RESUMO
(1) Background: Acute kidney injury (AKI) is a common complication following thoracic aortic surgery (TAS), with moderate hypothermic circulatory arrest (MHCA). However, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate the role of new biomarkers in patients after MHCA. (2) Methods: 101 consecutive patients were prospectively enrolled. Measurements of urinary [TIMP-2]*[IGFBP7] and Cystatin C in the blood were performed perioperatively. Primary endpoint was the occurrence of AKI stage 2 or 3 (KDIGO-classification) within 48 h after surgery (AKI group). (3) Results: Mean age of patients was 69.1 ± 10.9 years, 35 patients were female (34%), and 13 patients (13%) met the primary endpoint. Patients in the AKI group had a prolonged ICU-stay (6.9 ± 7.4 days vs. 2.5 ± 3.1 days, p < 0.001) as well as a higher 30-day-mortality (9/28 vs. 1/74, p < 0.001). Preoperative serum creatinine (169.73 ± 148.97 µmol/L vs. 89.74 ± 30.04 µmol/L, p = 0.027) as well as Cystatin C (2.41 ± 1.54 mg/L vs. 1.13 ± 0.35 mg/L, p = 0.029) were higher in these patients. [TIMP-2]*[IGFBP7] increased significantly four hours after surgery (0.6 ± 0.69 mg/L vs. 0.37 ± 0.56 mg/L, p = 0.03) in the AKI group. Preoperative Cystatin C (AUC 0.828, p < 0.001) and serum creatinine (AUC 0.686, p = 0.002) as well as [TIMP-2]*[IGFBP7] 4 h after surgery (AUC 0.724, p = 0.020) were able to predict postoperative AKI. The predictive capacity of Cystatin C was superior to serum creatinine (p = 0.0211) (4) Conclusion: Cystatin C represents a very sensitive and specific biomarker to predict AKI in patients undergoing thoracic surgery with MHCA even before surgery, whereas the predictive capacity of [TIMP-2]*[IGFBP7] is only moderate and inferior to that of serum creatinine.
RESUMO
The present study conducted in rats defines the requirements for neuroprotective effects of systemically administered AT1 receptor blockers (ARBs) in acute ischaemic stroke. The inhibition of central effects to angiotensin II (ANG II) after intravenous (i.v.) treatment with candesartan (0.3 and 3 mg/kg) or irbesartan and losartan (3 and 30 mg/kg) was employed to study the penetration of these ARBs across the blood-brain barrier. Verapamil and probenecid were used to assess the role of the transporters, P-glycoprotein and the multidrug resistance-related protein 2, in the entry of losartan and irbesartan into the brain. Neuroprotective effects of i.v. treatment with the ARBs were investigated after transient middle cerebral artery occlusion (MCAO) for 90 min. The treatment with the ARBs was initiated 3 h after the onset of MCAO and continued for two consecutive days. Blood pressure was continuously recorded before and during MCAO until 5.5 h after the onset of reperfusion. The higher dose of candesartan completely abolished, and the lower dose of candesartan and higher doses of irbesartan and losartan partially inhibited the drinking response to intracerebroventricular ANG II. Only 0.3 mg/kg candesartan improved the recovery from ischaemic stroke, and 3 mg/kg candesartan did not exert neuroprotective effects due to marked blood pressure reduction during reperfusion. Both doses of irbesartan and losartan had not any effect on the stroke outcome. An effective, long-lasting blockade of brain AT1 receptors after systemic treatment with ARBs without extensive blood pressure reductions is the prerequisite for neuroprotective effects in ischaemic stroke.