Reduced long-term memory in a rat model of 8 minutes ventricular fibrillation cardiac arrest: a pilot trial.

BACKGROUND: Evaluating beneficial effects of potential protective therapies following cardiac arrest in rodent models could be enhanced by exploring behavior and cognitive functions. The Morris Water Maze is a well-known cognitive paradigm to test spatial learning and memory. RESULTS: Behavioral testing with the Morris Water Maze in Sprague-Dawley rats (300 ± 25 g) resuscitated after 8 min of ventricular fibrillation cardiac arrest was carried out 5 and 12 weeks after cardiac arrest (CA) and compared to results of naïve rats (CONTROL). At 5 weeks, within each group latency time to reach the hidden platform (reflecting spatial learning) decreased equally from day 1 to 4 (CA: 105.6 ± 8.2 vs. 8.9 ± 1.2 s, p < 0.001; CONTROL: 75.5 ± 13.2 vs. 17.1 ± 4.5, p < 0.001) with no differences between groups (p = 0.138). In the probe trial 24 h after the last trial, time spent in the target sector (reflecting memory recall) within each group was significantly longer (CA: 25 ± 1.3; CONTROL: 24.7 ± 2.5 s) than in each of the three other sectors (CA: 7.7 ± 0.7, 14.3 ± 2.5, 8.4 ± 0.8 and CONTROL: 7.8 ± 1.2, 11.7 ± 1.5, 10.3 ± 1.6 s) but with no significantly differences between groups. Seven days later (reflecting memory retention), control group animals remained significantly longer in the target sector compared to every other sector, whereas the cardiac arrest group animals did not. Even 12 weeks after cardiac arrest, the single p values showed that the control animals displayed a trend to perform better than the resuscitated animals. CONCLUSIONS: Memory recall was impaired early after 8 min of ventricular fibrillation cardiac arrest and might be a more valuable tool for cognitive testing than learning recall after global ischemia due to cardiac arrest.

A ventricular fibrillation cardiac arrest model with extracorporeal cardiopulmonary resuscitation in rats: 8 minutes arrest time leads to increased myocardial damage but does not increase neuronal damage compared to 6 minutes.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging strategy in highly selected patients with refractory cardiac arrest (CA). Animal models can help to identify new therapeutic strategies to improve neurological outcome and cardiac function after global ischemia in CA. Aim of the study was to establish a reproducible ECPR rat model of ventricular fibrillation CA (VFCA) that leads to consistent neuronal damage with acceptable long-term survival rates, which can be used for future research. Materials and methods: Male Sprague Dawley rats were resuscitated with ECPR from 6 min (n = 15) and 8 min (n = 16) VFCA. Animals surviving for 14 days after return of spontaneous resuscitation (ROSC) were compared with sham operated animals (n = 10); neurological outcome was assessed daily until day 14. In the hippocampal cornu ammonis 1 region viable neurons were counted. Microglia and astrocyte reaction was assessed by Iba1 and GFAP immunohistochemistry, and collagen fibers in the myocardium were detected in Azan staining. QuPath was applied for quantification. Results: Of the 15 rats included in the 6 min CA group, all achieved ROSC (100%) and 10 (67%) survived to 14 days; in the 8 min CA group, 15 (94%) achieved ROSC and 5 (31%) reached the endpoint. All sham animals (n = 10) survived 2 weeks. The quantity of viable neurons was significantly decreased, while the area displaying Iba1 and GFAP positive pixels was significantly increased in the hippocampus across both groups that experienced CA. Interestingly, there was no difference between the two CA groups regarding these changes. The myocardium in the 8 min CA group exhibited significantly more collagen fibers compared to the sham animals, without differences between 6- and 8-min CA groups. However, this significant increase was not observed in the 6 min CA group. Conclusion: Our findings indicate a uniform occurrence of neuronal damage in the hippocampus across both CA groups. However, there was a decrease in survival following an 8-min CA. Consequently, a 6-min duration of CA resulted in predictable neurological damage without significant cardiac damage and ensured adequate survival rates up to 14 days. This appears to offer a reliable model for investigating neuroprotective therapies.

Rapid induction of hypothermia with a small volume aortic flush during cardiac arrest in pigs.

PURPOSE: The induction of deep cerebral hypothermia (15°C) via large-volume cold (4°C) saline aortic flush during cardiac arrest and resuscitation with cardiopulmonary bypass improves neurologic outcome in pigs. We hypothesized that induction of mild cerebral hypothermia (33°C) via smaller volume and resuscitation without bypass will improve survival and neurologic outcome after 15 minutes of cardiac arrest as compared with conventional resuscitation attempts. BASIC PROCEDURES: Twenty-four pigs (29-38 kg) underwent ventricular fibrillation cardiac arrest for 15 minutes. Conventional resuscitation (n=8) was compared with hypothermic (4°C, n=8) and normothermic (38.5°C, n=8) aortic flush (30 mL/kg) at the beginning of resuscitation efforts, with defibrillation attempts 2 minutes later. Outcomes after 9 days were compared. MAIN FINDINGS: In the hypothermic flush group, brain temperature decreased from 38.3°C±0.5°C to 33°C±0.5°C within 277±112 seconds. We observed considerably higher mean coronary perfusion pressures in the normothermic and hypothermic flush groups (hypothermic vs conventional, P=.023; normothermic vs conventional, P=.041). Three animals of each flush group, compared with none of the conventional group, achieved restoration of spontaneous circulation (P=.2); and 3 pigs of the hypothermic flush group and 2 pigs of the normothermic flush group survived to 9 days without differences in neurologic outcome. PRINCIPAL CONCLUSION: A smaller volume, cold saline aortic flush during prolonged cardiac arrest rapidly induces mild cerebral hypothermia to 33°C and improves coronary perfusion pressure but does not result in a significant improvement in outcome as compared with conventional resuscitation attempts.

Psychocardiological assessment in the acute phase of the takotsubo syndrome : Somatic and depressive disorders, resilience and illness perception.

OBJECTIVE: To analyze the psychocardiological profile and the clinical characteristics in the acute phase of takotsubo syndrome (TTS). METHODS: Prospective multicenter cohort study of TTS patients evaluating the clinical characteristics as well as the prevalence of somatic, depressive, panic, stress and anxiety disorders. Assessment of illness perception and resilience in the acute phase of the syndrome. RESULTS: All 27 evaluated TTS patients were female with a mean age of 68 years (±11.4 years). The apical type of TTS was found in 60% of patients, followed by the combined type of TTS in 30% of patients. Main clinical symptom leading to hospital admission was chest pain in nearly 80% of patients. An ST-segment elevation mimicking acute myocardial infarction was found in 44% of patients and T wave inversion in 26% of patients. An endogenous (emotional) stress event was found in 17 patients (63.0%), an exogenous (physical) stress event in 5 patients (18.5%) and a combined stress event in 2 patients (7.4%). In 11.1% of patients (n = 3) no stress event could be found. Moderate to high levels of illness threatening were found in 48% of patients and low to moderate resilience scores were found in 40% of patients. Somatic disorders were found in half of the patients (56%) followed by depressive disorders in 26% of patients. CONCLUSION: Moderate to low resilience scores and moderate to high levels of illness threatening can be seen in the acute phase of TTS, reflecting the severity of the experience as an adverse life event. Patients suffering from TTS present in the acute phase with a high prevalence of somatic disorders and relatively high prevalence of depressive disorders.

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs.

OBJECTIVE: The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: : Twenty-four female, large, white breed pigs (27-37 kg). INTERVENTIONS: Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). MEASUREMENTS AND MAIN RESULTS: Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/- 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). CONCLUSIONS: Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

CA1 Hippocampal Pyramidal Cells in Rats, Resuscitated From 8 Minutes of Ventricular Fibrillation Cardiac Arrest, Recover After 20 Weeks of Survival: A Retrospective Pilot Study.

PURPOSE: The cornu ammonis 1 (CA1) region of the hippocampus is specifically vulnerable to global ischemia. We hypothesized that histopathological outcome in a ventricular fibrillation cardiac arrest (VFCA) rat model depends on the time point of the examination. METHODS: Male Sprague-Dawley rats were put into VFCA for 8 min, received chest compressions for 2 min, and were defibrillated to achieve return of spontaneous circulation. Animals surviving for 80 min, 14 days and 140 days were compared with controls. Viable neurons were counted in a 500 µm sector of the CA1 region and layer thickness measured. Microglia cells and astrocytes were counted in a 250×300 µm aspect. RESULTS: Control and 80 min surviving animals had similar numbers of pyramidal neurons in the CA1 region. In 14 days and 140 days survivors neuron numbers and layer thickness were severely diminished compared with controls (P < 0.001). Two-thirds of the 140 days survivors showed significantly more viable neurons than the last third. Microglia was increased in 14 days survivors compared with controls and 140 days survivors, while astrocytes increased in 14 days and 140 days survivors compared with controls (P < 0.001). 140 days survivors had significantly higher astrocyte counts compared with 14 days survivors. CONCLUSIONS: The amount and type of brain lesions present after global ischemia depend on the survival time. A consistent reduction in pyramidal cells in the CA1 region was present in all animals 14 days after VFCA, but in two-thirds of animals a repopulation of pyramidal cells seems to have taken place after 140 days.

Motor Cortex and Hippocampus Display Decreased Heme Oxygenase Activity 2 Weeks After Ventricular Fibrillation Cardiac Arrest in Rats.

Heme oxygenase (HO) and biliverdin reductase (BVR) activities are important for neuronal function and redox homeostasis. Resuscitation from cardiac arrest (CA) frequently results in neuronal injury and delayed neurodegeneration that typically affect vulnerable brain regions, primarily hippocampus (Hc) and motor cortex (mC), but occasionally also striatum and cerebellum. We questioned whether these delayed effects are associated with changes of the HO/BVR system. We therefore analyzed the activities of HO and BVR in the brain regions Hc, mC, striatum and cerebellum of rats subjected to ventricular fibrillation CA (6 min or 8 min) after 2 weeks following resuscitation, or sham operation. From all investigated regions, only Hc and mC showed significantly decreased HO activities, while BVR activity was not affected. In order to find an explanation for the changed HO activity, we analyzed protein abundance and mRNA expression levels of HO-1, the inducible, and HO-2, the constitutively expressed isoform, in the affected regions. In both regions we found a tendency for a decreased immunoreactivity of HO-2 using immunoblots and immunohistochemistry. Additionally, we investigated the histological appearance and the expression of markers indicative for activation of microglia [tumor necrosis factor receptor type I (TNFR1) mRNA and immunoreactivity for ionized calcium-binding adapter molecule 1 (Iba1])], and activation of astrocytes [immunoreactivity for glial fibrillary acidic protein (GFAP)] in Hc and mC. Morphological changes were detected only in Hc displaying loss of neurons in the cornu ammonis 1 (CA1) region, which was most pronounced in the 8 min CA group. In this region also markers indicating inflammation and activation of pro-death pathways (expression of HO-1 and TNFR1 mRNA, as well as Iba1 and GFAP immunoreactivity) were upregulated. Since HO products are relevant for maintaining neuronal function, our data suggest that neurodegenerative processes following CA may be associated with a decreased capacity to convert heme into HO products in particularly vulnerable brain regions.

Therapeutic hypothermia with a novel surface cooling device improves neurologic outcome after prolonged cardiac arrest in swine.

OBJECTIVE: Devices for rapid induction of mild hypothermia after cardiac arrest are needed. We hypothesized that the Life Recovery Systems' ThermoSuit System provides effective core cooling by pumping ice water over the skin surface and improves neurologic outcome after prolonged cardiac arrest. DESIGN: Prospective experimental study. SETTING: University research laboratory. SUBJECTS: Large White breed pigs (29 to 35 kg). INTERVENTIONS: Swine were anesthetized and mechanically ventilated. Ten minutes of untreated ventricular fibrillation, 3 mins of basic life support, and 5 mins of advanced cardiac life support, including two 0.4 IU/kg doses of vasopressin, were followed by up to three countershocks. After restoration of spontaneous circulation, swine were randomized to two groups (normothermic control, hypothermia). The hypothermia group was cooled from a pulmonary artery temperature of 38.5 +/- 0.5 degrees C to 33.0 degrees C and kept for 14 hrs. At day 9 of the experiment, overall performance categories scores (1, normal; 2, slightly disabled; 3, severely disabled; 4, comatose; 5, dead, brain dead) and neurologic deficit scores (0%, normal; 100%, brain dead) were assessed. Data are presented as median and interquartile range; group comparison was done with a Mann-Whitney U test. MEASUREMENTS AND MAIN RESULTS: In total, 16 of 22 animals were randomized. Time to target temperature in the hypothermia group (n = 8) was 9.0 (5.3-11.9) mins (cooling rate 0.4 [0.3-0.8] degrees C/min), and all animals achieved an overall performance categories score of 1. In the control group, one swine achieved an overall performance categories score of 1, three achieved a score of 2, and four achieved a score of 3 (p = .002). Neurologic deficit score was 0% (0%-4%) in the hypothermia group and 39% (19%-55%) in the control group (p = .001). No harmful side effects could be observed. CONCLUSIONS: The Life Recovery Systems' ThermoSuit System rapidly and safely induced mild therapeutic hypothermia. Hypothermia improved neurologic outcome in swine after cardiac arrest as compared with normothermia. Further studies are warranted to compare the device with established cooling methods.

Limits of conventional therapies after prolonged normovolemic cardiac arrest in swine.

AIM: Patients' outcomes after prolonged cardiac arrest are often grim. The aim of this study was to find the longest period of normovolemic, normothermic, cardiac arrest no-flow after which good neurologic outcome can be achieved with conventional therapies. METHODS: Swine (28-37 kg) were subjected to ventricular fibrillation cardiac arrest, after which they were randomized into groups with 13 min (n=6), 15 min (n=6), or 17 min (n=6) of untreated cardiac arrest followed by advanced life support (ALS) for 20 min (epinephrine 0.04 mg/kg every 3 min and vasopressin 0.4 IE/kg every 6 min, no defibrillation attempts), followed by cardiopulmonary bypass (CPB). To mimic an unresuscitable situation after prolonged cardiac arrest, CPB was initiated 20 min after the start of resuscitation, followed by defibrillation attempts. Therapeutic mild hypothermia was applied for 20 h and a final neurologic evaluation (neurologic deficit score, NDS; overall performance category, OPC) was done after 9 days. RESULTS: In the 13-min group, restoration of spontaneous circulation (ROSC) was achieved in five of six swine, four of which survived to day 9, and all had favorable neurologic outcomes [one swine OPC 1, three swine OPC 2, NDS 15% (IQR 6-21)]. In the 15- and 17-min groups, ROSC was achieved in three of six and two of six swine, respectively, one survived to day 9 with OPC 3 in each group, and NDS values were 45 and 58%, respectively (Kruskal-Wallis test for OPC, p=0.048). CONCLUSIONS: In our model, the limit of normovolemic, normothermic, cardiac arrest no-flow time, followed by ACLS, CPB, and prolonged mild hypothermia, seems to be 13 min.

Establishing a Rodent Model of Ventricular Fibrillation Cardiac Arrest With Graded Histologic and Neurologic Damage With Different Cardiac Arrest Durations.

PURPOSE: The aim of the study was to establish a ventricular fibrillation (VF) cardiac arrest (CA) resuscitation model with consistent neurologic and neuropathologic damage as potential therapeutic target. METHODS: Prospectively randomized groups of experiments in two phases. In phase 1 four groups of male Sprague-Dawley rats (n = 5) were resuscitated after 6 min VFCA with 2 and 6 min basic life support durations (BLS) with and without adrenaline. In phase 2 the most promising group regarding return of spontaneous circulation (ROSC) and survival was compared with a group of 8 min CA. Resuscitability, neurologic deficit scores (NDS), and overall performance category (OPC) were assessed daily; histolopathology of the hippocampal CA1 region [hematoxylin and eosin- (viable neurons), Fluoro-Jade- (dying neurons), and Iba-1 immunostaining (microglial activation-semiquantitative)] on day 14. RESULTS: Two minutes BLS and with adrenaline as most promising group of phase 1 compared with an 8 min group in phase 2 exhibited ROSC in 8 (80%) vs. 9 (82%) animals and survivors till day 14 in 7 (88%) (all OPC 1, NDS 0 ±â€Š0) vs. 6 (67%) (5 OPC 1, 1 OPC 2, NDS 0.83 ±â€Š2.4) animals. OPC and NDS were only significantly different at day 1 (OPC: P = 0.035; NDS: P = 0.003). Histopathologic results between groups were not significantly different; however, a smaller variance of extent of lesions was found in the 8 min group. Both CA durations caused graded neurologic, overall, such as histopathologic damage. CONCLUSIONS: This dynamic global ischemia model offers the possibility to evaluate further cognitive and novel neuroprotective therapy testing after CA.

External cardiac defibrillation during wet-surface cooling in pigs.

OBJECTIVE: During surface cooling with ice-cold water, safety and effectiveness of transthoracic defibrillation was assessed. METHODS: In a pig ventricular fibrillation cardiac arrest model, once (n = 6), defibrillation was done first in a dry and then in a wet condition using the ThermoSuit System (Life Recovery Systems, HD, LLC, Kinnelon, NJ), which circulates a thin layer of ice-cold water (approximately 4 degrees C) over the skin surface. Another time (n = 6), defibrillation was done first in a wet and then in a dry condition. Success of defibrillation was defined as restoration of spontaneous circulation, and the current and voltage of the defibrillation signal was measured. RESULTS: There was a tendency toward less number of shocks needed for achieving restoration of spontaneous circulation in the wet condition as compared with the number of shocks needed in the dry condition. The energy delivered in both dry and wet conditions was 144 +/- 3 J. DISCUSSION: Transthoracic defibrillation is safe and effective in a wet condition after cooling with ice-cold water.

Feasibility of profound hypothermia as part of extracorporeal life support in a pig model.

OBJECTIVE: To investigate the feasibility of a refined aortic flush catheter and pump system to induce emergency preservation and resuscitation before extracorporeal cardiopulmonary resuscitation in a normovolemic cardiac arrest swine model simulating near real size/weight conditions of adults. METHODS: In this feasibility study, 8 female Large White breed pigs weighing 70 to 80 kg underwent ventricular fibrillation cardiac arrest for 15 minutes, followed by 4°C aortic flush (150 mL/kg for the brain; 50 mL/kg for the spine) via a new hardware ensued by resuscitation with extracorporeal cardiopulmonary resuscitation. RESULTS: Brain temperature was lowered from 39.9°C (interquartile range [IQR] 39.6-40.3) to 24.0°C (IQR 20.8-28.9) in 12 minutes (IQR 11-16) with a median cooling rate of 1.3°C (IQR 0.7-1.6) per minute. A median of 776 mL (IQR 673-840) per minute with a median pump pressure of 1487 mm Hg (IQR 1324-1545) were pumped to the brain. CONCLUSIONS: With the new hardware, we were able to cool the brain within a few minutes in a large pig cardiac arrest model. The exact position; the design, diameter, and length of the flush catheter; and the brain perfusion pressure seem to be critical to effectively reduce brain temperature. Redistribution of peripheral blood could lead to sterile inflammation again and might be avoided.

Extracorporeal Life Support Increases Survival After Prolonged Ventricular Fibrillation Cardiac Arrest in the Rat.

BACKGROUND: Extracorporeal life support (ECLS) for cardiopulmonary resuscitation (CPR) may increase end organ perfusion and thus survival when conventional CPR fails. The aim was to investigate, if after ventricular fibrillation cardiac arrest in rodents ECLS improves outcome compared with conventional CPR. METHODS: In 24 adult male Sprague-Dawley rats (460-510 g) resuscitation was started after 10 min of no-flow with ECLS (consisting of an open reservoir, roller pump, and membrane oxygenator, connected to cannulas in the jugular vein and femoral artery, n = 8) or CPR (mechanical chest compressions plus ventilations, n = 8) and compared with a sham group (n = 8). After return of spontaneous circulation (ROSC), all rats were maintained at 33°C for 12 h. Survival to 14 days, neurologic deficit scores and overall performance categories were assessed. RESULTS: ECLS leads to sustained ROSC in 8 of 8 (100%) and neurological intact survival to 14 days in 7 of 8 rats (88%), compared with 5 of 8 (63%) and 1 of 8 CPR rats. The median survival time was 14 days (IQR: 14-14) in the ECLS and 1 day (IQR: 0 to 5) for the CPR group (P = 0.004). CONCLUSION: In a rat model of prolonged ventricular fibrillation cardiac arrest, ECLS with mild hypothermia produces 100% resuscitability and 88% long-term survival, significantly better than conventional CPR.

A large Eustachian valve is a confounder of contrast but not of color Doppler transesophageal echocardiography in detecting a right-to-left shunt across a patent foramen ovale.

BACKGROUND: Transesophageal contrast echocardiography (cTEE) is considered to be the method of choice for diagnosing patent foramen ovale (PFO), but its diagnostic accuracy compared with color Doppler guided TEE in the presence of an Eustachian valve (EV) has not been evaluated. The main aim of this study was to assess the diagnostic accuracy for PFO diagnosis of color Doppler TEE at low pulse repetition frequency. METHODS: We ascertained the presence of PFO and EV using cTEE and transthoracic contrast echocardiography (cTTE) in 292 consecutive patients (age 42+/-12 years) with cryptogenic stroke. A diagnosis of PFO was based on the observation of right-to-left shunting of contrast bubbles or by color Doppler with pulse repetition frequency of 20-30 cm/s. An EV with a diameter of >1.5 cm in the bicaval view was considered large. RESULTS: Overall 204 patients (70%) had evidence of a right-to-left shunt by either contrast echo method. Shunting was demonstrated more frequently by color Doppler than by cTEE, either spontaneously (133 vs. 92; p=0.01) or during provocative maneuvers (166 vs. 184; p=0.01). The sensitivity of color Doppler was significantly higher than that of cTEE (90% vs. 81%; p=0.01). A large EV was found in 37 patients, 31 (84%) of whom had a PFO. The presence of a large EV did not significantly influence the sensitivity of color Doppler for detecting shunting through a PFO, but the sensitivity of cTTE and cTEE was significantly reduced (from 88% to 42%, p<0.001). CONCLUSIONS: Color Doppler TEE is more accurate than traditional cTEE for PFO diagnosis and is not negatively influenced by the presence of an EV, provided that a low pulse repetition frequency is used.

Perceval Sutureless Valve Dysfunction Caused by Valvular Thrombosis.

Until now, to our knowledge no case of bioprosthetic valvular thrombosis after implantation of the sutureless Sorin Perceval valve has been reported. Although sutureless aortic valve replacement has become a powerful tool in our daily practice, recent guidelines from the European Society of Cardiology, the European Association for Cardio-Thoracic Surgery, the American College of Cardiology, and the American Heart Association do not give specific recommendations on postoperative anticoagulation therapy. We report the first case of valve dysfunction resulting from thrombosis 12 months after implantation with a possible link to postoperative cortisole therapy.

Reduction of Serious Adverse Events Demanding Study Exclusion in Model Development: Extracorporeal Life Support Resuscitation of Ventricular Fibrillation Cardiac Arrest in Rats.

Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported.Anesthetized male Sprague-Dawley rats (350-600 g) (n = 126) underwent cardiac arrest induced with a pacing catheter placed into the right ventricle via a jugular cannula. Rats were resuscitated with extracorporeal life support, mechanical ventilation, defibrillation, and medication. Catheter and cannula explantation was performed if restoration of spontaneous circulation was achieved. All observed serious adverse events (SAEs) occurring in each of the experimental phases were analyzed.Restoration of spontaneous circulation could be achieved in 68 of 126 rats (54%); SAEs were observed in 76 (60%) experiments. Experimental procedures related SAEs were 62 (82%) and avoidable human errors were 14 (18%). The most common serious adverse events were caused by insertion or explantation of the venous bypass cannula and resulted in lethal bleeding, cannula dislocation, or air embolism.Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby.

Microdialysis Assessment of Cerebral Perfusion during Cardiac Arrest, Extracorporeal Life Support and Cardiopulmonary Resuscitation in Rats - A Pilot Trial.

Cerebral metabolic alterations during cardiac arrest, cardiopulmonary resuscitation (CPR) and extracorporeal cardiopulmonary life support (ECLS) are poorly explored. Markers are needed for a more personalized resuscitation and post-resuscitation care. Aim of this study was to investigate early metabolic changes in the hippocampal CA1 region during ventricular fibrillation cardiac arrest (VF-CA) and ECLS versus conventional CPR. Male Sprague-Dawley rats (350g) underwent 8min untreated VF-CA followed by ECLS (n = 8; bloodflow 100ml/kg), mechanical CPR (n = 18; 200/min) until return of spontaneous circulation (ROSC). Shams (n = 2) were included. Glucose, glutamate and lactate/pyruvate ratio were compared between treatment groups and animals with and without ROSC. Ten animals (39%) achieved ROSC (ECLS 5/8 vs. CPR 5/18; OR 4,3;CI:0.7-25;p = 0.189). During VF-CA central nervous glucose decreased (0.32±0.1mmol/l to 0.04±0.01mmol/l; p<0.001) and showed a significant rise (0.53±0.1;p<0.001) after resuscitation. Lactate/pyruvate (L/P) ratio showed a 5fold increase (31 to 164; p<0.001; maximum 8min post ROSC). Glutamate showed a 3.5-fold increase to (2.06±1.5 to 7.12±5.1µmol/L; p<0.001) after CA. All parameters normalized after ROSC with no significant differences between ECLS and CPR. Metabolic changes during ischemia and resuscitation can be displayed by cerebral microdialysis in our VF-CA CPR and ECLS rat model. We found similar microdialysate concentrations and patterns of normalization in both resuscitation methods used. Institutional Protocol Number: GZ0064.11/3b/2011.

Electrocardiogram changes and wall motion abnormalities in the acute phase of Tako-Tsubo syndrome.

BACKGROUND: The Tako-Tsubo syndrome is still rarely diagnosed in patients presenting with symptoms of acute myocardial ischaemia. It is accompanied by wall motion abnormalities of the left ventricle but significant narrowings or occlusions of epicardial coronary arteries are absent. We investigated a potential relationship between electrocardiogram (ECG) changes, wall motion abnormalities and gender influence of Tako-Tsubo syndrome in an Austrian cohort of Tako-Tsubo syndrome patients. METHODS AND RESULTS: We were recently able to describe four different anatomical types of Tako-Tsubo syndrome in 153 patients of the Austrian Tako-Tsubo syndrome registry. In the present retrospective analysis we investigated ischaemia-related changes in the first diagnostic ECG for the different types of Tako-Tsubo syndrome: the apical and the combined apical-midventricular type showed most frequently a ST elevation (41.1% and 35.3%), whereas the midventricular type of Tako-Tsubo syndrome was more often accompanied by T wave inversion (60%). ECG changes in relation to the Tako-Tsubo syndrome type were similar in women and men. There was no difference in the prevalence of clinical complications among patients presenting with ST elevation or left bundle branch block (14.5%) compared with patients without ST elevation (10.4%) (p=0.476). CONCLUSION: Patients with Tako-Tsubo syndrome show characteristic ECG changes in the first diagnostic ECG which are associated to some extent with the anatomical type of Tako-Tsubo syndrome, but these ECG changes were not related to clinical outcome.