Efficacy of hypothermic perfusion using University of Wisconsin solution in extended hepatectomy with hepatic inflow occlusion in a canine model

This study was designed to elucidate the efficacy of University of Wisconsin (UW) solution for preventing liver injury, when used as a hypothermic perfusate infused into the systemic circulation during extended hepatectomy with hepatic inflow occlusion. Adult mongrel dogs (9.5–17.5 kg, n= 14) were subjected to 75% hepatectomy under 60 min hepatic inflow occlusion. The animals were divided into two groups. The UW group (n= 7) underwent hypothermic perfusion using 4°C UW solution (core temperature of the liver: 12.3±0.2°C). The control group designated as the Ringer's lactate (LR) group (n= 7) underwent hypothermic perfusion using 4°C LR solution. The perfusate was introduced into the systemic circulation via the hepatic vein. Blood from the hepatic vein was sampled, and alanine amino-transferase, purine nucleoside phosphorylase activities and the ammonia concentration were measured. The 7 day survival rate was higher in the UW group than in the LR group. The parameters of liver function were less significantly altered in the UW group than in the LR group. The plasma ammonia concentration was significantly (P<0.05) lower 6h after reperfusion in the UW group than in the LR group. A small volume of hypothermic perfusion of the liver using UW solution was safe if it returned to systemic circulation. Hypothermic perfusion of the liver using UW solution may be effective for preventing hepatic tissue injury during extended hepatectomy with hepatic vascular occlusion.     

Steroid synthesis in the adrenal gland of the sea snake Hydrophis cyanocinctus: The metabolism of exogenous precursors

Sea snake (Hydrophis cyanocinctus) adrenal glands (whole homogenates, preincubated minces, or mitochondrial preparations) were incubated in vitro with exogenous radioactive precursors. Hydrophis adrenal tissue was capable of synthesizing 17-deoxycorticosteroids from exogenous cholesterol, pregnenolone, progesterone, and DOC, but not from sodium [¹⁴C]-acetate. Products identified after incubation were pregnenolone, progesterone, 11β-hydroxyprogesterone, DOC, corticosterone, 18-hydroxycorticosterone, and aldosterone. The major product was corticosterone with lesser quantities also of 18-hydroxycorticosterone and aldosterone. In the case of the mitochondrial preparation 11β-hydroxyprogesterone predominated. No evidence for the biosynthesis of cortisol from cholesterol was found. Two types of kinetic incubation were employed: One sampled the incubation medium alone, while the other sampled both medium plus tissue. It was concluded that sampling the medium only did not allow the identification of the biosynthetic pathways operating in vitro. However, from sampling both the medium and the tissue it was concluded that both the C21-C11 and C11-C21 sequences of hydroxylation operated in the conversion of progesterone to corticosterone. The data contrast with those obtained from previous studies on cobra adrenal tissue, particularly with regard to the ability of sea snake adrenals in vitro to 18-oxygenate exogenous precursors.     

Successful cardiac preservation for 12 hours using nondepolarizing cold cardioplegia. A canine model

Abstract Isolated canine hearts were preserved for 12 h at 5 °C followed by normothermic reperfusion for 2 h. Dogs were divided into two groups: group 1 ( n = 7) received a nondepolarizing preservation solution in multidose, and group 2 ( n = 6) received single-flushed University of Wisconsin (UW) solution, both administered in multidose fashion. At the end o reperfusion, the myocardial adenosine triphosphate concentration and left ventricular systolic and diastolic function were preserved better in group 1 than in group 2. Myocardial mitochondrial ultra-tructural integrity was identical in the two groups. These results suggested that in a 124 heart preservation, nondepolarizing solution administered in multidose fashion protects the myocardium from the deleterious effects of hypothermia and cardioplegia better than UW solution.     

Trimetazidine： Is it a promising drug for use in steatotic grafts？

AIM:Chronic organ-donor shortage has led to theacceptance of steatotic livers for transplantation,despitethe higher risk of graft dysfunction or nonfunctionassociated with the ischemic preservation period ofthese organs.The present study evaluates the effects oftrimetazidine(TMZ)on an isolated perfused liver model.METHODS:Steatotic and non-steatotic livers werepreserved for 24 h in the University of Wisconsin(UW)solution with or without TMZ.Hepatic injury and function(transaminases,bile production and sulfobromophthalein(BSP)clearance)and factors potentially involved in thesusceptibility of steatotic livers to ischemia-reperfusion(I/R)injury,including oxidative stress,mitochondrialdamage,microcirculatory diseases,and ATP depletionwere evaluated.RESULTS:Steatotic livers preserved in UW solutionshowed higher transaminase levels,lower bile productionand BSP clearance compared with non-steatotic livers.Alterations in perfusion flow rate and vascular resistance,mitochondrial damage,and reduced ATP content weremore evident in steatotic livers.TMZ addition to UWsolution reduced hepatic injury and ameliorated hepaticfunctionality in both types of the liver and protectedagainst the mechanisms potentially responsible for thepoor tolerance of steatotic livers to I/R.CONCLUSION:TMZ may constitute a useful approachin fatty liver surgery,limiting the inherent risk of steatoticliver failure following transplantation.     

Pharmacological strategies against cold ischemia reperfusion injury

Importance of the field: Good organ preservation is a determinant of graft outcome after revascularization. The necessity of increasing the quality of organ preservation, as well as of extending cold storage time, has made it necessary to consider the use of pharmacological additives.

Areas covered in this review: The complex physiopathology of cold-ischemia–reperfusion (I/R) injury – and in particular cell death, mitochondrial injury and endoplasmic reticulum stress – are reviewed. Basic principles of the formulation of the different preservation solutions are discussed.

What the reader will gain: Current strategies and new trends in static organ preservation using additives such as trimetazidine, polyethylene glycols, melatonin, trophic factors and endothelin antagonists in solution are presented and discussed. The benefits and mechanisms responsible for enhancing organ protection against I/R injury are also discussed. Graft preservation was substantially improved when additives were added to the preservation solutions.

Take home message: Enrichment of preservation solutions by additives is clinically useful only for short periods. For longer periods of cold ischemia, the use of such additives becomes insufficient because graft function deteriorates as a result of ischemia. In such conditions, the preservation strategy should be changed by the use of machine perfusion in normothermic conditions.     

A proposed method for the evaluation of body fat in Japanese adults that predicts obesity

The present study was designed to develop a simple predictive equation for the percent body fat (%BF) in Japanese adults based on variables collected during health examinations. We hypothesized that a benchmark for defining metabolic syndrome and obesity could be based on %BF, which was measured by underwater weighing (UW) as a gold standard for body composition assessment. Thus, we developed a predictive equation for %BF derived from UW that may contribute to the assessment of obesity status, characterized by an excess accumulation of visceral or subcutaneous fat. The subjects were 810 Japanese participants (283 men, 527 women, ages 18-59 years). Anthropometric variables, including height, weight, 7 circumferences, and 8 skinfold thicknesses, were measured. The developed predictive equation was as follows: %BF = 10.558 × sex (1 for men; 2 for women) + 0.069 × age + 0.667 × body mass index + 0.314 × abdominal circumference − 35.881.The coefficient of determination (r²) was 0.69. The predicted %BF derived from this equation was highly correlated with UW-measured values and did not show underestimation or overestimation in either sex. These data suggested that this predictive equation for %BF can be used for all Japanese adults and does not require the use of medical equipment and special measurement techniques. By combining the equation for %BF developed in this study with a %BF cutoff value of metabolic syndrome and obesity (>25.0% in men and >30.0% in women), all Japanese adults can easily and conveniently assess obesity status.     

Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins

The aim was to evaluate the effect of HTK compared to UW and Euro-Collins (EC) on the initial graft function and long term graft survival in two prospective randomized studies. Only kidneys from heart-beating, kidney-only or kidney + heart donors were eligible for entry. Initial non-function (INF) was defined as the absence of life-sustaining renal function, requiring dialysis treatment on two or more occasions, during the first week after transplantation. To evaluate the contribution of the preservation solutions on INF in relation to other factors, a multivariate, 2-step logistic regression model was used. Randomization was performed between July 1990 and September 1992. The UW-HTK study comprised 342 donors and 611 transplants (UW: 168 donors and 297 transplants, HTK: 174 donors and 314 transplants). In the EC-HTK study 317 donors and 569 transplants were included (EC: 155 donors and 277 transplants, HTK: 162 donors and 292 transplants). INF occurred in 33 % of either HTK-(n = 105) or UW-(n = 99) preserved kidneys (P = NS), and in 29 % of the HTK-(n = 85) and in 43 % of the EC-(n = 119) preserved kidneys (P = 0.001). Multivariate analysis showed no significant influence of the preservation solution on the incidence of INF in the UW-HTK study, but factors contributing to INF were donor age, cause of death, retransplantation, and cold ischemic period. The EC-HTK study showed a significantly higher risk of INF, using EC as preservation, in addition to cold ischemic period and donor quality. The 3-year graft survival of HTK-preserved kidneys was 73 %, compared to 68 % for UW-preserved kidneys in the UW-HTK study (P = NS); while the 3-year graft survival of HTK preserved kidneys was 70 % compared to 67 % for EC-preserved kidneys in the EC-HTK study (P = NS). We can conclude that HTK is comparable to UW in its preservative abilities, using kidneys from heart-beating kidney-only donors, whereas EC as renal preservation solution should be avoided. Received: 2 November 1998 Received after revision: 10 August 1999 Accepted: 16 September 1999