Min Of Cardiac Arrest Research Articles

A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest

To date there has been no reliable noninvasive real time monitoring available to determine cerebral perfusion during cardiac arrest. ObjectivesTo investigate the feasibility of using a commercially available cerebral oximeter during in-hospital cardiac arrest, and determine whether this parameter predicts return of spontaneous circulation (ROSC). MethodsCerebral oximetry was incorporated in cardiac arrest management in 19 in-hospital cardiac arrest cases, five of whom had ROSC. The primary outcome measure was the relationship between rSO2 and ROSC. ResultsThe use of cerebral oximetry was found to be feasible during in hospital cardiac arrest and did not interfere with management. Patients with ROSC had a significantly higher overall mean±SE rSO2 (35±5 vs. 18±0.4, p<0.001). The difference in mean rSO2 between survivors and non-survivors was most pronounced in the final 5min of cardiac arrest (48±1 vs. 15±0.2, p<0.0001) and appeared to herald imminent ROSC. Although spending a significantly higher portion of time with an rSO2>40% was found in survivors (p<0.0001), patients with ROSC had an rSO2 above 30% for >50% of the duration of cardiac arrest, whereas non-survivors had an rSO2 that was below 30%>50% of their cardiac arrest. Patients with ROSC also had a significantly higher change in rSO2 from baseline compared to non-survivors (310%±60% vs. 150%±27%, p<0.05). ConclusionCerebral oximetry may have a role in predicting ROSC and the optimization of cerebral perfusion during cardiac arrest.

Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice

Background: Since genetically engineered mice are becoming more and more available, these animals become of high interest to study physiologic and pathophysiologic pathways of brain ischemia. The aim of this study was to examine body temperature (Tb), physical activity variation and neurohistopathology in mice exposed to normothermic and hyperthermic cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Methods: Male C57Bl/6 mice weighing 22 - 27 g were implanted intraperitoneally with a radio telemeter and subjected to 10 min cardiac arrest followed by cardiopulmonary resuscitation. Normothermia (37.5°C) or hyperthermia (39.0°C) was induced by controlling pericranial temperature during the arrest period. Results: Hyperthermia during the arrest resulted in a Tb decrease during early recovery to a nadir of 28°C ± 0.8°C (mean ± SE) and partially recovered to 34.4°C ± 1°C 36 hrs after CA/CPR. With normothermia during the arrest, Tb depression was less pronounced (nadir of 32.3°C ± 0.3°C) and recovered to physiologic levels within 24 hrs. Coupling of physical activity and body temperature was absent in all animals after CA/CPR. Neuronal injury in the caudoputamen was greater in the hyperthermia group. Conclusions: This study demonstrates that CA/CPR eliminates normal connectivity between body temperature and physical activity and induces long-lasting hypothermia, the depth of which is related to severity of brain injury. Long term temperature monitoring is required in survival murine experiments, if body temperature is a study variable.

Post-cardiac arrest hyperoxia and mitochondrial function

Introduction Rapid post-ischemic re-oxygenation is necessary to minimize ischemic injury, but itself can induce further reperfusion injury through the induction of reactive oxygen species. Utilization of oxygen within the cell primarily occurs in the mitochondria. The objective of this study was to determine heart mitochondrial function after 1 h of controlled arterial oxygenation following cardiac arrest and restoration of spontaneous circulation (ROSC). We hypothesized that arterial hyper-oxygenation following ROSC would result in greater impairment of heart mitochondrial function. Methods KCl cardiac arrest was induced in anesthetized rats. Following 6.5 min of cardiac arrest, animals were resuscitated with standard thumper CPR, ventilation and epinephrine. Following ROSC, all animals were ventilated for 60 min with either 100% O 2 or 40% O 2 titrated to achieve normoxia utilizing pulse oximetry. At the end of 1 h, heart mitochondria were isolated and mitochondrial respiratory function was measured. Results Post-ROSC arterial PaO2 was 280 ± 40 in the 100% O2 group and 105 ± 10 in the 40% O2 group. One hour after ROSC, heart mitochondrial state 3 respirations and respiration control ratio (state 3/4 respiration) were significantly reduced from baseline in animals ventilated with 100% O 2, but not with 40% O 2. Conclusion Post-ROSC arterial hyperoxia after a short cardiac arrest exacerbates impaired mitochondrial function. The overall clinical significance of these findings is unclear and requires additional work to better understand the role of post-arrest hyperoxia on cardiac and mitochondrial function.

Abstract 17446: Intra-arrest Hypothermia Protection Requires Endothelial Nitric Oxide Synthase

Introduction: Intra-arrest hypothermia (IH), cooling the body to 30 - 32°C during cardiac arrest, has previously been shown as protective in a mouse model of cardiac arrest. Hypothermia has also been shown to protect cultured cardiomyocytes exposed to simulated ischemia/reperfusion (I/R) in a nitric oxide synthase-dependent manner. However, the effect of IH on NOS signaling in whole animal models of cardiac arrest has not been studied. We hypothesized that mice deficient in endothelial NOS (NOS3) would not be protected by IH following cardiac arrest. Furthermore, we hypothesized that IH would alter NOS3 signaling in WT mouse hearts. METHODS: Adult NOS3 -/- (B6.129P2-Nos3tm1Unc/J, n = 30) and WT (C57Bl/6J, n = 24) mice underwent 8 min of cardiac arrest. At 6 min, mice were randomized to normothermia (NT, 37°C) or IH (30°C) followed by re-warming to 37°C at 60 min post-ROSC. Animals were hemodynamically monitored for 2 h and then neurologically scored at regular intervals up to 48 h. In separated experiments, cardiac NOS3 signaling was evaluated in similarly randomized mice at the end of the arrest period. RESULTS: In NOS3-/- mice, IH and NT groups had similar 48 h neurologically-intact survival rates (20 % vs. 0%, p=0.80). By contrast survival rates were significantly higher in IH vs. NT treated WT mice (47% vs. 0%, p=0.03). After 8 min of arrest heart p-NOS3(Ser1177) was significantly lower in NT relative to sham controls (p&lt;0.05) and IH treated WT mice (p&lt;0.05). Also during arrest, phosphorylation of the metabolically-sensitive AMP activated protein kinase p-AMPK(Thr172) was similarly increased (p&lt;0.05) following arrest in both IH and NT groups. Cardiac p-Akt(Ser474/Thr308) content was unchanged at 8 min of arrest (p&gt;0.05) in both groups. CONCLUSIONS: Loss of NOS3 abrogates IH protection following cardiac arrest. Maintenance of cardiac NOS3 phosphorylation during cardiac arrest may play an important role in determining survival in this model. Such maintenance of phosphorylation appears to be independent of upstream kinase phosphorylation.

Abstract 9362: Argon Reduces Neurohistopathological Damage and Preserves Functional Recovery After Cardiac Arrest in Rats

Introduction: Xenon has profound neuroprotective effects in various models of neurological injury and is currently undergoing phase two clinical trials in cardiac arrest patients. However, xenon is very costly which might preclude a widespread use. We hypothesized that the more available Argon might also protect central nervous tissues and functional recovery in a rodent model of global cerebral ischemia. Material and Methods: 14 male Sprague-Dawley rats were subjected to 7 mins of cardiac arrest and 3 mins of cardiopulmonary resuscitation (CPR). One hour after successful CPR, animals were randomized to ventilation with 70% Argon for 1h in comparison to untreated controls receiving 70% Nitrogen. A neurologic deficit score was calculated on seven days following the experiment before the animals were killed and the brains harvested for histopathological analyses. Results: All animals survived. Untreated controls exhibited severe neurological dysfunction while animals from the Argon group showed significant improvements at all points in time (Fig. 1). This was paralleled by a significant reduction in the degree of necrotic cell damage in the neocortex and the hippocampal CA 3/4 region (Fig. 2). Conlusions: Our study demonstrates that a single one hour application of 70% Argon provided a significant reduction in histopathological damage of the neocortex and hippocampus which was associated with a marked improvement in functional neurological recovery.

Abstract 17002: Post-Arrest Arterial Hyper-Oxygenation and Cardiac Mitochondrial Function

Introduction: Post-ischemic re-oxygenation is necessary to minimize ischemic injury, but itself can induce further reperfusion injury through the induction of reactive oxygen species (ROS). Utilization of oxygen within the cell primarily occurs in the mitochondria. The objective of this study was to determine heart mitochondrial function following 1 hour of controlled arterial oxygenation following cardiac arrest and ROSC. We hypothesized that arterial hyper-oxygenation following ROSC would result in greater impairment of heart mitochondrial function. Methods: Two experimental protocols were completed using a rat KCl arrest model. In experiment 1, animals underwent a 6 min cardiac arrest and were resuscitated with standard thumper CPR, ventilation and epinephrine and then ventilated with 100% O2 (hyperoxia group) or 40% O2 (normoxia group) for 60 min. In experiment 2, animals underwent a 25 min cardiac arrest and were resuscitated with cardiopulmonary bypass. Arterial PO2 was titrated to either hyperoxic or normoxic levels for 60 min post ROSC. In both experiments, at the end of 60 min, heart mitochondria were isolated and mitochondrial respiratory function was compared between groups. Results: In experiment 1, post-ROSC arterial PaO2 was 280 ± 40 mm Hg in the hyperoxic group and 105 ± 10 mm Hg in the normoxic group. Mitochondrial respiration, defined as respiration control ratio (state 3/4 respiration), was significantly higher in the normoxic group compared to the hyperoxic group (n=6/group, p &lt;0.05). In experiment 2, during the 60 min post ROSC period, arterial PaO2 was 441 ± 10 mm Hg in the hyperoxic group and 107 ± 9 mm Hg in the normoxic group (n=6/group, p&lt;0.001). Mitochondrial respiration, 60 min after ROSC, was significantly higher in the hyperoxic group compared with the normoxic group (n=6/group, p&lt;0.05). Post-ROSC arterial hyperoxemia (compared with normoxemia) was associated with worse mitochondrial function after a short cardiac arrest but improved mitochondrial function after a prolonged cardiac arrest. We conclude that post-ischemic arterial hyperoxia is an important variable in mitochondrial functional recovery but the severity of the ischemia may attenuate this effect by limiting reperfusion oxygen delivery to the mitochondria.

Variable effects of high-dose adrenaline relative to standard-dose adrenaline on resuscitation outcomes according to cardiac arrest duration

Aim of the studyAdjustment of adrenaline (epinephrine) dosage according to cardiac arrest (CA) duration, rather than administering the same dose, may theoretically improve resuscitation outcomes. We evaluated variable effects of high-dose adrenaline (HDA) relative to standard-dose adrenaline (SDA) on resuscitation outcomes according to CA duration. MethodsTwenty-eight male domestic pigs were randomised to the following 4 groups according to the dosage of adrenaline (SDA 0.02mg/kg vs. HDA 0.2mg/kg) and duration of CA before beginning cardiopulmonary resuscitation (CPR): 6min SDA, 6min HDA, 13min SDA, or 13min HDA. After the predetermined duration of untreated ventricular fibrillation, CPR was provided. ResultsAll animals in the 6min SDA, 6min HDA, and 13min HDA groups were successfully resuscitated, while only 4 of 7 pigs in the 13min SDA group were successfully resuscitated (p=0.043). HDA groups showed higher right atrial pressure, more frequent ventricular ectopic beats, higher blood glucose, higher troponin-I, and more severe metabolic acidosis than SDA groups. Animals of 13min groups showed more severe metabolic acidosis and higher troponin-I than animals of 6min groups. All successfully resuscitated animals, except two animals in the 13min HDA group, survived for 7 days (p=0.121). Neurologic deficit score was not affected by the dose of adrenaline. ConclusionHDA showed benefit in achieving restoration of spontaneous circulation in 13min CA, when compared with 6min CA. However, this benefit did not translate into improved long-term survival or neurologic outcome.

Adrenal gland blood flow and noradrenaline plasma concentration during CPR in pigs

Aim of the study In comparison to adrenaline, administration of vasopressin increases adrenal gland perfusion, but decreases catecholamine plasma concentrations when compared to saline placebo. We directly compared the effects of adrenaline with different doses of vasopressin on adrenal gland perfusion, and noradrenaline plasma concentrations during CPR. Methods Twenty-one pigs received either 0.2 mg kg −1 adrenaline ( n = 7), 0.2 U kg −1 vasopressin ( n = 7), or 0.8 U kg −1 vasopressin ( n = 7) after 4 min of cardiac arrest and 3 min of CPR. Adrenal gland perfusion was determined using radiolabeled microspheres, noradrenaline plasma concentration was measured by high pressure liquid chromatography. Results Before administration of vasopressor drugs during CPR, adrenal gland perfusion, and noradrenaline plasma concentrations were not different between groups. Ninety seconds and 5 min after drug administration, adrenal gland perfusion was significantly higher with both doses of vasopressin when compared with adrenaline, but was not different between the vasopressin groups. Noradrenaline plasma concentrations were 23684 ± 5036 pg ml −1 with adrenaline, 11455 ± 2450 pg ml −1 with 0.2 U kg −1 vasopressin, and 12119 ± 2921 pg ml −1 with 0.8 U kg −1 vasopressin at 90 s after administration of vasopressors ( p < .05 for both doses of vasopressin vs adrenaline). Five of seven animals in the adrenaline group, five of seven animals in the 0.2 U kg −1 vasopressin group, and six of seven animals in the 0.8 U kg −1 vasopressin group were successfully defibrillated. Conclusions Vasopressin enhances adrenal gland perfusion, but decreases noradrenaline plasma concentration when compared to adrenaline during CPR. Neither adrenal gland perfusion nor noradrenaline plasma concentration affect survival in this pig model of cardiac arrest.

Inhibition of Endoplasm Reticulum Stress by Anisodamine Protects Against Myocardial Injury After Cardiac Arrest and Resuscitation in Rats

Anisodamine is a multi-functional bio-alkaloid with vascular activity. Our previous studies have revealed that anisodamine protects the heart from ischemia/reperfusion (I/R) injury induced by cardiac arrest (CA) and resuscitation. This study aimed to explore whether the protective effect of anisodamine is mediated by inhibition of the endoplasmic reticulum stress (ERS) response, which has been demonstrated to implicate in various I/R injuries. After 5 min of CA induced by electric stimulation, Wistar rats were randomly selected to receive cardiopulmonary resuscitation (CPR, including chest compression and epinephrine infusion) with or without anisodamine injection (n = 50/group). Hearts were harvested 24 h after the return of spontaneous circulation (ROSC). Sham-operated animals served as non-ischemic controls (n = 10). The survival rate, cardiomyocyte apoptosis, and the protein expression of ERS markers were detected. Thirty-three of the 50 rats in the Ani + CA/R group were successfully resuscitated, whereas only 18 of the 50 rats in the CA/R group gained ROSC. Survival to 24 h was significantly improved in the anisodamine treatment group (Ani + CA/R, n = 22/50) compared to the group with standard CPR (CA/R, n = 8/50). Anisodamine markedly decreased the number of apoptotic cardiomyocytes, the protein expression of GRP78, CHOP, and the active form of Caspase3 compared to the CA/R group. Our data suggest that anisodamine protects against cellular damage in rat hearts after CA and resuscitation, at least in part, by inhibiting myocardial ERS.

Transient brain ischemia due to cardiac arrest causes irreversible long-lasting cognitive injury

Herein, we used a clinically-relevant model of 10min cardiac arrest (CA) in Wistar rats. Histological analyses of the ischemic brains of old rats showed significant atrophy of CA1 sector of hippocampus (Nissl and NeuN stainings) corresponding with increase of glial fibrillary acidic protein expression. The long-term behavioral consequences of above manipulation producing global brain ischemia were assessed in young, middle-aged and old rats, i.e., 3-, 6- and 18-months post-treatment, respectively. In young animals no differences were found in the context-dependent memory in Fear Conditioning test. The most striking behavioral abnormalities were found in middle-aged rats (6 months post-ischemia). Ischemic rats showed hyperactivity and decreased level of anxiety in Open Field and problems with spatial learning and memory in a Novel Object Location test, T-maze and Morris Water Maze. In old animals, a decline of motor and cognitive functions was found not only in ischemic but also in sham/control ones. This study describes consequences of global brain ischemia in aging animals.

Reducing the duration of 100% oxygen ventilation in the early reperfusion period after cardiopulmonary resuscitation decreases striatal brain damage

Purpose Previous data indicate that 100% O 2 ventilation during early reperfusion after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) increases neuronal death. However, current guidelines encourage the use of 100% O 2 during resuscitation and for an undefined period thereafter. We retrospectively analyzed data from a porcine CA model and hypothesized that prolonged hyperoxic reperfusion would be associated with increased neurohistopathological damage and impaired neurological recovery. Methods Fifteen male pigs underwent 8 min of CA and 5 min of CPR. After resuscitation animals were ventilated with either 100% oxygen for 60 min (hyperoxia; n = 8) or 10 min (normoxia; n = 7). Physiological variables were obtained at baseline and 10, 60 and 240 min after resuscitation. Daily functional performance was assessed using an established neurocognitive test in parallel to a neurological deficit score (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for neurohistopathological analyses. Results At baseline there were no differences in hemodynamics and neurological status between groups. Post-arrest only PaO 2, as a result of the different inspired oxygen fractions, was significantly higher in the hyperoxia group. There was a numerical trend towards improved clinical recovery in both the NDS and the neurocognitive testing for animals exposed to 10 min of 100% oxygen. However, hyperoxic animals showed a significantly greater degree of necrotic neurons and perivascular inflammation in the striatum in comparison to normoxic animals. Conclusion In this retrospective analysis prolonged hyperoxia after CA aggravated necrotic brain damage and perivascular inflammation in the striatum of pigs.

HYDROGEN SULFIDE DOES NOT INCREASE RESUSCITABILITY IN A PORCINE MODEL OF PROLONGED CARDIAC ARREST

Treatment options to improve resuscitability and neurological prognosis after cardiac arrest (CA) are limited. Hydrogen sulfide has demonstrated remarkable improvements in outcomes in small animal models of severe hypoxia or hemorrhage. We investigated the influence of sodium sulfide (Na2S), a liquid hydrogen sulfide donor, on resuscitability, postresuscitation hemodynamics, and neurological performance in a porcine model of prolonged CA and cardiopulmonary resuscitation. Twenty-four male pigs were instrumented with arterial and pulmonary artery catheters before 10 min of CA was induced. During resuscitation, animals were randomized to receive either high-dose (1 mg/kg; n = 8) or low-dose (0.3 mg/kg; n = 8) Na2S (IK-1001; Ikaria, Clinton, NJ) or control (saline placebo; n = 8) i.v. injection and consecutive infusion. Cardiopulmonary resuscitation was performed for 6 min before defibrillation was attempted. Hemodynamic variables were taken at baseline and 10, 30, 60, 120, and 240 min after successful resuscitation. Neurological outcome was evaluated on 4 postoperative days before brains and hearts were harvested for histopathologic analysis. No differences in hemodynamic parameters were observed at baseline. Initial resuscitability was not improved by Na2S. Animals exposed to high- and low-dose Na2S showed significantly reduced cardiac output, heart rate, and pulmonary arterial pressure compared with control animals during the early postresuscitation period. Strikingly, two of the high-dose Na2S animals died during the postresuscitation period, whereas all other animals survived. High-dose Na2S significantly decreased microglial activation in striatal areas, although this did not translate into improved neurological outcome. Although animals receiving Na2S developed higher troponin T serum levels, these differences remained insignificant. In this investigation, Na2S did not improve resuscitability but significantly compromised postresuscitation hemodynamics.

Randomised comparison of percutaneous left ventricular assist device with open-chest cardiac massage and with surgical assist device during ischaemic cardiac arrest

Aims A percutaneous left ventricular assist device can maintain blood flow to vital organs during ventricular fibrillation and may improve outcomes in ischaemic cardiac arrest. We compared haemodynamic and clinical effects of a percutaneous left ventricular assist device with a larger device deployed via endovascular prosthesis and with open-chest cardiac massage during ischaemic cardiac arrest. Methods Eighteen swine were randomised into three groups. After thoracotomy, coronary ischaemia and ventricular fibrillation was induced. Cardiac output was measured with transit-time flowmetry. Tissue perfusion was measured with microspheres. Defibrillation was performed after 20 min. Results Cardiac output with cardiac massage was 1129 mL min −1 vs. 1169 mL min −1 with the percutaneous- and 570 mL min −1 with the surgical device ( P < 0.05 surgical vs. others). End-tidal CO 2 was 3.3 kPa with cardiac massage vs. 3.2 kPa with the percutaneous- and 2.3 kPa with the surgical device ( P < 0.05 surgical vs. others). Subepicardial perfusion was 0.33 mL min −1 g −1 with cardiac massage vs. 0.62 mL min −1 g −1 with both devices ( P < 0.05 devices vs. massage), cerebral perfusion was comparable between groups (all reported values after 3 min cardiac arrest, all P < 0.05 vs. baseline, all P = NS for 3 min vs. 15 min). Return of spontaneous circulation was achieved in 5/6 subjects with cardiac massage vs. 6/6 with the percutaneous- and 4/6 with the surgical device ( P = NS). Conclusion The percutaneous device improved myocardial perfusion, maintained cerebral perfusion and systemic circulation with similar rates of successful defibrillation vs. cardiac massage. Increased delivery was not obtained with the surgical device during cardiac arrest.

Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death after resuscitation. Proinflammatory cytokines are known to decrease myocardial function, and tumor necrosis factor-alpha has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of tumor necrosis factor-alpha with infliximab would prevent or minimize postresuscitation cardiac dysfunction. Randomized, placebo-controlled comparative study. Large animal research laboratory. Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg). Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest. Hemodynamic variables, indices of left ventricular function, and tumor necrosis factor-alpha were measured before and after 8 mins of cardiac arrest during the early postresuscitation period (3 hrs). Within 5 mins of restoration of spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30 mins. Fourteen animals received an infusion of normal saline. Inotropes and vasopressors were not administered to either group after resuscitation. Tumor necrosis factor-alpha increased after restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. Interleukin-1beta concentration did not change significantly during the observation period in either study group. Mean arterial pressure and stroke work were significantly greater in the infliximab group within 30 mins of resuscitation, and these differences were sustained throughout the 3-hr postresuscitation period. The effect of tumor necrosis factor-alpha blockade was evident only in animals with a significant increase (doubling) in plasma tumor necrosis factor-alpha at 30 mins after arrest. Tumor necrosis factor-alpha plays a role in cardiac dysfunction after arrest and infliximab may attenuate or prevent postresuscitation myocardial dysfunction when administered immediately after resuscitation.

Transpulmonary cardiac output measurement in a rat model of cardiac arrest and CPR: Impact of vascular access

Objective The present study investigated the impact of the vascular access site for cardiac output (CO) measurement by thermodilution on survival and neurohistopathological injury in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Secondary the influence of the vascular access site on cardiac output measurements was examined. Methods Rats underwent asphyxial CA and CPR. Thermocouple probes were either placed via the femoral artery into the bifurcation of abdominal aorta/iliac artery (Femoral) or via the carotid artery into the aortic arch (Carotid). CPR was initiated after 9 min CA. Local cerebral blood flow (lCBF) and CO were assessed for 120 min after restoration of spontaneous circulation. Neurohistopathological injury was determined using Fluoro-Jade B staining. Results Survival was reduced in the Carotid group compared to the Femoral group ( p < 0.01). Fluoro-Jade B staining in the hippocampus showed no difference between CA groups. CO measurements were comparable between femoral and carotid artery access sites. lCBF revealed a delayed hyperperfusion in the Carotid group only. Conclusions The present study demonstrates the influence of the vascular access site for placing thermocouple probes for CO measurement on animal survival after CA/CPR. CO did not differ between the two access sites with consequential different detection sites. Use of the femoral access for CO measurement is recommended for long-term survival after CA/CPR.

Effects of abciximab on postresuscitation microcirculatory dysfunction after experimental cardiac arrest in rats

Background The term “ postresuscitation syndrome” includes among other pathophysiology impaired microcirculation and endothelial leakage. GPIIb/IIIa receptor antagonists like abciximab have been shown to reduce endothelial leakage and to improve microcirculatory disturbances during experimental endotoxaemia where comparably similar endothelial dysfunction has been observed. Previous investigations on postresuscitation endothelial leakage have indicated a possible role of platelets. Therefore, we investigated effects of abciximab on postresuscitation microcirculation applying in vivo microscopy of postcapillary mesenteric venules after experimentally induced cardiac arrest and cardiopulmonary rescuscitation in rats. Methods After 6 min of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), male Wistar rats were randomised into two groups ( n = 10) to receive abciximab (1 mg/kg i.v.) or placebo (0.9% NaCl). Sham operated animals ( n = 10) served as non-ischaemic controls. At 360, 420 and 480 min after return of spontaneous circulation (ROSC) in vivo microscopy was performed to assess venular wall shear rate (WSR) and plasma extravasation (PE). Results Besides typical signs of severe endothelial leakage in both CA groups, no significant differences between the treatment groups were observed with regard to WSR and PE. Conclusion In our study, a distinct postresuscitation microcirculatory splanchnic impairment after CA and successful CPR was observed. However, abciximab had no effects on WSR and PE. Our data does not support a valid resemblance between postresuscitation microcirculatory dysfunction observed in connection with experimental endotoxaemia. Furthermore, our data indicate that mechanisms other than GPIIb/IIIa mediated platelet activation play a role in postresuscitation syndrome. A better understanding of “postresuscitation disease” should enable the development of future therapeutic strategies for cardiac arrest survivors.

Intranasal cooling with or without intravenous cold fluids during and after cardiac arrest in pigs

Intranasal balloon catheters circulated with cold saline have previously been used for the induction and maintenance of selective brain cooling in pigs with normal circulation. In the present study, we investigated the feasibility of therapeutic hypothermia initiation, maintenance and rewarming using such intranasal balloon catheters with or without addition of intravenous ice-cold fluids during and after cardiac arrest treatment in pigs. Cardiac arrest was induced in 20 anaesthetised pigs. Following 8 min of cardiac arrest and 1 min of cardiopulmonary resuscitation (CPR), cooling was initiated after randomisation with either intranasal cooling (N) or combined with intravenous ice-cold fluids (N+S). Hypothermia was maintained for 180 min, followed by 180 min of rewarming. Brain and oesophageal temperatures, haemodynamic variables and intracranial pressure (ICP) were recorded. Brain temperatures reductions after cooling did not differ (3.8 +/- 0.7 degrees C in the N group and 4.3 +/- 1.5 degrees C in the N+S group; P=0.47). The corresponding body temperature reductions were 3.6 +/- 1.2 degrees C and 4.6 +/- 1.5 degrees C (P=0.1). The resuscitation outcome was similar in both groups. Mixed venous oxygen saturation was lower in the N group after cooling and rewarming (P=0.024 and 0.002, respectively) as compared with the N+S group. ICP was higher after rewarming in the N group (25.2 +/- 2.9 mmHg; P=0.01) than in the N+S group (15.7 +/- 3.3 mmHg). Intranasal balloon catheters can be used for therapeutic hypothermia initiation, maintenance and rewarming during CPR and after successful resuscitation in pigs.

Preservation of mitochondrial function with cardiopulmonary resuscitation in prolonged cardiac arrest in rats

During cardiac arrest (CA), myocardial perfusion is solely dependent on cardiopulmonary resuscitation (CPR) although closed-chest compressions only provide about 10–20% of normal myocardial perfusion. The study was conducted in a whole animal CPR model to determine whether CPR-generated oxygen delivery preserves or worsens mitochondrial function. Male Sprague-Dawley rats (400–450 g) were randomly divided into four groups: (1) BL (instrumentation only, no cardiac arrest), (2) CA 15 (15 min cardiac arrest without CPR), (3) CA 25 (25 min cardiac arrest without CPR) and (4) CPR (15 min cardiac arrest, followed by 10 min CPR). The differences between groups were evaluated by measuring mitochondrial respiration, electron transport chain (ETC) complex activities and mitochondrial ultrastructure by transmission electron microscopy (TEM). The CA 25 group had the greatest impairment of mitochondrial respiration and ETC complex activities (I–III). In contrast, the CPR group was not different from the CA 15 group regarding all measures of mitochondrial function. Complex I was more susceptible to ischemic injury than the other complexes and was the major determinant of mitochondrial dysfunction. Observations of mitochondrial ultrastructure by TEM were compatible with the biochemical results. The findings suggest that, despite low blood flow and oxygen delivery, CPR is able to preserve heart mitochondrial function and viability during ongoing global ischemia. Preservation of complex I activity and mitochondrial function during cardiac arrest may be an important mechanism underlying the beneficial effects of CPR which have been shown in clinical studies.

Deep Hypothermia Attenuates Microglial Proliferation Independent of Neuronal Death After Prolonged Cardiac Arrest in Rats

Conventional resuscitation of exsanguination cardiac arrest (CA) victims is generally unsuccessful. Emergency preservation and resuscitation is a novel approach that uses an aortic flush to induce deep hypothermia during CA, followed by delayed resuscitation with cardiopulmonary bypass. Minocycline has been shown to be neuroprotective across a number of brain injury models via attenuating microglial activation. We hypothesized that deep hypothermia and minocycline would attenuate neuronal death and microglial activation and improve outcome after exsanguination CA in rats. Using isoflurane anesthesia, rats were subjected to a lethal hemorrhagic shock. After 5 min of no flow, hypothermia was induced with an aortic flush. Three groups were studied: ice-cold (IC) flush, room-temperature (RT) flush, and RT flush followed by minocycline treatment (RT-M). After 20 min of CA, resuscitation was achieved via cardiopulmonary bypass. Survival, Overall Performance Category (1 = normal, 5 = death), Neurologic Deficit Score (0%-10% = normal, 100% = max deficit), neuronal death (Fluoro-Jade C), and microglial proliferation (Iba1 immunostaining) in hippocampus were assessed at 72 h. Rats in the IC group had lower tympanic temperature during CA versus other groups (IC, 20.9 degrees C +/- 1.3 degrees C; RT, 28.4 degrees C +/- 0.6 degrees C; RT-M, 28.3 degrees C +/- 0.7 degrees C; P < 0.001). Although survival was similar in all groups (RT, 6/9; IC, 6/7; RT-M, 6/11), neurological outcome was better in the IC group versus other groups (Overall Performance Category: IC, 1 +/- 1; RT, 3 +/- 1; RT-M, 2 +/- 1; P < 0.05; Neurologic Deficit Score: IC, 8% +/- 9%; RT, 55% +/- 19%; RT-M, 27% +/- 16%; P < 0.05). Histological damage assessed in survivors showed selective neuronal death in CA1 and dentate gyrus, similar in all groups (P = 0.15). In contrast, microglial proliferation was attenuated in the IC group versus all other groups (P < 0.01). Deeper levels of hypothermia induced by the IC versus RT flush resulted in better neurological outcome in survivors. Surprisingly, deep hypothermia attenuated microglial activation but not hippocampal neuronal death. Minocycline had modest benefit on neurologic outcome in survivors but did not attenuate microglial activation in brain. Our findings suggest a novel effect of deep hypothermia on microglial proliferation during exsanguination CA.

Échographie et arrêt cardiaque intra- et extrahospitalier : mise au point et perspectives

Cardiac arrest is a frequent emergency for doctors and resuscitation teams. Patients displaying asystole or pulseless electrical activity are non-shockable. They have extremely poor outcomes. The use of sonographers might contribute to a better understanding of cardiac arrest (CA) etiology and facilitate its treatment. A systematic search in databases (NLM-Gateway ®, CNRS-INIST/Pascal ®, Science Direct ®, Ovid ®, and Bibliovie ®) of primary documents and notices allowed us to select clinical trial studies. Editorials, case report and animals studies were excluded from the analysis. The various physiopathological and semiological status revealed by echocardiography are useful to detect the aetiology of cardiac arrest. In the very first minutes following the arrest, a significant increase of right ventricle (RV) volume suggests a pulmonary thromboembolism or a RV infarction. After 4 min of CA, a physiological increase of RV volume is observed, in relation with the pressure balance between high and low arteriovenous pressures. RV and/or left ventricle collapses are straightaway pathological whichever due to pericardic effusion, pneumothorax or schock. A synthesis algorithm dedicated to care of CA, including transthoracic echocardiography for search of curable causes, is proposed. This algorithm fulfills the ILCOR, ERC and AHA recommendations. The echocardiography should be part of ACLS, nevertheless clinical studies are needed to assess its impact on morbimortality.