[Show abstract][Hide abstract] ABSTRACT: Background: Proper revascularization after transplantation is assumed to be crucial forappropriate islet graft function. Methods: We developed a novel non-invasive imagingmethod, based on adenoviral transduction of islets with a hypoxia responsive reporter gene,for continuous in vivo monitoring of hypoxia in islet grafts in a mouse model. In addition,morphological data was obtained from a deceased patient previously subject to intraportaltransplantation. Results: We detected only transient hypoxia in a minority of the animalstransplanted. Importantly, a clear response to hypoxia was observed in vitro after removal ofthe islet-grafts on day twenty-eight after transplantation. Also, the morphological data fromthe deceased patient demonstrated an extensive revascularization of the transplanted islets. Infact, no differences could be seen between native, in pancreas biopsies taken prior to isletisolation, and transplanted islets regarding the number, distribution and shape of the bloodvessels. However, fewer small islets (diameter <39μm) were found in the liver compared to those found in native pancreases. Notably, an absolute majority of the transplanted islets were found remaining within the venous lumen, in direct contact with the vessel wall. Conclusions:In conclusion results presented show less pronounced islet graft hypoxia after subcapsulartransplantation than previously reported using more invasive methods. Also, formation of anextensive intra-islet capillary network, similar to that seen in native islets in the pancreas, wasseen after clinical islet transplantation.
No preview · Article · May 2012 · Cell Transplantation
[Show abstract][Hide abstract] ABSTRACT: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model.
Six pigs of both sexes (10-12 wks old; mean weight, 24.5±1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death.
A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8±9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137±0.069 mL/mm Hg to 0.007±0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis.
The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.
No preview · Article · Mar 2011 · Critical care medicine