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Noteworthy in Cardiothoracic Surgery 2023 summarizes a few of the most high-impact trials and provocative trends in cardiothoracic surgery and transplantation this past year. Transplantation using organs procured from donation after circulatory death (DCD) continues to increase, and the American Society of Transplant Surgeons released recommendations on best practices in 2023. We review a summary of data on the impact of DCD on heart and lung transplantation. There has been increased interest in extracorporeal life support (ECLS), particularly after the COVID-19 pandemic, and we review the results of the highly discussed ECLS-SHOCK trial, which randomized patients in cardiogenic shock with planned revascularization to ECLS vs usual care. With improving survival outcomes in complex aortic surgery, there is a need for higher-quality evidence to guide which cooling and cerebral perfusion strategies may optimize cognitive outcomes in these patients. We review the short-term outcomes of the GOT ICE trial (Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest), a multicenter, randomized controlled trial of three different nadir temperatures, evaluating outcomes in cognition and associated changes in functional magnetic resonance imaging. Finally, both the Society of Thoracic Surgeons (STS) and the American College of Cardiology, American Heart Association, American College of Chest Physicians and Heart Rhythm Society (ACC/AHA/ACCP/HRS) updated atrial fibrillation guidelines in 2023, and we review surgically relevant updates to the guidelines and the evidence behind them.
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COVID-19 , Humanos , COVID-19/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Procedimientos Quirúrgicos Torácicos/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Trasplante de Corazón/métodos , Trasplante de Pulmón/métodosRESUMEN
OBJECTIVE: The study objective was to assess a machine learning model's ability to predict the occurrence of life-altering events in hemiarch surgery and determine contributing patient characteristics and intraoperative factors. METHODS: In total, 602 patients who underwent hemiarch replacement at a high-volume aortic center from 2009 to 2022 were included. Patients were randomly divided into training (80%) and testing (20%) sets with various eXtreme gradient boosting candidate models constructed to predict the risk of experiencing life-altering events, including stroke, mortality, or new renal replacement therapy requirement. A total of 64 input parameters from the index hospitalization were identified, including 24 demographic characteristics as well as 8 preoperative and 32 intraoperative variables. A SHapley Additive exPlanation beeswarm plot was generated to identify and interpret the impact of individual features on the predictions of the final model. RESULTS: A life-altering event was noted in 15% (90/602) of patients who underwent hemiarch replacement, including urgent/emergency cases and dissections. The final eXtreme Gradient Boosting model demonstrated a cross-validation accuracy of 88% on the testing set and was well calibrated as evidenced by a low Brier score of 0.12. The best performing model achieved an area under the receiver operating characteristic curve of 0.76 and an area under the precision recall curve of 0.55. The SHapley Additive exPlanation beeswarm plot provided insights into key features that significantly influenced model prediction. CONCLUSIONS: Machine learning demonstrated superior accuracy in predicting hemiarch patients who would experience a life-altering event. This model may help to guide patients and clinicians in stratifying risk on an individual basis, which may in turn influence clinical decision-making.
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Donation after circulatory death (DCD) could account for the largest expansion of the donor allograft pool in the contemporary era. However, the organ yield and associated costs of normothermic regional perfusion (NRP) compared to super-rapid recovery (SRR) with ex-situ normothermic machine perfusion, remain unreported. The Organ Procurement and Transplantation Network (December 2019 to June 2023) was analyzed to determine the number of organs recovered per donor. A cost analysis was performed based on our institution's experience since 2022. Of 43 502 donors, 30 646 (70%) were donors after brain death (DBD), 12 536 (29%) DCD-SRR and 320 (0.7%) DCD-NRP. The mean number of organs recovered was 3.70 for DBD, 3.71 for DCD-NRP (P < .001), and 2.45 for DCD-SRR (P < .001). Following risk adjustment, DCD-NRP (adjusted odds ratio 1.34, confidence interval 1.04-1.75) and DCD-SRR (adjusted odds ratio 2.11, confidence interval 2.01-2.21; reference: DBD) remained associated with greater odds of allograft nonuse. Including incomplete and completed procurement runs, the total average cost of DCD-NRP was $9463.22 per donor. By conservative estimates, we found that approximately 31 donor allografts could be procured using DCD-NRP for the cost equivalent of 1 allograft procured via DCD-SRR with ex-situ normothermic machine perfusion. In conclusion, DCD-SRR procurements were associated with the lowest organ yield compared to other procurement methods. To facilitate broader adoption of DCD procurement, a comprehensive understanding of the trade-offs inherent in each technique is imperative.
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BACKGROUND: The safety and effectiveness of the RelayPro endograft (Terumo Aortic) was assessed for the treatment of acute, complicated type B aortic dissection (TBAD). METHODS: A prospective pivotal trial analyzed a primary end point of all-cause mortality at 30 days. Secondary end points included technical success, major adverse events (disabling stroke, renal failure, and paraplegia/paralysis), endoleaks, patency, rupture, device integrity, false lumen perfusion, reinterventions, aortic expansion, and migration evaluated to 5 years. RESULTS: The study involved 22 United States centers and enrolled 56 patients (mean age, 59.5 ± 11.4 years) from 2017 to 2021; of whom, 73.2% were men and 53.6% were African American. TBAD was complicated by malperfusion of the kidneys (51.8%), lower extremities (35.7%), and viscera (33.9%), and rupture (10.7%). Dissection extended proximally to zones 1/2 (14.3%) and zone 3 (78.6%) and distally to the iliac arteries (67.3%). Most procedures were percutaneous (85.5%). Technical success was 100%. Median hospitalization was 7 days (interquartile range, 5-12 days). All-cause mortality at 30 days was 1.8% (1 of 56; upper 95% CI, 8.2%; P < .0001). Seven major adverse events occurred in 6 patients (10.7%), consisting of paraplegia (n = 3), paraparesis (n = 2), disabling stroke (n = 1), and renal failure (n = 1). All paraplegia/paraparesis resolved with lumbar drainage. Kaplan-Meier analysis estimated a freedom from major adverse events of 89.1% at each interval from 30 days to 3 years. There was 1 endoleak (Type Ia), 2 retrograde dissections, and aortic diameter growth occurred in 2. There has been no rupture, fistula, component separation, patency loss, stenosis, kinking, twisting, bird beak, loss of device integrity, or fracture. CONCLUSIONS: RelayPro is safe and effective in acute, complicated TBAD. Follow-up is ongoing to evaluate longer-term outcomes and durability.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Insuficiencia Renal , Accidente Cerebrovascular , Masculino , Humanos , Estados Unidos , Persona de Mediana Edad , Anciano , Femenino , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Estudios Prospectivos , Resultado del Tratamiento , Stents/efectos adversos , Disección Aórtica/cirugía , Endofuga/etiología , Paraplejía/etiología , Estudios Retrospectivos , Insuficiencia Renal/etiología , Accidente Cerebrovascular/etiología , Paraparesia/complicaciones , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: This study aims to examine the impact of home-to-transplantation center travel time as a potential barrier to healthcare accessibility. METHODS: Observational study examined adult heart transplant recipients who received a graft between 2012 and 2022 in the United States. Travel time was calculated using the Google Distance Matrix API between the recipient's residence and transplantation center. A multivariable parametric survival model was fitted to minimize confounding bias. RESULTS: Among the 25,923 recipients that met the selection criteria, the median travel time was 51 âmin and 95 â% of recipients lived within a 5-h radius of their center. White recipients experienced longer median travel times (62 âmin, p â< â0.001) compared to Black (36 âmin) or Hispanic (40 âmin) recipients. A travel time of 1-2 âh (survival time ratio [STR] 0.867, p â= â0.035) or >2 âh (STR 0.873, p â= â0.026) away from the transplantation center was independently associated with lower long-term survival rates. CONCLUSION: Extended travel times to transplantation centers may negatively impact long-term survival outcomes for heart transplant recipients, suggesting the need to address this potential barrier to healthcare accessibility.
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Trasplante de Corazón , Adulto , Humanos , Estados Unidos/epidemiología , Atención a la Salud , Factores de Tiempo , Viaje , Convulsiones , Supervivencia de Injerto , Estudios RetrospectivosRESUMEN
AIMS: There is wide variability in the practice of cardiac preservation for heart transplantation. Prior reports suggest that the type of solution may be linked with a reduced incidence of posttransplantation complications. METHODS: Adult (≥18âyears old) heart recipients who underwent transplantation between 2015 and 2021 in the United States were examined. Recipients were stratified by solution utilized for their grafts at the time of recovery: University of Wisconsin, histidine-tryptophan-ketoglutarate (HTK), or Celsior solution. The primary endpoint was a composite of 30-day mortality, primary graft dysfunction, or re-transplantation. Risk adjustment was performed for the recipient, donor, and procedural characteristics using regression modeling. RESULTS: Among 16â884 recipients, the group distribution was University of Wisconsin solution 53%, HTK 22%, Celsior solution 15%, and other 10%. The observed incidence of the composite endpoint (University of Wisconsin solutionâ=â3.6%, HTKâ=â4.0%, Celsior solutionâ=â3.7%, Pâ=â0.301) and 1-year survival (University of Wisconsin solutionâ=â91.7%, HTKâ=â91.3%, Celsior solutionâ=â91.7%, log-rank Pâ=â0.777) were similar between groups. After adjustment, HTK was associated with a higher risk of the composite endpoint [odds ratio (OR) 1.249, 95% confidence interval (CI) 1.019-1.525, Pâ=â0.030] in reference to University of Wisconsin solution. This association was substantially increased among recipients with ischemic periods of greater than 4âh (OR 1.817, 95% CI 1.188-2.730, Pâ=â0.005). The risks were similar between University of Wisconsin solution and Celsior solution (Pâ=â0.454). CONCLUSION: The use of the histidine-tryptophan-ketoglutarate solution during cold static storage for cardiac preservation is associated with increased rates of early mortality or primary graft dysfunction. Clinician discretion should guide its use, especially when prolonged ischemic times (>4âh) are anticipated.
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Trasplante de Corazón , Soluciones Preservantes de Órganos , Disfunción Primaria del Injerto , Adulto , Humanos , Adolescente , Preservación de Órganos/efectos adversos , Disfunción Primaria del Injerto/etiología , Disfunción Primaria del Injerto/prevención & control , Soluciones Preservantes de Órganos/efectos adversos , Trasplante de Corazón/efectos adversos , Insulina , Glucosa/efectos adversosRESUMEN
BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.
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Lesión Renal Aguda , Anemia , Procedimientos Quirúrgicos Cardíacos , Humanos , Estudios Prospectivos , Eritrocitos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Glutatión/farmacología , Hipoxia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
Objective: Donation after circulatory death (DCD) procurement and transplantation after thoracoabdominal normothermic regional perfusion (TA-NRP) remains a novel technique to improve cardiac and hepatic allograft preservation but may be complicated by lung allograft pulmonary edema. We present a single-center series on early implementation of a lung-protective protocol with strategies to mitigate posttransplant pulmonary edema in DCD lung allografts after TA-NRP procurement. Methods: Data from all lung transplantations performed using a TA-NRP procurement strategy from October 2022 to April 2023 are presented. Donor management consisted of key factors to reduce lung allograft pulmonary edema: aggressive predonation and early posttransplant diuresis, complete venous drainage at TA-NRP initiation, and early pulmonary artery venting upon initiation of systemic perfusion. Donor and recipient characteristics, procurement characteristics such as TA-NRP intervals, and 30-day postoperative outcomes were assessed. Results: During the study period, 8 lung transplants were performed utilizing TA-NRP procurement from DCD donors. Donor ages ranged from 16 to 39 years and extubation time to declaration of death ranged from 10 to 90 minutes. Time from declaration to TA-NRP initiation was 7 to 17 minutes with TA-NRP perfusion times of 49 to 111 minutes. Median left and right allograft warm ischemia times were 55.5 minutes (interquartile range, 46.5-67.5 minutes) and 41.0 minutes (interquartile range, 39.0-53.0 minutes, respectively, with 2 recipients supported with cardiopulmonary bypass or venoarterial extracorporeal membrane oxygenation during implantation. No postoperative extracorporeal membrane oxygenation was required. There were no pulmonary-related deaths; however, 1 patient died from complications of severe necrotizing pancreatitis with a normal functioning allograft. All patients were extubated within 24 hours. Index intensive care unit length of stay ranged from 3 to 11 days with a hospital length of stay of 13 to 37 days. Conclusions: Despite concern regarding quality of DCD lung allografts recovered using the TA-NRP technique, we report initial success using this procurement method. Implementation of strategies to mitigate pulmonary edema can result in acceptable outcomes following lung transplantation. Demonstration of short- and long-term safety and efficacy of this technique will become increasingly important as the use of TA-NRP for thoracic and abdominal allografts in DCD donors expands.
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This keynote lecture and corresponding presentation discuss the anatomy and pathophysiology surrounding spinal cord injury in aortic surgery. This article will discuss risk factors and mechanisms for spinal cord injury, including loss of direct and collateral spinal cord perfusion and ischemia-reperfusion injury. This review will examine these elements in both the laboratory and clinical setting, in addition to other neuroprotective strategies applied in clinical practice. Addressing spinal cord injury requires an integrated and considerate approach to simultaneously optimize spinal cord blood flow, promote collateralization and improve ischemic tolerance. Given the catastrophic clinical consequences for both the patient and their caregivers, continuing to investigate and examine spinal cord injury is of the utmost importance.
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Objective: A kaolin-based nonresorbable hemostatic gauze, QuikClot Control+, has demonstrated effective hemostasis and safety when used for severe/life-threatening (grade 3/4) internal organ space bleeding. We evaluated the efficacy and safety of this gauze for mild to moderate (grade 1-2) bleeding in cardiac surgery compared with control gauze. Methods: This was a randomized, controlled, single-blinded study of patients who underwent cardiac surgery between June 2020 and September 2021 across 7 sites with 231 subjects randomized 2:1 to QuikClot Control+ or control. The primary efficacy end point was hemostasis rate (ie, subjects achieving grade 0 bleed) through up to 10 minutes of bleeding site application, assessed using a semiquantitative validated bleeding severity scale tool. The secondary efficacy end point was the proportion of subjects achieving hemostasis at 5 and 10 minutes. Adverse events, assessed up to 30 days postsurgery, were compared between arms. Results: The predominant procedure was coronary artery bypass grafting, and 69.7% and 29.4% were sternal edge and surgical site (suture line)/other bleeds, respectively. Of the QuikClot Control+ subjects, 121 of 153 (79.1%) achieved hemostasis within 5 minutes, compared with 45 of 78 (58.4%) controls (P < .001). At 10 minutes, 137 of 153 patients (89.8%) achieved hemostasis compared with 52 of 78 controls (68.4%) (P < .001). At 5 and 10 minutes, hemostasis was achieved in 20.7% and 21.4% more QuikClot Control+ subjects, respectively, compared with controls (P < .001). There were no significant differences in safety or adverse events between treatment arms. Conclusions: QuikClot Control+ demonstrated superior performance in achieving hemostasis for mild to moderate cardiac surgery bleeding compared with control gauze. The proportion of subjects achieving hemostasis was more than 20% higher in QuikClot Control+ subjects at both timepoints compared with controls, with no significant difference in safety outcomes.
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Objective: The frozen elephant trunk procedure is a well-established technique for the repair of type A ascending aortic dissection and complex aortic arch pathology. The ultimate shape created by the repair may have consequences in long-term complications. The purpose of this study was to apply a machine learning technique to comprehensively describe 3-dimensional aortic shape variations after the frozen elephant trunk procedure and associate these variations with aortic events. Methods: Computed tomography angiography acquired before discharge of patients (n = 93) who underwent the frozen elephant trunk procedure for type A ascending aortic dissection or ascending aortic arch aneurysm was preprocessed to yield patient-specific aortic models and centerlines. Aortic centerlines were subjected to principal component analysis to describe principal components and aortic shape modulators. Patient-specific shape scores were correlated with outcomes defined by composite aortic event, including aortic rupture, aortic root dissection or pseudoaneurysm, new type B dissection, new thoracic or thoracoabdominal pathologies, residual descending aortic dissection with residual false lumen flow, or thoracic endovascular aortic repair complications. Results: The first 3 principal components accounted for 36.4%, 26.4%, and 11.6% of aortic shape variance, respectively, and cumulatively for 74.5% of the total shape variation in all patients. The first principal component described variation in arch height-to-length ratio, the second principal component described angle at the isthmus, and the third principal component described variation in anterior-to-posterior arch tilt. Twenty-one aortic events (22.6%) were encountered. The degree of aortic angle at the isthmus described by the second principal component was associated with aortic events in logistic regression (hazard ratio, 0.98; 95% confidence interval, 0.97-0.99; P = .046). Conclusions: The second principal component, describing angulation at the region of the aortic isthmus, was associated with adverse aortic events. Observed shape variation should be evaluated in the context of aortic biomechanical properties and flow hemodynamics.
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Increasing the number of available hearts for transplantation is the best strategy to decrease waitlist mortality. This study examines organ procurement organizations (OPOs) and their role in the transplantation network to determine whether variability in performance exists across them. Adult deceased donors who met the criteria for brain death between 2010 and 2020 (inclusive) in the United States were examined. A regression model was fitted and internally validated using donor characteristics available at the time of organ recovery to predict the likelihood of heart transplantation. Subsequently, an expected heart yield was calculated for each donor using this model. Observed-to-expected (O/E) heart yield ratios for each OPO were calculated by dividing the number of hearts recovered for transplantation by the expected number of recoveries. There were 58 OPOs active during the study period, and on average, OPO activity grew over time. The mean O/E ratio among OPOs was 0.98 (standard deviation ± 0.18). Twenty-one OPOs consistently performed below the expected level (95% confidence intervals < 1.0) and generated a deficit of 1,088 expected transplantations during the study period. The proportion of hearts that were recovered for transplantation varied significantly by OPO categories: low tier 31.8%, mid tier 35.6%, and high tier 36.2% (p < 0.01), even as the expected yield was similar across tiers (p = 0.69). OPO performance accounts for 28% of the variability in successfully transplanting a heart after accounting for the role of referring hospitals, donor families, and transplantation centers. In conclusion, there is significant variability in volume and heart yield from brain-dead donors across OPOs.
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Trasplante de Corazón , Obtención de Tejidos y Órganos , Humanos , Adulto , Muerte Encefálica , Donantes de Tejidos , CorazónRESUMEN
INTRODUCTION: Retrograde cerebral perfusion (RCP) is a safe and effective technique to augment cerebral protection during lower body circulatory arrest in patients undergoing elective hemiarch replacement. However, recommendations guiding optimal temperature, flow rate, and perfusion pressure are outdated and potentially overly limiting. We report our experience using RCP for elective hemiarch replacement with parameters that challenge the currently accepted paradigm. METHODS: This was a single-center, retrospective analysis of 319 adult patients who underwent elective hemiarch replacement between February 2010 and 2021 using hypothermic lower body circulatory arrest with RCP alone, RCP followed by antegrade cerebral perfusion (ACP), or ACP alone. Flow rates were adjusted to maintain cerebral perfusion pressure between 30 and 50 mm Hg for RCP and between 40 and 60 mm Hg for ACP. RESULTS: RCP was used in 22.6% (n = 72) of cases, whereas ACP alone was performed in 77.4% (n = 247) of cases. Baseline patient characteristics were similar between groups. Patients undergoing RCP demonstrated shorter cross-clamp time (97.0 min versus 100.0 min, P = 0.034) and shorter lower body circulatory arrest time (7.0 min versus 10.0 min, P < 0.0001) compared with ACP alone. Nadir bladder temperature was equivalent between groups (27.3°C versus 27.5°C, P = 0.752). There were no significant differences in postoperative complications, neurologic outcomes, or mortality. CONCLUSIONS: Moderate hypothermic lower body circulatory arrest combined with RCP at target perfusion pressures of 30-50 mm Hg in patients undergoing elective hemiarch replacement results in equivalent neurologic outcomes and overall morbidity to cases using ACP alone. These results challenge the currently accepted paradigm for RCP, which typically uses deep hypothermia while keeping perfusion pressures below 25 mm Hg.
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Paro Cardíaco , Hipotermia Inducida , Adulto , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Paro Circulatorio Inducido por Hipotermia Profunda , Perfusión/métodos , Circulación Cerebrovascular , Aorta Torácica/cirugía , Hipotermia Inducida/métodosRESUMEN
OBJECTIVES: The mitochondrial adenosine triphosphate-sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide-dependent indirect activation of the adenosine triphosphate-sensitive potassium channel contribute to the induction of ischemic metabolic tolerance. METHODS: Spinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate-sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate-sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia. RESULTS: Motor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P < .001), but worse than in the Nicorandil group (P = .078). Motor preservation in the diazoxide group was similar to the Nicorandil + carboxy-PTIO group. There was no significant difference between the diazoxide and diazoxide + carboxy-PTIO groups. CONCLUSIONS: Both direct and nitric oxide-dependent indirect activation of the mitochondrial adenosine triphosphate-sensitive potassium channel play an important role in pharmacologically induced motor function preservation.