Time to adequate oxygenation following ventilation using the Enk oxygen flow modulator versus a jet ventilator via needle cricothyrotomy in rabbits.

INTRODUCTION: Limited information is available on the management of the 'cannot intubate, cannot ventilate' (CICV) situation in infants. We compared the time to achieve adequate oxygenation following rescue ventilation using the Enk oxygen flow modulator (OFM) with a jet ventilator in a simulated CICV situation using the rabbit as an infant respiratory model. METHODS: Following institutional ethics committee approval, needle cricothyrotomy was performed under direct vision in nine anesthetized rabbits following surgical exposure of the larynx. After ensuring adequate level of anesthesia and analgesia, and confirming proper positioning of the 18G cannula, apnea was induced by the administration of myorelaxant and the SpO2 was allowed to drop to 75% before initiating rescue ventilation via either the OFM or jet ventilator. RESULTS: Five rabbits were ventilated with the OFM and four with the jet ventilator. Ventilation was maintained with either device for 15 min. All rabbits were successfully rescued using either device. There was no statistical difference in the time required for SpO2 to return to 80%, 85%, 90%, and 95%. CONCLUSIONS: Both devices facilitated successful rescue ventilation through a needle cricothyrotomy.

Therapeutic potential of cardiotrophin 1 in fulminant hepatic failure: dual roles in antiapoptosis and cell repair.

HYPOTHESIS: Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF). DESIGN: Rat model with FHF induced by D-galactosamine (D-gal). SETTING: Fulminant hepatic failure is a rapidly progressive disease that lacks effective nonsurgical treatment. Cardiotrophin 1 is a member of the interleukin 6 family that can protect cells from damage in some animal disease models. ANIMALS: A rat model of FHF was induced by an intraperitoneal injection of D-gal (1.4 g/kg of body weight). Cardiotrophin 1 was administered at different time points after D-gal injection. RESULTS: Administration of CT-1 at 12 and 18 hours had a survival rate of 80% (12/15) and 70% (7/10), respectively, which was significantly higher than that of nontreatment (28% [5/18]). In addition, improvement of liver histologic findings, shortening of activated clotting time, and decrease in serum levels of total bilirubin and alanine aminotransferase were detected with CT-1 treatment. Administration of CT-1 decreased apoptotic cells and increased Ki-67 cells in the liver tissues. In vitro, CT-1 administration significantly decreased apoptotic cells and sequentially down-regulated the expression of proapoptotic molecules and up-regulated the expression of antiapoptotic molecules at different culture periods. D-galactosamine culture induced morphologic damage in a hepatocyte cell line, which was greatly improved by CT-1 administration. In addition, CT-1-treated cells demonstrated increased expression of glycoprotein 130 and up-regulation of cyclin D1 and heat shock protein 90. CONCLUSION: Cardiotrophin 1 may improve the outcome of D-gal-induced FHF through its effects on antiapoptosis and cell repair.

The potential role of hypoxia inducible factor 1alpha in tumor progression after hypoxia and chemotherapy in hepatocellular carcinoma.

This study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. Hypoxia was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. High-dose sodium salicylate was administered to achieve transcriptional blockade. Significant prolongation of animal survival was observed in the groups receiving hepatic artery ligation with cisplatin or sodium salicylate. Massive tumor cell necrosis and apoptosis were found in the ligation and all of the combined treatment groups. Up-regulation of hypoxia inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at both mRNA and protein levels were detected in the groups receiving ligation and ligation with cisplatin, whereas a decreased level of von Hippel-Lindau tumor suppressor protein was identified in the group receiving ligation with cisplatin. Sodium salicylate enhanced expression of von Hippel-Lindau tumor suppressor protein but down-regulated HIF-1alpha and VEGF levels after ligation with or without cisplatin. An increased number of activated hepatic stellate cells in the tumors were observed in the ligation and ligation with cisplatin groups, whereas they were greatly reduced by sodium salicylate. In vitro study revealed that under hypoxic condition, both cisplatin and sodium salicylate could remarkably augment P53 and caspase 3 levels. Cisplatin stimulated HIF-1alpha up-regulation, whereas sodium salicylate suppressed HIF-1alpha expression. In conclusion, tumor progression after hypoxia and chemotherapy might be related to up-regulation of HIF-1alpha and subsequent VEGF production, and transcriptional blockade by sodium salicylate could enhance the therapeutic efficacy of hypoxia and chemotherapy.

Galactosamine-induced fulminant liver failure--observation in a porcine model.

Fulminant hepatic failure can only be treated successfully by liver transplantation, which, however, is not always available. To "bridge" the patient with fulminant hepatic failure until a liver graft is available, various forms of liver support devices had been designed but they were not uniformly successful. To prove the efficacy of a liver support device for fulminant hepatic failure, testing in an animal model is necessary. We attempted to induce a pig model with fulminant hepatic failure by administering galactosamine into pigs and reported the observation. Three pigs were given a dose of 0.5 gm/kg of galactosamine and five pigs were given 1 gm/kg of galactosamine. One pig receiving 0.5 gm/kg galactosamine survived after manifestation of liver failure, while all the other pigs died. The two pigs receiving 0.5 gm/kg galactosamine survived longer than the five pigs receiving 1 gm/kg galactosamine. Before death, a significant elevation of parenchymal liver enzymes, lactate dehydrogenase, bilirubin, bile acid, ammonia, tumour necrosis factor-alpha, activated clotting time, a decrease of platelet concentration, ketone bodies ratio, blood glucose and plasma albumin, and serious impairment of indocyanine green clearance were indicated. At post-mortem, severe liver necrosis was observed. The model may be suitable for testing the efficacy of liver support device for fulminant hepatic failure, preferably 24-48 hours after administration of galactosamine.

Porcine liver: morphologic characteristics and cell viability at experimental radiofrequency ablation with internally cooled electrodes.

PURPOSE: To evaluate morphologic characteristics and cell viability of radiofrequency ablation zones in porcine liver. MATERIALS AND METHODS: Approval of the study protocol was obtained from the Ethics Committee on Use of Live Animals for Teaching and Research at University of Hong Kong. Internally cooled electrodes were used to produce 120 ablated zones ex vivo and 60 ablated zones in vivo with single electrodes (1-, 2-, and 3-cm exposed lengths) or clustered electrodes (1.0-, 2.0-, and 2.5-cm exposed lengths) at 4, 8, 12, and 16 minutes of ablation (ex vivo) and 8 and 12 minutes of ablation (in vivo). Morphologic measurements of each ablated zone were performed. Cell viability in each ablated zone was assessed qualitatively with histochemical staining and quantitatively with measurement of intracellular adenosine 5'-triphosphate (ATP) concentration. RESULTS: Exposed length of electrode (coefficient = 0.79, standard error = 0.04, P < .001), duration of ablation (coefficient = 0.14, standard error = 0.01, P < .001), and clustered electrode design (coefficient = 1.21, standard error = 0.05, P < .001) were independent factors that affected minimal transverse diameter and volume of ablated zone in ex vivo study. Similar morphologic characteristics existed among ablated zones in in vivo study. Mean distance of ablation beyond the electrode tip remained constant (ex vivo, 1.0 cm +/- 0.08 [standard deviation]; in vivo, 0.5 cm +/- 0.05) regardless of different ablation conditions. Histochemical staining revealed no viable hepatocytes from center to margins of white zone in each ablated area. Mean intracellular ATP concentration in margins of white zone (9.5 x 10(-12) mol/microg DNA +/- 1.43) was lower than that in red zone (4088 x 10(-12) mol/microg DNA +/- 65.97, P < .001) and in adjacent normal liver (4528 x 10(-12) mol/microg DNA +/- 52.74, P < .001). CONCLUSION: Distance of ablation beyond the tip of the electrode remained constant (ex vivo, 1.0 cm; in vivo, 0.5 cm) with different conditions of ablation. Complete and uniform cellular destruction was achieved in the white zone of ablated area.

Demonstration of calcium-activated transient outward chloride current and delayed rectifier potassium currents in Swine atrial myocytes.

Cellular electrophysiology is not fully understood in the atrium of pig heart. The objective of the present study was to determine whether transient outward current (I(to)), ultra-rapid delayed rectifier potassium current (I(Kur)), and rapid and slow delayed rectifier K(+) currents (I(Kr) and I(Ks)) were present in pig atrium. The whole-cell patch technique was applied to record membrane currents and action potentials in myocytes isolated from pig atrium. It was found that an I(to) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig atrial cells, and the I(to) was sensitive to the inhibition by the blockade of L-type calcium (Ca(2+)) current, showed a "bell-shaped" I-V relationship, typical of I(to2) (i.e. I(Cl.Ca)). The I(to2) was inhibited by the chloride (Cl(-)) channel blocker anthracene-9-carboxylic acid (9-AC, 200 micromol/l) or 4,4'-diisothiocyanostilben-2,2'disulfonic acid (200 micromol/l), and by Cl(-) substitution in the superfusate. I(Kur) was found in pig atrial myocytes, and the current showed properties of weak inward rectification and use- and frequency-dependent reduction. I(Kur) was resistant to tetraethylammonium, but sensitive to inhibition by 4-aminopyridine (4-AP) (IC(50) = 71.7 +/- 3.5 micromol/l). In addition, E-4031-sensitive I(Kr) and chromanol 293B-sensitive I(Ks) were observed in pig atrial myocytes. Blockade of I(to2), I(Kur), I(Kr) or I(Ks) with corresponding blockers significantly prolonged atrial action potentials. These results indicate that Ca(2+)-activated I(to2), 4-AP-sensitive I(Kur), E-4031-sensitive I(Kr), and 293B-sensitive I(Ks) are present in pig atrial myocytes, and these currents play important roles in action potential repolarization of pig atria.

Comparison of systemic responses of radiofrequency ablation, cryotherapy, and surgical resection in a porcine liver model.

BACKGROUND: The degree of systemic response after hepatic radiofrequency ablation (RFA) has not been well investigated. METHODS: An in vivo study was conducted on 23 domestic swine. Different hepatic procedures (RFA, cryotherapy, hepatic pedicle ligation, and hepatectomy) were performed on the medial lobe of the liver (30% of the liver volume). Systemic responses in terms of systemic inflammatory marker changes and end-organ functions were determined. RESULTS: During the early postoperative period, the systemic inflammatory marker concentrations (tumor necrosis factor-alpha and interleukin-1beta) in the RFA group were significantly lower than in the cryotherapy group but significantly higher than in the control group. The corresponding concentrations in the hepatectomy group remained similar to those in the control group. The pattern of changes of serum inflammatory marker concentrations in the pedicle ligation group followed the pattern in the RFA group. The serum intracellular content concentrations (lactate dehydrogenase and urate) of the cryotherapy group peaked at 6 hours after operation, which was significantly later than in the other groups. Liver function, renal function, and coagulation profiles remained normal in the RFA group. However, the renal function deteriorated in the cryotherapy group on day 1. Both platelet count and activated clotting time showed significant derangement in the cryotherapy group compared with the control group. There was more severe interstitial pneumonitic change of the porcine lung after cryotherapy than after RFA. CONCLUSIONS: The systemic responses of RFA were significantly less severe than those of cryotherapy in this porcine model. However, the increase in serum inflammatory markers and pneumonitis after RFA was substantial when compared with hepatectomy.