Dorsal recruitment with flow-controlled expiration (FLEX): an experimental study in mechanically ventilated lung-healthy and lung-injured pigs.

BACKGROUND: Concepts for optimizing mechanical ventilation focus mainly on modifying the inspiratory phase. We propose flow-controlled expiration (FLEX) as an additional means for lung protective ventilation and hypothesize that it is capable of recruiting dependent areas of the lungs. This study investigates potential recruiting effects of FLEX using models of mechanically ventilated pigs before and after induction of lung injury with oleic acid. METHODS: Seven pigs in the supine position were ventilated with tidal volume 8 ml·kg- 1 and positive end-expiratory pressure (PEEP) set to maintain partial pressure of oxygen in arterial blood (paO2) at ≥ 60 mmHg and monitored with electrical impedance tomography (EIT). Two ventilation sequences were recorded - one before and one after induction of lung injury. Each sequence comprised 2 min of conventional volume-controlled ventilation (VCV), 2 min of VCV with FLEX and 1 min again of conventional VCV. Analysis of the EIT recordings comprised global and ventral and dorsal baseline levels of impedance curves, end-expiratory no-flow periods, tidal variation in ventral and dorsal areas, and regional ventilation delay index. RESULTS: With FLEX, the duration of the end-expiratory zero flow intervals was significantly shortened (VCV 1.4 ± 0.3 s; FLEX 0.7 ± 0.1 s, p < 0.001), functional residual capacity was significantly elevated in both conditions of the lungs (global: healthy, increase of 87 ± 12 ml, p < 0.001; injured, increase of 115 ± 44 ml, p < 0.001; ventral: healthy, increase of 64 ± 11 ml, p < 0.001; injured, increase of 83 ± 22 ml, p < 0.001; dorsal: healthy, increase of 23 ± 5 ml, p < 0.001; injured, increase of 32 ± 26 ml, p = 0.02), and ventilation was shifted from ventral to dorsal areas (dorsal increase: healthy, 1 ± 0.5%, p < 0.01; dorsal increase: injured, 6 ± 2%, p < 0.01), compared to conventional VCV. Recruiting effects of FLEX persisted during conventional VCV following FLEX ventilation mostly in the injured but also in the healthy lungs. CONCLUSIONS: FLEX shifts regional ventilation towards dependent lung areas in healthy and in injured pig lungs. The recruiting capabilities of FLEX may be mainly responsible for lung-protective effects observed in an earlier study.

Standardized model of porcine resuscitation using a custom-made resuscitation board results in optimal hemodynamic management.

AIM: Standardized modeling of cardiac arrest and cardiopulmonary resuscitation (CPR) is crucial to evaluate new treatment options. Experimental porcine models are ideal, closely mimicking human-like physiology. However, anteroposterior chest diameter differs significantly, being larger in pigs and thus poses a challenge to achieve adequate perfusion pressures and consequently hemodynamics during CPR, which are commonly achieved during human resuscitation. The aim was to prove that standardized resuscitation is feasible and renders adequate hemodynamics and perfusion in pigs, using a specifically designed resuscitation board for a pneumatic chest compression device. METHODS AND RESULTS: A "porcine-fit" resuscitation board was designed for our experiments to optimally use a pneumatic compression device (LUCAS® II, Physio-Control Inc.), which is widely employed in emergency medicine and ideal in an experimental setting due to its high standardization. Asphyxial cardiac arrest was induced in 10 German hybrid landrace pigs and cardiopulmonary resuscitation was performed according to ERC/AHA 2015 guidelines with mechanical chest compressions. Hemodynamics were measured in the carotid and pulmonary artery. Furthermore, arterial blood gas was drawn to assess oxygenation and tissue perfusion. The custom-designed resuscitation board in combination with the LUCAS® device demonstrated highly sufficient performance regarding hemodynamics during CPR (mean arterial blood pressure, MAP 46 ±â€¯1 mmHg and mean pulmonary artery pressure, mPAP of 36 ±â€¯1 mmHg over the course of CPR). MAP returned to baseline values at 2 h after ROSC (80 ±â€¯4 mmHg), requiring moderate doses of vasopressors. Furthermore, stroke volume and contractility were analyzed using pulse contour analysis (106 ±â€¯3 ml and 1097 ±â€¯22 mmHg/s during CPR). Blood gas analysis revealed CPR-typical changes, normalizing in the due course. Thermodilution parameters did not show persistent intravascular volume shift. CONCLUSION: Standardized cardiopulmonary resuscitation is feasible in a porcine model, achieving adequate hemodynamics and consecutive tissue perfusion of consistent quality.

The Impact of Head Position on Neurological and Histopathological Outcome Following Controlled Automated Reperfusion of the Whole Body (CARL) in a Pig Model.

Introduction: Based on extracorporeal circulation, targeted reperfusion strategies have been developed to improve survival and neurologic recovery in refractory cardiac arrest: Controlled Automated Reperfusion of the whoLe Body (CARL). Furthermore, animal and human cadaver studies have shown beneficial effects on cerebral pressure due to head elevation during conventional cardiopulmonary resuscitation. Our aim was to evaluate the impact of head elevation on survival, neurologic recovery and histopathologic outcome in addition to CARL in an animal model. Methods: After 20 min of ventricular fibrillation, 46 domestic pigs underwent CARL, including high, pulsatile extracorporeal blood flow, pH-stat acid-base management, priming with a colloid, mannitol and citrate, targeted oxygen, carbon dioxide and blood pressure management, rapid cooling and slow rewarming. N = 25 were head-up (HUP) during CARL, and N = 21 were supine (SUP). After weaning from ECC, the pigs were extubated and followed up in the animal care facility for up to seven days. Neuronal density was evaluated in neurohistopathology. Results: More animals in the HUP group survived and achieved a favorable neurological recovery, 21/25 (84%) versus 6/21 (29%) in the SUP group. Head positioning was an independent factor in neurologically favorable survival (p < 0.00012). Neurohistopathology showed no significant structural differences between HUP and SUP. Distinct, partly transient clinical neurologic deficits were blindness and ataxia. Conclusions: Head elevation during CARL after 20 min of cardiac arrest independently improved survival and neurologic outcome in pigs. Clinical follow-up revealed transient neurologic deficits potentially attributable to functions localized in the posterior perfusion area, whereas histopathologic findings did not show corresponding differences between the groups. A possible explanation of our findings may be venous congestion and edema as modifiable contributing factors of neurologic injury following prolonged cardiac arrest.

Thoracic endovascular stent grafting inhibits aortic growth: an experimental study.

OBJECTIVE: Dilatation of the aorta at the landing zone site may be exaggerated by the radial force of stent grafts potentially limiting long-term results of endovascular therapy. We evaluated growth patterns and morphology of the thoracic aorta in young piglets after thoracic stent-graft placement. METHODS: Eight domestic piglets (37+/-2 kg) had an endovascular stent graft placed in the proximal descending thoracic aorta using retroperitoneal access. At implantation, the stent was oversized by 10%. Aortic size was documented after thoracotomy by intraoperative measurement and angiography. Subsequently the piglets were grown to adult size (181+/-42 kg). At explantation 6-15 months later, CT scan and surgical evaluation for endoleaks, defined as perigraft flow, was performed. Histopathological assessment of the explanted aorta was performed in stented and non-stented segments and compared to five normal porcine aortas. RESULTS: No endoleak (perigraft flow) or stent migration occurred even in 230kg pigs. The stent grafts expanded to full size, but there was no further growth in the stented area. The aortic diameter increased significantly by 32+/-9% 1cm proximal to the stents (p=0.0012) and by 45+/-13% 1cm distal to the stents (p=0.0033). The stented area grew less than the proximal (p=0.0011) and distal aorta (p<0.0001). In all pigs, the distal aorta was larger than the proximal overstented segment. Histology of the stented aorta showed significant thickening of the intima (p=0.018) and media (p=0.006) with neointimal formation and segmental fibrosis of the inner 1/3 of the media with loss of smooth muscle cells and compression of the elastic fibers but normal architecture in the outer 2/3 of the media. CONCLUSIONS: Endovascular stent grafting may inhibit growth of the nonatherosclerotic normal aorta and lead to intimal hyperplasia and focal fibrosis in the inner media part adjacent to the stent. Stent-graft interaction with aortic tissue over time is important and should receive more detailed evaluation. Testing this interaction in an animal model of nonatherosclerotic dilative aortic disease could be of great interest.

Autologous heterotopic transplantation of ovarian tissue in sheep.

The aims of this study were [1] to test the feasibility of autologous heterotopic transplantation of large ovarian tissue samples (approximately 2 cm in diameter and 2 or 3 mm thick) without vascular anastomosis and [2] to compare follicle count and microvessel density in fresh and grafted 2-mm vs. 3-mm tissue samples in an animal model. After transplantation, we observed regular menstrual cycles and ovulation proved by high E(2) levels and intermittent P peaks in all Suffolk sheep, and histologic examination revealed no statistically significant differences in the number of primordial follicles and microvessel density between samples 2 mm and 3 mm in diameter.

Heterotopic transplantation of cryopreserved tracheae in a rat model.

INTRODUCTION: The successful use of cryopreserved tracheal allografts in canine models suggests their use in humans. The grade of genetic difference, the mechanism of revascularisation and the method of cryopreservation are not clearly defined. The purpose of our study was to investigate the rejection of tracheal transplants in a standardised heterotopic rat model using different forms of cryopreservation. METHODS: Tracheae from Brown Norway rats were implanted into the omentum from Brown Norway rats or Lewis rats. We transplanted fresh isografts or allografts and pretreated isografts or allografts. Cryopreservation was performed in a medium containing 10% dimethyl sulphoxide at -80 degrees C for 28 days (I) or -196 degrees C for 84 days (II) or without medium at -80 degrees C for 28 days (III). The transplants were excised after 7 and 21 days, respectively. RESULTS: Histological examinations revealed normal structure and function of isografts after 21 days. In the cryopreserved isograft, the epithelium had disappeared and the tracheal lumen was partially obstructed by a non-compact fibrous tissue. In the fresh allografts, the epithelium was replaced by aggressive fibrous tissue, infiltrating the membranous part of the trachea and occluding the tracheal lumen. The cartilage was vital without any sign of rejection. In the cryopreserved allografts, the tracheal lumen was obstructed by dense fibrous tissue with an inflammatory reaction. The cartilage of cryopreserved allografts (II) and (III) had lost the nuclei corresponding to non-vital tissue. Only in the cryopreserved allografts (I) did we find nodular regeneration at the edges of the cartilaginous bow. CONCLUSIONS: The heterotopic transplantation model allows the study of the mechanisms leading to tracheal obstruction. Cryopreservation was found to have no clear advantage in reducing transplant immunogenicity. Cryopreservation leads to significant damage to the cartilage, the intensity of which is dependent on the mode of cryopreservation.

Mapping of sheep sensory cortex with a novel microelectrocorticography grid.

Microelectrocorticography (µECoG) provides insights into the cortical organization with high temporal and spatial resolution desirable for better understanding of neural information processing. Here we evaluated the use of µECoG for detailed cortical recording of somatosensory evoked potentials (SEPs) in an ovine model. The approach to the cortex was planned using an MRI-based 3D model of the sheep's brain. We describe a minimally extended surgical procedure allowing placement of two different µECoG grids on the somatosensory cortex. With this small craniotomy, the frontal sinus was kept intact, thus keeping the surgical site sterile and making this approach suitable for chronic implantations. We evaluated the procedure for chronic implantation of an encapsulated µECoG recording system. During acute and chronic recordings, significant SEP responses in the triangle between the ansate, diagonal, and coronal sulcus were identified in all animals. Stimulation of the nose, upper lip, lower lip, and chin caused a somatotopic lateral-to-medial, ipsilateral response pattern. With repetitive recordings of SEPs, this somatotopic pattern was reliably recorded for up to 16 weeks. The findings of this study confirm the previously postulated ipsilateral, somatotopic organization of the sheep's sensory cortex. High gamma band activity was spatially most specific in the comparison of different frequency components of the somatosensory evoked response. This study provides a basis for further acute and chronic investigations of the sheep's sensory cortex by characterizing its exact position, its functional properties, and the surgical approach with respect to macroanatomical landmarks.

Fat marrow embolism during intramedullary bone endoscopy: an experimental study in sheep.

We present a study designed to investigate whether the intramedullary bone endoscopy (IBE) procedure within the cavity of an intact long bone will create embolic loads on the lungs similar to that of other orthopedic procedures (e.g., stem implantation in total hip arthroplasty [THA]). In a sheep model, 10 animals underwent the IBE procedure with complete perioperative anesthesiology monitoring. The lungs were harvested postoperatively and examined for fat embolisms. One animal showed evidence of intraoperative fat embolism with temporary increases in mean pulmonary arterial pressure (MPAD) and the mean CO(2)-gradient. The histological examination in this animal revealed fat embolism with a 2% surface area of the investigated fields covered with fat vacuoles. All peri- and postoperative data on the other nine animals were normal. Our findings indicate that, as with other intramedullary manipulation in intact long bones, there is a potential risk for systemic fat excavation during IBE. However, the embolic load is much lower than the rates reported for other orthopedic interventions.