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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.

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.

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., (© 2022. The Author(s).)

Objectives: The aim of this study was to quantify and understand the unloading effect of percutaneous balloon atrial septostomy (BAS) in acute cardiogenic shock (CS) treated with venoarterial (VA) extracorporeal membranous oxygenation (ECMO)., Background: In CS treated with VA ECMO, increased left ventricular (LV) afterload is observed that commonly interferes with myocardial recovery or even promotes further LV deterioration. Several techniques for LV unloading exist, but the optimal strategy and the actual extent of such procedures have not been fully disclosed., Methods: In a porcine model (n = 11; weight 56 kg [53-58 kg]), CS was induced by coronary artery balloon occlusion (57 minutes [53-64 minutes]). Then, a step-up VA ECMO protocol (40-80 mL/kg/min) was run before and after percutaneous BAS was performed. LV pressure-volume loops and multiple hemoglobin saturation data were evaluated. The Wilcoxon rank sum test was used to assess individual variable differences., Results: Immediately after BAS while on VA ECMO support, LV work decreased significantly: pressure-volume area, end-diastolic pressure, and stroke volume to ∼78% and end-systolic pressure to ∼86%, while superior vena cava and tissue oximetry did not change. During elevating VA ECMO support (40-80 mL/kg/min) with BAS vs without BAS, we observed 1) significantly less mechanical work increase (122% vs 172%); 2) no end-diastolic volume increase (100% vs 111%); and 3) a considerable increase in end-systolic pressure (134% vs 144%)., Conclusions: In acute CS supported by VA ECMO, atrial septostomy is an effective LV unloading tool. LV pressure is a key component of LV work load, so whenever LV work reduction is a priority, arterial pressure should carefully be titrated low while maintaining organ perfusion., Competing Interests: Funding Support and Author Disclosures This work was supported by a Euro ELSO research grant; by the Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, Mediterranean Institute for Transplantation and Advanced Specialized Therapies; by the Cardio-Thoracic Surgery Department, Maastricht University Medical Centre; and by the Technology Agency of the Czech Republic (project FW01010679). Dr Lorusso is principal investigator of the PERSIST-AVR study (sponsored by LivaNova); is a consultant to LivaNova, Getinge, and Medtronic; and is an advisory board member for Eurosets. Dr Belohlavek is a consultant to Abiomed, Medtronic, Eurosets, and Getinge. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The peripheral venoarterial extracorporeal life support (V-A ECLS) in cardiogenic shock (CS) may lead to LV overload. The transaortic suction device (Impella, ABIOMED Inc., Danvers, MA) was compared to the pulmonary artery (PA) drainage, for LV unloading efficacy during V-A ECLS in a porcine cardiogenic shock model. A dedicated CS model included 12 swine (21 ± 1.8-week-old and weighing 54.3 ± 4.6 kg) supported with V-A ECLS and randomized to Impella or PA-related LV drainage. LV unloading and end-organ perfusion were evaluated through the PA catheter and LV pressure/volume analysis. The LV end-diastolic volume sharply dropped with Impella (143.6 ± 67.4 vs 123 ± 75.7 mL) compared to a slight decrease in the PA cannula group (134.1 ± 39.9 vs 130.1 ± 34.7 mL), resulting in an overall stroke work and pressure-volume area reductions with both techniques. However, stroke work reduction was more significant in the Impella group (V-A ECLS 3998.8 ± 2027.6 vs V-A ECLS + Impella 1796.9 ± 1033.9 mm Hg × mL, P = 0.016), leading to a more consistent pressure-volume area reduction (Impella reduction 34.7% vs PA cannula reduction 9.7%) In terms of end organ perfusion, central and mixed O 2 saturation improved with V-A ECLS, and subsequently, remaining unchanged with either Impella or PA cannula as unloading strategy (SVmO2: Impella 86.0 ± 5.8 vs 87.8 ± 5.8; PA cannula 82.5 ± 10.7 vs 82.5 ± 11.3 %). Transaortic suction and PA drainage provided effective LV unloading during V-A ECLS while maintaining adequate end-organ perfusion. Impella provides a greater LV unloading effect and reduces more effectively the total LV stroke work., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Norway spruce (Picea abies L.) is among the most sensitive coniferous species to ongoing climate change. However, previous studies on its growth response to increasing temperatures have yielded contrasting results (from stimulation to suppression), suggesting highly site-specific responses. Here, we present the first study that applies two independent approaches, i.e. the nonlinear, process-based Vaganov-Shashkin (VS) model and linear daily response functions. Data were collected at twelve sites in Slovenia differing in climate regimes and ranging elevation between 170 and 1300 m a.s.l. VS model results revealed that drier Norway spruce sites at lower elevations are mostly moisture limited, while moist high-elevation sites are generally more temperature limited. Daily response functions match well the pattern of growth-limiting factors from the VS model and further explain the effect of climate on radial growth: prevailing growth-limiting factors correspond to the climate variable with higher correlations. Radial growth correlates negatively with rising summer temperature and positively with higher spring precipitation. The opposite response was observed for the wettest site at the highest elevation, which positively reacts to increased summer temperature and will most likely benefit from a warming climate. For all other sites, the future radial growth of Norway spruce largely depends on the balance between spring precipitation and summer temperature.

New insights into the intra-annual dynamics of tree-ring formation can improve our understanding of tree-growth response to environmental conditions at high-resolution time scales. Obtaining this information requires, however, a weekly monitoring of wood formation, sampling that is extremely time-intensive and scarcely feasible over vast areas. Estimating the timing of cambial and xylem differentiation by modeling thus represents an interesting alternative for obtaining this important information by other means. Temporal dynamics of cambial divisions can be extracted from the daily tree-ring growth rate computed by the Vaganov-Shashkin (VS) simulation model, assuming that cell production is tightly linked to tree-ring growth. Nonetheless, these predictions have yet to be compared with direct observations of wood development, i.e., via microcoring, over a long time span. We tested the performance of the VS model by comparing the observed and predicted timing of wood formation in black spruce [ Picea mariana (Mill.)]. We obtained microcores over 15 years at 5 sites along a latitudinal gradient in Quebec (Canada). The measured variables included cell size and the timing of cell production and differentiation. We calibrated the VS model using daily temperature and precipitation recorded by weather stations located on each site. The predicted and observed timing of cambial and enlarging cells were highly correlated ( R 2 = 0.8); nonetheless, we detected a systematic overestimation in the predicted timing of cambial cells, with predictions delayed by 1-20 days compared with observations. The growth rate of cell diameter was correlated with the predicted growth rate assigned to each cambial cell, confirming that cell diameter developmental dynamics have the potential to be inferred by the tree-ring growth curve of the VS model. Model performances decrease substantially in estimating the end of wood formation. The systematic errors suggest that the actual relationships implemented in the model are unable to explain the phenological events in autumn. The mismatch between the observed and predicted timing of wood formation in black spruce within our study area can be reduced by better adapting the VS model to wet sites, a context for which this model has been rarely used., (Copyright © 2020 Buttò, Shishov, Tychkov, Popkova, He, Rossi, Deslauriers and Morin.)

The aims were to explore the effect of head-up tilt (HUT) to 30 and 60 degrees on hemodynamics and tissue oxygenation in anesthetized healthy swine. The data serve as a reference for a study of resuscitation efficacy at HUT such as during transport. Nine healthy swine (49+/-4 kg) were anesthetized and multiple sensors including myocardial pressure-volume loops catheter, carotid flow probe, blood pressure catheters, near infrared spectroscopy (NIRS) tissue oximetry and mixed venous oximetry (SVO2) catheter were introduced and parameters continuously recorded. Experimental protocol consisted of baseline in supine position (15 min), 30 degrees HUT (15 min), recovery at supine position (15 min) and 60 degrees HUT (5 min). Vacuum mattress was used for body fixation during tilts. We found that 30 and 60 degrees inclination led to significant immediate reduction in hemodynamic and oximetry parameters. Mean arterial pressure (mm Hg) decreased from 98 at baseline to 53 and 39, respectively. Carotid blood flow dropped to 47 % and 22 % of baseline values, end diastolic volume to 49 % and 53 % and stroke volume to 47 % and 45 % of baseline. SVO2 and tissue oximetry decreased by 17 and 21 percentage points. The values are means. In conclusions, within minutes, both 30 and 60 degrees head-up tilting is poorly tolerated in anesthetized swine. Significant differences among individual animals exist.

A comparative comet-assay study of X-ray influence on DNA of leukocytes of peripheral blood from both cancer patients in the course of chemotherapy and on healthy donors was carried out. The amount of DNA registered in comet tails of blood samples from 18 healthy donors was between 0.8-3.6%. The mean value was 2.9 +/- 0.5%. In the preparations of cancer patients, an increase in comet tail DNA was observed for each chemotherapy course and in each subsequent course compared to the previous one. The individual variations were found in the level of DNA damage in the response to the administration of cyclophosphane, of methotrexate, of 5-fluorourocil (CMF protocol). The X-ray radiation (4 Gy) challenge test of blood cells showed an increase in comet tail DNA, the dynamics of radiation-induced lesions varying between individuals. The combined use of X-ray radiation and of the comet-assay in evaluating the capacity of the defence systems of the whole blood cells during chemotherapy let us to hold the monitoring of the state of genome of leukocytes without their isolation. This approach enables additional information on leukocyte genome to be rapidly obtained.