Egidijus Semenas

Central nervous tissue damage after hypoxia and reperfusion in conjunction with cardiac arrest and cardiopulmonary resuscitation: mechanisms of action and possibilities for mitigation.

Only approximately 10% of patients encountering a cardiac arrest (CA) and subsequent cardiopulmonary resuscitation survive to a meaningful life. One of the most important causes for this low survival rate is the ischemia-reperfusion injury that hits the brain. This review summarizes some of the more important mechanisms causing cerebral injury. Thus, we describe some of our findings when performing genome-wide transcriptional profiling as well as histological and immunohistological staining of cerebral cortical areas. In order to shed some light on therapeutic opportunities, our findings relating to the use of induced mild hypothermia and methylene blue as neuroprotective agents are reviewed. Furthermore, we would like to share some interesting data on gender differences and effects of estrogen on the ensuing cerebral injury occurring after hypovolemic CA.

Sex differences in cerebral injury after severe haemorrhage and ventricular fibrillation in pigs

Background: Experimental studies of haemorrhagic shock have documented a superior haemodynamic response and a better outcome in female animals as compared with male controls. Such sexual dimorphism has, nevertheless, not been reported after circulatory arrest that follows exsanguination and shock. We aimed to study differences in cerebral injury markers after exsanguination cardiac arrest in pre‐pubertal piglets. The hypothesis was that cerebral injury is less extensive in female animals, and that this difference is independent of sexual hormones or choice of resuscitative fluid.

Sex differences in cardiac injury after severe haemorrhage and ventricular fibrillation in pigs

AIM OF THE STUDY Experimental studies have shown sex differences in haemodynamic response and outcome after trauma and haemorrhagic shock. We recently reported that female sex protects against cerebral injury after exsanguination cardiac arrest (CA), independent of sexual effects of hormones. The current study examines if female sex is also cardioprotective. METHODS In this study 21 sexually immature piglets (12 males and 9 females) were subjected to 5 min of haemorrhagic shock followed by 2 min of ventricular fibrillation and 8 min of cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3 ml kg(-1) hypertonic saline-dextran (HSD) solution for 20 min. Sexually immature animals were used to differentiate innate sex differences from the effects of sexual hormones. Sex differences in haemodynamics, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. RESULTS After resuscitation female animals had a higher blood pressure, lower heart rate, lower troponin I concentrations, and higher survival rate (100% and 63% in 3 h) despite comparable sex hormone levels. CONCLUSIONS After resuscitation from haemorrhage and circulatory arrest, haemodynamic parameters are better preserved and myocardial injury is smaller in female piglets. This difference in outcome is independent of sexual hormones.

Neuroprotective effects of 17β-estradiol after hypovolemic cardiac arrest in immature piglets: the role of nitric oxide and peroxidation.

We recently reported that cerebral and cardiac injuries are mitigated in immature female piglets after severe hemorrhage with subsequent cardiac arrest. Female sex was also associated with a smaller increase in the cerebral expression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). In the current study, we tested the hypothesis that exogenously administered 17&bgr;-estradiol (E2) can improve neurological outcome by NOS modulation. Thirty-nine sexually immature piglets were bled to a mean arterial pressure of 35 mmHg over 15 min. Fifty micrograms per kilogram of E2 was then administered to 10 male and 10 female animals (estradiol group), whereas control animals (n = 10 males and 9 females) received equal volume of normal saline. The animals were then subjected to ventricular fibrillation (4 min) followed by up to 15 min of open-chest cardiopulmonary resuscitation. Vasopressin 0.4 U · kg−1 and amiodarone 0.5 mg · kg−1 were given, and 3 mL · kg−1 of 7.5% saline with 6% dextran was administered over 20 min. All surviving animals were killed after 3 h, and their brains examined for histological injury and NOS expression. No significant differences were observed in survival or hemodynamics between the groups. Compared with the control group, animals in the E2 group exhibited a significantly smaller increase in nNOS and iNOS expression, a smaller blood-brain-barrier disruption, and a mitigated neuronal injury. There was a significant correlation between nNOS and iNOS levels and neuronal injury. Interestingly, estradiol attenuated cerebral damage (including lower activation of nNOS and iNOS) both in male and female piglets. In conclusion, in our immature piglet model of hypovolemic cardiac arrest, E2 downregulates iNOS and nNOS expression and results in decreased blood-brain-barrier permeability disruption and smaller neuronal injury.

Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest

Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia.

Adrenaline increases blood‐brain‐barrier permeability after haemorrhagic cardiac arrest in immature pigs

Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood–brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR.

Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest.

Long‐term survival after cardiac arrest (CA) due to shock‐refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.

Resuscitation with amiodarone increases survival after hemorrhage and ventricular fibrillation in pigs

Supplemental digital content is available in the text. BACKGROUND The aim of this experimental study was to compare survival and hemodynamic effects of a low-dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac arrest model in piglets. METHODS Eighteen anesthetized male piglets (with a weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15-minute period. Afterward, the piglets were subjected to 4 minutes of untreated ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was intravenously administered in the amiodarone group (n = 9), while the control group received the same amount of saline (n = 9). At the same time, all piglets received vasopressin 0.4 U/kg intravenously administered and hypertonic-hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation was attempted from 7 minutes of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 hours after resuscitation. RESULTS Three-hour survival was greater in the amiodarone group (p = 0.02). After the successful resuscitation, the amiodarone group piglets had significantly lower heart rate as well as greater systolic, diastolic, and mean arterial pressure. Troponin I plasma concentrations were lower and urine output was greater in the amiodarone group. CONCLUSION Combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters, and smaller myocardial injury compared with resuscitation with vasopressin only.

Modulation of nitric oxide expression with methylene blue does not improve outcome after hypovolemic cardiac arrest

AIM OF THE STUDY We recently reported that female sex protects against cerebral and cardiac injury after hypovolemic cardiac arrest (CA), independent of sex hormone effects. As female sex was also associated with a smaller increase in inducible and neuronal nitric oxide synthase (NOS), we hypothesised that nitric oxide inhibition with methylene blue (MB) improves the outcome, primarily in male animals. METHODS Twenty sexually immature piglets (10 males and 10 females) were bled to mean arterial blood pressure of 35mmHg, and were subjected to 2 min of untreated CA followed by 8 min of open chest cardiopulmonary resuscitation (CPR). Volume resuscitation was started during CPR with intravenous administration of 3mlkg(-1) hypertonic saline-dextran. Methylene blue was then administered as bolus of 2.5mgkg(-1) over 20 min, followed by 1.5mgkg(-1) infusion over 40 min. Historical data from 21 animals were used as control (no MB). Hemodynamic parameters, myocardial injury (troponin I), and short-term survival (3-h) were evaluated. Histopathological evaluation of heart specimens was performed. RESULTS There were no differences between male and female animals in survival or resuscitation rate. After CA female piglets had significantly greater systolic and mean arterial pressures, and had lower troponin I plasma concentrations compared to male piglets, with or without MB. No difference was observed in histopathological analysis of heart specimens between sexes. CONCLUSIONS After resuscitation from hypovolemic CA, female sex protects against cardiac injury, independent of sex hormones. Modulation of NO expression with MB does not improve survival or myocardial histological injury in either sex.

Combining functional dependency and ASA III classification for risk stratification-predictors, risk factors, and outcomes following major surgery study (NCT02626546)

Background: Postoperative complications increase the risk of death 2–3 years postoperatively. Prediction of complications can support clinical decisions. Before clinical use of any prediction model, validation is reasonable. We aimed to validatethree models: Revised Cardiac Risk Index (RCRI), ARISCAT and POSSUM.Methods: The PROF S-study was performed in four Swedish university hospitals. Patients werere cruited between 2015-11-01 and 2016-02-15. Inclusion criteria were adults, ASA classification ≥3, major/complex upper and lower gastrointestinal, urogenital or orthopedic surgery. Complications were screened on days 3, 7 and 10 by the postoperative morbidity survey (POMS). Only patients with grade≥2 (Clavien-Dindo classification) were accounted for. Study outcomes were cardiovascular (RCRI model) and pulmonary (ARISCAT model) complications, and a composite of the POMS domains (POSSUM model). Discrimination was evaluated by C-statistics (area under receiver operator characteristic curve; AUC ROC).Results: The number of patients included was 1089. Thirteen patients were excluded due to wrong inclusion, and another three were lost to follow-up. Presen ce of malignancy was 41%. Patient characteristics and outcomes are displayed in Table 1. The RCRI underestimated the risk for cardiovascular complications, and discrimination was low (AUC ROC 0.64; 95% CI 0.59–0.68). The prediction by the ARISCAT model was fair (AUC 0.72; CI 0.69–0.76). The POSSUM model had poor /fair discrimination (AUC 0.70; CI 0.67–0.73).Conclusions: The ARISCAT model predicted pulmonary complications with fair discrimina-tion and so could be used as decision support. Parameters with significant odds ratios of the RCRI and POSSU M models might be used as complements of clinical judgement.Background: In elderly reclassification of ASA3 class by functional dependency improved prediction of postoperative mortality. We hypothesized that such a reclassification could improve the risk pred ...