Background: Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. Methods: We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD ⁺ ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD ⁺ pool also were tested. Results: Increased NADH/NAD ⁺ and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD ⁺ levels by stimulating the NAD ⁺ salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD ⁺ ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD ⁺ redox balance either genetically or pharmacologically. Conclusions: We show that mitochondrial protein hyperacetylation due to NAD ⁺ redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD ⁺ imbalance in the failing hearts. These findings have a high translational potential as the pharmacologic strategy of increasing NAD ⁺ precursors are feasible in humans.

This study compared the effects of the pericapsular nerve group (PENG) block and supra-inguinal fascia iliaca compartment block (FICB) on postoperative analgesia and quadriceps strength following total hip arthroplasty under general anesthesia. A total of 58 patients were randomized to receive either PENG block (PENG group) or supra-inguinal FICB (FICB group) following anesthetic induction. The primary outcomes were the postoperative pain scores. Patients were randomized to receive either PENG block or supra-inguinal FICB following anesthetic induction. Pain scores at rest and with movement were assessed preoperatively, at the postanesthesia care unit (only at rest), and at 6, 24, 36, and 48 h postoperatively. Opioid consumption was also assessed for 48 h postoperatively. Quadriceps strength measurements were performed preoperatively, at 6, 24, and 36 h postoperatively. In total, 54 patients completed the study: 27 in the PENG group and 27 in the FICB group. Despite lower pain scores at rest in the PENG group at postoperative 6 and 24 h, there were no significant differences in the pain scores at rest and during movement between the two groups during postoperative 48 h in the linear mixed model analysis (p = 0.079 and p = 0.323, respectively). Cumulative opioid consumption up to postoperative 48 h was also similar in the two groups (p = 0.265). The changes in quadriceps strength measurements in the operative leg and the nonoperative leg were not significantly different between the groups (p = 0.513 and p = 0.523, respectively). The PENG block may have similar analgesic efficacy to the supra-inguinal FICB. No difference was detected in the quadriceps strength between the patients receiving these two blocks.

A prospective, randomized, controlled, and double-blind trial. To evaluate the effects of 2 different doses of perioperative pregabalin administration, twice on the day of surgery, on acute postoperative pain after spinal surgery. Besides its well-established role on neuropathic pain, pregabalin seems to be a promising adjunct to multimodal analgesic regimen following surgery. No comprehensive data exist regarding the optimal dosage of pregabalin on reducing postoperative pain and opioid consumption in spinal surgery. Patients were randomly assigned to 1 of 3 groups. The placebo group (n = 28) received placebo capsules 1 hour before the anesthetic induction and 12 hours after surgery. The pregabalin groups received pregabalin 75 mg (P75 group, n = 28) or 150 mg (P150 group, n = 28), respectively at the same points. Assessed variables were total amount of administered fentanyl-based intravenous patient-controlled analgesia, pain intensity, and the frequency of rescue analgesic administered during the first 48 hours after surgery, subdivided into the following 4 periods: on arrival of patient to the postanesthesia care unit, 1 to 6 hours, 6 to 24 hours, and 24 to 48 hours. RESULTS.: The amount of patient-controlled analgesia volume infused until 24 hours (P 5 0.025) and 48 hours (P 5 0.028) after surgery was significantly less in the P150 group compared with the control group. The frequency of additional anodynes administered until 6 hours (P 5 0.049) and 24 hours (P 5 0.045) after surgery was significantly less in the P150 group compared with the control group. Perioperative administration of pregabalin 150 mg before and 12 hours after surgery, but not 75 mg, significantly reduced opioid consumption and the use of additional pain rescue for 48 hours after surgery without significant side effects in patients undergoing spinal fusion surgery.

Objective: Postoperative cognitive dysfunction (POCD) commonly develops after cardiac surgery affecting patients’ outcome. Cerebral oximetry noninvasively measures regional cerebral oxygen saturation (rSO₂) and significant correlation has been reported between intraoperative cerebral desaturation and POCD, as well as patients’ outcome following coronary artery bypass grafting. However, evidence is limited in valvular heart surgery (VHS). We investigated the relationship of intraoperative rSO₂ values with POCD and length of postoperative hospitalization in patients undergoing VHS. Methods: One hundred patients undergoing elective VHS were enrolled. Neurocognitive evaluation was performed with Mini-Mental State Examination, Trail-Making Test (Part A), and Grooved Pegboard Test at 1 day before and 7th day after surgery. During surgery, rSO₂ was continuously monitored and the incidence and duration of decrease in rSO₂ values for five consecutive minutes were recorded as follows; (1) decrease in absolute rSO₂ values to less than 50%, (2) 40%, and (3) a 20% decrease compared to baseline value. Results: Twenty-three patients (23%) demonstrated POCD. We could not observe any significant differences in either the incidence or duration of decrease in rSO₂ values between patients with and without POCD. Low education level and higher baseline temperature had significant correlation with POCD. Patients with cerebral desaturation required significantly longer postoperative hospitalization. Conclusion: In patients undergoing VHS, POCD could not be predicted with cerebral oximetry. However, patients with intraoperative cerebral desaturation required significantly longer postoperative hospitalization and cerebral oximetry appears to be promising in terms of monitoring the brain as the index organ for systemic perfusion and improving patients’ outcome.