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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.

Objective Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. Methods Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). Results Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11–13.64; p I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84–13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD − 13.66; 95% CI − 18.6 to –8.71; p I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD − 1.63; 95% CI − 10.77–7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31–2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression–decompression (ACD) and impedance threshold (ITD) devices. Conclusion In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

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.

To evaluate the mean aortic-right atrial pressure (AoP-RAP) gradients and mean coronary perfusion pressures (CPPs) observed during open cardiac massage (OCM) versus those obtained with selective aortic arch perfusion (SAAP) in post-mortem hypovolemic swine.Post-mortum, male swine, utilized in prior studies of hemorrhage, were included in the study. Animals were bled ∼25-50% of circulating volume prior to death. Animals either underwent clamshell thoracotomy and OCM immediately after death was confirmed (n = 6) or underwent SAAP within 5-15 min of death (n = 6). Aortic root and right atrial pressures were recorded continuously during each method of resuscitation using solid state blood pressure catheters. Representative five beat samples were extracted; short, similarly timed segments of SAAP were also extracted. Mean AoP-RAP gradient and CPPs were calculated and compared.Mean AoP-RAP gradient and CPP were significantly higher in SAAP animals compared to OCM animals (mean ± SD; 29.1 ± 8.4 vs. 24.5 ± 5.0, p 0.001; 28.9 ± 8.5 vs. 9.9 ± 6.0, p 0.001). Mean CPP was not significantly different from mean AoP-RAP gradient in SAAP animals (p = 0.92); mean CPP was significantly lower than mean AoP-RAP gradient in OCM animals (p 0.001). While 97% of SAAP segments had a CPP 15 mmHg, only 17% of OCM segments had a CPP 15 mmHg (p 0.001).SAAP appears to create a more favorable and efficient hemodynamic profile for obtaining ROSC when compared to OCM in this preclinical porcine study.

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.

Objectives The effect of oestrogen in hormonal dysfunction is not clear, especially in the coronary vascular bed. This study aimed at estradiol action (E2) in the coronary vascular bed from sham-operated and gonadectomized female and male spontaneously hypertensive rats (SHRs). Methods Male and female SHRs had their mean arterial pressure (MAP) and baseline coronary perfusion pressure (CPP) determined. The effects of E2 (10 μM) were evaluated in isolated hearts by in bolus infusion before and after endothelium denudation (0.25 μM sodium deoxycholate) or perfusion with 100 μM NG-nitro-l-arginine methyl ester (L-NAME), 2.8 μM indomethacin, 0.75 μM clotrimazole, L-NAME after endothelium denudation, L-NAME plus indomethacin, or 4 mM tetraethylammonium (TEA). Results MAP was higher in males than in females, with gonadectomy increasing in females and reducing in males. CPP was higher in female group, remaining unaltered after gonadectomy. E2-induced vasorelaxation was observed in all groups, with no differences having been found between sexes even after gonadectomy. Perfusion with TEA, L-NAME, L-NAME plus indomethacin, and L-NAME after endothelium removal attenuated the relaxing response in all groups. Clotrimazole inhibited vasorelaxation only in female groups, and indomethacin did so only in gonadectomized groups. Endothelium participation was confirmed in female groups and in the gonadectomized male group. Conclusions Our results indicated that the vasodilator effect of E2 was mediated by an indirect mechanism – via endothelium – as well as by direct action – via vascular smooth muscle – in both groups. The characterization of these mechanisms in coronary arteries might shed light on the functional basis of hormonal dysfunction symptoms in hypertension.

Physiological or supraphysiological levels of testosterone appear to be associated with the development of risk factors for cardiovascular diseases such as hypertension, as this hormone modulates the release of endothelial factors. However, its actions are still controversial, especially in the coronary circulation of hypertensive animals. This study was designed to assess the effects of testosterone treatment (T) on endothelium-dependent coronary vascular reactivity in orchiectomized SHR. The animals were divided into SHAM, orchiectomized (ORX), ORX+T and ORX+T+aromatase inhibitor (AI). All treatments lasted 15 days. Blood pressure (BP) was measured. Dose–response curves to bradykinin (BK) were constructed using the Langendorff technique, followed by inhibition of endothelium mediators (NO, prostanoids, EETs) and potassium channels. The intensity of eNOS, COX-1, COX-2, Akt, and gp91phox protein expression was quantified by Western blotting. BP was elevated in SHAM, ORX+T, and ORX+T+AI groups. However, we did not observe differences in the ORX group. Baseline coronary perfusion pressure (CPP) remained unaffected. Orchiectomy did not change the BK-induced relaxation compared to the SHAM group, whereas testosterone treatment increased it. This response was diminished in the absence of NO, prostanoids, and EETs in the SHAM and ORX groups, while in ORX+T group the relaxation was diminished only in the absence of NO and EETs. There was no difference in eNOS, COX-1, COX-2, and gp91phox protein expression, though Akt expression was increased in ORX and ORX+T groups. These results show that testosterone treatment can modulate endothelial function, especially in the coronary circulation under hypertension conditions, via NO and EETs pathways.

Objectives To determine whether shock index, coronary perfusion pressure, or rate pressure product in the first 24 hours after congenital heart surgery are independent predictors of subsequent clinically significant adverse outcomes. Design A retrospective cohort study. Setting A tertiary care center. Patients All patients less than 18 years old who underwent cardiac surgery at Boston Children's Hospital between January 1, 2010, and December 31, 2018. Interventions None. Measurements and main results Shock index (heart rate/systolic blood pressure), coronary perfusion pressure (diastolic blood pressure-right atrial pressure), and rate pressure product (heart rate × systolic blood pressure) were calculated every 5 seconds, and the median value for the first 24 hours of cardiac ICU admission for each was used as a predictor. The composite, primary outcome was the occurrence of any of the following adverse events in the first 7 days following cardiac ICU admission: cardiopulmonary resuscitation, extracorporeal cardiopulmonary resuscitation, mechanical circulatory support, unplanned surgery, heart transplant, or death. The association of each variable of interest with this outcome was tested in a multivariate logistic regression model. Of the 4,161 patients included, 296 (7%) met the outcome within the specified timeframe. In a multivariate regression model adjusted for age, surgical complexity, inotropic and respiratory support, and organ dysfunction, shock index greater than 1.83 was significantly associated with the primary outcome (odds ratio, 6.6; 95% CI, 4.4-10.0), and coronary perfusion pressure greater than 35 mm Hg was protective against the outcome (odds ratio, 0.5; 0.4-0.7). Rate pressure product was not found to be associated with the outcome. However, the predictive ability of the shock index and coronary perfusion pressure models were not superior to their component hemodynamic variables alone. Conclusions Both shock index and coronary perfusion pressure may offer predictive value for adverse outcomes following cardiac surgery in children, although they are not superior to the primary hemodynamic variables.

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.

Aim Controlled sequential elevation of the head and thorax (CSE) during active compression–decompression (ACD) CPR with an impedance threshold device (ITD) augments cerebral (CerPP) and coronary (CorPP) perfusion pressures. The optimal CSE is unknown. Methods After 8 minutes of untreated VF, 40 kg anesthetized female pigs were positioned on a customized head and thorax elevation device (CED). After 2 min of automated ACD + ITD-16 CPR to ‘prime the system’, 12 pigs were randomized to CSE to the highest CED position over 4-min or 10-min. The primary outcome was CerPP after 7 minutes of CPR. Secondarily, 24-sec (without a priming step) and 2-min CSE times were similarly tested (n = 6 group) in a non-randomized order. Values expressed as mean ± SD. Results After 7 min of CPR, CerPPs were significantly higher in the 4-min vs 10-min CSE groups (53 ± 14.4 vs 38.5 ± 3.6 mmHg respectively, p = 0.03) whereas CorPP trended higher. The 4-min CSE group achieved 50% of baseline (50% BL) CerPP faster than the 10-min group (2.5 ± 1.2 vs 6 ± 3.1 minutes, p = 0.03). CerPP values in the 2-min and 4-min CSE groups were significantly higher than in the 24-sec group. With CSE, CerPPs and CorPPs increased over time in all groups. Conclusions By optimizing controlled sequential elevation timing, CerPP values achieved 50% of baseline within less than 2.5 minutes and >80% of baseline after 7 minutes of CPR. This novel CPR approach rapidly restored CerPPs to near normal values non-invasively and without vasopressors.

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.

Visual Abstract, Highlights • SNPeCPR improves coronary perfusion pressure, tissue perfusion, and carotid blood flow compared to epinephrine-based standard advanced cardiac life support. • In a porcine model of prolonged resuscitation, SNPeCPR was associated with decreased arterial oxygen saturation but improved tissue oxygen delivery due to improvement in blood flow. • Oxygen supplementation led to alleviation of hypoxemia and maintenance of the SNPeCPR hemodynamic benefits. • Arterial oxygen saturation must be a safety endpoint that will be prospectively assessed in the first SNPeCPR clinical trial in humans., Summary Sodium nitroprusside–enhanced cardiopulmonary resuscitation has shown superior resuscitation rates and neurologic outcomes in large animal models supporting the need for a randomized human clinical trial. This study is the first to show nonselective pulmonary vasodilation as a potential mechanism for the hemodynamic benefits. The pulmonary shunting that is created requires increased oxygen treatment, but the overall improvement in blood flow increases minute oxygen delivery to tissues. In this context, hypoxemia is an important safety endpoint and a 100% oxygen ventilation strategy may be necessary for the first human clinical trial.

The search for safe and effective patient management strategies during weaning from cardiopulmonary bypass is ongoing; intravenous calcium is occasionally used as a first-line drug. The physiologic role of calcium suggests that it can support the function of the cardiovascular system during this critical period. Patients may be mildly hypocalcemic after cardiopulmonary bypass; however, this degree of hypocalcemia does not significantly impair the cardiovascular system. The transient beneficial effects of calcium administration (increase in arterial blood pressure, systemic vascular resistance, cardiac index, stroke volume, and coronary perfusion pressure) might be helpful in cases of moderate contractility reduction or vasoplegia. Nonetheless, effects on clinically relevant endpoints are unknown, and possible systemic side effects, such as transient reduction in internal mammary artery graft flow, attenuation of the effects of β-sympathomimetics, "stone heart" phenomenon, and pancreatic cellular injury, may limit the use of calcium salts. Further studies are needed to expand the understanding of the effects of calcium administration on patient outcomes.

Introduction:Cardiopulmonary resuscitation (CPR) in the shunted single-ventricle population is associated with poor outcomes. Interposed abdominal compression-cardiopulmonary resuscitation, or IAC-CPR, is an adjunct to standard CPR in which pressure is applied to the abdomen during the recoil phase of chest compressions.Methods:A lumped parameter model that represents heart chambers and blood vessels as resistors and capacitors was used to simulate blood flow in both Blalock-Taussig-Thomas and Sano circulations. For standard CPR, a prescribed external pressure waveform was applied to the heart chambers and great vessels to simulate chest compressions. IAC-CPR was modelled by adding phasic compression pressure to the abdominal aorta. Differential equations for the model were solved by a Runge-Kutta method.Results:In the Blalock-Taussig-Thomas model, mean pulmonary blood flow during IAC-CPR was 30% higher than during standard CPR; cardiac output increased 21%, diastolic blood pressure 16%, systolic blood pressure 8%, coronary perfusion pressure 17%, and coronary blood flow 17%. In the Sano model, pulmonary blood flow during IAC-CPR increased 150%, whereas cardiac output was improved by 13%, diastolic blood pressure 18%, systolic blood pressure 8%, coronary perfusion pressure 15%, and coronary blood flow 14%.Conclusions:In this model, IAC-CPR confers significant advantage over standard CPR with respect to pulmonary blood flow, cardiac output, blood pressure, coronary perfusion pressure, and coronary blood flow. These results support the notion that single-ventricle paediatric patients may benefit from adjunctive resuscitation techniques, and underscores the need for an in-vivo trial of IAC-CPR in children.

This study evaluated the effects of extracorporeal membrane oxygenation (ECMO) in combination with a percutaneous adjunctive left ventricular assist device (LVAD) in a porcine model during 60 minutes of refractory cardiac arrest (CA). Twenty-four anesthetized swine were randomly allocated into three groups given different modes of circulatory assist: group 1: ECMO 72 ml/kg/min and LVAD; group 2: ECMO 36 ml/kg/min and LVAD; and group 3: ECMO 72 ml/kg/min. During CA and extracorporeal cardiopulmonary resuscitation (ECPR), mean left ventricular pressure (mLVP) was lower in group 1 (p = 0.013) and in group 2 (p = 0.003) versus group 3. Mean aortic pressure (mAP) and coronary perfusion pressure (CPP) were higher in group 1 compared with the other groups. In group 3, mean pulmonary artery flow (mPAf) was lower versus group 1 (p = 0.003) and group 2 (p = 0.039). If the return of spontaneous circulation (ROSC) was achieved after defibrillation, up to 180 minutes of unsupported observation followed. All subjects in groups 1 and 3, and 5 subjects in group 2 had ROSC. All subjects in group 1, five in group 2 and four in group 3 had sustained cardiac function after 3 hours of spontaneous circulation. Subjects that did not achieve ROSC or maintained cardiac function post-ROSC had lower mAP (p < 0.001), CPP (p= 0.002), and mPAf (p = 0.004) during CA and ECPR. Add-on LVAD may improve hemodynamics compared with ECMO alone during refractory CA but could not substitute reduced ECMO flow. Increased mAP and CPP could be related to ROSC rate and sustained cardiac function. Increased mLVP was related to poor post-ROSC cardiac function.

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.

Objective Two-Thumb(TT) technique provides superior quality chest compressions compared with Two-Finger(TF) in an instrumented infant manikin. Whether this translates to differences in blood flow, such as carotid arterial blood flow(CABF), has not been evaluated. We hypothesized that TT-CPR generates higher CABF and Coronary Perfusion Pressure(CPP) compared with TF-CPR in a neonatal swine cardiac arrest model. Methods Twelve anesthetized & ventilated piglets were randomized after 3 min of untreated VF to receive either TT-CPR or TF-CPR by PALS certified rescuers delivering a compression rate of 100/min. The primary outcome, CABF, was measured using an ultrasound transonic flow probe placed on the left carotid artery. CPP was calculated and end-tidal CO2(ETCO2) was measured during CPR. Data(mean ± SD) were analyzed and p-value ≤0.05 was considered statistically significant. Results Carotid artery blood flow (% of baseline) was higher in TT-CPR (66.2 ± 35.4%) than in the TF-CPR (27.5 ± 10.6%) group, p = 0.013. Mean CPP (mm Hg) during three minutes of chest compression for TT-CPR was 12.5 ± 15.8 vs. 6.5 ± 6.7 in TF-CPR, p = 0.41 and ETCO2 (mm Hg) was 29.0 ± 7.4 in TT-CPR vs. 20.7 ± 5.8 in TF-CPR group, p = 0.055. Conclusion TT-CPR achieved more than twice the CABF compared with TF-CPR in a piglet cardiac arrest model. Although CPP and ETCO2 were higher during TT-CPR, these parameters did not reach statistical significance. This study provides direct evidence of increased blood flow in infant swine using TT-CPR and further supports that TT chest compression is the preferred method for CPR in infants.

Background We investigated the effectiveness of automated pupillometry on monitoring cardiopulmonary resuscitation (CPR) and predicting return of spontaneous circulation (ROSC) in a swine model of cardiac arrest (CA). Methods Sixteen male domestic pigs were included. Traditional indices including coronary perfusion pressure (CPP), end-tidal carbon dioxide (ETCO2), regional cerebral tissue oxygen saturation (rSO2) and carotid blood flow (CBF) were continuously monitored throughout the experiment. In addition, the pupillary parameters including the initial pupil size before constriction (Init, maximum diameter), the end pupil size at peak constriction (End, minimum diameter), and percentage of change (%PLR) were measured by an automated quantitative pupillometer at baseline, at 1, 4, 7 min during CA, and at 1, 4, 7 min during CPR. Results ROSC was achieved in 11/16 animals. The levels of CPP, ETCO2, rSO2 and CBF were significantly greater during CPR in resuscitated animals than those non-resuscitated ones. Init and End were decreased and %PLR was increased during CPR in resuscitated animals when compared with those non-resuscitated ones. There were moderate to good significant correlations between traditional indices and Init, End, and %PLR (|r| = 0.46–0.78, all P Conclusion The automated pupillometry may serve as an effective surrogate method to monitor cardiopulmonary resuscitation efficacy and predict ROSC in a swine model of cardiac arrest.

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

Importance Pediatric in-hospital cardiac arrest (IHCA) occurs frequently and is associated with high morbidity and mortality. The objective of this narrative review is to summarize the current knowledge and recommendations regarding pediatric IHCA and cardiopulmonary resuscitation (CPR). Observations Each year, more than 15 000 children receive CPR for cardiac arrest during hospitalization in the United States. As many as 80% to 90% survive the event, but most patients do not survive to hospital discharge. Most IHCAs occur in intensive care units and other monitored settings and are associated with respiratory failure or shock. Bradycardia with poor perfusion is the initial rhythm in half of CPR events, and only about 10% of events have an initial shockable rhythm. Pre-cardiac arrest systems focus on identifying at-risk patients and ensuring that they are in monitored settings. Important components of CPR include high-quality chest compressions, timely defibrillation when indicated, appropriate ventilation and airway management, administration of epinephrine to increase coronary perfusion pressure, and treatment of the underlying cause of cardiac arrest. Extracorporeal CPR and measurement of physiological parameters are evolving areas in improving outcomes. Structured post-cardiac arrest care focused on targeted temperature management, optimization of hemodynamics, and careful intensive care unit management is associated with improved survival and neurological outcomes. Conclusions and relevance Pediatric IHCA occurs frequently and has a high mortality rate. Early identification of risk, prevention, delivery of high-quality CPR, and post-cardiac arrest care can maximize the chances of achieving favorable outcomes. More research in this field is warranted.

Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP). To further develop this scientific point, this study aimed to investigate the effects of long-term treatment with BAY 41–2272 (a sGC stimulator) on cardiovascular reactivity of spontaneously hypertensive rats (SHR) as a model of metabolic syndrome. SHR were randomly divided into 3 groups: control group, cafeteria diet (CD)-fed group and CD-fed group treated daily with BAY 41–2272 (5 mg/kg) by gastric gavage for 12 weeks. In vivo measurements of body weight, abdominal circumference, blood pressure and glucose tolerance test were performed. At the end of the feeding period, ex vivo cumulative concentration-response curves were performed on isolated perfused heart (isoproterenol (0.1 nM - 1 μM)) and thoracic aorta (phenylephrine (1 nM–10 μM), acetylcholine (1 nM–10 μM), and sodium nitroprusside (SNP) (0.1 nM–0.1 μM)). We showed that chronic CD feeding induced abdominal obesity, hypertriglyceridemia, glucose intolerance and exacerbated arterial hypertension in SHR. Compared to control group, CD-fed group showed a decrease in β-adrenoceptor-induced cardiac inotropy, in coronary perfusion pressure and in aortic contraction to phenylephrine. While relaxing effects of acetylcholine and SNP were unchanged. BAY 41–2272 long-term treatment markedly prevented arterial hypertension development and glucose intolerance, enhanced the α1-adrenoceptor-induced vasoconstriction, and restored cardiac inotropy and coronary vasodilation. These findings suggest that BAY 41–2272 may be a potential novel drug for preventing metabolic and cardiovascular complications of metabolic syndrome.

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.

Introduction: Survival rates for patients in out-of-hospital cardiac arrest have remained around 10% in the United Kingdom for the past seven years. If outcomes are to be improved, research into new methods of advanced life support is required. One such method may be ‘heads-up’ cardiopulmonary resuscitation.Methods: A systematic review of literature exploring heads-up cardiopulmonary resuscitation was conducted in an attempt to identify its effects on survival to discharge and neurological outcome.Results: A comprehensive search of CINAHL, MEDLINE and Google Scholar was undertaken. Six papers were classed as sufficiently relevant for inclusion. Included studies were generally of low quality and none studied the effect of heads-up cardiopulmonary resuscitation on out-of-hospital cardiac arrest patients. Animal studies identified a significant reduction in intracranial pressure and increase in cerebral and coronary perfusion pressure for use of augmented heads-up cardiopulmonary resuscitation in the porcine model of cardiac arrest.Conclusion: Further research is required to analyse the effects and potential benefits of augmented heads-up cardiopulmonary resuscitation in out-of-hospital cardiac arrest.

Background and objective The “Cardiac pump theory” and “Thoracic pump theory” are representative theories of cardiopulmonary resuscitation (CPR) mechanisms. Based on these theories, many studies on mathematical modeling have been performed to help understand hemodynamics during CPR. However, there are parts that do not yet properly reflect the physiology of CPR. Therefore, this study aims to develop a lumped parameter model of CPR that can more accurately reflect the current CPR physiology. Methods By adding compartments of the superior and inferior vena cava of the thoracic cavity to the existing CPR model, and the “Hybrid pump” mechanism was applied to simulate CPR. To compare the hemodynamics of the conventional CPR model and the developed CPR model, various conditions, such as active compression–decompression CPR with an impedance threshold valve device (ACD–CPR+ITV), head-up-tilt (HUT), and head-down-tilt (HDT), were simulated. The coronary perfusion pressure (CPP) was compared by modulating the compression ratio of the atrium and ventricle with the thoracic pump factor. Results The result for the comparison of coronary blood flow showed that the existing model is predominant in the compression phase, whereas the developed model is dominant in the relaxation phase. ACD–CPR + ITV results showed that the CPP decreased by 5 % in the existing model, and increased by about 46 % in the developed model, revealing a distinct hemodynamic difference between the two models. Likewise, as a result of comparing the hemodynamic differences of the two models according to the changes in tilt angle, the HUT showed similar trends, while the HDT showed slightly different results. The CPP varied accordingly with the ratio of the ventricular and atrial thoracic pump factor. Conclusion Comparison of the hemodynamics with the existing model by simulating various conditions showed that the developed CPR model reflects the CPR physiology better. The model suggests that the hemodynamics may vary depending on the ventricle and atrium compression ratio. This study may provide an important basis for helping understand various situations and patient-specific hemodynamic characteristics during CPR through in-depth research, such as patient-specific model and parameter optimization.

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.

Aim: Compare vasopressin to a second dose of epinephrine as rescue therapy after ineffective initial doses of epinephrine in diverse models of pediatric in-hospital cardiac arrest. Methods: 67 one- to three-month old female swine (10−30 kg) in six experimental cohorts from one laboratory received hemodynamic-directed CPR, a resuscitation method where high quality chest compressions are provided and vasopressor administration is titrated to coronary perfusion pressure (CoPP) ≥20 mmHg. Vasopressors are given when CoPP is

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.

Objectives We evaluated the feasibility of optimising coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) with a closed-loop, machine-controlled CPR system (MC-CPR) that sends real-time haemodynamic feedback to a set of machine learning and control algorithms which determine compression/decompression characteristics over time. Background American Heart Association CPR guidelines (AHA-CPR) and standard mechanical devices employ a “one-size-fits-all” approach to CPR that fails to adjust compressions over time or individualise therapy, thus leading to deterioration of CPR effectiveness as duration exceeds 15–20 ​min. Methods CPR was administered for 30 ​min in a validated porcine model of cardiac arrest. Intubated anaesthetised pigs were randomly assigned to receive MC-CPR (6), mechanical CPR conducted according to AHA-CPR (6), or human-controlled CPR (HC-CPR) (10). MC-CPR directly controlled the CPR piston’s amplitude of compression and decompression to maximise CPP over time. In HC-CPR a physician controlled the piston amplitudes to maximise CPP without any algorithmic feedback, while AHA-CPR had one compression depth without adaptation. Results MC-CPR significantly improved CPP throughout the 30-min resuscitation period compared to both AHA-CPR and HC-CPR. CPP and carotid blood flow (CBF) remained stable or improved with MC-CPR but deteriorated with AHA-CPR. HC-CPR showed initial but transient improvement that dissipated over time. Conclusion Machine learning implemented in a closed-loop system successfully controlled CPR for 30 ​min in our preclinical model. MC-CPR significantly improved CPP and CBF compared to AHA-CPR and ameliorated the temporal haemodynamic deterioration that occurs with standard approaches.

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.

Background Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight ( PEG ‐20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest. Methods and Results Twenty‐four male rats were randomized into 4 groups: (1) PEG ‐20k, (2) epinephrine, (3) saline control–intravenous, and (4) saline control–intra‐aortic. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. In PEG ‐20k and Saline‐A, either PEG ‐20k (10% weight/volume in 10% estimated blood volume infused over 3 minutes) or saline was administered intra‐aortically after 4 minutes of precordial compression. In epinephrine and placebo groups, either epinephrine (20 μg/kg) or saline placebo was administered intravenously after 4 minutes of precordial compression. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Sublingual microcirculation was measured at baseline and 1, 3, and 5 hours after return of spontaneous circulation. Myocardial function was measured at baseline and 2, 4, and 6 hours after return of spontaneous circulation. Neurologic deficit scores were recorded at 24, 48, and 72 hours after return of spontaneous circulation. Aortic infusion of PEG ‐20k increased coronary perfusion pressure to the same extent as epinephrine. Postresuscitation sublingual microcirculation, myocardial and cerebral function, and duration of survival were improved in PEG ‐20k ( P P Conclusions Aortic infusion of PEG ‐20k during cardiopulmonary resuscitation increases coronary perfusion pressure to the same extent as epinephrine, improves postresuscitation myocardial and cerebral function, and increases duration of survival in a rat model of cardiac arrest.

Introduction Cerebral blood flow during cardiopulmonary resuscitation (CPR) is a major neuroprognostic factor although not clinically feasible for routine assessment and monitoring. In this context, a surrogate marker for cerebral perfusion during CPR is highly desirable. Yet, cerebral blood flow hemodynamic determinants remain poorly understood and their significance might be altered by changes in head positioning such as flat, head up, and head down during CPR. Hypothesis We hypothesized that routinely measured hemodynamic parameters would correlate with cerebral brain flow during CPR, independently of the head position. Methods Associations between cerebral blood flow, measured using microsphere techniques, and hemodynamic parameters were studied from two prior publications. Eight pigs receiving CPR with an automated device and an impedance threshold device in the flat or supine, whole body head down and whole body head up tilt positions were analysed for the derivation sample. Relevant associations were examined for consistency in an external validation sample consisting of 18 pigs randomized to supine position versus head and torso elevation. Results After adjusting for position, arterial blood pressure and cerebral perfusion pressure during decompression were significantly associated with cerebral blood flow, in the derivation and the external validation samples. No significant associations were found between cerebral blood flow during CPR and right atrial pressure, intracranial pressure, end tidal CO2, carotid blood flow, and coronary perfusion pressure in the derivation sample. Conclusion Decompression arterial blood pressure and cerebral perfusion pressure are relevant candidate surrogate markers for cerebral blood flow during CPR, independently of head position.

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.

Each year in the United States, over 500,000 patients are treated for unexpected cardiac arrest either outside or inside the hospital. Survival rates are approximately 10% for EMS treated out-of-hospital cardiac arrest (OHCA) and 20% for in-hospital cardiac arrest (IHCA). The most important contributors to survival and good neurologic outcome are early CPR and early defibrillation resulting in early return of spontaneous circulation (ROSC). The quality of CPR also plays a key role. The evidence supporting advanced life support measures such as airway management, vasopressors, and antiarrhythmic drugs is less robust. Diagnosing and treating the underlying cause of cardiac arrest during CPR is challenging but can be lifesaving. Extracorporeal cardiopulmonary resuscitation (ECPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is emerging as a rescue strategy for cardiac arrest refractory to standard resuscitation efforts in appropriate patients and settings. It is essential to recognize that resuscitation efforts do not end with ROSC. Management of post-cardiac arrest syndrome requires additional diagnostics, continuous monitoring and active treatment to achieve optimal outcomes.

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.