BackgroundDespite recent advances in resuscitation algorithms, neurological injury after cardiac arrest due to cerebral ischemia and reperfusion is one of the reasons for poor neurological outcome. There is currently no adequate means of measuring cerebral perfusion during cardiac arrest. It was the aim of this study to investigate the feasibility of measuring near infrared spectroscopy (NIRS) as a potential surrogate parameter for cerebral perfusion in patients with out-of-hospital resuscitations in a physician-staffed emergency medical service.MethodsAn emergency physician responding to out-of-hospital emergencies was equipped with a NONIN cerebral oximetry device. Cerebral oximetry values (rSO2) were continuously recorded during resuscitation and transport. Feasibility was defined as >80% of total achieved recording time in relation to intended recording time.Results10 patients were prospectively enrolled. In 89.8% of total recording time, rSO2 values could be recorded (213 minutes and 20 seconds), thus meeting feasibility criteria. 3 patients experienced return of spontaneous circulation (ROSC). rSO2 during manual cardiopulmonary resuscitation (CPR) was lower in patients who did not experience ROSC compared to the 3 patients with ROSC (31.6%, ± 7.4 versus 37.2% ± 17.0). ROSC was associated with an increase in rSO2. Decrease of rSO2 indicated occurrence of re-arrest in 2 patients. In 2 patients a mechanical chest compression device was used. rSO2 values during mechanical compression were increased by 12.7% and 19.1% compared to manual compression.ConclusionsNIRS monitoring is feasible during resuscitation of patients with out-of-hospital cardiac arrest and can be a useful tool during resuscitation, leading to an earlier detection of ROSC and re-arrest. Higher initial rSO2 values during CPR seem to be associated with the occurrence of ROSC. The use of mechanical chest compression devices might result in higher rSO2. These findings need to be confirmed by larger studies.

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Purpose: There is evidence that vascular endothelial growth factor (VEGF) is a critical microenvironmental factor that exerts angiogenesis-independent effects on the survival of chronic lymphocytic leukemia (CLL) cells. Vatalanib and pazopanib are potent orally available VEGF receptor tyrosine kinase inhibitors. We investigated the efficacy and selectivity of both compounds in CLL cells, simulated potential combination with conventional cytostatics, and tested the effect of both substances on CLL-like tumor xenografts.Experimental Design: Primary CLL and normal peripheral blood cells were tested for viability after incubation with varying concentrations of both inhibitors. Further, phosphorylation status of VEGF receptor on treatment, caspase activation, and poly(ADP-ribose) polymerase cleavage were assessed. Combinations of each inhibitor with fludarabine, vincristine, and doxorubicin were analyzed for possible synergistic effects in vitro. For in vivo testing, mice grafted with the CLL-like cell line JVM-3 were treated orally with each inhibitor.Results: Vatalanib and pazopanib decreased phosphorylation of the VEGF receptor, along with induction of apoptosis in CLL cells in clinically achievable concentrations. Healthy B cells were only mildly affected. Immunoblots showed downregulation of the antiapoptotic proteins XIAP and MCL1, whereas poly(ADP-ribose) polymerase cleavage was increased. Combinations with conventional cytostatic agents resulted in synergistic effects. Treatment of xenografted mice with 100 mg/kg of body weight for 21 days resulted in tumor inhibition rates of 76% (vatalanib) and 77% (pazopanib). In two mice, a total tumor eradication could be observed. No gross systemic toxicity occurred.Conclusion: We conclude that VEGF inhibition is a promising new therapeutic approach in CLL. Vatalanib and pazopanib seem to be effective and safe candidates to be further evaluated for this purpose.

In this study we investigated the responsiveness of near-infrared spectroscopy (NIRS) recordings measuring regional cerebral tissue oxygenation (rSO2) during hypoxia in apneic divers. The goal was to mimic dynamic hypoxia as present during cardiopulmonary resuscitation, laryngospasm, airway obstruction, or the "cannot ventilate cannot intubate" situation. Ten experienced apneic divers performed maximal breath hold maneuvers under dry conditions. SpO2 was measured by Masimo™ pulse oximetry on the forefinger of the left hand. NIRS was measured by NONIN Medical's EQUANOX™ on the forehead or above the musculus quadriceps femoris. Following apnea median cerebral rSO2 and SpO2 values decreased significantly from 71 to 54 and from 100 to 65%, respectively. As soon as cerebral rSO2 and SpO2 values decreased monotonically the correlation between normalized cerebral rSO2 and SpO2 values was highly significant (Pearson correlation coefficient = 0.893). Prior to correlation analyses, the values were normalized by dividing them by the individual means of stable pre-apneic measurements. Cerebral rSO2 measured re-saturation after termination of apnea significantly earlier (10 s, SD = 3.6 s) compared to SpO2 monitoring (21 s, SD = 4.4 s) [t(9) = 7.703, p < 0.001, r(2) = 0.868]. Our data demonstrate that NIRS monitoring reliably measures dynamic changes in cerebral tissue oxygen saturation, and identifies successful re-saturation faster than SpO2. Measuring cerebral rSO2 may prove beneficial in case of respiratory emergencies and during pulseless situations where SpO2 monitoring is impossible.