Background The adenosine triphosphate-sensitive potassium (KATP) channel opener, diazoxide, preserves myocyte volume homeostasis and contractility during stress via an unknown mechanism. Pharmacologic overlap has been suggested between succinate dehydrogenase (SDH) activity and KATP channel modulators. Diazoxide may be cardioprotective due to the inhibition of SDH which may form a portion of the mitochondrial KATP channel. To determine the role of inhibition of SDH in diazoxide's cardioprotection, this study utilized glutathione to prevent the inhibition of SDH. Methods SDH activity was measured in isolated mitochondria exposed to succinate (control), malonate (inhibitor of succinate dehydrogenase), diazoxide, and varying concentrations of glutathione alone or in combination with diazoxide. Enzyme activity was measured by spectrophotometric analysis. To evaluate myocyte volume and contractility, cardiac myocytes were superfused with Tyrode's physiologic solution (20 minutes), followed by test solution (20 minutes) including: Tyrode's, hyperkalemic cardioplegia (stress), cardioplegia + diazoxide, cardioplegia + diazoxide + glutathione, or glutathione alone; followed by Tyrode's (20 minutes). Myocyte volume and contractility were recorded using image grabbing software. Results Both malonate and diazoxide inhibited succinate dehydrogenase. Glutathione prevented the inhibition of succinate dehydrogenase by diazoxide in a dose dependent manner. The addition of diazoxide prevented the detrimental myocyte swelling due to cardioplegia alone and this benefit was lost with the addition of glutathione. However, glutathione elicited an independent cardioprotective effect on myocyte contractility. Conclusion The ability of diazoxide to provide beneficial myocyte homeostasis during stress involves the inhibition of succinate dehydrogenase, which may also involve the opening of a purported mitochondrial KATP channel.

Pump positional change may contribute to LVAD dysfunction or failure, but it does not entirely account for observed pump dysfunction or failure.

Background Tranexamic acid (TXA) has shown safety and efficacy in reducing blood loss associated with various surgical procedures. However, to our knowledge there are no studies evaluating the effect of TXA on blood loss and transfusion requirements associated with periacetabular osteotomy (PAO). Questions/purposes The main purpose of this study is to determine whether TXA reduces blood loss and transfusion use in patients undergoing PAO for symptomatic acetabular dysplasia. Our secondary purpose was to compare the frequency of symptomatic thromboembolic events between patients undergoing surgery with and without TXA. Methods A consecutive series of 100 periacetabular osteotomies performed by one surgeon was reviewed to compare the groups immediately before and after implementation of routine use of tranexamic acid (two retrospective cohorts). TXA dosing followed an established protocol with a standard dose of 1 g infused intravenously during 10 minutes before skin incision and an additional 1 g intravenously at wound closure. Outcome measures include total estimated blood loss perioperatively and transfusion requirements. Total estimated blood loss was calculated using a formula built from the National Surgical Quality Improvement Program data regarding surgical blood loss. Results The mean perioperative total estimated blood loss was less in the patients receiving TXA compared with blood loss in patients who did not receive TXA (706 mL versus 1021 mL; p \ 0.001; 95% CI, À495 to À134). Twenty-six (52%) of the 50 patients who did not receive TXA had postoperative blood transfusions compared with 15 (30%) of 50 who received TXA (odds ratio, 0.395; 95% CI, p = 0.0414). No symptomatic deep vein thromboses or symptomatic pulmonary emboli were identified in either group. Conclusions TXA reduces estimated blood loss and the frequency of transfusions in patients undergoing PAO for treatment of symptomatic acetabular dysplasia. Future prospective studies should confirm our findings to determine whether patients undergoing PAO should receive routine perioperative TXA. Level of Evidence Level III, therapeutic study.