Effect of esaxerenone on ischaemia and reperfusion injury in rat hearts.

OBJECTIVES: In myocardial infarction, the addition of mineralocorticoid receptor blockers to standard therapies, such as angiotensin-converting enzyme inhibitors or beta-blockers, reportedly reduces mortality and cardiac events. We investigated whether the non-steroidal mineralocorticoid receptor blocker esaxerenone has cardioprotective effects and its protective mechanisms. METHODS: Isolated rat hearts were Langendorff-perfused (constant pressure, 80 mmHg) with oxygenated Krebs-Henseleit bicarbonate buffer and reperfused for 60 min; afterwards, recovery of function (left ventricular pressure, measured with an intraventricular balloon) and myocardial injury were measured. In a preliminary study, we determined the optimal concentration of esaxerenone required for myocardial protection. Next, esaxerenone was administered in the pre- and post-ischaemic phases to determine the optimal timing of administration. In addition, we assessed coronary flow response to acetylcholine with and without esaxerenone. We examined whether esaxerenone-induced cardioprotection was prevented by targeting putative components in the preconditioning manner (the mitochondrial ATP-sensitive potassium [KATP] channel). RESULTS: Myocardial protection by esaxerenone was observed when esaxerenone was administered before ischaemia but not after ischaemia. The coronary flow response to acetylcholine was significantly better in the esaxerenone group than in the control group. The cardioprotective effect of esaxerenone was eliminated by the mitochondrial KATP channel blocker, 5-hydroxy decanoate. CONCLUSIONS: This study confirmed the myocardial protective effect of the pre-ischaemic administration of esaxerenone. Esaxerenone may contribute to coronary endothelial protection and exert pharmacological preconditioning via the mitochondrial KATP channel.

Successful surgical experience for acute severe aortic valve regurgitation with acquired Gerbode defect: A case report.

INTRODUCTION AND IMPORTANCE: The incidence of acquired Gerbode defect has been increasing due to advances in cardiac imaging technology, and some closure methods have been introduced. PRESENTATION OF CASE: A 58-year-old man developed cardiogenic shock due to acute severe aortic valve regurgitation with an acquired Gerbode defect caused by infective endocarditis. Emergency surgery was performed. A large patch with a 0.4 mm extended-polytetrafluoroethylene (e-PTFE) sheet covered with autologous pericardium was used to close the Gerbode defect, and a bioprosthetic valve was used for aortic valve replacement. CLINICAL DISCUSSION: Large patch closure with 0.4 mm e-PTFE sheet and autologous pericardium for fragile Gerbode defect caused by infective endocarditis might be effective with regard to sturdiness, good fitting to the tissue, and excellent resistance to bacteria. CONCLUSION: We encountered a rare case of cardiogenic shock due to acute severe aortic valve regurgitation and acquired Gerbode defect caused by infective endocarditis. In our case, large-patch closure for perforation in a fragile membranous septum was effective.

Cardioprotective effect of St. Thomas' Hospital No. 2 solution against age-related changes in aquaporin-7-deficient mice.

OBJECTIVE: This study aimed to investigate whether St. Thomas' Hospital No. 2 solution (STH2) is equally effective in both young and aged aquaporin-7-knockout (AQP7-KO) mice and the mechanisms by which the intra-myocardial adenosine triphosphate (ATP) content is altered during ischemia without aquaporin-7. METHODS: In study 1, isolated hearts of male wild-type (WT) and AQP7-KO mice (< 12 weeks old) were Langendorff perfused with 5-min STH2 prior to a 20-min global ischemia (GI) or 25-min GI without STH2. Similarly, in Study 2, hearts from WT and AQP7-KO mice (≥ 24 weeks old) were subjected to 2-min STH2 infusion prior to GI. In study 3, intra-myocardial ATP content was compared before (sham) and after (control or STH2) ischemia in mature WT and AQP7-KO mice. RESULTS: In study 1, troponin T levels (ng/g wet weight) of WT and AQP7-KO hearts were significantly lower in the STH2 groups (75.6 ± 45.9 and 80.2 ± 52.2, respectively) than in the GI groups (934.0 ± 341.1 and 1089.3 ± 182.5, respectively). In Study 2, troponin T levels in aged WT and AQP7-KO mice were 566.5 ± 550.0 and 547.8 ± 594.3, respectively (p = 0.9561). In Study 3, ATP levels (µmol/g protein) in the sham, control, and STH2 AQP7-KO mice groups were 4.45, 2.57, and 3.37, respectively(p = 0.0005). CONCLUSIONS: The present study revealed the cardio-protective efficacy of STH2 in an experimental model of isolated AQP7-KO young and aged murine hearts. Further, STH2 preserved intra-myocardial ATP during ischemia with Krebs-Henseleit buffer perfusion in the Langendorff setting.

Neuroprotection during Open Aortic Arch Surgery: Cerebral Perfusion Methods and Temperature.

Neuroprotection is important in open aortic arch surgery because of the dependence of brain tissues on cerebral perfusion. Therefore, several techniques have been developed to reduce cerebral ischemia and improve outcomes in open aortic arch surgery. In this review, I describe various neuroprotective strategies, such as profound and deep hypothermic circulatory arrest, selective antegrade cerebral perfusion, retrograde cerebral perfusion, and lower body circulatory arrest; compare their advantages and disadvantages, and discuss their evolution and current status by reviewing relevant literature.

Total endovascular repair for a persistent sciatic artery aneurysm with widespread limb-threatening arterial occlusion.

In the present report, we have described the case of a 79-year-old woman who presented with acute right lower limb ischemia and was diagnosed with bilateral persistent sciatic arteries and a right persistent sciatic artery aneurysm. Concomitant widespread thrombotic occlusion was present, extending from the orifice of the right internal and external iliac arteries to the below-the-knee popliteal artery. These complicated lesions were successfully treated using only percutaneous endovascular procedures, including stent-graft placement, bare metal stent implantation, and thrombolysis. Our report illustrates how a combination of techniques can achieve total endovascular repair of a persistent sciatic artery aneurysm accompanied by occlusion of the internal and external iliac arteries.

Preoperative Assessment of Pulmonary Function Tests and Outcomes After Cardiac Surgery.

BACKGROUND: To investigate the association between preoperative pulmonary function evaluations and surgical outcomes of patients with chronic lung disease following cardiac surgery. METHODS: This retrospective observational study evaluated 148 patients using preoperative pulmonary function tests before undergoing cardiac surgery. Patients were divided into 4 groups (normal, obstructive, restrictive, and combined disorder), based on the result of the pulmonary function tests. Additionally, we evaluated the percent predicted forced expiratory volume in 1 second. Finally, we investigated the mechanical ventilation duration, length of postoperative hospital stay, and the 30-day mortality rate between the groups in each study. RESULTS: The mechanical ventilation duration and length of postoperative hospital stay in the combined group was significantly longer than that in the other groups (P < .0001, P < .0001, respectively). Patients in the restrictive group had a significantly longer postoperative ventilation or hospitalization than those in the normal group (P = .0479, P = .0164, respectively). However, there were no significant differences in the 30-day mortality rates between the groups. There also was a significant negative correlation between the percent predicted forced expiratory volume in 1 second and mechanical ventilation (R2 = 0.052, P = .0054) and postoperative hospitalization (R2 = 0.042, P = .0122). CONCLUSION: Risk stratification by preoperative pulmonary function tests may be used to accurately identify the postoperative outcomes in chronic lung disease patients following cardiac surgery.

"Squid-Capture" Modified In Situ Stent-Graft Fenestration Technique for Recurrent Abdominal Aortic Occlusive Disease after Collapse of Balloon-Expandable Stent.

We present a case of an 85-year-old woman with bilateral limb-threatening ischemia caused by acute-on-chronic occlusion of the infrarenal aorta. The patient once underwent endovascular recanalization using nitinol and stainless-steel bare-metal stent implantation; however, the stainless-steel stent collapsed 3 months later. In the second endovascular therapy, "Squid-Capture" modified in situ stent-graft fenestration technique followed by stent-in-stent implantation with stent graft and bare-metal stent was successfully applied, and it can be regarded as a promising treatment option for the repair of abdominal aortic occlusive disease in some limited anatomical conditions.

Temporal Dispersion of Atrial Activation Causes Postoperative Atrial Fibrillation.

BACKGROUND: Spatial dispersion of atrial activation is a cause of postoperative atrial fibrillation (PoAF) after cardiac surgery. This study evaluated whether temporal dispersion of atrial activation causes PoAF after surgery in a clinical setting. METHODS: Nineteen patients were enrolled. Postoperative atrial activation was evaluated by 24-hour Holter electrocardiography, with atrial pacing wires on the right atrium, for 5 days after cardiac surgery. No patient received antiarrhythmic drugs, including beta-blockers. The cycle length of 15 continuous atrial beats was measured at 4 time points: (i) earlier than 12 hours before PoAF, as a control, (ii) just before PoAF onset, (iii) during PoAF, and (iv) just before cessation of PoAF. Inhomogeneity of atrial activation was quantified by using the variation coefficient for a cycle length of 15 atrial beats during each phase. RESULTS: The median inhomogeneity index of atrial activation (interquartile range) was 0.102 (0.046-0.136) in controls, 0.943 (0.582-1.610) just before PoAF onset (vs. control; p=0.009), 0.966 (0.631-1.117) during PoAF, and 0.471 (0.138-0.645) just before cessation of PoAF. CONCLUSIONS: Dispersion of atrial activation significantly increased just before PoAF onset. Temporal dispersion of atrial activation is a precursory variation of PoAF.

Perioperative urinary excretion of aquaporin-2 dependent upon vasopressin in cardiac surgery.

Aquaporin-2 is found in the apical cell membranes of the principal cells of the collecting duct of the kidney. Plasma arginine vasopressin has been reported to be markedly elevated during cardiac surgery. However fluctuations in urine aquaporin-2 levels have never been reported. We aimed to determine the responses of urine aquaporin-2 and evaluated the relationship between urine aquaporin-2 and plasma arginine vasopressin levels during perioperative periods in cardiac surgical patients. Eight patients undergoing elective isolated aortic valve replacement in normothermia were enrolled prospectively. Blood and urine samples were collected preoperatively and on postoperative days 1, 4, and 7. Patients received furosemide and spironolactone, as needed, during the clinical course; tolvaptan was not needed. Median plasma arginine vasopressin levels [with interquartile range] significantly increased to 1.5 [1.3-2.0], 15.3 [11.4-22.2]*, 2.2 [2.1-2.3], 1.7 [1.5-1.9] pg/mL preoperatively, on postoperative days 1, 4, and 7, respectively (*: p = 0.0001). Similarly, levels of urine aquaporin-2 markedly increased in 3.4 [1.9-5.6], 25.8 [18.4-33.5]**, 9.3 [5.9-14.0], 5.4 [5.3-6.1] (ng/mL), respectively (**p = 0.0004). A significant correlation between plasma arginine vasopressin and urine aquaporin-2 was observed during the entire investigation (R2 = 0.616, p < 0.0001). Plasma arginine vasopressin and urine aquaporin-2 levels were significantly elevated on postoperative day 1 in patients who underwent aortic valve replacement with cardiopulmonary bypass. A significant correlation between plasma arginine vasopressin and urine aquaporin-2 was observed. Urine aquaporin-2 should be further investigated as a potential biomarker for postoperative cardiac dysfunction.

Neutrophil Elastase Inhibitor Sivelestat Attenuates Myocardial Injury after Cardioplegic Arrest in Rat Hearts.

PURPOSE: Sivelestat, a neutrophil elastase inhibitor, attenuates global ischemia-induced myocardial damage and coronary endothelial dysfunction. Here, we investigated whether sivelestat exerts the cardioprotective effects against cardioplegic arrest in rat hearts. METHODS: Isolated Langendorff-perfused rat hearts were randomly allocated to three groups and subjected to 2-min infusions with St. Thomas' Hospital cardioplegic solution No. 2 (STH2) and 30-min global ischemia followed by 60-min reperfusion as follows: (i) control (STH2 treatment only), (ii) sivelestat (19 µmol/L) infusion for the first 10 min of reperfusion, and (iii) sivelestat (19 µmol/L) infusion for 10 min before ischemia and for the first 10 min of reperfusion. Left ventricular developed pressure (LVDP) recovery and troponin T leakage were measured at the end of reperfusion. Coronary flow response to acetylcholine (ACh) was assessed. RESULTS: Single and multiple doses of sivelestat significantly improved LVDP recovery (69 ± 15 and 69 ± 14 vs 48 ± 15 [control]; p <0.05) and decreased troponin T leakage (0.4 ± 0.3 and 0.7 ± 0.5 vs 1.7 ± 0.6 [control]; p <0.05). Multiple doses of sivelestat significantly improved coronary flow response to ACh (121 ± 9 vs 105 ± 4; p <0.05). CONCLUSIONS: Addition of sivelestat to STH2 attenuates myocardial injury after cardioplegic arrest in rat hearts. This cardioprotective effect was achieved even when sivelestat was administered during early reperfusion.

Negative-pressure sternal wound closure with interrupted subcuticular suturing and a subcutaneous drain tube reduces the incidence of poststernotomy wound infection after coronary artery bypass grafting surgery.

PURPOSES: To retrospectively evaluate the effect of negative-pressure sternal wound closure (NPSWC) with a subcutaneous closed drain tube on the sternal surgical site infection (SSI) incidence. METHODS: After propensity score matching of 231 patients undergoing coronary artery bypass grafting (CABG), we compared 104 pairs in the NPSWC and historical control groups. In the molecular analysis, the interleukin-6 (IL-6), basic fibroblast growth factor (b-FGF), and transforming growth factor ß1 (TGF-ß1) levels in the wound fluid were measured using two different reservoir types at postoperative days 2 and 7. RESULTS: NPSWC significantly reduced the SSI incidence from 10.6 to 2.9%. No mediastinitis occurred in the NPSWC group. A multivariate logistic regression analysis identified female sex (p = 0.0040) and no NPSWC (p = 0.0084) as significant risk factors for sternal SSI development. The Negative-pressure value was 49.4 ± 4.1 and 115.5 ± 15.2 mmHg in the standard-type (SSR) and bulb-type suction reservoirs (BSR), respectively. Given that growth factors were affected by the difference in negative pressure, the IL-6, b-FGF, and TGF-ß1 levels were significantly higher in the BSR than in the SSR. CONCLUSIONS: NPSWC using a subcutaneous closed drain tube was effective in preventing sternal SSI after CABG and may accelerate wound healing even when both internal thoracic arteries are harvested. CLINICAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trials Registry, registration number: UMIN000037060.

Cardioprotective effect of hyperkalemic cardioplegia in an aquaporin 7-deficient murine heart.

BACKGROUND: Hyperkalemic cardioplegia using St. Thomas' Hospital solution No. 2 (STH2) is commonly used to protect the myocardium during surgery. Mice deficient in the myocyte channel aquaporin 7 (AQP7) show significantly reduced glycerol and ATP contents and develop obesity; however, the influence of AQP7 on cardioplegia effectiveness remains unclear. METHODS: After determining the influence of ischemic duration on cardiac function, isolated hearts of male wild-type (WT) and AQP7-knockout (KO) mice (> 13 weeks old) were aerobically Langendorff-perfused with bicarbonate buffer, and randomly allocated to the control group (25 min of global ischemia) and STH2 group (5 min of STH2 infusion before 20 min of global ischemia, followed by 60 min of reperfusion). RESULTS: Final recovery of left ventricular developed pressure (LVDP) of WT and AQP7-KO hearts in the control group was 24.5 ± 12.4% and 20.6 ± 8.4%, respectively, which were significantly lower than those of the STH2 group (96.4 ± 12.7% and 92.9 ± 27.6%). Troponin T levels of WT and AQP-KO hearts significantly decreased in the STH2 groups (142.9 ± 27.2 and 219.9 ± 197.3) compared to those of the control (1725.0 ± 768.6 and 1710 ± 819.9). CONCLUSIONS: AQP7 was not involved in the protective efficacy of STH2 in this mouse model, suggesting its clinical utility even in complications of metabolic disease.

Three Year Follow-Up of a Vein Patch Repair for a Coronary Artery Saccular Aneurysm of the Left Main Bifurcation.

This report describes a case of surgical treatment for a coronary artery saccular aneurysm of the left main bifurcation. A coronary artery saccular aneurysm (7 mm × 10 mm) and three vessel disease, including the left main trunk, were diagnosed by coronary angiography. A surgical resection and saphenous vein patch repair of the left main coronary artery aneurysm was performed concomitantly with coronary artery bypass grafting. The pathological findings of the aneurysm clarified that the aneurysm wall was atrophic and extremely thin because of a collapsed trilaminar arterial structure due to atherosclerosis. A coronary computed tomographic scan revealed no aneurysmal formation in the patent left main trunk and patent grafts 3 years after surgery.

Thoracic aortic aneurysms in octogenarians: the results of open surgical repair using hypothermic circulatory arrest with antegrade selective cerebral perfusion.

OBJECTIVE: Although recent progress has expanded the indications for thoracic aortic surgery to include elderly patients, the procedure remains extremely invasive. We performed a chart review to determine the early and late outcomes of thoracic aortic surgery using hypothermic circulatory arrest (HCA) and antegrade selective cerebral perfusion (ASCP) in octogenarians. MATERIALS AND METHODS: Of 79 patients who underwent surgery for thoracic aortic aneurysms from April 2007 through December 2012, 8 patients 80 years or older were selected for analysis. Mean age at the time of surgery was 84.3±1.39 years. The diagnoses were aortic dissection in 5 patients and degenerative thoracic aneurysm in 3 patients. All patients underwent surgery with HCA. The lowest body temperature was 25℃ ASCP was used as an additional brain-protection technique. Emergency operations were performed in 5 patients (62.5%). RESULTS: The mean duration of HCA was 60.4±19.7 minutes, that of aortic cross-clamping time was 143.0±30.4 minutes, and mean pump time was 207.8±44.4 minutes. The hospital mortality rate was 0%. Major postoperative complications occurred in 3 (37.5%) patients: stroke, temporary neurologic dysfunction, and paraparesis in 1 patient each. No patients required temporary dialysis for new-onset renal dysfunction. There were no deaths during the 65-month follow-up period. CONCLUSION: The early and late outcomes after thoracic aortic surgery at our hospital using HCA with ASCP in octogenarians are acceptable. The operations are performed with an acceptable operative risk, even under emergency situations, including acute aortic dissection.

Video-assisted thoracoscopic thymectomy (VAT-T) with lateral thoracotomy for stage II and III thymoma.

Thymoma has malignant potential and is the most common anterior mediastinal tumor. Video-assisted thoracic surgery (VATS), which is less invasive surgical procedure, is a good option for resecting Masaoka stage I tumors. Whether VATS is appropriate, depends on the surgeon's judgment and accurate imaging diagnosis. We introduce a technique involving a combination of video-assisted thoracoscopic thymectomy (VAT-T) and lateral thoracotomy for stage II and some stage III thymomas that have locally invaded the lung and/or pericardium.

Mature teratoma of the posterior mediastinum: report of a case.

Mediastinal teratoma generally arises in the anterior mediastinum. Posterior mediastinal teratomas have been rarely reported to date, especially in adults. We report a case of posterior mediastinal teratoma in a 57-year-old woman. The pre-operative diagnostic work-up revealed a posterior mediastinal tumor with calcification and fluid components. The tumor, adhering to the descending aorta, was radically removed through video-assisted thoracic surgery. Histological examination was concluded for a mature teratoma with cystic change. The imaging features of posterior mediastinal teratomas are identical to those in the anterior mediastinum, except for their location. To be different from anterior mediastinal teratomas, benign teratomas in the posterior mediastinum are often involved with a major surrounding structure, including aorta, chest wall, and esophagus. When a posterior mediastinal tumor has the typical features of a mature teratoma in the pre-operative findings, the adhesion to the surrounding structure should be considered.

Open stent grafting with a trifurcated graft for an infected aortic arch aneurysm concomitant with severe calcified aorta.

An infected aortic arch aneurysm is a rare but life-threatening condition. Moreover, surgical treatment for patients with severe calcified aorta is challenging and needs a well-planned strategy. We report a patient with an infected aortic arch aneurysm concomitant with severe calcification of the aorta in whom good results were obtained with open stent grafting in combination with a trifurcated graft.

Choriocarcinoma of the lung: report of a case.

In this report, a 27-year-old woman with a solitary pulmonary nodule is described. Because computed tomography-guided biopsy could not confirm the diagnosis, surgical treatment was performed by video-assisted thoracic surgery. Histological findings showed cytotrophoblasts and syncytiotrophoblasts, suggesting choriocarcinoma. However, there were no abnormal findings on gynecological examination, including ultrasonography, magnetic resonance imaging, and positron-emission tomography. Choriocarcinoma is a malignant neoplasm and can arise after a pregnancy, as a component of germ cell tumors, or in association with a poorly differentiated somatic carcinoma. Our patient, a young female with an antecedent gestation, has no recurrence after surgery. There were tumor emboli in pulmonary arteries and no component of primary lung carcinoma on histological examination. These findings indicate that the lesion was a metastasis of gestational choriocarcinoma. A rare case of a patient with metastatic gestational choriocarcinoma of a solitary pulmonary nodule without any uterine abnormality is presented.

Effective intravenous thrombolytic therapy in a patient with cerebral infarction associated with left atrial myxoma.

A 70-year-old man presented with sudden onset of global aphasia and right hemiplegia. Brain MRI revealed occlusion of the left middle cerebral artery. He was diagnosed as having a hyperacute cerebral infarction. Intravenous thrombolytic therapy was started, and the neurological symptoms were resolved after 11 h. Echocardiography showed a mobile mass in the left atrium, suspicious of a myxoma. The tumor was resected and pathologically diagnosed as a myxoma. In this patient, intravenous thrombolytic therapy was effective, and no adverse effects were observed. This suggests that, even with complications of myxoma, thrombolytic therapy can be considered if there are no contraindications.