Masayuki Miyabe

Hemodynamic responses to tracheal intubation with laryngoscope versus lightwand intubating device (Trachlight®) in adults with normal airway

Lightwand devices are effective and safe as an aid to tracheal intubation. Theoretically, avoiding direct-vision laryngoscopy could allow for less stimulation by intubation than the conventional laryngoscopic procedure. We designed this prospective randomized study to assess the cardiovascular changes after either lightwand or direct laryngoscopic tracheal intubation in adult patients anesthetized with sevoflurane. Sixty healthy adult patients with normal airways were randomly assigned to one of three groups according to intubating procedure under sevoflurane/nitrous oxide anesthesia (fraction of inspired oxygen = 0.33) (n = 20 each). The lightwand group received tracheal intubation with Trachlight®, the laryngoscope-intubation group received tracheal intubation with a direct-vision laryngoscope (Macintosh blade), and the laryngoscopy-alone group received the laryngoscope alone. Heart rate and systolic blood pressure were recorded continuously for 5 min after tracheal intubation or laryngoscopy with enough time to intubate. All procedures were successful on the first attempt. The maximum heart rate and systolic blood pressure values obtained after intubation with Trachlight (114 ± 20 bpm and 143 ± 30 mm Hg, respectively) did not differ from those with the Macintosh laryngoscope (114 ± 20 bpm and 138 ± 23 mm Hg), but they were significantly larger than those in the laryngoscopy-alone group (94 ± 19 bpm and 112 ± 21 mm Hg) (P < 0.05). Direct stimulation of the trachea appears to be a major cause of the hemodynamic changes associated with tracheal intubation.

Correlation of the Average Water Diffusion Constant with Cerebral Blood Flow and Ischemic Damage After Transient Middle Cerebral Artery Occlusion in Cats

Magnetic resonance water diffusion imaging can detect early ischemic changes in stroke. Using a middle cerebral artery occlusion model, we examined which range of values of the orientation-independent diffusion quantity is an early noninvasive indicator of reduced cerebral perfusion and focal brain injury. Cats underwent either a 30-min occlusion followed by 3.5 h reperfusion (n = 7) or a 60-min occlusion followed by 4-h reperfusion (n = 6). Repeated measurements of CBF were made with radiolabeled microspheres, and acute focal injury was measured with triphenyltetrazolium chloride (TTC) staining. During occlusion, the decrease in Dav correlated with CBF for caudate [30-min occlusion (n = 13): p < 0.0001; 60-min occlusion (n = 6): p < 0.02] and for cortex [30-min occlusion (n = 12): p < 0.0001; 60-min occlusion (n = 5): p < 0.04]. Variable caudate and hemispheric injury levels were found among cats in both groups. The area of tissue injury demarcated by TTC began to correlate with the area of reduced Dav by 30 min of occlusion (p < 0.02), and this correlation improved (p < 0.0001) at 1, 1.5, and 2.0 h after the onset of occlusion. The time necessary to reach a one-to-one correspondence between the percent of hemisphere injured and the percent of hemispheric area with Dav < 0.65 × 10−9 m2/s was 2 h after occlusion. Thus, the absolute value of Dav is a good indicator of the risk of tissue injury, whereas the combination of Dav and the length of time of Dav reduction is an excellent predictor of acute focal tissue injury demarcated by TTC staining.

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.

Background and Purpose We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. Methods Halothane‐anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N&ohgr;‐nitro‐l‐arginine methyl ester (L‐NAME; 10 mg/kg, n=10) or an equal volume of diluent (10 mL saline, n=10) over 30 minutes before ischemia. Posttreatment groups received intravenous L‐NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n=10) or intravenous L‐NAME (10 mg/kg) plus l‐arginine (200 mg/kg) over the same period followed by continuous l‐arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n=10). Results Microsphere‐determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazoliumdetermined injury volume of ipsilateral caudate nucleus in cats treated with L‐NAME before or during ischemia (42±7% and 42±3% of caudate nucleus, respectively; mean±SE) was less (P<.05) compared with that in cats pretreated with saline (72±5%) or cats treated with L‐NAME plus l‐arginine (68±5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23±5%, 13±3%, 18±5%, and 29±5% of hemisphere in groups treated with L‐NAME before ischemia and during ischemia, the saline‐treated group, and the group treated with L‐NAME plus l‐arginine, respectively). Conclusions Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by l‐arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L‐NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury. (Stroke. 1994;25:877‐885.)

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino- 4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of reperfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5). Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetrazolium-determined injury volume of ipsilateral cerebral hemisphere (saline, 24±8%; NPC-5, 4±2%; NPC-50, 5±2% of hemisphere; mean±SE) and caudate nucleus (saline, 72±6%; NPC-5, 37±10%; NPC-50, 26±4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36±14%; NPC-5, 58±8%; NPC-50, 51±15% of baseline). Conclusions These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.

Effect of PEEP and Jugular Venous Compression on Canine Cerebral Blood Flow and Oxygen Consumption in the Head Elevated Position

Cerebral blood flow (CBF) (radiolabelled microspheres) and oxygen consumption (CMRO2) were studied in nine dogs during 30 min of either neck vein compression or application of positive end-expiratory pressure (PEEP) ventilation. With the animal in the prone position, elevation of the head from horizontal to 30 cm above the heart markedly decreased cisterna magna (PCSF) and dorsal sagittal sinus pressure (PCV). With the head elevated, compression of neck veins using neck tourniquet (pressure 40 mmHg) increased PCSF and PCV from 3.6 2.2 to 6.8 4.8 and −2.5 2.7 to 2.3 2.3 mmHg (mean SE, P < 0.05), respectively, while total or regional CBF and CMRO2 remained unchanged. Application of PEEP (15 cm H2O) increased right atrial pressure (-4.7 1.7 to −0.1 3.4 mmHg, P < 0.05), but did not affect PCSF or PCV (3.4 3.3 to 3.3 3.7 and −3.5 2.6 to −4.1 2.4 mmHg, respectively, P > 0.05). Total or regional CBF and CMRO2 were also unaffected. These data demonstrate that, although neither maneuver affects CBF or CMRO2, neck vein compression elevates PCV above atmospheric pressure, but PEEP does not. In patients at risk for cerebral venous embolism, intermittent neck vein compression should be used as a prophylactic measure to prevent air embolism.

The analgesic effect of xenon on the formalin test in rats: a comparison with nitrous oxide.

To investigate the analgesic effects of xenon, we performed formalin tests in rats under 0.5 minimum alveolar anesthetic concentration xenon or nitrous oxide and stained the lumbar spinal cord for c-fos (n = 18) and the phosphorylated N-methyl-d-aspartate (NMDA) receptor (n = 24) by using the avidin-biotin-peroxidase method. After 20 min of 79% xenon, 68% nitrous oxide, or 100% inhaled oxygen, 10% formalin (100 &mgr;L) was injected into the left rear paw of the animals except for a control group. Nociceptive behavior was observed for 1 h. The rats were killed 2 h after the formalin injection, and the lumbar spinal cord was stained for c-fos or the phosphorylated NMDA receptor immunohistochemically. Animals in the xenon and nitrous oxide groups showed less nociceptive behavior than did the oxygen group. Although the number of c-fos-positive cells in the lumbar spinal cord in the nitrous oxide group was not decreased, that in the xenon group decreased. The number of phosphorylated NMDA receptor-positive cells in the xenon group was significantly less than in the nitrous oxide and oxygen groups. Inhaled xenon suppressed nociceptive behaviors, c-fos expression, and activation of the NMDA receptor during the formalin test in rats. These results confirm that xenon’s analgesic effects result from inhibition of the NMDA receptor.

The effects of 30% and 60% xenon inhalation on pial vessel diameter and intracranial pressure in rabbits.

Xenon may increase cerebral blood flow and intracranial pressure (ICP). To evaluate the effects of xenon on brain circulation, we measured pial vessel diameter changes, CO2 reactivity, and ICP during xenon inhalation in rabbits. Minimum alveolar anesthetic concentration (MAC) for xenon was established in rabbits (n = 6). By using a cranial window model, pial vessel diameters were measured at 30% and 60% xenon inhalation and in time control groups (n = 15). ICP, mean arterial blood pressure, and heart rate were recorded during 30% and 60% xenon inhalation (n = 5). Pial vessel diameters were measured during hypocapnia and hypercapnia conditions in 60% Xenon and Control groups (n = 14). MAC for xenon was 85%. Xenon (0.35 and 0.7 MAC) dilated the arterioles (10% and 18%, respectively) and venules (2% and 4%, respectively) (P < 0.05). Dilation of arterioles was more prominent than that of venules. ICP, mean arterial blood pressure, and heart rate did not change during xenon inhalation. No difference in CO2 reactivity was observed between Xenon and Control groups (P = 0.79). Sixty percent xenon (0.7 MAC) dilated brain vessels, but venule changes were small. Xenon did not increase ICP and preserved CO2 reactivity of the brain vessels.

Comparative analysis of brain protection by N-methyl-D-aspartate receptor antagonists after transient focal ischemia in cats

OBJECTIVE We tested the hypothesis that the administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid) (NPC 17742) or cis-4-(phosphonomethyl) piperidine-2-carboxylic acid (CGS 19755) or the noncompetitive NMDA receptor antagonist dizocilpine (MK-801), at the appropriate doses, would all have efficacy in decreasing early postischemic brain injury in a feline model of transient focal ischemia. DESIGN Prospective, randomized, controlled animal trial. SETTING University research laboratory. SUBJECTS Forty mixed-breed cats. INTERVENTIONS Halothane-anesthetized cats underwent 90 mins of left middle cerebral artery occlusion plus 4 hrs of reperfusion. At 75 mins of ischemia, control cats received intravenous saline (n = 10). Experimental cats (n = 10 in each group) were treated with NPC 17742 (5 mg/kg bolus and 2.5 mg/kg/hr throughout reperfusion), MK-801 (5 mg/kg intravenous bolus), or CGS 19755 (40 mg/kg intravenous bolus) in a randomized fashion. MEASUREMENTS AND MAIN RESULTS Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia, and recovered to the same extent during early reperfusion, in the four groups. Triphenyltetrazolium-determined injury volume of the ipsilateral caudate nucleus in cats treated with NPC 17742 (105 +/- 25 [SEM] mm3), MK-801 (97 +/- 22 mm3), and CGS 19755 (97 +/- 13 mm3) was less than in control cats (198 +/- 21 mm3). Hemisphere injury volumes with NPC 17742 (1209 +/- 405 mm3) and MK-801 (1338 +/- 395 mm3) were less than that value in controls (2193 +/- 372 mm3), whereas injury volume with CGS 19755 (1553 +/- 519 mm3) treatment did not attain significance (p < .09). CONCLUSIONS NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions after 90 mins of transient focal ischemia in the cat. At the doses chosen, there appear to be no major differences in therapeutic efficacy for competitive and noncompetitive NMDA receptor antagonists.

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

There is no report concerning oral clonidine’s effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1–9 yr, were randomly allocated to the Control or Clonidine 4 &mgr;g/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (Fio2 40%). Epidural puncture and tubing were carefully performed at the Th11–12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg · kg−1 · h−1. Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 &mgr;g/kg decreases plasma lidocaine concentration in children.

The residual effects of hemorrhagic shock on pain reaction and c-fos expression in rats.

UNLABELLED To investigate the residual effects of hemorrhagic shock on pain reaction and c-fos expression, we performed formalin tests after hemorrhage and reinfusion in rats. Twenty adult male Sprague-Dawley rats were divided into Control (n = 10) and Postshock (n = 10) groups. The mean blood pressure of the Control group was 100-120 mm Hg, and that of the Postshock group was kept at 50-60 mm Hg for 30 min by draining blood. After 15 min of returning mean blood pressure to normal levels in the Postshock group, 10% formalin (3.7% formaldehyde solution, 100 microL) was injected into the left rear paw of both groups. Nociceptive behaviors were observed for 1 h after the formalin injection. The rats were killed at 2 h after the formalin injection, and the lumbar spinal cord was then stained for c-fos immunohistochemistry by using the avidin-biotin-peroxidase method. Animals in the Postshock group showed considerably less nociceptive behavior than those in the Control group. C-fos expression in the deep layer (IV-VI) of the spinal cord was significantly less in the Postshock group. In conclusion, decreases of nociceptive behaviors and c-fos expression were observed under normotensive conditions after hemorrhagic shock. The mechanisms governing these reactions remain unclear. IMPLICATIONS Formalin tests were performed after hemorrhage and reinfusion in rats. A stress-induced analgesia was observed under normotensive conditions after hemorrhagic shock. The mechanisms remain unclear.