Socioeconomic status as a predictor of post-operative mortality and outcomes in carotid artery stenting vs. carotid endarterectomy.

Background: The association between low socioeconomic status (SES) and worse surgical outcomes has become an emerging area of interest. Literature has demonstrated that carotid artery stenting (CAS) poses greater risk of postoperative complications, particularly stroke, than carotid endarterectomy (CEA). This study aims to compare the impact of low SES on patients undergoing CAS vs. CEA. Methods: The National Inpatient Sample (NIS) was queried for patients undergoing CAS and CEA from 2010 to 2015. Patients were stratified by highest and lowest median income quartiles by zip code and compared through demographics, hospital characteristics, and comorbidities defined by the Charlson Comorbidity Index (CCI). Primary outcome was in-hospital mortality. Secondary outcomes included acute kidney injury (AKI), post-operative stroke, sepsis, and bleeding requiring reoperation.Multivariable logistic regression was used to determine the effect of SES on outcomes. Results: Five thousand four hundred twenty-five patients underwent CAS (Low SES: 3,516 (64.8%); High SES: 1,909 (35.2%) and 38,399 patients underwent CEA (Low SES: 22,852 (59.5%); High SES: 15,547 (40.5%). Low SES was a significant independent predictor of mortality [OR = 2.07 (1.25-3.53); p = 0.005] for CEA patients, but not for CAS patients [OR = 1.21 (CI 0.51-2.30); p = 0.68]. Stroke was strongly associated with low SES, CEA patients (Low SES = 1.5% vs. High SES = 1.2%; p = 0.03), while bleeding was with high SES, CAS patients (Low SES = 5.3% vs. High SES = 7.1%; p = 0.01). CCI was a strong predictor of mortality for both procedures [CAS: OR1.45 (1.17-1.80); p < 0.001. CEA: OR1.60 (1.45-1.77); p < 0.001]. Advanced age was a predictor of mortality post-CEA [OR = 1.03 (1.01-1.06); p = 0.01]. While not statistically significant, advanced age and increased mortality trended towards a positive association in CAS [OR = 1.05 (1.00-1.10); p = 0.05]. Conclusions: Low SES is a significant independent predictor of post-operative mortality in patients who underwent CEA, but not CAS. CEA is also associated with higher incidence of stroke in low SES patients. Findings demonstrate the impact of SES on outcomes for patients undergoing carotid revascularization procedures. Prospective studies are warranted to further evaluate this disparity.

Analysis of Operating Room Personnel Perspectives to Enhance Medical Student Readiness for Surgery.

OBJECTIVE: We sought to better define surgical etiquette and elucidate operating room (OR) personnel expectations of medical students to determine areas for medical education improvement. DESIGN: A questionnaire probing medical student performance regarding elements of OR etiquette was developed. Questions were designed to obtain structured feedback through Likert scales and open-ended responses. Descriptive and thematic analysis was conducted on Likert scale and free-text responses, respectively. SETTING: Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. Tertiary academic center. PARTICIPANTS: A questionnaire was distributed to nurses, surgical and anesthesia faculty and residents. The survey was distributed via email amongst various hospitals, predominantly our home institution. RESULTS: We received 126 complete responses. About half of respondents (46.3%) self-identified as female. Most respondents were part of the surgical team (74.7%), with most (57.8%) from attending physicians. A majority of respondents agreed that medical students responded well to feedback. Roughly half of respondents agreed that medical students understand their role, maintain sterility, and assist in delivery of effective patient care. More than half of respondents did not believe that medical students understand traffic patterns. The majority of respondents indicated that medical students are not appropriately prepared with basic surgical skills prior to entering the OR. Two-thirds of respondents did not feel that medical students contribute towards maintaining safety in the OR. We identified 4 themes from free text responses: students should assume an active role in the OR, utilize situational awareness, understand sterility and OR workflow, and have knowledge of basic operative technique and anatomy. CONCLUSIONS: Medical students are not meeting OR personnel expectations and may benefit from early educational interventions to optimize the OR as a learning environment.

Arsenic and cancer: Evidence and mechanisms.

Arsenic is a potent carcinogen and poses a significant health concern worldwide. Exposure occurs through ingestion of drinking water and contaminated foods and through inhalation due to pollution. Epidemiological evidence shows arsenic induces cancers of the skin, lung, liver, and bladder among other tissues. While studies in animal and cell culture models support arsenic as a carcinogen, the mechanisms of arsenic carcinogenesis are not fully understood. Arsenic carcinogenesis is a complex process due its ability to be metabolized and because of the many cellular pathways it targets in the cell. Arsenic metabolism and the multiple forms of arsenic play distinct roles in its toxicity and contribute differently to carcinogenic endpoints, and thus must be considered. Arsenic generates reactive oxygen species increasing oxidative stress and damaging DNA and other macromolecules. Concurrently, arsenic inhibits DNA repair, modifies epigenetic regulation of gene expression, and targets protein function due its ability to replace zinc in select proteins. While these mechanisms contribute to arsenic carcinogenesis, there remain significant gaps in understanding the complex nature of arsenic cancers. In the future improving models available for arsenic cancer research and the use of arsenic induced human tumors will bridge some of these gaps in understanding arsenic driven cancers.

Pediatric Extracorporeal Cardiopulmonary Resuscitation: Development of a Porcine Model and the Influence of Cardiopulmonary Resuscitation Duration on Brain Injury.

Background The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22- to 24-hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results Ten-kilogram, 4-week-old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof-of-concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0-6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra-abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group (P=0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4-7.4] versus CPR30: 7.5 [IQR 7.4-7.5], P=0.022), higher lactate (CPR60: 6.8 [IQR 6.8-11] versus CPR30: 4.2 [IQR 4.1-4.3] mmol/L; P=0.012), and higher ICP (CPR60: 19.3 [IQR 11.7-29.3] versus CPR30: 7.9 [IQR 6.7-9.3] mm Hg; P=0.037). Both groups had greater mitochondrial injury than shams (CPR60: P<0.001; CPR30: P<0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24-hour survival with more severe lactic acidosis in the 60-minute cohort.

Is cardiopulmonary bypass standby still required for laser lead extractions?

OBJECTIVE: Over the last two decades there has been an increase in the number of cardiac implantable electronic devices and consequently, there has also been an increased need for lead extractions. Fibrotic attachments develop between the lead and the venous and cardiac structures that may require the use of a laser to mobilize the lead. Cardiothoracic surgeons (CTS) have traditionally provided backup for surgical emergencies for these extractions. This study evaluates the surgical outcomes of patients undergoing transvenous laser lead extractions (TLE) and determines if CTS are still needed for backup. METHODS: A retrospective review of consecutive patients undergoing laser lead extractions at a single academic center. Lead extractions using only laser sheaths were analyzed. The clinical characteristics, complications, and mortality of the patients were evaluated. RESULTS: One hundred and twenty-one patients underwent TLEs from January 1st, 2014 to December 31st, 2018. The majority were male (N = 80, 66.1%), and the average age was 66.48 ± 14 years. The indication for removal was either laser lead malfunction or infection. A total of 30 patients (24.8%) had complications postoperatively including wound hematomas, superficial infections, and arrhythmias. The average length of stay was 9 ± 12 for all the patients in the study. 2 patients (1.6%) had injuries that required emergency surgical repair with injuries to the posterior superior vena cava and right ventricle. Both patients survived the initial injury with one patient was discharged home on day 4 and the other succumbing to his injuries on postoperative day 20. CONCLUSION: Although the incidence of surgical emergencies is rare the morbidity and mortality for TLE require that surgical backup be available.

Risk of Stroke with Impella Placement Is Not Associated with Access Vessel.

Objective: The Impella heart pump is an intravascular microaxial device that provides short-term mechanical circulatory support and can be placed through the femoral, axillary, or central vessels. One of the most feared complications is stroke. It is unclear if patient stroke risk varies based on access vessel. Methods: A retrospective review of consecutive patients who underwent Impella placement at an academic institution from January 1, 2007, through September 15, 2018, was performed. Four groups were compared: (1) minimally invasive Impella (femoral or axillary access), (2) minimally invasive Impella upgraded to another minimally invasive Impella, (3) minimally invasive Impella upgraded to a central Impella (ascending aorta), and (4) central Impella. Patient charts were reviewed to identify baseline characteristics. Outcome measures included length of stay, stroke, and mortality. Results: A total of 349 patients (or 407 Impellas) were identified, and the majority of the devices were inserted through a minimally invasive approach (n = 248, 60.9%), while the remainder were implanted via central access (n = 159, 39.1%). Minimally invasive Impellas were upgraded in 44 patients. The risk of stroke for the entire cohort was 10.3% (n = 36), with no difference observed in any particular group. Overall mortality was 44.4% (n = 155). Of the patients who initially received a minimally invasive Impella, those who were upgraded had higher rates of mortality (56.8% vs 39.4%, P = 0.03), postoperative dialysis (50.0% vs 27.4%, P < 0.01), and sepsis (43.2% vs 20.0%, P < 0.01). Conclusions: This study found no statistically significant difference in rates of postoperative stroke based on initial access vessel.

Contribution of NADPH oxidase to the retention of UVR-induced DNA damage by arsenic.

Arsenic is a naturally occurring element present in food, soil and water and human exposure is associated with increased cancer risk. Arsenic inhibits DNA repair at low, non-cytotoxic concentrations and amplifies the mutagenic and carcinogenic impact of other DNA-damaging agents, such as ultraviolet radiation (UVR). Arsenic exposure leads to oxidation of zinc coordinating cysteine residues, zinc loss and decreased activity of the DNA repair protein poly(ADP)ribose polymerase (PARP)-1. Because arsenic stimulates NADPH oxidase (NOX) activity leading to generation of reactive oxygen species (ROS), the goal of this study was to investigate the role of NOX in arsenic-induced inhibition of PARP activity and retention of DNA damage. NOX involvement in the arsenic response was assessed in vitro and in vivo. Keratinocytes were treated with or without arsenite, solar-simulated UVR, NOX inhibitors and/or isoform specific NOX siRNA. Knockdown or inhibition of NOX decreased arsenite-induced ROS, PARP-1 oxidation and DNA damage retention, while restoring arsenite inhibition of PARP-1 activity. The NOX2 isoform was determined to be the major contributor to arsenite-induced ROS generation and DNA damage retention. In vivo DNA damage was measured by immunohistochemical staining and analysis of dorsal epidermis sections from C57BI/6 and p91phox knockout (NOX2-/-) mice. There was no significant difference in solar-simulated UVR DNA damage as detected by percent PH2AX positive cells within NOX2-/- mice versus control. In contrast, arsenite-dependent retention of UVR-induced DNA damage was markedly reduced. Altogether, the in vitro and in vivo findings indicate that NOX is involved in arsenic enhancement of UVR-induced DNA damage.

Does supply meet demand? A comparison of perfusion strategies on cerebral metabolism in a neonatal swine model.

OBJECTIVE: We aimed to determine the effects of selective antegrade cerebral perfusion compared with other perfusion strategies on indices of cerebral blood flow, oxygenation, cellular stress, and mitochondrial function. METHODS: One-week-old piglets (n = 41) were assigned to 5 treatment groups. Thirty-eight were placed on cardiopulmonary bypass. Of these, 30 were cooled to 18°C and underwent deep hypothermic circulatory arrest (n = 10), underwent selective antegrade cerebral perfusion at 10 mL/kg/min (n = 10), or remained on continuous cardiopulmonary bypass (deep hypothermic cardiopulmonary bypass, n = 10) for 40 minutes. Other subjects remained on normothermic cardiopulmonary bypass (n = 8) or underwent sham surgery (n = 3). Novel, noninvasive optical measurements recorded cerebral blood flow, cerebral tissue oxyhemoglobin concentration, oxygen extraction fraction, total hemoglobin concentration, and cerebral metabolic rate of oxygen. Invasive measurements of cerebral microdialysis and cerebral blood flow were recorded. Cerebral mitochondrial respiration and reactive oxygen species generation were assessed after the piglets were killed. RESULTS: During hypothermia, deep hypothermic circulatory arrest piglets experienced increases in oxygen extraction fraction (P < .001), indicating inadequate matching of oxygen supply and demand. Deep hypothermic cardiopulmonary bypass had higher cerebral blood flow (P = .046), oxyhemoglobin concentration (P = .019), and total hemoglobin concentration (P = .070) than selective antegrade cerebral perfusion, indicating greater oxygen delivery. Deep hypothermic circulatory arrest demonstrated worse mitochondrial function (P < .05), increased reactive oxygen species generation (P < .01), and increased markers of cellular stress (P < .01). Reactive oxygen species generation was increased in deep hypothermic cardiopulmonary bypass compared with selective antegrade cerebral perfusion (P < .05), but without significant microdialysis evidence of cerebral cellular stress. CONCLUSIONS: Selective antegrade cerebral perfusion meets cerebral metabolic demand and mitigates cerebral mitochondrial reactive oxygen species generation. Excess oxygen delivery during deep hypothermia may have deleterious effects on cerebral mitochondria that may contribute to adverse neurologic outcomes. We describe noninvasive measurements that may help guide perfusion strategies.

Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine.

BACKGROUND: Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies. METHODS: Neonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements. RESULTS: Cerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26]; final: 0.45, [0.27, 0.74]; p = 0.02). LDx was not altered in those undergoing DHCA (p > 0.99) or SCP (p = 0.13). These differences were not explained by other risk factors. CONCLUSIONS: In a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not. IMPACT: Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

Short-term and intermediate outcomes of cardiogenic shock and cardiac arrest patients supported by venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Cardiogenic shock and cardiac arrest are life-threatening emergencies with high mortality rates. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (e-CPR) provide viable options for life sustaining measures when medical therapy fails. The purpose of this study is to determine the utilization and outcomes of VA ECMO and eCPR in patients that require emergent cardiac support at a single academic center. METHODS: A retrospective chart review of prospectively collected data was performed at an academic institution from January 1st, 2018 to June 30th, 2020. All consecutive patients who required VA ECMO were evaluated based on whether they underwent traditional VA ECMO or eCPR. The study variables include demographic data, duration on ECMO, length of stay, complications, and survival to discharge. RESULTS: A total of 90 patients were placed on VA ECMO for cardiac support with 44.4% (40) of these patients undergoing eCPR secondary to cardiac arrest and emergent placement on ECMO. A majority of the patients were male (n = 64, 71.1%) and the mean age was 58.8 ± 15.8 years. 44.4% of patients were transferred from outside hospitals for a higher level of care and 37.8% of patients required another primary therapy such as an Impella or IABP. The most common complication experienced by patients was bleeding (n = 41, 45.6%), which occurred less often in eCPR (n = 29, 58% vs. n = 12, 30%). Other complications included infections (n = 11, 12.2%), limb ischemia (n = 13, 14.4%), acute kidney injury (n = 17, 18.9%), and cerebral vascular accident (n = 4, 4.4%). The length of stay was longer for patients on VA ECMO (32.1 ± 40.7 days vs. 17.7 ± 18.2 days). Mean time on ECMO was 8.1 ± 8.3 days. Survival to discharge was higher in VA ECMO patients (n = 23, 46% vs. n = 8, 20%). CONCLUSION: VA ECMO provided an effective rescue therapy in patients in acute cardiogenic shock with a survival greater than the expected ELSO guidelines of 40%. While the survival of eCPR was lower than expected, this may reflect the severity of patient's condition and emphasizes the importance of careful patient selection and planning.

Arsenic co-carcinogenesis: Inhibition of DNA repair and interaction with zinc finger proteins.

Arsenic is widely present in the environment and is associated with various population health risks including cancers. Arsenic exposure at environmentally relevant levels enhances the mutagenic effect of other carcinogens such as ultraviolet radiation. Investigation on the molecular mechanisms could inform the prevention and intervention strategies of arsenic carcinogenesis and co-carcinogenesis. Arsenic inhibition of DNA repair has been demonstrated to be an important mechanism, and certain DNA repair proteins have been identified to be extremely sensitive to arsenic exposure. This review will summarize the recent advances in understanding the mechanisms of arsenic carcinogenesis and co-carcinogenesis, including DNA damage induction and ROS generation, particularly how arsenic inhibits DNA repair through an integrated molecular mechanism which includes its interactions with sensitive zinc finger DNA repair proteins.

Impact of risk factors on in-hospital mortality for octogenarians undergoing cardiac surgery.

BACKGROUND: Octogenarians undergoing cardiac surgery have higher mortality than their younger counterparts. OBJECTIVES: To determine if various risk factors have the same effect on mortality in octogenarians as in younger patients. METHODS: The National Inpatient Sample data set from 2004 to 2014 was queried to select patients aged 65 years and older who underwent either coronary artery bypass grafting (CABG), valvular heart surgery (VHS), or both (CABG + VHS) within 10 days of hospital admission. The patients were divided into two groups 65-79 years and 80 years and greater. Hospital mortality, patient demographics, comorbidities, and type of hospital admission was evaluated and compared using χ2 and multivariable logistic regressions. RESULTS: About 397,713 patients were identified including 86,345 (21.7%) aged 80 and above. Octogenarians had higher in-hospital mortality for all procedures: CABG (4.94% vs. 2.39%, p < .001), VHS (5.49% vs. 4.08%, p < .001), and CABG + VHS (7.59% vs. 5.95%, p < .001), and this relationship persisted when gender, race, comorbidities, and type of hospital admission were controlled for: CABG (odds ratio [OR] = 1.71; 95% confidence interval [CI] 1.62-1.81); VHS (OR = 1.18; 95% CI 1.11-1.27); and CABH + VHS (OR = 1.17; 95%CI 1.10-1.26). Female gender, renal, or heart failure, nonelective admission, and CABG + VHS were associated with increased risk of in-hospital mortality. Octogenarians had higher rates of these factors (p < .001). The effect size of renal and heart failure and type of surgery was smaller for octogenarians. CONCLUSIONS: Octogenarians undergoing cardiac surgery have higher rates of nonelective admissions, renal and heart failure, and female gender, which are most strongly associated with in-hospital mortality. Differing effect sizes suggest that certain risk factors, such as renal and heart failure, contribute more to mortality in younger patients.

A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation.

AIM: Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. METHODS: After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. RESULTS: During CPR, the iNO group had higher mean aortic pressure (41.6 ±â€¯2.0 vs. 36.0 ±â€¯1.4 mmHg; p = 0.005); diastolic BP (32.4 ±â€¯2.4 vs. 27.1 ±â€¯1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ±â€¯2.6 vs. 19.1 ±â€¯1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ±â€¯54.1 vs. 115.5 ±â€¯37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. CONCLUSIONS: Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass.

OBJECTIVES: Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS: Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS: There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P < 0.001) and maximal phosphorylating respiration capacity via convergent input through complexes I and II (OXPHOSCI+CII) (7.40 ± 0.24 vs 4-h CPB: 3.91 ± 0.20, P < 0.0001). At 4-h, experimental animals had significantly higher ROS related to non-phosphorylating respiration through complexes I and II (ETSCI+CII) than shams (1.08 ± 0.13 vs 0.64 ± 0.04, P = 0.026). CONCLUSIONS: Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.

Deep hypothermic circulatory arrest in cyanotic piglets is associated with increased neuronal necrosis.

BACKGROUND: The contribution of neonatal cyanosis, inherent to cyanotic congenital heart disease, to the magnitude of neurologic injury during deep hypothermic circulatory arrest has not been fully delineated. This study investigates the impact of cyanosis and deep hypothermic circulatory arrest on brain injury. METHODS: Neonatal piglets were randomised to placement of a pulmonary artery to left atrium shunt to create cyanosis or sham thoracotomy. At day 7, animals were randomised to undergo deep hypothermic circulatory arrest or sham. Arterial oxygen tension and haematocrit were obtained. Neurobehavioural performance was serially assessed. The animals were sacrificed on day 14. Brain tissue was assessed for neuronal necrosis using a 5-point histopathologic score. RESULTS: Four experimental groups were analysed (sham, n = 10; sham + deep hypothermic circulatory arrest, n = 8; shunt, n = 9; shunt + deep hypothermic circulatory arrest, n = 7). Cyanotic piglets had significantly higher haematocrit and lower partial pressure of oxygen at day 14 than non-cyanotic piglets. There were no statistically significant differences in neurobehavioural scores at day 1. However, shunt + deep hypothermic circulatory arrest piglets had evidence of greater neuronal injury than sham animals (median (range): 2 (0-4) versus 0 (0-0), p = 0.02). DISCUSSION: Cyanotic piglets undergoing deep hypothermic circulatory arrest had increased neuronal injury compared to sham animals. Significant injury was not seen for either cyanosis or deep hypothermic circulatory arrest alone relative to shams. These findings suggest an interaction between cyanosis and deep hypothermic circulatory arrest and may partially explain the suboptimal neurologic outcomes seen in children with cyanotic heart disease who undergo deep hypothermic circulatory arrest.

Epinephrine's effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation.

BACKGROUND: Despite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first. METHODS: One-month-old piglets (n = 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10-20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO2]) and noninvasive (diffuse correlation spectroscopy and diffuse optical spectroscopy) measurements of CBF and cerebral tissue oxygenation were simultaneously recorded. Effects of subsequent epinephrine doses were compared to the first. RESULTS: With the first epinephrine dose during CPR, CBF and cerebral tissue oxygenation increased by > 10%, as measured by each of the invasive and noninvasive measures (p < 0.001). The effects of epinephrine on CBF and cerebral tissue oxygenation decreased with subsequent doses. By the fifth dose of epinephrine, there were no demonstrable increases in CBF of cerebral tissue oxygenation. Invasive and noninvasive CBF measurements were highly correlated during asphyxia (slope effect 1.3, p < 0.001) and CPR (slope effect 0.20, p < 0.001). CONCLUSIONS: This model suggests that epinephrine increases CBF and cerebral tissue oxygenation, but that effects wane following the third dose. Noninvasive measurements of neurological health parameters hold promise for developing and directing resuscitation strategies.

Delay in coronary artery bypass grafting for STEMI patients improves hospital morbidity and mortality.

OBJECTIVES: The optimal timing of coronary artery bypass grafting (CABG) in patients with ST elevated acute myocardial infarction (STEMI) is unclear. The purpose of the study is to evaluate and compare the outcomes in STEMI patients who underwent CABG within the various time intervals within the first 7 days of either emergent or urgent hospital admission. METHODS: Patients aged 30 years old and older diagnosed with STEMI who underwent CABG within first 7 days after non-elective hospital admission were selected from the National Inpatient Sample 2010-2014 using the appropriate ICD-9-CM diagnosis and procedure codes. These patients were divided into 3 cohorts based on timing of surgery: within 24 h (group A), 2nd-3rd day (group B), and 4th-7th day (group C). The rates of postoperative complications, mortality, and postoperative hospital length of stay (LOS) were compared using the Chi-square test, multivariable logistic regression analysis, and Wilcoxon rank sum test. RESULTS: A total of 5963 patients were identified: group A = 28.5%, group B = 36.1%, group C = 35.4%. Mean age overall was 63.1 ± 11.1 years; 76.9% were males and 72.9% were whites. Compared to groups B and C, patients in group A were more likely to develop cardiac complications (OR [odds ratio] =1.33, 95%CI [confidence interval] 1.12-1.59 and OR = 1.39, 95%CI 1.17-1.67, respectively) and respiratory complications (OR = 1.31, 95%CI 1.13-1.51 and OR = 1.53, 95%CI 1.32-1.78, respectively). They were also more likely to have renal complications (OR = 1.31, 95%CI 1.11-1.54) and bleeding (OR = 1.20, 95%CI 1.05-1.37) than patients in group B and had a similar tendency compared to group C. We did not find significant differences in the above complications between groups B and C. Postoperative stroke and sternal wound infection rates were similar between all three groups. In-hospital mortality was also higher in group A (8.2%) compared to group B (3.5%) and group C (2.9%, P < 0.0001 for both); differences between groups B and C were not significant. This was confirmed in the multivariable logistic regression analysis with controlling for age, gender, race, the Elixhauser Comorbidity Index, and complications (group A vs B: OR = 1.85, 95%CI 1.52-2.25; group A vs C: OR = 2.21; 95%CI 1.82-2.68). Patients in group A had a significantly longer postoperative LOS (median 7 days with IQR [interquartile range] 5-10 days) compared to those in group B (median 6 days, IQR 5-8 days) and group C (median 6 days, IQR 4-8 days; P < 0.0001 for both). CONCLUSIONS: The results of this study show that despite the urgency and severity of STEMI, patients who undergo CABG within the first 24 h after non-elective hospital admission have increased hospital morbidity and mortality. These findings suggest that a delay in surgery beyond the first 24 h may be beneficial to patient outcomes. Furthermore, there is a significant cost effectiveness when the patients delay surgery because the hospital length of stay is reduced as well as the subsequent hospital costs.