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.

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.

Quadruple Valve Replacement for Repaired Transposition of the Great Arteries.

A 37-year-old man with repaired transposition of the great arteries had extensive infective endocarditis, and a multidisciplinary therapeutic strategy was planned based on surgical indications, invasiveness, and future prospects. After adequate antibiotic treatment, simultaneous replacement of quadruple valve and aortic root using mechanical valves was performed to intervene in the healed valvular disease and the concurrent anatomic and functional abnormalities. We believe that this extensive one-stage surgery contributed to maximizing the quality of life and minimizing the number of future reoperations. Our approach can provide suggestions for the management of adult patients with repaired congenital heart disease.

Successful off-pump surgical release for extrinsic compression of outflow graft obstruction of a left ventricular assist device.

A 36-year-old woman had received support with the Jarvik 2000 left ventricular assist device for 3 years. Cardiac computed tomography revealed outflow graft obstruction, which appeared as external compression of the outflow graft. The patient underwent surgical release of the obstruction after resternotomy. Yellow sediment had become encrusted in the enclosed space between the covering graft and outflow graft and appeared to have been derived from plasma contents. Successful release of the obstruction was achieved by cutting open the covering graft without cardiopulmonary bypass. Neither pump exchange nor outflow graft exchange was required. This off-pump surgery can be a beneficial procedure in terms of less invasiveness and good curability.

Surgery for Bacterial Endocarditis Complicated by Diffuse Alveolar Hemorrhage.

Diffuse alveolar hemorrhage is a very rare but potentially lethal condition resulting from various disorders. We report the case of a patient who suffered diffuse alveolar hemorrhage subsequent to bacterial endocarditis and survived aortic valve replacement, which was applied after improvement in respiratory distress. We believe that the strategy of respiratory functional recovery by aggressive rehabilitation is essential for the achievement of a successful surgical outcome in patients with alveolar hemorrhage.

Adjunctive Ischemic Lower-Limb Perfusion during Aortic Repair with Cardiopulmonary Bypass Prevents Fatal Reperfusion Injury.

Acute aortic dissection can be complicated by malperfusion syndromes, including ischemia of the lower limbs. In some cases, delayed correction of leg ischemia leads to reperfusion injury, potentially resulting in renal failure. We describe the case of a 64-year-old woman who presented with acute aortic dissection manifesting itself as lower-limb ischemia. During and after aortic surgery with cardiopulmonary bypass, the patient developed myonephropathic metabolic syndrome. Hyperkalemia was corrected and acute kidney injury was prevented by infusing large volumes of intravenous fluids and administering human atrial natriuretic peptide. Peripheral bypass surgery was unnecessary. This case suggests that restoring blood flow to an ischemic leg by means of adjunctive perfusion during aortic repair with cardiopulmonary bypass is a viable way to overcome the biochemical instability associated with prolonged ischemia, especially hyperkalemia in the early phase of reperfusion.