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Embaràs i malaltia cardíaca; Resultats de l’embaràs; Transposició de les grans artèries Embarazo y enfermedad cardíaca; Resultados del embarazo; Transposición de las grandes arterias Pregnancy and cardiac disease; Pregnancy outcomes, Transposition of the great arteries Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate. Funding from “Zabawas Foundation” and “De Hoop Foundation” in addition to the support from EURObservational Research Programme (EORP) is greatly acknowledged. Since the start of EORP, the following companies have supported the program: Abbott Vascular Int (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc (2014–2016), Menarini Int Op (2009–2012), MSD‐Merck & Co (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), SERVIER (2009–2021), and Vifor (2019–2022).

Amyloidosis is a rare multiorgan disease defined by a process of irreversible, extracellular accumulation of fibrillar proteins in the tissues, including the heart. Cardiac involvement is seen in most forms of amyloidosis, but it is frequently present and clinically significant in light chain (AL)-amyloidosis as well as transthyretin amyloidosis (ATTR). Cardiac amyloid accumulation leads to a restrictive filling pattern, which must be differentiated from other forms of restrictive and hypertrophic cardiomyopathies due to consequences for the treatment. Evolving knowledge of the disease has led to a definite diagnosis of the cardiac amyloidosis (CA) using non-invasive and low-risk diagnostic features, such as scintigraphy (gamma scan) and cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) and T1 mapping technics. The availability and diagnostic accuracy of these technics has reduced the need for cardiac biopsy. In the following chapter, we will describe common types of CA, the basic concepts, and updates of non-invasive diagnostic features.

An 8-year-old Warmblood gelding presented with a history of progressive ataxia for 6 weeks. Intra- and intervertebral ratios measured from lateral radiographs of the cervical spine were within normal limits. Computed tomographic myelography of the cervical spine revealed focal compression of the dorsal and the ventral contrast column as well as a ventral displacement of the spinal cord within the spinal canal due to a bulging of soft tissue attenuating material in the dorsal half of the intervertebral junction of C6 and C7. Post-mortem histopathological examination confirmed chondroid metaplasia of the ligamentum flavum at C6-C7.

Acute interstitial pneumonia (AIP) in foals is a rare but challenging syndrome. Diagnostic imaging is crucial for its diagnosis. While there are some reports on radiographic findings, ultrasound is sparsely described. Variability in the evaluation of radiographs in AIP has been well described in human literature. Part one of this study is a prospective, observational, observer agreement study investigating inter- and intraobserver agreement in the assessment of thoracic radiographs. Part two is a prospective, controlled, descriptive study on thoracic ultrasonography in foals with AIP. Eighteen foals with AIP were examined daily by thoracic ultrasound. Thoracic radiographs were taken on three successive occasions. Blinded radiographs were assessed by three observers based on two semi-quantitative scores (pattern recognition, subjective evaluation). Foals that died underwent postmortem examination (n = 9); postmortem findings were compared to ultrasound findings on the day of death. Ultrasonographic findings were consistent with postmortem findings. Comet tail scores in foals with AIP were significantly higher (p < 0.0001) than in control foals. Interrater agreement for the assessment of radiographs was none to moderate (κ = 0.07-0.65) for pattern recognition and weak to moderate (κ = 0.58-0.62) for subjective scoring. Intrarater agreement varied from minimal to strong (κ = 0.30-0.80) for pattern recognition but was strong (κ = 0.83) for subjective scoring. In conclusion, the diagnostic value of thoracic ultrasound in foals with AIP is high due to good conformity with postmortem findings. The evaluation of thoracic radiographs showed high variability in inter- and intra-agreement.

Magnetic resonance imaging and the correlation to histopathological findings of the equine palmar foot of lame horses have been described previously, using 0.27 and 1.5 T systems. Compared to these, 3 T systems provide superior spatial resolution and imaging contrast. The aim of our prospective anatomic study was to characterize the imaging anatomy of the navicular region on 3 T MRI in comparison to histopathological findings. We hypothesized that 3 T MRI allows a good visualization of the entire navicular apparatus and reliable measurements of navicular cartilage and cortical bone thickness. Twenty front feet of sound horses were examined using a 3 T MRI system. For histopathological examination, sagittal tissue sections of the navicular bones and adjacent ligaments were prepared. Alterations in magnetic resonance signal were graded for each region and compared to corresponding histological slices. Overall, there was good visualization of the anatomical detail and a very good agreement between MRI and histology for compact bone and spongiosa, good agreement for the fibrocartilage and the distal sesamoidean impar ligament, but only moderate agreement for the hyaline cartilage and the collateral sesamoidean ligament. A comparative measurement of cartilage and cortical bone thickness on magnetic resonance images and histological sections was performed. In MRI, the hyaline cartilage of the articular surface appeared significantly thinner and the fibrocartilage of the flexor surface appeared significantly thicker compared to histology. Findings indicated that MRI at a field strength of 3 T allows reliable depiction of anatomic details of the navicular apparatus.

Introduction The incidence of geriatric acetabular fractures continues to increase due to demographic changes. In the elderly, anterior column fractures are common, and standard approaches are associated with a considerable risk for surgery-associated complications. Therefore, a minimally invasive approach was developed in our department. The aim of this study was to examine early and mid-term results regarding the use of this novel two-incision minimally invasive (TIMI) approach in patients aged over 55 years with acetabular fractures. Methods From July 2007 to April 2014, 47 patients aged over 55 years were treated via the TIMI approach; these patients were included in the present prospective study. The patients' characteristics, data, and early phase of care were assessed during acute care. A radiological evaluation comprised pre- and postoperative CT scans and x-rays, including Judet views at follow-up. Follow-up examinations were performed after 6 and 24 months and comprised a clinical and radiological examination and an evaluation of hip function (Harris Hip Score) and health-related quality of life (EQ-5D). Results The mean age of the patients was 74 ± 11 years, with a gender ratio of 35/12 (m/f). The average operation time was 93 ± 30 min, and perioperative blood loss amounted to 858 ± 463 ml. In total, five (11%) complications associated with the operative procedure occurred, and revision surgery was necessary in three patients. We observed no wound infections, abdominal wall hernias or cases of heterotopic ossification in our sample. The Harris Hip Score at six months after surgery was 81, and it slightly improved to 84 after 24 months. The mean EQ5D index was 0.91 at six months after surgery and 0.92 at 24 months after surgery. Conclusion The TIMI approach represents a valuable alternative to the ilioinguinal and modified Stoppa approach for the treatment of acetabular fractures located in the anterior column, which are often observed in geriatric patients. Level of evidence Therapeutic Level II (Prospective cohort study).

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment. peerReviewed

Background: Cardiac disease is 1 of the major causes of maternal mortality. We studied pregnancy outcomes in women with rheumatic mitral valve disease. Methods: The Registry of Pregnancy and Cardiac Disease is an international prospective registry, and consecutive pregnant women with cardiac disease were included. Pregnancy outcomes in all women with rheumatic mitral valve disease and no prepregnancy valve replacement is described in the present study (n=390). A maternal cardiac event was defined as cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, and hospitalization for other cardiac reasons or cardiac intervention. Associations between patient characteristics and cardiac outcomes were checked in a 3-level model (patient–center–country). Results: Most patients came from emerging countries (75%). Mitral stenosis (MS) with or without mitral regurgitation (MR) was present in 273 women, isolated MR in 117. The degree of MS was mild in 20.9%, moderate in 39.2%, severe in 19.8%, and severity not classified in the remainder. Maternal death during pregnancy occurred in 1 patient with severe MS. Hospital admission occurred in 23.1% of the women with MS, and the main reason was heart failure (mild MS 15.8%, moderate 23.4%, severe 48.1%; P 1 was an independent predictor of maternal cardiac events. Follow-up at 6 months postpartum was available for 53%, and 3 more patients died (1 with severe MS, 1 with moderate MS, 1 with moderate to severe MR). Conclusions: Although mortality was only 1.9% during pregnancy, ≈50% of the patients with severe rheumatic MS and 23% of those with significant MR developed heart failure during pregnancy. Prepregnancy counseling and considering mitral valve interventions in selected patients are important to prevent these complications.

Therapeutic regimens in chronic lymphocyte leukemia/small lymphocytic lymphoma (CLL/SLL) are undergoing tremendous changes. In 2014, the Bruton tyrosine kinase inhibitor (TKI) ibrutinib was approve...

Summary An 8-year-old Warmblood gelding was referred for evaluation of headshaking to the Clinic for Horses, University of Veterinary Medicine Hannover. Based on clinical signs and computed tomography – as well as magnetic resonance imaging – findings, otitis media was diagnosed. Medical treatment including trimethoprim potentiated sulfadimethoxine and meloxicam for 3 weeks did not result in cessation of clinical signs. Therefore, the tympanic cavity was opened transendoscopically using an Nd:YAG-laser via the guttural pouch according to surgical procedures in human and small animal medicine, leading to a considerable improvement of clinical signs.

We studied the influence of three gravity levels (0, 1 and 1.8 g) on unilateral lung aeration in a left lateral position by the application of absolute electrical impedance tomography. The electrical resistivity of the lung tissue was considered to be a meaningful indicator for lung aeration since changes in resistivity have already been validated in other studies to be proportional to changes in lung volume. Twenty-two healthy volunteers were studied during parabolic flights with three phases of different gravity, each lasting ∼20-22 s. Spontaneous breathing at normal tidal volume VT and at increased VT was performed. During transition to hyper-gravity mean expiratory resistivities (±SD in Ωm) increased at normal VT in the upper (right) lung from 7.6 ± 1.5 to 8.0 ± 1.7 and decreased from 5.8 ± 1.2 to 5.7 ± 1.2 in the lower (left) lung. Inspiratory resistivity values are 8.3 ± 1.6 to 8.8 ± 1.8 (right) and 6.3 ± 1.3 to 6.0 ± 1.3 (left). At increased VT, the changes in resistivities at end-expiration were 7.7 ± 1.5 to 8.0 ± 1.7 (right) and 5.8 ± 1.2 to 5.7 ± 1.2 (left). Corresponding end-inspiratory values are 9.9 ± 1.9 to 10.0 ± 2.0 (right) and 8.6 ± 2.1 to 7.9 ± 2.0 (left). During weightlessness, the distortion in the lungs disappeared and both lungs showed a nearly identical aeration, which was between the levels displayed at normal gravity. The small increase in resistivity for the upper lung during transition to hyper-gravity from 1 to 1.8 g at increased VT suggests that the degressive part of the pressure-volume curve has already been reached at end-inspiration. The results for a left lateral position are in agreement with West's lung model which has been introduced for cranio-caudal gravity dependence in the lungs.

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 (P0.02), 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.

We present an improved approach to image ventilation in functional electrical impedance tomography (f-EIT). It combines the advantages of the two established procedures of calculating standard deviation as a functional parameter of ventilation (SD method) and the so-called filling capacity (FC method). The SD method quantifies the local impedance variation over a series of tomograms for each pixel; the FC method is based on the slope of a linear fit of regional versus the global impedance change. Tidal volume V(T) is displayed linearly by the SD method in f-EIT; it is, however, sensitive to noisy data. The FC method is much more robust with respect to noise but does not display the tidal volume V(T). We combined the advantages of both techniques in a new VT method which is based on raw data. It saves computing time and is suitable for both f-EIT and absolute EIT (a-EIT). We separated the raw data into two representative sets: end expiratory and end inspiratory. This was accomplished by calculating the global time course of the relative impedance changes from the raw data. In this time course, we determined all frame numbers (indices) of end expiration and end inspiration. These frame numbers were used to calculate one mean expiratory and one mean inspiratory raw data frame. Reconstruction by difference imaging directly reflects the mean tidal volume V(T) during the acquired frame series. The effect of the improvement by the VT method was investigated at different noise levels by adding artificial noise from 0 to 100 microV(rms) to a real raw dataset. The robustness with regard to noise of the VT method was similar to that of the FC method. The practical value of suppression of non-ventilatory impedance changes, artefacts and noise was tested by studying ten healthy subjects (four females, six males) during normal breathing. We found a highly significant improvement in the image quality (p < 0.001) of ventilation for this group of volunteers.

Using a recently developed, percutaneously introduced cardiopulmonary support system (PCPS) seven high-risk patients (four men, three women; mean age 61 [41-77] years) underwent percutaneous transluminal coronary angioplasty. In one patient, with unstable angina and in incipient cardiogenic shock, perfusion with PCPS was begun immediately before coronary angioplasty. In six patients it was undertaken with the PCPS on stand-by, but eventually not needed. Coronary angioplasty was successful in six patients, partially successful in one. Angina was considerably improved long-term in all patients, but one of them died 2.5 months afterwards at home. In two other patients (men, aged 41 and 71 years) with acute myocardial infarction, the PCPS was employed under circumstances of emergency resuscitation. In both cases recanalization of the occluded coronary artery was achieved mechanically during perfusion with PCPS; one patient survived. Availability of PCPS, also in an emergency, makes it possible to extend the indications for coronary angioplasty to include even high-risk patients.

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) has become an accepted tool for monitoring regional ventilation. Interest is growing to derive additional information on pulmonary perfusion and ventilation/perfusion distribution. Favoured ap-proach 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°C by a conductivity meter (LF39, Meinsberg GmbH, Germany) in the indica-tor 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 deter-mined 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

To determine the effect of age and posture on regional lung ventilation, eight young (26 +/- 1 years, mean +/- S.D.) and eight old (73 +/- 5 years) healthy men were studied by electrical impedance tomography in four body positions (sitting, supine, right and left lateral). The distribution of gas into the right and left lung regions was determined in the chest cross-section during tidal breathing at the resting lung volume, near residual volume and total lung capacity, as well as forced and slow vital capacity maneuvers. In the young, significant posture-dependent changes in gas distribution occurred during resting tidal breathing whereas they were absent in the elderly. In the older subjects, the contribution of the right lung to global ventilation fell with the transition from sitting to supine posture during both full expiration maneuvers. During forced vital capacity, the high flow rate and early airway closure in the dependent lung, occurring at higher volumes in the elderly, minimized the posture-dependency in gas distribution which was present during the slow maneuver. Our study revealed the significant effect of age on posture-dependent changes in ventilation distribution.

OBJECTIVE Ketamine was shown to increase coronary blood flow. It was the aim of this study to answer the question whether ketamine directly dilates coronary arteries. METHODS Using the model of isolated vessel rings we studied the effects of ketamine (2.5, 25, and 250 microg ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine, and serotonin in porcine coronary artery segments. Other rings were contracted with KCl or PGF (2a) and then treated with ketamine (5 up to 500 microg ml(-1) added cumulatively). RESULTS Ketamine dose-dependently dilated coronary arteries in concentrations beyond those used in clinical practice. In intact rings ketamine racemate (250 microg ml(-1)) attenuated contractions mediated by acetylcholine by 38.8 +/- 2.8%, histamine by 33.0 +/- 4.4% and serotonin by 42.1 +/- 3.7% (p < 0.05). There were no differences between intact and denuded rings (acetylcholine 38.5 +/- 2.8%, histamine 26.6 +/- 4.7%, serotonin 30.0 +/- 3.2%). With low concentrations of ketamine (2.5 microg ml(-1)) a slight tendency towards a contraction was recorded (n. s.). In rings precontracted with either KCl or PGF (2a) ketamine caused a small enhancement of contraction (KCl: 101.4 +/- 0.4%, PGF (2a): 101.3 +/- 1.4%) when administered in low concentration (5 microg ml(-1)), but almost complete relaxation (KCl: 0.4 +/- 1.3%, PGF (2a): 0.0 +/- 5.4%) in high concentration (500 microg ml(-1)). CONCLUSIONS It is concluded that ketamine dose-dependently dilates porcine coronary arteries in concentrations beyond those used in clinical practice and that this effect is independent of endothelial function.

BACKGROUND AND OBJECTIVE Benzodiazepines may cause hypotension and are reported to interfere with smooth vascular muscle activity. The aim was to elucidate the influence of three different benzodiazepines on the vascular reactivity of coronary arteries. METHODS Using the model of isolated vessels, we studied the impact of midazolam (0.15, 1.5, 15 microg mL(-1)), diazepam (0.1, 1.0, 10 microg mL(-1)) and flunitrazepam (0.01, 0.1, 1.0 microg mL(-1)) on the contractile responses to histamine (2 x 10(-5) mol L(-1)) and serotonin (3 x 10(-5) mol L(-1)) in isolated intact and denuded coronary arteries. RESULTS Midazolam significantly attenuated the contractile response when administered in high concentrations (15 microg mL(-1)). This effect was more pronounced in intact than in denuded preparations (histamine: -22.7 versus -7.3%, P = 0.0079; serotonin: -47.1 versus -15.9%, P < 0.0001). Diazepam and flunitrazepam exerted no significant effects on the vascular tone of coronary arteries. CONCLUSIONS Midazolam, but not diazepam or flunitrazepam, attenuates the contractile responses to vasoconstrictors in concentrations beyond those used in clinical practice. This effect is in part mediated by endothelial factors.

Myoglobin is known to become nephrotoxic when released in greater amounts from skeletal muscle into the general circulation during shock. The present study deals with the question as to whether a myoglobin-induced increase in vascular tone additionally contributes to the detrimental role of this protein in hypovolemic shock. Anesthetized rats were subjected to 250 mg kg x h(-1) myoglobin infused i.v. during hemorrhagic hypotension of 50 mmHg. Shock survival time was measured, as were blood flow and vascular resistance in kidney, intestine, brain, and heart, using the microsphere method. Rats subjected to only myoglobin or hemorrhage survived a period of120 min; in contrast, rats, exposed to both myoglobin and hemorrhage died at 68 +/- 9 min. When the animals subjected to only hemorrhage and to myoglobin/ hemorrhage were compared, significantly lower values were found in the latter group with respect to blood flow in the kidney (1.7 +/- 0.1 vs. 0.2 +/- 0.05 ml x min(-1) x g(-1)), small intestine (1.0 +/- 0.1 vs. 0.5 +/- 0.1 ml x min(-1) x g(-1)), cardiac output (112 +/- 5 vs. 62 +/- 10 ml(-1) x min(-1) x kg(-1)), and significantly higher values of total peripheral vascular resistance (0.45 +/- 0.02 vs. 0.81 +/- 0.12 mmHg x min x ml(-1) x kg) at 50 min of hypotension. It is assumed that these effects of myoglobin are induced by its ability to scavenge endogenous nitric oxide, because a modified, non-nitrosylable myoglobin was unable to induce such effects. The results support the view that a pathological release of myoglobin into the general circulation causes increases in vascular resistance of vital organs that may contribute to decompensation of tissue supply when occurring in hypovolemic shock.

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 Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent manner. Significant differences between neonatal, juvenile and adult hearts could be demonstrated in a repeated measurement ANOVA model on the concentration-response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was significantly higher in adult compared to neonatal hearts (t-test, p0.01). The significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein], p0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p0.01, dP/dtmin r = 0.62, p0.01). Contractility, relaxation and the observed positive inotropic effects were in general significantly lower in neonatal compared to adult hearts. In the individual heart an increase in contractility and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.

Two widely used electrical tomography systems, the Sheffield Mark I and the DAS-01P, were quantitatively evaluated and compared to the newly developed Goe-MF system. The performance was quantified using a hardware phantom which closely matches the real input and transfer impedances of the human thorax and allows measurements equivalent to different states of lung inflation. Our results demonstrate that adequate averaging is necessary for noise reduction for the Mark I and especially for the DAS-01P system to get meaningful results even in visualizing maximal respiratory manoeuvres. The Goe-MF system showed a notably improved signal-to-noise ratio which allows also dynamic measurements at low levels of lung volume changes, e.g., in intensive care lung injury patients.

BACKGROUND It was the aim of this study to elucidate the influence of opioids on coronary vascular tone using the model of isolated porcine coronary artery segments. METHODS We studied the effects of fentanyl (0.01, 0.1, 1.0 microg ml(-1)), alfentanil (0.1, 1.0, 10 microg ml(-1)), and sufentanil (0.01, 0.1, 1.0 microg ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine and serotonin. RESULTS Fentanyl (0.1, 1.0 microg x ml(-1)) dose-dependently attenuated the contractile response to acetylcholine, but not to histamine and serotonin. There were no differences in fentanyl's vasorelaxing potency between rings with intact and denuded endothelium. Alfentanil and sufentanil did not exert any significant influence on any of the vasoconstrictors tested. CONCLUSION It is concluded that, in isolated porcine coronary artery rings, fentanyl at high concentrations has an attenuating effect on acetylcholine-induced contractions, which is independent of endothelial function, whereas alfentanil and sufentanil do not influence coronary vascular tone.

The main limitation in the use of circulatory support in children is the lack of an adequate system with regard to size and pumping capacity Recently, two pneumatically driven ventricular support systems with low volume chambers for use in a pediatric population became available. We have developed a hydraulic drive system with an advantageous exact control of the stroke volume. The system enables two different modes of operation: the full-empty and the filled-empty modes. In both cases the ventricle is empty at the end of systole. This new system was tested in experimental animals (6 pigs, body weight 9.5–14.0 kg) with normal and reduced left ventricular function (MAP Results showed that sufficient ventricular support was achieved during all pumping modes due to the possibility of controlling and modifying the stroke volume of the hydraulically driven support system employed according to necessity. This is a promising feature for its future application in infants with congenital or acquired heart diseases.

Background: Electrical impedance tomography (EIT) is a noninvasive technique providing cross-sectional images of the thorax. We have tested an extended evaluation procedure, the functional EIT (f-EIT), to identify the local shifts of ventilation known to occur during the transition between spontaneous, controlled and assisted ventilation modes. Methods: Ten patients scheduled for elective laparotomy were studied in the surgical ward, operating theatre and ICU during spontaneous and different modes of mechanical ventilation. Sixteen ECG electrodes were placed on the circumference of the thorax and connected with an EIT device (APT System Mark I, IBEES, Sheffield, UK). Measurements lasting 180 s were performed and f-EIT images of regional ventilation computed. The geometrical centre of ventilation was determined to quantify the regional distribution of lung ventilation during individual modes of ventilation. Results: F-EIT confirmed the differences in the distribution of ventilation associated with various modes of artificial ventilation. Accentuated ventilation of the dependent lung regions was observed during spontaneous breathing, whereas a shift of the centre of ventilation to the nondependent regions was found during controlled ventilation. In the course of assisted ventilation a continuous displacement of the centre of ventilation back towards the dependent lung regions, consistent with an increased proportion of spontaneous breathing, was detected. Unassisted spontaneous breathing after weaning from mechanical ventilation resulted in a similar ventilation distribution as during tidal breathing prior to surgery. Conclusion: F-EIT determined the redistribution of lung ventilation during different modes of mechanical ventilation. We expect that f-EIT will become a useful noninvasive bedside monitoring technique for imaging regional ventilation in pulmonary diseased patients during mechanical ventilation.

Electrical impedance tomography (EIT) is a new noninvasive imaging technique which utilizes the different electrical properties of biological tissues to produce cross-sectional images of selected parts of the body. When applied on the thorax, the cyclic fluctuations of electrical impedance of the lung tissue, associated with different air contents of the lungs in the course of the respiratory cycle, can be used to generate derived EIT tomograms which represent the spatial distribution of ventilation in the chosen transverse plane. The corresponding evaluation technique, the functional EIT, was used for the first time to follow the regional ventilation in three intensive care patients. The method was shown (1) to identify the redistribution of inspired air in the lungs associated with controlled ventilation in a patient undergoing elective laparotomy, (2) to follow the improvement of locally impaired lung ventilation in the course of severe pneumonia, and (3) to detect regional reduction of ventilation due to lobar atelectasis with stasis pneumonia in a patient with bronchial carcinoma.

The measured concentration time curve of an injected substance is often used as a basis for calculating the distribution volume. For the first time, the present paper describes a generally applicable formula for calculating the asymptote of a concentration time curve in medical applications. With a knowledge of this formula, previously unexplained phenomena (varying results obtained from two different methods of calculating the distribution volume) can now be understood. At the same time, errors of methodology (choice of injection and measuring sites) can be avoided.

A new functional EIT (f-EIT) evaluation technique providing information on the local dynamic behaviour of the lungs is presented. Out of a series of single EIT thoracic images local time courses of the impedance change are extracted. To detect regional differences in the dynamic behaviour of the lung tissue the local time courses at different locations are related to the average time course of the impedance change over the whole thoracic cross section. The time shifts between this reference signal and the signals from separate positions are calculated from the phase information of the complex cross spectra and evaluated in terms of the local phase angle. The computed phaseshifts are imaged over the cross section creating an `f-EIT phase image' characterizing the local dynamic properties. To relate the observed differences to the proper lung location the resulting images are presented as a combination of the f-EIT ventilation images, which represent the local amplitude of ventilation and the f-EIT phase images. The new imaging technique was tested in spontaneously breathing humans. Alterations to pulmonary dynamics were induced by changing the body posture of the subjects. The f-EIT phase imaging procedure was shown to identify lung regions with different dynamics and it is expected that this technique will also distinguish pathologically determined alterations.

Gravity exerts an effect on the distribution of intrapulmonary ventilation. A study on the detection of gravity-dependent inhomogeneity of ventilation by a functional EIT technique is presented. The study was performed on five human subjects, whose ventilation distribution was modified by changes in body position. The subjects were studied during spontaneous tidal breathing. The qualitative and quantitative analysis of the functional EIT images revealed that the ventilation is higher in the dependent lung regions when compared with the non-dependent ones. These EIT findings correspond to current knowledge of the physiological behaviour of the lungs as derived from the radioactive-gas methods and raise the possibility of applying the less complicated functional EIT in future studies on ventilation distribution in the lungs. This may be of major interest in the monitoring of intensive care patients with severe pulmonary disorders.

In einer tierexperimentellen Studie wurden 18 Lauferschweine untersucht, von denen je 6 Tiere (1) Propanidid in Liposomendispersion (abgekurzt PropaLip), (2) Propanidid in Cremophor (abgekurzt PropaCrem) und (3) Propofol erhielten. Nach Narkoseeinleitung mit 60 mg/kg PropaLip, 15 mg/kg PropaCrem bzw. 5 mg/kg Propofol wurden die Tiere intubiert, fur die weiteren Messungen instrumentiert und in einer anschliesenden 60minutigen Narkose untersucht. Der Anasthetikaverbrauch betrug 16 mg/kg·h Propofol, 120 mg/kg·h PropaCrem und 410 mg/kg·h PropaLip. Trotz dieser hohen Dosierung und der damit verbundenen Volumenbelastung von 16,4 ml/kg·h war die Anasthesiequalitat in der PropaLip-Gruppe unbefriedigend. Bei diesen Tieren traten die ausgepragtesten Anstiege von Herzfrequenz, HZV, Katecholamin- und Histaminspiegeln auf, weitgehend konstant blieben die genannten Parameter bei der Propofolgruppe, wahrend die PropaCrem-Tiere eine Mittelstellung einnahmen. Offenbar ist die Verfugbarkeit von Propanidid in der Liposomenpraparation schlechter als in der Cremophorlosung. Ein Zusammenhang der geringen Wirksamkeit mit der gezielten Aufnahme von Liposomen in die Zellen des RES, z.B. der Leber, wo Propanidid inaktiviert wird, wird diskutiert.

Effective rewarming devices have only become available recently. This investigation compares the efficiency of an new overhead radiant heater (ARAGONA Thermal Ceilings TM, CTCX, 1000 W) with that of an electric blanket (50 W) or a standard hospital blanket. 35 patients undergoing postoperative assisted ventilation and continued sedation were randomly assigned to one of the treatments. Shivering, oxygen uptake, heart rate and invasive blood pressure were measured and the increase in total body heat minus body heat production was calculated as heat balance. Results are given as medians (range). Subcutaneous temperatures were taken to calculate the mean skin temperature. The evaluation was undertaken for an oesophageal temperature interval of 35 to 37C. All groups exhibited a similar mean oxygen uptake i.e. thermogenesis (3.5 (2.7–4.0) ml kg-1 min-1; 3.3 (2.7–4.9) ml kg-1·min-1; 3.2 (2.4–5.1) ml kg-1. min-1) which correspond to a resting energy expenditure. The time of rewarming of the radiant heat treated group (n = 12) (100 (76–143) min) for this interval was significantly reduced in comparison to both other groups (183 (116–320) min; 231 (115–340) min). A slightly positive heat balance was only achieved in the group treated by radiant heat, indicating that all metabolic heat was conserved or heat losses were compensated by transfer of external heat. Shivering was significantly reduced in the radiant heater group whereas the rate pressure product was insignificantly higher. We did not find any significant effect for the electric heating blanket in comparison to the control group. We conclude that the ARAGONA Thermal Ceilings TM seems to be an effective device for postoperative rewarming without related side effects. For the investigated temperature interval it can reduce the time of rewarming to about 50% of control values at the same rate of thermogenesis.

The aim of this study was to develop a widely applicable model for circulatory indicator dispersion which could describe the pharmacokinetics of early drug distribution. The model assumes that the substance is injected into the right atrium and measured in the aorta. The dilution curve results from the dispersion and recirculation of the indicator in the body. The concentration time curve in the aorta, r, can be described as r = c0 + g* r, where g is the transport function of the body and c0 is the concentration time course, which is measured for the first time in the aorta. If the body transport function is known, then the aortic dilution curve of a drug can be predicted for different elimination rates and injection times. The site of interest can be chosen arbitrarily, i.e. the concentration of inflow into the kidney or any other organ can be described.

A new catheter mounted, transvalvular left ventricular assist device has been designed for percutaneous transfemoral access. The device, the Hemopump™ [14 French (Fr.) outer diameter], is based on a mixed flow rotary pump and is capable of flow rates of 1.5–2.2 1/min. The pump is inserted using a specialized 16 Fr. femoral introducer sheath. The first application of the percutaneous Hemopump™ in man was performed in two patients with hemodynamic compromise during high risk coronary angioplasty. In these patients, Hemopump™ support resulted in hemodynamic stabilization (increase in aortic pressure from 60/42 to 87/61 and from 80/60 to 100/70 mm Hg, respectively) and marked left ventricular unloading (decrease in pulmonary capillary wedge pressure from 25 to 10 and from 14 to 10 mm Hg) during balloon inflation. In both patients, percutaneous transluminal coronary angioplasty (PTCA) could be accomplished successfully. Using the system for periods of about 2 hr in each patient, we observed no vascular, hemorrhagic, or embolic complications. In both patients, only a minor increase in both plasma free hemoglobin and lactate dehydrogenase levels was noted. Our preliminary experiences suggest that the percutaneous Hemopump™ is safe and effective and may be a powerful alternative to other devices used for supported angioplasty.

A phantom has been designed for measuring flow velocities; using pipes of specified diameter and selectable pulse rates, flow rates varying from 0-250 cm/s can be determined. The measurements are made in a superconductive magnet with a field strength of 1.5 Tesla, employing a RACE technique. The reference technique was electromagnetic flow measurement. There was good linear correlation between the electromagnetic and the MRT results with a correlation coefficient of 0.98. It is necessary in the first place to estimate flow speed; if flow velocity is unknown initially, there is no correlation. Hence, in everyday use erroneous results may be obtained, particularly since one cannot always demonstrate vessels in all parts of the body without superimposition. Further clinical studies are required in various vascular territories to evaluate the usefulness of the RACE technique for flow measurements.

We investigated five different methods which can be applied to quantitatively construct functional tomograms of the lungs. The focus was on the sensitivity of functional tomograms to errors in acquired data. To quantify this sensitivity, theoretical, error-free data sets of well-known properties were artificially generated based on a 'living thorax model'. Physiological time courses and a typical distribution of errors caused by a typical Goe-MF II EIT system were used for the calculations which encompassed a range up to 50 times greater than the initial error level (4 microV(rms max)-400 microV(rms max)). Additionally, low-pass filtering and principal component analysis (PCA) were used to quantify the effect of preprocessing the raw data. The results demonstrate that all methods based on fitting the local to the global time course were superior to the common functional tomograms utilizing standard deviation or maximum and minimum detection. Ventilation distribution was best quantified by the so-called VT methods. Filling capacity--a lung tissue property--was least dependent on increasing error levels. The errors introduced by filtering are significant with respect to a quantitative analysis of ventilation distribution. A preprocessing of raw data by applying a PCA performed well on the data sets which had been constructed but were, nonetheless, realistic. This approach appears to be highly promising for application on real data which is known to be erroneous.

In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

A method was developed to quantify the intensity of tissue staining using a CCD (charge-coupled device) camera. Reflection spectra of NBT-stained (nitro-blue tetrazolium-stained) and unstained myocardium were recorded via fibre optics coupled to a CCD camera, connected to a microcomputer. The calculation of the intensity of staining was based on evaluation of the NBT-related changes of the reflectance spectrum. In each of six anaesthetized sheep, global ischaemia was induced by cross-clamping of the aorta. The hearts were removed and incubated at 35 degrees C. At predetermined times two sections of ventricular myocardium were taken, one of which was then stained with NBT, the other being left unstained. Evaluation of the reflectance spectra from stained sections during the first phase of ischaemia showed a slight loss of NBT colour intensity followed by a more rapid loss of staining until the values of the unstained sections were reached. In contrast to the conventional visual evaluation, the method provides quantitative data on the intensity of staining, and allows use of the NBT technique for statistical evaluation of what happens over time, and the regional distribution of ischaemic injury of tissue. This method may also be applied to other staining techniques.

We present a simple method to determine systematic errors that will occur in the measurements by EIT systems. The approach is based on very simple scalable resistive phantoms for EIT systems using a 16 electrode adjacent drive pattern. The output voltage of the phantoms is constant for all combinations of current injection and voltage measurements and the trans-impedance of each phantom is determined by only one component. It can be chosen independently from the input and output impedance, which can be set in order to simulate measurements on the human thorax. Additional serial adapters allow investigation of the influence of the contact impedance at the electrodes on resulting errors. Since real errors depend on the dynamic properties of an EIT system, the following parameters are accessible: crosstalk, the absolute error of each driving/sensing channel and the signal to noise ratio in each channel. Measurements were performed on a Goe-MF II EIT system under four different simulated operational conditions. We found that systematic measurement errors always exceeded the error level of stochastic noise since the Goe-MF II system had been optimized for a sufficient signal to noise ratio but not for accuracy. In time difference imaging and functional EIT (f-EIT) systematic errors are reduced to a minimum by dividing the raw data by reference data. This is not the case in absolute EIT (a-EIT) where the resistivity of the examined object is determined on an absolute scale. We conclude that a reduction of systematic errors has to be one major goal in future system design.

Because tracer techniques are gaining an increasing importance for imaging flow (and metabolism) in the heart, experimental evidence is needed on the role of convection and diffusion in the transcoronary transport of solutes. In the present work, the transport of four different inert gases through the coronary system is studied in five closed-chest dog experiments and is compared with a digital multicapillary convection-diffusion model. Transport may be defined as flow dependent, as judged by the gross similarity of shape of the time-normalized dilution curves. However, the results show that the transcoronary transport of helium and xenon is more dispersed than that of argon and krypton, probably because of differences in diffusibility and solubility. A comparison of the animal and model experiments emphasizes the importance of diffusive transport of the gases. It is suggested that there is a diffusion shunt that is mainly located within the capillary network itself rather than between conduit vessels. Only for helium (which has the highest diffusivity) was a small arteriovenous shunt fraction seen that is thought to bypass the capillary exchange region. The conclusion is that although there is evidence of diffusional shunting at a capillary level, the inert gas kinetics in the heart are compatible with a basically flow-limited transport.

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.

An established procedure in functional EIT (f-EIT) to image ventilation is the calculation of the standard deviation of the local impedance variation over a series of tomograms for each pixel. We present an improved approach based on the raw data. It saves computing time and is suitable for f-EIT and absolute EIT (a-EIT) just as well. Furthermore, tidal volume, end-expiratory and end-inspiratory ventilatory level can be quantified separately. From the raw data we calculate the time course of the global relative impedance changes. It is used to determine separately the indices (frame number) of all frames that correspond to the maximum (inspiratory) and minimum (expiratory) level of ventilation. According to these indices two data sets of raw data are generated: one mean inspiratory and one mean expiratory frame. Based on these two frames functional images of ventilation or absolute images of lung tissue resistivity can be calculated representing the whole time series. These functional images of ventilation now correspond directly to the tidal volume of respiration which is more common in physiology than standard deviation.

Summary Objectives: The objective of the study was to determine regional pulmonary filling characteristics in 20 mechanically ventilated patients with acute lung injury. Methods: Regional filling characteristics were calculated from tracings of regional tidal volumes vs. global tidal volumes measured by electrical impedance tomography (EIT). These plots were fitted to a polynomial function of the second degree. Regional polynomial coefficients of the second degree characterized the curve linearity of the plots. Near-zero values of the polynomial coefficient indicated a homogeneous increase in regional tidal volumes during the whole inspiration. Positive values hinted at initial low regional tidal volume change suggesting lung volume recruitment. Negative values indicated late low regional tidal volume change implying hyperinflation of this lung region. Results: We found a broad heterogeneity of regional lung filling characteristics. The minimal regional polynomial coefficients varied from 22.80 to 20.56 (median 21.16), while the maximal regional polynomial coefficients varied from 0.58 to 3.65 (median 1.41). Conclusions: Measurements of regional filling characteristics by EIT may be a helpful tool to adjust the respiratory settings during mechanical ventilation to optimize lung recruitment and to avoid overdistension. It applies a non-pressure-related assessment to the mechanics of lung inflation and gives a view of the real problems underlying ventilatory strategies dependent on global characteristics.

Background: We hypothized, that in mechanically ventilated patients with acute respiratory failure, regional pressure volume curves differ markedly from conventional global pressure volume curves of the whole lung. Methods: In nine mechanically ventilated patients with acute respiratory failure during an inspiratory low-flow manoeuvre, conventional global pressure volume curves were registered by spirometry and regional pressure volume curves in up to 912 regions were assessed simultaneously using electrical impedance tomography. We compared the lower (LIP) and upper (UIP) inflection points obtained from the conventional global pressure volume curve and regional pressure volume curves. Results: We identified from the conventional global pressure volume curves LIP [3–11 (8) cmH2O] in eight patients and UIP [31–39 (33) cmH2O] in three patients. Using electrical impedance tomography (EIT), LIP [3–18 (8) cmH2O] in 54–264 (180) regions and UIP [23–42 (36) cmH2O] in 149–324 (193) regions (range and median) were identified. Lung mechanics measured by conventional global pressure volume curves are similar to the median of regional pressure volume curves obtained by EIT within the tomographic plane. However, single regional pressure volume curves differ markedly with a broad heterogeneity of lower and upper inflection points. Conclusion: Lower and upper inflection points obtained from conventional global pressure volume curves are not representative of all regions of the lungs.

Background and objective: Hypotension, especially in elderly and hypovolaemic patients, is frequently associated with intravenous midazolam administration. The mechanisms are not completely understood. This study was designed to investigate the mechanisms involved in the relaxing effect of midazolam on coronary arteries. Methods: The substance was studied in isolated porcine coronary artery rings precontracted by either potassium chloride or prostaglandin F 2 α . Results: Midazolam caused vasodilatation in a concentration-dependent manner. Relaxation was more pronounced in prostaglandin F 2 α precontracted segments than in those treated with potassium chloride (P < 0.001). Vasodilatation was unaffected by N ω -nitro-L-arginine, indomethacin and glibenclamide. Tetraethylammonium chloride, an inhibitor of the BK C a K + channel (a high conductance Ca 2 + -sensitive K + channel), dose dependently attenuated the vasodilating effect of midazolam (P < 0.01). Conclusions: Hyperpolarization of the smooth muscle cell in the vessel wall, elicited by the activation the BK C a K + channel, may contribute to the vasorelaxing effect of midazolam.

The aim of our study was to check the effect of varying blood volume in the chest and gravity on the distribution of ventilation and aeration in the lungs. The change in intrathoracic blood volume was elicited by application of lower body negative pressure (LBNP) of -50 cmH2O. The variation of gravity in terms of hypogravity (approximately 0g) and hypergravity (approximately 2g) was induced by changes in vertical acceleration achieved during parabolic flights. Local ventilation magnitude and end-expiratory lung volume were determined in eight human subjects in the ventral and dorsal lung regions within a transverse cross-section of the lower chest by electrical impedance tomography. The subjects were studied in a 20 degrees head-down tilted supine body position during tidal breathing and full forced expirations. During tidal breathing, a significant effect of gravity on local magnitude of ventilation and end-expiratory lung volume was detected in the dorsal lung regions both with and without LBNP. In the ventral regions, this gravity dependency was only observed during LBNP. During forced expiration, LBNP had almost no effect on local ventilation and end-expiratory lung volume in either lung region. Gravity significantly influenced the end-expiratory lung volumes in dorsal lung regions. The results indicate that exposure to LBNP exerts a less appreciable effect on regional lung ventilation than the acute changes in gravity.

The aim of the experiments was to check the feasibility of pulmonary perfusion imaging by functional electrical impedance tomography (EIT) and to compare the EIT findings with electron beam computed tomography (EBCT) scans. In three pigs, a Swan-Ganz catheter was positioned in a pulmonary artery branch and hypertonic saline solution or a radiographic contrast agent were administered as boli through the distal or proximal openings of the catheter. During the administration through the proximal opening, the balloon at the tip of the catheter was either deflated or inflated. The latter case represented a perfusion defect. The series of EIT scans of the momentary distribution of electrical impedance within the chest were obtained during each saline bolus administration at a rate of 13/s. EBCT scans were acquired at a rate of 3.3/s during bolus administrations of the radiopaque contrast material under the same steady-state conditions. The EIT data were used to generate local time-impedance curves and functional EIT images showing the perfusion of a small lung region, both lungs with a perfusion defect and complete both lungs during bolus administration through the distal and proximal catheter opening with an inflated or deflated balloon, respectively. The results indicate that EIT imaging of lung perfusion is feasible when an electrical impedance contrast agent is used.

The aim of the study was to validate the ability of electrical impedance tomography (EIT) to detect local changes in air content, resulting from modified ventilator settings, by comparing EIT findings with electron beam computed tomography (EBCT) scans obtained under identical steady-state conditions. The experiments were carried out on six anesthetized supine pigs ventilated with five tidal volumes (Vt) at three positive end-expiratory pressure (PEEP) levels. The lung air content changes were determined both by EIT (Goe-MF1 system) and EBCT (Imatron C-150XP scanner) in six regions of interest, located in the ventral, middle, and dorsal areas of each lung, with respect to the reference air content at the lowest Vt and PEEP, as a change in either local electrical impedance or lung tissue density. An increase in local air content with Vt and PEEP was identified by both methods at all regions studied. A good correlation between the changes in lung air content determined by EIT and EBCT was revealed. Mean correlation coefficients in the ventral, middle, and dorsal regions were 0.81, 0.87, and 0.93, respectively. The study confirms that EIT is a suitable, noninvasive method for detecting regional changes in air content and monitoring local effects of artificial ventilation.

Controversies exist concerning myocardial performance in hypothermia. We have studied the effects of epinephrine on myocardial function at various calcium concentrations in moderate hypothermia (28 degrees C) and normothermia (37 degrees C) using an isolated antegrade perfused rat heart. The maximum pressure velocity (dP/dt(max)) developed was significantly higher in normothermia compared with hypothermia and was improved by the addition of calcium in both circumstances. Peak negative pressure velocity (dP/dt(min)) was significantly higher at 37 degrees C compared with 28 degrees C, and was increased by the addition of calcium in normothermia; in contrast to hypothermia, in which no change of dP/dt(min) was observed. A reduction in cardiac output and stroke volume by hypercalcaemia was observed in hypothermia. The addition of epinephrine improved dP/dt(max) and dP/dt(min), but had a depressive effect on stroke volume and cardiac output at normal and elevated calcium concentrations. Myocardial efficiency was significantly higher during hypothermia compared with normothermia, but was impaired by epinephrine during hypothermia. The variable or even paradoxical effects of epinephrine suggest the need for careful haemodynamic monitoring and determination of calcium levels in hypothermia. The impairment of myocardial performance may be explained by impaired diastolic relaxation and calcium overload.