Michael Talcott

Novel, Magnetically Guided Catheter for Endocardial Mapping and Radiofrequency Catheter Ablation

Background—Ablation of complex arrhythmias would be greatly facilitated by more precise control of ablation catheters. A feasibility study was performed in animals to evaluate a novel magnetic guidance system (MGS) that generates a magnetic field to control the movement and position of a magnetic ablation catheter. Methods and Results—The MGS is composed of a digital biplanar fluoroscope within an array of superconducting electromagnets that surround the torso of the experimental animal and a computer control system that generates a composite magnetic field for directional catheter deflection. Magnetic catheter navigation was performed in dogs and pigs (20 to 30 kg). A 7F magnetic ablation catheter was used for intracardiac navigation and radiofrequency ablation. The performance of a standard 7F deflectable catheter was not affected by the MGS. The magnetic catheter was navigated successfully to 51 predefined targets throughout the heart in 6 animals. In 5 animals, the magnetic catheter, guided by a 3D computed tomogram, was successfully navigated to all pulmonary veins. Navigation accuracy was estimated as <1 mm displacement from the target. The magnetic catheter was used to ablate the atrioventricular node in 4 animals and to perform linear ablations across the endocardial surface underlying an epicardial multielectrode recording plaque in 4 animals. Conclusions—These results demonstrate that the MGS can navigate and stabilize an ablation catheter at endocardial targets. Linear or focal radiofrequency ablation with the magnetic catheter is not compromised by the magnetic field. This technology provides precise control of endocardial catheters.

Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.

Magnetically Controllable Gastrointestinal Steering of Video Capsules

Wireless capsule endoscopy (WCE) allows for comfortable video explorations of the gastrointestinal (GI) tract, with special indication for the small bowel. In the other segments of the GI tract also accessible to probe gastroscopy and colonscopy, WCE still exhibits poorer diagnostic efficacy. Its main drawback is the impossibility of controlling the capsule movement, which is randomly driven by peristalsis and gravity. To solve this problem, magnetic maneuvering has recently become a thrust research area. Here, we report the first demonstration of accurate robotic steering and noninvasive 3-D localization of a magnetically enabled sample of the most common video capsule (PillCam, Given Imaging Ltd, Israel) within each of the main regions of the GI tract (esophagus, stomach, small bowel, and colon) in vivo, in a domestic pig model. Moreover, we demonstrate how this is readily achievable with a robotic magnetic navigation system (Niobe, Stereotaxis, Inc, USA) already used for cardiovascular clinical procedures. The capsule was freely and safely moved with omnidirectional steering accuracy of 1°, and was tracked in real time through fluoroscopic imaging, which also allowed for 3-D localization with an error of 1 mm. The accuracy of steering and localization enabled by the Stereotaxis system and its clinical accessibility world wide may allow for immediate and broad usage in this new application. This anticipates magnetically steerable WCE as a near-term reality. The instrumentation should be used with the next generations of video capsules, intrinsically magnetic and capable of real-time optical-image visualization, which are expected to reach the market soon.

Comparison of four energy-based vascular sealing and cutting instruments: A porcine model

AimTo compare the safety and efficacy of four energy-based vascular sealing and cutting instruments.MethodsBlood vessels of various types and diameters were harvested from four pigs using four instruments: Harmonic ACE™ (Ethicon Endo-Surgery, Cincinnati, OH), LigaSure™ V and LigaSure Atlas™ (Valleylab, Inc., Boulder, CO; a division of Tyco Healthcare), and EnSeal™ vessel fusion system (SurgRx, Inc. Redwood City, CA). The diameters of the vessels, speed and adequacy of the cutting and sealing process, and bursting pressures were compared. An additional set of specimens was sealed and left in situ for up to 4 h after which the vessels were harvested and histopathologically analyzed for the degree of thermal injury.ResultsThe bursting pressures were significantly higher with EnSeal™ compared to all other instruments (p < 0.0001). The sealing process was significantly shorter with Harmonic ACE™ and significantly longer with LigaSure Atlas™ (p <0.0001). The mean seal width was larger with the LigaSure Atlas™ compared to the other instruments, and it was smaller with EnSeal™ and Harmonic ACE™. Less radial adventitial collagen denaturation was present with EnSeal™ and LigaSure™ V than with the other two instruments; there were no significant differences in collagen denaturation although proximal thermal injury to the smooth muscle in the media of the vessel wall was less common with LigaSure Atlas™ than with the other instruments; however, the numbers were too small for statistical analysis.ConclusionsThe bursting pressures with EnSeal™ were significantly higher than with all the other instruments. Harmonic ACE™ was the fastest sealing instrument and LigaSure Atlas™ was slowest. EnSeal™ created less radial thermal damage to the adventitial collagen of the vessels and LigaSure Atlas™ created less thermal damage to the media of the vessels. The clinical significance of these findings is unknown.

Perils of intravascular methylprednisolone injection into the vertebral artery. An animal study.

BACKGROUND Intravascular injection of particulate steroids during cervical nerve root blocks has been postulated to be a source of catastrophic neurologic complications that might be avoided with the use of non-particulate steroids. The objective of this study was to compare the effects of direct intravascular injection of particulate and non-particulate steroids on the spinal cord and central nervous system. METHODS Eleven adult pigs underwent direct injection, under fluoroscopic guidance, into the vertebral artery while under general anesthesia. A particulate steroid (methylprednisolone) was injected into four animals (Group 1), whereas seven animals received a non-particulate steroid (dexamethasone in four animals [Group 2] and prednisolone in three [Group 3]). Following injection, the animals were assessed by direct observation of physical activity and with magnetic resonance imaging. After the animals were killed, brain and spinal cord material was retrieved, fixed in paraformaldehyde for one week, and then subjected to histopathologic analysis. RESULTS All four animals in Group 1 failed to regain consciousness after the injection and required ventilatory support. The animals in Groups 2 and 3 recovered fully and demonstrated no evidence of neurologic injury. Magnetic resonance imaging revealed upper cervical cord and brain stem edema in Group 1, but not in Groups 2 and 3. Histologic analysis showed early evidence of hypoxic and ischemic damage-specifically, early eosinophilic neuronal necrosis, nuclear condensation, white-matter pallor, and extracellular edema-in Group 1 but not in Groups 2 and 3. CONCLUSIONS These data suggest that one etiology of neurologic complications following cervical nerve blocks may be inadvertent intravascular injection of particulate steroids, as all animals injected with methylprednisolone had neurologic deficits while none of the controls injected with non-particulate steroids were affected. To our knowledge, this study is the first to demonstrate that particulate steroids cause neurologic deficits and to suggest that use of non-particulate steroids might prevent such complications.

Transplantation of pig metanephroi.

To determine whether pig metanephroi grow and differentiate after allotransplantation or xenotransplantation across a highly disparate barrier, we implanted metanephroi from embryonic day 28 (E28) pig embryos into the omentum of unilaterally nephrectomized adult pigs or C57Bl/6J mice (hosts). Some mouse hosts received anti-CD45RB, anti-CD154, and anti-CD11a (costimulatory blockade). E28 pig metanephroi were <0.2 mm in diameter and contained only metanephric blastema and segments of ureteric bud. Pig metanephroi transplanted into pigs underwent growth and differentiation of nephrons over a 2 week period without the need for costimulatory blockade of hosts. In contrast, pig metanephroi did not grow or differentiate in mice that received no costimulatory blockade. However, by 2 weeks posttransplantation in mice in which costimulation was blocked, metanephroi from E28 pigs had enlarged, become vascularized, and had formed mature tubules and glomeruli. By 3 weeks posttransplantation in mice, metanephroi had grown to the point that they were approximately half the volume of the native mouse kidney. Here we show that growth and development of pig metanephroi occurs posttransplantation across an allogeneic or highly disparate xenogeneic barrier.

Selective versus nonselective arterial clamping during laparoscopic partial nephrectomy: impact upon renal function in the setting of a solitary kidney in a porcine model.

INTRODUCTION Laparoscopic partial nephrectomy has emerged as a standard of care for small renal masses. Nevertheless, there remains concern over the potential for irreversible insult to the kidney as a result of exposure to warm ischemia. We aim to investigate the utility of selective segmental arterial clamping as a means to reduce the potential for ischemic damage to a solitary kidney during laparoscopic partial nephrectomy utilizing a porcine model. MATERIALS AND METHODS A total of 20 domestic swine were randomized into four equal groups. Each subject underwent laparoscopic radical nephrectomy to create the condition of a solitary kidney. On the contralateral side, a laparoscopic lower pole partial nephrectomy was performed, employing either selective or nonselective vascular clamping for either 60 or 90 minutes. Postoperatively, clinical status and serial serum studies were closely monitored for 1 week. RESULTS There were no intraoperative complications. The 90-minute nonselective clamping produced devastating effects, resulting in rapid deterioration into florid renal failure within 72 hours. The 60-minute nonselective clamping group experienced modest but significant rises in both blood urea nitrogen and creatinine. Both 60- and 90-minute selective clamping groups performed well, with no significant rises in creatinine over a 7-day period, and no instances of renal failure. CONCLUSIONS Selective arterial clamping is a safe and feasible means of vascular control during laparoscopic partial nephrectomy. In the porcine model, selective clamping appears to improve functional outcomes during prolonged periods of warm ischemic insult. Prospective evaluation of the technique in humans is necessary to determine if selective arterial control confers long-term functional benefits in patients with limited renal reserve.

Supplemental Oxygen and Carbon Dioxide Each Increase Subcutaneous and Intestinal Intramural Oxygenation

Oxidative killing by neutrophils, a primary defense against surgical pathogens, is directly related to tissue oxygenation. We tested the hypothesis that supplemental inspired oxygen or mild hypercapnia (end-tidal PCO2 of 50 mm Hg) improves intestinal oxygenation. Pigs (25 ± 2.5 kg) were used in 2 studies in random order: 1) Oxygen Study: 30% versus 100% inspired oxygen concentration at an end-tidal PCO2 of 40 mm Hg, and 2) Carbon Dioxide Study: end-tidal PCO2 of 30 mm Hg versus 50 mm Hg with 30% oxygen. Within each study, treatment order was randomized. Treatments were maintained for 1.5 h; measurements were averaged over the final hour. A tonometer inserted in the subcutaneous tissue of the left upper foreleg measured subcutaneous oxygen tension. Tonometers inserted into the intestinal wall measured intestinal intramural oxygen tension from the small and large intestines. Oxygen 100% administration doubled subcutaneous oxygen partial pressure (PO2) (57 ± 10 to 107 ± 48 mm Hg, P = 0.006) and large intestine intramural PO2 (53 ± 14 to 118 ± 72 mm Hg, P = 0.014); intramural PO2 increased 40% in the small intestine (37 ± 10 to 52 ± 25 mm Hg, P = 0.004). An end-tidal PCO2 of 50 mm Hg increased large intestinal PO2 approximately 16% (49 ± 10 to 57 ± 12 mm Hg, P = 0.039), whereas intramural PO2 increased by 45% in the small intestine (31 ± 12 to 44 ± 16 mm Hg, P = 0.002). Supplemental oxygen and mild hypercapnia each increased subcutaneous and intramural tissue PO2, with supplemental oxygen being most effective.

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

Abstract:  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.

Intrawound vancomycin powder eradicates surgical wound contamination: An in vivo rabbit study

BACKGROUND Surgical site infection remains a complication of spine surgery despite routine use of prophylactic antibiotics. Retrospective clinical studies of intrawound vancomycin use have documented a decreased prevalence of surgical site infection after spine surgery. The purpose of the present study was to assess the efficacy of intrawound vancomycin powder in terms of eradicating a known bacterial surgical site contamination in a rabbit spine surgery model. METHODS Twenty New Zealand White rabbits underwent lumbar partial laminectomy and wire implantation. The surgical sites were inoculated, prior to closure, by injecting 100 μL of cefazolin-sensitive and vancomycin-sensitive Staphylococcus aureus (S. aureus) (1 × 10⁸ colony-forming units [CFU]/mL) into the wound. Preoperative cefazolin was administered to all rabbits, and vancomycin powder (100 mg) was placed into the wound of ten rabbits prior to closure. The rabbits were killed on postoperative day four, and tissue and wire samples were obtained for bacteriologic assessment. An independent samples t test was used to assess mean group differences, and a Fisher exact test was used to assess differences in categorical variables. RESULTS The vancomycin-treated and the control rabbits were similar in weight (mean [and standard deviation], 4.1 ± 0.5 kg and 4.0 ± 0.4 kg, respectively; p = 0.60) and sex distribution and had similar durations of surgery (21.7 ± 7.7 minutes and 16.9 ± 6.7 minutes; p = 0.15). The bacterial cultures of the surgical site tissues were negative for all ten vancomycin-treated rabbits and positive for all ten control rabbits (p < 0.0001). Bacterial growth occurred in thirty-nine of forty samples from the control group but in zero of forty samples from the vancomycin group (p < 0.0001). All blood and liver samples were sterile. No rabbit had evidence of sepsis or vancomycin toxicity. Gross examination of the surgical sites showed no differences between the groups. CONCLUSIONS In a rabbit spine-infection model, intrawound vancomycin powder in combination with preoperative cefazolin eliminated S. aureus surgical site contamination. All rabbits that were managed with only prophylactic cefazolin had persistent S. aureus contamination. CLINICAL RELEVANCE This animal study supports the findings in prior clinical reports that intrawound vancomycin powder helps reduce the risk of surgical site infections.