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.

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.

Atrial Septostomy for Left Ventricular Unloading During Extracorporeal Membrane Oxygenation for Cardiogenic Shock: Animal Model.

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.

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.

Vancomycin-releasing cross-linked collagen sponges as wound dressings.

The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.

Transaortic or Pulmonary Artery Drainage for Left Ventricular Unloading in Venoarterial Extracorporeal Life Support: A Porcine Cardiogenic Shock Model.

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 O2 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.

Rifampin-Releasing Triple-Layer Cross-Linked Fresh Water Fish Collagen Sponges as Wound Dressings.

OBJECTIVES: Surgical wounds resulting from biofilm-producing microorganisms represent a major healthcare problem that requires new and innovative treatment methods. Rifampin is one of a small number of antibiotics that is able to penetrate such biofilms, and its local administration has the potential to serve as an ideal surgical site infection protection and/or treatment agent. This paper presents two types (homogeneous and sandwich structured) of rifampin-releasing carbodiimide-cross-linked fresh water fish collagen wound dressings. METHODS: The dressings were prepared by means of the double-lyophilization method and sterilized via gamma irradiation so as to allow for testing in a form that is able to serve for direct clinical use. The mechanical properties were studied via the uniaxial tensile testing method. The in vivo rifampin-release properties were tested by means of a series of incubations in phosphate-buffered saline. The microbiological activity was tested against methicillin-resistant staphylococcus aureus (MRSA) employing disc diffusion tests, and the in vivo pharmacokinetics was tested using a rat model. A histological examination was conducted for the study of the biocompatibility of the dressings. RESULTS: The sandwich-structured dressing demonstrated better mechanical properties due to its exhibiting ability to bear a higher load than the homogeneous sponges, a property that was further improved via the addition of rifampin. The sponges retarded the release of rifampin in vitro, which translated into at least 22 hours of rifampin release in the rat model. This was significantly longer than was achieved via the administration of a subcutaneous rifampin solution. Microbiological activity was proven by the results of the disc diffusion tests. Both sponges exhibited excellent biocompatibility as the cells penetrated into the scaffold, and virtually no signs of local irritation were observed. CONCLUSIONS: We present a novel rifampin-releasing sandwich-structured fresh water fish collagen wound dressing that has the potential to serve as an ideal surgical site infection protection and/or treatment agent.

Influence of the new standardized clinical cryopreservation/slow thawing protocol on immunogenicity of arterial allografts in rats.

OBJECTIVES AND DESIGN: At the present time there are two waiting list for patients with vascular prosthetic infection indicated for arterial transplantation in the Czech Republic. The inclusion of each patient for cold-stored or cryopreserved arterial transplantation is the preference of indicating surgeon. In this experimental work we studied the immunogenicity of rat aortal allografts treated by our new clinical cryopreservation/slow thawing protocol. MATERIAL AND METHODS: Brown-Norway (BN) (N = 6, 203-217 g) or Lewis (LEW) (N = 6, 248-254 g) abdominal aortal grafts treated in accordance with our new clinical cryopreservation/slow thawing protocol were orthotopically transplanted to Lewis recipients (N = 12, 191-245 g). Aortal wall histology and infiltration by recipient immune cells, as well as donor specific anti MHC class I and II antibodies in recipient serum were studied in both isografts and allografts on day 30 postransplant. Core data of cryopreserved allografts were compared to our previous data of cold-stored aortal allografts treated in accordance with our clinical cold-storage protocol. RESULTS: Cryopreserved allografts showed regular morphology of aortal wall with clear differentiation of all three basic anatomical layers on day 30 postransplant. Intimal layer showed no hyperplasia, luminal surface was covered by endothelial cells. No statistical difference was observed in tunica media thickness between isografts and allografts. The medial layer showed no necrosis, shrinkage or immunoglobuline G deposition in any experimental group. The adventitial infiltration by immune cells was significantly higher (P<0.05) in allografts. Cryopreserved allografts showed significant lower activation of both cell- and antibody mediated immunity compared to historical data of cold-stored allografts. CONCLUSION: Aortal wall histology of rat allografts treated by our new standardized clinical cryopreservation/slow thawing protocol was comparable to that of the cryopreserved isografts on day 30 posttranspant. The immunogenicity of cryopreserved aortal allografts was significantly lower compared to that of cold-stored aortal allografts.

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.

Evaluation of the Immunogenicity of a Vascular Graft Covered with Collagen Derived from the European Carp (Cyprinus carpio) and Bovine Collagen.

AIM: To assess the systemic and local immunological response to subcutaneous implants of a vascular graft covered with collagen extracted from the European carp (freshwater fish) or with collagen of bovine origin. METHODS: Pieces of a vascular graft covered by pure bovine (Bos taurus, BOV, n=14) or carp (Cyprinus carpio, CYP, n=14) collagen 5 mm in size were implanted subcutaneously in the dorsum of a Balb/cOla mice. A sham operation group of 12 animals served as the control. At 7 and 14 days after the operation, one-half of each group was terminated and blood for serum, spleen, and implant with surrounding tissue were collected. Mean cytokine (TNF-α, IL-10, IL-4, IL-1ß, IL-13, and IFN-γ) levels in serum were determined using ELISA. Spleen cell cultures were used for in vitro testing of lymphocyte proliferation and cytokine secretion. Local expressions of IL-6, IL-10, TNF-α, TGF-ß, CCL-2, and CCL-3 were determined using PCR. RESULTS: We found no significant difference among control, BOV, and CYP groups in mean cytokine serum levels at seven days. At day 14, the BOV group had higher levels of TNF-α (P=.018) and both the BOV and CYP groups had lower levels of IL-4 (P=.011 and P=.047, respectively) compared with the control group. Both tested implants showed only a minimal effect on the production of selected cytokines. Cell proliferation in the CYP group stimulated by CYP gel at 14 days was significantly lower than by BOV gel in BOV group (P=.0031) or by CYP gel in the control group (P=.041). The difference between the groups in the local RNA expression of all the tested mediators both at 7 and at 14 days was not significant apart from a lower level of TNF-α in the BOV group compared to CYP at 14 days (P=.013). CONCLUSIONS: Implants covered with carp collagen induce an immunological response that is comparable to that of bovine collagen covered implants in a mouse model.

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.

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.