H Baschnegger

Ludwig-Maximilian-University of Munich, München, Bavaria, Germany

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Publications (11)27.76 Total impact

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    ABSTRACT: Whilst macrohemodynamic function of porcine xenografts transplanted into baboons has been assessed perioperatively, the ability of the xenograft to maintain systemic microcirculatory perfusion has not been investigated after pig-to-baboon xenotransplantation so far. We investigated the sublingual microcirculation of six baboons undergoing orthotopic transplantation of hCD46-transgenic pig hearts using orthogonal polarization spectral imaging. Microvascular measurements were performed after induction of anesthesia, in the early phase of cardiopulmonary bypass (CPB), during reperfusion of the porcine heart and 1 h after the xenograft had resumed its life-supporting function. Microvascular blood flow was analyzed semiquantitatively and the number of visualized cell-to-cell interactions was counted. The proportion of continuously perfused microvessels was 97 (96 to 97) % at baseline and 95 (94 to 97) % in the early phase of CPB. It decreased significantly (P < 0.05) during CPB to 89 (84 to 91), and alterations were still present (P < 0.05) when CPB was terminated and the xenograft had taken over systemic perfusion 83 (81 to 85) %. The microcirculatory changes correlated with the lactate levels (y = 18.1-0.18 x; r(2) = 0.55; P < 0.001), but no correlation with macrohemodynamic parameters was found. Microvascular blood flow is altered after orthotopic pig-to-baboon heart transplantation, despite systemic hemodynamic parameters being well maintained by the porcine xenograft. These changes are moderate but persist after termination of CPB. Further studies need to elucidate whether these changes are transient or add to the mortality associated with cardiac xenotransplantation.
    Xenotransplantation 07/2011; 18(4):232-8. · 2.57 Impact Factor
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    ABSTRACT: Orthotopic pig-to-baboon xenogeneic heart transplantation (oXHTx) is the only accepted preclinical animal model for cardiac xenotransplantation. We compared the hemodynamic stability of a propofol- and isoflurane-based anesthetic regimen during oXHTx. Hearts from 12 hDAF or hCD46 transgenic pigs (Sus scrofa; body weight 7 to 32 kg) were transplanted into baboons (Papio anubis and Papio hamadryas; body weight 9 to 26 kg) in the orthotopic life-supporting position. Animals received a propofol-based intravenous regimen or inhalation anesthesia with isoflurane. Analgesia was achieved with fentanyl in both groups. Systemic hemodynamic variables were measured before, during and after cardiopulmonary bypass (CPB) and the need for inotropic or vasoactive pharmacological support was compared before and after CPB. Global hemodynamic variables [i.e. heart rate, mean arterial pressure (MAP) and cardiac output] were not significantly different in propofol-anesthetized baboons compared to baboons anesthetized with isoflurane. Baboons anesthetized with isoflurane showed a trend towards less pharmacological support required to achieve an adequate MAP of >60 mmHg after CPB (propofol: epinephrine 0.13 [0.05; 0.16] and norepinephrine 0.15 [0.02; 0.16] microg/kg/min vs. isoflurane: epinephrine 0.05 [0.02; 0.08] and norepinephrine 0.06 [0.02; 0.19] microg/kg/min; no significant difference). Propofol and isoflurane appear to provide equal hemodynamic stability in orthotopic cardiac pig-to-baboon xenotransplantation prior to the start of CPB. The trend of a reduced catecholamine support needed after CPB, however, suggests that isoflurane may be the preferred drug for maintenance of anesthesia in this primate model.
    Xenotransplantation 05/2007; 14(3):249-54. · 2.57 Impact Factor
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    ABSTRACT: Pig organs are at risk for hyperacute and acute vascular rejection mediated by anti-pig antibodies, mainly binding to the Galalpha(1,3)Gal epitope. Acute cellular rejection is characterized by progressive infiltration of mononuclear cells. There is an ongoing search for immunosuppressive regimens that provide adequate protection against all patterns of xenograft rejection, but have no severe impact on the condition of xenograft recipients. Herein orthotopic heart transplantations were performed from hDAF or hCD46 piglets to nonsplenectomized baboons. Basic immunosuppression consisted of tacrolimus, sirolimus, GAS914, steroids, and ATG. Group 1 received basic immunosuppression. Group 2 was additionally treated with rituximab and group 3 with half-dose cyclophosphamide. Group 4 received cyclophosphamide and an anti-HLA-DR antibody. Three baboons received GAS914 and TPC. Monitoring included the regular assessment of anti-porcine antibodies, blood counts, therapeutic drug monitoring, and graft histology. Two grafts failed due to technical mistakes. In group 1, baboons died after 1 and 9 days. In group 2, maximum survival was 30 hours. In group 3, baboons lived 20 hours, 25 days, and 14 days. Group 4 survival times were 9.5 hours, 5.5 hours, 4 days, 34 hours, and 3 days. An increase of non-Galalpha(1,3)Gal antibodies was observed. Depositions of immunoglobulins and complement revealed a humoral rejection process. No cellular infiltration could be observed. In conclusion, suppressing cellular rejection with half-dose cyclophosphamide together with tacrolimus and sirolimus produced longer graft survival with a good general condition. Prevention of acute xenograft rejection further needs inhibition of non-Galalpha(1,3)Gal cytotoxicity by sufficient depression of B-cell activation.
    Transplantation Proceedings 04/2007; 39(2):577-8. · 0.95 Impact Factor
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    ABSTRACT: The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface shear forces.
    Clinical Science 02/2006; 110(2):207-15. · 4.86 Impact Factor
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    ABSTRACT: Only limited data are available on the physiological functional compatibility of cardiac xenografts after orthotopic pig to baboon transplantation (oXHTx). Thus we investigated hemodynamic parameters including cardiac output (CO) before and after oXHTx. Orthotopic xenogeneic heart transplantation from nine hDAF transgeneic piglets to baboons was performed. We used femoral arterial thermodilution for the invasive assessment of CO and stroke volume. Baseline CO of the baboons after induction of anesthesia was 1.36 (1.0-1.9) l/min. 30 to 60 min after termination of the cardiopulmonary bypass, CO of the cardiac xenograft was significantly increased to 1.72 (1.3-2.1) l/min (P < 0.01). The stroke volumes of the baboon heart before transplantation and the cardiac xenograft was comparable [14.9 (11-26) vs. 11.8 (10-23) ml]. Thus the higher CO was achieved by an increase in heart rate after oXHTx [75.0 (69-110) vs. 140.0 (77-180)/min; P < 0.01]. Despite the increased CO, oxygen delivery was reduced [256 (251-354) vs. 227 (172-477) ml/min; P < 0.01] due to the inevitable hemodilution during the cardiopulmonary bypass and the blood loss caused by the surgical procedures. Our results demonstrate that in the early phase after orthotopic transplantation of hDAF pig hearts to baboons, cardiac function of the donor heart is maintained and exceeds baseline CO. However, in the early intraoperative phase this was only possible by using inotropic substances and vasopressors due to the inevitable blood loss and dilution by the priming of the bypass circuit.
    Xenotransplantation 11/2005; 12(6):444-9. · 2.57 Impact Factor
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    ABSTRACT: Long-term survival of transgenic cardiac xenografts is currently limited by a form of humoral rejection named acute vascular rejection. Preformed and elicited cytotoxic antibodies against Galalpha(1,3)Gal terminating carbohydrate chains, known as the primary cause of hyperacute rejection, are crucial for this process. We investigated whether GAS914, a soluble, polymeric form of a Galalpha(1,3)Gal trisaccharide would sufficiently minimize xenograft rejection of hDAF-transgenic pig hearts orthotopically transplanted into baboons. Orthotopic heart transplantations were performed using hDAF transgenic piglets as donors and four non-splenectomized baboons as recipients. Baseline immunosuppression consisted of tacrolimus, sirolimus, ATG, steroids. In addition two animals received low-dose GAS914, and two animals high-dose GAS914. One of these baboons received high dose GAS914 and cyclophosphamide induction therapy. Serum levels of anti-Galalpha(1,3)Gal IgM and IgG antibodies, and anti-pig antibodies were controlled daily by anti-Galalpha(1,3)Gal enzyme-linked immunosorbant assay and anti-pig hemolytic assays. Histomorphological (hematoxylin and eosin, elastic van Gieson) and immunohistochemical (IgM, IgG) evaluations were performed on tissue specimens. Following low-dose GAS914 therapy survival time was 1 and 9 days, respectively. In baboons treated with high dosages of GAS914 a survival of 30 h and 25 days could be obtained. GAS914 caused an immediate and significant reduction of both anti-Galalpha(1,3)Gal IgM and IgG antibodies. However, sufficient antibody reduction was independent of dosage and form of application of GAS914. A pre-transplant GAS914 treatment was not necessary to effectively reduce antibody levels and prevent hyperacute rejection. In the early postoperative period preformed anti-pig antibodies corresponded predominantly to anti-Galalpha(1,3)Gal antibodies making them susceptible to GAS914. Subsequently, while anti-Galalpha(1,3)Gal antibodies remained low, anti-pig antibodies increased despite of GAS914 application. Corresponding to increased anti-pig antibody titers depositions of IgM and IgG immunoglobulins were detected, which were possibly non-Galalpha(1,3)Gal-specific. Following orthotopic transplantation of hDAF-transgenic pig hearts into baboons, GAS914 is able to maintain a sufficient reduction of Galalpha(1,3)Gal-specific cytotoxicity to the graft. GAS914 therefore is able to prevent not only hyperacute rejection, but also acute vascular rejection at its beginning, when serum cytotoxicity to the pig heart appears to be predominantly Galalpha(1,3)Gal-specific. A sustained prevention of acute vascular rejection, however, still requires the identification of antibody specificities other than to Galalpha(1,3)Gal.
    Xenotransplantation 04/2005; 12(2):134-41. · 2.57 Impact Factor
  • The Journal of Heart and Lung Transplantation 01/2003; 22(1). · 5.11 Impact Factor
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    ABSTRACT: Photoplethysmography enables non-invasive investigation of the volume pulse in the microvasculature of patients. We previously have shown that time-discrete analysis enables identification of highly reproducible characteristics of the volume pulse in absolute values. The method would be of particular interest, if the perfusion of deeper tissue layers like the skeletal muscle can be assessed. The aim of the current study was to investigate the attenuation of the photoplethysmographic signal by different tissues and up to which depth of tissue a time-discrete analysis of the photoplethysmographic signal would be possible. For the recordings we used the time-discrete near-infra-red photoplethysmography (NIRP), a reflection photoplethysmograph measuring at wavelengths of 840 nm and 640 nm. In an in vitro circuit filled with bovine blood we generated a typical and exactly reproducible volume pulse. On a platform the NIRP sensor probe was placed above the artificial vessel and recordings of the volume pulse were obtained by varying the sensor-vessel-distance with increasing layers of water, blood-agar or bovine skeletal muscle tissue. - The amplitude of the NIR signal was attenuated to 50% by each layer of 2.01 mm of water, 1.42 mm of blood-agar and 1.05 mm of bovine skeletal muscle tissue. A time-discrete analysis could be performed up to a depth of 15 mm of water, 6 mm of blood-agar and 5 mm of bovine skeletal muscle tissue. - As the photoplethysmographic curve is strongly attenuated even by a few millimetres of water we suggest that the NIRP signal mirrors the perfusion of the superficial tissue layer and mainly originates from the subpapillary capacious plexus. - We conclude that with the equipment used in this study volume pulsations in deeper layers of tissue like skeletal musculature can not be assessed.
    European journal of medical research 06/1998; 3(5):241-8. · 1.10 Impact Factor
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    F Christ, J Gamble, H Baschnegger, I B Gartside
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    ABSTRACT: 1. Venous congestion strain-gauge plethysmography enables the non-invasive assessment of arterial blood flow, fluid filtration capacity (Kf), venous pressure (Pv) and isovolumetric venous pressure (Pvi) in man. One of the major assumptions of this technique, that cuff pressure (Pcuff) applied to the limb equals Pv at the level of the strain gauge, was tested in this study. 2. In nine healthy male volunteers (mean age, 29.3 +/- 1.2 years) the saphenous vein was cannulated with an 18-gauge catheter proximal to the medial malleolus. The subjects were supine and Pv was continuously measured during the application of small step (8-10 mmHg) increases in congestion Pcuff (up to 70 mmHg). Pcuff, changes in limb circumference and Pv were recorded by computer for off-line analysis. Since the determination of Kf is influenced by the changes in plasma oncotic pressure, venous blood samples were obtained at the start of the study, when Pcuff was raised to 30 mmHg and again to 65 mmHg and 4 min after deflation of the cuff. 3. The relationship between Pv and Pcuff was linear over the range of 10-70 mmHg (n = 9, 69 measurements, slope 0.91, r = 0.97, P < 0.001). The non-invasively measured calf Pv, based on the intercept of the relationship between the vascular compliance component (Va) and Pcuff, was 8.0 +/- 0.4 mmHg, which was not significantly different from the corrected invasively measured Pv value of 8.8 +/- 0.3 mmHg (P = 0.08). 4. Venous blood lactate and haemoglobin concentrations, as well as colloid osmotic pressure, total protein and albumin concentrations were unchanged throughout the protocol, whereas significant decreases in PO2 and blood glucose concentration were observed when Pcuff reached 65 mmHg. Assuming a constant oxygen consumption, this may suggest a reduction in tissue perfusion. 5. This study demonstrates the close correlation between Pcuff and Pv in the saphenous vein. Since the small congestion Pcuff step protocol does not cause significant increase in plasma oncotic pressure, we conclude that Pv, as well as Kf, can be accurately determined with this venous congestion plethysmography protocol.
    The Journal of Physiology 09/1997; 503 ( Pt 2):463-7. · 4.38 Impact Factor
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    ABSTRACT: Biological signals like arterial blood pressure (ABP) and electrocardiograms are usually displayed in a linear fashion. The often very complex structure may, however, be better described by phase space plots and time-delayed vectors, enabling an advantageous display of the dynamics contained in the signal. The potentials of such a display were investigated during elective aortic aneurysm repair, where profound haemodynamic changes frequently occur. The peripheral volume pulse was recorded at a digit using noninvasive near infrared photoplethysmography (NIRP). All patients (n = 20, mean age 72.8 years) were invasively monitored using arterial and Swan Ganz catheters. The ABP signal was continuously recorded with a computer (sample rate 128 Hz). Two different phase space plots, [x(t), y(t + 8/128 s) and x(t), d(x(t + 8/128 s) - x(t))/dt] were calculated for the NIRP and the ABP signals and continuously displayed. The stability was subjectively assessed and the fractal dimension calculated using the 'Hausdorff dimension'. The correlation between stability, fractal dimension and frequently used parameters of patient monitoring were investigated. All patients included in the study had an uncomplicated operation. Cardiac index (CI) and oxygen delivery (DO2) increased, and systemic vascular resistance (SVR) decreased following declamping of the aorta. The ABP signal was generally more stable. After declamping of the aorta, 14 of 16 NIRP signals became unstable, and 9 of 14 ABP signals destabilised. The time required for stabilisation of the signal varied between the individual patients. Thirty minutes after declamping, 11 of 12 ABP signals were stable, whereas 3 out of 9 NIRP signals still revealed an unstable pattern. A fractal dimension was calculated by box counting, which revealed a linear regression over two orders of magnitude in a log-log plot (Hausdorff dimension between 1.19 and 1.71). The mean fractal dimension for NIRP was significantly higher than that of the ABP signal. On clamping and declamping of the aorta, a trend to a higher fractal dimension (p = 0.08) was observed for both signals analysed. No correlation was observed between the fractal dimension and ABP, SVR index, CI, DO2 index and oxygen consumption. The dynamic changes of the signals were emphasised when they were displayed as phase space plots calculated by time-delayed vectors. The time series of the signal revealed a fractal dimension, and the observed increase at the critical time points of the operation, where the need for cardiovascular regulation is most pronounced, support the contention that a physiological system based on non-linear behaviour may enable a rapid response to haemodynamic challenges. An on-line display of phase space plots calculated by time-delayed vectors may in future provide a valuable method of monitoring for high-risk patients.
    International Journal of Microcirculation 01/1997; 17(6):374-84.
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    ABSTRACT: In pulse oximetry the principles of photoplethysmography are used for determination of heart rate and in some devices to also display the volume pulse. It has been suggested, that a more detailed analysis of the signal may allow quantitative analysis of peripheral hemodynamic events. We describe a new computer assisted time discrete analysis of the volume pulse, studying its reliability and the method s fundamental assumption of a linear relationship between changes in amplitude and changes in time sequences of the volume pulse. In a finger clip two diodes emit near infrared (840 nm, NIR) and red light (640nm, RED) into the finger tip, where it is remitted mainly by the erythrocytes. 70 sec of recorded signal is filtered and the resulting volume pulse analysed off-line using a computer. On each volume pulse the time of the first (Tmax), the second maximum (time of dicrote, Td) and the duration of the volume pulse (Tp) are measured and the mean values displayed. In addition, the fundamental arterial oscillation Tag = Td - Tmax and all the above values in relation to Tp are calculated. Using NIRP, 54 healthy young volunteers (19 female, mean age 27.0 +/- 3.4 years) were studied and the individual mean values calculated from 960 measurements. The reliability during 10 repetitive measurements was investigated in 26 of the 54 volunteers. In 12 subjects 5 repetitive measurements were obtained from each finger and compared with each other. In 11 subjects the linear relationship between amplitude and time sequence was tested on > 30 000 single volume pulses. The finger clip photoelectrode was levelled with the right atrium in all measurements, skin close to the clip and room temperature were recorded. From the mean individual values the following time discrete values were calculated for the NIR signal (n = 41): Tp = 882.3 +/- 142.6 ms, Tmax = 214.8 +/- 28.3 ms, Td = 452.7 +/- 32.4 ms, Tdec = 667.4 +/- 133.6 ms, Tag = 237.9 +/- 36.3 ms, Tmax/Tdec = 0.34 +/- 0. 07, Td/Tdec = 0.7 +/- 0.11. For each parameter the individual standard deviation during 10 repetitive measurements (26 subjects) ranged between 2.2 and 6.1%. The time sequences found were not significantly different between the individual fingers. A linear relationship between changes in time sequence and changes in amplitude was found in all tested subjects (mean r = 0.96). These results show, that the values obtained with time discrete NIRP are highly reproducible and show an individual SD of less than 6.5% under steady state conditions. The linear relationship between time sequence and amplitude found in the present study has to be confirmed in further studies on patients with pathologies of the macro- and microcirculation.
    European journal of medical research 02/1996; 1(5):237-43. · 1.10 Impact Factor