Liver ischemia, catecholamines and preoperative condition influencing postoperative tachycardia in liver surgery

The aim of our study was to assess the influence of intraoperative hypoxic stress -unavoidably brought about by so called Pringle maneuver - on free and conjugated catecholamines during major hepatic resection. Judging from earlier results of fatigue-experiments in rats we also wanted to check the relationship between of poor general preoperative condition and conspicuously low triglyceride serum concentrations. The study included 26 patients with primary and secondary liver tumors. The mean age was 54 years (range 27-79). Twenty-one patients had segmental liver resections, 3 had hemihepatectomies and 2 hydatid cysts were treated by cystectomy. Blood samples were taken 2 days before and throughout surgery. Catecholamine plasma values were determined by high performance liquid chromatography. Statistical comparisons were made by t-test, ANOVA and chi square test. Free plasma catecholamines increased significantly during prolonged intraoperative ischemia (Pringle time 50-125 minutes). Patients with elevated intraoperative catecholamines had a significant correlation to postoperative episodes of tachycardia, and prolonged hospital stay. On the other hand, we could also see postoperative tachycardias in patients with short Pringle times (18-49 minutes) but with decreased preoperative serum triglycerides as an indicator of chronic stress and reduced general condition. Intraoperative hypoxic stress is associated with increased catecholamine values. Elevated catecholamines may well cause postoperative sinus-tachycardias (mean 20 hours) and are strongly related to postoperative liver failure and prolonged hospital stay.     

Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine

We have used immature commercial swine (13-25 kg) successfully in a variety of experimental cardiopulmonary surgical procedures in our laboratories since 1981. Multiple drug anesthetic protocols using barbiturates, narcotics, paralytic and antiarrhythmic agents have been employed in over 400 procedures per year. Complications, including fatal cardiac arrhythmias, have been greatly reduced by anesthetic protocols and surgical procedures developed through experience.     

Gastric resection; preoperative and postoperative care

Perhaps in no other field of surgery does attention to minute detail play so important a role in determining success as it does in gastric operations. As surgery of the stomach develops toward even greater security and favorable results can be expected with greater confidence, the several aspects of preoperative and postoperative care hitherto regarded as secondary demand closer consideration.     

Determination, proprerties and postnatal development of galactokinase in the swine liver]

1. Starting from the spectrophotometric method of Ballard optimal reaction conditions for measurements of galactokinase in piglet liver were systematically studied. These are (final conc. in the test): 100 mM triethanolamine-HCl buffer, 33 mM KCl, 16.5 mM NaF (inhibiting ATPase), 5 mM cysteine hydrochloride, 0.33 mM NADH2, 1 U pyruvate kinase and lactic dehydrogenase, 0.5 mM phosphoenolpyruvate, 1.5 mM galactose, 0.5 mM ATP and 1 mM MgCl2, final pH 7.5. 2. An optimal substrate concentration, a Mg: ATP-ratio of 2:1, pH-stability and addition of activators are important for the determination of galactokinase activity in the supernatant fraction of pig liver. 3. Using the optimized method galactokinase activity of pig liver in dependence on age, with particular reference to the perinatal period, was determined. 4. Galactokinase activity of liver of newborn piglets is 7 times that of adult pigs. In the suckling period the activity remains relatively constant at this high level and decreases remarkably immediately after weaning. 5. Galactokinase of liver of newborn piglets differs in kinetic properties (lower Km of ATP, higher maximal reaction velocity) from the enzyme of adult pigs, which is still insufficient to make sure the existence of two different forms of the enzyme.     

Bioengineering considerations in liver regenerative medicine

Background

Liver disease contributes significantly to global disease burden and is associated with rising incidence and escalating costs. It is likely that innovative approaches, arising from the emerging field of liver regenerative medicine, will counter these trends.

Main body

Liver regenerative medicine is a rapidly expanding field based on a rich history of basic investigations into the nature of liver structure, physiology, development, regeneration, and function. With a bioengineering perspective, we discuss all major subfields within liver regenerative medicine, focusing on the history, seminal publications, recent progress within these fields, and commercialization efforts. The areas reviewed include fundamental aspects of liver transplantation, liver regeneration, primary hepatocyte cell culture, bioartificial liver, hepatocyte transplantation and liver cell therapies, mouse liver repopulation, adult liver stem cell/progenitor cells, pluripotent stem cells, hepatic microdevices, and decellularized liver grafts.

Conclusion

These studies highlight the creative directions of liver regenerative medicine, the collective efforts of scientists, engineers, and doctors, and the bright outlook for a wide range of approaches and applications which will impact patients with liver disease.

     

Stem cells, cell transplantation and liver repopulation

Liver transplantation is currently the only therapeutic option for patients with end-stage chronic liver disease and for severe acute liver failure. Because of limited donor availability, attention has been focused on the possibility to restore liver mass and function through cell transplantation. Stem cells are a promising source for liver repopulation after cell transplantation, but whether or not the adult mammalian liver contains hepatic stem cells is highly controversial. Part of the problem is that proliferation of mature adult hepatocytes is sufficient to regenerate the liver after two-thirds partial hepatectomy or acute toxic liver injury and participation of stem cells is not required. However, under conditions in which hepatocyte proliferation is blocked, undifferentiated epithelial cells in the periportal areas, called "oval cells", proliferate, differentiate into hepatocytes and restore liver mass. These cells are referred to as facultative liver stem cells, but they do not repopulate the normal liver after their transplantation. In contrast, epithelial cells isolated from the early fetal liver can effectively repopulate the normal liver, but they are already traversing the hepatic lineage and may not be true stem cells. Mesenchymal stem cells and embryonic stem cells can be induced to differentiate along the hepatic lineage in culture, but at present these cells are inefficient in repopulating the liver. This review will characterize these various cell types and compare the properties of these cells and the conditions under which they do or do not repopulate the liver following their transplantation.     

尿道下裂患者术前术后尿道细菌的研究

目的了解尿道下裂患者尿道修复前后尿道及其周围细菌的分布,为临床预防尿道下裂术后感染提供依据。方法采集30例尿道下裂患者术前尿道、会阴部,术后重建尿道、会阴部皮肤作细菌分离、培养、鉴定、统计分析、药敏试验。结果术前术后尿道与会阴部细菌分布差异无显著性（P〉0．05）,有革兰阳性菌表皮葡萄球菌、肠球菌等,革兰阴性菌变形杆菌、阴沟肠杆菌、大肠埃希菌等,以表皮葡萄球菌占多数。结论术后重建尿道内存在的细菌由会阴部皮肤表面细菌转移而入。菌株以革兰阳性菌表皮葡萄球菌占多数,菌株耐药率较高,临床选择药物要慎重。     

Vascularized composite islet-kidney transplantation in a miniature swine model

Previous work from this laboratory has demonstrated that transplantation of allogeneic thymic tissue as part of a composite vascularized graft is far more successful in terms of both engraftment and long-term survival than transplantation of thymic tissue or cells alone. We have subsequently extended this concept to transplantation of allogeneic islets, comparing survival of islet cell suspensions to that of vascularized composite islet-kidneys (IK), prepared by injection of autologous islets underneath the renal capsule 2-3 months prior to allogeneic transplantation of the composite organ. We have utilized partially inbred miniature swine with defined MHC loci as the experimental large animals for this study, permitting reproducible transplantation across specific MHC barriers. Composite IK have been transplanted successfully across minor and full MHC mismatch barriers, using treatment regimens previously demonstrated to induce long-term tolerance of kidney allografts across these barriers. IK allografts containing ≥5000 islet equivalents (IE)/kg recipient body weight were found capable of reversing surgically induced diabetes, while injection of comparable numbers of purified islets via the portal vein or under the renal capsule did not. Studies are also being directed toward preparation of autologous “thymo-islet-kidneys” (TIK), for potential use as xenografts, in which the thymic component is intended to induce tolerance and the islets to reverse diabetic hyperglycemia. The use of both types of composite organ transplants may eventually be applicable to the treatment of type I diabetic patients suffering from end-stage diabetic nephropathy.     

Multiple vascular and gastric cannulation of swine for studies of gastrointestinal, liver, and peripheral tissue metabolism.

The implantation of multiple chronic indwelling vascular cannulas and of a gastric cannula into swine was described. Technics for housing, care, and handling of the animals pre- and post-surgically were established to reduce the incidence of infection and to allow collection of urine and feces in metabolic studies. This regimen has been used in 20 gilts to study absorption, tissue distribution, metabolism, and excretion of nutrients. On the average, the cannulas remained patent for 4 wk.     

Recurrent pilonidal cyst and sinus; a plan of preoperative preparation,operation and postoperative care

Evaluation ten years following radical excision and primary closure of recurrent pilonidal cysts led to the conclusion that the method of preoperative and postoperative care and the surgical technique employed gave satisfactory results. In 50 patients operated upon, the duration of symptoms varied from ten days to six years. Primary healing was achieved in all but one case in which there was slight skin overlapping. Thirty-three of the 50 patients were located for appraisal at the end of ten years. Three had had recurrences. The procedure involved eradication of acute infection preoperatively, wide, en bloc radical excision, with primary closure reattaching flaps centrally to the presacral fascia, and drainage of the depths of the wound.     

Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models

Streptozotocin (STZ)-induced diabetes mellitus (DM) offers a very cost-effective and expeditious technique that can be used in most strains of rodents, opening the field of DM research to an array of genotypic and phenotypic options that would otherwise be inaccessible. Despite widespread use of STZ in small animal models, the data available concerning drug preparation, dosing and administration, time to onset and severity of DM, and any resulting moribundity and mortality are often limited and inconsistent. Because of this, investigators inexperienced with STZ-induced diabetes may find it difficult to precisely design new studies with this potentially toxic chemical and account for the severity of DM it is capable of inducing. Until a better option becomes available, attempts need to be made to address shortcomings with current STZ-induced DM models. In this paper we review the literature and provide data from our pancreatic islet transplantation experiments using single high-dose STZ-induced DM in NCr athymic nude mice with hopes of providing clarification for study design, suggesting refinements to the process, and developing a more humane process of chemical diabetes induction.     

Determination and postnatal development of fructokinase activity in swine liver]

Starting from the spectrophotometric method, described in ADELMAN et al., optimal reaction conditions for the measurement of fructokinase (ketohexokinase) in pig liver were systematically studied. It was necessary to increase the concentration of the substrate and further to lower the concentration of ATP for an optimal Mg: ATP-radio of 2:1. Using the optimized method fructokinase activity was determined in pig liver in relation to age, beginning from the last days of pregnancy to puberty. In liver of fetuses and newborn piglets during the first two days of life no or only a minute activity of the fructokinase was recorded. Therefore, the high level of fructose in fetal blood results from the inability of the fetus to metabolize fructose synthezised in the placenta or the fetal organs. At the end of the first week of life the activity of fructokinase was 10 times, after the second week 15-20 times higher than at birth. This high level remains constant during the suckling period and after weaning. For this reason, piglets after the first week of life are able to metabolize fructose and after the third week to form glucose and to release it into circulation. In adult pigs the activity of fructokinase in the liver decreases slightly. It corresponds-as in rat and human-to the elimination rate of experimentally applied fructose from the circulation. Therefore, this enzyme even in pigs is of significant importance for the utilization of fructose.     

Relationships of liver weight, cholesterol, albumin and alpha2-macroglobulin concentrations with ovarian function in swine

In two genetic swine models selected for diversity in ovulation rates (White composite controls and ovulation rate selection line, n = 131; 1/2 White composite: 1/2 Meishan crossbreds, n = 387), a positive relationship was established with liver weight and ovulation rate (P < 0.01). Serum changes of cholesterol, albumin and alpha2-macroglobulin were monitored during various stages of the luteal phase and follicular phase (days 17 and 19 of the estrous cycle; 1/2 White composite: 1/2 Meishan gilts). Serum cholesterol concentrations increased with liver weights (r = 0.19; P < 0.01) and corpora lutea numbers (r = 0.14; P < 0.01). Albumin concentrations were negatively correlated with corpora luteal numbers (r = -0.3; P < 0.01) but had no relationship with liver weight. Serum concentrations of alpha2-macroglobulin were not related to liver weight or corpora lutea numbers. Circulating concentrations of cholesterol and alpha2-macroglobulin increased with day of the estrous cycle (P < 0.01). Testosterone concentrations were inversely related to circulating cholesterol concentrations during the estrous cycle, but testosterone concentrations on day 17 or 19 of the cycle were unrelated to corpora lutea numbers. Concentrations of estrone on day 17 or 19 (as an index of follicles destined to ovulate) were also not related to numbers of corpora lutea. Many interactions between liver and ovarian function involving metabolic and endocrine systems are plausible, but defined mechanisms resulting in coordinate increases in liver weight and ovulation rates are presently unelucidated.     

Lesions in the liver of guinea-pigs infected with the swine lungworm, Metastrongylus apri

Clear spot lesions were formed on the liver surface in guinea-pigs repeatedly infected with swine lungworm, Metastrongylus apri. The largest lesion, measuring 0.25 cm in diameter, was hard and yellow and showed a large granuloma in the lobule. The nematode larva was located at the centre of the lesion. This finding is likely to be an example of erratic parasitism in guinea-pigs with metastrongylidiasis.     

Determination and developmental changes in carbonic anhydrase III in swine liver.

1. CA-III was measured by enzyme-immunoassay in the livers of male and female swine aged from the fetus to 5 years old. 2. No sexual dimorphism in porcine liver could be detected at 6 months, but stag showed twice as much as swine of the same age. 3. The concentration of CA-III in the liver increased during development up to 6 months of age, followed by decline due to senescence.