Remote ischemic preconditioning and hypoxia-induced biomarkers in acute myocardial infarction: study on a porcine model.

Objectives. Remote ischemic preconditioning (RIPC) mitigates acute myocardial infarction (AMI). We hypothesized that RIPC reduces the size and severity of AMI and explored molecular mechanisms behind this phenomenon. Design. In two series of experiments, piglets underwent 60 min of the circumflex coronary artery occlusion, resulting in AMI. Piglets were randomly assigned into the RIPC groups (n = 7 + 7) and the control groups (n = 7 + 7). The RIPC groups underwent four 5-min hind limb ischemia-reperfusion cycles before AMI. In series I, the protective efficacy of RIPC was investigated by using biomarkers and echocardiography with a follow-up of 24 h. In series II, the heart of each piglet was harvested for TTC-staining to measure infarct size. Muscle biopsies were collected from the hind limb to explore molecular mechanisms of RIPC using qPCR and Western blot analysis. Results. The levels of CK-MBm (p = 0.032) and TnI (p = 0.007) were lower in the RIPC group. Left ventricular ejection fraction in the RIPC group was greater at the end of the follow-up. The myocardial infarct size in the RIPC group was smaller (p = 0.033). Western blot indicated HIF1α stabilization in the skeletal muscle of the RIPC group. PCR analyses showed upregulation of the HIF target mRNAs for glucose transporter (GLUT1), glucose transporter 4 (GLUT4), phosphofructokinase 1 (PFK1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), enolase 1 (ENO1), lactate dehydrogenase (LDHA) and endothelial nitric oxidate synthase (eNOS). Conclusions. Biochemical, physiologic, and histologic evidence confirms that RIPC decreases the size of AMI. The HIF pathway is likely involved in the mechanism of the RIPC.

Ultrasound-guided closure of the femoral artery during venoarterial decannulation using a large-bore closure device.

BACKGROUND: Peripheral femoro-femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is viable for fast hemodynamic assistance during cardiogenic shock. Ultrasound-guided closure with a large-bore device (MANTA®) is a feasible option potentially replacing surgical arteriotomy closure in peripheral VA-ECMO decannulation. METHODS: This retrospective study included patients weaning from percutaneously inserted femoro-femoral VA-ECMO at the Helsinki University Hospital, Finland in 2012-2020. The primary endpoints were access-site complications, a composite of hematomas/seromas/surgical site infections (SSIs), and the safety endpoint of vascular complications (VCs). RESULTS: A total of 100 consecutive percutaneously implanted and weaned VA-ECMO patients were stratified into two groups by decannulation strategy: percutaneous ultrasound-guided MANTA device (n = 21, 21.0%) or surgical approach (n = 79, 79.0%). The mean age of the cohort was 51 ± 13 years and females represented 25.0%. The technical success rate of the percutaneous ultrasound-guided MANTA technique was 95.2%. In multivariate analysis, surgical closure was associated with a higher incidence of combined access site hematomas/seromas/SSIs compared to percutaneous ultrasound-guided deployment of MANTA device (44.3% versus 9.5%, odds ratio (OR): 7.162, 95% confidence interval (CI): 1.544-33.222; p = 0.012). Similarly, access-site complications necessitating interventions were more frequent in the surgical closure group compared to US-MANTA (ultrasound-guided MANTA) group (26.6% versus 0.0%, p = 0.005). VCs were infrequent in both groups without any significant intergroup difference (p > 0.99). CONCLUSIONS: Percutaneous ultrasound-guided MANTA closure of the femoral artery after VA-ECMO decannulation was associated with high technical success rate and low incidence of VCs. Compared to surgical closure, access-site complications were significantly less frequent, along with access-site complications necessitating interventions.

Impact of high-risk features on outcome of acute type B aortic dissection.

Background: Acute type B aortic dissection (TBAD) is a severe condition associated with significant morbidity and mortality. The optimal classification and treatment strategy of TBAD remain controversial and inconsistent. Methods: This analysis includes patients treated for acute TBAD at the Helsinki University Hospital, Finland between 2007 and 2019. The endpoints were early and late mortality, intervention of the aorta, and a composite of death and aortic intervention in uncomplicated patients and high-risk patients. Results: This study included 162 consecutive TBAD patients (27.8% females), 114 in the high-risk group and 48 in the uncomplicated group, with a mean age of 67.6 ± 13.9 years. Intramural hematoma was reported in 63 cases (38.9%). The mean follow-up was 5.1 ± 3.9 years. In-hospital/30-day mortality (n = 4; 3.5%) occurred solely in the high-risk group (P = .32). Additionally, TBAD-related adverse events (n = 23; 20.2%) were observed only in the high-risk group (P < .001). The cumulative incidences of the composite TBAD outcome with non-TBAD-related death as a competing risk were 6.6% (95% CI, 1.7%-16.5%) in the uncomplicated group and 29.5% (95% CI, 21.1%-38.3%) in the high-risk group at 5 years and 6.6% (95% CI, 1.7%-16.5%) and 33.0% (95% CI, 23.7%-42.6%) at 10 years (P = .001, Gray test). Extracardiac arteriopathy (subdistribution hazard ratio [SHR], 2.61; 95% CI, 1.08-6.27) and coronary artery disease (SHR, 2.24; 95% CI, 1.07-4.71) were risk factors for adverse aortic-related events in univariable competing-risk regression analysis. Conclusions: Recognition of risk factors underlying adverse events related to TBAD is essential because the disease progression impacts both early and late outcomes. Early aortic repair in high-risk TBAD may reduce long-term morbidity and mortality.

Preparing the spinal cord - priming or preconditioning? A systematic review of experimental studies.

Objectives. Paraplegia is devastating complication associated with thoracic and thoracoabdominal aortic aneurysm repair. Vast evidence has been gathered on pre-, peri- and postoperative protective adjuncts aiming to minimize spinal cord ischemia. This review focuses on the pretreatment phase of open surgical or endovascular aortic procedures and gathers the experimental data on the interventional preconditioning and priming methods that increase the spinal cord ischemic tolerance. Design. By the start of March 2021, a systematic review was performed in PubMed, Scopus and Web of Science core collection to identify the articles that reported (i) either an ischemic preconditioning, remote ischemic preconditioning or priming method prior to (ii) experimental spinal cord ischemia performed in endovascular or open surgical fashion mimicking either thoracic, abdominal or thoracoabdominal aortic aneurysm procedures. (iii) The outcomes were reported via neurological, motor-evoked potential, somatosensory-evoked potential, histopathological, immunohistochemical, physiological analysis, or in different combinations of these measurements. Results. The search yielded 7802 articles, and 57 articles were included in the systematic review. The articles were assessed by the evaluated species, the utilized pretreatment, the measured protective effects, and the suggested underlying mechanisms. Conclusions. The reviewed articles showed several possible mechanisms in ischemic and remote ischemic preconditioning for prevention of spinal cord ischemia. The main suggested method for priming was arteriogenetic stimulus. Future studies should confirm these hints of arteriogenetic stimulus with more precise quantification of the protective recruitment process.

13-year single-center experience with the treatment of acute type B aortic dissection.

Background. Acute type B aortic dissection (TBAD) is catastrophic event associated with significant mortality and lifelong morbidity. The optimal treatment strategy of TBAD is still controversial. Methods. This analysis includes patients treated for TBAD at the Helsinki University Hospital, Finland in 2007-2019. The endpoints were early and late mortality, and intervention of the aorta. Results. There were 205 consecutive TBAD patients, 59 complicated and 146 uncomplicated patients (mean age of 66 ± 14, females 27.8%). In-hospital and 30-day mortality rates were higher in complicated patients compared with uncomplicated patients with a statistically significant difference (p = 0.035 and p = 0.015, respectively). After a mean follow-up of 4.9 ± 3.8 years, 36 (25.0%) and 22 (37.9%) TBAD -related adverse events occurred in the uncomplicated and complicated groups, respectively (p = 0.066). Freedom from composite outcome was 83 ± 3% and 69 ± 6% at 1 year, 75 ± 4% and 63 ± 7% at 5 years, 70 ± 5% and 59 ± 7% at 10 years in the uncomplicated group and in the complicated group, respectively (p = 0.052). There were 25 (39.1%) TBAD-related deaths in the overall series and prior aortic aneurysm was the only risk factor for adverse aortic-related events in multivariate analysis (HR 3.46, 95% CI 1.72-6.96, p < 0.001). Conclusion. TBAD is associated with a significant risk of early and late adverse events. Such a risk tends to be lower among patients with uncomplicated dissection, still one fourth of them experience TBAD-related event. Recognition of risk factors in the uncomplicated group who may benefit from early aortic repair would be beneficial.

Impact of distal aortic perfusion on 'segmental steal' depleting spinal cord blood flow-a quantitative experimental approach.

OBJECTIVES: Aortic steal is an underestimated risk factor for intraoperative spinal cord ischaemia. A negative effect on spinal cord perfusion in thoraco-abdominal aneurysm repair has been suspected if blood drains away from the cord initiated by a reversal of the arterial pressure gradient. The amount of blood and pressure loss via back-bleeding of segmental arteries and the impact of distal aortic perfusion (DaP) have not been analysed yet. The aim of our study was to quantify 'segmental steal' in vivo during simulated thoraco-abdominal aneurysm repair and to determine the impact of DaP on steal and spinal cord perfusion. METHODS: Ten juvenile pigs were put on cardiopulmonary bypass with DaP and visceral arteries were ligated. 'Segmental steal' was quantified by draining against gravity with/without DaP. Blood volume of 'segmental steal' was quantified and microspheres were injected for Post mortem spinal cord perfusion analysis. 'Segmental steal' was quantified with/without DaP-and with stopped DaP. RESULTS: Quantification revealed a significantly higher steal on cardiopulmonary bypass with DaP with a mean difference of 24(11) ml/min. In all spinal cord segments, blood flow was diminished during steal drainage on DaP, compared to 'no steal'. The least perfused region was the low thoracic to upper lumbar segment. CONCLUSIONS: 'Segmental steal' is a relevant threat to spinal cord perfusion-even with the utilization of DaP-diminishing spinal cord perfusion. The blood volume lost by back-bleeding of segmental arteries is not to be underestimated and occlusion of segmental arteries should be considered in thoraco-abdominal aneurysm repair.

Priming protects the spinal cord in an experimental aortic occlusion model.

OBJECTIVES: Paraplegia is a devastating complication in aortic aneurysm surgery. Modifying the spinal cord vasculature is a promising method in spinal cord protection. The aim of this study was to assess whether the spinal cord can be primed by occluding thoracic segmental arteries before simulated aneurysm repair in a porcine model. METHODS: Twelve piglets were randomly assigned to the priming group (6) and the control group (6). Eight uppermost thoracic segmental arteries were occluded at 5-minute intervals in the priming group before a 25-minute aortic crossclamp. In the control group, the aorta was crossclamped for 25 minutes. During the first 5 minutes, 8 segmental arteries were occluded. After the aortic crossclamping, piglets were observed under anesthesia for 5 hours and followed up 5 days postoperatively. Near-infrared spectroscopy, motor-evoked potentials, blood samples, neurology with the modified Tarlov score, and histopathology of the spinal cord were assessed. RESULTS: The median Tarlov score during the first postoperative day was higher in the priming group than in the control group (P = .001). At the end, 50% of the control animals had paraplegia compared with 0% of paraplegia in the priming group. The mean regional histopathologic score differed between the priming group and the control group (P = .02). The priming group had higher motor-evoked potentials during the operation at separate time points. The lactate levels were lower in the priming group compared with the control group (Pg = .001, Pg×t = .18). CONCLUSIONS: Acute priming protects the spinal cord from ischemic injury in an experimental aortic crossclamp model.

Effect of cerebrospinal fluid pressure elevation on spinal cord perfusion during aortic cross-clamping with distal aortic perfusion.

OBJECTIVES: Distal aortic perfusion (DaP) is a widely accepted protective adjunct facilitating early reinstitution of visceral perfusion during extended thoracic and thoraco-abdominal aortic repair. DaP has also been suggested to secure distal inflow to the paraspinal collateral network via the hypogastric arteries and thereby reduce the risk of spinal cord ischaemia. However, an increase in cerebrospinal fluid (CSF) pressure is frequently observed during thoracoabdominal aortic aneurysm repair. The aim of this study was to evaluate the effects of DaP on regional spinal cord blood flow (SCBF) during descending aortic cross-clamping and iatrogenic elevation of cerebrospinal fluid pressure. METHODS: Eight juvenile pigs underwent central cannulation for cardiopulmonary bypass according to our established experimental protocol followed by aortic cross-clamping of the descending thoracic and abdominal aorta-mimicking sequential aortic clamping-with the initiation of DaP. Thereafter, CSF pressure elevation was induced by the infusion of blood plasma until baseline CSF pressure was tripled. At each time-point, microspheres of different colours were injected allowing for regional SCBF analysis. RESULTS: DaP led to a pronounced hyperperfusion of the distal spinal cord [SCBF up to 480%, standard deviation (SD): 313%, compared to baseline]. However, DaP provided no or only limited additional flow to the upper and middle segments of the spinal cord (C1-Th7: 5% of baseline, SD: 5%; Th8-L2: 24%, SD: 39%), which was compensated by proximal flow only at C1-Th7 level. Furthermore, DaP could not counteract an experimental CSF pressure elevation, which led to a further decrease in regional SCBF most pronounced in the mid-thoracic spinal cord segment. CONCLUSIONS: Protective DaP during thoraco-abdominal aortic repair may be associated with inadequate spinal protection particularly at the mid-thoracic spinal cord level ('watershed area') and result in the adverse effect of a potentially dangerous hyperperfusion of the distal spinal cord segments.

Alcohol consumption is associated with a later need for ICU admission: a Northern Finland Birth Cohort 1966-study.

BACKGROUND: Alcohol-related problems are common in intensive care unit (ICU) admitted patients. The aim of the present study is to assess the impact of alcohol consumption on the need of intensive care in 19 years follow-up period. METHODS: The study population consists of Northern Finland Birth Cohort 1966 participants, who responded alcohol-related questions at 31 years of age and Intensive Care Unit (ICU admissions from 1997 to 2016. RESULTS: There were a total of 8379 assessed people and 136 (1.6%) of them were later admitted to ICU. A total of 44 (32.4%) of the ICU-admitted persons had their alcohol consumption at the highest quartile of the cohort (P = 0.047). These patients had a lower number of malignancy-related admissions (3.6% versus 14.0%, P = 0.027), neurological admissions (14.3 versus 30.6%, P = 0.021), and were more often admitted due to poisonings (12.5% versus 5.0%, P = 0.07). There were no differences in 28-day post-ICU mortality but long-term mortality of ICU-admitted patients with lower alcohol consumption was higher than non-ICU-admitted population. CONCLUSION: Among ICU-admitted population, there was higher alcohol consumption at age of 31 years. People in the lower alcohol consumption quartiles were more often admitted to ICU due to malignancy-related causes and they had higher long-term mortality.

Treatment profile and long-term outcome of intensive care unit-admitted patients with liver cirrhosis or other liver disease in relation to alcohol consumption.

OBJECTIVE: To examine the impact of alcohol consumption on the treatment profile, mortality and causes of death in intensive care unit (ICU)-admitted patients with liver cirrhosis and other liver disease. METHODS: Data on liver disease and ICU treatment of patients with previously diagnosed liver disease between 2015 and 2017 were retrospectively collected from medical records at Oulu University Hospital, Finland. The median follow-up was 367 days. The causes of death were obtained from Statistics Finland. RESULTS: From 250 patients, high-risk alcohol consumption was present in 74.7% (71 of 95) cirrhotic patients and 43.2% (67 of 155) patients in the other liver disease group. Gastrointestinal causes were the most common admission causes. Despite the higher SOFA scores in the alcoholic liver cirrhosis patients compared with the non-alcoholic cirrhosis, there were no differences in the need for organ support, length of ICU stay or outcome between the groups or the subgroups. There were no differences in 1-year mortality between the cirrhosis groups (alcoholic cirrhosis 43.7% versus non-alcoholic cirrhosis 45.8%, p = 1.0) or between the other liver disease groups (patients with alcohol consumption 37.3% versus patients without alcohol consumption 36.4%, p = 1.0). The patients with high-risk alcohol consumption died more often due to liver disease, whereas the patients without high-risk alcohol consumption died often due to malignancies. CONCLUSIONS: We report no significant impact of alcohol consumption on the ICU treatment profile or mortality of patients with cirrhosis or other liver disease. The high mortality underlines the importance of preventive measures after ICU admission.

Remote Ischemic Preconditioning in Spinal Cord Protection: A Surviving Porcine Study.

Surgical repair of thoracic aorta can compromise blood flow of the spinal cord. To mitigate spinal cord ischemia (SCI) additional protection methods are needed. In experimental studies remote ischemic preconditioning (RIPC) has proven to be an effective method of protecting organs from ischemia. The aim of the study was to assess efficacy of RIPC in spinal cord protection in a chronic porcine model. Sixteen piglets were assigned into the RIPC group (8) and the control group (8). RIPC was performed using blood pressure cuff in a 5-minute ischemia followed by a 5-minute reperfusion repeating cycles 4 times. The left subclavian artery and all segmental arteries above diaphragm were ligated at 5-minute intervals to accomplish SCI. The follow-up comprised a 4-hour intensive monitoring and a 7-day recovery phase. Blood samples were obtained, motor-evoked potentials and near-infrared spectroscopy (NIRS) of longitudinal back muscles were measured. Paraplegia was assessed every day postoperatively. Histopathological analysis of the spinal cord was performed after 7 days. NIRS values 4 hours after SCI were higher in the RIPC group, 45.5 (44.5-47.0), than in the control group, 41.5 (40.5-44.0) (P = 0.042). Nadir value of NIRS was 43.4 (39.3-46.0) in the RIPC group and 38.9 (38.-40.0) in the control group (P = 0.014). On the first postoperative day the RIPC group reached modified Tarlov score of 3 (2-3) vs 2 (1-2) in the control group (P = 0.024). RIPC hastens the recovery from SCI during the first postoperative day.

Characteristics of subjects with alcoholic cardiomyopathy and sudden cardiac death.

OBJECTIVE: To study social and clinical characteristics of victims of sudden cardiac death (SCD) due to alcoholic cardiomyopathy (ACM). METHODS: The study population comprised a subset of Fingesture cohort. All subjects were verified SCD victims determined to have ACM as cause of death in medico-legal autopsy between 1998 and 2017 in Northern Finland. The Finnish Population Register Centre provided SCD victims' last place of residence. Population data of residential area were obtained from Statistics Finland. RESULTS: From a total of 5869 SCD victims in Fingesture cohort, in 290 victims the cause of SCD was ACM (4.9%; median age 56 (50-62) years; 83% males). In 64 (22.1%) victims, the diagnosis of cardiac disease was made prior to death and in 226 (77.9%) at autopsy. There were no significant differences in autopsy findings between victims with or without known cardiac diagnosis, but steatohepatitis (94.5%) and liver cirrhosis (64,5%) were common in both groups. Alcoholism was more often recorded in the known cardiac disease group (64.1% vs 47.3%, p=0.023). Majority were included in the working age population (ie, under 65 years) (54.8% and 53.1%, p=0.810). In high-income communities, 28.8% of ACM SCD victims had previously diagnosed cardiac disease, the proportion in the middle-income and low-income communities was 18.6% (p=0.05). CONCLUSIONS: Majority of SCD victims due to ACM did not have previously diagnosed cardiac disease, but documented risk consumption of alcohol was common. This emphasises the importance of routine screening of alcohol consumption and signs of cardiomyopathy in heavy alcohol users in primary healthcare.

Remote ischaemic preconditioning may prolong permissible period of hypothermic circulatory arrest in a porcine model.

Objectives. The hypothermic circulatory arrest (HCA) is still of paramount importance in aortic arch surgery, but the safe period of the arrest is limited. Remote ischaemic preconditioning (RIPC) prepares the cerebral tissue for ischaemic insult. Prolongation of the permissible period of HCA with RIPC may have a major impact on the outcome of aortic operations requiring cessation of blood flow by decreasing the rate of neurological deficits. Design. Twenty pigs were randomised into the RIPC group (n = 10) and the control group (n = 10). The RIPC group underwent four cycles of transient hind limb ischaemia. Both groups underwent cooling with cardiopulmonary bypass to 11 °C followed by a 45-minute HCA and re-warming to 36 °C. Cerebral blood flow was measured with a transit time ultrasonic flowmeter from the right common carotid artery, and the arteriovenous oxygen difference was calculated from sagittal sinus and arterial blood samples. Measurements were taken at several time points during cooling and warming. Temperature coefficient (Q10) was calculated to determine estimated permissible periods of HCA. Results. The Q10 was 2.27 (1.98-2.58) for the RIPC group and 1.87 (1.61-2.25) for the control group. The permissible period of HCA at 18 °C was 26 minutes (20-33) in the RIPC group and 17 minutes (13-25) in the control group (p = .063)(Data expressed in medians and interquartile ranges). Conclusions. RIPC tends to suppress cerebral metabolism during cooling with cardiopulmonary bypass and may prolong estimated permissible period of HCA.

Immunohistochemical Analysis of the Spinal Cord Ischemia- Effect of Remote Ischemic Preconditioning in a Porcine Model.

BACKGROUND: In experimental settings, remote ischemic preconditioning (RIPC) has shown a positive effect regarding spinal cord protection after local ischemia. In this study, we conducted spinal cord immunohistochemistry to demonstrate the protective effect of RIPC after 24 hours of the regional ischemia. Methods: Twenty piglets were randomized into an RIPC group (n = 10) and a control group (n = 10). The RIPC group underwent transient left hind limb ischemia before systematic left subclavian artery and segmental artery occlusion at the level of the diaphragm. Twenty-four hours later, the thoracic and lumbar spinal cords were harvested, and the oxidative stress markers were immunohistochemically analysed. Results: A total of 18 animals survived the 4-hour follow up (10 in the RIPC group, 8 in the control group) and 14 animals survived the 24-hour follow up (7 in each group). In the single sections of the spinal cord, the antioxidant pathway activation was seen in the RIPC group, as OGG1 and DJ-1/PARK7 activation was higher (P = .038 and P = .047, respectively). Conclusions: The results indicate that the neuroprotective effect of RIPC on the spinal cord after local ischemic insult remains controversial.

Diazoxide Attenuates Ischemic Myocardial Injury in a Porcine Model.

BACKGROUND: We hypothesized that diazoxide, a mitochondrial ATP-sensitive potassium channel opener, has cardioprotective effects during acute myocardial ischemia. Diazoxide is suggested to act through protein kinase Cε (PKCε) activation. METHODS: Twelve piglets were randomly assigned to receive intravenous infusion of diazoxide (3.5 mg/kg) with solvent or only solvent (6 animals per group) before cardiac ischemia. Myocardial ischemia was induced by occluding the left circumflex artery (LCX) for 40 minutes. The reperfusion and follow-up period lasted for three hours. Throughout the experiment hemodynamic measurements and blood samples were collected, and after the follow-up period the hearts were harvested for transmission electron microscopy (TEM) as well as histopathological and immunohistochemical analyses. RESULTS: TEM showed less ischemic damage on a cellular level in the diazoxide group (P = .004) than in the control group. Creatinine kinase MB levels (Pt*g = .030) were lower, and oxygen consumption (Pt*g = .037) and delivery (Pg = .038) were higher in the diazoxide group compared to the controls. CONCLUSION: Diazoxide preserves myocardial cellular structure and cellular function, and thus it may have benefits in treating ischemic myocardial injury.

Pharmacological Preconditioning with Diazoxide in the Experimental Hypothermic Circulatory Arrest Model.

BACKGROUND: Hypothermic circulatory arrest includes a remarkable risk for neurological injury. Diazoxide, a mitochondrial adenosine triphosphate-dependent potassium ion (K+ATP) channel opener, is known to have cardioprotective effects. We assessed its efficacy in preventing ischemic injury in a clinically relevant animal model. Methods: Eighteen piglets were randomized into a diazoxide group (n = 9) and a control group (n = 9). Animals underwent 60 minutes of hypothermic circulatory arrest at 18°C. Diazoxide (5 mg/kg + 10 mL NaOH + 40 mL NaCl) was infused during the cooling phase. Metabolic and hemodynamic data were collected throughout the experiment. After 24-hour follow-up, whole brain, heart, and kidney biopsy specimens were collected for analysis. Results: Cerebellar Cytochrome-C and caspase-3 activation was higher in the control group (P = .02 and P = .016, respectively). Antioxidant activity tended to be higher in the diazoxide group (P = .099). Throughout the experiment, the oxygen consumption ratio was higher in the control animals (Pg = .04), as were the lactate levels (Pg = .02). Cardiac function tended to be better in diazoxide-treated animals. Conclusion: Diazoxide might confer neuroprotective effect as implied by the immunohistochemical analysis of the brain. Additionally, the circulatory effects of diazoxide were beneficial, supporting its neuroprotective effect.

Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest.

OBJECTIVES: During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA. DESIGN: Twenty-two pigs were randomized into the RIPC group (n = 11) and the control group (n = 11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60 min DHCA at 18 °C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses. RESULTS: Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4 hours of the arrest, (p < .05). Systemic lactate levels were lower and cardiac index was higher in the RIPC group postoperatively. Immunohistochemical cerebellum regional scores of antioxidant response regulator Nrf2 were better in the RIPC group (mean: 1.1, IQR: 0.0-2.5) compared with the control group (mean: 0.0, IQR: 0.0-0.0), reaching borderline statistical significance (p = .064). RIPC induced detectable modulations of plasma proteome and metabolites. CONCLUSIONS: The faster recovery of S100B, lower systemic lactate levels and favourable regional antioxidant response suggest possible neuronal cellular and mitochondrial protection by RIPC, whereas better cardiac index underlines functional effects of RIPC. The exact humoural factor remains unclear.

Exploring Spinal Cord Protection by Remote Ischemic Preconditioning: An Experimental Study.

BACKGROUND: Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. METHODS: The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery. All animals underwent systematic closure of the left subclavian artery and segmental arteries of the descending thoracic aorta to the level of diaphragm. Motor-evoked potential monitoring was performed in both hind limbs. Continuous electrocardiogram and hemodynamics were monitored, and pulmonary artery blood samples were collected. A neurologic assessment was performed 6 hours after the procedure. The thoracic and lumbar portions of the spinal cord were collected for histologic and immunohistochemical analysis. RESULTS: The bilateral motor-evoked potential amplitude responses were higher in the RIPC group (p < 0.05) than in the control group; the difference was detected already before spinal cord ischemia. Paraplegia occurred in 1 control animal. Immunohistochemical total scores of antioxidant response regulator nuclear factor erythroid 2-related factor 2 were better in the RIPC group (11.0; range, 8.5 to 14.0) than in the control group (5.2; range, 1.0 to 9.0; p = 0.023). CONCLUSIONS: RIPC induces electrophysiologic changes in the central nervous system that may confer spinal cord protection extending the resistance to ischemia. The significantly higher nuclear factor erythroid 2-related factor 2 scores suggest better neuronal cell protection against oxidative stress in the RIPC group.

Review of remote ischemic preconditioning: from laboratory studies to clinical trials.

In remote ischemic preconditioning (RIPC) short periods of non-lethal ischemia followed by reperfusion of tissue or organ prepare remote tissue or organ to resist a subsequent more severe ischemia-reperfusion injury. The signaling mechanism of RIPC can be humoral communication, neuronal stimulation, systemic modification of circulating immune cells, and activation of hypoxia inducible genes. Despite promising evidence from experimental studies, the clinical effects of RIPC have been controversial. Heterogeneity of inclusion and exclusion criteria and confounding factors such as comedication, anesthesia, comorbidities, and other risk factors may have influenced the efficacy of RIPC. Although the cardioprotective pathways of RIPC are more widely studied, there is also evidence of benefits in CNS, kidney and liver protection. Future research should explore the potential of RIPC, not only in cardiac protection, but also in patients with threatening ischemia of the brain, organ transplantation of the heart, liver and kidney and extensive cardiovascular surgery. RIPC is generally well-tolerated, safe, effective, and easily feasible. It has a great prospect for ischemic protection of the heart and other organs.