Mikulas Mlcek’s research while affiliated with Charles University in Prague and other places

The effects of a large arteriovenous fistula (AVF) on pulmonary perfusion remains to be elucidated. We aimed to study, for the first time, the real-time acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. Ten healthy swine under general anesthesia were studied. AVF was created by the connection of femoral artery and femoral vein using high-diameter perfusion cannulas. The AVF was closed and after 30 min of stabilization the first values were recorded. The fistula was then opened, and new data were collected after reaching stable state. Continuous hemodynamic monitoring was performed throughout the protocol. The following functional images were analyzed by electrical impedance tomography (EIT): perfusion and ventilation distributions. We found an increased cardiac output and right ventricular work, which was strongly correlated to an increased pulmonary artery mean pressure (r=0.878, P=0.001). The ventral/dorsal ratio of pulmonary perfusion decreased from 1.9±1.0 to 1.5±0.7 (P=0.025). The percentage of total pulmonary blood flow through the dorsal lung region increased from 38.6±11.7 to 42.2±10.4 (P=0.016). In conclusion, we have used EIT for the first time for studying the acute effects of a large AVF on regional distribution of pulmonary perfusion in a novel porcine model. In this new experimental model of hyperkinetic circulation caused by AVF, we documented an increased percentage of total pulmonary blood flow through the dorsal lung region and a more homogeneous perfusion distribution.

Background Adrenaline (ADR) is a cornerstone of advanced life support (ALS) in cardiac arrest (CA), although its neurologically favourable survival outcomes remain unclear. ADR increases coronary perfusion pressure (CPP), with levels >15 mmHg associated with successful defibrillation. This study aimed to elucidate the relationship between ADR, myocardial microvascular blood flow, and resuscitation outcomes using a porcine CA model simulating refractory ventricular fibrillation (VF). Methods This study involved 24 domestic pigs. After instrumentation, intubation, and baseline measurements, the animals were randomised into the ADR or control (saline) groups. VF was induced, and cardiopulmonary resuscitation was initiated using continuous mechanical chest compressions and ventilation. ADR or saline was administered following ALS guidelines. After 21 min of ALS, defibrillation was performed. Continuous measurements of arterial and venous blood pressures using an electrocardiogram and index of myocardial resistance (IMR) and transit mean time (Tmn) 1 min before and after each injection or peak blood pressure were recorded and compared between the groups. CPP–IMR, amplitude spectrum area (AMSA)–IMR, CPP–Tmn, and AMSA–Tmn correlations were assessed. Results Compared with six animals in the control group, three in the ADR group achieved a return of spontaneous circulation. No difference was observed in IMR or AMSA; however, significant increases in CPP and arterial end-diastolic blood pressure were observed at several time points. Tmn differed between groups only at two time points. Conclusion Repeated ADR doses during prolonged ALS simulating refractory VF did not improve myocardial microvascular blood flow, as measured using IMR, despite leading to an increase in CPP.

Introduction: Many post-cardiac arrest (CA) therapies shown to be effective in animal models have failed to translate in human clinical trials. The predominance of single site pre-clinical studies, which lacks the heterogeneity and variability inherent in multicenter human clinical trials, could contribute to this failure. Multicenter pre-clinical studies might yield variability that more closely approximates human clinical trials, and thus result in reduction of bias and better initial screening of interventions. Here we describe the variability of CA characteristics among participating centers of an international multicenter preclinical CA research network. Methods: This is a retrospective analysis of control group subject data from swine CA studies submitted to the TRANSatlantic Cardiac arrEst Neuroprotection aDvancement (TRANSCEND) Network pre-clinical registry. Data for 101 animals from ten different models at seven institutions across the U.S.A, Europe, and Asia were included in this analysis. Data related to CA characteristics (intervals), post-CA characteristics (hemodynamics and blood gas at 1 hour post-ROSC), and neurological outcome were compiled and compared between the ten models. One-way ANOVA and Bartlett Test were used to estimate differences in means and standard deviations (SD). Chi Square test was used to compare proportions. Results: There were significant differences in CA characteristics between all ten models. The mean (SD) interval from CA to start of cardiopulmonary resuscitation was 8 (4)min (range of 2 to 14min) and from onset of CA to ROSC was 19 (7)min (range 13 to 38min) ( p <0.0001). There were also significant differences between models when comparing sex, weight, post-ROSC hemodynamics, arterial blood gas results, and neurological outcome ( p <0.0001). Data is detailed in the table. Conclusion: This analysis illustrates significant variability in CA and post-ROSC characteristics and neurologic outcomes when comparing different swine CA models in an international pre-clinical registry. Such variability could make interventional CA studies performed in a multicenter network more predictive of human clinical trials.

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 cmH 2 O 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 cmH 2 O. Next, the optimal PEEP was identified by EIT-guided decremental PEEP titration, probing PEEP levels between 9 and 2 cmH 2 O 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 (SpO 2 ) and end-tidal pressure of CO 2 , were recorded hourly and analysed before PEEP titration and after PEEP adjustment. Results The mean PEEP value before titration was 4.75 ± 0.94 cmH 2 O (ranging from 3 to max 8 cmH 2 O), 4.29 ± 1.24 cmH 2 O after titration and before PEEP adjustment, and 4.26 ± 1.5 cmH 2 O 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 cmH 2 O, 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 cmH 2 O. Thus, a reduction in PEEP determined through PEEP titration that is not greater than 3 cmH 2 O from an initial value of 5 cmH 2 O is unlikely to affect ventilation homogeneity significantly, which could benefit mechanically ventilated neurocritical care patients.

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.

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.