David M. Colonna

Ischemic preconditioning reduces neurologic injury in a rat model of spinal cord ischemia

Background. Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. Methods. Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n 5 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n 5 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. Results. Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. Conclusions. Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event. (Ann Thorac Surg 1999;68:874 ‐ 80)

Nitric oxide promotes arteriolar dilation during cortical spreading depression in rabbits.

Pial arterioles transiently dilate during cortical spreading depression (CSD), although the mechanisms are unclear. We tested the hypothesis that increased production of nitric oxide (NO) promotes arteriolar dilation. Methods Urethane-anesthetized rabbits were equipped with cranial windows, and the diameter (reported in micrometers) of a pial arteriole was determined via intravital microscopy. In each rabbit, a baseline CSD was elicited by microapplication of KC1 onto the cortex, and resultant pial arteriolar dilation was measured. Either 100 μmolfL Nw-nitro-L-arginine methyl ester (L-NAME) or 50 μmol/L NG-nitro-L-arginine (L-NA), both competitive NO synthase inhibitors, was then applied to the brain surface. A CSD was elicited as before. The L-NAME and L-NA were then removed by artificial cerebrospinal fluid washes. An additional CSD was induced with KC1 as before. Results Control CSD in the L-NAME group dilated pial arterioles: baseline diameter, 66±7 mm, with CSD=106±8 mm (59% increase). After topically applied L-NAME, CSD dilated pial arterioles less: baseline diameter, 61 ±7 mm, with CSD=77±6 mm (26% increase), P<.05 compared with control CSD diameter. Topical L-NA had similar effects on CSD: control CSD dilated pial arterioles 51%; after topical L-NA, only 14% (P<.05). After removal of L-NAME or L-NA, CSD-induced pial arteriolar dilation was similar to original control values. Conclusions The reversible inhibition of CSD-induced pial arteriolar dilation by either L-NAME or L-NA suggests that NO contributes to arteriolar dilation observed with CSD.

Thoracic epidural analgesia with bupivacaine and fentanyl for postoperative thoracotomy pain

This study was designed to evaluate the potential fentanyl-sparing effect of a dilute local anesthetic, bupivacaine, administered in fixed combinations with fentanyl for post-thoracotomy analgesia via a continuous thoracic epidural infusion. Forty adult patients scheduled for thoracotomy were randomly allocated in a double-blind fashion to receive an epidural infusion containing 0, 0.03, 0.06, or 0.125% bupivacaine in combination with fentanyl (4 micrograms/mL). The epidural infusions were initiated in the operating room at 10 mL/hr. During the first 24 hours, there were no between-group differences in pain scores. Total fentanyl use was significantly decreased 24% to 33% in all bupivacaine treatment groups. However, fentanyl plasma levels at 24 hours were not significantly different between groups. Arterial blood gas measurements performed on the morning after surgery revealed significant reductions in PaCO2 values, 38 +/- 4, 36 +/- 4, 37 +/- 4 mmHg for 0.03, 0.06, and 0.125% bupivacaine groups respectively, versus 44 +/- 6 for the plain fentanyl group. Arterial pH values were significantly higher in all bupivacaine treatment groups. These findings suggest that the combination of dilute bupivacaine with fentanyl for thoracic epidural analgesia for post-thoracotomy pain may have beneficial effects on pulmonary gas exchange.

Fluoroscopy-assisted intubation of a child with an unstable subluxation of C1/C2.

Patients presenting with unstable cervical spine injuries are at risk for additional neurological injury as a consequence of airway manipulation. Techniques of awake intubation may not always be desirable or practical, particularly in the pediatric patient. We describe the use of fluoroscopy during the induction of anesthesia and intubation of a child with an unstable C1/C2 spinal subluxation. Fluoroscopy is readily available and noninvasive. This technique allows for rapid establishment and maintenance of optimal head and neck positioning during induction of general anesthesia and performance of laryngoscopy and tracheal intubation.

Plasma bupivacaine concentrations and effects of epinephrine after superficial cervical plexus blockade in patients undergoing carotid endarterectomy

OBJECTIVE To determine if epinephrine (EPI) added to a solution of bupivacaine (BUP) injected for use in superficial cervical plexus blockade (SCPB) lowers plasma BUP concentrations after injection and whether this addition of EPI resulted in tachycardia, cardiac arrhythmias, or both. DESIGN Randomized, unblinded prospective clinical interventional study. PARTICIPANTS Patients scheduled to undergo carotid endarterectomy using SCPB consenting to study. SETTING University-affiliated tertiary care hospital operating room. INTERVENTIONS Twenty patients were given SCPB with BUP 0.5% and were randomized to receive either no EPI or 1:300,000 EPI. This study block was followed by a second period in which 20 patients were given SCPB with BUP 0.25% randomized to receive either no EPI or 1:300,000 EPI. Continuous electrocardiogram monitoring was performed during and after the block and analyzed for heart rate and rhythm changes. MEASUREMENTS AND MAIN RESULTS Arterial plasma BUP concentrations were measured 2.5 to 120 minutes after initiation of SCPB. Plasma BUP concentrations were highest in the 0.5% no EPI group, followed by the 0.5% EPI, 0.25% no EPI, and 0.25% EPI groups. The use of EPI did not significantly affect heart rate or change the incidence of cardiac arrhythmias. CONCLUSIONS BUP 0.25% consistently produced the lowest plasma BUP concentrations, particularly when EPI was added to the solution. BUP 0.5% without EPI can produce plasma BUP concentrations previously reported to be associated with central nervous system effects. The use of EPI in this setting does not produce untoward cardiac side effects.

Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8), and control (CTRL, n = 8). Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7), ischemic preconditioning (IPC, n = 7), and time control (TC, n = 4). Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

ISCHEMIC PRECONDITIONING REDUCES NEUROLOGIC INJURY IN A RAT MODEL OF SPINAL CORD ISCHEMIA

BACKGROUND Ischemic preconditioning (IPC) is an endogenous cellular protective mechanism whereby brief, noninjurious periods of ischemia render a tissue more resistant to a subsequent, more prolonged ischemic insult. We hypothesized that IPC of the spinal cord would reduce neurologic injury after experimental aortic occlusion in rats and that this improved neurologic benefit could be induced acutely after a short reperfusion interval separating the IPC and the ischemic insult. METHODS Forty male Sprague-Dawley rats under general anesthesia were randomly assigned to one of two groups. The IPC group (n = 20) had 3 minutes of aortic occlusion to induce spinal cord ischemia 30 minutes of reperfusion, and 12 minutes of ischemia, whereas the controls (n = 20) had only 12 minutes of ischemia. Neurologic function was evaluated 24 and 48 hours later. Some animals from these groups were perfusion-fixed for hematoxylin and eosin staining of the spinal cord for histologic evaluation. RESULTS Survival was significantly better at 48 hours in the IPC group. Sensory and motor neurologic function were significantly different between groups at 24 and 48 hours. Histologic evaluation at 48 hours showed severe neurologic damage in rats with poor neurologic test scores. CONCLUSIONS Ischemic preconditioning reduces neurologic injury and improves survival in a rat model of spinal cord ischemia. The protective benefit of IPC is acutely invoked after a 30-minute reperfusion interval between the preconditioning and the ischemic event.