Acute Dapagliflozin Administration Ameliorates Cardiac Surgery-Associated Acute Kidney Injury in a Rabbit Model.

BACKGROUND: Several studies have shown that sodium-glucose cotransporter-2 inhibitors have a renoprotective effect on acute kidney injury (AKI), but their effect on cardiac surgery-associated AKI is unknown.Methods and Results: AKI was induced in 25 rabbits without diabetes mellitus by cardiopulmonary bypass (CPB) for 2 h and they were divided into 5 groups: sham; dapagliflozin-treated sham; CPB; dapagliflozin-treated CPB; and furosemide-treated CPB (n=5 in each group). Dapagliflozin was administered via the femoral vein before initiating CPB. Kidney tissue and urine and blood samples were collected after the surgical procedure. There were no differences in the hemodynamic variables of each group. Dapagliflozin reduced serum creatinine and blood urea nitrogen concentrations, and increased overall urine output (all P<0.05). Hematoxylin and eosin staining showed that the tubular injury score was improved after dapagliflozin administration (P<0.01). Dapagliflozin administration mitigated reactive oxygen species and kidney injury molecule-1 as assessed by immunohistochemistry (both P<0.0001). Protein expression analysis showed improvement of inflammatory cytokines and apoptosis, and antioxidant enzyme expression was elevated (all P<0.05) through activation of the nuclear factor erythroid 2-related factor 2 pathway (P<0.01) by dapagliflozin. CONCLUSIONS: Acute intravenous administration of dapagliflozin protects against CPB-induced AKI. Dapagliflozin may have direct renoprotective effects in renal tubular cells.

Cannula to Femoral Artery Diameter Ratio Predicts Potential Lower-Limb Ischemia in Minimally Invasive Cardiac Surgery With Femoral Cannulation.

OBJECTIVE: Lower-limb ischemia is a complication of minimally invasive cardiac surgery with femoral cannulation. Herein, we verified our strategy using distal perfusion cannulation (DPC) against this complication. METHODS: We retrospectively assessed 91 cases of aortic valve replacement with femoral cannulation between January 2019 and March 2023. DPC was applied when lower-limb tissue oxygenation index declined by ≥20%. The cannula to femoral artery diameter ratio (C/FA) was calculated by dividing the cannula size (Fr) divided by 3 by the femoral artery inner diameter (mm). Postoperative maximum creatinine kinase (CKmax), lactate dehydrogenase (LDHmax), and lactate levels were analyzed, and univariable logistic regression and receiver operating characteristic curve analyses were employed to determine DPC predictors and the cutoff C/FA for DPC, respectively. Patients without DPC were divided into 2 subgroups based on the cutoff C/FA for further comparisons. RESULTS: DPC was required in 9 patients. Symptomatic ischemia was not observed. All laboratory data were similar in the DPC and non-DPC groups. C/FA was significantly associated with DPC (odds ratio = 1.27, 95% confidence interval: 1.09 to 1.47, P = 0.002), and the cutoff C/FA was 0.70 (sensitivity = 0.89, specificity = 0.80). In the non-DPC group, CKmax (P = 0.027) and LDHmax (P = 0.041) were significantly higher in patients with C/FA ≥0.7 (n = 16) than in those with C/FA <0.7 (n = 66). CONCLUSIONS: Our strategy for preventing symptomatic ischemia is reasonable and could be almost achieved without DPC when C/FA is <0.7. C/FA also predicts asymptomatic potential ischemia, and proactive DPC is preferable when C/FA is ≥0.7.

Efficacy of Sac Coil Embolization in Endovascular Aortic Repair for Sac Shrinkage in Patients at a High Risk of Type II Endoleak from Lumbar Arteries.

BACKGROUND: In endovascular aortic repair (EVAR), preemptive embolization of sac branch vessels is effective in preventing postoperative type II endoleak (T2EL). However, this technique has not been widely adopted especially for lumbar arteries (LAs) because of technical difficulties and time constraints. This study aimed to investigate the efficacy of nonselective sac coil embolization, which is a simpler surgical method, in postoperative sac shrinkage for patients at a high risk of T2EL from LAs. METHODS: We retrospectively assessed 76 patients who underwent elective EVAR for abdominal aortic aneurysm with 4 or more patent LAs or at least 1 patent LA of ≥2 mm at our hospital between January 2014 and December 2022. The patients who underwent sac coil embolization were included in Group Ⅰ (n = 20), and the others were divided into 2 groups: those with an inferior mesenteric artery that was originally occluded or embolized by coils or stent graft bodies (Group Ⅱ, n = 21), and those without that (Group Ⅲ, n = 35). In Group Ⅰ, 0.035-inch coils were inserted into the sac after complete stent graft deployment. The cumulative incidence of sac shrinkage (≥5 mm) was compared between the groups. Further, univariable and multivariable Cox regression analyses were used to determine the predictors of sac shrinkage. RESULTS: Sac shrinkage (≥5 mm) was observed more frequently in Group Ⅰ (50%) than in Group Ⅱ (19%) and Group Ⅲ (17%) (P = 0.052 and 0.043, respectively). The cumulative incidence of sac shrinkage was significantly higher in Group Ⅰ than in Group Ⅱ (log-rank P = 0.039) and Group Ⅲ (log-rank P = 0.024). Multivariable Cox regression analyses revealed that sac embolization was a significant predictor of sac shrinkage (hazard ratio, 4.23; 95% confidence interval, 1.66-10.8; P = 0.003). CONCLUSIONS: Nonselective sac coil embolization in EVAR is potentially effective for sac shrinkage in the early postoperative phase in patients at high risk of T2EL from LAs. This simple procedure may improve prognosis after EVAR.

Necrostatin-1 Attenuates Delayed Paraplegia after Transient Spinal Cord Ischemia in Rabbits by Inhibiting the Upregulation of Receptor-Interacting Protein Kinase 1 and 3.

BACKGROUND: Delayed-onset paraplegia is a disastrous complication after thoracoabdominal aortic open surgery and thoracic endovascular aortic repair. Studies have revealed that transient spinal cord ischemia caused by temporary occlusion of the aorta induces delayed motor neuron death owing to apoptosis and necroptosis. Recently, necrostatin-1 (Nec-1), a necroptosis inhibitor, has been reported to reduce cerebral and myocardial infarction in rats or pigs. In this study, we investigated the efficacy of Nec-1 in delayed paraplegia after transient spinal cord ischemia in rabbits and assessed the expression of necroptosis- and apoptosis-related proteins in motor neurons. METHODS: This study used rabbit transient spinal cord ischemia models using a balloon catheter. They were divided into a vehicle-treated group (n = 24), Nec-1-treated group (n = 24), and sham-controls (n = 6). In the Nec-1-treated group, 1 mg/kg of Nec-1 was intravascularly administered immediately before ischemia induction. Neurological function was assessed using the modified Tarlov score, and the spinal cord was removed 8 hr and 1, 2, and 7 days after reperfusion. Morphological changes were examined using hematoxylin and eosin staining. The expression levels of necroptosis-related proteins (receptor-interacting protein kinase [RIP] 1 and 3) and apoptosis-related proteins (Bax and caspase-8) were assessed using western blotting and histochemical analysis. We also performed double-fluorescence immunohistochemical studies of RIP1, RIP3, Bax, and caspase-8. RESULTS: Neurological function significantly improved in the Nec-1-treated group compared with that in the vehicle-treated group 7 days after reperfusion (median 3 and 0, P = 0.025). Motor neurons observed 7 days after reperfusion were significantly decreased in both groups compared with the sham group (vehicle-treated, P < 0.001; Nec-1-treated, P < 0.001). However, significantly more motor neurons survived in the Nec-1-treated group than in the vehicle-treated group (P < 0.001). Western blot analysis revealed RIP1, RIP3, Bax, and caspase-8 upregulation 8 hr after reperfusion in the vehicle-treated group (RIP1, P = 0.001; RIP3, P = 0.045; Bax, P = 0.042; caspase-8, P = 0.047). In the Nec-1-treated group, the upregulation of RIP1 and RIP3 was not observed at any time point, whereas that of Bax and caspase-8 was observed 8 hr after reperfusion (Bax, P = 0.029; caspase-8, P = 0.021). Immunohistochemical study revealed the immunoreactivity of these proteins in motor neurons. Double-fluorescence immunohistochemistry revealed the induction of RIP1 and RIP3, and that of Bax and caspase-8, in the same motor neurons. CONCLUSIONS: These data suggest that Nec-1 reduces delayed motor neuron death and attenuates delayed paraplegia after transient spinal cord ischemia in rabbits by selectively inhibiting necroptosis of motor neurons with minimal effect on their apoptosis.

Ascending aortic extension to enlarge the retroaortic space in children after the Norwood procedure.

Left pulmonary artery stenosis is a well-recognized complication following the Norwood procedure. We herein report two cases in which ascending aortic extension was performed to enlarge the retroaortic space in children with left pulmonary artery stenosis after the Norwood procedure. We used graft interposition in the ascending aorta to increase the retroaortic apace and concomitantly performed extended left pulmonary artery reconstruction. This procedure obtains a more balanced distribution of the pulmonary blood flow, which is crucial to achieve good Fontan circulation.

A staged surgical strategy for cardiogenic shock and iatrogenic ventricular septal perforation due to a malpositioned catheter.

A 59-year-old woman fell into cardiogenic shock due to acute myocardial infarction with total occlusion of the left anterior descending artery. Although intra-aortic balloon pump was inserted and a coronary stent was placed, she went into cardiopulmonary arrest and percutaneous veno-arterial extracorporeal membrane oxygenation (ECMO) was initiated. She was transferred to our hospital after drainage for pericardial effusion. Computed tomography revealed the drainage catheter lying through the right ventricular free wall and the ventricular septum, and leading into the left ventricle. She showed multiple organ failure and disseminated intravascular coagulation syndrome due to insufficient ECMO flow. Conversion to central ECMO after catheter removal was performed and her general condition improved; however, ventricular septal shunt remained. Repair of the perforation and ECMO removal was performed 15 days after the first operation. The combination of optimal mechanical circulatory support and the staged surgical repair contributed to her dramatic recovery.

Atypical Hemolytic Uremic Syndrome following Acute Type A Aortic Dissection.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)-related disease that manifests as a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused by uncontrolled activation of the complement system. We report the case of a 61-year-old woman with acute type A aortic dissection that subsequently developed into aHUS. The hematologic disorders underlying aHUS improved after treatment with the complement inhibitor eculizumab. It is important to consider aHUS when a patient clinically develops a triad of microangiopathic hemolytic anemia, thrombocytopenia, and an increasing creatinine level following cardiovascular surgery.

Pectoral Muscle Atrophy After Axillary Artery Cannulation for Aortic Arch Surgery.

To investigate postoperative pectoral atrophy in 141 patients undergoing aortic arch surgery involving bilateral axillary artery cannulations with side grafts. The depth from the skin to the axillary artery surrounding the thoracoacromial artery (zone 1), and the thicknesses of pectoralis major (zone 2) and pectoralis minor (zone 3) were measured by computed tomography before surgery, at 1 and 6 months after surgery, and at the most recent follow-up assessment (PostT2) (mean = 41 months, range 11-75 months). Based on the median value (47.4 mm) of zone 1, the preoperative pectoral thickness was categorized into 2 groups: pectoral thickness >47.4 mm (thick group) and ≤47.4 mm (thin group). Mean changes in the pectoral thickness from baseline were evaluated using the longitudinal mixed-effects model. Forty-three of 110 patients underwent total arch replacements and extra-anatomical bypasses for left subclavian artery anastomoses. In 3 patients, axillary artery grafts became infected. There was no obvious harm associated with muscle wasting. Mean changes from baseline in zones 1, 2, and 3 showed significant declines at PostT2 (-13.40 ± 9.73 mm [P < 0.0001], -7.00 ± 5.23 mm [P < 0.0001], and -7.23 ± 6.42 mm [P < 0.0001], respectively). In the thick group, the progression of pectoral atrophy in zones 1 and 3 was significantly more than that of the thin group (P < 0.0001 for both zones). Postoperative pectoral atrophy progressed rapidly. The preoperative pectoral size might be of no use in the prevention of pectoral atrophy. Further investigation to prevent the pectoral atrophy is needed.

Single-crystalline nanogap electrodes: enhancing the nanowire-breakdown process with a gaseous environment.

A method for fabricating single-crystalline nanogaps on Si substrates was developed. Polycrystalline Pt nanowires on Si substrates were broken down by current flow under various gaseous environments. The crystal structure of the nanogap electrode was evaluated using scanning electron microscopy and transmission electron microscopy. Nanogap electrodes sandwiched between Pt-large-crystal-grains were obtained by the breakdown of the wire in an O(2) or H(2) atmosphere. These nanogap electrodes show intense spots in the electron diffraction pattern. The diffraction pattern corresponds to Pt (111), indicating that single-crystal grains are grown by the electrical wire breakdown process in an O(2) or H(2) atmosphere. The Pt wires that have (111)-texture and coherent boundaries can be considered ideal as interconnectors for single molecular electronics. The simple method for fabrication of a single-crystalline nanogap is one of the first steps toward standard nanogap electrodes for single molecular instruments and opens the door to future research on physical phenomena in nanospaces.