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Background Guidelines for neonatal resuscitation recommend a 3:1 compression to ventilation ratio. However, this recommendation is based on expert opinion and consensus rather than strong scientific evidence. Our primary aim was to assess whether continuous chest compressions with asynchronous ventilations would increase return of spontaneous circulation (ROSC) rate and survival compared to the 3:1 chest compression to ventilation ratio. Methods This was a prospective, randomized, laboratory study. Twenty male Landrace-Large White pigs, aged 1–4 days with an average weight 1.650 ± 228.3 g were asphyxiated and left untreated until heart rate was less than 60 bpm or mean arterial pressure was below 15 mmHg. Animals were then randomly assigned to receive either continuous chest compressions with asynchronous ventilations (n = 10), or standard (3:1) chest compression to ventilation ratio (n = 10). Heart rate and arterial pressure were assessed every 30 s during cardiopulmonary resuscitation (CPR) until ROSC or asystole. All animals with ROSC were monitored for 4 h. Results Coronary perfusion pressure (CPP) at 30 s of CPR was significantly higher in the experimental group (45.7 ± 16.9 vs. 21.8 ± 6 mmHg, p Conclusion Continuous chest compressions with asynchronous ventilations significantly improved CPP, ETCO2, time to ROSC, ROSC at 30 s and survival in a porcine model of neonatal resuscitation.

Aims Right ventricle adaptation to prolonged exposure against pulmonary hypertension (PH) includes structural and functional abnormalities, translated into modifications of blood flow pattern through the right coronary artery. Given these changes, we investigate the relationship between right coronary artery diastolic perfusion pressure (RCDPP) and clinical outcome, in patients with PH secondary to left‐sided heart failure (HF). Methods and results We studied 108 HF patients who underwent right heart catheterization. PH was present in 75 (69.4%). Mean RCDPP was lower in patients with PH (59.4 ± 14.0 mmHg) as compared with no PH patients (65.5 ± 11.6 mmHg) (P = 0.03). Aortic diastolic pressure accounted for 79% of RCDPP variability explained by the model (P

Introduction Mortality for out-of-hospital cardiac arrest is high when traditional chest compressions are used without adjuncts. The abdominal aortic and junctional tourniquet (AAJT) is a device with a wedge-shaped air bladder that occludes the aortic bifurcation, augmenting blood flow to the heart and brain. Previously, the addition of AAJT during chest compression led to an increase in rate of survival in a model of traumatic cardiac arrest. Hypothesis This study was designed to determine if application of the AAJT would lead to more effective chest compressions as measured by improved hemodynamic parameters and an increased rate of return of spontaneous circulation (ROSC). Methods Yorkshire swine (n = 6 per group) underwent general anesthesia and instrumentation. Ventricular fibrillation (Vfib) was electrically induced and animals were allocated into groups with or without the AAJT. The AAJT was inflated if selected after four minutes of compressions. Following a total of ten minutes of compressions, the animals entered into a ten-minute advanced cardiac life support phase. Hemodynamics and blood gas measurements were compared between groups. Results ROSC or cardioversion from Vfib was not achieved in either group. The AAJT group had improved hemodynamic parameters with significantly higher carotid diastolic pressure and higher blood flow in the carotid artery (p = 0.016 and 0.028 respectively). However, no significant differences were observed with coronary perfusion pressure or end tidal CO2. Conclusion The AAJT did not confer a survival advantage during chest compressions, but hemodynamic improvements were observed while the AAJT was in place.

OBJECTIVE To determine whether the use of invasively measured hemodynamics improves the prognostic ability of a shock index (SI). BACKGROUND SI such as Admission-SI, Age-SI, Modified SI (MSI), and Age-MSI predict short-term mortality in ST-elevation myocardial infarction (STEMI). METHODS Single-center study of 510 patients who underwent primary percutaneous coronary intervention. STEMI SI was defined as age × heart rate (HR) divided by coronary perfusion pressure (CPP). RESULTS The mean age was 62 ± 14 years, 66% were males with hypertension (69%), tobacco use (38%), diabetes (28%) and chronic kidney disease (6%). The mean HR, systolic blood pressure (SBP), and CPP were 81 ± 18 bpm, 124 ± 28 mmHg, and 52.8 ± 16.3 mmHg, respectively. Patients with STEMI SI ≥182 (n = 51) were more likely to experience a cardiac arrest in the catheterization laboratory (9.8% vs. 2.0%; p = .001), require mechanical circulatory support (47.1% vs. 8.5%; p

Background/Aim. Dysfunctions at the cellular, tissue, and organ level, which can result in death, are caused by metabolic changes and affection on the regulation of gene transcription and micro- and macrocirculation. The aim of the present study was to assess the impact of hyperbaric oxygenation (HBO) on isolated heart as well as on the oxidative status of rats with sepsis. Methods. The investigation included male Wistar albino rats classified into three groups: the first group was a control group (CTRL); the second group included animals exposed only to the induction of sepsis without HBO treatment (the Sepsis group), while the third group included animals treated with HBO after the induction of sepsis (the Sepsis + HBO group). For the induction of sepsis, fecal peritonitis model was used (3 mL/kg of fecal suspension administered intraperitoneally). After the induction of sepsis, the rats were exposed twice a day (on 12 hours) to HBO treatment at 2.8 atmospheres absolute (ATA) for 90 minutes over a period of 3 days. 72 h after the confirmation of sepsis, the animals were sacrificed and the hearts were retrogradely perfused on the Langendorff apparatus at a gradually increased coronary perfusion pressure (CPP = 40?120 cm H2O). The following parameters of heart function were continuously recorded: maximum and minimum rate of left ventricular pressure development (dp/dt max, dp/dt min); systolic and diastolic left ventricular pressure (SLVP and DLVP); heart rate (HR). Coronary flow (CF) was measured flowmetrically. Following oxidative stress markers were measured: nitrites (NO2?), superoxide anion radical (O2?), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), activity of superoxide dismutase (SOD) and catalase (CAT) and the level of reduced glutathione (GSH). Results. There were no significant differences in dp/dt max, dp/dt min, SLVP and HR between the groups. CF was statistically significantly higher (p < 0.01) in the sepsis group. The values of all cardiac oxidative markers were lower in the sepsis + HBO group (p < 0.05), while systemic pro-oxidative and antioxidative parameters were unchanged. Conclusion. Our results showed that HBO treatment was not associated with improved cardiac function and coronary perfusion, while expressed promising beneficial effects on cardiac oxidative stress.

Pralidoxime potentiated the pressor effect of adrenaline and facilitated restoration of spontaneous circulation (ROSC) after prolonged cardiac arrest. In this study, we hypothesised that pralidoxime would hasten ROSC in a model with a short duration of untreated ventricular fibrillation (VF). We also hypothesised that potentiation of the pressor effect of adrenaline by pralidoxime would not be accompanied by worsening of the adverse effects of adrenaline. After 5 min of VF, 20 pigs randomly received either pralidoxime (40 mg/kg) or saline, in combination with adrenaline, during cardiopulmonary resuscitation (CPR). Coronary perfusion pressure (CPP) during CPR, and ease of resuscitation were compared between the groups. Additionally, haemodynamic data, severity of ventricular arrhythmias, and cerebral microcirculation were measured during the 1-h post-resuscitation period. Cerebral microcirculatory blood flow and brain tissue oxygen tension (PbtO2) were measured on parietal cortices exposed through burr holes. All animals achieved ROSC. The pralidoxime group had higher CPP during CPR (P = 0.014) and required a shorter duration of CPR (P = 0.024) and smaller number of adrenaline doses (P = 0.024). During the post-resuscitation period, heart rate increased over time in the control group, and decreased steadily in the pralidoxime group. No inter-group differences were observed in the incidences of ventricular arrhythmias, cerebral microcirculatory blood flow, and PbtO2. Pralidoxime improved CPP and hastened ROSC in a model with a short duration of untreated VF. The potentiation of the pressor effect of adrenaline was not accompanied by the worsening of the adverse effects of adrenaline.

Aim We aimed to investigate whether the ability of the volumetric capnography-derived parameter, the volume of CO2 eliminated per minute and per kg body weight (V’CO2 kg−1), in monitoring the quality of CPR and predicting the return of spontaneous circulation (ROSC) remains undisturbed by hyperventilation. Methods This randomised crossover study included 12 male domestic pigs. After 4 min of untreated ventricular fibrillation, mechanical CPR was administered. Following 5-min washout periods, each animal underwent two sessions of experiments; four 5-min ventilation trials followed by advanced life support, consecutively in the two sessions. Results Different ventilation types had no significant impact on V’CO2 kg−1 or haemodynamics. However, PETCO2 was significantly affected by the ventilation type and coronary perfusion pressure (P Conclusions V’CO2 kg−1 performs better than PETCO2 in monitoring the quality of CPR during hyperventilation. In predicting ROSC during variations in a ventilation state, V’CO2 kg−1 has good predictive ability.

Mechanical assist devices in refractory cardiac arrest are increasingly employed. We compared the hemodynamics and organ perfusion during cardiac arrest with either veno-arterial extracorporeal membrane oxygenation (ECMO) or biventricular assisted circulation combining left- and right-sided impeller devices (BiPella) in an acute experimental setting. Twenty pigs were randomized in two equal groups receiving circulatory support either by ECMO or by BiPella during 40 minutes of ventricular fibrillation (VF) followed by three attempts of cardioversion, and if successful, 60 minute observation with spontaneous, unsupported circulation. Hemodynamic variables were continuously recorded. Tissue perfusion was evaluated by fluorescent microsphere injections. Cardiac function was visualized by intracardiac echocardiography. During VF device output, carotid flow, kidney perfusion, mean aortic pressure (AOPmean), and mean left ventricular pressure (LVPmean) were all significantly higher in the ECMO group, and serum-lactate values were lower compared with the BiPella group. No difference in myocardial or cerebral perfusion was observed between groups. In 15 animals with sustained cardiac function for 60 minutes after return of spontaneous circulation, left ventricular subendocardial blood flow rate averaged 0.59 ± 0.05 ml/min/gm during VF compared with 0.31 ± 0.07 ml/min/gm in five animals with circulatory collapse (p = 0.005). Corresponding values for the midmyocardium was 0.91 ± 0.06 vs. 0.65 ± 0.15 ml/min/gm (p = 0.085). Both BiPella and ECMO could sustain vital organ function. ECMO provided a more optimal systemic circulatory support related to near physiologic output. Myocardial tissue perfusion and sustained cardiac function were related to coronary perfusion pressure during VF, irrespective of mode of circulatory support.

Objective: The two objectives of this report are: first, to describe a comparison of chest compressions unsynchronized or synchronized to native cardiac activity in a porcine model of hypotension, and second, to develop an algorithm to provide synchronized chest compressions throughout a range of native heart rates likely to be encountered when treating PEA cardiac arrest. Methods: We adapted our previously developed signal-guided CPR system to provide compressions synchronized to native electrical activity in a porcine model of hypotension as a surrogate of PEA arrest. We describe the first comparison of unsynchronized to synchronized compressions in a single animal as a proof-of-concept. We developed an algorithm to provide optimal synchronized chest compressions regardless of intrinsic PEA heart rate while simultaneously maintaining the chest compression rate within a desired range. We tested the algorithm with computer simulations measuring the proportion of intrinsic and compression beats that were synchronized, and the compression rate and its standard deviation, as a function of intrinsic heart rate and heart rate jitter. Results: We demonstrate and compare unsynchronized versus synchronized chest compressions in a single porcine model with an intrinsic rhythm and hypotension. Synchronized, but not unsynchronized, chest compressions were associated with increased blood pressure and coronary perfusion pressure. Our synchronized chest compression algorithm is able to provide synchronized chest compressions to over 90% of intrinsic beats for most heart rates while maintaining an average compression rate between 90 and 140 compressions per minute with relatively low variability. Conclusions: Synchronized chest compression therapy for pulseless electrical rhythms is feasible. A high degree of synchronization can be maintained over a broad range of intrinsic heart rates while maintaining the compression rate within a satisfactory range. Further investigation to assess benefit for treatment of PEA is warranted.

Traumatic brain injury remains a leading cause of morbidity and mortality in children. The use of hyperosmolar therapy to offset increased intracranial pressure (ICP) is described in pediatric guidelines, yet some controversy remains regarding which option to select. A search was conducted using the PubMed, MEDLINE, Cumulative Index of Nursing and Allied Health, Academic Search Premier, PsycInfo, and Cochrane Library databases. Studies were included if they described the hyperosmolar therapy use, involved severe traumatic brain injury (TBI), and patient age was 0 to 18 years. A total of 331 studies published between 1987 and 2017 were retrieved; of these, 9 met the inclusion criteria. Included studies were evaluated for the type and concentration of hyperosmolar therapy, associated mortality outcomes, ICP and coronary perfusion pressure (CPP) measurements, concurrent medications, and reported serum sodium and serum osmolarity or osmolality values. Hypertonic saline was the most commonly reported hyperosmolar therapy. Mannitol was less studied, but collectively demonstrated a higher incidence of mortality than hypertonic saline. There were several studies that did not report monitoring outcomes associated with serum sodium and/or serum osmolarity, despite the use of hyperosmolar therapies. Inconsistencies were noted between the studies in the overall study design as well as reported monitoring parameters and length of stay. Hypertonic saline appears to be safe and efficacious at several concentrations for treatment of increased ICP associated with severe TBI in pediatric patients. The limited available data regarding the use of mannitol do not allow a strong conclusion to be made regarding its use.

Background Elevated systolic blood pressure and decreased diastolic blood pressure increase systolic load, with concurrent decrease in coronary perfusion pressure. Researches suggested a relation between elevated pulse pressure and morbidity and mortality due to cardiovascular events. This study set out to investigate whether pulse pressure is a predisposing risk factor for coronary heart disease or an aggravating risk factor in patients with coronary artery disease. Methods A total of 5,027 pressure registers were evaluated. Pulse pressure was determined invasively [...]

Aortic balloon occlusion (ABO) facilitates the success of cardiopulmonary resuscitation (CPR) in non-traumatic cardiac arrest, and is also effective in controlling traumatic hemorrhage; however, a prolonged occlusion results in irreversible organ injury and death. In this study, we investigated the effects of ABO on CPR outcomes and its optimal duration for post-resuscitation organ protection in a porcine model of traumatic cardiac arrest (TCA).Twenty-seven male domestic pigs weighing 33 ± 4 kg were utilized. Forty percent of estimated blood volume was removed within 20 min. The animals were then subjected to 5 min of untreated ventricular fibrillation and 5 min of CPR. Coincident with the start of CPR, the animals were randomized to receive either 30-min ABO (n = 7), 60-min ABO (n = 8) or control (n = 12). Meanwhile, fluid resuscitation was initiated by the infusion of normal saline with 1.5 times of hemorrhage volume in 1 h, and finished by the reinfusion of 50% of the shed blood in another 1 h. The resuscitated animals were monitored for 6 h and observed for an additional 18 h.During CPR, coronary perfusion pressure was significantly increased followed by a higher rate of resuscitation success in the 30 and 60-min ABO groups compared with the control group. However, post-resuscitation cardiac, neurologic dysfunction, and injuries were significantly milder accompanied with less renal and intestinal injuries in the 30-min ABO group than in the other two groups.In conclusion, ABO augmented the efficacy of CPR after TCA, and furthermore a 30-min ABO improved post-resuscitation cardiac and neurologic outcomes without exacerbating the injuries of kidney and intestine.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm H2O. After a stabilization period, CPP was lowered to 60 cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2−. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2− in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

Scientific statements and publications have recommended the use of vasoconstrictors as the first-line pharmacologic choice for most cases of cardiogenic shock (CS), without the abundance of strong clinical evidence. One challenge of guidelines is that the way recommendations are stated can potentially lead to oversimplification of complex situations. Except for acute coronary syndrome with CS, in which maintenance of coronary perfusion pressure seems logical prior to revascularization, physiologic consequences of increasing afterload by use of vasoconstrictors should be analyzed. Changing the CS conceptual frame, emphasizing inflammation and other vasodilating consequences of prolonged CS, mixes causes and consequences. Moreover, the considerable interpatient differences regarding the initial cause of CS and subsequent consequences on both macro- and microcirculation, argue for a dynamic, step-by-step, personalized therapeutic strategy. In CS, vasoconstrictors should be used only after a reasoning process, a review of other possible options, and then should be titrated to reach a reasonable pressure target, while checking cardiac output and organ perfusion.

BACKGROUND/PURPOSE Appropriate patient selection for mechanical circulatory support following percutaneous coronary intervention (PCI) remains a challenge. This study aims to evaluate the role of coronary perfusion pressure and other left ventricular hemodynamics to predict cardiovascular collapse following PCI. METHODS/MATERIALS We retrospectively analyzed all patients who underwent PCI for acute coronary syndrome (ACS) from 2003 to 2016. Coronary perfusion pressure was calculated for each patient and defined as the difference in mean arterial pressure and left ventricular end diastolic pressure (LVEDP). Logistic regression analysis was performed to determine predictor of composite outcome of in-hospital mortality, myocardial infarction (MI), congestive heart failure (CHF), and cardiogenic shock. RESULTS Nine hundred twenty-two patients were analyzed. Two-hundred twenty-eight (25%) presented with ST-elevation MI (STEMI) while 694 (75%) underwent PCI for unstable angina or non-Q-wave MI. The mean LVEDP was significantly higher in the STEMI patients (24 ± 9 vs. 19 ± 8 mm Hg, p

Spontaneous coronary artery dissection (SCAD) can lead to acute coronary syndrome and sudden cardiac death, particularly in young women. Observational data show that, in SCAD patients, both percutaneous coronary intervention and coronary artery bypass grafting seem to be hampered by higher technical complexity, lower success rates, and worse outcomes. As spontaneous healing is a common occurrence, expert consensus advices medical management of the acute phase, when feasible. We present the case of a young woman with SCAD of left anterior descending artery causing myocardial infarction with ST‐segment elevation. High‐anatomical complexity and unstable conditions of the patient made both medical management and immediate revascularization unfeasible options. Therefore, we decided to implant a percutaneous off‐loading mechanical support device to improve coronary perfusion pressure by unloading the left ventricle and preserve cardiac function, preventing worse complications of acute myocardial infarction. This strategy was successful in stabilizing the patient, until the definitive revascularization treatment became an option.

BACKGROUND: Current guidelines recommend a 50 mm or greater compression depth for manual chest compression in adults. However, whether this uniform compression depth is a suitable requirement for mechanical CPR remains to be determined. We hypothesized that a relatively shallow compression depth (30 mm) would have similar hemodynamic efficacy but fewer complications versus the standard compression depth (50 mm) during mechanical cardiopulmonary resuscitation (CPR) with the miniaturized chest compressor (MCC) in a porcine model. METHODS: In the current study, we used a total of 16 domestic male pigs (38±2 kg). All pigs were exposed to 7 min of ventricular fibrillation (VF) followed by 5 min of CPR. Then the animals were randomly assigned to the shallow (30 mm) group and the standard (50 mm) group. At the second min of CPR, every pig was given epinephrine (20 µg/kg) through the femoral vein and repeated every 3 min. First defibrillation was delivered with a single 120 J shock at 5 min of CPR. Hemodynamics, carotid blood flow (CBF), end-tidal carbon dioxide (ETCO(2)), coronary perfusion pressure (CPP), intrathoracic pressure (ITP) and arterial blood gas were measured. Rib fractures and lung injuries, as indicated by ground-glass opacification (GGO), as well as intense parenchymal opacification (IPO), were assessed and calculated by quantitative computed tomography (QCT) scan. RESULTS: We found no significant differences in CPP, CBF, or ETCO(2) between the both groups throughout the CPR period. After administration of epinephrine, the CPP of all animals increased while ETCO(2) and CBF decreased during CPR. A significantly lower intrathoracic positive pressure (ITPP) and systolic artery pressure (SAP) were measured in the shallow group at the first min of CPR. However, we didn’t find remarkable differences in these values between the both groups for the next 4 min of CPR. All animals were successfully resuscitated. The shallow group had significantly lower IPO QCT scores compared with the standard group. We found no significant differences in GGO QCT scores after resuscitation between both groups. CONCLUSIONS: Relatively shallow compression depth has similar hemodynamic efficacy but fewer complications versus the standard compression depth.

Primary vasopressor efficacy of epinephrine during cardiopulmonary resuscitation (CPR) is due to its α-adrenergic effects. However, epinephrine plays β1-adrenergic actions, which increasing myocardial oxygen consumption may lead to refractory ventricular fibrillation (VF) and poor outcome. Effects of a single dose of esmolol in addition to epinephrine during CPR were investigated in a porcine model of VF with an underlying acute myocardial infarction. VF was ischemically induced in 16 pigs and left untreated for 12 min. During CPR, animals were randomized to receive epinephrine (30 µg/kg) with either esmolol (0.5 mg/kg) or saline (control). Pigs were then observed up to 96 h. Coronary perfusion pressure increased during CPR in the esmolol group compared to control (47 ± 21 vs. 24 ± 10 mmHg at min 5, p p p p

Background A ‘catecholamine storm’ in a case of pheochromocytoma can lead to a transient left ventricular dysfunction similar to Takotsubo cardiomyopathy. A cardiogenic shock can thus develop, with high left ventricular end-diastolic pressure and a reduction in coronary perfusion pressure. This scenario can ultimately lead to a cardiac arrest, in which unloading the left ventricle with a peripheral left ventricular assist device (Impella®) could help in achieving the return of spontaneous circulation (ROSC). Case summary A patient affected by Takotsubo cardiomyopathy caused by a pheochromocytoma presented with cardiogenic shock that finally evolved into refractory cardiac arrest. Cardiopulmonary resuscitation was performed but ROSC was achieved only after Impella® placement. Discussion In the clinical scenario of Takotsubo cardiomyopathy due to pheochromocytoma, when cardiogenic shock develops treatment is difficult because exogenous catecholamines, required to maintain organ perfusion, could exacerbate hypertension and deteriorate the cardiomyopathy. Moreover, as the coronary perfusion pressure is critically reduced, refractory cardiac arrest could develop. Although veno-arterial extra-corporeal membrane oxygenation (va-ECMO) has been advocated as the treatment of choice for in-hospital refractory cardiac arrest, in the presence of left ventricular overload a device like Impella®, which carries fewer complications as compared to ECMO, could be effective in obtaining the ROSC by unloading the left ventricle.

Aim Pseudo-pulseless electrical activity (pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG with no clinically detectable pulses. The role of standard external chest compressions (CPR) and its associated intrinsic hemodynamics remains unclear in the setting of pseudo-PEA. We undertook an experimental trial to compare epinephrine alone versus epinephrine with CPR in the treatment of pseudo-PEA. Methods Using a porcine model of hypoxic pseudo-PEA, we randomized 12 Yorkshire male swine to resuscitation with epinephrine only (control) (0.0015 mg/kg) versus epinephrine plus standard CPR (intervention). Animals who achieved return of spontaneous circulation (ROSC) were stabilized, fully recovered to hemodynamic and respiratory baseline, and rearrested up to 6 times. Primary outcome was ROSC defined as a sustained systolic blood pressure (SBP) of 60 mmHg for 2 min. Secondary outcomes included time to ROSC, coronary perfusion pressure (CoPP), and end-tidal carbon dioxide (ETCO2). Results Among 47 events of pseudo-PEA in 12 animals, we observed significantly higher proportion of ROSC when treatment included CPR (14/21 – 67%) compared to epinephrine alone (4/26 – 15%) (p = 0.0007). CoPP, aortic pressures and ETCO2 were significantly higher, and right atrial pressures were lower in the intervention group. Conclusions In a swine model of hypoxia-induced pseudo-PEA, epinephrine plus CPR was associated with improved intra-arrest hemodynamics and higher probability of ROSC. Thus, epinephrine plus CPR may be superior to epinephrine alone in the treatment of patients with pseudo-PEA.

Although progesterone has the ability to promote dilation of vascular smooth muscle, its role in coronary circulation is still poorly characterized, especially in essential hypertension and in a model of endogenous deficiency of ovarian hormones. Thus, this study evaluated the effect of progesterone treatment on endothelium-dependent coronary vascular reactivity in hypertensive (SHR) and ovariectomized rats. Adult SHR aged 8–10 weeks were divided into: SHAM, Ovariectomized (OVX) and Ovariectomized + treatment with 2 mg/kg/day of progesterone for 15 days (OVX-P4). Coronary vascular reactivity was investigated using the modified Langendorff method. After stabilization, baseline coronary perfusion pressure (CPP) was recorded and vascular reactivity to bradykinin (BK, 0.1–1000 ng) were assessed before and after infusion, either individually or in combination, with Nω-nitro-l-arginine methyl ester (l-NAME), indomethacin or clotrimazole. Scanning electron microscopy was used for qualitative analysis of the endothelium. OVX and OVX-P4 groups had a higher baseline CPP compared to that of the SHAM group. BK was able to promote vasodilation in all groups. However, relaxation to BK was less pronounced in the OVX group when compared to SHAM, with architecture loss and areas of cell atrophy having been observed. Progesterone treatment prevented this injury. Perfusion with l-NAME induced greater damage to the SHAM group, while the use of indomethacin led to a significant reduction in the vasodilator response to BK in the OVX-P4 group. Taken together, our results show that progesterone modulates endothelium-dependent coronary vasodilation in SHR ovariectomized, preventing damage caused by ovarian hormonal deficiency through a mechanism that involves prostanoid pathway.

Aim of the study Controlled sequential elevation of the head and thorax (CSE) during active compression decompression (ACD) cardiopulmonary resuscitation (CPR) with an impedance threshold device (ITD) has been shown to increase cerebral perfusion pressure and cerebral blood flow in previous animal studies as compared to the traditional supine position. The potential for this novel bundled treatment strategy to improve survival with intact neurological function is unknown. Methods Female farm pigs were sedated, intubated, and anesthetized. Central arterial and venous access were continuously monitored. Regional brain tissue perfusion (CerO2) was also measured transcutaneous. Ventricular fibrillation (VF) was induced and untreated for 10 min. Pigs were randomized to (1) Conventional CPR (C-CPR) flat or (2) ACD + ITD CSE CPR that included 2 min of ACD + ITD with the head and heart first elevated 10 and 8 cm, and then gradual elevation over 2 min to 22 and 9 cm, respectively. After 19 min of CPR, pigs were defibrillated and recovered. A veterinarian blinded to the intervention assessed cerebral performance category (CPC) at 24 h. A neurologically intact outcome was defined as a CPC score of 1 or 2. Categorical outcomes were analyzed by Fisher's exact test and continuous outcomes with an unpaired student's t-test. Results In 16 animals, return of spontaneous circulation rate was 8/8 (100%) with ACD + ITD CSE and 3/8 (25%) for C-CPR (p = 0.026). For the primary outcome of neurologically intact survival, 6/8 (75%) pigs had a CPC score 1 or 2 with ACD + ITD CSE versus 1/8 (12.5%) with C-CPR (p = 0.04). Coronary perfusion pressure (mmHg, mean ± SD) was higher with CSE at 18 min (41 ± 24 versus 10 ± 5, p = 0.004). rSO2 (%, mean ± SD) and ETCO2 (mmHg, mean ± SD) values were higher at 18 min with CSE (32 ± 9 versus 17 ± 2, p = 0.01, and 55 mmHg ± 10 versus 21 mmHg ± 4, p Conclusions The novel bundled resuscitation approach of CSE with ACD + ITD CPR increased favorable neurological survival versus C-CPR in a swine model of cardiac arrest.

Intraaortic balloon pump counterpulsation is the most common form of mechanical circulatory support used in patients with myocardial ischemia and cardiogenic shock. The physiologic principles of counterpulsation include diastolic augmentation of aortic pressure and systolic reduction of left ventricular afterload, resulting in hemodynamic benefits through increased coronary perfusion pressure and improved myocardial oxygen balance in patients with myocardial ischemia. Major trials have failed to conclusively demonstrate improvements in morbidity and mortality with counterpulsation therapy for patients with acute myocardial infarction (MI), cardiogenic shock, and/or severe coronary artery disease undergoing revascularization therapy, and the debate over its applications continues. Part I of this review focuses on the history of the development of counterpulsation, technical considerations, and complications associated with its use, its physiologic effects, and evidence for its use in myocardial ischemia and cardiogenic shock.

Introduction Amiodarone represents the most widely used antiarrhythmic drug, even though it has been shown that it has negative inotropic and lusitropic effect in healthy hears. On the other hand, dronedarone reduces the risk of recurrent atrial fibrillation, but with increased early mortality related to the worsening of heart failure. However, the mechanisms responsible for these fatal outcomes remain unclear and require further examinations. Purpose To investigate acute, direct effects of Dronedarone and Amiodarone on cardiac contractility, coronary flow and oxidative stress parameters in isolated rat heart with hypertension. Methods The present study was carried out on 18 isolated hearts of spontaneously hypertensive Wistar Kyoto male rats (6 weeks old, bodyweight 200 ± 10 g). After isolation, all hearts were retrogradely perfused according to Langendorff technique with a gradually increment of coronary perfusion pressure (CPP from 40 to 120 cm H2O) and randomly divided into 3 groups: Control (n = 6), Amiodarone (n = 6, isolated hearts perfused with Amiodarone in dose of 3 umol), Dronedarone (n = 6, isolated hearts perfused with Dronedarone in dose of 1.8 umol). During ex vivo protocol continuously were registered cardiac contractility parameters and coronary flow, while from collected coronary venous effluent markers of oxidative stress were measured. All hearts were then fixated and stained with Hematoxylin/eosin. Results Dronedarone severely depressed the function of all cardiodynamic parameters of the heart compared with Amiodarone or Control while Amiodarone intensified the function of the isolated rat heart with hypertension compared to Control (dp/dt max mmHg/s at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 579.733 ± 202.27 vs. 3063.65 ± 467.93 vs. 2682.88 ± 368.75; p Conclusions Acute administration of Dronedarone depresses cardiac function in isolated, working rat heart with hypertension, with decreasing the NO2- levels, increasing the level of H2O2 and enhanced structural changes when compared to Amiodarone.

Aims The described association of low diastolic blood pressure (DBP) with increased cardiovascular outcomes could be due to reduced coronary perfusion or is simply due to reverse causation. If DBP is physiologically relevant, coronary reperfusion after myocardial infarction (MI) might influence DBP–risk association. Methods and results The relation of achieved DBP with cardiovascular death or cardiovascular hospitalization, cardiovascular death, and all-cause death was explored in 5929 patients after acute myocardial infarction (AMI) with impaired left ventricular function, signs and symptoms of heart failure, or diabetes in the EPHESUS trial according to their reperfusion status. Cox regression models were used to assess the impact of reperfusion status on the association of DBP and systolic blood pressure (SBP) with outcomes in an adjusted fashion. In patients without reperfusion, lower DBP Conclusion Patients after AMIs with a low DBP had an increased risk, which was sensitive to reperfusion therapy. Low blood pressure after MI identifies in patients with particular higher risk. These data support the hypothesis that low DBP in patients with stenotic coronary lesions is associated with risk, potentially involving coronary perfusion pressure and the recommendations provided by guidelines suggesting lower DBP boundaries for these high-risk patients.

The cardioprotective effect of oxytocin (OT) has been well established. However, there are no related studies on the role of endothelia in oxytocin-induced cardioprotection. Endothelial dysfunction (ED) model was established by injection of 0.01 % Triton X-100 in the isolated rat heart. Oxytocin pretreatment was conducted at the end of stabilization for 40 min, followed by 30 min global ischemia and 60 min reperfusion to induce I/R injury. Coronary perfusion pressure, hemodynamics and arrhythmia severity scores were measured respectively. High-sensitivity cardiac troponin T (hs-cTnT) was evaluated by enzyme-linked immunosorbent assay. Infarct size was detected by triphenyltetrazolium chloride staining. The morphological changes in coronary endothelium were observed by scanning electron microscopy. Injection of 0.01 % Triton X-100 caused significant reduction of CPP induced by histamine and endothelium removal from scanning electron microscopy, but SNP had no significant effect. Oxytocin pretreatment showed significant recovery in LVDP, ±dp/dtmax, RPP and SI after reperfusion (P 0.05). I/R injury exacerbated the decrease in CPP and worsened the migration, deformation, and fracture of coronary endothelium, while oxytocin reversed these injuries. Despite the presence of endothelial damages, oxytocin partially alleviated I/R- and Triton-induced endothelial damages. The cardioprotective effects of oxytocin are independent of endothelial function in alleviating I/R injury and I/R-induced coronary endothelial dysfunction.

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Background The aim of this study was to investigate whether 33% duty cycle increases end-tidal carbon dioxide (ETCO2) level, a surrogate measurement for cardiac output during cardiopulmonary resuscitation (CPR), compared with 50% duty cycle. Methods Six pigs were randomly assigned to the DC33 or DC50 group. After 3 min of induced ventricular fibrillation (VF), CPR was performed for 5 min with 33% duty cycle (DC33 group) or with 50% duty cycle (DC50 group) (phase I). Defibrillation was delivered until return of spontaneous circulation (ROSC) thereafter. After 30 min of stabilization, the animals were re-assigned to the opposite groups. VF was induced again, and CPR was performed (phase II). The primary outcome was ETCO2 during CPR, and the secondary outcomes were coronary perfusion pressure (CPP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and right atrial pressure (RAP). Results Mean ETCO2 was higher in the DC33 group compared with the DC50 group (22.5 mmHg vs 21.5 mmHg, P = 0.018). In a linear mixed model, 33% duty cycle increased ETCO2 by 1.0 mmHg compared with 50% duty cycle (P < 0.001). ETCO2 increased over time in the DC33 group [0.6 mmHg/min] while ETCO2 decreased in the DC50 group [-0.6 mmHg/min] (P < 0.001). Duty cycle of 33% increased SAP (6.0 mmHg, P < 0.001), DAP (8.9 mmHg, P < 0.001) RAP (2.6 mmHg, P < 0.001) and CPP (4.7 mmHg, P < 0.001) compared with the duty cycle of 50%. Conclusion Duty cycle of 33% increased ETCO2, a surrogate measurement for cardiac output during CPR, compared with duty cycle of 50%. Moreover, ETCO2 increased over time during CPR with 33% duty cycle while ETCO2 decreased with 50% duty cycle.

Aim To investigate the molecular mechanisms and cellular signaling pathways involved in the activation of TP receptors and the consequent induction of contractile responses in coronary arteries of renal hypertensive (2K-1C) rats. Methods and results The coronary perfusion pressure (CPP) was lower in 2K-1C rats during increased coronary flow as measured by the Langendorff technique. The coronary contraction and relaxation were evaluated by vascular reactivity studies, and the molecular mechanisms were investigated on the basis of the protein expression of TP receptors, Cav-1, eNOS, COX-1, and COX-2, as measured by Western blot. The levels of eicosanoids were determined by ELISA immunoassay and analyzed by reverse-phase HPLC coupled to electrospray ionization mass spectrometry (HPLC-MS/MS). The metabolites from NO production were evaluated by the Griess reaction. The coronary arteries of 2K-1C rats expressed COX-2 to a larger extent and TP receptors to a lesser extent than the coronary arteries of normotensive (2K) rats. Selective COX-1 and non-selective COX inhibitors reversed the reduction in the contraction induced by TP receptors in the coronary arteries of 2K-1C rats. U46619, an agonist of TP receptors, induced a contractile response that was relaxed by acetylcholine (ACh). In the coronary arteries of 2K-1C rats, this ACh-induced relaxation depended on COX. The activation of TP receptors increased the production of PGI2 in the coronary arteries of 2K-1C rats. The results demonstrated that increased COX signaling in the coronary arteries of 2K-1C rats mediated the low levels of CPP, the contraction induced by the activation of TP receptors, and the endothelium-dependent relaxation. The vasodilator PGI2 seemed to be the major product. Conclusion Activation of TP receptors increases production of PGI2 in coronary arteries of 2K-1C rats.

Background: There is a conflict in the superiority of each of the vasopressin and epinephrine compared to the other. Vasopressin has a vasoconstrictive action that results in an increase of the coronary perfusion pressure. Due to the expensive and sometimes scarce of vasopressin in most hospitals, this study aims to evaluate the response rate of vasopressin compared with epinephrine, in return of ROSC. Methods: In this descriptive-analytical study all patients in the emergency medicine department were enrolled in the study suffered a cardiopulmonary arrest and resuscitation will be done instantly for them (According to the guidelines AHA 2010). Their data were extracted from the hospital records and the success rate of recovery, 3-month survival and complications in patients recovering from the drug used during the CPR were analyzed. Results: A total of 61 patients record were analyzed. 31 patients had received epinephrine alone and 30 patients received a combination of epinephrine and vasopressin. No significant difference was observed between the two groups in terms of sex, sepsis, hypovolemia, renal failure, cancers, drug toxicity, brady, dysrhythmia, PEA, VT, VF, defibrillator, duration of CPR and three month outcome. The mean time of CPR in combination of epinephrine and vasopressin group was 27.26±12.72 and the mean time of CPR in epinephrine group was 27.24±13.510 (p-value= 0.99).Conclusion: Among patients with in-hospital cardiopulmonary arrest in this study no statistically significant difference was obtained between the results of treatment with epinephrine alone and combination of epinephrine and vasopressin.

Background: A compression-ventilation (C:V) ratio of 30:2 is recommended for adult cardiopulmonary resuscitation (CPR) by the current American Heart Association (AHA) guidelines. However, continuous chest compression (CCC) is an alternative strategy for CPR that minimizes interruption especially when an advanced airway exists. In this study, we investigated the effects of 30:2 mechanical CPR when compared with CCC in combination with regular ventilation in a porcine model. Methods: Sixteen male domestic pigs weighing 39±2 kg were utilized. Ventricular fibrillation was induced and untreated for 7 min. The animals were then randomly assigned to receive CCC combined with regular ventilation (CCC group) or 30:2 CPR (VC group). Mechanical chest compression was implemented with a miniaturized mechanical chest compressor. At the same time of beginning of precordial compression, the animals were mechanically ventilated at a rate of 10 breaths-per-minute in the CCC group or with a 30:2 C:V ratio in the VC group. Defibrillation was delivered by a single 150 J shock after 5 min of CPR. If failed to resuscitation, CPR was resumed for 2 min before the next shock. The protocol was stopped if successful resuscitation or at a total of 15 min. The resuscitated animals were observed for 72 h. Results: Coronary perfusion pressure, end-tidal carbon dioxide and carotid blood flow in the VC group were similar to those achieved in the CCC group during CPR. No significant differences were observed in arterial blood gas parameters between two groups at baseline, VF 6 min, CPR 4 min and 30, 120 and 360 min post-resuscitation. Although extravascular lung water index of both groups significantly increased after resuscitation, no distinct difference was found between CCC and VC groups. All animals were successfully resuscitated and survived for 72 h with favorable neurologic outcomes in both groups. However, obviously more numbers of rib fracture were observed in CCC animals in comparison with VC animals Conclusions: There was no difference in hemodynamic efficacy and gas exchange during and after resuscitation, therefore identical 72 h survival with intact neurologic function was observed in both VC and CCC groups. However, the incidence of rib fracture increases during the mechanical CPR strategy of CCC combined with regular ventilations.

Compared with age-matched men, premenopausal women are largely protected from coronary artery disease, a difference that is lost after menopause. The effects of oestrogens are mediated by the activation of nuclear receptors (ERα and ERβ) and by the G protein-coupled oestrogen receptor (GPER). This study aims to evaluate the potential role of GPER in coronary circulation in female and male rats. The baseline coronary perfusion pressure (CPP) and the concentration–response curve with a GPER agonist (G-1) were evaluated in isolated hearts before and after the blockade of GPER. GPER, superoxide dismutase (SOD-2), catalase and gp91phox protein expression were assessed by Western blotting. Superoxide production was evaluated ‘in situ’ via dihydroethidium fluorescence (DHE). GPER blockade significantly increased the CPP in both groups, demonstrating the modulation of coronary tone by GPER. G-1 causes relaxation of the coronary bed in a concentration-dependent manner and was significantly higher in female rats. No differences were detected in GPER, SOD-2 and catalase protein expression. However, gp91phox expression and DHE fluorescence were higher in male rats, indicating elevated superoxide production. Therefore, GPER plays an important role in modulating coronary tone and reactivity in female and male rats. The observed differences in vascular reactivity may be related to the higher superoxide production in male rats. These findings help to elucidate the role of GPER-modulating coronary circulation, providing new information to develop a potential therapeutic target for the treatment of coronary heart disease.

Background Centhaquin citrate is a novel agent being developed for use in the treatment of haemorrhagic shock. The aim of our study was to assess whether the administration of centhaquin would improve initial resuscitation success, 24-hour survival, and neurologic outcome compared with adrenaline alone in a porcine model of ventricular fibrillation. Methods Ventricular fibrillation was induced in 20 healthy Landrace/Large White piglets. The animals were randomised to receive placebo plus adrenaline 0.02mg/kg (n=10, Group C) and adrenaline 0.02mg/kg plus centhaquin 0.015mg/kg (n=10, Group S). All animals were resuscitated according to the 2010 European Resuscitation Council guidelines. Haemodynamic variables were measured before arrest, during arrest and resuscitation, and during the first two hours after return of spontaneous circulation (ROSC). Survival and a neurologic alertness score were measured at 24hours after ROSC. Results A significant difference was observed in ROSC rate between the two groups, as 10 animals (100%) from Group S and 4 animals (40%) from Group C achieved ROSC (p=0.011). Systolic, diastolic, and mean aortic pressure and coronary perfusion pressure were significantly higher in Group S at the end of the second cycle of CPR. In our study, all subjects with ROSC survived for 24hours, while we observed no statistically significant differences in neurologic examination (Group C 100±0, Group S 96±12.64; p=0.527). Conclusion The addition of centhaquin to adrenaline improved ROSC rates in a swine model of VF cardiac arrest.

The main areas of emphasis in the Advanced Cardiac Life Support (ACLS) guidelines are: early recognition of cardiac arrest and call for help; good-quality chest compressions; early defibrillation when applicable; early administration of drugs; appropriate airway management ensuring normoventilation; and delivery of appropriate post-resuscitation care to enhance survival. Of note, it is important to monitor the quality of the various care procedures. The resuscitation team needs to reduce unnecessary interruptions to chest compressions in order to maintain adequate coronary perfusion pressure during the ACLS drill. In addition, the team needs to continually look out for reversible causes of the cardiac arrest.

Background Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. Aim of Study To test the effects of CFZ (10− 9 to 10− 7 mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. Methods and Results CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic strips with contraction plateau reached after 10 min. This spasmogenic effect doubled following ablation of the endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreated with CFZ exhibited impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium-dependent vasodilating agent, on the plateau of NA contraction (p, Highlights • In the isolated aorta, carfilzomib increased basal tone and vasospastic action of KCl, noradrenaline and angiotensin II. • In the isolated aorta, carfilzomib impaired the anti-spasmogenic activity of nitroglycerin, nifedipine and acetylcholine. • In the isolated heart, carfilzomib increased coronary perfusion pressure, and mildly left ventricular pressure and heart rate. Carfilzomib is a new chemotherapeutic agent used for the treatment of multiple myeloma. Our study shows that carfilzomib increases coronary perfusion pressure, resting vasoconstricting tone, and the spasmogenic effect of noradrenaline and angiotensin II, while it curbs the vasodilatory action of nitroglycerine and nifedipine. Our findings are relevant to human health as they warrant caution in the use of carfilzomib in elderly patients with cardiovascular risk factors and, even more importantly, in those with preexisting heart conditions, who are also eligible to receive carfilzomib, even though they were excluded from the safety trials, based on which carfilzomib use was approved.

Highlights •The Minnesota Resuscitation Consortium has established a protocol for rapid transport of patients with refractory out-of-hospital VF cardiac arrest to the cardiac catheterization laboratory for rapid evaluation and stabilization often requiring ECMO. This protocol provides new challenges to treatment paradigms that were created to rapidly achieve return of spontaneous circulation in the field. •A porcine model of refractory VF cardiac arrest was developed, including initiation of VF using endovascular occlusion of the proximal LAD followed by 5 min of untreated VF. Resuscitation begins with 10 min of high-quality CPR followed by 35 min of ACLS and reconstitution of coronary flow. •A 2 × 2 study design was used with animals randomized to use of epinephrine or placebo during ACLS and then again randomized to ECMO or no ECMO at the time of reinitiation of coronary flow. •ECMO-facilitated coronary reperfusion and hemodynamic stabilization improved 4-h survival compared with CPR-facilitated reperfusion and standard ACLS in a porcine model of refractory VF cardiac arrest. •Repeated epinephrine boluses provided in accordance with standard ACLS protocols increased systemic blood pressure and coronary perfusion pressure but provided no benefit in survival compared with placebo. •Over 50% of the animals receiving ECMO met criteria for decannulation at 4 h, suggesting that rapid cardiac and hemodynamic recovery is possible in severely injured animals treated with ECMO.

Non-traumatic cardiac arrest is a major public health problem that carries an extremely high mortality rate. If we hope to increase the survivability of this condition, it is imperative that alternative methods of treatment are given due consideration. Balloon occlusion of the aorta can be used as a method of circulatory support in the critically ill patient. Intra-aortic balloon pumps have been used to temporize patients in cardiogenic shock for decades. More recently, resuscitative endovascular balloon occlusion of the aorta (REBOA) has been utilized in the patient in hemorrhagic shock or cardiac arrest secondary to trauma. Aortic occlusion in non-traumatic cardiac arrest has the effect of reducing the vascular volume that the generated cardiac output is distributed across. This augments myocardial and cerebral perfusion, increasing the probability of a return to a good quality of life for the patient. This phenomenon has been the subject of numerous animal studies dating back to the early 1980s; however, the human evidence is limited to several small case series. Animal research has demonstrated improvements in cerebral and coronary perfusion pressure during ACLS that lead to statistically significant differences in mortality. Several case series in humans have replicated these findings, suggesting the efficacy of this procedure. The objectives of this review are to: 1) introduce the reader to REBOA 2) review the physiology of NTCA and examine the current limitations of traditional ACLS 3) summarize the literature regarding the efficacy and feasibility of aortic balloon occlusion to support traditional ACLS.

Aim Most pediatric in-hospital cardiac arrests (IHCAs) occur in ICUs where invasive hemodynamic monitoring is frequently available. Titrating cardiopulmonary resuscitation (CPR) to the hemodynamic response of the individual improves survival in preclinical models of adult cardiac arrest. The objective of this study was to determine if titrating CPR to systolic blood pressure (SBP) and coronary perfusion pressure (CoPP) in a pediatric porcine model of asphyxia-associated ventricular fibrillation (VF) IHCA would improve survival as compared to traditional CPR. Methods After 7min of asphyxia followed by VF, 4-week-old piglets received either hemodynamic-directed CPR (HD-CPR; compression depth titrated to SBP of 90mmHg and vasopressor administration to maintain CoPP ≥20mmHg); or Standard Care (compression depth 1/3 of the anterior–posterior chest diameter and epinephrine every 4min). All animals received CPR for 10min prior to the first defibrillation attempt. CPR was continued for a maximum of 20min. Protocolized intensive care was provided to all surviving animals for 4h. The primary outcome was 4-h survival. Results Survival rate was greater with HD-CPR (12/12) than Standard Care (6/10; p=0.03). CoPP during HD-CPR was higher compared to Standard Care (point estimate +8.1mmHg, CI 95 : 0.5–15.8mmHg; p=0.04). Chest compression depth was lower with HD-CPR than Standard Care (point estimate −14.0mm, CI95: −9.6 to −18.4mm; p Conclusions Hemodynamic-directed CPR improves short-term survival compared to standard depth-targeted CPR in a porcine model of pediatric asphyxia-associated VF IHCA.

According to the European Resuscitation Council guidelines, the use of mechanical chest compression devices is a reasonable alternative in situations where manual chest compression is impractical or compromises provider safety. The aim of this study is to compare the performance of a recently developed chest compression device (Corpuls CPR) with an established system (LUCAS II) in a pig model. Methods. Pigs (n = 5/group) in provoked ventricular fibrillation were left untreated for 5 minutes, after which 15 min of cardiopulmonary resuscitation was performed with chest compressions. After 15 min, defibrillation was performed every 2 min if necessary, and up to 3 doses of adrenaline were given. If there was no return of spontaneous circulation after 25 min, the experiment was terminated. Coronary perfusion pressure, carotid blood flow, end-expiratory CO2, regional oxygen saturation by near infrared spectroscopy, blood gas, and local organ perfusion with fluorescent labelled microspheres were measured at baseline and during resuscitation. Results. Animals treated with Corpuls CPR had significantly higher mean arterial pressures during resuscitation, along with a detectable trend of greater carotid blood flow and organ perfusion. Conclusion. Chest compressions with the Corpuls CPR device generated significantly higher mean arterial pressures than compressions performed with the LUCAS II device.

Introduction: Epinephrine is the primary drug given during cardiopulmonary resuscitation (CPR), when given early, to reverse cardiac arrest (CA) by stimulation of α-adrenergic receptors in vascular smooth muscle. This increases coronary perfusion pressure (CPP) and increases rate of return of spontaneous circulation (ROSC). However, the use of epinephrine is not associated with a significant difference in long-term survival or favorable neurologic outcome when given late after arrest onset. In the present study, we compared the effects of aortic injection of polyethylene glycol-20k (PEG-20k) vs. epinephrine during CPR on CPP and postresuscitation myocardial and cerebral function in a rat model of CA. Hypothesis: Aortic injection of PEG-20k during CPR will increase CPP to the same extent as epinephrine without adversely affecting post-resuscitation myocardial and cerebral function. Methods: Twenty four male Sprague-Dawley rats weighing between 450-550 g were randomized into four groups: 1) PEG-20k 2) epinephrine 3) saline placebo 4) saline-intra-aorta (IA). Eight minutes of CPR was initiated after 6 minutes of untreated ventricular fibrillation. PEG-20k IA (10% est. total blood volume [1.8ml]), saline IA, saline IV or epinephrine IV (20ug/kg) was given after 4 minutes of CPR by continuous infusion over 3 minutes. CPP was recorded continuously and resuscitation was attempted with 4 Joule defibrillation. Myocardial function was measured at baseline, 2, 4, and 6 hours after ROSC by echocardiography and neurologic deficit scores (NDS) were recorded at 24, 48, and 72 hours after ROSC. Results: In both saline groups, CPP did not change. However, aortic injection of PEG-20k increased CPP significantly to the same extent as epinephrine (Fig 1). Post-resuscitation ejection fraction was significantly greater in PEG-20k compared to epinephrine (64 + 1 vs 45 + 3, p+ 50 vs 450 + 50, p

Background and purposes: Dexmedetomidine preconditioning (DP) can mimic pharmacological preconditioning and induce cardiac protection. There are controversies on the roles of coronary endothelia in cardioprotection of dexmedetomidine. Herein, we tested the hypothesis that protection of dexmedetomidine is not endothelial dependent in heart against myocardial ischemia/reperfusion (I/R) injury. Methods: Langendorff-perfused rat hearts were pretreated by 60 mM of potassium to produce endothelial dysfunction (ED), then medicated with dexmedetomidine, and subsequently subjected to 30 min of global ischemia followed by 60 min of reperfusion. To investigate the cardioprotective effect of dexmedetomidine in heart with ED, isolated rat hearts were randomly divided into the following six groups: sham, I/R, DP, ED, ED + I/R, and ED + DP + I/R. Heart rates, left ventricular function, and coronary perfusion pressure were assessed for each heart. Infarct size was evaluated by triphenyltetrazolium chloride staining. High-sensitivity cardiac troponin T (hs-cTNT) of coronary flow perfusion was determined. Results: After the isolated hearts with pretreatment of 60 mM of potassium chloride, diastolic function of coronary endothelia in performance of response to histamine was significantly decreased (P

Background. Different mechanisms have been proposed to relate atrial fibrillation (AF) and coronary flow impairment, even in absence of relevant coronary artery disease (CAD). However, the underlying hemodynamics remains unclear. Aim of the present work is to computationally explore whether and to what extent ventricular rate during AF affects the coronary perfusion. Methods. AF is simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) through a 0D-1D multiscale validated model, which combines the left heart-arterial tree together with the coronary circulation. Artificially-built RR stochastic extraction mimics the \emph{in vivo} beating features. All the hemodynamic parameters computed are based on the left anterior descending (LAD) artery and account for the waveform, amplitude and perfusion of the coronary blood flow. Results. Alterations of the coronary hemodynamics are found to be associated either to the heart rate increase, which strongly modifies waveform and amplitude of the LAD flow rate, and to the beat-to-beat variability. The latter is overall amplified in the coronary circulation as HR grows, even though the input RR variability is kept constant at all HRs. Conclusions. Higher ventricular rate during AF exerts an overall coronary blood flow impairment and imbalance of the myocardial oxygen supply-demand ratio. The combined increase of heart rate and higher AF-induced hemodynamic variability lead to a coronary perfusion impairment exceeding 90-110 bpm in AF. Moreover, it is found that coronary perfusion pressure (CPP) is no longer a good measure of the myocardial perfusion for HR higher than 90 bpm., 8 pages, 5 figures, 3 tables

OBJECTIVES Less than half of the thousands of children who suffer in-hospital cardiac arrests annually survive, and neurologic injury is common among survivors. Hemodynamic-directed cardiopulmonary resuscitation improves short-term survival, but its impact on longer term survival and mitochondrial respiration-a potential neurotherapeutic target-remains unknown. The primary objectives of this study were to compare rates of 24-hour survival with favorable neurologic outcome after cardiac arrest treated with hemodynamic-directed cardiopulmonary resuscitation versus standard depth-guided cardiopulmonary resuscitation and to compare brain and heart mitochondrial respiration between groups 24 hours after resuscitation. DESIGN Randomized preclinical large animal trial. SETTING A large animal resuscitation laboratory at a large academic children's hospital. SUBJECTS Twenty-eight 4-week-old female piglets (8-11 kg). INTERVENTIONS Twenty-two swine underwent 7 minutes of asphyxia followed by ventricular fibrillation and randomized treatment with either hemodynamic-directed cardiopulmonary resuscitation (n = 10; compression depth titrated to aortic systolic pressure of 90 mm Hg, vasopressors titrated to coronary perfusion pressure ≥ 20 mm Hg) or depth-guided cardiopulmonary resuscitation (n = 12; depth 1/3 chest diameter, epinephrine every 4 min). Six animals (sham group) underwent anesthesia and instrumentation without cardiac arrest. The primary outcomes were favorable neurologic outcome (swine Cerebral Performance Category ≤ 2) and mitochondrial maximal oxidative phosphorylation utilizing substrate for complex I and complex II (OXPHOSCI+CII) in the cerebral cortex and hippocampus. MEASUREMENTS AND MAIN RESULTS Favorable neurologic outcome was more likely with hemodynamic-directed cardiopulmonary resuscitation (7/10) than depth-guided cardiopulmonary resuscitation (1/12; p = 0.006). Hemodynamic-directed cardiopulmonary resuscitation resulted in higher intra-arrest coronary perfusion pressure, aortic pressures, and brain tissue oxygenation. Hemodynamic-directed cardiopulmonary resuscitation resulted in higher OXPHOSCI+CII (pmol oxygen/s × mg/citrate synthase) in the cortex (6.00 ± 0.28 vs 3.88 ± 0.43; p < 0.05) and hippocampus (6.26 ± 0.67 vs 3.55 ± 0.65; p < 0.05) and higher complex I respiration (pmol oxygen/s × mg) in the right (20.62 ± 1.06 vs 15.88 ± 0.81; p < 0.05) and left ventricles (20.14 ± 1.40 vs 14.17 ± 1.53; p < 0.05). CONCLUSIONS In a model of asphyxia-associated pediatric cardiac arrest, hemodynamic-directed cardiopulmonary resuscitation increases rates of 24-hour survival with favorable neurologic outcome, intra-arrest hemodynamics, and cerebral and myocardial mitochondrial respiration.

AIM: We examined the use of a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) catheter during cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) to assess its effect on haemodynamics such as coronary perfusion pressure (CPP), common carotid artery blood flow (CCA-flow) and end-tidal CO(2) (PetCO(2)) which are associated with increased return of spontaneous circulation (ROSC). METHODS: Six male swine were instrumented to measure CPP, CCA-Flow, and PetCO2. A 7Fr REBOA was advanced into zone-1 of the aorta through the femoral artery. Ventricular fibrillation was induced and untreated for 8 min. CPR (manual then mechanical) was initiated for 24 min. Continuous infusion of adrenaline (epinephrine) was started at minute-4 of CPR. The REBOA balloon was inflated at minute-16 for 3 min and then deflated/inflated every 3 min for 3 cycles. Animals were defibrillated up to 6 times after the final cycle. Animals achieving ROSC were monitored for 25 min. RESULTS: Data showed significant differences between balloon deflation and inflation periods for CPP, CCA-Flow, and PetCO(2) (p < 0.0001) with an average difference (SD) of 13.7 (2.28) mmHg, 15.5 (14.12) mL min(−1) and −4 (2.76) mmHg respectively. Three animals achieved ROSC and had significantly higher mean CPP (54 vs. 18 mmHg), CCA-Flow (262 vs. 135 mL min(−1)) and PetCO(2) (16 vs. 8 mmHg) (p < 0.0001) throughout inflation periods than No-ROSC animals. Aortic histology did not reveal any significant changes produced by balloon inflation. CONCLUSION: REBOA significantly increased CPP and CCA-Flow in this model of prolonged CA. These increases may contribute to the ability to achieve ROSC.

We hypothesized that chest compressions located directly over the left ventricle (LV) would improve hemodynamics, including coronary perfusion pressure (CPP), and return of spontaneous circulation (ROSC) in a swine model of cardiac arrest.Transthoracic echocardiography (echo) was used to mark the location of the aortic root and the center of the left ventricle on animals (n = 26) which were randomized to receive chest compressions in one of the two locations. After a period of ten minutes of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation (CPR) was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) for an additional ten minutes. During BLS the area of maximal compression was verified using transesophageal echo. CPP and other hemodynamic variables were averaged every two minutes.Mean CPP was not significantly higher in the LV group during all time intervals of resuscitation; mean CPP was significantly higher in the LV group during the 12-14 minute interval of BLS and during minutes 22-30 of ACLS (p0.05). Aortic systolic and diastolic pressures, right atrial systolic pressures, and end-tidal CO2 (ETCO2) were higher in the LV group during all time intervals of resuscitation (p0.05). Nine of the left ventricle group (69%) achieved ROSC and survived to 60 minutes compared to zero of the aortic root group (p0.001).In our swine model of cardiac arrest, chest compressions over the left ventricle improved hemodynamics and resulted in a greater proportion of animals with ROSC and survival to 60 minutes.

Objective Ischemic postconditioning (PC) using three intentional pauses at the start of cardiopulmonary resuscitation (CPR) improves outcomes after cardiac arrest in pigs when epinephrine (epi) is used before defibrillation. We hypothesized PC, performed during basic life support (BLS) in the absence of epinephrine, would reduce reperfusion injury and enhance 24h functional recovery. Design Prospective animal investigation. Setting Animal laboratory Subjects Female farm pigs ( n =46, 39±1kg). Interventions Protocol A: After 12min of ventricular fibrillation (VF), 28 pigs were randomized to four groups: (A) Standard CPR (SCPR), (B) active compression-decompression CPR with an impedance threshold device (ACD-ITD), (C) SCPR+PC (SCPR+PC) and (D) ACD-ITD CPR+PC. Protocol B: After 15min of VF, 18 pigs were randomized to ACD-ITD CPR or ACD-ITD+PC. The BLS duration was 2.75min in Protocol A and 5min in Protocol B. Following BLS, up to three shocks were delivered. Without return of spontaneous circulation (ROSC), CPR was resumed and epi (0.5mg) and defibrillation delivered. The primary end point was survival without major adverse events. Hemodynamic parameters and left ventricular ejection fraction (LVEF) were also measured. Data are presented as mean±SEM. Measurements and Main Results Protocol A: ACD-ITD+PC (group D) improved coronary perfusion pressure after 3min of BLS versus the three other groups (28±6, 35±7, 23±5 and 47±7 for groups A, B, C, D respectively, p =0.05). There were no significant differences in 24h survival between groups. Protocol B LVEF 4h post ROSC was significantly higher with ACD-ITD+PC vs ACD-ITD alone (52.5±3% vs. 37.5±6.6%, p =0.045). Survival rates were significantly higher with ACD-ITD+PC vs. ACD-ITD alone ( p =0.027). Conclusions BLS using ACD-ITD+PC reduced post resuscitation cardiac dysfunction and improved functional recovery after prolonged untreated VF in pigs. Protocol number 12-11.

Background We sought to investigate the utility of arterial pressure, end-tidal carbon dioxide (ETCO2), and central venous oxygen saturation (SCVO2) to guide compression depth adjustment. Thus, in a pig model of cardiac arrest, we observed these parameters during cardiopulmonary resuscitation (CPR) with optimal and suboptimal compression depths. Methods Sixteen pigs underwent three experimental sessions after induction of ventricular fibrillation. First, the animals received two 4-min CPR trials with either optimal (20% of the anteroposterior diameter) or suboptimal (70% of the optimal depth) compression depth. Second, the animals received two 5-min CPR trials with optimal compression depth, in which adrenaline (0.02 mg/kg) or saline placebo was administered. Third, the animals randomly received compression with either optimal or suboptimal depth during advanced cardiovascular life support. Results The systolic arterial pressure reflected compression depth most accurately and immediately (area under the curve [AUC], 0.895–0.939 without adrenaline and 0.928–1.000 with adrenaline). Although the response of ETCO2 to the change in compression depth was 0.5 min slower than that of the systolic arterial pressure, the performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth. Adrenaline administration remarkably increased systolic arterial pressure, diastolic arterial pressure, and coronary perfusion pressure but did not affect the ETCO2 readings. Conclusion In a pig model of cardiac arrest, systolic arterial pressure reflected compression depth immediately and accurately. The performance of ETCO2 was comparable with that of systolic arterial pressure. SCVO2 did not reflect compression depth.

BACKGROUND Systemic hypertension and left ventricular hypertrophy (LVH) are major risk factors of cardiac arrest. However, the impacts of hypertension and LVH on the outcome of cardiopulmonary resuscitation (CPR) and post-resuscitation hypothermia are still undetermined. METHODS After 4 min of untreated ventricular fibrillation (VF) and 4 min of CPR, defibrillation was attempted in 16 male spontaneously hypertensive rats (SHR) with LVH and 16 male normotensive Wistar Kyoto (WKY) rats. When restoration of spontaneous circulation (ROSC) was achieved, animals were randomized into either hypothermia or normothermia. For animals subjected to hypothermia, rapid cooling was started immediately after ROSC and a temperature of 33.0 ± 0.4°C was maintained for 2 h. Normothermic animals were maintained at 37.0 ± 0.4°C. RESULTS Baseline mean arterial pressure, heart rate, and left ventricle mass were significantly higher but ejection fraction was lower for hypertensive animals. Coronary perfusion pressure was higher for SHR, but no differences in duration of CPR and number of defibrillations required for resuscitation compared with WKY. All of the animals were successfully resuscitated but post-resuscitation cardiac function was severely impaired in hypertensive animals. Serum levels of cardiac troponin T, amino-terminal pro-brain natriuretic peptide, and S100B measured after ROSC were also markedly higher in SHR groups. Fourteen WKY rats (87.5%) survived, whereas only 1 SHR (6.3%, P < 0.001) survived to 96 h. CONCLUSIONS In this rat model, systemic hypertension and LVH did not affect ROSC. However, survival was dismal due to elevated severity of cardiac and cerebral injury in hypertensive animals regardless of short-duration hypothermia.

Cardiac arrest (CA) results in a sepsis-like syndrome with activation of the innate immune system and increased mitochondrial bioenergetics. Objective: To determine if platelet mitochondrial respiration increases following CA in a porcine pediatric model of asphyxia-associated ventricular fibrillation (VF) CA, and if this readily obtained biomarker is associated with decreased brain mitochondrial respiration. CA protocol: 7 min of asphyxia, followed by VF, protocolized titration of compression depth to systolic blood pressure of 90 mmHg and vasopressor administration to a coronary perfusion pressure greater than 20 mmHg. Primary outcome: platelet integrated mitochondrial electron transport system (ETS) function evaluated pre- and post-CA/ROSC four hours after return of spontaneous circulation (ROSC). Secondary outcome: correlation of platelet mitochondrial bioenergetics to cerebral bioenergetic function. Platelet maximal oxidative phosphorylation (OXPHOSCI+CII), P