Development of an ultra mini-oxygenator for use in low-volume, buffer-perfused preparations

Introduction: Small animal models are widely used in basic research. However, experimental systems requiring extracorporeal circuits are frequently confronted with limitations related to equipment size. This is particularly true for oxygenators in systems with limited volumes. Thus we aimed to develop and validate an ultra mini-oxygenator for low-volume, buffer-perfused systems. Methods: We have manufactured a series of ultra mini-oxygenators with approximately 175 aligned, microporous, polypropylene hollow fibers contained inside a shell, which is sealed at each of the two extremities to isolate perfusate and gas compartments. With this construction, gas passes through hollow fibers, while perfusate circulates around fibers. Performance of ultra mini-oxygenators (oxygen partial pressure (PO2 ), gas and perfusate flow, perfusate pressure and temperature drop) were assessed with modified Krebs-Henseleit buffer in an in vitro perfusion circuit and an ex vivo rat heart preparation. Results: Mean priming volume of ultra mini-oxygenators was 1.2±0.5 mL and, on average, 86±6% of fibers were open (n=17). In vitro, effective oxygenation (PO2=400-500 mmHg) was achieved for all flow rates up to 50 mL/min and remained stable for at least 2 hours (n=5). Oxygenation was also effective and stable (PO2=456±40 mmHg) in the isolated heart preparation for at least 60 minutes ("venous" PO2=151±11 mmHg; n=5). Conclusions: We have established a reproducible procedure for fabrication of ultra mini-oxygenators, which provide reliable and stable oxygenation for at least 60-120 min. These oxygenators are especially attractive for pre-clinical protocols using small, rather than large, animals.

Pressure-temperature estimates of the lizardite/antigorite transition in high pressure serpentinites

Serpentine minerals in natural samples are dominated by lizardite and antigorite. In spite of numerous laboratory experiments, the stability fields of these species remain poorly constrained. This paper presents petrological observations and the Raman spectroscopy and XRD analyses of natural serpentinites from the Alpine paleo-accretionary wedge. Serpentine varieties were identified from a range of metamorphic pressure and temperature conditions from sub-greenschist (P < 4 kbar, T ~ 200–300 °C) to eclogite facies conditions (P > 20 kbar, T > 460 °C) along a subduction geothermal gradient. We use the observed mineral assemblage in natural serpentinite along with the Tmax estimated by Raman spectroscopy of the carbonaceous matter in associated metasediments to constrain the temperature of the lizardite to antigorite transition at high pressures. We show that below 300 °C, lizardite and locally chrysotile are the dominant species in the mesh texture. Between 320 and 390 °C, lizardite is progressively replaced by antigorite at the grain boundaries through dissolution–precipitation processes in the presence of SiO2 enriched fluids and in the cores of the lizardite mesh. Above 390 °C, under high-grade blueschist to eclogite facies conditions, antigorite is the sole stable serpentine mineral until the onset of secondary olivine crystallization at 460 °C.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator.

OBJECTIVES Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. METHODS The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. RESULTS Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. CONCLUSIONS We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion.

Oxygen-transfer performance of a newly designed, very low-volume membrane oxygenator

Gebiet: Chirurgie Biomedizintechnik Biophysik Transplantationsmedizin Kardiologie Abstract: OBJECTIVES: – Oxygenation of blood and other physiological solutions are routinely required in fundamental research for both in vitro and in vivo experimentation. However, very few oxygenators with suitable priming volumes (<2-3 ml) are available for surgery in small animals. We have designed a new, miniaturized membrane oxygenator and investigated the oxygen-transfer performance using both buffer and blood perfusates. – – METHODS: – The mini-oxygenator was designed with a central perforated core-tube surrounded by parallel-oriented microporous polypropylene hollow fibres, placed inside a hollow shell with a lateral-luer outlet, and sealed at both extremities. With this design, perfusate is delivered via the core-tube to the centre of the mini-oxygenator, and exits via the luer port. A series of mini-oxygenators were constructed and tested in an in vitro perfusion circuit by monitoring oxygen transfer using modified Krebs-Henseleit buffer or whole porcine blood. Effects of perfusion pressure and temperature over flows of 5-60 ml × min(-1) were assessed. – – RESULTS: – Twelve mini-oxygenators with a mean priming volume of 1.5 ± 0.3 ml were evaluated. With buffer, oxygen transfer reached a maximum of 14.8 ± 1.0 ml O2 × l(-1) (pO2: 450 ± 32 mmHg) at perfusate flow rates of 5 ml × min(-1) and decreased with an increase in perfusate flow to 7.8 ± 0.7 ml ml O2 × l(-1) (pO2: 219 ± 24 mmHg) at 60 ml × min(-1). Similarly, with blood perfusate, oxygen transfer also decreased as perfusate flow increased, ranging from 33 ± 5 ml O2 × l(-1) at 5 ml × min(-1) to 11 ± 2 ml O2 × l(-1) at 60 ml × min(-1). Furthermore, oxygen transfer capacity remained stable with blood perfusion over a period of at least 2 h. – – CONCLUSIONS: – We have developed a new miniaturized membrane oxygenator with an ultra-low priming volume (<2 ml) and adequate oxygenation performance. This oxygenator may be of use in overcoming current limitations in equipment size for effective oxygenation in low-volume perfusion circuits, such as small animal extracorporeal circulation and ex vivo organ perfusion. – – © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Metamorphic and geochronogical study of the Triassic El Oro metamorphic complex, Ecuador: Implications for high-temperature metamorphism in a forearc zone

In the forearc of the Andean active margin in southwest Ecuador, the El Oro metamorphic complex exhibits a well exposed tilted forearc section partially migmatized. We used Raman spectroscopy on carbonaceous matter (RSCM) thermometry and pseudosections coupled with mineralogical and textural studies to constrain the pressure–temperature (P–T) evolution of the El Oro metamorphic complex during Triassic times. Our results show that anatexis of the continental crust occurred by white-mica and biotite dehydration melting along a 10 km thick crustal domain (from 4.5 to 8 kbar) with increasing temperature from 650 to 700 °C. In the biotite dehydration melting zone, temperature was buffered at 750–820 °C in a 5 km thick layer. The estimated average thermal gradient during peak metamorphism is of 30 °C/km within the migmatitic domain can be partitioned into two apparent gradients parts. The upper part from surface to 7 km depth records a 40–45 °C/km gradient. The lower part records a quasi-adiabatic geotherm with a 10 °C/km gradient consistent with an isothermal melting zone. Migmatites U–Th–Pb geochronology yielded zircon and monazite ages of 229.3 ± 2.1 Ma and 224.5 ± 2.3 Ma, respectively. This thermal event generated S-type magmatism (the Marcabeli granitoid) and was immediately followed by underplating of the high-pressure low-temperature (HP-LT) Arenillas–Panupalí unit at 225.8 ± 1.8 Ma. The association of high-temperature low-pressure (HT-LP) migmatites with HP-LT unit constitutes a new example of a paired metamorphic belt along the South American margin. We propose that in addition to crustal thinning, underplating of the Piedras gabbroic unit before 230 Ma provided the heat source necessary to foster crustal anatexis. Furthermore, its MORB signature shows that the asthenosphere was involved as the source of the heat anomaly. S-type felsic magmatism is widespread during this time and suggests that a large-scale thermal anomaly affected a large part of the South American margin during the late Triassic. We propose that crustal anatexis is related to an anomaly that arose during subduction of the Panthalassa ocean under the South American margin. Slab verticalization or slab break-off can be invoked as the origin of the upwelling of the asthenosphere.

Exploring Multi-Component Superconducting Compounds by a High-Pressure Method and Ceramic Combinatorial Chemistry

In this short review, we provide some new insights into the material synthesis and characterization of modern multi-component superconducting oxides. Two different approaches such as the high-pressure, high-temperature method and ceramic combinatorial chemistry will be reported with application to several typical examples. First, we highlight the key role of the extreme conditions in the growth of Fe-based superconductors, where a careful control of the composition-structure relation is vital for understanding the microscopic physics. The availability of high-quality LnFeAsO (Ln = lanthanide) single crystals with substitution of O by F, Sm by Th, Fe by Co, and As by P allowed us to measure intrinsic and anisotropic superconducting properties such as Hc2, Jc. Furthermore, we demonstrate that combinatorial ceramic chemistry is an efficient way to search for new superconducting compounds. A single-sample synthesis concept based on multi-element ceramic mixtures can produce a variety of local products. Such a system needs local probe analyses and separation techniques to identify compounds of interest. We present the results obtained from random mixtures of Ca, Sr, Ba, La, Zr, Pb, Tl, Y, Bi, and Cu oxides reacted at different conditions. By adding Zr but removing Tl, Y, and Bi, the bulk state superconductivity got enhanced up to about 122 K.

Origin of the high upconversion green luminescence efficiency in -NaYF4:2% Er3+,20% Yb3+

Site-selective spectroscopy in hexagonal beta-NaYF4:Er3+,Yb3+ has revealed different environments for Er3+ ions (multisite formation). The low-temperature S-4(3/2) -> (I15/2Er3+)-I-4 green emission depends on the excitation wavelength associated with the F-4(7/2) Er3+ level. We have studied the effect of hydrostatic pressure on the green, red, and blue Er3+ emission upon NIR excitation at similar to 980 nm, in order to establish the role played by energy resonance conditions and the multiple Er3+ sites due to the disordered structure for the upconversion (UC) process (energy tuning). The variation of photoluminescence spectra and lifetimes as a function of pressure and temperature reveals that the origin of the high green UC efficiency of the beta-NaYF4:Er3+,Yb3+ compound is mainly due to the multisite distribution, and the low phonon energy of the host lattice.

A novel interface for hybrid mock circulations to evaluate ventricular assist devices

This paper presents a novel mock circulation for the evaluation of ventricular assist devices (VADs), which is based on a hardware-in-the-loop concept. A numerical model of the human blood circulation runs in real time and computes instantaneous pressure, volume, and flow rate values. The VAD to be tested is connected to a numerical-hydraulic interface, which allows the interaction between the VAD and the numerical model of the circulation. The numerical-hydraulic interface consists of two pressure-controlled reservoirs, which apply the computed pressure values from the model to the VAD, and a flow probe to feed the resulting VAD flow rate back to the model. Experimental results are provided to show the proper interaction between a numerical model of the circulation and a mixed-flow blood pump.

Changes in respiratory mechanics and gas exchange during the acute respiratory distress syndrome

BACKGROUND: The time course of impairment of respiratory mechanics and gas exchange in the acute respiratory distress syndrome (ARDS) remains poorly defined. We assessed the changes in respiratory mechanics and gas exchange during ARDS. We hypothesized that due to the changes in respiratory mechanics over time, ventilatory strategies based on rigid volume or pressure limits might fail to prevent overdistension throughout the disease process. METHODS: Seventeen severe ARDS patients {PaO2/FiO2 10.1 (9.2-14.3) kPa; 76 (69-107) mmHg [median (25th-75th percentiles)] and bilateral infiltrates} were studied during the acute, intermediate, and late stages of ARDS (at 1-3, 4-6 and 7 days after diagnosis). Severity of lung injury, gas exchange, and hemodynamics were assessed. Pressure-volume (PV) curves of the respiratory system were obtained, and upper and lower inflection points (UIP, LIP) and recruitment were estimated. RESULTS: (1) UIP decreased from early to established (intermediate and late) ARDS [30 (28-30) cmH2O, 27 (25-30) cmH2O and 25 (23-28) cmH2O (P=0.014)]; (2) oxygenation improved in survivors and in patients with non-pulmonary etiology in late ARDS, whereas all patients developed hypercapnia from early to established ARDS; and (3) dead-space ventilation and pulmonary shunt were larger in patients with pulmonary etiology during late ARDS. CONCLUSION: We found a decrease in UIP from acute to established ARDS. If applied to our data, the inspiratory pressure limit advocated by the ARDSnet (30 cmH2O) would produce ventilation over the UIP, with a consequent increased risk of overdistension in 12%, 43% and 65% of our patients during the acute, intermediate and late phases of ARDS, respectively. Lung protective strategies based on fixed tidal volume or pressure limits may thus not fully avoid the risk of lung overdistension throughout ARDS.

ECG-triggered muscular counterpulsation for treatment of low cardiac output

BACKGROUND: Skeletal muscular counterpulsation (MCP) has been used as a new noninvasive technique for treatment of low cardiac output. The MCP method is based on ECG-triggered skeletal muscle stimulation. The purpose of the present study was to evaluate acute hemodynamic changes induced by MCP in the experimental animal. METHODS: Eight anaesthetized pigs (43+/-4 kg) were studied at rest and after IV â-blockade (10 mg propranolol) before and after MCP. Muscular counterpulsation was performed on both thighs using trains (75 ms duration) of multiple biphasic electrical impulses with a width of 1 ms and a frequency of 200 Hz at low (10 V) and high (30 V) amplitude. ECG-triggering was used to synchronize stimulation to a given time point. LV pressure-volume relations were determined using the conductance catheter. After baseline measurements, MCP was carried out for 10 minutes at low and high stimulation amplitude. The optimal time point for MCP was determined from LV pressure-volume loops using different stimulation time points during systole and diastole. Best results were observed during end-systole and, therefore, this time point was used for stimulation. RESULTS: Under control conditions, MCP was associated with a significant decrease in pulmonary vascular resistance (-18%), a decrease in systemic vascular resistance (-11%) and stroke work index (-4%), whereas cardiac index (+2%) and ejection fraction (+6%) increased slightly. Pressure-volume loops showed a leftward shift with a decrease in end-systolic volume. After â-blockade, cardiac function decreased (HR, MAP, EF, dP/dt max), but it improved with skeletal muscle stimulation (HR +10% and CI +17%, EF +5%). There was a significant decrease in pulmonary (-19%) and systemic vascular resistance (-29%). CONCLUSIONS: In the animal model, ECG-triggered skeletal muscular counterpulsation is associated with a significant improvement in cardiac function at baseline and after IV â-blockade. Thus, MCP represents a new, non-invasive technique which improves cardiac function by diastolic compression of the peripheral arteries and veins, with a decrease in systemic vascular resistance and increase in cardiac output.

Transdermal nitroglycerin in patients with subarachnoid hemorrhage

Delayed ischemic neurological deficit (DIND) following cerebral vasospasm remains a cause for high morbidity and mortality in patients with subarachnoid hemorrhage (SAH). There is experimental and clinical evidence of positive effects of nitric oxide (NO) donors on cerebral vasospasm. We therefore analysed the effect of transdermal nitroglycerin in patients with SAH measuring transcranial Doppler velocities (TCD), cerebral blood flow (CBF) and DIND. Nitroglycerin was used in a target dose of 14 microg/kg/h. TCD assessment was performed daily. CBF measurements were done using the perfusion CT-technique. Blood pressure, volume intake and vasopressor administration, were registered. Nine patients were randomly assigned either to the nitroglycerin group (N-group) and eight patients in the control group (C-group). Mean TCD values in the extracranial portion of the internal carotid artery (ICA) were lower in the N-group (p<0.005). Mean TCD in the middle cerebral arteries (MCA) showed no difference. The Lindegaard ratio was higher in the N-group (p<0.04). CBF in the N-group was higher than in the C-group (p<0.03). Even though nitroglycerin reduces blood pressure and lowers ICA TCD-values and increases the Lindegaard ratio, a higher CBF was measured in the N-group. Thus, nitroglycerin influences the cerebral vascular tone and increases CBF. SAH therapy with nitroglycerin is possible without increasing the risk of DIND. The exact timing of onset, duration and reduction of nitroglycerin administration in respect to the appearance of vasospasm may have a strong impact on the success of such a therapy.

A cardiovascular mathematical model of graded head-up tilt

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

Monitoring of emergency and intensive care patients: simple diagnostic aids

This article describes in short sections the use and interpretation of indirect blood pressure measurements, central venous pressure, body temperature, pulse oximetry, end tidal CO2 measurements, pulse and heart rate, urine production and emergency laboratory values. Most of these parameters are directly or indirectly linked to the perfusion of the patient. Optimizing these values are one of the most important goals in emergency and critical care medicine.

Impact of epinephrine and norepinephrine on two dynamic indices in a porcine hemorrhagic shock model

Abstract BACKGROUND: Pulse pressure variations (PPVs) and stroke volume variations (SVVs) are dynamic indices for predicting fluid responsiveness in intensive care unit patients. These hemodynamic markers underscore Frank-Starling law by which volume expansion increases cardiac output (CO). The aim of the present study was to evaluate the impact of the administration of catecholamines on PPV, SVV, and inferior vena cava flow (IVCF). METHODS: In this prospective, physiologic, animal study, hemodynamic parameters were measured in deeply sedated and mechanically ventilated pigs. Systemic hemodynamic and pressure-volume loops obtained by inferior vena cava occlusion were recorded. Measurements were collected during two conditions, that is, normovolemia and hypovolemia, generated by blood removal to obtain a mean arterial pressure value lower than 60 mm Hg. At each condition, CO, IVCF, SVV, and PPV were assessed by catheters and flow meters. Data were compared between the conditions normovolemia and hypovolemia before and after intravenous administrations of norepinephrine and epinephrine using a nonparametric Wilcoxon test. RESULTS: Eight pigs were anesthetized, mechanically ventilated, and equipped. Both norepinephrine and epinephrine significantly increased IVCF and decreased PPV and SVV, regardless of volemic conditions (p < 0.05). However, epinephrine was also able to significantly increase CO regardless of volemic conditions. CONCLUSION: The present study demonstrates that intravenous administrations of norepinephrine and epinephrine increase IVCF, whatever the volemic conditions are. The concomitant decreases in PPV and SVV corroborate the fact that catecholamine administration recruits unstressed blood volume. In this regard, understanding a decrease in PPV and SVV values, after catecholamine administration, as an obvious indication of a restored volemia could be an outright misinterpretation.