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Progesterone seems to play a role in cardiovascular physiology since its receptors are expressed on endothelial cells from both sexes of mammals. However, little is known about its role on the coronary circulation. Thus, this study aims to evaluate the effect of acute administration of progesterone on the coronary bed and the endothelial pathways involved in this action in normotensive rats of both sexes. A dose–response curve of progesterone (1–50 μmol/L) in isolated hearts using the Langendorff preparation was performed. Baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effect of progesterone was evaluated before and after infusion with Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin, catalase, and Tiron. The analysis of nitric oxide (NO) and superoxide anion (O2 · −) was performed by DAF-2DA and DHE, respectively. Female group showed higher CPP. Nevertheless, progesterone promoted a similar relaxing response in both sexes. The use of L-NAME increased vasodilatory response in both sexes. When indomethacin was used, only the males showed a reduced relaxing response, and in the combined inhibition with L-NAME, indomethacin, and catalase, or with the use of Tiron, only the females presented reduced responses. NO and O2 ·− production has increased in female group, while the male group has increased only NO production. Our results suggest that progesterone is able to modulate vascular reactivity in coronary vascular bed with a vasodilatory response in both sexes. These effects seem to be, at least in part, mediated by different endothelial pathways, involving NO and EDH pathways in females and NO and prostanoids pathways in males.

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

Aim Although progesterone (P4) has a beneficial effect on the cardiovascular system, P4 actions on the coronary bed have not yet been fully elucidated. This study evaluated the effect of progesterone treatment on endothelium-dependent coronary vascular reactivity in Wistar rats. Main methods Eight-week-old adult rats were divided into Sham, Ovariectomized (OVX), Ovariectomized and progesterone treated (OVX P4). The OVX P4 group received daily doses of progesterone (2 mg/kg/day). Vascular reactivity was assessed by a modified Langendorff technique. The intensity of eNOS, Akt, and gp91phox protein expression was quantified by Western blotting. Superoxide anion (O2●-) and hydrogen peroxide (H2O2) production was measured by dihydroethidium and 2′,7′-dichlorofluorescein, respectively. Key findings Treatment with P4 was able to prevent the reduction in baseline coronary perfusion pressure induced by ovariectomy. We observed that endothelium-dependent coronary vasodilation was reduced in the OVX group and potentiated in the OVX P4 group. Following the inhibition of the nitric oxide (NO) pathway, the bradykinin-induced relaxing response was potentiated in the OVX P4 group. With regard to the combined inhibition of NO and prostanoids pathways, the OVX P4 group showed a greater relaxing response, similar to what was found upon individual inhibition of NO. After the combined inhibition of NO, prostanoids and epoxyeicosatrienoic acids' pathways, the vasodilatory response induced by BK was abolished in all groups. Significance Treatment with P4 prevented oxidative stress induced by ovariectomy. These results suggest that progesterone has a beneficial action on the coronary vascular bed.

BACKGROUND The optimal blood flow and pressure to perfuse pediatric hearts from donation after circulatory death (DCD) on the ex vivo perfusion system has not been elucidated. This study sought to investigate the optimal perfusion strategy for pediatric DCD hearts by using a juvenile porcine model comparing pressure- vs flow-targeted strategy. METHODS The hearts of the juvenile DCD pigs were explanted, and the coronary arteries were perfused for 2 hours by the ex vivo heart perfusion system with 2 different perfusion strategies; pressure-targeted perfusion (target coronary perfusion pressure: 40 mm Hg, group A) and flow-targeted perfusion (target coronary perfusion flow: 10 ml/kg/min, group B). The working model heart perfusion was used to assess systolic and diastolic myocardial performance. RESULTS The body weight, warm and cold ischemic time, and ex vivo perfusion time were comparable between the groups. In the working model, group B showed significantly preserved cardiac output (A: 70.5 ± 15.3 ml/kg/min vs B: 113.8 ± 15.0 ml/kg/min, p < 0.01), stroke volume (A: 0.4 ± 0.1 ml/kg vs B: 0.7 ± 0.1 ml/kg, p < 0.01), and ejection fraction (A: 18.8% ± 5.9% vs B: 35.0% ± 10.6%, p < 0.01). E/e' and Tei index were also significantly preserved in group B. The percentage gain of heart weight after ex vivo (net increase of the heart weight divided by heart weight at baseline) was significantly smaller in group B (A: 20.0% ± 5.3% vs B: 11.6% ± 5.0%, p < 0.05). Troponin-I, myocardial hemorrhage, oxidative stress markers; myeloperoxidase and 8-hydroxy-2'-deoxyguanosine were also significantly lower after ex vivo perfusion in group B (p < 0.05). CONCLUSIONS The tightly controlled flow-targeted myocardial perfusion strategy for DCD donor hearts achieved better myocardial performance by causing less myocardial edema and limiting myocardial reperfusion injury.

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

When a cardiac arrest occurs, it is necessary to perform cardiopulmonary resuscitation (CPR) as soon as possible. This requires maintaining the pressure depth at 5 cm at a rate of 100 cpm. For CPR machines, which are frequently used in ambulances, the return of spontaneous circulation (ROSC) is not superior to that of manual CPR, although CPR machines can maintain the compression rate and reciprocal distance of the compression plate more accurately. When the thoracic cavity is deformed due to repeated chest compressions, CPR machines must be adjusted. It is necessary to develop a method for measuring whether adequate CPR is achieved using CPR machines. CPR was performed on two pigs with a CPR machine, commencing 1 minute after the heart was stopped. Four CPR modes were used, with compression rates of 60 or 100 cpm and compression depths of 3 or 5 cm. The CPR machine was equipped with a load cell for measuring compression force, and a potentiometer for measuring compression depth. The measurement results obtained from the sensor were used to calculate the frequency components. The compression force and depth data were used to calculate the mechanical power of the CPR machine and mechanical impedance of the thoracic cavity. Changes in end-tidal carbon dioxide (ETCO2), coronary perfusion pressure (CPP), carotid blood flow (CBF), and right atrial pressure (RAP) were measured during performance of CPR; change in RAP refers to variation therein with chest compressions. Continuous CPR in both animals resulted in deformation of the chest cavity and a steady decline in impedance. The correlation between CPR power and change in RAP was 0.78, and that between compression force and CBF was 0.64. Impedance was not correlated with blood pressure or CBF. When the condition of the animal deteriorated due to cardiac arrest, the CPP decreased and ETCO2 increased. The CPR power and RAP varied according to the CPR mode rather than the condition of the animal. Measuring the CPR machine power does not require a separate procedure, such as catheter intubation, so should be suitable as an index of the quality of CPR in emergency situations.

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

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

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

Background Mechanical chest compression (CC) is currently suggested to deliver sustained high‐quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results In a simulated urban ambulance transport, 16 pigs in cardiac arrest were randomized to 18 minutes of mechanical CC with the LUCAS (n=8) or manual CC (n=8). ECG, arterial and right atrial pressure, together with end‐tidal CO 2 and transthoracic impedance curve were continuously recorded. Arterial lactate was assessed during cardiopulmonary resuscitation and after resuscitation. During the initial 3 minutes of cardiopulmonary resuscitation, the ambulance was stationary, while then proceeded along a predefined itinerary. When the ambulance was stationary, CC‐generated hemodynamics were equivalent in the 2 groups. However, during ambulance transport, arterial and coronary perfusion pressure, and end‐tidal CO 2 were significantly higher with mechanical CC compared with manual CC (coronary perfusion pressure: 43±4 versus 18±4 mmHg; end‐tidal CO 2 : 31±2 versus 19±2 mmHg, P P P Conclusions This model adds evidence in favor of the use of mechanical devices to provide ongoing high‐quality CC and tissue perfusion during ambulance transport.

Purpose: It has previously been shown that continuous intratracheal insufflation of oxygen (CIO) is superior to intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics. The purpose of this study was to investigate gas exchanged and haemodynamics with a new technique of phase-controlled intermittent insufflation of oxygen (PIIO) compared to CIO. Method: Twenty (20) pigs were used, stratified into two groups (CIO, PIIO), with 10 animals each. Upon induction of ventricular fibrillation, standard ventilator support was replaced by either of CIO or PIIO ventilation. Chest compressions were delivered by the LUCAS I mCPR device. Following 20 min of CPR in normothermia, defibrillation was attempted. Results: Return of spontaneous circulation (ROSC) occurrence was not significantly higher (P

Objective Cerebral 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 24 h after CA between two cardiopulmonary resuscitation (CPR) strategies. Interventions Piglets (1 month), previously randomized to three groups: (1) Std-CPR (n = 5); (2) HD-CPR (n = 5; goal systolic blood pressure 90 mmHg, goal coronary perfusion pressure 20 mmHg); (3) Shams (n = 7). Std-CPR and HD-CPR groups underwent 7 min of asphyxia, 10 min 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 24 h. Results HD-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 24 h compared to Std-CPR. Conclusions Following 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 number IAC 16-001023.

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

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

Dexmedetomidine is a selective α2 adrenergic agonist. Although dexmedetomidine is widely used for sedation and analgesia, it frequently produces hypotension and bradycardia. The present study aimed to evaluate the effects of dexmedetomidine on cardiac function and coronary circulation using Langendorff-perfused guinea pig hearts. Coronary perfusion pressure (CPP) and left ventricular pressure (LVP) were continuously monitored, and electric field stimulation (EFS) was applied to stimulate sympathetic nerve terminals. Dexmedetomidine almost completely inhibited the EFS-induced increase in LVP at all ages. The effect of dexmedetomidine on coronary artery resistance varied according to postnatal age, i.e., dexmedetomidine had little effect on CPP in young hearts (8 weeks. The increase in CPP in adult hearts was inhibited by imiloxan, an α2B antagonist, and prazosin, an α1 antagonist. The results suggest that dexmedetomidine acts on α2 adrenergic receptors at sympathetic nerve terminals to suppress the release of norepinephrine. In addition, the findings suggest that dexmedetomidine directly affects α1 adrenoceptors and/or α2B adrenoceptors on coronary smooth muscles to increase CPP. The age-related changes in α adrenoceptor subtypes may be linked to the cardiodepressant effects of dexmedetomidine.

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

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

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

Aims Heart rate variability (HRV) is a measure of the balance between the sympathetic and parasympathetic autonomic nervous system and lack thereof an ominous sign in many cardiac and neurological conditions including post-cardiac arrest syndrome. Whole body periodic acceleration (pGz) has been shown to be cardio protective when applied prior to during and after cardiac arrest (CA). Here, we investigate whether or not pGz pre or post treatment after CA preserves HRV. Methods Eight min of unsupported ventricular fibrillation followed by CPR and defibrillation was carried out in 32 anesthetized and paralyzed male swine who were randomized to pretreatment (1 h pGz prior to CA, pre-pGz [ n = 8]) or post-treatment (pGz beginning at 30 min after return of spontaneous circulation ([ROSC], post-pGz [ n = 8]) or none (CONT [ n = 8]). pGz was applied together with conventional mechanical ventilation. In a separate group ( n = 8), infusion of TRIM (nNOS inhibitor) was used to determine the effects of nNOS inhibition on HRV. Results Time and frequency domain measures of HRV were determined along with measurements of blood gases and hemodynamics, obtained at baseline and at 30, 60, 120 and 180 min after ROSC. All animals had ROSC and there were no significant differences for arterial blood gases, mean blood pressure and coronary perfusion pressure after ROSC among the groups. HRV was significantly depressed after cardiac arrest and remained depressed in CONT group. In contrast, both pre and post pGz treated groups had significantly higher and preserved time domain measures of HRV (RMSSD and SDNN) from 60 to 180 min after ROSC, and nNOS inhibition markedly reduced HRV. The frequency domain of HRV did not show changes. Conclusions In a pig model of CA, pre or post treatment with pGz preserves HRV. Inhibition of nNOS markedly reduced HRV. Post-treatment with pGz is a novel therapeutic strategy that might serve as an adjunct to current pharmacological or hypothermia modalities to potentially improve outcomes from post-cardiac arrest syndrome.

Atrial fibrillation (AF) has several effects on the cardiovascular system responses. This study focuses on the consequences of AF on the coronary blood flow, by exploiting a computational approach. 2000 heartbeat periods (RR) were simulated for 5 different mean heart rates (HR), ranging from 50 to 130 bpm. The resulting flow rate signals at the coronary level were analysed through a specific set of hemodynamic parameters. Three main results emerge during AF: (i) maximal coronary flow rates modify with HR, (ii) the coronary perfusion begins to be impaired when exceeding 90-110 bpm, and (iii) the coronary perfusion pressure is not a good estimate of the coronary blood flow at HRs higher than 90-110 bpm.

Background There currently are no well-defined animal models for traumatic pulseless electrical activity (PEA). Our objective was to develop a swine model of traumatic PEA that would be useful for laboratory research where mortality is an outcome of interest. In this pilot study, we hypothesized that animals that remained in PEA without intervention for a longer period would have increased mortality. Materials and methods Sixteen Yorkshire swine were alternately allocated to either 5 or 10 min of traumatic PEA without intervention. After the nonintervention period, basic life support (BLS) with mechanical cardiopulmonary resuscitation was initiated and performed for 10 min followed by advanced life support (ALS) for an additional 10 min. Hemodynamic and laboratory values are reported for baseline, posthemorrhage, end of BLS, and end of ALS periods. Results Mortality in the 10-min PEA group (100%) was higher than the 5-min group (38%) (P = 0.03). Animals in the 5-min group had improved aortic diastolic blood pressure, coronary perfusion pressure, and end-tidal CO2 at the end of both the BLS (P = 0.02, 0.002, and 0.02, respectively) and ALS (P = 0.009, 0.005, and 0.008, respectively). The 10-min animals had increased hyperkalemia at the end of the BLS (P = 0.004) and ALS (P = 0.005) periods. All animals in the 10-min group developed ventricular fibrillation (VF) and 38% of the 5-min animals developed VF (P = 0.03). Conclusions In our pilot study of traumatic PEA in a swine model, a shorter period of nonintervention resulted in increased survival, improved hemodynamics during resuscitation, decreased hyperkalemia, and less incidence of conversion to VF arrest.

The local metabolic hypothesis proposes that myocardial oxygen tension determines the degree of autoregulation by increasing the production of vasodilator metabolites as perfusion pressure is reduced. Thus, normal physiologic levels of coronary venous PO(2), an index of myocardial oxygenation, are proposed to be required for effective autoregulation. The present study challenged this hypothesis through determination of coronary responses to changes in coronary perfusion pressure (CPP 140–40 mmHg) in open-chest swine in the absence (n = 7) and presence of euvolemic hemodilution (~ 50% reduction in hematocrit), with (n = 5) and without (n = 6) infusion of dobutamine to augment MVO(2). Coronary venous PO(2) decreased over similar ranges (~ 28–15 mmHg) as CPP was lowered from 140 to 40 mmHg in each of the groups. However, coronary venous PO(2) was not associated with changes in coronary blood flow (r = − 0.11; P = 0.29) or autoregulatory gain (r = − 0.29; P = 0.12). Coronary zero-flow pressure (Pzf) was measured in 20 mmHg increments and determined to be directly related to vascular resistance (r = 0.71; P < 0.001). Further analysis demonstrated that changes in coronary blood flow remained minimal at Pzf > 20 mmHg, but progressively increased as Pzf decreased below this threshold value (r = 0.68; P < 0.001). Coronary Pzf was also positively correlated with autoregulatory gain (r = 0.43; P = 0.001). These findings support that coronary autoregulatory behavior is predominantly dependent on an adequate degree of underlying vasomotor tone, independent of normal myocardial oxygen tension.

The aim of the study was comparison of contractile function of isolated hearts of rats with doxorubicin-induced myocardial injury which were tentatively divided according to the level of ejection fraction determined by echocardiography in vivo. After 4 weeks of doxorubicin administration (2 mg/kg subcutaneously once a week) about half of animals had normal (86±1 %) and the other half reduced (61±4 %) ejection fraction. The first group was defined as diastolic heart failure (DHF) and the other as systolic (SHF). The maximal pressure developed by the isolated heart in isovolumic mode was reduced in DHF by 13 %, and in SHF by 34 %. The relaxation index in both groups was lowed by 22-24 %. Both groups were characterized by a decline in the ability to raise developed pressure while increasing coronary perfusion pressure, as well as by the loss of the ability of coronary vessels to maintain a stable flow rate while increasing perfusion pressure. The hearts of control animals were able to raise the cardiac work index (the product of developed pressure and heart rate) during prolonged high frequency (7-9 Hz) stimulation, while the two groups treated with doxorubicin reduced the level of this index. The content of basic energy metabolites (ATP, phosphocreatine, creatine) in both groups was reduced by 20-38 %. The results showed that the hearts in DHF and SHF groups showed approximately the same level of reduction of the contractile function and energy metabolism, and hence their difference in vivo was probably due to varying degrees of mobilization of compensatory mechanisms.

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity. Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human vasculature model based on known experimental coronary morphometry and a space filling algorithm was implemented. Steady state simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity. Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF. Improved aortic blood pressure may improve total BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis. The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalized assessment of patient BF status.

Dialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity.Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human coronary vasculature model was implemented. Simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity which was quantified using relative dispersion, fractal dimension, and transmural BF distribution.Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure (CPP) was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF.Improved aortic blood pressure may lead to improved BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis.The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalised assessment of patient BF status.

Background Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post‐resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post‐resuscitation myocardial dysfunction caused by epinephrine; however, the relationship between myocardial adrenoceptor expression and myocardial protective effects by hypothermia remains unclear. Methods and Results Rats weighing between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo, (2) normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation). Ventricular fibrillation was induced and untreated for 8 minutes for all other groups. Hypothermia was initiated coincident with the start of CPR and maintained at 33±0.2°C for 4 hours. Placebo or epinephrine was administered 5 minutes after the start of CPR and 3 minutes before defibrillation. Post‐resuscitation ejection fraction was measured hourly for 4 hours then hearts were harvested. Epinephrine increased coronary perfusion pressure during CPR (27±6 mm Hg versus 21±2 mm Hg P cAMP doubled in the normothermic epinephrine group (655.06±447.63 μmol/L) compared with the hypothermic epinephrine group (302.51±97.98 μmol/L; P 1 ‐adrenoceptor expression decreased with normothermia cardiac arrest but not with hypothermia regardless of epinephrine. Conclusions Epinephrine, administered during normothermic CPR , increased the severity of post‐resuscitation myocardial dysfunction. This adverse effect was inhibited by intra‐arrest hypothermia resuscitation. Declined cAMP with more preserved β 1 ‐adrenoceptors in hypothermia‐resuscitated myocardium is associated with improved post‐resuscitated myocardial function in vivo.

Although there is not uniform definition of high-risk percutaneous coronary intervention (PCI), patients with severe three-vessel disease, left main disease, single remaining patent vessel and/or depressed left ventricular ejection fraction are considered a high-risk population. In this setting, periprocedural hemodynamic instability represents a serious issue. Percutaneous mechanical circulatory support (MCS) devices may improve both safety and efficacy of high-risk PCI. Indeed, MCS help to maintain coronary perfusion pressure and reduce myocardial workload, providing the operator sufficient time to reach the target of complete revascularization. The most used MCS are intra-aortic balloon pump and Impella. There are a plenty of data in literature about the efficacy and safety of the use of MCS in high-risk PCI performed through the femoral access. However, there is a paucity of data about the use of MCS in transradial high-risk PCI. Radial over femoral access has been showed to reduce bleeding complications and therefore may further improve the outcome of high-risk PCI. Herein we report a case of transradial high-risk PCI supported by the Impella 2.5 L and review the available data on this topic.

Objective: Compare the hemodynamic changes and cardiac function between active abdominal compressiondecompression cardiopulmonary resuscitation and standard cardiopulmonary resuscitation. Methods: A prospective controlled trial was conducted. The patients staying in EICU or ICU were the study subjects which were divided into active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR) group and standard cardiopulmonary resuscitation (STD-CPR) group randomly. Central venous pressure (CVP), diastolic blood pressure (DBP) and coronary perfusion pressure (CPP) were recorded continuously. Transesophageal echocardiography (TEE) was used to observe the cardiac valves and assess left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF) during CPR. Results: During CPR, LVEDV of two groups both decreased compared with pre-cardiac arrest, which was not statistically significant(P>0.05). LVEDV in AACD-CPR group was larger than STD-CPR group during CPR. But there was not statistically significant (P>0.05). During CPR, LVESV of two groups both increased compared with pre-cardiac arrest, which was statistically significant(P 0.05). Both AACD-CPR group and STD-CPR group showed significantly decreased LVEF compared with pre-cardic arrest, of which the difference was statistically significant(P

The Langendorff Perfused Heart Model is an experimental procedure developed at the end of the nineteenth century by Oskar Langendorff. In this procedure, an excised heart has a cannula inserted into its aorta so that the heart can be retrogradely perfused via the coronary artery. The procedure has been improved in recent times, and these improvements are used to evaluate the direct effect of medication on the heart as well as the effect of ischemia-reperfusion injury on heart function. In this chapter, we describe protocols for evaluating heart function in Langendorff perfused rat heart.

3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) is considered as an activator of the skeletal muscle sarcoplasmic reticulum (SR) Ca2+-uptake, endowed with antioxidant and L-type Ca2+ channel blocking activities. In this study we assessed the cardiac effects of DTBHA on Langendorff perfused rat hearts, isolated rat atria and rat cardiac SR membrane vesicles, as well as on several SERCA isoforms of membrane preparations. Moreover, in order to clarify its molecular mechanism of action Ca2+ imaging experiments were carried out on HEK293 cells transiently transfected with RyR2 channel. Docking of DTBHA at the rat RyR2 protein was investigated in silico. In Langendorff perfused rat hearts, DTBHA significantly increased, in a concentration-dependent manner, left ventricular pressure and diastole duration, while reducing heart rate and the time-constant of isovolumic relaxation, leaving unaltered coronary perfusion pressure. At the maximum concentration tested (30 µM), it significantly prolonged PQ interval, but left the corrected QT intervals unaffected. In spontaneously beating atria, DTBHA decreased sinus rate in a concentration-dependent manner. DTBHA, at concentrations higher than 10 µM, increased Ca2+ uptake in cardiac SR without affecting Ca2+-dependent ATPase activity assayed on several SERCA isoforms. Moreover, DTBHA antagonized thapsigargin-stimulated Ca2+ leak in cardiac SR and reduced caffeine-induced, RyR2-activated Ca2+ release in RyR2 expressing HEK293 cells. Using computational approaches, DTBHA showed a good affinity outline into binding sites of RyR2 protein. In conclusion, DTBHA behaved like a negative chronotropic, a positive inotropic and a lusitropic agent on rat heart preparations and improved cardiac SR Ca2+ uptake by lowering SR Ca2+ leak.