Coronary Perfusion Pressure Research Articles

2-ЭТИЛТИОБЕНЗИМИДАЗОЛА ГИДРОБРОМИД ПРЕДУПРЕЖДАЕТ СНИЖЕНИЕ ТОНУСА КОРОНАРНЫХ СОСУДОВ И СОКРАТИТЕЛЬНОЙ СПОСОБНОСТИ МИОКАРДА У КРЫС ПРИ ЭКСПЕРИМЕНТАЛЬНОМ САХАРНОМ ДИАБЕТЕ

Objectives. To assess the possibility of preventing the disturbances of coronary vascular tone and myocardial contractile function caused by diabetes mellitus with the help of 2-ethylthiobenzimidazole hydrobromide. Material and methods. Coronary vascular tone and myocardial contractile function were studied on preparations of rat hearts isolated by the Langendorff method. The iNOS blockade was carried out with S-methylisothiourea (S-MT, 10<sup>-6</sup>M). Diabetes mellitus in rats was modelled by means of a single intraperitoneal injection of streptozocin (50 mg / kg). 2-ethylthiobenzimidazole hydrobromide (2-ETG) was injected intraperitoneally at a dose of 3 mg / kg. The concentration of stable degradation products of NO (NO<sub>2</sub><sup>-</sup>/NO<sub>3</sub><sup>-</sup>), superoxide dismutase, catalase, diene conjugates and malondialdehyde in the left ventricular homogenate was determined by spectrophotometric method. The content of inducible and endothelial NO-synthases (eNOS), interleukin 1β, C-reactive protein in the blood serum of experimental animals was determined by enzyme immunoassay. Results. In the hearts of «2-ETG + Diabetes mellitus» animal group no changes in the coronary perfusion pressure and developed intraventricular pressure were observed before and after the use of the highly selective iNOS blocker S-methylisothiourea. In the blood serum of these animals group, an increase in the concentration of eNOS was observed, against the background of a decrease in the accumulation of iNOS, a decrease in the concentration of lipid peroxidation products was determined against the background of an increase in the activity of the antioxidant system and a decrease of systemic inflammation. Conclusions. Intraperitoneal injection of 2-ethylthiobenzimidazole hydrobromide prevents a decrease in coronary vascular tone and myocardial contractile function caused by hyperproduction of nitrogen monoxide of inducible NO-synthase in diabetes mellitus. This effect of 2-ethylthiobenzimidazole hydrobromide is associated with: limiting the formation of oxidative stress; limiting the nitrosative stress; the decrease in the concentration of inflammatory markers.

Mechanism and potential treatment of the "no reflow" phenomenon after acute myocardial infarction: role of pericytes and GPR39.

The "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments, we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, before reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared with controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39-knockout and VC43-treated mice compared with controls. We conclude that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI and that smaller no reflow zones in GPR39-knockout and VC43-treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI, as well as providing a therapeutic pathway for the condition.NEW & NOTEWORTHY The mechanism of "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction but tissue perfusion is not restored, is unknown. This condition is associated with worse outcome. Here, we show that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow. Smaller no-reflow zones in GPR39-knockout animals and those treated with a GPR39 inhibitor are associated with smaller infarct size. These results could have important therapeutic implications.

Relationship of Laser-Doppler-Flow and coronary perfusion and a concise update on the importance of coronary microcirculation in donor heart machine perfusion.

Machine perfusion (MP) is a novel method for donor heart preservation. The coronary microvascular function is important for the transplantation outcome. However, current research on MP in heart transplantation focuses mainly on contractile function. We aim to present the application of Laser-Doppler-Flowmetry to investigate coronary microvascular function during MP. Furthermore, we will discuss the importance of microcirculation monitoring for perfusion-associated studies in HTx research. Porcine hearts were cardioplegically arrested and harvested (Control group, N = 4). In an ischemia group (N = 5), we induced global ischemia of the animal by the termination of mechanical ventilation before harvesting. All hearts were mounted on an MP system for blood perfusion. After 90 minutes, we evaluated the effect of coronary perfusion pressures from 20 to 100 mmHg while coronary laser-doppler-flow (LDF) was measured. Ischemic hearts showed a significantly decreased relative LDF compared to control hearts (1.07±0.06 vs. 1.47±0.15; p = 0.034). In the control group, the coronary flow was significantly lower at 100 mmHg of perfusion pressure than in the ischemia group (895±66 ml vs. 1112±32 ml; p = 0.016). Laser-Doppler-Flowmetry is able to reveal coronary microvascular dysfunction during machine perfusion of hearts and is therefore of substantial interest for perfusion-associated research in heart transplantation.

VASOPRESSIN-INDUCED ST-ELEVATION MYOCARDIAL INFARCTION

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Vasopressin is commonly used to restore blood pressure in hyperdynamic hemodynamic states, thereby reducing catecholamine requirements. The effects of vasopressin are primarily caused by the rise in the mean arterial pressure (MAP) due to systemic vasoconstriction, which, depending on the infusion rate, can also produce notable vasoconstrictive effects on the coronary microvasculature thereby reducing coronary blood flow despite an increase in coronary perfusion pressure. Here we present an interesting case of vasopressin-induced ST-elevation myocardial infarction (STEMI) on postoperative day two of cardiac catheterization for initial STEMI. CASE PRESENTATION: A 67-year-old male with a past medical history of hypertension, hypothyroidism presented to the emergency department (ED) with the complaint of left shoulder pain. In the ED waiting room, the patient suddenly collapsed losing consciousness, and was found to be in cardiac arrest. ACLS protocol was immediately started and ROSC was achieved. An electrocardiogram (EKG) was performed which showed STEMI in the anterolateral leads. Code STEMI was activated, and the patient was taken for the cardiac catheterization where LAD stenosis was observed and stented. Post-procedure, the patient was transferred to Cardiac ICU, where an amiodarone drip was initiated for recurrent episodes of non-sustained ventricular tachycardia. The hospital course was further complicated with pneumonia leading to acute hypoxemic respiratory failure and septic shock. The patient was placed on norepinephrine and appropriate antibiotics. Vasopressin was added to reduce catecholamine requirements and to achieve a target MAP. On postoperative day two, the patient was noted to have ST elevation on the tele monitor, a twelve lead EKG confirmed anteroseptal STEMI. A left heart catheterization revealed a patent LAD stent with no new findings and recommendations were made to stop vasopressin infusion and to continue the rest of the treatment. The patient was successfully extubated to BiPAP, eventually made a slow and steady recovery, and was discharged home with follow-up appointments. DISCUSSION: It has been shown that the levels of vasopressin increase as part of the stress response, which has been shown to exert vasoconstrictive effects on the coronary arteries mainly in the non-epicardial vessels of the microcirculation. These high levels in states like myocardial infarction can lead to coronary slow phenomenon mediating ischemia-perfusion injury. CONCLUSIONS: In advanced distributive shock with accompanied cardiogenic shock state, utmost caution should be taken as the vasoconstrictor properties of vasopressin are not accompanied by positive inotropic qualities, which may depress cardiac function even further as a result of impaired coronary blood flow despite increased coronary artery perfusion pressure and in severe cases can lead to myocardial ischemia. REFERENCE #1: Nobian A, Mohamed A, Spyridopoulos I. The role of arginine vasopressin in myocardial infarction and reperfusion. Kardiol Pol. 2019 Oct 25;77(10):908–17. REFERENCE #2: Hauser B, Asfar P, Calzia E, Laporte R, Georgieff M, Radermacher P. Vasopressin in vasodilatory shock: is the heart in danger? Crit Care. 2008;12(2):132. REFERENCE #3: Asfar P, Radermacher P. Vasopressin and ischaemic heart disease: more than coronary vasoconstriction? Crit Care. 2009;13(4):169. DISCLOSURES: No relevant relationships by Mohammed Ali, source=Web Response No relevant relationships by Humayun Anjum, source=Web Response No relevant relationships by Rahul Dadhwal, source=Web Response No relevant relationships by Salim Surani, source=Web Response

Compression depth of 30 mm has similar efficacy and fewer complications versus 50 mm during mechanical chest compression with miniaturized chest compressor in a porcine model of cardiac arrest.

BackgroundCurrent 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.MethodsIn 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 (ETCO2), 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.ResultsWe found no significant differences in CPP, CBF, or ETCO2 between the both groups throughout the CPR period. After administration of epinephrine, the CPP of all animals increased while ETCO2 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.ConclusionsRelatively shallow compression depth has similar hemodynamic efficacy but fewer complications versus the standard compression depth.

Standard CPR versus interposed abdominal compression CPR in shunted single ventricle patients: comparison using a lumped parameter mathematical model

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. 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. 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%. 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.

Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic-Reperfusion Injury Due to 4-Hydroxy-2-Nonenal Induced Coronary Endothelial Cell Damage.

BackgroundAldehyde dehydrogenase‐2 (ALDH2), a mitochondrial enzyme, detoxifies reactive aldehydes such as 4‐hydroxy‐2‐nonenal (4HNE). A highly prevalent E487K mutation in ALDH2 (ALDH2*2) in East Asian people with intrinsic low ALDH2 activity is implicated in diabetic complications. 4HNE‐induced cardiomyocyte dysfunction was studied in diabetic cardiac damage; however, coronary endothelial cell (CEC) injury in myocardial ischemia‐reperfusion injury (IRI) in diabetic mice has not been studied. Therefore, we hypothesize that the lack of ALDH2 activity exacerbates 4HNE‐induced CEC dysfunction which leads to cardiac damage in ALDH2*2 mutant diabetic mice subjected to myocardial IRI.Methods and ResultsThree weeks after diabetes mellitus (DM) induction, hearts were subjected to IRI either in vivo via left anterior descending artery occlusion and release or ex vivo IRI by using the Langendorff system. The cardiac performance was assessed by conscious echocardiography in mice or by inserting a balloon catheter in the left ventricle in the ex vivo model. Just 3 weeks of DM led to an increase in cardiac 4HNE protein adducts and, cardiac dysfunction, and a decrease in the number of CECs along with reduced myocardial ALDH2 activity in ALDH2*2 mutant diabetic mice compared with their wild‐type counterparts. Systemic pretreatment with Alda‐1 (10 mg/kg per day), an activator of both ALDH2 and ALDH2*2, led to a reduction in myocardial infarct size and dysfunction, and coronary perfusion pressure upon cardiac IRI by increasing CEC population and coronary arteriole opening.ConclusionsLow ALDH2 activity exacerbates 4HNE‐mediated CEC injury and thereby cardiac dysfunction in diabetic mouse hearts subjected to IRI, which can be reversed by ALDH2 activation.

Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

Right coronary artery diastolic perfusion pressure on outcome of patients with left heart failure and pulmonary hypertension.

AimsRight 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 resultsWe 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 < 0.0001). During a median follow‐up of 26 months, the RCDPP 1st tertile (<55 mmHg) [hazard ration (HR) 5.19, 95% confidence interval (CI) 1.08–25.12, P = 0.04] and left ventricular ejection fraction <45% [HR 7.26, 95% CI 1.77–29.73, P = 0.006] were independent predictors of mortality.ConclusionsRight coronary artery diastolic perfusion pressure is a strong independent haemodynamic maker of mortality in left‐sided HF and PH. Excessive reduction of aortic diastolic pressure may be detrimental. Future research is necessary to determine the therapeutic approach to blood pressure in this population.

Effects of Add-On Left Ventricular Assist Device to Extracorporeal Membrane Oxygenation During Refractory Cardiac Arrest in a Porcine Model.

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.

Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis.

To investigate the association between experimentally induced apical periodontitis (AP) and heart function in hypertensive rats. Forty-eight normotensive Wistar albino and spontaneously hypertensive (SHR) rats were divided into four equal groups: control (C), normotensive with AP (AP), SHR and SHR with AP (SHR+AP). AP was induced on the first right mandibular molars by exposing the pulp chambers to the oral environment for four weeks and confirmed radiographically. Thereafter, the animals were sacrificed by cervical dislocation, whilst hearts were isolated and perfused according to the Langendorff technique gradually increasing coronary perfusion pressures 40-120cmH2 O. The hemimandibles were analysed radiographically (mm2 and pixels) to verify the presence of AP. Biomarkers of cardiac oxidative stress (OS) were determined in coronary venous effluent and cardiac tissue homogenate. Cardiac tissue was analysed histopathologically for signs of heart damage (oedema, fibrosis and necrosis). All data were analysed by Kruskal-Wallis and one-way anova tests (p<.05). The levels of the maximum left ventricular pressure development rate of the SHR+AP group were significantly increased compared to the AP and C groups, and of the SHR group compared with the C group (p<.05). The levels of the minimum left ventricular pressure development rate of the SHR+AP group were significantly decreased compared to the AP, SHR and C groups, and of the SHR group compared to the C group (p<.05). The radiographic AP area was significantly larger in the SHR+AP group than in the AP group (p<.01). The levels of superoxide anion were significantly higher in the SHR+AP group than in the AP, SHR and C groups (p<.05). The activities of superoxide dismutase in cardiac tissue homogenate were significantly lower in the SHR+AP and AP groups compared with the SHR and C groups (p<.05). In rats, AP was associated with impaired cardiodynamics, disturbed cardiac OS, antioxidant defence and cardiac pathologic changes in hypertensive conditions. Hypertension was associated with an increase in the AP radiographic area. Further studies should confirm whether root canal treatment can have a cardioprotective effect and reduce cardiac OS in hypertensive conditions.

Esmolol during cardiopulmonary resuscitation reduces neurological injury in a porcine model of cardiac arrest

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 < 0.05). In both groups, 7 animals were successfully resuscitated and 4 survived up to 96 h. No significant differences were observed between groups in the total number of defibrillations delivered prior to final resuscitation. Brain histology demonstrated reductions in cortical neuronal degeneration/necrosis (score 0.3 ± 0.5 vs. 1.3 ± 0.5, p < 0.05) and hippocampal microglial activation (6 ± 3 vs. 22 ± 4%, p < 0.01) in the esmolol group compared to control. Lower circulating levels of neuron specific enolase were measured in esmolol animals compared to controls (2[1–3] vs. 21[16–52] ng/mL, p < 0.01). In this preclinical model, β1-blockade during CPR did not facilitate VF termination but provided neuroprotection.

Resuscitative endovascular balloon occlusion of the aorta vs epinephrine in the treatment of non-traumatic cardiac arrest in swine

BackgroundThe administration of epinephrine in the management of non-traumatic cardiac arrest remains recommended despite controversial effects on neurologic outcome. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an interesting alternative. The aim of this study was to compare the effects of these 2 strategies on return of spontaneous circulation (ROSC) and cerebral hemodynamics during cardiopulmonary resuscitation (CPR) in a swine model of non-traumatic cardiac arrest.ResultsAnesthetized pigs were instrumented and submitted to ventricular fibrillation. After 4 min of no-flow and 18 min of basic life support (BLS) using a mechanical CPR device, animals were randomly submitted to either REBOA or epinephrine administration before defibrillation attempts. Six animals were included in each experimental group (Epinephrine or REBOA). Hemodynamic parameters were similar in both groups during BLS, i.e., before randomization. After epinephrine administration or REBOA, mean arterial pressure, coronary and cerebral perfusion pressures similarly increased in both groups. However, carotid blood flow (CBF) and cerebral regional oxygenation saturation were significantly higher with REBOA as compared to epinephrine administration (+ 125% and + 40%, respectively). ROSC was obtained in 5 animals in both groups. After resuscitation, CBF remained lower in the epinephrine group as compared to REBOA, but it did not achieve statistical significance.ConclusionsDuring CPR, REBOA is as efficient as epinephrine to facilitate ROSC. Unlike epinephrine, REBOA transitorily increases cerebral blood flow and could avoid its cerebral detrimental effects during CPR. These experimental findings suggest that the use of REBOA could be beneficial in the treatment of non-traumatic cardiac arrest.

Haemodynamic-directed cardiopulmonary resuscitation promotes mitochondrial fusion and preservation of mitochondrial mass after successful resuscitation in a pediatric porcine model

ObjectiveCerebral mitochondrial dysfunction is a key mediator of neurologic injury following cardiac arrest (CA) and is regulated by the balance of fusion and fission (mitochondrial dynamics). Under stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion promotes oxidative phosphorylation efficiency. This study evaluates mitochondrial dynamics and content in brain tissue 24h after CA between two cardiopulmonary resuscitation (CPR) strategies. InterventionsPiglets (1 month), previously randomized to three groups: (1) Std-CPR (n=5); (2) HD-CPR (n=5; goal systolic blood pressure 90mmHg, goal coronary perfusion pressure 20mmHg); (3) Shams (n=7). Std-CPR and HD-CPR groups underwent 7min of asphyxia, 10min of CPR, and standardized post-resuscitation care. Primary outcomes: (1) cerebral cortical mitochondrial protein expression for fusion (OPA1, OPA1 long to short chain ratio, MFN2) and fission (DRP1, FIS1), and (2) mitochondrial mass by citrate synthase activity. Secondary outcomes: (1) intra-arrest haemodynamics and (2) cerebral performance category (CPC) at 24h. ResultsHD-CPR subjects had higher total OPA1 expression compared to Std-CPR (1.52; IQR 1.02–1.69 vs 0.67; IQR 0.54−0.88, p=0.001) and higher OPA1 long to short chain ratio than both Std-CPR (0.63; IQR 0.46−0.92 vs 0.26; IQR 0.26−0.31, p=0.016) and shams. Citrate synthase activity was lower in Std-CPR than sham (11.0; IQR 10.15–12.29 vs 13.4; IQR 12.28–15.66, p=0.047), but preserved in HD-CPR. HD-CPR subjects had improved intra-arrest haemodynamics and CPC scores at 24h compared to Std-CPR. ConclusionsFollowing asphyxia-associated CA, HD-CPR exhibits increased pro-mitochondrial fusion protein expression, preservation of mitochondrial mass, improved haemodynamics and superior neurologic scoring compared to Std-CPR. Institutional protocol numberIAC 16-001023.

Mathematical model of modified hybrid pump mechanism for cardiopulmonary resuscitation

Background and objectiveThe “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. MethodsBy 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. ResultsThe 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. ConclusionComparison 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.

Selective aortic arch perfusion versus open cardiac massage in exsanguination cardiac arrest: A comparison of coronary pressure dynamics in swine

AimTo 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. MethodsPost-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. ResultsMean 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). ConclusionSAAP appears to create a more favorable and efficient hemodynamic profile for obtaining ROSC when compared to OCM in this preclinical porcine study.

Chest compression by two-thumb encircling method generates higher carotid artery blood flow in swine infant model of cardiac arrest

ObjectiveTwo-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. MethodsTwelve anesthetized & ventilated piglets were randomized after 3min 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. ResultsCarotid 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. ConclusionTT-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.

Alternating fast and slow chest compression rates during CPR improved hemodynamics

IntroductionMechanical chest compression devices allow for variation in chest compression (CCs) characteristics from moment to moment, enabling therapy that is not feasible for manual CCs. Effects of varying compressions over time have not been studied. In a randomized trial in an experimental model of prolonged cardiac arrest, we compared time-varying CPR (TVCPR), alternating between 100 and 200 compressions per minute (cpm) every 6 s, to guidelines CPR (Control). MethodsVentricular fibrillation (VF) was electrically induced in 20 anesthetized pigs (28.4–45.8 kg). Following 10 min of untreated VF, cardiopulmonary resuscitation (CPR) began, randomized to TVCPR or Control. Rate of return of spontaneous circulation (ROSC), 4-h survival, and hemodynamics during the first 5 min of CPR were compared between groups. Moment-to-moment hemodynamic effects of changing the CC rate were analyzed. ResultsTVCPR improved the proportion of ROSC over time compared to Control (p < 0.05) but ROSC (9/10 vs. 5/10) and 4-h survival (8/10 vs 5/10) did not differ significantly between groups. During CPR, coronary and cerebral perfusion pressures and femoral artery pressure did not differ between groups; however, end-tidal CO2 and mixed venous O2 saturation were higher, and pulmonary artery pressure was lower (p < 0.05) for TVCPR than Control. During TVCPR, switching to 100 cpm increased coronary perfusion pressure (p < 0.05), and switching to 200 cpm increased cerebral perfusion pressure (p < 0.05). ConclusionsTime-varying CPR significantly improved indicators of net forward blood flow and proportion of ROSC over time without negatively impacting perfusion pressures. Alternating CC rate alternates between perfusion pressures favoring the brain and those favoring the heart. Time-varying CPR represents a new avenue of research for optimizing CPR. Institutional Protocol NumberUniversity of Alabama at Birmingham Institutional Animal Care and Use Committee (IACUC) Protocol Number 140406860.

Continuous chest compressions with asynchronous ventilation improve survival in a neonatal swine model of asphyxial cardiac arrest.

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. 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. 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 < 0.001) and remained significantly elevated throughout the experiment. End-tidal carbon dioxide (ETCO2) was also significantly higher in the experimental group throughout the experiment (23.4 ± 5.6 vs. 14.7 ± 5.9 mmHg, p < 0.001). ROSC was observed in six (60%) animals treated with 3:1 compression to ventilation ratio and nine (90%) animals treated with continuous chest compressions and asynchronous ventilation (p = 0.30). Time to ROSC was significantly lower in the experimental group (30 (30-30) vs. 60 (60-60) sec, p = 0.021). Of note, 7 (77.8%) animals in the experimental group and 1 (16.7%) animal in the control group achieved ROSC after 30 s (0.02). At 4 h, 2 (20%) animals survived in the control group compared to 7 (70%) animals in the experimental group (p = 0.022). 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.

Epinephrine plus chest compressions is superior to epinephrine alone in a hypoxia-induced porcine model of pseudo-pulseless electrical activity

AimPseudo-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. MethodsUsing 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). ResultsAmong 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. ConclusionsIn 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.