory HF, early surgery may be a reasonable option for IE patients, especially those with S. aureus infection.

The uricosuric effects of dihydropyridine calcium channel blockers in vivo using urate under-excretion animal models.

The purpose of this study was to create novel urate under-excretion animal models using pyrazinamide and to evaluate whether dihydropyridine calcium channel blockers (CCBs) have uricosuric effects in vivo. Adult male ICR mice were treated with pyrazinamide, vehicle (dimethyl sulfoxide: DMSO), or tap water. Thirty minutes later, pyrazinamide-treated mice were given benzbromarone, losartan, nilvadipine, nitrendipine, nifedipine or azelnidipine. Six hours after the second administration, urine (by urinary bladder puncture) and plasma were collected to measure uric acid and creatinine levels, and fractional excretion of uric acid (FEUA) and creatinine clearance (Ccr) were calculated and evaluated. There was no significant difference in the levels of plasma uric acid, plasma creatinine, Ccr, urinary N-acetyl-ß-d-glucosaminidase (NAG) and urinary NAG-creatinine ratio between water, DMSO, and pyrazinamide-treated mice. But the FEUA of pyrazinamide-treated mice was significantly lower than water mice. The FEUA was significantly higher in mice taking the dihydropyridine CCBs (nilvadipine, nitrendipine, nifedipine, and high-dose azelnidipine) than in pyrazinamide-treated mice. There was no significant difference in Ccr. Thus, a novel animal model created with PZA administration was useful as a urate under-excretion animal model that was probably URAT1-mediated, and the uricosuric effects of dihydropyridine CCBs were confirmed in vivo.

[Structural Deterioration of a Bovine Pericardial Valve in a Tricuspid Position 14 Years Postoperatively;Report of a Case].

Although nonstructural dysfunction of a bioprosthesis caused by pannus formation or native valve attachment has been well described, structural valve deterioration( SVD) caused by calcification or tear of a bioprosthesis, especially a bovine pericardial valve, is very rare in the tricuspid position. We report a case of redo tricuspid valve surgery for SVD 14 years after tricuspid valve replacement( TVR) using a Carpentier-Edwards Perimount (CEP) pericardial valve. A 71-year-old woman was referred to our hospital because of exertional dyspnea and pre-syncope. She had undergone mitral valve replacement with a St. Jude Medical mechanical valve and TVR with a CEP pericardial valve 14 years previously. Transthoracic echocardiography revealed tricuspid valve stenosis with a mean trans-tricuspid valve pressure gradient (TVPG) of 7.3 mmHg. Redo TVR using a CEP Magna Mitral Ease valve was performed under cardiac arrest. Severe calcification was observed on the ventricular side of the leaflets of the explanted valve. The mean TVPG decreased to 3.2 mmHg after surgery, and the patient's postoperative course was uneventful.