Corrigendum: Real-time effects of lateral positioning on regional ventilation and perfusion in an experimental model of acute respiratory distress syndrome.

[This corrects the article DOI: 10.3389/fphys.2023.1113568.].

Real-time effects of lateral positioning on regional ventilation and perfusion in an experimental model of acute respiratory distress syndrome.

Low-volume lung injury encompasses local concentration of stresses in the vicinity of collapsed regions in heterogeneously ventilated lungs. We aimed to study the effects on ventilation and perfusion distributions of a sequential lateral positioning (30°) strategy using electrical impedance tomography imaging in a porcine experimental model of early acute respiratory distress syndrome (ARDS). We hypothesized that such strategy, including a real-time individualization of positive end-expiratory pressure (PEEP) whenever in lateral positioning, would provide attenuation of collapse in the dependent lung regions. A two-hit injury acute respiratory distress syndrome experimental model was established by lung lavages followed by injurious mechanical ventilation. Then, all animals were studied in five body positions in a sequential order, 15 min each: Supine 1; Lateral Left; Supine 2; Lateral Right; Supine 3. The following functional images were analyzed by electrical impedance tomography: ventilation distributions and regional lung volumes, and perfusion distributions. The induction of the acute respiratory distress syndrome model resulted in a marked fall in oxygenation along with low regional ventilation and compliance of the dorsal half of the lung (gravitational-dependent in supine position). Both the regional ventilation and compliance of the dorsal half of the lung greatly increased along of the sequential lateral positioning strategy, and maximally at its end. In addition, a corresponding improvement of oxygenation occurred. In conclusion, our sequential lateral positioning strategy, with sufficient positive end-expiratory pressure to prevent collapse of the dependent lung units during lateral positioning, provided a relevant diminution of collapse in the dorsal lung in a porcine experimental model of early acute respiratory distress syndrome.

Translational Rabbit Model of Chronic Cardiac Pacing.

Animal models of cardiac pacing are beneficial for testing novel devices, studying the pathophysiology of artificially paced heart rhythms, and studying arrhythmia-induced cardiomyopathies and subsequent heart failure. Currently, only a few such models are available, and they mostly require extensive resources. We report a new experimental cardiac pacing model in small mammals with the potential to study arrhythmia-induced heart failure. In six New Zealand white rabbits (mean weight: 3.5 kg) under general inhalational anesthesia the jugular region was dissected and a single pacing lead was inserted via the right external jugular vein. Using fluoroscopic guidance, the lead was further advanced to the right ventricular apex, where it was stabilized using passive fixation. A cardiac pacemaker was then connected and buried in a subcutaneous pocket. The pacemaker implantation was successful with good healing; the rabbit anatomy is favorable for the lead placement. During 6 months of follow-up with intermittent pacing, the mean sensed myocardial potential was 6.3 mV (min: 2.8 mV, max: 12 mV), and the mean lead impedance measured was 744 Ω (min: 370 Ω, max: 1014 Ω). The pacing threshold was initially 0.8 V ± 0.2 V and stayed stable during the follow-up. This present study is the first to present successful transvenous cardiac pacing in a small-mammal model. Despite the size and tissue fragility, human-size instrumentation with adjustments can safely be used for chronic cardiac pacing, and thus, this innovative model is suitable for studying the development of arrhythmia-induced cardiomyopathy and consequent heart failure pathophysiology.

Aortic stenosis and mitral regurgitation modify the effect of venoarterial extracorporeal membrane oxygenation on left ventricular function in cardiogenic shock.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used in the treatment of patients experiencing cardiogenic shock (CS). However, increased VA-ECMO blood flow (EBF) may significantly impair left ventricular (LV) performance. The objective of the present study was to assess the effect of VA-ECMO on LV function in acute CS with concomitant severe aortic stenosis (AS) or mitral regurgitation (MR) in a porcine model. Eight female swine (45 kg) underwent VA-ECMO implantation under general anaesthesia and mechanical ventilation. Acute CS was induced by global myocardial hypoxia. Subsequently, severe AS was simulated by obstruction of the aortic valve, while severe MR was induced by mechanical destruction of the mitral valve. Haemodynamic and LV performance variables were measured at different rates of EBF rates (ranging from 1 to 4 L/min), using arterial and venous catheters, a pulmonary artery catheter, and LV pressure-volume catheter. Data are expressed as median (interquartile range). Myocardial hypoxia resulted in declines in cardiac output to 2.7 (1.9-3.1) L/min and LV ejection fraction to 15.2% (10.5-19.3%). In severe AS, increasing EBF from 1 to 4 L/min was associated with a significant elevation in mean arterial pressure (MAP), from 33.5 (24.2-34.9) to 56.0 (51.9-73.3) mmHg (P ˂ 0.01). However, LV volumes (end-diastolic, end-systolic, stroke) remained unchanged, and LV end-diastolic pressure (LVEDP) significantly decreased from 24.9 (21.2-40.0) to 19.1 (15.2-29.0) mmHg (P ˂ 0.01). In severe MR, increasing EBF resulted in a significant elevation in MAP from 49.0 (28.0-53.4) to 72.5 (51.4-77.1) mmHg (P ˂ 0.01); LV volumes remained stable and LVEDP increased from 17.1 (13.7-19.1) to 20.8 (16.3-25.6) mmHg (P ˂ 0.01). Results of this study indicate that the presence of valvular heart disease may alleviate negative effect of VA-ECMO on LV performance in CS. Severe AS fully protected against LV overload, and partial protection was also detected with severe MR, although at the cost of increased LVEDP and, thus, higher risk for pulmonary oedema.

Prone positioning may increase lung overdistension in COVID-19-induced ARDS.

Real-time effects of changing body position and positive end-expiratory pressure (PEEP) on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension in mechanically ventilated patients with coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse. In this prospective observational study, patients with COVID-19-induced ARDS under mechanical ventilation were included. We used electrical impedance tomography (EIT) with decremental PEEP titration algorithm (PEEPEIT-titration), which provides information on regional lung overdistension and collapse, along with global respiratory system compliance, to individualize PEEP and body position. PEEPEIT-titration in supine position followed by PEEPEIT-titration in prone position were performed. Immediately before each PEEPEIT-titration, the same lung recruitment maneuver was performed: 2 min of PEEP 24 cmH2O and driving pressure of 15 cmH2O. Forty-two PEEPEIT-titration were performed in ten patients (21 pairs supine and prone positions). We have found larger % of overdistension along the PEEP titration in prone than supine position (P = 0.042). A larger % of collapse along the PEEP titration was found in supine than prone position (P = 0.037). A smaller respiratory system compliance was found in prone than supine position (P < 0.0005). In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H2O.Trial registration number: NCT04460859.

New Porcine Model of Arteriovenous Fistula Documents Increased Coronary Blood Flow at the Cost of Brain Perfusion.

Background: Arteriovenous fistulas (AVF) represent a low resistant circuit. It is known that their opening leads to decreased systemic vascular resistance, increased cardiac output and other hemodynamic changes. Possible competition of AVF and perfusion of other organs has been observed before, however the specific impact of AVF has not been elucidated yet. Previous animal models studied long-term changes associated with a surgically created high flow AVF. The aim of this study was to create a simple AVF model for the analysis of acute hemodynamic changes. Methods: Domestic female pigs weighing 62.6 ± 5.2 kg were used. All the experiments were held under general anesthesia. The AVF was created using high-diameter ECMO cannulas inserted into femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Near-infrared spectroscopy sensors, flow probes and flow wires were inserted to study brain and heart perfusion. Results: AVF blood flow was 2.1 ± 0.5 L/min, which represented around 23% of cardiac output. We observed increase in cardiac output (from 7.02 ± 2.35 L/min to 9.19 ± 2.99 L/min, p = 0.0001) driven dominantly by increased heart rate, increased pulmonary artery pressure, and associated right ventricular work. Coronary artery flow velocity rose. On the contrary, carotid artery flow and brain and muscle tissue oxygenation measured by NIRS decreased significantly. Conclusions: Our new non-surgical AVF model is reproducible and demonstrated an acute decrease of brain and muscle perfusion.

Acute Severe Heart Failure Reduces Heart Rate Variability: An Experimental Study in a Porcine Model.

There are substantial differences in autonomic nervous system activation among heart (cardiac) failure (CF) patients. The effect of acute CF on autonomic function has not been well explored. The aim of our study was to assess the effect of experimental acute CF on heart rate variability (HRV). Twenty-four female pigs with a mean body weight of 45 kg were used. Acute severe CF was induced by global myocardial hypoxia. In each subject, two 5-min electrocardiogram segments were analyzed and compared: before the induction of myocardial hypoxia and >60 min after the development of severe CF. HRV was assessed by time-domain, frequency-domain and nonlinear analytic methods. The induction of acute CF led to a significant decrease in cardiac output, left ventricular ejection fraction and an increase in heart rate. The development of acute CF was associated with a significant reduction in the standard deviation of intervals between normal beats (50.8 [20.5−88.1] ms versus 5.9 [2.4−11.7] ms, p < 0.001). Uniform HRV reduction was also observed in other time-domain and major nonlinear analytic methods. Similarly, frequency-domain HRV parameters were significantly changed. Acute severe CF induced by global myocardial hypoxia is associated with a significant reduction in HRV.

Current Aspects of the Role of Autoantibodies Directed Against Appetite-Regulating Hormones and the Gut Microbiome in Eating Disorders.

The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.

Targeted lateral positioning decreases lung collapse and overdistension in COVID-19-associated ARDS.

BACKGROUND: Among the challenges for personalizing the management of mechanically ventilated patients with coronavirus disease (COVID-19)-associated acute respiratory distress syndrome (ARDS) are the effects of different positive end-expiratory pressure (PEEP) levels and body positions in regional lung mechanics. Right-left lung aeration asymmetry and poorly recruitable lungs with increased recruitability with alternating body position between supine and prone have been reported. However, real-time effects of changing body position and PEEP on regional overdistension and collapse, in individual patients, remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP and body positioning in order to reduce the mechanisms of ventilator-induced lung injury: collapse and overdistension. METHODS: We here report a series of five consecutive mechanically ventilated patients with COVID-19-associated ARDS in which sixteen decremental PEEP titrations were performed in the first days of mechanical ventilation (8 titration pairs: supine position immediately followed by 30° targeted lateral position). The choice of lateral tilt was based on X-Ray. This targeted lateral position strategy was defined by selecting the less aerated lung to be positioned up and the more aerated lung to be positioned down. For each PEEP level, global and regional collapse and overdistension maps and percentages were measured by electrical impedance tomography. Additionally, we present the incidence of lateral asymmetry in a cohort of forty-four patients. RESULTS: The targeted lateral position strategy resulted in significantly smaller amounts of overdistension and collapse when compared with the supine one: less collapse along the PEEP titration was found within the left lung in targeted lateral (P = 0.014); and less overdistension along the PEEP titration was found within the right lung in targeted lateral (P = 0.005). Regarding collapse within the right lung and overdistension within the left lung: no differences were found for position. In the cohort of forty-four patients, ventilation inequality of > 65/35% was observed in 15% of cases. CONCLUSIONS: Targeted lateral positioning with bedside personalized PEEP provided a selective attenuation of overdistension and collapse in mechanically ventilated patients with COVID-19-associated ARDS and right-left lung aeration/ventilation asymmetry. TRIAL REGISTRATION: Trial registration number: NCT04460859.

Increasing venoarterial extracorporeal membrane oxygenation flow puts higher demands on left ventricular work in a porcine model of chronic heart failure.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in the treatment of circulatory failure, but repeatedly, its negative effects on the left ventricle (LV) have been observed. The purpose of this study is to assess the influence of increasing extracorporeal blood flow (EBF) on LV performance during VA ECMO therapy of decompensated chronic heart failure. METHODS: A porcine model of low-output chronic heart failure was developed by long-term fast cardiac pacing. Subsequently, under total anesthesia and artificial ventilation, VA ECMO was introduced to a total of five swine with profound signs of chronic cardiac decompensation. LV performance and organ specific parameters were recorded at different levels of EBF using a pulmonary artery catheter, a pressure-volume loop catheter positioned in the LV, and arterial flow probes on systemic arteries. RESULTS: Tachycardia-induced cardiomyopathy led to decompensated chronic heart failure with mean cardiac output of 2.9 ± 0.4 L/min, severe LV dilation, and systemic hypoperfusion. By increasing the EBF from minimal flow to 5 L/min, we observed a gradual increase of LV peak pressure from 49 ± 15 to 73 ± 11 mmHg (P = 0.001) and an improvement in organ perfusion. On the other hand, cardiac performance parameters revealed higher demands put on LV function: LV end-diastolic pressure increased from 7 ± 2 to 15 ± 3 mmHg, end-diastolic volume increased from 189 ± 26 to 218 ± 30 mL, end-systolic volume increased from 139 ± 17 to 167 ± 15 mL (all P < 0.001), and stroke work increased from 1434 ± 941 to 1892 ± 1036 mmHg*mL (P < 0.05). LV ejection fraction and isovolumetric contractility index did not change significantly. CONCLUSIONS: In decompensated chronic heart failure, excessive VA ECMO flow increases demands and has negative effects on the workload of LV. To protect the myocardium from harm, VA ECMO flow should be adjusted with respect to not only systemic perfusion, but also to LV parameters.

Validation of new marker of fluid responsiveness based on Doppler assessment of blood flow velocity in superior vena cava in mechanically ventilated pigs.

BACKGROUND: We studied a novel approach for the evaluation and management of volemia: minimally invasive monitoring of respiratory blood flow variations in the superior vena cava (SVC). We performed an experiment with 10 crossbred (Landrace × large white) female pigs (Sus scrofa domestica). METHODS: Hypovolemia was induced by bleeding from a femoral artery, in six stages. This was followed by blood return and then an infusion of 1000 ml saline, resulting in hypervolemia. Flow in the SVC was measured by Flowire (Volcano corp., USA), located in a distal channel of a triple-lumen central venous catheter. The key parameters measured were venous return variation index (VRV)-a new index for fluid responsiveness, calculated from the maximal and minimal velocity time intervals during controlled ventilation-and systolic peak velocity (defined as peak velocity of a systolic wave using the final end-expiratory beat). A Swan-Ganz catheter (Edwards Lifesciences, USA) was introduced into the pulmonary artery to measure pulmonary arterial pressure, pulmonary capillary wedge pressure, and continuous cardiac output measurements, using the Vigilance monitor (Edwards Lifesciences, USA). RESULTS: We analyzed 44 VRV index measurements during defined hemodynamic status events. The curves of VRV indexes for volume responders and volume non-responders intersected at a VRV value of 27, with 10% false negativity and 2% false positivity. We compared the accuracy of VRV and pulse pressure variations (PPV) for separation of fluid responders and fluid non-responders using receiver operating characteristic (ROC) curves. VRV was better (AUCROC 0.96) than PPV (AUCROC 0.85) for identification of fluid responders. The VRV index exhibited the highest relative change during both hypovolemia and hypervolemia, compared to standard hemodynamic measurement. CONCLUSIONS: The VRV index provides a real-time method for continuous assessment of fluid responsiveness. It combines the advantages of echocardiography-based methods with a direct and continuous assessment of right ventricular filling during mechanical ventilation.

Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study.

INTRODUCTION: Relationship between regional tissue oxygenation (rSO2) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO2, microcirculation and systemic hemodynamic parameters in a porcine model of CA. METHODS: Ventricular fibrillation was induced in 24 female pigs (50±3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. RESULTS: Brain and peripheral rSO2 showed a gradual decrease during CA and only an increase of brain rSO2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). CONCLUSIONS: Our experimental study confirmed that monitoring brain and peripheral rSO2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO2 reflects the CPR efforts and might be used as a potential quality indicator for CPR.

Electrocardiogram-synchronized pulsatile extracorporeal life support preserves left ventricular function and coronary flow in a porcine model of cardiogenic shock.

INTRODUCTION: Veno-arterial extracorporeal life support (ECLS) is increasingly being used to treat rapidly progressing or severe cardiogenic shock. However, it has been repeatedly shown that increased afterload associated with ECLS significantly diminishes left ventricular (LV) performance. The objective of the present study was to compare LV function and coronary flow during standard continuous-flow ECLS support and electrocardiogram (ECG)-synchronized pulsatile ECLS flow in a porcine model of cardiogenic shock. METHODS: Sixteen female swine (mean body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock, with documented signs of tissue hypoperfusion, was induced by initiating global myocardial hypoxia. Hemodynamic cardiac performance variables and coronary flow were then measured at different rates of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter, an LV pressure-volume loop catheter, and a Doppler coronary guide-wire. RESULTS: Myocardial hypoxia resulted in declines in mean cardiac output to 1.7±0.7 L/min, systolic blood pressure to 64±22 mmHg, and LV ejection fraction (LVEF) to 22±7%. Synchronized pulsatile flow was associated with a significant reduction in LV end-systolic volume by 6.2 mL (6.7%), an increase in LV stroke volume by 5.0 mL (17.4%), higher LVEF by 4.5% (18.8% relative), cardiac output by 0.37 L/min (17.1%), and mean arterial pressure by 3.0 mmHg (5.5%) when compared with continuous ECLS flow at all ECLS flow rates (P<0.05). At selected ECLS flow rates, pulsatile flow also reduced LV end-diastolic pressure, end-diastolic volume, and systolic pressure. ECG-synchronized pulsatile flow was also associated with significantly increased (7% to 22%) coronary flow at all ECLS flow rates. CONCLUSION: ECG-synchronized pulsatile ECLS flow preserved LV function and coronary flow compared with standard continuous-flow ECLS in a porcine model of cardiogenic shock.

Tachycardia-Induced Cardiomyopathy As a Chronic Heart Failure Model in Swine.

A stable and reliable model of chronic heart failure is required for many experiments to understand hemodynamics or to test effects of new treatment methods. Here, we present such a model by tachycardia-induced cardiomyopathy, which can be produced by rapid cardiac pacing in swine. A single pacing lead is introduced transvenously into fully anaesthetized healthy swine, to the apex of the right ventricle, and fixated. Its other end is then tunneled dorsally to the paravertebral region. There, it is connected to an in-house modified heart pacemaker unit that is then implanted in a subcutaneous pocket. After 4 - 8 weeks of rapid ventricular pacing at rates of 200 - 240 beats/min, physical examination revealed signs of severe heart failure - tachypnea, spontaneous sinus tachycardia, and fatigue. Echocardiography and X-ray showed dilation of all heart chambers, effusions, and severe systolic dysfunction. These findings correspond well to decompensated dilated cardiomyopathy and are also preserved after the cessation of pacing. This model of tachycardia-induced cardiomyopathy can be used for studying the pathophysiology of progressive chronic heart failure, especially hemodynamic changes caused by new treatment modalities like mechanical circulatory supports. This methodology is easy to perform and the results are robust and reproducible.

Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study.

BACKGROUND: Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. METHODS: Cardiac arrest was induced in 18 female pigs (50 ± 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (≤20 µm) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). RESULTS: In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05-100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's ρ 0.02-0.51) and after adjustment for multiple correlations it was non-significant. CONCLUSIONS: Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR.

Ischemic Postconditioning and Nitric Oxide Administration Failed to Confer Protective Effects in a Porcine Model of Extracorporeal Cardiopulmonary Resuscitation.

The protective effects of ischemic postconditioning (IPC) and nitric oxide (NO) administration have been demonstrated in several ischemic scenarios. However, current evidence regarding the effect of IPC and NO in extracorporeal cardiopulmonary resuscitation remains lacking. Fifteen female swine (body weight 45 kg) underwent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation; cardiac arrest-ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of cardiac arrest, blood flow was restored by increasing the ECMO flow rate to 4.5 L/min. The animals (five per group) were then randomly assigned to receive IPC (three cycles of 3 min ischemia and reperfusion), NO (80 ppm via oxygenator), or mild hypothermia (HT; 33.0°C). Cerebral oximetry and aortic blood pressure were monitored continuously. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I, myoglobin, creatine-phosphokinase, alanine aminotransferase, neuron-specific enolase, cystatin C, and reactive oxygen metabolite (ROM) levels. Significantly higher blood pressure and cerebral oxygen saturation values were observed in the HT group compared with the IPC and NO groups (P < 0.05). The levels of troponin I, myoglobin, creatine phosphokinase, and alanine aminotransferase were significantly lower in the HT group (P < 0.05); levels of neuron-specific enolase, cystatin C, and ROM were not significantly different. IPC and NO were comparable in all monitored parameters. The results of the present study indicate that IPC and NO administration are not superior interventions to HT for the maintenance of blood pressure, cerebral oxygenation, organ protection, and suppression of oxidative stress following extracorporeal cardiopulmonary resuscitation.

The Cortisol to Cortisone Ratio during Cardiac Catheterisation in Sows.

A possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis and conversion of cortisone to cortisol were studied. We have analysed two stress markers levels (cortisol, cortisone) and cortisol/cortisone ratio in 25 sows using minimally invasive heart catheterisation as the stress factor. The values of studied parameters were assessed in four periods of the experiment: (1) the baseline level on the day before intervention, (2) after the introduction of anaesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. We have found the highest level of cortisol/cortisone ratio in unstressed conditions, then it decreased to the minimal level at the end of the intervention. We have concluded that cortisol levels are blunted by the influence of anaesthesia after its administration, and therefore decrease back to the baseline at the end of the operation.

Acute Digital Ischemia Associated with Closed Injury.

Injury of an artery has a significantly worse prognosis for the patient than a venous injury. Blunt injuries of lower limb digital arteries with the development of acute ischemia present a very rare phenomenon. A crush mechanism with a defect of the non-wetted surface of vessel's inner part and the development of subsequent thromboischemic lesion is essential for the development of ischemia. We report a blunt injury of the right lower limb in a patient after incorrect stepping with subsequent lesion of digital arteries and the development of acute acral ischemia of the right toes.

Increasing venoarterial extracorporeal membrane oxygenation flow negatively affects left ventricular performance in a porcine model of cardiogenic shock.

BACKGROUND: The aim of this study was to assess the relationship between extracorporeal blood flow (EBF) and left ventricular (LV) performance during venoarterial extracorporeal membrane oxygenation (VA ECMO) therapy. METHODS: Five swine (body weight 45 kg) underwent VA ECMO implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypoxia was induced. Hemodynamic and cardiac performance parameters were then measured at different levels of EBF (ranging from 1 to 5 L/min) using arterial and venous catheters, a pulmonary artery catheter and a pressure-volume loop catheter introduced into the left ventricle. RESULTS: Myocardial hypoxia resulted in a decline in mean (±SEM) cardiac output to 2.8 ± 0.3 L/min and systolic blood pressure (SBP) to 60 ± 7 mmHg. With an increase in EBF from 1 to 5 L/min, SBP increased to 97 ± 8 mmHg (P < 0.001); however, increasing EBF from 1 to 5 L/min significantly negatively influences several cardiac performance parameters: cardiac output decreased form 2.8 ± 0.3 L/min to 1.86 ± 0.53 L/min (P < 0.001), LV end-systolic volume increased from 64 ± 11 mL to 83 ± 14 mL (P < 0.001), LV stroke volume decreased from 48 ± 9 mL to 40 ± 8 mL (P = 0.045), LV ejection fraction decreased from 43 ± 3 % to 32 ± 3 % (P < 0.001) and stroke work increased from 2096 ± 342 mmHg mL to 3031 ± 404 mmHg mL (P < 0.001). LV end-diastolic pressure and volume were not significantly affected. CONCLUSIONS: The results of the present study indicate that higher levels of VA ECMO blood flow in cardiogenic shock may negatively affect LV function. Therefore, it appears that to mitigate negative effects on LV function, optimal VA ECMO blood flow should be set as low as possible to allow adequate tissue perfusion.

Arteriovenous grafts: early ultrasonography tells their fortune.

BACKGROUND: The patency of arteriovenous grafts (AVG) for hemodialysis is mostly limited by growing stenoses that lead to decreasing of blood flow, thromboses and finally to access failure. The aim of this study was to find out if detection of any pathology by duplex Doppler ultrasonography (DDU) early after creation of AVG could identify those with lower survival. METHODS: We retrospectively enrolled AVG examined by DDU in our center within 40 days after their creation during the last 10 years. The findings were divided into 4 subgroups: (1a) normal finding, (1b) DDU risk factor (low flow volume, medial calcinosis of the feeding artery, presence of intimal hyperplasia in the venous anastomosis), (2a) non-significant or (2b) significant stenosis. The primary outcome measure was the cumulative survival of people with AVGs, and the secondary was the primary (unassisted) survival. All patients underwent DDU surveillance every 3 months with pre-emptive treatment of significant stenoses. RESULTS: Overall, 340 cases were found; the median follow-up was 565 days. Normal DDU finding had 60% cases, DDU risk factor 18% cases, non-significant stenosis 13% cases and significant stenosis 9% cases. Occurrence of early significant stenosis was associated with high risk of access loss (hazards ratio (HR) 14.73; 95% CI 5.10-42.58; p < 0.0001). Similarly, the presence of a DDU risk factor and of a non-significant stenosis were related to significantly shorter access lifespan (HR 2.86; 95% CI 1.10-7.40; p = 0.03 and HR 2.83; 95% CI 1.12-7.17; p = 0.03, respectively). CONCLUSION: DDU examination of AVG early after their creation can identify those at higher risk and may contribute to individualize the surveillance strategy.