No abstract

Orthogonal polarization spectral imaging revealed no major changes of microvascular perfusion during uncomplicated hypothermic CPB. The slightly reduced functional capillary density during CPB may be caused by several factors all present during CPB, including hypothermia, the artificial extracorporeal perfusion, surgical trauma, hemodilution, and inflammatory reaction. The current data do not allow differentiation between the effects of those possible causes.

Background: As a step towards clinical cardiac xenotransplantation, our experimental heterotopic intrathoracic xenotransplantation model offers a beating and ejecting donor heart while retaining the recipient 0 s native organ as a backup in case of graft failure. Clinically applicable immunosuppressive regimens (IS) were investigated first, then treatments known to be effective in hypersensitized patients or those with recalcitrant rejection reactions. Methods: Consecutive experiments were carried out between 2009 and 2013. Twenty-one genetically modified pigs (GGTA1-knockout/hCD46/ AE thrombomodulin, in one case HLA-E instead) were used as donors. In all experiments, two cycles of immunoabsorption reduced preformed antibodies. Recipient baboons were divided into two groups according to IS regimen: In group one (n = 10), pre-treatment started either one (anti-CD20) or four weeks (anti-CD20 plus the proteasome inhibitor bortezomib) prior to transplantation. The extended conventional (as for allotransplantation) immunosuppressive maintenance regimen included anti-thymocyte globuline, tacrolimus, mycophenolate mofetil, methylprednisolone and weekly anti-CD20. In group two (n = 11), myeloablative pre-treatment as in multiple myeloma patients (long and short regimens) was added to extended conventional IS; postoperative total thoracic and abdominal lymphoid irradiation (TLI; single dose of 600 cGY) was used to further reduce antibody-producing cells. Results: In the perioperative course, the surgical technique was safely applied: 19 baboons were weaned off extracorporeal circulation and 17 extubated. Nine animals were lost in the early postoperative course due to causes unrelated to surgical technique or IS regimen. Excluding these early failures, median graft survival times of group 1 and 2 were 18.5 (12-50) days and 16 (7-35) days. Necropsy examination of group 1 donor organs revealed hypertrophy of the left ventricular wall in the six longer-lasting grafts; myocardial histology confirmed preclinical suspicion of humoral rejection, which was not inhibited by the extended conventional IS including intensified treatments, and signs of thrombotic microangiopathy. Grafts of group 2 presented with only mild-to-moderate features of humoral rejection and thrombotic microangiopathy, except in one case of delayed rejection on day 17. The other experiments in this group were Jan-Michael Abicht, terminated because of untreatable pulmonary oedema, recurring ventricular fibrillation, Aspergillus sepsis, as well as a combination of a large donor organ and late toxic side effects due to TLI. Conclusions: Longer-term results were difficult to achieve in this model due to the IS regimens used. However, we conclude that heterotopic intrathoracic heart transplantation may be an option for clinical xenotransplantation.

The decreased CFC in response to sevoflurane may result in less extravasation of fluids into the interstitial space, thereby reducing intraoperative fluid requirements. These data suggest that sevoflurane may be the preferred anesthetic agent in subjects susceptible to large intraoperative fluid shifts.

ABSTRACT:In adults with severe sepsis, the disturbances of the sublingual microcirculation can be quantified with orthogonal polarization spectral imaging. We investigated the cutaneous microcirculation of preterm infants with proven infection (PosInf) and with suspected but unproven infection (NegInf). In 25 infants, orthogonal polarization spectral images were obtained daily, videos of the images were blinded, and analyzed off-line. Functional small vessel density (FSVD) was prospectively calculated from day 3 to day 30 of life. There were 17 episodes of proven and nine episodes of suspected but unproven nosocomial late onset infection. Four infants remained healthy. The data were analyzed for the 5 d before the start of antibiotics (day Ϫ5 until day Ϫ1). FSVD varied widely, but in the PosInf-group, we found a 10% decline from day Ϫ5 to day Ϫ1 (p ϭ 0.013). There was no significant change over time in the NegInfgroup (p ϭ 0.58). Thus, in infants with proven infection, FSVD decreases already 1 d before changes in laboratory parameters. However, these changes in FSVD during infection are not represented by absolute values, but must be identified by daily intraindividual observation. (Pediatr Res 66: 461-465, 2009) V ery low-birth weight infants are at increased risk for episodes of nosocomial infection, which contributes significantly to mortality and morbidity (1). Early diagnosis and prompt administration of appropriate antibiotics are crucial to improve outcome but clinical signs of infection are very unspecific. White blood cell count has not been shown to improve early diagnosis; C-reactive protein (CRP) is quite specific but not very sensitive for neonatal infection. Cytokines such as interleukine (IL)-6 increase early in neonatal infection before the rise of CRP, and the combination of both increases sensitivity and specificity (2). The need for early treatment in combination with nonspecific clinical signs leads to significant iatrogenic blood loss (3) and an increased exposure to antibiotics.Most clinical signs of infection such as change of skin color, a prolonged capillary filling time, and temperature instability are caused by altered microcirculation. Changes in microcirculation play an important role in the development of septic organ dysfunction (4,5) and the severity of change may even predict outcome (6). Improved technology has made observation and quantification of microcirculatory parameters possible. One of the most promising instrumentation in the regard is the orthogonal polarization spectral (OPS) imaging technique, which allows new insights in the human microcirculation and semiquantified assessment. This method provides high-resolution images of the microvascular architecture to a depth of 1 mm. OPS has been validated by multiple studies in animals and humans (7,8). Using OPS Sakr et al. (6) recently found an association between microcirculatory alterations, organ dysfunction, and death in patients with septic shock. We have previously shown that OPS imaging and measurement of small vess...