Percutaneous Spinal Ablation in a Sheep Model: Protective Capacity of an Intact Cortex, Correlation of Ablation Parameters with Ablation Zone Size, and Correlation of Postablation MRI and Pathologic Findings.

BACKGROUND AND PURPOSE: Despite the growing use of percutaneous ablation therapy for the treatment of metastatic spine disease, several issues have yet to be fully addressed. Our aims were to determine whether the vertebral body cortex protects against ablation-induced spinal cord injury; correlate radiofrequency, cryo-, and microwave ablation parameters with resulting spinal ablation zone dimensions and describe normal spinal marrow postablation changes on MR imaging. MATERIALS AND METHODS: Ten thoracolumbar vertebrae in 3 sheep were treated with radiofrequency ablation, cryoablation, or microwave ablation under fluoroscopic guidance. Technique parameters were chosen to produce ablation zones that exceeded the volume of the vertebral bodies in sheep 1 and were confined to the vertebrae in sheep 2 and 3. Expected ablation zone dimensions were based on data provided by the device manufacturers. Postablation MR imaging was performed at 48 hours (sheep 1) or 7 days (sheep 2 and 3). RESULTS: In sheep 1, cryoablation and microwave ablations extended into the spinal canal and caused histologically confirmed neurologic injury, but radiofrequency ablation did not. The mean difference between the lengths of the radiofrequency ablation zone dimensions measured on gross pathology compared with those expected was 9.6 ± 4.1 mm. The gross pathologic cryo- and microwave ablation zone dimensions were within 1 mm of those expected. All modalities produced a nonenhancing ablation zone with a rim of enhancement, corresponding histologically to marrow necrosis and hemorrhagic congestion. CONCLUSIONS: An intact cortex appears to protect against radiofrequency ablation-induced spinal cord injury, but not against non-impedance-based modalities. Ablation dimensions produced by microwave and cryoablation are similar to those expected, while radiofrequency ablation dimensions are smaller. Ablation of normal marrow produces a rim of enhancement at the margin of the ablation zone on MR imaging.

Long-term engraftment following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic rhesus macaques.

BACKGROUND: Transplantation therapy for human diabetes is limited by a shortage of donor organs, and transplant function diminished over time by cell death and limited potential for expansion of beta cells in pancreas or islets. Outcomes are complicated by immunosuppression. A way to overcome supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin (STZ)-diabetic (type 1) Lewis rats or Zucker Diabetic Fatty (ZDF) diabetic (type 2) rats engraft and normalize glucose tolerance without the need for host immune-suppression. METHODS: In this study, we transplant E28 pig pancreatic primordia in the mesentery of STZ-diabetic rhesus macaques. RESULTS: Long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into STZ-diabetic rhesus macaques is demonstrated by electron microscopy, positive immune-histochemistry for insulin, and positive RT-PCR and in situ hybridization for porcine proinsulin mRNA. Insulin requirements were reduced in one macaque followed over 22 months post-transplantation and porcine insulin detected in plasma using sequential affinity chromatography, HPLC and mass spectrometry. Of potential importance for application of this transplantation technology to treatment of diabetes in humans and confirmatory of our previous findings in Lewis and ZDF rats, no host immunosuppression is required. CONCLUSIONS: Under selected circumstances, pancreatic primordia elicit a muted immune response relative to more differentiated tissue, such that engraftment occurs in non-immunosuppressed hosts. Our findings that pig pancreatic primordia engraft long-term in non-immunosuppressed STZ-diabetic rhesus macaques establishes the potential for their use in human diabetics.

Use of intraosseous blood for repeated hematologic and biochemical analyses in healthy pigs.

OBJECTIVE: To evaluate the clinical and histologic effects of repeated intraosseous (IO) needle placement in domestic pigs and determine whether blood and serum obtained intraosseously could be used for CBC and biochemical analyses. ANIMALS: 5 healthy 10-week-old pigs. PROCEDURE: An IO needle was placed in the proximomedial region of the tibia of anesthetized pigs every other week for 2 months, and IO blood was obtained for CBC and serum biochemical analyses. Results were compared with those obtained for blood collected at the same time from the auricular vein. Two weeks after the final samples were obtained, pigs were euthanatized and tibias were processed for histologic examination. RESULTS: Clinical abnormalities, including lameness, were not detected following IO needle placement. Histologic examination revealed only mild multifocal periosteal fibrosis and slight thickening of the periosteum without evidence of osteomyelitis. Chloride, creatinine, glucose, total protein, sodium, and BUN concentrations, alanine transaminase and gamma glutamyl transpeptidase activities, RBC count, mean corpuscular volume, and Hct did not significantly differ between IO and venous samples. However, aspartate transaminase activity, potassium, hemoglobin, and mean corpuscular hemoglobin concentrations, mean corpuscular hemoglobin, and platelet and WBC counts were significantly different. CONCLUSION AND CLINICAL RELEVANCE: Repeated placement of 10 needles may be a safe and clinically useful method to obtain serial blood samples from domestic pigs, particularly when other vascular sites are not accessible. Intraosseous blood can be used for many of the tests comprising CBC and serum biochemical analyses.

Laparoscopic hepatic lobectomy in the porcine model.

BACKGROUND: To date, there have been only a few anecdotal reports of laparoscopic hepatectomy, most of which are limited to wedge resections. The aim of this study was to assess the feasibility of laparoscopic hepatic lobectomy in a porcine model. METHODS: Eight pigs were anesthetized before placement of an abdominal wall lift device and five laparoscopic ports. With the porta hepatis clamped, the left lateral hepatic lobe was divided with an ultrasonic dissector. Small vessels and ducts were clipped, larger vascular structures were transected with staplers, and surface hemorrhage was controlled with an argon beam coagulator. Serum liver enzymes (LFTs) and blood counts were drawn pre- and postoperatively. All animals were killed after 1 week. RESULTS: Mean +/- SEM operating and clamp times were 131 +/- 8 and 39 +/- 2 min, respectively. There were four intraoperative complications in three animals (three lacerations of the hepatic vein and one tear of the splenic capsule), all of which were controlled at surgery. Mean blood loss was 189 +/- 52 ml, and the mass of the resected specimen was 139 +/- 11 g. There were no postoperative complications or deaths. White blood cell count, hematocrit, and LFTs did not change postoperatively, except for aspartate aminotransferase (AST), which was elevated transiently. There were no bile leaks or intraabdominal abscesses. CONCLUSIONS: Laparoscopic left hepatic lobectomy was technically feasible in the porcine model using an abdominal wall lift device for exposure. Clinical trials are needed to assess its feasibility and limitations before laparoscopic hepatic lobectomy is deemed safe for human use.

Evaluation of noninvasive monitoring techniques in domestic ferrets (Mustela putorius furo).

OBJECTIVE: To evaluate instrument placement and accuracy of indirect physiologic monitoring techniques in anesthetized domestic ferrets. ANIMALS: 10 healthy adult female ferrets (Mustela putorius furo). PROCEDURE: Direct arterial blood pressure measurement and arterial blood sample collection were performed in ferrets. A pulse oximeter probe was clipped to a forefoot or hind foot; an airway adaptor for capnography was attached to the endotracheal tube; and a sphygmomanometer cuff and Doppler flow probe were positioned on the tail. Isoflurane and nitrous oxide concentrations were varied to induce episodes of hypotension or hypoxia, respectively. Aforementioned noninvasive techniques were compared with direct methods of arterial blood gas analysis, hemoximetry, and arterial blood pressure measurement. Simultaneously obtained direct and indirect measurements were statistically evaluated for mean and SD of the differences, and SEM, and subjectively, for ease of use and relevance to the clinical situation. RESULTS: Values obtained from pulse oximetry were closely related to oxygen saturation measured by blood gas analysis (O2sat). The mean (+/- SD) difference for all results was -0.49 (+/- -4.09)%. The most precise measurements were obtained when O2sat was between 90 and 100%. Capnography measurements varied between ranges. The most accurate measurements were obtained when PaCO2 was < 25 mm of Hg, when the mean difference was 1.6 (+/- -3.01) mm of Hg. Indirect blood pressure measurement consistently underestimated the direct blood pressure value. CONCLUSIONS AND CLINICAL RELEVANCE: Pulse oximetry is a convenient and accurate method for monitoring oxygen saturation in domestic ferrets. Capnography is useful for monitoring respiratory rate and pattern, but may present difficulties in interpretation of actual PaCO2. Indirect blood pressure monitoring is not accurate by use of current methods in ferrets.

Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade.

Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence.

Partial lobectomy via a ligature fracture technique: a method for multiple hepatic biopsies in nonhuman primates.

A ligature fracture technique was used to obtain multiple large (2 to 4 g) liver biopsy samples in both African green and cynomolgus monkeys. The technique was performed 195 times in 84 animals using three different surgical approaches, with no associated illness or mortality. In a subset of 18 animals, a slight decline in hematocrit percentage was noted during 14 days postsurgery (44.6 to 39.4%), but total plasma protein remained unchanged (5.98 to 5.95 g/dl). Serum alanine aminotransferase concentrations rose to 178.11 U/l at day 1 postoperatively, from a baseline value of 93.61 U/l. This elevation was transient, however, and declined to 49.65 U/l by day 14. Our experience has shown that the partial lobectomy via the ligature fracture technique is a safe and effective means to obtain multiple large samples of liver in nonhuman primates.