First real-time imaging of bronchoscopic lung volume reduction by electrical impedance tomography.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (FIO2) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of FIO2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV. METHODS: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with FIO2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces. RESULTS: Following balloon occlusion, a steep decrease in left ROI-EELI with FIO2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher FIO2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher FIO2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher FIO2. CONCLUSIONS: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high FIO2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place. TRIAL REGISTRATION: Not applicable.

Tidal volume significantly affects oxygenation in healthy pigs during high-frequency oscillatory ventilation compared to conventional ventilation.

BACKGROUND: The role of high-frequency oscillatory ventilation (HFOV) has long been debated. Numerous studies documented its benefits, whereas several more recent studies did not prove superiority of HFOV over protective conventional mechanical ventilation (CV). One of the accepted explanations is that CV and HFOV act differently, including gas exchange. METHODS: To investigate a different level of coupling or decoupling between oxygenation and carbon dioxide elimination during CV and HFOV, we conducted a prospective crossover animal study in 11 healthy pigs. In each animal, we found a normocapnic tidal volume (VT) after the lung recruitment maneuver. Then, VT was repeatedly changed over a wide range while keeping constant the levels of PEEP during CV and mean airway pressure during HFOV. Arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) were recorded. The same procedure was repeated for CV and HFOV in random order. RESULTS: Changes in PaCO2 intentionally induced by adjustment of VT affected oxygenation more significantly during HFOV than during CV. Increasing VT above its normocapnic value during HFOV caused a significant improvement in oxygenation, whereas improvement in oxygenation during CV hyperventilation was limited. Any decrease in VT during HFOV caused a rapid worsening of oxygenation compared to CV. CONCLUSION: A change in PaCO2 induced by the manipulation of tidal volume inevitably brings with it a change in oxygenation, while this effect on oxygenation is significantly greater in HFOV compared to CV.

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.

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.

Three-layer collagen-based vascular graft designed for low-flow peripheral vascular reconstructions.

INTRODUCTION: The aim of this study was to develop a prototype of an artificial blood vessel which has similar mechanical properties to a human saphenous vein graft and to experimentally verify the function of the prosthesis via ovine carotid bypass implantation. MATERIAL AND METHODS: The prototype of an artificial graft prosthesis for low flow was developed and manufactured from a collagenous matrix and reinforcing polyester mesh. We compared the results of both the pressurisation and the mechanical stress evaluation tests of VSM with four types of hybrid vascular graft. The most similar graft (type II) was chosen for the first ovine model implantation. RESULTS: Dominant behavior e.g. mechanical response of VSM graft in plots of circumferential and axial stress during loading is observed in circumferential direction. Average results of used VSM showed area of ideal mechanical response and the properties of artificial blood vessels were fitted into this area. Developed graft remained patent after 161 days of follow up in ovine model. CONCLUSIONS: The mechanical properties of the graft were designed and adjusted to be similar to the behaviour of human saphenous veins. This approach showed promising results and enhanced the final performance of the prosthesis.

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.

The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study).

BACKGROUND: Renal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin-angiotensin-aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury. METHODS: An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. RESULTS: Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups. CONCLUSIONS: In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

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.

Renal denervation decreases effective refractory period but not inducibility of ventricular fibrillation in a healthy porcine biomodel: a case control study.

BACKGROUND: Ventricular arrhythmias play an important role in cardiovascular mortality especially in patients with impaired cardiac and autonomic function. The aim of this experimental study was to determine, if renal denervation (RDN) could decrease the inducibility of ventricular fibrillation (VF) in a healthy porcine biomodel. METHODS: Controlled electrophysiological study was performed in 6 biomodels 40 days after RDN (RDN group) and in 6 healthy animals (control group). The inducibility of VF was tested by programmed ventricular stimulation from the apex of right ventricle (8 basal stimuli coupled with up to 4 extrastimuli) always three times in each biomodel using peripheral extracorporeal oxygenation for hemodynamic support. Further, basal heart rate (HR), PQ and QT intervals and effective refractory period of ventricles (ERP) were measured. Technical success of RDN was evaluated by histological examination. RESULTS: According to histological findings, RDN procedure was successfully performed in all biomodels. Comparing the groups, basal HR was lower in RDN group: 79 (IQR 58; 88) vs. 93 (72; 95) beats per minute (p = 0.003); PQ interval was longer in RDN group: 145 (133; 153) vs. 115 (113; 120) ms (p < 0.0001) and QTc intervals were comparable: 402 (382; 422) ms in RDN vs. 386 (356; 437) ms in control group (p = 0.1). ERP was prolonged significantly in RDN group: 159 (150; 169) vs. 140 (133; 150) ms (p = 0.001), but VF inducibility was the same (18/18 vs. 18/18 attempts). CONCLUSIONS: RDN decreased the influence of sympathetic nerve system on the heart conduction system in healthy porcine biomodel. However, the electrophysiological study was not associated with a decrease of VF inducibility after RDN.

Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model.

INTRODUCTION: Mild therapeutic hypothermia (MTH) is being used after cardiac arrest for its expected improvement in neurological outcome. Safety of MTH concerning inducibility of malignant arrhythmias has not been satisfactorily demonstrated. This study compares inducibility of ventricular fibrillation (VF) before and after induction of MTH in a whole body swine model and evaluates possible interaction with changing potassium plasma levels. METHODS: The extracorporeal cooling was introduced in fully anesthetized swine (n = 6) to provide MTH. Inducibility of VF was studied by programmed ventricular stimulation three times in each animal under the following: during normothermia (NT), after reaching the core temperature of 32°C (HT) and after another 60 minutes of stable hypothermia (HT60). Inducibility of VF, effective refractory period of the ventricles (ERP), QTc interval and potassium plasma levels were measured. RESULTS: Starting at normothermia of 38.7 (IQR 38.2; 39.8)°C, HT was achieved within 54 (39; 59) minutes and the core temperature was further maintained constant. Overall, the inducibility of VF was 100% (18/18 attempts) at NT, 83% (15/18) after reaching HT (P = 0.23) and 39% (7/18) at HT60 (P = 0.0001) using the same protocol. Similarly, ERP prolonged from 140 (130; 150) ms at NT to 206 (190; 220) ms when reaching HT (P < 0.001) and remained 206 (193; 220) ms at HT60. QTc interval was inversely proportional to the core temperature and extended from 376 (362; 395) at NT to 570 (545; 599) ms at HT. Potassium plasma level changed spontaneously: decreased during cooling from 4.1 (3.9; 4.8) to 3.7 (3.4; 4.1) mmol/L at HT (P < 0.01), then began to increase and returned to baseline level at HT60 (4.6 (4.4; 5.0) mmol/L, P = NS). CONCLUSIONS: According to our swine model, MTH does not increase the risk of VF induction by ventricular pacing in healthy hearts. Moreover, when combined with normokalemia, MTH exerts an antiarrhythmic effect despite prolonged QTc interval.

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.

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.

Standard versus individualised positive end-expiratory pressure (PEEP) compared by electrical impedance tomography in neurocritical care: a pilot prospective single centre study.

BACKGROUND: Individualised bedside adjustment of mechanical ventilation is a standard strategy in acute coma neurocritical care patients. This involves customising positive end-expiratory pressure (PEEP), which could improve ventilation homogeneity and arterial oxygenation. This study aimed to determine whether PEEP titrated by electrical impedance tomography (EIT) results in different lung ventilation homogeneity when compared to standard PEEP of 5 cmH2O in mechanically ventilated patients with healthy lungs. METHODS: In this prospective single-centre study, we evaluated 55 acute adult neurocritical care patients starting controlled ventilation with PEEPs close to 5 cmH2O. Next, the optimal PEEP was identified by EIT-guided decremental PEEP titration, probing PEEP levels between 9 and 2 cmH2O and finding the minimal amount of collapse and overdistension. EIT-derived parameters of ventilation homogeneity were evaluated before and after the PEEP titration and after the adjustment of PEEP to its optimal value. Non-EIT-based parameters, such as peripheral capillary Hb saturation (SpO2) and end-tidal pressure of CO2, were recorded hourly and analysed before PEEP titration and after PEEP adjustment. RESULTS: The mean PEEP value before titration was 4.75 ± 0.94 cmH2O (ranging from 3 to max 8 cmH2O), 4.29 ± 1.24 cmH2O after titration and before PEEP adjustment, and 4.26 ± 1.5 cmH2O after PEEP adjustment. No statistically significant differences in ventilation homogeneity were observed due to the adjustment of PEEP found by PEEP titration. We also found non-significant changes in non-EIT-based parameters following the PEEP titration and subsequent PEEP adjustment, except for the mean arterial pressure, which dropped statistically significantly (with a mean difference of 3.2 mmHg, 95% CI 0.45 to 6.0 cmH2O, p < 0.001). CONCLUSION: Adjusting PEEP to values derived from PEEP titration guided by EIT does not provide any significant changes in ventilation homogeneity as assessed by EIT to ventilated patients with healthy lungs, provided the change in PEEP does not exceed three cmH2O. Thus, a reduction in PEEP determined through PEEP titration that is not greater than 3 cmH2O from an initial value of 5 cmH2O is unlikely to affect ventilation homogeneity significantly, which could benefit mechanically ventilated neurocritical care patients.

Hypothermia After Cardiac Arrest in Large Animals (HACA-LA): Study protocol of a randomized controlled experimental trial.

Background: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. Methods: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. Conclusion: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest.Trial registration:Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.

Mild therapeutic hypothermia is superior to controlled normothermia for the maintenance of blood pressure and cerebral oxygenation, prevention of organ damage and suppression of oxidative stress after cardiac arrest in a porcine model.

BACKGROUND: Mild therapeutic hypothermia (HT) has been implemented in the management of post cardiac arrest (CA) syndrome after the publication of clinical trials comparing HT with common practice (ie, usually hyperthermia). Current evidence on the comparison between therapeutic HT and controlled normothermia (NT) in CA survivors, however, remains insufficient. METHODS: Eight female swine (sus scrofa domestica; body weight 45 kg) were randomly assigned to receive either mild therapeutic HT or controlled NT, with four animals per group. Veno-arterial extracorporeal membrane oxygenation (ECMO) was established and at minimal ECMO flow (0.5 L/min) ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of CA, circulation was restored by increasing the ECMO flow to 4.5 L/min; 90 min of reperfusion followed. Target core temperatures (HT: 33°C; NT: 36.8°C) were maintained using the heat exchanger on the oxygenator. Invasive blood pressure was measured in the aortic arch, and cerebral oxygenation was assessed using near-infrared spectroscopy. After 60 min of reperfusion, up to three defibrillation attempts were performed. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I (TnI), myoglobin (MGB), creatine-phosphokinase (CPK), alanin-aminotransferase (ALT), neuron-specific enolase (NSE) and cystatin C (CysC) levels. Reactive oxygen metabolite (ROM) levels and biological antioxidant potential (BAP) were also measured. RESULTS: Significantly higher blood pressure and cerebral oxygenation values were observed in the HT group (P<0.05). Sinus rhythm was restored in all of the HT animals and in one from the NT group. The levels of TnI, MGB, CPK, ALT, and ROM were significantly lower in the HT group (P<0.05); levels of NSE, CysC, and BAP were comparable in both groups. CONCLUSIONS: Our results from animal model of cardiac arrest indicate that HT may be superior to NT for the maintenance of blood pressure, cerebral oxygenation, organ protection and oxidative stress suppression following CA.

Early vancomycin, amikacin and gentamicin concentrations in pulmonary artery and pulmonary tissue are not affected by VA ECMO (venoarterial extracorporeal membrane oxygenation) in a pig model of prolonged cardiac arrest.

BACKGROUND: ECMO (extracorporeal membrane oxygenation) is increasingly used in severe hemodynamic compromise and cardiac arrest (CA). Pulmonary infections are frequent in these patients. Venoarterial (VA) ECMO decreases pulmonary blood flow and antibiotic availability in lungs during VA ECMO treated CA is not known. We aimed to assess early vancomycin, amikacin and gentamicin concentrations in the pulmonary artery as well as tracheal aspirate and to determine penetration ratios of these antibiotics to lung tissue in a pig model of VA ECMO treated CA. METHODS: Twelve female pigs, body weight 51.5 ± 3.5 kg, were subjected to prolonged CA managed by different modes of VA ECMO. Anesthetized animals underwent 15 min of ventricular fibrillation (VF) followed by continued VF with ECMO flow of 100 mL/kg/min. Immediately after institution of ECMO, a 30 min vancomycin infusion (10 mg/kg) was started and amikacin and gentamicin boluses (7.5 and 3 mg/kg, respectively) were administered. ECMO circuit, aortic, pulmonary arterial, and tracheal aspirate concentrations of antibiotics were measured at 30 and 60 min after administration; penetration ratios were calculated. RESULTS: All 30 min antibiotic concentrations and 60 min concentration for gentamicin in the pulmonary artery were no different than the aorta. However, the 60 min pulmonary artery vancomycin and amikacin values were significantly higher than aortic, 19.8 (14.3-21.6) vs. 17.6 (14.2-19.0) mg/L, p = 0.009, and 15.6 mg/L (11.0-18.6) vs. 11.2 (10.4-17.2) mg/L, p = 0.036, respectively. One hour penetration ratios were 18.5% for vancomycin, 34.9% for gentamicin and 38.8% for amikacin. CONCLUSION: In a pig model of VA ECMO treated prolonged CA, despite diminished pulmonary flow, VA ECMO does not decrease early vancomycin, gentamicin, and amikacin concentrations in pulmonary artery. Within 1 h post administration, antibiotics can be detected in tracheal aspirate in adequate concentrations.

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.