Electrical impedance tomography (EIT) has become an accepted tool for monitoring regional ventilation. Interest is growing to derive additional information on pulmonary perfusion and ventilation/perfusion distribution. Favoured approach is the impedance indicator dilution technique. Until now hyperosmolar sodium chloride solutions (5.8% and 20%NaCl) have been used as indicators in experiments which, however, may be problematic in view of side effects and are not approved for application in patients.Different radiographic contrast media ( CM) approved for use in patients and five reference solutions were tested in vitro. Resistivities were measured in blood at 37 degrees C by a conductivity meter ( LF39, Meinsberg GmbH, Germany) in the indicator content range from 0 to 28 Vol%. Three non-ionic CM: Iodixanol, Iomeprol, Iobitridol and two ionic CM: Ioxaglate and Diatrizoate were examined. As references 0.9%, 5.8% and 20%NaCl as well as isotonic ( 4.5%) and hypertonic (18.2%) glucose solutions were included. Proportionality Proportionality between test solution concentration and determined resistivity changes was proven by regression/correlation analysis.Non-ionic CM induced linear increases of blood resistivity by 80% (Iodixanol), 75% (Iomeprol) and 66% (Iobitridol) at the highest test concentration of 28Vol%. Ionic CM changed resistivity by 13% (Ioxaglate) and 24% (Diatrizoate). The determined r(2)-values were > 0.988. Both hyperosmolar NaCl solutions caused marked but non-linear resistivity lowering by -82% resp. -95% with poor r(2)-values < 0.6. Glucose solutions increased resistivity by 17% resp. 29%, r(2)-value 0.98. Hyperosmolar NaCl-solutions effect impressive changes of resistivity but may imply errors in the evaluation of indicator dilution curves by non-linearity. The resistivity changes by the approved non-ionic radiographic CM are not complicated by linearity problems. A comparison with the simple blood dilution effect by isotonic non-ionic reference solutions indicates additional mechanisms of resistivity increment by CM. In conclusion CM should be evaluated further on in view of EIT-based perfusion assessment in patients.

Electrical impedance tomography has become a tool for monitoring regional ventilation. Interest is growing to derive additional information on pulmonary perfusion and ventilation/perfusion distribution. Since signals recorded by electrical impedance tomography also contain cardiac-related impedance changes, attempts are made to evaluate them in view of perfusion. Recently in Critical Care a corresponding study applying an advanced filtering technique for separating cardiac signals from the dominant ventilation component was published [1]. The quality of the concept is demonstrated by comparing the results with solitary cardiac signals during breath-hold. Similar to other publications dealing with this approach, the correct term cardiac-related impedance changes is substituted by perfusion. Although major aspects of limitations and missing validation are addressed in the discussion, the key message presented is that 'it is possible to distinguish between lung ventilation and perfusion using electrical impedance tomography'. Vascular volume pulses which are the reasons for cardiac-related impedance changes in the lung area obviously do not unequivocally represent perfusion. Even peripherally occluded arteries will pulsate without flow. These pulsations are dependent on blood pressure and vascular as well as surrounding tissue compliance. A reasonable approach to assess perfusion by electrical impedance tomography is the impedance indicator dilution technique, which is clearly favoured by recent publications [2-4]. In contrast to the questionable pulsation approach, a homogeneous distribution of perfusion and ventilation/perfusion ratios was obtained [5]. In summary, the interpretation of cardiac-related impedance changes in view of perfusion will not be permissible until validation by established reference techniques including relevant pathophysiological conditions.

Ischemic preconditioning (IP) has been found to intensify ischemia-induced spreading of connexin 43 (Cx43) into the extrajunctional plasma membrane of the rat heart. Since ischemia is known to induce connexin dephosphorylation and plasmalemmal permeabilization, we considered whether IP might delay dephosphorylation of also extrajunctional connexin and thus impede myocyte permeabilization. Regional myocardial ischemia of both 15 and 45 min duration with and without IP, respectively, was induced in anesthetized rats. Sections of the hearts were immunostained for phosphorylated and dephosphorylated Cx43. The ratios of immunofluorescence in gap junctions and extrajunctional membranes, respectively, versus myocyte interiors were determined as relative fluorescence units (RFU). IP, however, was not found to reduce gap junctional dephosphorylated Cx43 (normal perfusion: 1.23 +/- 0.06 RFU; 15 min ischemia without and with IP: 1.80 +/- 0.09 and 2.10 +/- 0.24 RFU; 45 min ischemia without and with IP: 3.12 +/- 0.55 and 2.57 +/- 0.33 RFU, respectively). Extrajunctionally, only dephosphorylated Cx43 was found. Its occurrence was not prevented by IP, it was rather intensified by IP (normal perfusion: 1.02 +/- 0.01 RFU, 15 min ischemia without and with IP: 1.06 +/- 0.03 and 1.15 +/- 0.05 RFU (P < 0.02), and 45 min ischemia without and with IP: 1.30 +/- 0.07 and 1.27 +/- 0.07 RFU, respectively). Although under ischemia, junctional and extrajunctional Cx43 predominated in the dephosphorylated state, only a small fraction of myocytes were found permeabilized to propidium iodide. In conclusion, IP did not prevent ischemia-induced Cx43 dephosphorylation in gap junctions and extrajunctional plasma membranes. It is thus more likely that changes in non-channel functions or other localizations of Cx43 are involved in IP-induced myocardial protection.

Numerous attempts have been made to improve image reconstruction algorithms in EIT. In contrast, the magnitude of measurement errors of an EIT system was not an exploratory focus in the past. Especially in absolute EIT (a-EIT) where the resistivity of the examined object is determined on an absolute scale the influence of these errors can not be ignored since systematic errors are not cancelled by dividing the raw data by reference data (cf. Sheffield back projection). We present very simple phantoms and provocative adapters for a 16 electrode system using adjacent drive pattern to determine the measurement errors. The trans-impedance of each phantom is determined by only one component and output voltage is constant for all combinations of current injection and measurement. Therefore the electrical properties of the phantoms can be determined fast and precisely. Input and output impedance can be chosen independently of output voltage similar to that of the human thorax. Parameters like the absolute error of each driving/sensing channel, signal to noise ratio in each channel and especially the several kinds of crosstalk can be determined. The EIT system runs at normal speed during the measurement which is important since dynamic properties of the system often influence the real errors. We exemplarily present the results of systematic errors of a Goe-MF II EIT system under two different simulated operational conditions. Although this system has been optimized for a sufficient signal to noise ratio we conclude that the absolute measurement errors will have to be reduced.

Connexins are known to play an essential role in the ischemic preconditioning (IP) of the heart; their functional role in this process, however, has not been clearly defined. For this reason, anesthetized rats were subjected to regional myocardial ischemia, with or without IP or reperfusion. In frozen sections of hearts, fluorescence immunohistochemical staining for connexin43 (Cx43) was performed. In contrast to undisturbed zones, tissue that had been subjected to ischemia revealed Cx43 immunostaining not only in the gap junctions but also in a conspicuous pattern in the free cellular membranes of the myocytes. In myocardium that was exposed to IP only, the ratio of immunofluorescence intensity in the free cellular membrane to that in the interior of the cell was 1.22 +/- 0.04 (ratio in non-ischemia-exposed area = 1.04 +/- 0.01). When 15 or 45 min of permanent ischemia followed IP, the effect became more evident (ratio = 1.31 +/- 0.03 and 1.46 +/- 0.03, respectively) and proved to be significantly greater than in the corresponding non-IP groups (ratio = 1.16 +/- 0.03 and 1.30 +/- 0.03, respectively, P < 0.01). Reperfusion led to an overall weakening of fluorescence intensities and a disappearance of the observed IP-specific differences. We conclude that IP initiates a redistribution of Cx43 from its natural position in the gap junctions toward the free plasma membrane, thereby improving the cell's chance of survival during the subsequent phase of prolonged ischemia by an unknown, supposedly gap junction-independent, mechanism.

Background: Neonatal hearts are less susceptible to developing myocardial dysfunction after hypoxia and/or ischemia than adult hearts. Differences in intracellular calcium homeostasis may be responsible for reduced calcium overload of the immature myocardium leading to the observed protection against ischemia. Objective: To assess differences in baseline and post-ischemic gene expression of calcium handling proteins after ischemia in neonatal and adult rabbit hearts. Methods: We used isolated antegrade perfused rabbit hearts (age 2 days, 28 days, n = 32), which were exposed to ischemia and hypothermia simulating myocardial stunning comparable to neonatal asphyxia. Gene and protein expression of the sodium–calcium exchanger (NCX), the sarco-endoplasmatic reticulum Ca2+-ATPase 2a (SERCA) and calsequestrin (CSQ) were measured using quantitative real-time PCR and Western blotting. Results: After ischemia and reperfusion in neonatal and adult hearts, a significant decrease in myocardial performance was recorded. At the mRNA level, significant differences in the baseline expression of NCX, SERCA and CSQ between neonatal and adult hearts were observed. In neonatal post-ischemic hearts, NCX and CSQ expression were significantly higher at the mRNA level than in controls. In contrast, SERCA expression remained unchanged in neonatal hearts and decreased in adult hearts compared to the non-ischemic controls. Conclusion: These findings suggest that changes in gene expression of calcium handling proteins may be involved in the different susceptibility of neonatal compared to adult hearts to developing myocardial dysfunction after ischemia.

Electrical Impedance Tomography (EIT) is a non-invasive imaging technique suitable for medical application. Most of the previous investigations have been done under laboratory conditions and only few projects under real hospital environment. This paper presents a novel concept of EIT application for clinical lung ventilation monitoring. A virtual EIT lung ventilation monitor suitable for application in clinical environment was designed and successfully implemented into the GoeMF II EIT device developed in our lab. The software together with its operational concept is described here. The problems of device handling, extraction of physiological relevant information from measurements, and data storage and retrieval are addressed. During data acquisition, comprehensive status information is displayed: the contact of all electrodes to the patient's body, the correctness of the wiring of the electrodes, and properties of electric or magnetic fields that produce noise at electrodes or cables. To give a quick overview about the patients' lung function, dynamic functional images are introduced for the first time with the essential property that their screen display only changes if the patient’s physiological status changes, but not during the breathing steady state condition. Additional evaluation procedures are available for series of EIT images to generate functional images in offline evaluation mode. Four different display windows are available: lung ventilation, shift-in-lung-volume, filling capacity, and pressure-volume relation. The described features of the virtual EIT ventilation monitor will be helpful to optimize the respirator’s parameters for each individual patient.

OBJECTIVE:To compare the efficacy of forced-air warmers and radiant heaters on rewarming after cardiac surgery in a prospective randomized study.METHODS:Fifty male patients who had undergone coronary artery bypass graft surgery were studied. The control group (Gr. C, n=10) was nursed under a standard hospital blanket. Two groups were treated with forced-air warmers: WarmTouch 5700 (Gr. WT, n=10) and Bair Hugger 500 (Gr. BH, n=10). Two other groups were treated by radiant heaters: the Aragona Thermal Ceilings CTC X radiant heater (Gr. TC, n=10) and a self assembled radiant heater of 4 Hydrosun 500 infrared lamps (Gr. HY, n=10). Changes of oesophageal temperature, mean skin temperature, mean body temperature and relative heat balance were calculated from oesophageal temperature, 4 skin temperatures and oxygen consumption (VO(2)).RESULTS:All actively treated groups with exception of the TC group showed significantly faster oesophageal warming than the control group. The mean body temperature increased 1.1 (0.7-1.7) degrees Ch(-1) in Gr. WT, 1.3 (0.7-1.5) degrees Ch(-1) in Gr. BH, 0.8 (0.5-1.4) degrees Ch(-1) in Gr. TC and 0.7 (0.4-1.0) degrees Ch(-1) in Gr. HY compared to Gr. C with 0.4 (0.2-0.7) degrees Ch(-1). The mean VO(2) and the maxima of the VO(2) during the study period did not differ significantly between the groups.CONCLUSION:In the current setting active warming, forced-air warming more than radiant warming, increased speed of rewarming two- to threefold in comparison to insulation with a blanket.

The aim of our study was to determine the effect of the irregular spontaneous breathing pattern and posture on the spatial distribution of ventilation in neonates free from respiratory disease by the non-invasive imaging method of electrical impedance tomography (EIT). Scanning of spontaneously breathing neonates is the prerequisite for later routine application of EIT in babies with lung pathology undergoing ventilator therapy.

Na+-channel modulators exert their positive inotropic action without affecting the adenylate-cyclase pathway by an increase in the open probability of the sarcolemmal Na+ channels. Although inotropic effects in neonatal hearts are less pronounced compared with adult hearts, the Na+-channel modulator BDF 9148 increases contractility and relaxation velocity in immature myocardium. Effects on hemodynamics and myocardial energetics are not known. Therefore, we studied the Na+-channel modulator BDF 9148 in isolated antegrade perfused rabbit hearts of different ages (2-28 d) and compared the effects with isoproterenol, enoximone, and ouabain. ANOVA showed significant effects in the concentration response curves for heart rate, stroke volume, cardiac output, and oxygen consumption but not for myocardial efficiency (p = 0.06). Age-dependent differences were observed for heart rate and stroke volume. Administration of BDF 9148 resulted in a maximal increase in stroke volume and cardiac output up to 25% in neonatal and 40% to 60% in adult preparations. Heart rate decreased by 15% in adult hearts only. Myocardial oxygen consumption was increased in a concentration-dependent manner between 25% in neonatal and 50% in adult hearts. Myocardial efficiency was increased by 35% in adult and by 10% in neonatal preparations. Although positive hemodynamic and energetic effects were less pronounced in immature compared with adult hearts, neonatal hearts also profited from the administration of the Na+-channel modulator BDF 9148. Further studies are necessary to clarify the risk of arrhythmia during application of Na+-channel modulators such as BDF 9148.

BACKGROUND AND AIM OF THE STUDY:The study aim was to investigate whether: (i) by detection of changing acoustic sound phenomena, minimal changes in prosthetic valve function may be detected earlier than with echocardiography, invasive diagnosis or clinically; (ii) patients can record and pass on signals with a high level of reproducibility from any location via the Internet; and (iii) clinical data evaluation permits conclusions to be drawn on changes in the functional state of a prosthetic replacement valve.METHODS:Simulation studies were carried out using a mock circulation device. Aortic valve replacement (AVR) using extracorporeal circulation was performed in pigs, valve function was artificially disturbed, and valve sounds were recorded. Patients were equipped with briefcase-like devices to record their valve sounds after AVR and to transfer them via the Internet.RESULTS:Simulation studies produced a typical sound spectrum for each tested valve that remained constant under variable conditions. Experiments in animals proved that minimal changes in prosthetic valve function led to a significant change in the sound phenomena. The degree of sensitivity was significantly greater than that in echocardiographic control experiments. All patients in the clinical study regularly recorded and passed on their signals. Surveys revealed high acceptance and easy handling of the compiled devices. Valve dysfunctions were not detected.CONCLUSION:On-line registration of acoustic sound phenomena and ECG seems suited to detect minimal changes in prosthetic function. In particular, the registration of flow, acoustics and ECG envisaged at the next level opens up diverse potential applications for Internet-based, remote monitoring of patients following cardiac surgery or cardiologic treatment.

The development of the mammalian heart is characterized by substantial changes in myocardial performance. We studied the ontogeny of myocardial function with and without various inotropic interventions in the developing isolated, antegrade-perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related to the protein expression of the sarcolemmal Na+-Ca2+ exchanger and to the sarcoplasmic Ca2+-ATPase.

Introduction: Compromised cerebrovascular autoregulation (CA) is a consequence of acute cerebrovascular events and/or immaturity of CA. We studied CA capacity in response to tilting in healthy term neonates longitudinally using a transcranial Doppler system.

This paper describes the investigation of a new mathematical method of calculating blood volume. The new method determines the blood volume by calculating the product of the mean circulation transit time. The mean transit time is calculated from the body transport function. To examine the accuracy of the LOGNORMAL-NLSQ technique, 45 concentration time curves were measured in an in vitro recirculation model with variable clearance. The calculated volume was 4 % smaller than the actual volume. This may be attributed to the functional dead space within the model, and is tolerable for clinical situations. The LOGNORMAL-NLSQ technique might acquire considerable importance in future, especially since it provides accurate results very quickly.

Imipramine was administered to sheep (n=10) by intravenous infusion in high doses (450 mg-900 mg) to elicit cardiovascular shock. A cardiac assist device was then employed to manage the acute overdose situation. The concentration-time course of imipramine and its metabolite desmethylimipramine in plasma was measured by HPLC. As an indicator of imipramine's cardiotoxic effect, cardiac output was monitored. The aim of the study was to evaluate the pharmacokinetics under these conditions and to assess the efficiency of a cardiac assist device with (n=5) and without (n=5) an integrated haemoperfusion unit in removing drug from the circulation. The kinetics of imipramine could be described by a three compartment body model with concentration-dependent clearance resulting in non-linear kinetics. The changes in cardiac output with time could be linked to the pharmacokinetic model by a linear relationship. The cardiac assist device was found to contribute to the overall elimination of imipramine whereas the haemoperfusion unit had no clinically relevant impact.

Intoxication with tricyclic antidepressants (TCA) like imipramine (IMI) has a high lethality due to cardiovascular toxicity. The influence of percutaneous cardio pulmonary bypass (p-CPB) in IMI-induced cardiogenic shock (SH) on arrhythmias, hemodynamic and pharmacokinetic parameters was studied in 10 sheep (S). After IMI infusion of 0.54 mg/kg/min, S developed arrhythmias, hypotension and decrease of cardiac output within 30 min. All S survived SH after p-CPB support for approximately 170 min and were observed for additional 120 min in spontaneous circulation (SC). Beside normalisation of arrhythmias and hemodynamics a rapid decrease of toxic IMI plasma concentrations (IMI-C) to the therapeutic range within 50 min was noted. p-CPB enhances elimination of IMI from the central compartment and apparently supports metabolic clearance by maintaining sufficient organ perfusion.

Background. Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine release were caused by the solvent cremophor rather than by propanidid itself. A new liposomal preparation of propanidid was examined in this animal study and compared with propanidid in cremophor solution and with propofol.Methods. Eighteen pigs were randomly assigned to one of the following groups:Group 1 (n = 6): Propanidid in liposomal preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60 mg/kg, followed by continuous infusion of 400 mg/kg . h.Group 2 (n = 6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, Budapest) 15 mg/kg, 100 mg/kg . h.Group 3 (n = 6): Propofol (Disoprivan, Zeneca, Plankstadt, Germany) 5 mg/kg, 20 mg/kg . h.After induction and tracheal intubation, the animals were ventilated with 50% oxygen in air. Basic monitoring included noninvasive blood pressure measurements, electrocardiographic monitoring, and capnography. In a short surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, respectively. As soon as the animals responded to a pain stimulus a second anaesthetic induction was performed, followed by a 60-min continuous infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac output. Blood samples were taken for the measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hormone, and histamine.Results. Intubation conditions and quality of anaesthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg . h, resulting in a volume load of as much as 16.4 ml/kg . h, the PropaLip animals showed evidence of poor anaesthetic quality. In group 1 we recorded the highest increases in heart rate (91 vs, 115/min), cardiac output (5.4 vs. 7.7 1/min), plasma catecholamine levels, and histamine concentrations (124-268 ng/ml).Conclusions. In our animal study, propanidid in liposomal preparation failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloendothelial system, especially the liver, where liposomes are eliminated from the blood. This may result in the transport of propanidid to one of its major places of inactivation.