Maike Grosse Hartlage

Percutaneous fetoscopic patch coverage of experimental lumbosacral full-thickness skin lesions in sheep

Background: In order to minimize maternal trauma from open fetal surgery for prenatal coverage of fetal myelomeningoceles in humans, we assessed the feasibility of a percutaneous fetoscopic approach in sheep. Methods: In seven ewes between 90 and 100 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was postured and a full-thickness skin lesion was created in the lumbosacral region. Then, the feasibility of covering this lesion with a patch and fetal skin by standard endoscopic suturing techniques (n = 3) or robot assistance (n = 4) was assessed. Results: Percutaneous fetoscopic patch and skin coverage of the full-thickness skin lesion was achieved in six of the seven fetal sheep. Five fetuses survived gestation and were delivered healthy. Conclusions: Percutaneous fetoscopic posturing and patch coverage of lumbosacral full-thickness skin lesions can effectively and safely be achieved in sheep. This approach promises to provide a substantial reduction of maternal trauma from fetal surgery for myelomeningoceles.

Xenon improves recovery from myocardial stunning in chronically instrumented dogs.

In this study we tested the hypothesis that inhalational administration of xenon improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate; left atrial, aortic, and left ventricular pressure; coronary blood-flow velocity; and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography. An occluder around the left anterior descending artery (LAD) allowed the induction of a reversible LAD ischemia. Animals underwent 2 experimental conditions in a randomized crossover fashion on separate days: (a) 10 min of LAD occlusion under fentanyl (25 μg · kg−1 · h−1) and midazolam (0.6 mg · kg−1 · h−1) (control) and (b) a second ischemic episode under the same basal anesthesia with concomitant inhalational administration of 75 ± 1 vol% xenon (intervention). Anesthesia was induced 35 min before LAD occlusion and was discontinued after 20 min of reperfusion. Dogs receiving xenon showed a significantly better recovery of wall-thickening fraction up to 12 h after ischemia. The increase in plasma epinephrine during emergence from anesthesia and in the early reperfusion period was significantly attenuated in the xenon group. There were no differences between groups concerning global hemodynamics, blood-flow velocity, or regional myocardial blood flow. In conclusion, inhalational administration of 75 vol% xenon improves recovery from myocardial stunning in chronically instrumented dogs under fentanyl/midazolam anesthesia.

Intra-amniotic multimodal fetal echocardiography in sheep: a novel imaging approach during fetoscopic interventions and for assessment of high-risk pregnancies in which conventional imaging methods fail

During fetoscopic interventions, intraesophageal placement of intravascular ultrasound (US) catheters for fetal hemodynamic monitoring may result in esophageal injury in very small fetuses. Moreover, conventional fetal imaging by the transvaginal or transabdominal routes may be impossible in some high-risk pregnancies. The purpose of our study in sheep was to assess the potential of a phased-array intravascular US catheter for intra-amniotic fetal echocardiography. The catheter was percutaneously inserted into the amniotic cavity in seven pregnant ewes at between 78 to 98 days of gestation and permitted high-quality 2-D imaging of the fetal heart and multimodal Doppler assessment of fetal cardiovascular flows. Fetoscopic examination of intra-amniotic contents after intra-amniotic imaging was finished did not display any injury to intra-amniotic contents. The intra-amniotic imaging approach may provide an effective alternative in humans for monitoring during fetoscopic interventions, and to assess fetal anatomy and hemodynamics in high-risk pregnancies when sufficient images cannot be obtained by conventional routes.

Naloxone Improves Splanchnic Perfusion in Conscious Dogs through Effects on the Central Nervous System

Background In patients undergoing colonoscopy, naloxone has vasodilative properties. However, it remains unclear whether this effect is mediated by central or peripheral mechanisms. The aim of this study was to investigate whether these effects are mediated by an effect of naloxone on the central nervous system. Methods Twenty dogs were chronically instrumented for measurement of hemodynamic parameters. Splanchnic blood flow was determined using colored microspheres. Transthoracic echocardiographic examinations were performed to measure cardiac output. In each animal, two experiments were performed in a random order: experiment 1 was determination of splanchnic blood flow before and 5 min after intravenous administration of naloxone (63 &mgr;g/kg), and experiment 2 was determination of splanchnic blood flow before and 5 min after administration of naloxone methiodide (63 &mgr;g/kg), which does not cross the blood–brain barrier. Results Naloxone, but not naloxone methiodide, significantly increased blood flow to the stomach (from 0.41 ± 0.022 to 0.9 ± 0.016 # ml · g−1 · min−1 with naloxone), jejunum (from 0.31 ± 0.024 to 0.83 ± 0.083 # ml · g−1 · min−1 with naloxone), colon (from 0.41 ± 0.057 to 0.68 ± 0.008 # ml · g−1 · min−1 with naloxone), spleen (from 1.45 ± 0.21 to 2.13 ± 0.25 # ml · g−1 · min−1 with naloxone), pancreas (from 0.97 ± 0.021 to 1.25 ± 0.005 # ml · g−1 · min−1 with naloxone), and kidneys (from 3.24 ± 0.108 to 5.31 ± 0.26 # ml · g−1 · min−1 with naloxone), without altering cardiac output or arterial blood pressure in conscious dogs. There were no differences in the hemodynamics or cardiac output between the two experiments. Data are presented as mean ± SD. Conclusions The increased splanchnic perfusion after naloxone is not caused by direct peripheral vascular effects or increased cardiac output. Indirect vasodilative effects on splanchnic vessels mediated by actions of naloxone on the central nervous system account for the increased gastrointestinal perfusion after naloxone in dogs.

Opioid Receptor Antagonism Improves Recovery from Myocardial Stunning in Chronically Instrumented Dogs

We tested the hypothesis that the selective &kgr;-opioid receptor antagonist nor-binaltorphimine (nor-BNI) improves recovery from myocardial stunning. Ten dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), and the maximum rate of LVP increase (LV dP/dtmax) and decrease (LV dP/dtmax), coronary blood flow velocity and myocardial wall-thickening fraction. Regional myocardial blood flow was determined with fluorescent microspheres. Catecholamine plasma levels were measured by high-performance liquid chromatography, and &bgr;-endorphin and dynorphin plasma levels by radioimmunoassay. An occluder around the left anterior descending artery (LAD) allowed induction of a reversible LAD-ischemia. Animals underwent two experiments in a randomized crossover fashion on separate days: (a) 10 min LAD-occlusion (control experiment), (b) second ischemic episode 24 h after nor-BNI (2.5 mg/kg IV) (intervention). Dogs receiving nor-BNI showed an increase in wall-thickening fraction, LV dP/dtmax and LV dP/dtmin before ischemia and during the whole reperfusion (P < 0.05 versus control experiment). After nor-BNI pretreatment, dynorphin levels increased after induction of ischemia to a peak level of 15.1 ± 3.6 pg/mL (P < 0.05 versus control experiment). The increase in plasma &bgr;-endorphin during ischemia and early reperfusion was attenuated after nor-BNI. Compared with the control experiment, nor-BNI left global hemodynamics, regional myocardial blood flow, and catecholamine levels unchanged. In conclusion, nor-BNI improves recovery from myocardial stunning after regional myocardial ischemia in chronically instrumented dogs.