Coronary Perfusion Pressure Research Articles

Abstract 321: Manual vs Automated Ventilation During Automated Head-Up Cardiopulmonary Resuscitation in a Porcine Model

Background: The efficacy of mechanical ventilation during CPR with the combination of active compression-decompression, an impedance threshold device, and head-up positioning, collectively termed automated head-up (AHUP)-CPR, is unknown. Hypothesis: Hemodynamic and ventilatory parameters will be similar with manual bag ventilation (MBV) versus automated bag ventilation (ABV) during AHUP-CPR in a porcine model of cardiac arrest. Aim: Assess the proof-of-concept that ABV is safe and effective during AHUP-CPR. Methods: Nine male and female swine (~40 kg) were anesthetized and ventilated. VF was induced and left untreated for 8 min. AHUP-CPR was performed at 105 compressions/min for 7 min using MBV, followed by 6 min using an automated mechanical bag compressor to deliver 10ml/kg of tidal volume (TV) over 1 sec at 10 breaths/min. Pigs were randomized during ABV to a synchronized (Sync) breath delivered at the start of decompression or an asynchronous (Async) breath. Cerebral perfusion pressure, coronary perfusion pressure, end-tidal CO2, intracranial pressure, esophageal intrathoracic pressure, peak airway pressure (PAP), inspiratory and expiratory TVs as well as arterial blood gases were continuously measured. Values (mean ± SD) were compared by paired and unpaired student’s t-tests with a Bonferroni correction. Results: Parameters during the last minute of MBV and ABV are summarized in the table. No significant differences were observed in hemodynamic and ventilatory parameters, except for PAP and pO2 values which were significantly lower with MBV. No significant differences were also observed between the Sync and Async ABV modes. Conclusion: Manual and mechanical ventilation resulted in overall similar physiological effects. The clinical relevance of the observed significant differences in PAP and pO2 is unclear. Additional studies are warranted to further assess the safety and effectiveness of mechanical ventilation during AHUP-CPR.

Abstract 104: Photoplethysmogram Signal Characteristics as a Non-Invasive Surrogate of Diastolic Blood Pressure During Cardiopulmonary Resuscitation

Background: During cardiopulmonary resuscitation (CPR), diastolic blood pressure (DBP) is a key driver of coronary perfusion pressure and thereby, blood flow during CPR. Although resuscitation guidelines advise measuring DBP as an indicator of CPR quality, the need for an invasive arterial catheter to measure DBP limits scope of patients for whom a BP-directed CPR strategy can be implemented. Aims and Hypothesis: We aimed to study the photoplethysmogram (PPG) signal acquired from pulse oximetry monitoring as a non-invasive indicator of CPR quality. We hypothesized that a machine learning algorithm using dynamic PPG features would accurately classify CPR segments according to whether they met established pediatric DBP thresholds associated with improved outcomes (≥25mmHg in infants and ≥30 mmHg in older children). Methods/Approach: This was an NHLBI-funded ancillary study of the ICU-RESUScitation clinical trial (NCT02837497). This initial pilot study included 12 children who received CPR for an IHCA and had both arterial BP and pulse oximetry monitoring in place. Physiologic data were summarized into five-second epochs and DBP for each epoch was dichotomized by whether it met age-based DBP thresholds. Time-domain features ( k =25) were systematically engineered from the PPG signal, and a Support Vector Machine (SVM) model with a Gaussian kernel was trained to classify the CPR quality samples. Results: The analysis yielded n= 268 five-second CPR epochs, of which 147 (55.9%) met DBP thresholds. In the testing set of 134 previously unseen samples (50% of n , n low =59, n high =75), the SVM model achieved a classification accuracy of 91% with 100% precision and specificity, 79.7% sensitivity, and a negative predictive value of 86.2% only influenced by false negatives. Throughout development, six features describing the dicrotic notch characteristics reflected in the PPG waveform were empirically observed as significant CPR quality indicators. Conclusion: In this multicenter pilot investigation, the PPG waveform derived from pulse oximetry readings showed promise as a non-invasive surrogate of invasively measured DBP during pediatric CPR. This has the potential to greatly broaden the population for whom physiologic monitoring during CPR is possible.

Abstract 361: Effect of Percutaneous Ventricular Assisted Device on a Recovery of Myocardial Function in Swine Model With Prolonged Cardiac Arrest

Background: Percutaneous ventricular assist device (pLVAD) support and Transient aortic balloon occlusion (AO) can preserve cerebral and cardiac blood flow during cardiopulmonary resuscitation (CPR), but it remains unclear if pLVAD reduces post-cardiac arrest myocardial dysfunction. Hypothesis: pLVAD support immediately after the return of spontaneous circulation (ROSC) improves early recovery of myocardial function following prolonged cardiac arrest. Aims: Evaluate the association between early post-ROSC pLVAD support and recovery of myocardial function in a swine model of prolonged cardiac arrest. Methods: This is a secondary analysis of a subset of animals that achieved ROSC in a study comparing pLVAD, transient AO or both during CPR after prolonged cardiac arrest. pLVAD, aortic occlusion, or both were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to <1.0 L/min while maintaining a MAP >70 mmHg, and subsequently removed at 4 hours when feasible. The primary outcome was the recovery of cardiac index (CI) and left ventricular ejection fraction (LVEF) at 4 hours post-ROSC. Data are shown as mean (standard error). Results: Seventeen animals achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 [8 were removed from pLVAD], and standard care group, n = 6). For the primary outcome, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m2 (p=0.043) and LVEF 60(3) vs. 49(4) % (p=0.029) at 4 hours after ROSC, respectively, when compared with the standard care group. Focusing on the early period within 60 minutes after ROSC when maximum pLVAD flow was maintained, the pLVAD group had significantly higher coronary perfusion pressure (62[4] vs. 47[5] mmHg, p=0.019), lower LV stroke work index (3.9[3.0] vs. 14.9[4.4] cJ/m2, p=0.043), and lower total pulmonary resistance index (13.2[4.8] vs. 21.5[14.4] Wood Unit, p=0.001). Conclusion: These results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.

Abstract 185: Regional Oxygen Saturation and Capnography Monitoring During Resuscitation After Cardiac Arrest in a Swine Pediatric ARDS Model

Introduction: Survival and outcomes after cardiac arrest (CA) depend largely on the effectiveness of cardiopulmonary resuscitation (CPR). Traditional invasive methods of monitoring CPR can be challenging out-of-hospital and are lacking in more than 50% of in-hospital pediatric CA. Regional oxygen saturation (rSO 2 ) monitoring with Near Infrared Spectroscopy (NIRS) and volumetric capnography offers a noninvasive approach that could potentially overcome these challenges. Aim: To determine the feasibility and effectiveness of NIRS and volumetric capnography monitoring in a swine model of pediatric hypoxia induced CA. Approach: Juvenile pigs were sedated and mechanically ventilated. Mild to moderate Acute Respiratory Distress Syndrome (ARDS) was induced by continuous oleic acid infusion. Respiratory and hemodynamic variables were monitored using invasive and noninvasive (NIRS and capnography) monitoring to assess efficacy of CPR. Animals were randomized into one of the two groups: High-quality CPR (hqCPR) to achieve coronary perfusion pressure of 25-30 mmHg and low-quality CPR (lqCPR) to achieve coronary perfusion pressure of 10-15 mmHg. Trajectories over time were analyzed using regression analyses. The discriminatory ability to distinguish between groups based on trajectories were analyzed using receiver operating characteristics curve (ROC) analysis. Results: 39 animals (23±3 kg) were included in our study. In the hqCPR group, there are generally higher values for cerebral and renal rSO 2 , ETCO 2 , volume of CO 2 elimination (VCO 2 ), and carotid blood flow, compared to the lqCPR group (p<0.0001). Cerebral and renal rSO 2 values increase over time, while ETCO 2 , VCO 2 , and carotid flow values decrease in the hqCPR group. Cerebral rSO2 had a ROC AUC of 0.76 (95% CI: 0.58-0.94), whereas renal rSO2 had a ROC AUC of 0.54 (95% CI: 0.22-0.87) representing nearly no discrimination ability. ETCO 2 had a ROC AUC of 0.66 (95% CI: 0.49-0.84), whereas VCO 2 had a ROC AUC of 0.62 (95% CI: 0.38-0.85). Conclusions: Higher mean cerebral rSO2 values during CPR might be used to assess quality of CPR effectiveness and provide real-time adjustments as needed. This could guide healthcare providers in optimizing CPR quality and improving outcomes for cardiac arrest patients.

Treatment of cardiogenic shock due to right ventricular involvement

The right ventricle is susceptible to changes in preload, afterload, and contractility. The answer is its dilation with dysfunction/acute failure; filling is limited to the left ventricle and cardiac output. Systemic venous congestion is retrograde to the right heart, it is involved in the genesis of cardiogenic shock due to right ventricle involvement. This form of shock is less well known than that which occurs due to left ventricular failure, therefore, treatment may differ. Once the primary treatment has been carried out, since no response is obtained, supportive treatment aimed at ventricular pathophysiology will be the next option. It is suggested to evaluate the preload for the reasoned indication of liquids, diuretics or even ultrafiltration. Restore or maintain heart rate and sinus rhythm, treat symptomatic bradycardia, arrhythmias that make patients unstable, use of temporary pacing or cardioversion procedures. Improving contractility and vasomotility, using vasopressors and inotropes, alone or in combination, the objective will be to improve right coronary perfusion pressure. Balance the effect of drugs and maneuvers on preload and/or afterload, such as mechanical ventilation, atrial septostomy and pulmonary vasodilators. And the increasing utility of mechanical support of the circulation that has become a useful tool to preserve/restore right heart function.

Cerebral hemodynamic effects of head-up CPR in a porcine model

AimTo assess the hemodynamic effects of head elevation on cerebral perfusion during cardiopulmonary resuscitation (CPR) in a porcine model of cardiac arrest. MethodsVF was induced in eight 65 kg pigs that were treated with CPR after five minutes of no flow. Mean arterial pressure (MAP) was measured at the descending thoracic aorta. Internal carotid artery blood flow (CBF) was measured with an ultrasound probe. Cerebral perfusion pressure (CerPP) was calculated in two ways (CerPPICAP and CerPPreported) using the same intracranial pressure (ICP) measurement. CePPreported was calculated as MAP-ICP. CerPPICAP was calculated by using intracranial arterial pressure (ICAP) – ICP. The animals were switched between head up (HUP) and supine (SUP) CPR every five minutes for a total of twenty minutes of resuscitation. ResultsMAP and coronary perfusion pressure measurements were similar in both CPR positions (p = 0.36 and p = 0.1, respectively). ICP was significantly lower in the HUP CPR group (14.7 ± 1 mm Hg vs 26.9 ± 1 mm Hg, p < 0.001) as was ICAP (30.1 ± 2 mm Hg vs 42.6 ± 1 mmHg, p < 0.001). The proportional decrease in ICP and ICAP resulted in similar CerPPICAP comparing HUP and SUPCPR (p = 0.7). CBF was significantly lower during HUPCPR when compared to SUPCPR (58.5 ± 3 ml/min vs 78 ± 4 ml/min, p < 0.001). A higher CerPPreported was found during the HUP compared to SUP-CPR, when MAP was used (36.6 ± 2 mm Hg vs 23 ± 2 mm Hg, p < 0.001) without correcting for the hydrostatic pressure drop. ConclusionHUP did not affect cerebral perfusion pressure and it significantly decreased internal carotid blood flow.

Effect of percutaneous ventricular assisted device on post-cardiac arrest myocardial dysfunction in swine model with prolonged cardiac arrest

BackgroundIt remains unclear if percutaneous left ventricular assist device (pLVAD) reduces post-cardiac arrest myocardial dysfunction. MethodsThis is a prespecified analysis of a subset of swine that achieved return of spontaneous circulation (ROSC) in a study comparing pLVAD, transient aortic occlusion (AO), or both during cardiopulmonary resuscitation (CPR). Devices were initiated after 24 minutes of ventricular fibrillation cardiac arrest (8 min no-flow and 16 min mechanical CPR). AO was discontinued post-ROSC, and pLVAD support or standard care were continued. Beginning 60 minutes post-ROSC, pLVAD support was weaned to < 1.0 L/min and subsequently removed at 240 minutes. The primary outcome was cardiac index (CI), stroke volume index (SVI), and left ventricular ejection fraction (LVEF) at 240 minutes post-ROSC. Data are shown as mean (standard error). ResultsSeventeen swine achieved ROSC without complication and were included in this analysis (pLVAD group, n = 11 and standard care group, n = 6). For the primary outcomes, the pLVAD group had significantly higher CI of 4.2(0.3) vs. 3.1(0.4) L/min/m2 (p = 0.043) and LVEF 60(3) vs. 49(4) % (p = 0.029) at 240 minutes after ROSC when compared with the standard care group, while SVI was not statistically significantly different (32[3] vs. 23[4] mL/min/m2, p = 0.054). During the first 60 minutes post-ROSC, the pLVAD group had significantly higher coronary perfusion pressure, lower LV stroke work index, and total pulmonary resistance index. ConclusionThese results suggest that early pLVAD support after ROSC is associated with better recovery myocardial function compared to standard care after prolonged cardiac arrest.

Prediction of Return of Spontaneous Circulation in a Pediatric Swine Model of Cardiac Arrest Using Low-Resolution Multimodal Physiological Waveforms.

Monitoring physiological waveforms, specifically hemodynamic variables (e.g., blood pressure waveforms) and end-tidal CO2 (EtCO2), during pediatric cardiopulmonary resuscitation (CPR) has been demonstrated to improve survival rates and outcomes when compared to standard depth-guided CPR. However, waveform guidance has largely been based on thresholds for single parameters and therefore does not leverage all the information contained in multimodal data. We hypothesize that the combination of multimodal physiological features improves the prediction of the return of spontaneous circulation (ROSC), the clinical indicator of short-term CPR success. We used machine learning algorithms to evaluate features extracted from eight low-resolution (4 samples per minute) physiological waveforms to predict ROSC. The waveforms were acquired from the 2nd to 10th minute of CPR in pediatric swine models of cardiac arrest (N = 89, 8-12 kg). The waveforms were divided into segments with increasing length (both forward and backward) for feature extraction, and machine learning algorithms were trained for ROSC prediction. For the full CPR period (2nd to 10th minute), the area under the receiver operating characteristics curve (AUC) was 0.93 (95% CI: 0.87-0.99) for the multivariate model, 0.70 (0.55-0.85) for EtCO2 and 0.80 (0.67-0.93) for coronary perfusion pressure. The best prediction performances were achieved when the period from the 6th to the 10th minute was included. Poor predictions were observed for some individual waveforms, e.g., right atrial pressure. In conclusion, multimodal waveform features carry relevant information for ROSC prediction. Using multimodal waveform features in CPR guidance has the potential to improve resuscitation success and reduce mortality.

Effects of Prolonged Serum Calcium Suppression during Extracorporeal Cardiopulmonary Resuscitation in Pigs.

Controlled reperfusion by monitoring the blood pressure, blood flow, and specific blood parameters during extracorporeal reperfusion after cardiac arrest has the potential to limit ischemia-reperfusion injury. The intracellular calcium overload as part of the ischemia-reperfusion injury provides the possibility for the injury to be counteracted by the early suppression of serum calcium with the aim of improving survival and the neurological outcome. We investigated the effects of prolonged serum calcium suppression via sodium citrate during extracorporeal resuscitation using the CARL protocol (CARL-controlled automated reperfusion of the whole body) compared to a single-dose approach in a porcine model after prolonged cardiac arrest. A control group (N = 10) was resuscitated after a 20 min cardiac arrest, initially lowering the intravascular calcium with the help of a single dose of sodium citrate as part of the priming solution. Animals in the intervention group (N = 13) received additional sodium citrate for the first 15 min of reperfusion. In the control group, 9/10 (90.0%) animals survived until day 7 and 7/13 (53.8%) survived in the intervention group (p = 0.09). A favorable neurological outcome on day 7 after the cardiac arrest was observed in all the surviving animals using a species-specific neurological deficit score. The coronary perfusion pressure was significantly lower with a tendency towards more cardiac arrhythmias in the intervention group. In conclusion, a prolonged reduction in serum calcium levels over the first 15 min of reperfusion after prolonged cardiac arrest tended to be unfavorable regarding survival and hemodynamic variables compared to a single-dose approach in this animal model.

Efficacy of Cardiopulmonary Resuscitation Using Automatic Compression-Defibrillation Apparatus: An Animal Study and A Manikin-Based Simulation Study.

Chest compression and defibrillation are essential components of cardiac arrest treatment. Mechanical chest compression devices (MCCD) and automated external defibrillators (AED) are used separately in clinical practice. We developed an automated compression-defibrillation apparatus (ACDA) that performs mechanical chest compression and automated defibrillation. We investigated the performance of cardiopulmonary resuscitation (CPR) with automatic CPR (A-CPR) compared to that with MCCD and AED (conventional CPR: C-CPR). Pigs were randomized into A-CPR or C-CPR groups: The A-CPR group received CPR+ACDA, and the C-CPR group received CPR+MCCD+AED. Hemodynamic parameters, outcomes, and time variables were measured. During a simulation study, healthcare providers performed a basic life support scenario for manikins with an ACDA, MCCD, and AED, and time variables and chest compression parameters were measured. The animals showed no significant in hemodynamic effects, including aortic pressures, coronary perfusion pressure, carotid blood flow, and end-tidal CO2, and resuscitation outcomes between the two groups. In both animal and simulation studies, the time to defibrillation, time to chest compression, and hands-off time were significantly shorter in the A-CPR group than those in the C-CPR group. CPR using ACDA showed similar hemodynamic effects and resuscitation outcomes as CPR using AED and MCCD separately, with the advantages of a reduction in the time to compression, time to defibrillation, and hands-off time.

Development of an automatic device performing chest compression and external defibrillation: An animal-based pilot study.

Automatic chest compression devices (ACCDs) can promote high-quality cardiopulmonary resuscitation (CPR) and are widely used worldwide. Early application of automated external defibrillators (AEDs) along with high-quality CPR is crucial for favorable outcomes in patients with cardiac arrest. Here, we developed an automated CPR (A-CPR) apparatus that combines ACCD and AED and evaluated its performance in a pilot animal-based study. Eleven pigs (n = 5, A-CPR group; n = 6, ACCD CPR and AED [conventional CPR (C-CPR)] group) were enrolled in this study. After 2 min observation without any treatment following ventricular fibrillation induction, CPR with a 30:2 compression/ventilation ratio was performed for 6 min, mimicking basic life support (BLS). A-CPR or C-CPR was applied immediately after BLS, and resuscitation including chest compression and defibrillation, was performed following a voice prompt from the A-CPR device or AED. Hemodynamic parameters, including aortic pressure, right atrial pressure, coronary perfusion pressure, carotid blood flow, and end-tidal carbon dioxide, were monitored during resuscitation. Time variables, including time to start rhythm analysis, time to charge, time to defibrillate, and time to subsequent chest compression, were also measured. There were no differences in baseline characteristics, except for arterial carbon dioxide pressure (39 in A-CPR vs. 33 in C-CPR, p = 0.034), between the two groups. There were no differences in hemodynamic parameters between the groups. However, time to charge (28.9 ± 5.6 s, A-CPR group; 47.2 ± 12.4 s, C-CPR group), time to defibrillate (29.1 ± 7.2 s, A-CPR group; 50.5 ± 12.3 s, C-CPR group), and time to subsequent chest compression (32.4 ± 6.3 s, A-CPR group; 56.3 ± 10.7 s, C-CPR group) were shorter in the A-CPR group than in the C-CPR group (p = 0.015, 0.034 and 0.02 respectively). A-CPR can provide effective chest compressions and defibrillation, thereby shortening the time required for defibrillation.

A Narrative Review of Drug Therapy in Adult and Pediatric Cardiac Arrest.

Drugs are used during cardiopulmonary resuscitation (CPR) in association with chest compressions and ventilation. The main purpose of drugs during resuscitation is either to improve coronary perfusion pressure and myocardial perfusion in order to achieve return of spontaneous circulation (ROSC). The aim of this up-to-date review is to provide an overview of the main drugs used during cardiac arrest (CA), highlighting their historical context, pharmacology, and the data to support them. Epinephrine remains the only recommended vasopressor. Regardless of the controversy about optimal dosage and interval between doses in recent papers, epinephrine should be administered as early as possible to be the most effective in non-shockable rhythms. Despite inconsistent survival outcomes, amiodarone and lidocaine are the only two recommended antiarrhythmics to treat shockable rhythms after defibrillation. Beta-blockers have also been recently evaluated as antiarrhythmic drugs and show promising results but further evaluation is needed. Calcium, sodium bicarbonate, and magnesium are still widely used during resuscitation but have shown no benefit. Available data may even suggest a harmful effect and they are no longer recommended during routine CPR. In experimental studies, sodium nitroprusside showed an increase in survival and favorable neurological outcome when combined with enhanced CPR, but as of today, no clinical data is available. Finally, we review drug administration in pediatric CA. Epinephrine is recommended in pediatric CA and, although they have not shown any improvement in survival or neurological outcome, antiarrhythmic drugs have a 2b recommendation in the current guidelines for shockable rhythms.

The effect of external counterpulsation on angiopoietin-1 and angiopoietin-2 levels in nondiabetic patients with refractory angina

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Health Research and Development of the Ministry of Health of Indonesia. Background External counterpulsation (ECP) is a noninvasive therapy that employs external compression on the lower extremities to augment coronary perfusion pressure. Numerous studies reported that ECP possesses potential benefits in enhancing the angiogenesis process by promoting expressions of several growth factors. Nondiabetic patients are believed to be more reliable in portraying the angiogenesis process. Unfortunately, the effect of ECP on angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) as angiogenesis markers has not been elucidated. Purpose The objective of this study is to evaluate the effect of ECP on Ang-1 and Ang-2 levels in nondiabetic patients with refractory angina. Methods This is a randomised, double-blind, sham-controlled clinical trial. Nondiabetic patients with refractory angina, who were not contraindicated to ECP therapy, were enrolled and randomised into ECP or sham groups. The treatment consisted of optimal medical therapy plus 35 sessions of ECP or sham, with an hour duration for each session. The pressure applied was up to 300 mmHg in the ECP group, while only 75 mmHg in the sham group. Subjective symptoms, laboratory, echocardiographic, and functional capacity parameters were measured before and after 35 sessions of treatment. Appropriate statistical tests were performed and a p-value of &amp;lt;0.05 was considered statistically significant. Results A total of 26 nondiabetic patients with refractory angina were enrolled and randomised into ECP (n=11) and sham (n=15) groups. All patients successfully followed every treatment session until the 35th session. The baseline characteristics were comparable between the two groups (p&amp;gt;0.05). After 35 sessions, there were increases in Ang-1 median levels in both ECP (1663.4 pg/ml versus 891.6 pg/ml, p=0.477) and sham groups (1577.0 pg/ml versus 1295.0 pg/ml, p=0.496). The Ang-2 median levels after the treatments were slightly lower in ECP (2849.5 pg/ml versus 2902.3 pg/ml, p=0.594), while higher in sham groups (2728.3 pg/ml versus 2376.2 pg/ml, p=0.826). Meanwhile, the ECP group also showed an improvement in the Canadian Cardiovascular Society (CCS) angina class from class III to class I/II in 18% (2 out of 11) patients, while in the sham group only 13% (2 out of 15) patients. Interestingly, the ECP group seemed to elicit a noticeable increase in Ang-1 median levels and a decrease in Ang-2 median levels. However, the effects of ECP shown in this study were not statistically significant (p&amp;gt;0.05). Conclusion The ECP group exhibited a higher trend of increase in Ang-1 level compared to the sham group. The Ang-2 level was slightly lowered in the ECP group, while increased in the sham group. Although it was not statistically significant, the increasing trend in the Ang-1 level may provide an additional understanding of the ECP angiogenic effects. Therefore, further studies to validate these results are warranted.

Effect of transcatheter aortic valve replacement on bicuspid coronary hemodynamics: A numerical study

To investigate the effects of transcatheter heart valve (THV) poses and bicuspid aortic valve (BAV) subtypes on coronary hemodynamics after transcatheter aortic valve replacement (TAVR). The computational models for BAV included left-right fusion (LR), non-coronary-left fusion (LN) and non-coronary-right fusion (RN). THV deployment height is defined as the distance below the aortic annulus of the lowest point of the stent, H1 ​= ​2 ​mm, H2 ​= ​5 ​mm and H3 ​= ​8 ​mm, Orientations include O1 (one commissure is aligned with the raphe) and O2 (one commissure is aligned with the axis of non-fused leaflet symmetry). The maximum flow velocity (Vmax), mean wall shear stress (mWSS) and coronary perfusion pressure (CPP) of coronary were obtained by computational fluid dynamics (CFD) simulation. The CPP was 59% in left coronary and 82% in right coronary higher than that before deployment. At O1, the CPP of the LN left coronary and the RN right coronary was 74% and 79% higher than that before deployment. At O2, the CPP of the LN right coronary and the RN left coronary was 83% and 82% higher than that before deployment. When the THV deployment height is less than 2 ​mm, Vmax and CPP of coronary arteries do not return to healthy TAV levels or changed weakly. The overlap of the THV commissure with the coronary ostium makes the coronary CPP so large that it exceeds the level of a healthy TAV.

Contribution of local metabolic control to coronary pressure-flow autoregulation

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. This study interrogated the local metabolic hypothesis, which proposes that myocardial oxygen tension, indexed by coronary venous PO 2 (CvPO 2 ), determines the degree of coronary pressure-flow autoregulation by increasing the production of vasodilator metabolites as coronary perfusion pressure (CPP) is reduced. We tested this hypothesis by examining the extent to which dobutamine-induced increases in myocardial oxygen consumption (MVO 2 ) under both normoxic and hypoxemic conditions, influences coronary autoregulatory capability. Experiments were performed on open-chest anesthetized swine during 20 mmHg stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg, via servo-controlled roller pump. Measurements were made in 3 conditions: a) normoxia (n = 7); b) normoxia with dobutamine (10 μg/kg/min, iv; n = 7); and c) hypoxemia (PaO 2 36-38 mmHg) plus dobutamine (n = 5). Under control-normoxic conditions, CvPO 2 decreased from 38 ± 2 to 22 ± 1 mmHg and coronary blood flow fell from 0.93 ± 0.15 to 0.32 ± 0.03 ml/min/g as CPP was reduced from 140 to 40 mmHg. Administration of dobutamine significantly increased heart rate (~60%; P &lt; 0.001), but the combination of hypoxemia plus dobutamine did not further influence heart rate. Further, dobutamine with and without hypoxemia significantly increased MVO 2 (P &lt; 0.001); however, CvPO 2 was reduced (P &lt; 0.001) only in the presence of hypoxemia. Calculation of closed-loop autoregulatory gain (Gc) over a CPP range of 120 to 60 mmHg (value of 1 represents perfect autoregulation) was unaffected by dobutamine alone but tended to increase when dobutamine infusion was combined with reductions in PaO 2 ≤ 40 mmHg (P = 0.069). Additional analysis of the autoregulatory slope within this same CPP range revealed no differences between groups. However, there was a significant inverse association between Gc and CvPO 2 , measured at CPP of 100 mmHg, in the absence and presence of dobutamine-induced increases in MVO 2 ± hypoxemic conditions (P &lt; 0.001, r = -0.722). The relationship of coronary resistance (CPP range of 120 to 60 mmHg) relative to respective CvPO 2 revealed that decreases in CvPO 2 were not associated with changes in coronary resistance until CvPO 2 fell below a relative threshold of ~ 25 mmHg (r = 0.88). These findings support the interpretation that the sensitivity of coronary autoregulatory behavior is directly coupled with the activation of local metabolic vasodilator pathways below a critical level of myocardial oxygenation. This work was supported by National Institutes of Health grant R01 HL158723. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Intraaortic Ballon-pump: Physiology, Indication, Management

The intraaortic ballon-pump (IABP) is a percutaneous mechanical circulatory support device, which is used in patients either with insufficient cardiac output or in patients with high-risk situation before cardiac intervention, like surgical revascularisation or percutaneous coronary intervention (PCI). Due to electrocardiographic or arterial pressure pulse the IABP augments diastolic coronary perfusion pressure and reduces systolic afterload. Thereby, myocardial oxygen supply-demand ratio is improved and cardiac output is increased. Many national and international cardiology, cardiothoracic and intensive care medicine societies and associations worked together in order to develop evidence-based recommendations and guidelines for the preoperative, intraoperative and postoperative management of the IABP. This manuscript is mainly based on the S3 guideline "Use of intraaortic balloon-pump in cardiac surgery" from the German Society for Thoracic and Cardiovascular Surgery (DGTHG).

Doppler flow velocity profile of the left anterior descending in a patient with hypertrophic cardiomyopathy and markedly elevated left ventricular end-diastolic pressure: a novel observation.

Left anterior descending (LAD) coronary artery blood flow predominantly occurs in diastole and depends on the pressure differential across the myocardium, referred to as the coronary perfusion pressure (CPP). LAD flow can be visualized using two-dimensional/Doppler echocardiography. Restrictive diastolic filling patterns were previously described in the coronary artery Doppler profile as the ‘Doppler square root sign’ [EHJ CVI. 2017; 18(9):1067. doi: 10.1093/ehjci/jex061]. We present a case of a 44-year-old male with hypertrophic cardiomyopathy and no left ventricular outflow tract obstruction. The echocardiogram demonstrated septal wall thickness of 35 mm (Panel A), normal left ventricular ejection fraction (75%), impaired global longitudinal strain (−10%) (Panel B), and grade II diastolic dysfunction with a left atrial volume index of 56 mL/m2, E/A ratio 1.9 (Panel C), and septal e’ velocity 0.05 m/s. Further assessment of diastology revealed a mitral A wave duration of 120 ms (Panel D) and a pulmonary venous A wave duration of 220 ms (Panel E). The difference between the venous and transmitral A wave durations was 100 ms (normal < 30 ms). This degree of difference in the duration of flows is consistent with and indicative of a marked increase in left ventricular end-diastolic pressure (LVEDP). The LAD pulsed wave doppler flow (Panel F) profile (Panel G, see Supplementary data online, Video S1) demonstrated a transient reduction in end-diastolic velocity (‘a’ dip), which correlated with a decrease in CPP secondary to elevated LVEDP from a powerful atrial contraction, indeed a novel observation. Also noted is a small systolic flow reversal.

Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure.

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. However, the mechanisms responsible for coronary autoregulation remain a fundamental and highly contested question. This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5-7). Hypoxemia (PaO2 < 40mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0.001) and increased coronary blood flow ~ 100% (P < 0.001), sufficient to maintain myocardial oxygen delivery (P = 0.14) over a wide range of CPPs. Autoregulatory responsiveness during hypoxemia-induced reductions in CvPO2 were associated with increases of autoregulatory gain (Gc; P = 0.033) but not slope (P = 0.585) over a CPP range of 120 to 60mmHg. Preservation of autoregulatory Gc (P = 0.069) and slope (P = 0.264) was observed during dobutamine administration ± hypoxemia. Reductions in coronary resistance in response to decreases in CPP predominantly occurred below CvPO2 values of ~ 25mmHg, irrespective of underlying vasomotor reserve. These findings support the presence of an autoregulatory threshold under which oxygen-sensing pathway(s) act to preserve sufficient myocardial oxygen delivery as CPP is reduced during increases in MVO2 and/or reductions in arterial oxygen content.

The Role of the Superoxide Radical in the Regulation of the K&lt;sub&gt;V&lt;/sub&gt;-Channels Function in the Coronary Vessels Following Posttraumatic Stress Disorder

The purpose of the research was to study the contribution of the superoxide radical (\({\text{O}}_{2}^{{\centerdot - }}\)) to the mechanisms of the coronary KV-channels functional activity impairment in rats with posttraumatic stress disorder (PTSD). The study was performed on 117 outbred white male rats (Rattus, Muridae weighing 210–240 g). To reproduce the experimental analogue of PTSD, the modified model of “a predator presence imitation” was applied (contact with cats’ excrements for 10 days, 15 minutes daily). The PTSD development was confirmed by behavioral changes of affected animals in the “Open Field” test. The coronary vessels’ tone was studied on the isolated by the Langendorf’s method isotonically contracted hearts, which were perfused under constant flow with Krebs–Henseleit solution. The contribution of \({\text{O}}_{2}^{{\centerdot - }}\) to the coronary vascular tone regulation was studied by infusion of the superoxide radical “scavenger” Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) in the perfusion solution. The functional activity of KV-channels was assessed by the degree of increase in the coronary perfusion pressure (CPP) in response to 4-aminopyridine (4-AP), a blocker of KV-channels. To elucidate the role of \({\text{O}}_{2}^{{\centerdot - }}\) in the KV‑channels functional activity of coronary vessels, Tiron and 4-AP were infused in the perfusion solution. The concentration of diene conjugates (DCs), malondialdehyde (MDA), C‑reactive protein (C-RP) and interleukin 1β (IL-1β) as well as catalase (CAT) and superoxide dismutase (SOD) activity were detected in the blood serum of experimental animals. The CPP in the isolated rats’ hearts after PTSD was 30% lower at coronary flow rate 10 mL/min compared to the control group. Under the influence of 4-AP, CPP increased by 70% and by 24% in the “Control” and “PTSD” groups, respectively. Under influence of Tiron, the CPP in the “PTSD” group at coronary flow rate 10 mL/min was 52% lower than in the control. In the “PTSD + Tiron + 4-AP” group the CPP augmentation (71.5%) was comparable to that in the hearts of the “Control” group after 4-AP exposure. The IL-1β, C-RP, DCs and MDA concentration in the blood serum of rats with PTSD was 3, 1.6, 3.3 and 3.6 times higher than in the control rats’ blood serum, while SOD and CAT activity was by 27 and 59% lower, compared to control, respectively. In the course of the investigation, it was found that \({\text{O}}_{2}^{{\centerdot - }}\) overproduction due to oxidative stress might be an important mechanism of a poststressor “channelopathy”, which is characterized by the decreased functional activity of the KV-channels of coronary vessels following PTSD.

Dietary Fish Oil Supplementation Attenuates Myocardial Dysfunction and Injury Caused by Global Ischemia and Reperfusion in Isolated Rat Hearts

To determine the effect of dietary fish oil supplementation on myocardial dysfunction following ischemia-reperfusion, independent of plasma and blood cells, Sprague-Dawley rats were fed fish oil-rich nonpurified diet or butter-enriched diet for 5 d. Myocardial content of long-chain and (n-3) polyunsaturated fatty acids was greater in the fish oil-fed rats (P < 0.01), whereas (n-6) fatty acid content was lower compared with controls (P < 0.01). Platelet aggregation in fish oil-fed rats was also inhibited. Hearts from all rats were subjected to 15 min of global ischemia and 10 min of reperfusion. In hearts of control rats, ischemia-reperfusion resulted in a marked decrease in force of cardiac contraction, increase in coronary perfusion pressure, appearance of ventricular arrhythmias and release of creatine kinase and thromboxane B2 in the coronary effluent. Dietary fish oil supplementation attenuated myocardial dysfunction induced by ischemia-reperfusion, as indicated by smaller change in force of cardiac contraction (-77% vs. -89%, P < 0.05) and coronary perfusion pressure (+37% vs. +71%, P < 0.001). Concomitantly, release of creatine kinase as well as thromboxane B2 in coronary effluent was lower (P < 0.01). Ventricular arrhythmias occurred less frequently in hearts from fish oil-fed rats. Thus, short-term dietary fish oil supplementation attenuates myocardial dysfunction caused by ischemia-reperfusion by a direct effect on the heart independent of blood and plasma components.