Hypothermic machine preservation facilitates successful transplantation of "orphan" extended criteria donor livers.

Hypothermic machine preservation (HMP) remains investigational in clinical liver transplantation. It is widely used to preserve kidneys for transplantation with improved results over static cold storage (SCS). At our center, we have used HMP in 31 adults receiving extended criteria donor (ECD) livers declined by the originating United Network for Organ Sharing region ("orphan livers"). These cases were compared to ECD SCS cases in a matched cohort study design. Livers were matched for donor age, recipient age, cold ischemic time, donor risk index and Model for End-Stage Liver Disease (MELD) score. HMP was performed for 3-7 h at 4-8 °C using our previously published protocol. Early allograft dysfunction rates were 19% in the HMP group versus 30% in the control group (p = 0.384). One-year patient survival was 84% in the HMP group versus 80% in the SCS group (p = NS). Post hoc analysis revealed significantly less biliary complications in the HMP group versus the SCS group (4 vs. 13, p = 0.016). Mean hospital stay was significantly shorter in the HMP group (13.64 ± 10.9 vs. 20.14 ± 11.12 days in the SCS group, p = 0.001). HMP provided safe and reliable preservation in orphan livers transplanted at our center.

The benefits of hypothermic machine perfusion are enhanced with Vasosol and α-tocopherol in rodent donation after cardiac death livers.

The use of hypothermic machine perfusion (HMP) has recently been used to show an improvement in both standard and extended criteria donor liver grafts but creating a more dynamic preservation environment that can be supplemented with a variety of additives to aid in cold temperature metabolism and vasodilatation. Increasing the benefits of HMP, we explore the use of α-tocopherol in reducing inflammatory markers and apoptotic pathways to reduce the incidence of preservation injury. We explored the use of a donation after cardiac death (DCD) rodent model to test the additive benefits of α-tocopherol in HMP. The addition of α-tocopherol reduced the level of alanine aminotransferase (ALT) over the course of reperfusion as well, reduced the levels of inflammatory cytokines within a 90 minute reperfusion biopsy. Further benefit was seen with α-tocopherol through the reduction of the level of caspase 3/7 in the circulation, shown to be a result of the reduction of the levels of Cytochrome C mRNA. Liver perfusion with Vasosol® and HMP could benefit further from the addition of α-tocopherol to existing formulations of Vasosol®.

Liver defatting: an alternative approach to enable steatotic liver transplantation.

Macrovesicular steatosis in greater than 30% of hepatocytes is a significant risk factor for primary graft nonfunction due to increased sensitivity to ischemia reperfusion (I/R) injury. The growing prevalence of hepatic steatosis due to the obesity epidemic, in conjunction with an aging population, may negatively impact the availability of suitable deceased liver donors. Some have suggested that metabolic interventions could decrease the fat content of liver grafts prior to transplantation. This concept has been successfully tested through nutritional supplementation in a few living donors. Utilization of deceased donor livers, however, requires defatting of explanted organs. Animal studies suggest that this can be accomplished by ex vivo warm perfusion in a time scale of a few hours. We estimate that this approach could significantly boost the size of the donor pool by increasing the utilization of steatotic livers. Here we review current knowledge on the mechanisms whereby excessive lipid storage and macrosteatosis exacerbate hepatic I/R injury, and possible approaches to address this problem, including ex vivo perfusion methods as well as metabolically induced defatting. We also discuss the challenges ahead that need to be addressed for clinical implementation.

Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation.

Hypothermic machine perfusion (HMP) is in its infancy in clinical liver transplantation. Potential benefits include diminished preservation injury (PI) and improved graft function. Molecular data to date has been limited to extrapolation of animal studies. We analyzed liver tissue and serum collected during our Phase 1 trial of liver HMP. Grafts preserved with HMP were compared to static cold stored (SCS) transplant controls. Reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and transmission electron microscopy (TEM) were performed on liver biopsies. Expression of inflammatory cytokines, adhesion molecules and chemokines, oxidation markers, apoptosis and acute phase proteins and the levels of CD68 positive macrophages in tissue sections were evaluated. RT-PCR of reperfusion biopsy samples in the SCS group showed high expression of inflammatory cytokines, adhesion molecules and chemokines, oxidative markers and acute phase proteins. This upregulation was significantly attenuated in livers that were preserved by HMP. Immunofluorescence showed larger numbers of CD68 positive macrophages in the SCS group when compared to the HMP group. TEM samples also revealed ultrastructural damage in the SCS group that was not seen in the HMP group. HMP significantly reduced proinflammatory cytokine expression, relieving the downstream activation of adhesion molecules and migration of leukocytes, including neutrophils and macrophages when compared to SCS controls.

Hypothermic machine preservation in human liver transplantation: the first clinical series.

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

Coronary dissection resulting from angioplasty with slow oscillating vs. rapid inflation and slow vs. rapid deflation.

To determine if slow inflation or slow deflation (compared to standard rapid inflation/deflation) would minimize coronary arterial dissection, we randomized 162 lesions from 136 patients undergoing coronary angioplasty with polyolefin copolymer balloons to slow oscillating (1 atmosphere/20 sec) vs. rapid (over 30 sec) inflation and slow (over 15 sec) vs. rapid deflation. The incidence of any dissection was nearly identical in the four inflation/deflation groups. The incidence of severe dissection, however, was significantly higher for the slow inflation/slow deflation group compared to the other three groups (38% vs. 15%, P = .024). For angioplasty performed with polyolefin copolymer balloons, slow deflation combined with slow oscillating inflation is associated with more frequent severe dissections.

Results of coronary artery bypass grafting using multiple arterial conduits.

Between January 1991 and June 1993, a total of 128 patients underwent coronary artery bypass grafting employing multiple autologous arterial conduits, including 157 internal mammary arteries, 69 inferior epigastric arteries, 44 gastroepiploic arteries, and 72 radial artery grafts. Their mean age was 61.4 years (range 29 to 82 years). The patients were divided into 2 groups: group A, consisted of 69 patients (mean age 60.3 years), in whom multiple arterial conduits were used exclusively (no vein grafts); group B, included 59 patients (mean age 62.7 years) in whom, in addition to multiple arterial conduits, 89 saphenous vein grafts were used concomitantly. The mean number of grafts was 3.1 and 3.7, for groups A and B, respectively. The preoperative left ventricular function, and the prevalence of unstable angina, a recent myocardial infarction, and diabetes, were not significantly different between both groups. Our series included 11 "redo" operations (8 in group A, and 3 in group B). There were 6 early deaths (4.7% mortality) (1 in group A, and 5 in group B), and 4 perioperative myocardial infarctions (1 in group A, 3 in group B). During a mean follow-up of 12.9 months (range 1 to 28 months) there were no late deaths or reoperations in any group. All patients in group A are free of symptoms. In group B, 2 patients have recurrent angina, and 1 had a late myocardial infarction, in the distribution of a vein graft. A myocardial SPECT scan with exercise revealed new perfusion defects in 4 of 49 patients (1 in group A, 3 in group B), studied 1 year after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Benign intracranial hypertension in pregnancy.

Benign intracranial hypertension, an unusual case of headaches, was associated with pregnancy in a gravid female with the chief complaint of headache. Symptoms resolved after three days of prednisone therapy. In benign intracranial hypertension, the possibilities of intracranial mass lesions, intracranial infection, obstruction of the cerebral ventricles, and hypertensive encephalopathy are excluded by evaluation with skull films, computerized axial tomography, electroencephalography and lumbar puncture. The only symptom may be headache and the only physical sign, papilledema. Therefore, neurological examination must include visualization of the fundi.