Intraoperative evaluation of EuroCollins and University of Wisconsin preservation solutions in patients undergoing hepatic transplantation.

The effects of cold liver preservation with two solutions, EuroCollins and University of Wisconsin, were compared in terms of hepatic function and hemodynamic parameters obtained intraoperatively during orthotopic liver transplantation. Data from 101 consecutive liver transplants were analyzed retrospectively, comparing 50 grafts preserved with EC with 51 preserved with UW solution. Hepatic hemodynamics parameters included portal venous and hepatic arterial flows, determined with an electromagnetic flowmeter. Vascular pressures, blood gases and pH measurements were obtained directly from the portal vein, hepatic vein, and peripheral artery. Serial measurements of serum glucose, SGOT, and SGPT were performed following reperfusion. Preservation related graft failure occurred in 4 of 50 patients in the EC group, but not in any of 51 patients in the UW group. Cold Ischemia time (hours +/- SEM) was significantly prolonged in UW group (7.23 +/- 1.4 vs. 5.21 +/- 0.9). Rate of temperature change (degrees C/hour +/- SEM) after reperfusion was similar in both groups (EC = 0.62 +/- 0.35, UW = 0.71 +/- 0.4). Peak serum SGOT, SGPT, and glucose levels following reperfusion were significantly higher in the EC group, as was PRBC and FFP administration. Systemic hemodynamics in both groups of patients were similar. However, UW-preserved grafts demonstrated a significantly higher hepatic artery resistance, with no other differences in hepatic hemodynamics seen. UW solution appears to extend cold ischemia time without adversely affecting liver function. However, the etiology and clinical significance of the increased hepatic artery resistance seen in UW-stored liver grafts are unknown.

Perioperative renal function in patients undergoing orthotopic liver transplantation. A randomized trial of the effects of verapamil.

Patients who undergo orthotopic liver transplantation often experience a significant drop in GFR postoperatively. Postulated mechanisms include intraoperative hemodynamic changes, suboptimal renal perfusion during the anhepatic stage, and cyclosporine administration. We undertook a prospective double-blind study to investigate these factors, as well as to determine the protective effects of verapamil on perioperative renal function. Twenty-five patients with normal renal function undergoing OLT received either placebo (n = 13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was administered until after reperfusion of the graft liver, and venovenous bypass (VVB) was utilized in all cases. Patients completing six weeks of the study experienced 61% and 48% decreases in GFR within the placebo and verapamil groups respectively. A significant decrease in GFR occurred in the placebo group between one and six weeks post-OLT, and a significant drop in GFR occurred in the verapamil group by one week post-OLT. Differences between the groups were not significant, however. Systemic, renal, and hepatic hemodynamics were similar at all times between groups, and renal hemodynamics and urine output were unchanged during VVB. We conclude that (1) perioperative factors do not contribute to renal dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics during the anhepatic phase; (3) CsA is the most likely causative agent for post-OLT renal dysfunction; and (4) intraoperative verapamil serves no protective role, as administered in this study.

Danger of amiodarone therapy and elevated inspired oxygen concentrations in mice.

Our study showed a statistically significant incidence of pulmonary edema in mice receiving amiodarone and 100% oxygen. This finding, together with a variety of clinical reports, indicates that in patients receiving amiodarone therapy, FiO2 should be maintained at the lowest possible level, consistent with adequate oxygenation.

Catalytic and immunologic characterization of hepatic and lung cytochromes P450 in the polar bear.

The Arctic Ocean is subject to considerable influx of anthropogenic pollutants including halogenated organic compounds. The polar bear (Ursus maritimus) is at the top of the arctic marine food web and is an ideal species for monitoring the level and distribution of contaminants in the arctic ecosystem. As the first step in the development of a biological method for assessing the functional exposure of polar bears to xenobiotics, biochemical studies were undertaken to characterize polar bear cytochromes P450. Liver and lung samples were obtained in the field from four, freshly killed, adult, male polar bears and immediately frozen at -196 degrees. Microsomes were subsequently prepared and used for the measurement of total cytochrome P450 content and aminopyrine N-demethylase, benzphetamine N-demethylase, ethylmorphine N-demethylase, p-nitrophenol hydroxylase and testosterone hydroxylase activities. Immunoblots containing hepatic and lung microsomal samples from the polar bears were probed using antibodies generated against several purified rat cytochrome P450 isozymes. Monoclonal antibody to rat cytochrome P450 1A1 and polyclonal antibodies to rat cytochromes P450 1A1, 2B1 and 3A1, as well as antibody to epoxide hydrolase, cross-reacted to varying degrees with polar bear hepatic microsomes. In addition, polyspecific antibody to the rat cytochrome P450 2C subfamily gave several immunostained protein bands, but antibodies specific to rat cytochrome P450 2C7 and 2C13 did not react, while antibody specific to cytochrome P450 2C11 yielded an ambiguous result. Except for anticytochrome P450 2B1 and polyspecific antibody to the cytochrome P450 2C subfamily, the antibodies listed above did not cross-react with polar bear lung microsomes at the protein concentrations used. The results demonstrate that polar bear liver contains multiple forms of cytochrome P450 that are catalytically active toward diverse substrates and that several of these forms are immunochemically related to rat cytochrome P450 isozymes. Immunochemical homologues of rat cytochrome P450 1A, 2B, 2C and 3A subfamilies, and of rat epoxide hydrolase are present in polar bear liver. In addition, the polar bears all had high levels of immunoreactive cytochrome P450 1A and 2B proteins, probably as a consequence of induction by environmental contaminants.

Liver transplant in complete situs inversus: a case report.

BACKGROUND: Several technical solutions have been proposed for patients with situs inversus (SI) needing liver transplantation. This report describes the hepatic replacement in a patient with complete SI with dextrocardia. In the only other reported patient with complete SI the donor right lobe was placed over the vertebral column and the stomach to align the donor cava with that of the recipient. METHODS: A 45-year-old woman with complete SI, suffering from Laënnec's cirrhosis with frequent upper gastrointestinal hemorrhages, underwent transplantation in June 1991. The recipient weighed 48.2 kilograms and was 155 centimeters tall. The donor weighed 77.3 kilograms and was 188 centimeters tall. The weight of the native liver was 1934 grams, and the donor liver weighed 1595 grams. RESULTS: At hepatectomy of the native liver an intact vena cava was left behind. Donor liver was rotated 90 degrees to the left, making the donor left lobe point into the left iliac fossa and the donor right lobe fall into the recipient hepatic fossa. Donor infrahepatic vena cava was sewn end-to-side to the recipient vena cava. Suprahepatic vena cava was oversewn. Donor and recipient hila were well aligned, allowing a standard arterial reconstruction and a choledocholedochostomy. Patient's recovery was uneventful with no problems during the following 6 months. CONCLUSIONS: The proposed technique for a patient with complete SI and dextrocardia offers several advantages: no need to downsize the donor in comparison with the recipient; no need for cutdown of the liver; no risk of kinking of the venous outflow; hepatic hila are aligned; and it allows for a standard arterial and biliary reconstruction. We recommend this technique as a procedure of choice for patients with SI and an intact vena cava.

Polar bears make little use of terrestrial food webs: evidence from stable-carbon isotope analysis.

The mean stable-carbon isotope ratios (δ13C) for polar bear (Ursus maritimus) tissues (bone collagen -15.7‰, muscle -17.7‰, fat -24.7‰) were close to those of the same tissues from ringed seals (Phoca hispida) (-16.2‰, -18.1‰, and -26.1‰, respectively), which feed exclusively from the marine food chain. The δ13C values for 4 species of fruits to which polar bears have access when on land in summer ranged from -27.8 to -26.2‰, typical of terrestrial plants in the Arctic. An animal's δ13C signature reflects closely the δ13C signature of it's food. Accordingly, the amount of food that polar bears consume from terrestrial food webs appears negligible, even though some bears spend 1/3 or more of each year on land during the seasons of greatest primary productivity.

The mechanical properties of the dentine and cement of the tusk of the narwhal Monodon monoceros compared with those of other mineralized tissues.

Values for Young's modulus of elasticity, ultimate and yield stresses, ultimate and yield strains, work under the stress-strain curve and work of fracture were obtained from tensile and bending tests on specimens of narwhal tusk dentine and cement, femoral bone from young and mature cattle, and reindeer antler. Compared with the cattle bone the narwhal tissues had low Young's moduli, low yield stresses, rather low ultimate stresses and high ultimate strains. In all these properties they were similar to reindeer antler. The calcium content and hardness of the narwhal tissues were compared with those of human and cattle dental tissues. The narwhal dentine was considerably softer and less mineralized than human and cattle dentine. Human cementum was softer and less mineralized than cattle cementum, and was like narwhal cementum. In general, the mechanical properties of the narwhal tusk tissues were as would be expected from their mineral content, except that the stiffness of the cementum was low. It is likely that narwhal dentine is not very similar to human and cattle dentine in its mechanical properties.

Body burdens and tissue concentrations of organochlorines in polar bears (Ursus maritimus) vary during seasonal fasts.

Lipophilic organochlorines (OCs) are ingested by mammals through their foods and are generally stored in adipose tissue depots. For some species, such as polar bears, the size of these depots can fluctuate seasonally by several-fold. However, the effect of these fluctuations on the fate of stored OCs in an animal with such labile lipid depots is unknown. We determined the whole body burden and tissue concentrations of OCs in free-ranging polar bears categorized by age (cubs-of-the-year, yearlings and adults) and sex before and after a fast averaging 56 days. Adipose tissue, plasma, and milk samples were analysed for sum of chlorobenzenes (sigma-ClBzs), hexachlorocyclohexanes (sigma-HCHs), chlordanes (sigma-CHLORs), dichlorodiphenyltrichloroethane compounds (sigma-DDTs) and polychlorinated biphenyls (sigma-PCBs). Decline in body mass during fasting ranged from 0.2 kg/day for cubs-of-the-year to 0.9 kg/day for sub-adult and adult males. Although all bears showed a decline in both lipid and lean mass during fasting, patterns of OC whole body burden changes were not consistent among compounds and bear classes. The burdens of sigma-DDTs declined by 11-50% for most bears during fasting, those of sigma-CHLORs declined by 67% during fasting in sub-adult and adult males but remained constant for all females, indicating male-specific metabolism of sigma-CHLORs. As fat depots became depleted, OC concentrations in the remaining adipose tissue varied; sigma-DDTs and sigma-HCHs declined while those of sigma-CHLORs and sigma-PCBs generally increased. Thus. within a 3-4 month fast, most polar bears were able to significantly rid their adipose tissue of sigma-DDTs and sigma-HCHs. Burdens of sigma-CHLORs (except males), sigma-ClBzs and sigma-PCBs remained constant for all classes of bears, therefore there was no significant excretion or metabolism during the fast of the specific congeners in these compound classes typically found in polar bears. The ratio of plasma/adipose tissue and milk/adipose tissue OC concentrations was the same for before and after the fast indicating that OC concentrations in polar bears are probably at a steady state among various body compartments. Concentrations of sigma-CHLORs and sigma-PCBs in milk almost doubled during the fast. As a consequence of this rise in milk OC concentrations, the whole body concentrations of these compounds increased in nursing cubs. Since developing young may be susceptible to the effects of environmental contaminants, the increased exposure of nursing cubs to OCs during a fast by their mothers is noteworthy.

Preliminary results of fasting on the kinetics of organochlorines in polar bears (Ursus maritimus).

We determined concentrations of polychlorinated biphenyls (PCBs), chlordanes (CHLORs), chlorobenzenes (CBzs), hexachlorocyclohexanes (HCHs), and dichlorodiphenyltrichloroethane (DDT) and its metabolites (DDD and DDE) in the tissues of individual polar bears (Ursus maritimus) before and after a lengthy period of fasting. Polar bears are an ideal model for such studies. They undergo one of the most extreme fasts known for any mammal and are located at the top of a long food chain, thus biomagnification of organochlorines (OC) is significant. Adipose tissue and milk were collected from different reproductive classes of adult females (solitary/pregnant, with cubs-of-the-year, with yearling cubs) and were analyzed for organochlorine content. As the fasting period progressed and adipose reserves decreased, concentrations of some organochlorines in the adipose tissue and milk increased on a lipid weight basis. The transfer of contaminants from mothers to offspring thus also increases with duration of the fasting period. This phenomenon could adversely influence the survival and growth of cubs during the critical early phase of their development.

The management of a child with a major airway abnormality.

A technique of guided blind intubation is reported utilizing a small-bore needle and guide wire passed transtracheally. The advantage of this technique is that because of the minimal trauma involved, it can be used in small infants as well as adults.

Use of yohimbine hydrochloride to reverse immobilization of polar bears by ketamine hydrochloride and xylazine hydrochloride.

Yohimbine hydrochloride (YH) effectively reversed the immobilizing effects of ketamine hydrochloride (KH) combined with xylazine hydrochloride (XH) in 48 wild polar bears (Ursus maritimus) handled in the summer. Single intravenous doses of YH ranging between 0.029 and 0.198 mg/kg resulted in a median time of 10 min (range: 1-123 min) to post-injection recovery from KH-XH immobilization. Convulsions and muscle twitching were observed in some bears after YH was administered and one death occurred. Median respiratory rate and heartbeat rate increased from 5 br/min to 12 br/min and 51 BPM to 79 BPM, respectively, soon after yohimbine was administered. The median time to recovery after KH-XH administration, including processing and handling time, was 113 min for bears administered yohimbine and 202 min for bears not administered YH. After YH-induced recovery, polar bears showed signs of reduced awareness and many remained recumbent for undetermined periods although they could coordinate movements, stand, and walk or run if disturbed. YH proved to be a useful antagonist to immobilization induced by KH-XH in a field situation.

Cardiopulmonary response of anesthetized polar bears to suspension by net and sling.

Since 1995, at least three polar bears (Ursus maritimus) have died in the area of Churchill (Manitoba, Canada) as a direct result of being suspended in a net during helicopter-assisted translocations. To assess and improve methods of suspending anesthetized polar bears, we conducted a study during November 1997 to determine the cardiopulmonary responses of eight captive polar bears to suspension by net and by sling. Each bear was anesthetized on two occasions in which the sequence of activities followed and the type of data collected was identical, with only the method of suspension differing. Control data obtained from 11 captive polar bears during 1995-96 was included in the statistical analyses of cardiopulmonary data to help clearly differentiate the cardiopulmonary effects of suspension from those of drug metabolism. Suspending polar bears above the ground by net caused acute hypertension (e.g., 17 to 49% increase in mean arterial pressure), possibly as a result of increased venous return due to body compression. Increased arousal (e.g., head, tongue, and limb movement) also occurred consistently during net-suspension and suggested a stress response. Surprisingly, most suspended bears showed little change in blood gas values, but at least one bear became hypoxemic (i.e., PaO2 < 60 mm Hg) with each method of suspension. Because of the potential health risks of hypertension and hypoxemia, we recommend modifying the method by which polar bears are suspended with the goal of reducing body compression.

Reversible immobilization of free-ranging polar bears with medetomidine-zolazepam-tiletamine and atipamezole.

The objective of this study was to determine if the potent alpha 2 agonist, medetomidine, and its specific antagonist, atipamezole, could be effectively used to immobilize polar bears (Ursus maritimus). Specifically, our goal was to develop a drug combination containing medetomidine that addressed some of the problems such as prolonged recovery time, non-reversibility, and poor analgesia that have been identified with the currently preferred drug combination, zolazepamtiletamine (Telazol or Zoletil). During 1995 and 1996, 51 free-ranging polar bears along the western coast of Hudson Bay, Canada, were immobilized with a combination of medetomidine, zolazepam, and tiletamine (MZT). Immobilization with MZT was characterized by a short induction time, low volume, reliable and predictable immobilization and reversibility, adequate analgesia, and relative safety in handling for field personnel. Few adverse physiological effects were observed in any target animals with the exception of a single bear which convulsed and died shortly after it was reversed from anesthesia with atipamezole. We conclude that MZT is an effective drug combination for immobilizing polar bears. However, because of an unexplained mortality, further investigation of the physiological effects of MZT and atipamezole is warranted.

Pharmacokinetics and tissue residues of Telazol in free-ranging polar bears.

A pharmacokinetic and tissue residue study was conducted to assess the risks associated with human consumption of polar bears in arctic Canada that have been exposed to the immobilizing drug Telazol, a mixture of tiletamine hydrochloride and zolazepam hydrochloride. Twenty-two bears were remotely injected with about 10 mg/kg of Telazol. Following immobilization, serum samples were collected serially at regular intervals until the bears awakened. Sixteen of the bears were relocated and killed under permit by local hunters at various times from 0.5 to 11 days after dosing. Serum, kidney, muscle and adipose tissue samples were collected immediately after death. All samples were stored at -70 C until analysis by HPLC. The concentration-time data of tiletamine and zolazepam in serum during the immobilization period were fitted to curves by computer and the pharmacokinetic parameters assessed. In addition, the serum and tissue samples collected at the time of death were analyzed for both parent drugs, for one metabolite of tiletamine (CI-398), and for three metabolites of zolazepam (metabolites 1, 2 and 4). A one-compartment model with first-order absorption and elimination best fit the time-series data for the drugs in serum during the immobilization period. This model gave half-lives (mean +/- SE) for tiletamine and zolazepam of 1.8+/-0.2 h and 1.2+/-0.08 h, respectively, clearance values of 2.1+/-0.3 l x h(-1) x kg(-1) and 1.1+/-0.1 l x h(-1) x kg(-1), and volumes of distribution of 5.2+/-0.6 l/kg and 1.8+/-0.2 l/kg. The concentrations of both drugs and their metabolites declined rapidly to trace levels by 24 h post-dosing, although extremely low concentrations of some metabolites were encountered sporadically over the entire sampling period. In particular, zolazepam metabolite 2, remained detectable in fat and muscle tissue at the end of the study, 11 days after dosing. It was concluded that during immobilization, both tiletamine and zolazepam levels decline rapidly in a monoexponential fashion, and their pharmacokinetic parameters in polar bears are similar to those observed in other species. Tissue levels of the drugs and their metabolites declined sufficiently rapidly that individuals eating meat from exposed bears would be unlikely to experience pharmacological effects from the drugs. Nevertheless, slight exposure to the drugs and/or their metabolites might be possible for an indeterminate time after dosing.

Hemodynamic changes during laparoscopic cholecystectomy in patients with severe cardiac disease.

STUDY OBJECTIVE: To evaluate the hemodynamic changes and need for pharmacologic interventions during laparoscopic cholecystectomy in patients with severe cardiac dysfunction. DESIGN: Prospective open study. SETTING: University hospital. PATIENTS: 17 ASA physical status III and IV patients with severe cardiac dysfunction undergoing elective laparoscopic cholecystectomy. INTERVENTIONS: A standardized general anesthetic and surgical technique was used for all patients. In addition to routine monitoring, invasive hemodynamic monitoring included radial and pulmonary artery (PA) cannulation. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded prior to induction of anesthesia, 5 minutes after induction of anesthesia but prior to incision, 5 minutes after carbon dioxide (CO2) insufflation and head-up tilt, every 10 minutes after change of position, after deflation of the abdomen and return to supine position, and 10 minutes after attaining supine position. Need for any pharmacologic interventions [to maintain mean arterial pressure (MAP) < 100 mmHg and/or systemic vascular resistance (SVR) < 2,000 dynes sec/cm-5, and/or cardiac index (CI) > 1.5 L/min/m2] and the incidence of any myocardial morbidity and mortality was noted. CI decreased significantly (p < 0.05) following insufflation and remained low until exsufflation. MAP, SVR, and PA occlusion pressure increased significantly (p < 0.05) after CO2 insufflation. Three of the 17 patients required administration of nitroglycerin to maintain the MAP and SVR within the accepted limits, one of whom also required administration of dobutamine to maintain CI. There was no myocardial morbidity or mortality in the perioperative period. CONCLUSION: Laparoscopic cholecystectomy in patients with severe cardiac dysfunction results in significant hemodynamic changes.

Anesthesia of polar bears (Ursus maritimus) with zolazepam-tiletamine, medetomidine-ketamine, and medetomidine-zolazepam-tiletamine.

A 1:1 combination (by weight) of zolazepam and tiletamine is the drug of choice for anesthetizing polar bears (Ursus maritimus), but recovery time is prolonged when additional doses are administered. Recoveries may last 24 hr and may threaten the health of the bears. We compared the anesthetic effects of zolazepam-tiletamine (ZT) with those of medetomidine-ketamine (MK) and medetomidine-zolazepam-tiletamine (MZT) in 93 free-ranging polar bears. The MZT combination was administered in smaller dose and volume, resulted in more rapid, safer, and more predictable induction, provided more reliable anesthesia, and was safely reversed with atipamezole. Frequent occurrence of sudden recoveries during anesthesia with MK limited our use of this combination. MK and MZT sometimes caused apnea and bradycardia initially and hyperthermia at increased ambient temperatures. Hypoxemia occurred transiently with all combinations. When anesthesia with ZT and MK exceeded 1 hr, frequent necessary top-up doses caused irregular physiologic function. ZT is recommended for short duration anesthesia (< or = 1 hr), but MZT is better for anesthesia of longer duration and under circumstances where reversibility is desirable.