Does hypothermic circulatory arrest or prolonged cardiopulmonary bypass time affect early outcome in reoperative aortic surgery?

AIM: Prolonged cardio-pulmonary bypass (CPB) time, usually necessary for reoperations, is known to increase mortality in coronary bypass procedures and aortic reoperations. We investigated if prolonged CPB time and arch reconstruction in reoperations of the thoracic aorta affect in-hospital outcome. METHODS: Twenty-nine patients underwent reoperations on the thoracic aorta. The reoperations performed were aortic root replacement with composite graft without aortic arch involvement in ten patients, isolated ascending aorta replacement in six patients, aortic arch replacement as a primary procedure in two patients, and aortic arch in conjunction with ascending or descending aorta replacement in 11 patients. RESULTS: Fourteen patients had aortic reoperation with deep hypothermic circulatory arrest (DHCA) and 15 without DHCA. The in-hospital mortality rate was 13.8%. The use deep hypothermic circulatory arrest or CPB time did not affect early outcome. Previous coronary artery bypass procedure was independent predictor of in-hospital mortality. Seven patients required re-exploration for bleeding. One patient suffered from stroke and finally five patients had prolonged ventilation, two requiring tracheostomy. There have been no deaths in the follow-up period. None of the patients has required repeat surgical intervention on the heart or the aorta. CONCLUSION: The use of DHCA or prolonged CPB time do not affect early outcome in reoperations of the thoracic aorta.

Clopidogrel and aspirin in cardiovascular medicine: responders or not--current best available evidence.

Dual antiplatelet therapy represents an important advance for patients with established coronary artery disease. It is an important strategy for patients with acute coronary syndromes and those undergoing percutaneous transcatheter coronary interventions. Clopidogrel effectively inhibits ADP-induced platelet activation and aggregation by selectively and irreversibly blocking the P2Y(12) receptor on the platelet membrane. Aspirin works by irreversibly acetylating the cyclooxygenase (COX-1) enzyme, thus suppressing the production of thromboxane A(2) (TxA(2)) and inhibiting platelet activation and aggregation. Variable platelet response and potential resistance to therapy has emerged with aspirin and clopidogrel. The definitions of antiplatelet agents variability in responsiveness and nonresponsiveness are discussed. Clopidogrel and aspirin responsiveness as they are measured in the laboratory by various techniques (platelet aggregometry and point-of-care assays such as platelet function analyzer [PFA-100] and rapid platelet function assay [RPFA]) are evaluated. The mechanisms responsible for variations in responsiveness to antiplatelet agents such as clinical, cellular and genetic factors are defined. Aspirin and clopidogrel resistance are emerging clinical entities with potentially severe consequences such as myocardial infarction, stroke or death. The therapeutic interventions to deal with nonresponsiveness are reported, although specific recommendations are not clearly established. In the future, routine measurement of platelet function in patients with cardiovascular disease may become the standard of care. Personalized antithrombotic treatment strategies may be determined by ex-vivo measurements that identify critical pathways influencing thrombotic risk in the individual patient.

Independent predictors for early and midterm mortality after thoracic surgery.

BACKGROUND: The purpose of the present study was to determine independent predictors for early and midterm mortality for the whole context of thoracic surgery. METHODS: We studied 1453 consecutive patients who underwent thoracic surgery between 2002 and 2005. Operations included lung resections (n = 504), mediastinal (n = 468), pleural and pericardial (n = 226), esophageal (n = 83), chest wall (n = 85), tracheal (n = 50) and other procedures (n = 37). Midterm survival data (mean follow-up 2.0 +/- 1.1 years) were obtained from the National Death Index. Multivariate logistic regression was used to assess in-hospital mortality. Independent predictors for midterm mortality were determined by multivariate Cox regression analysis. RESULTS: There were 47 (3.2 %) in-hospital and 312 (21.5 %) late deaths. Independent predictors for in-hospital mortality included Zubrod score (OR 2.72, P < 0.001), ASA score (OR 3.42, P < 0.001), pneumonectomy (OR 20.71, P = 0.001) and no history of cerebrovascular events (OR 0.27, P = 0.011). Independent predictors for midterm mortality included age (HR 1.03, P < 0.001), weight loss (HR 1.57, P = 0.005), Zubrod score (HR 1.47, P < 0.001), primary lung cancer (HR 1.98 P < 0.001), intrathoracic extrapulmonary metastases (HR 2.78, P < 0.001), primary chest wall tumor (HR 0.14, P = 0.008), diabetes requiring insulin (HR 1.71, P = 0.017), no preoperative renal failure (HR 0.57, P = 0.004), no comorbidities (HR 0.54, P = 0.009), ASA score (HR 1.69, P < 0.001), postoperative radiation treatment (HR 1.90, P = 0.016), pneumonectomy (HR 2.18, P = 0.040), reoperation for bleeding and/or postoperative transfusion (HR 3.10, P = 0.027) and postoperative pulmonary complications (HR 1.89, P = 0.013). CONCLUSIONS: We determined independent predictors for in-hospital and midterm mortality for the whole context of thoracic surgery. Zubrod and ASA scores affect both early and midterm mortality.

Laparoscopic management of large retroperitoneal lymphoceles complicating aortic surgery.

Retroperitoneal lymphocele is a rare but debilitating complication of aortic replacement with synthetic graft. The only effective treatment reported to date is surgical reexploration and ligation of leaking lymphatics. This report illustrates the successful management of two patients with large retroperitoneal lymphoceles formed after aortic surgery using laparoscopic techniques. The available literature is reviewed. Laparoscopic fenestration of the lymphocele and laparoscopically assisted ligation of the leaking lymphatics combined with internal drainage resulted in long-term relief of compression symptoms, as observed, respectively, over the 5-year and 3-month follow-up periods. Percutaneous catheter drainage before laparoscopic management was unsuccessful in both cases. In addition, the unique presentation of a large retroperitoneal lymphocele with intestinal obstruction is reported, and currently available treatment options are discussed.

Single-stage reoperative repair of chronic type A aortic dissection by means of the arch-first technique.

OBJECTIVE: Management of the enlarged, chronically dissected aorta after previous repair of acute aortic dissection or after a previous cardiac operation may present a formidable technical challenge. Marked enlargement of the proximal descending thoracic aorta precludes safe use of staged procedures, including the elephant trunk technique. METHODS: Sixteen patients with chronic type A aortic dissection (mean age, 56 years) underwent resection of the ascending aorta, the aortic arch, and varying segments of the descending thoracic aorta. We used single-stage replacement, with perfusion of the aortic arch first to minimize the duration of brain ischemia, with a bilateral anterior thoracotomy (clamshell) incision. Eleven patients had undergone previous repair of acute type A dissection. Five patients had type A dissection after aortic valve replacement (2 patients) and coronary artery bypass (3 patients). Marked enlargement of the aorta distal to the left subclavian artery precluded a 2-stage repair. The mean interval between the initial and reoperative procedures was 62 months (range, 5-137 months). RESULTS: There was 1 (6.2%; 70% confidence limits, 0.3%-24.7%) hospital death. Four patients required reoperation for bleeding. One patient required a right ventricular assist device that was successfully removed. Six patients required assisted ventilation for more than 72 hours, and 3 patients required a tracheostomy. All were successfully weaned from ventilatory support. No patient had a stroke or other adverse neurologic outcome. CONCLUSION: The single-stage, arch-first replacement technique is a safe and effective procedure for patients who require extensive reoperations for chronic expanding type A dissection.

Safety and efficacy of hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with circulatory arrest is an important adjunct for operations on the distal aortic arch and the descending thoracic and thoracoabdominal aorta. Its safety and efficacy compared with other techniques (eg, simple aortic clamping, partial cardiopulmonary bypass, and regional hypothermia) are not clearly established. METHODS: One hundred sixty-one patients (ranging from 20 to 83 years old) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the involved aortic segments using hypothermic cardiopulmonary bypass usually with intervals of circulatory arrest (mean interval, 38 minutes). RESULTS: The 30-day mortality rate was 6.2% (10 patients). It was 41% (7 of 17) for patients having emergent operations (rupture or acute dissection) and 2.1% (3 of 144) for all other patients (p < 0.001). The 90-day mortality rate was 11.8% (19 patients). Paraplegia occurred in 4 and paraparesis in 1 of the 156 operative survivors whose lower limb function could be assessed postoperatively (3.2%). Among the 91 survivors with thoracoabdominal aortic disease, early paraplegia occurred in 1 of 33 patients with Crawford type I disease, 0 of 34 with type II disease, and 2 of 24 with type III disease. One patient (type II disease) had development of paraplegia on the tenth postoperative day. None of the 50 patients with aortic dissection experienced paralysis. Renal dialysis was required in 4 (2.5%) of the 157 operative survivors, prolonged inotropic support (> 48 hours) in 17 (11%), reoperation for bleeding in 8 (5%), mechanical ventilation (> 48 hours) in 31 (20%), and tracheostomy in 13 (8%). Three patients (1.9%) sustained a stroke. CONCLUSIONS: Hypothermic cardiopulmonary bypass provides safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure that equals or exceeds that of other currently used techniques but without the need of other adjuncts.

Cryoablation of ventricular tachycardia guided by return cycle mapping after entrainment.

BACKGROUND: Although the implantable cardioverter-defibrillator effectively prevents sudden cardiac death, patients are still prone to recurrence of ventricular tachyarrhythmias. Electrophysiologically guided surgery is the most effective modality in abolishing ventricular tachycardia, having a lower recurrence rate than pharmacologic therapy or catheter ablation. Return cycle mapping after entrainment has been shown to localize the central common pathway, which is the target region for ablation, without pacing at the pathway or recording the potentials from the pathway. METHODS: To determine the accuracy and usefulness of return cycle mapping in surgery for ventricular tachycardia, we cryoablated 8 morphologies of ventricular tachycardia induced in postinfarction dogs with the guidance of return cycle mapping. The ventricular tachycardia was entrained from 3 to 5 different epicardial sites at a paced cycle length 10 to 20 ms shorter than the ventricular tachycardia cycle length and the epicardium was mapped with 61 unipolar electrodes during cessation of entrainment to construct return cycle maps. The return cycle was determined by subtracting the first activation time from the second activation time after the last stimulus in each electrode location, and the maps were then displayed on a computer. RESULTS: The total analysis process was completed within 3 minutes by means of a computer with custom-made programs. The activation map during ventricular tachycardia did not localize the central common pathway in any morphology of ventricular tachycardia, because the pattern of activation was concentric and diastolic potentials were not recorded. Cryoablation of the region where the isotemporal lines of the return cycle equal to the ventricular tachycardia cycle length intersected resulted in termination of ventricular tachycardia in all morphologies. The intersection was 26 +/- 9 mm from the earliest activation site. Epicardial mapping with 253 electrodes during cryothermia showed that the region localized by return cycle mapping was the central common pathway sandwiched between the lines of conduction block and that the cryolesion connected the lines of block, blocked the rotating wave front, and resulted in termination of the ventricular tachycardia. CONCLUSION: Return cycle mapping provides an accurate and rapid means of localizing the central common pathway without the need for recording potentials from the pathway or pacing at the pathway in ablation for ventricular tachycardia.

Hypothermic cardiopulmonary bypass for spinal cord protection: rationale and clinical results.

BACKGROUND: Hypothermic cardiopulmonary bypass with or without circulatory arrest has been used successfully for the treatment of complex aneurysms of the descending thoracic and thoracoabdominal aorta. Hypothermia has a protective effect on spinal cord function, and its use has been associated with a low incidence of paraplegia in traditionally high-risk patients. Experimentally, the protective effect of hypothermia has been related to amelioration of excitotoxic injury by reduction of neurotransmitter release and to inhibition of delayed apoptotic cell death. METHODS: During a 12-year period, 114 patients with descending thoracic or thoracoabdominal aortic disease underwent replacement of the involved aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest. RESULTS: The hospital mortality was 8% (9 patients). Paraplegia occurred in 2 and paraparesis in 1 of the 108 patients whose lower limb function was assessed postoperatively (2.8%). None of 40 patients with aortic dissection and none of the last 81 patients in the series developed paralysis. CONCLUSIONS: Our experience with hypothermic cardiopulmonary bypass and circulatory arrest confirms that hypothermia provides substantial protection against paraplegia, and it allows complex operations on the descending thoracic and thoracoabdominal aorta to be performed with acceptable mortality.

Single-stage extensive replacement of the thoracic aorta: the arch-first technique.

BACKGROUND: Single-stage extensive replacement of the thoracic aorta usually involves a period of circulatory arrest with performance of the graft-to-lower descending thoracic aorta anastomosis before performing the anastomosis to the arch vessels. To minimize the period of brain ischemia and reduce the potential for neurologic injury, we developed an alternative technique. METHODS: In 6 patients with extensive aneurysms involving the entire thoracic aorta, exposure was obtained via a bilateral thoracotomy in the anterior fourth intercostal space with transverse sternotomy. A 10-mm graft was anastomosed to the aortic graft, opposite the site of the planned anastomosis to the arch vessels. During a single period of circulatory arrest (34-46 minutes), the aortic graft was attached to a cuff of aorta containing the arch vessels. The graft was then clamped on either side, and the arch was perfused with cold blood for 20 to 36 minutes. After the distal aortic anastomosis was completed, antegrade perfusion was established via the 10-mm graft. The proximal aortic anastomosis was performed last. RESULTS: No patient sustained a permanent neurologic deficit. All 6 patients were discharged from the hospital. CONCLUSIONS: The "arch-first" technique, combined with a bilateral transverse thoracotomy, allows expeditious replacement of the thoracic aorta with an acceptable interval of hypothermic circulatory arrest and minimizes the risk of retrograde atheroembolism by establishing antegrade perfusion.

Surgical management of the severely atherosclerotic ascending aorta during cardiac operations.

Severe atherosclerosis of the ascending aorta is associated with an increased incidence of stroke after cardiac surgery. Direct intraoperative epiaortic scanning is a rapid and accurate means for detection of ascending aortic atherosclerosis. When severe atheromatous disease is detected, graft replacement of the ascending aorta is our preferred method of management. During an 11-year period, 81 patients (mean age 71 years) who underwent coronary artery bypass were found to have severe ascending aortic atherosclerosis by epiaortic scanning. Using hypothermic circulatory arrest, 80 patients underwent partial (5) or complete (75) ascending aortic replacement. One patient underwent resection of a protruding aortic atheroma. In addition to partial or total replacement of the ascending aorta, 34 patients had replacement of the aortic arch, 19 had a valve replacement, and 6 had carotid endarterectomy. The 30-day mortality was 8.6% (7 patients). Four patients (4.9%) sustained perioperative strokes and 2 (2.5%) sustained transient perioperative ischemic neurological deficits. The 3-year survival rate was 40%. There was one stroke 4 months postoperatively that eventually led to late death. Elective resection and graft replacement of the severely atherosclerotic ascending aorta using hypothermic circulatory arrest in patients undergoing cardiac operations is a safe procedure, associated with an acceptable incidence of postoperative stroke. The procedure may provide long-term protection from subsequent embolic cerebral vascular events. However, long-term survival has been disappointing and is primarily related to generalized atherosclerosis.

Return cycle mapping after entrainment of ventricular tachycardia.

BACKGROUND: The central common pathway, which is the target for ablation in reentrant ventricular tachycardia, can be localized by entrainment mapping techniques. However, localization of the pathway is not always possible because of the elevated pacing threshold and the low voltage and fractionated potentials at the pathway. We examined whether return cycle mapping after entrainment localizes the pathway without pacing at the pathway or recording the potentials from the pathway and determined the required electrode resolution to localize the pathway. METHODS AND RESULTS: Epicardial mapping was performed with 253 unipolar electrodes during and after entrainment of 13 morphologies of ventricular tachycardia that were induced in dogs 4 days after infarction. The return cycle was calculated by subtracting the first activation time from the second activation time after the last stimulus and the return cycle distribution map was constructed for each stimulation site. The return cycle isochrones equal to the ventricular tachycardia cycle length converged on the lines of conduction block irrespective of the stimulation site, and the central common pathway was localized at the region between the intersections of the return cycle isochrones after entrainment from different stimulation sites. The potentials from the central common pathway were not required to localize the pathway, and the mapping accuracy did not change with or without analysis of the potentials from the pathway. According to the correlation between the electrode resolution and the mapping accuracy, an interelectrode distance of 8.5 mm was estimated as sufficient resolution for successful tachycardia termination during radiofrequency ablation guided by return cycle mapping. CONCLUSIONS: Return cycle mapping after entrainment localizes the central common pathway without pacing at the pathway or recording the potentials from the pathway. This new mapping technique could improve the success rate of the ablative procedures.

Profound hypothermia for spinal cord protection in operations on the descending thoracic and thoracoabdominal aorta.

Elective hypothermic cardiopulmonary bypass with or without circulatory arrest has been used successfully for the treatment of complex aneurysms of the descending thoracic and thoracoabdominal aorta. Hypothermia has a protective effect on spinal cord function, and its use has been associated with a low incidence of paraplegia in traditionally high-risk patients. In our series, 96 consecutive patients underwent resection and graft replacement of diseased aortic segments of the distal aortic arch, the descending thoracic aorta, or the thoracoabdominal aorta. Thirty-day mortality was 7.3%, and the incidence of spinal cord ischemic injury was 3.4%. Our experience with hypothermic cardiopulmonary bypass and circulatory arrest confirms the safety and efficacy of the technique for operations on the descending thoracic and thoracoabdominal aorta.

Functional and oximetric assessment of patients after lung reduction surgery.

OBJECTIVE: The goal of this study was to clarify the issue of functional oxygen requirement by regimented exercise oximetry in patients undergoing lung reduction surgery. METHODS: Thirty-seven patients underwent lung reduction surgery and were followed up for at least 3 months. Patients routinely completed a 6-week program of cardiopulmonary rehabilitation. Preoperative and postoperative spirometry, dyspnea scores, 6-minute walk distances, respiratory mechanics, and exercise oximetry were recorded. RESULTS: After the operation, patients had a 37% increase in forced vital capacity and a 59% increase in forced expiratory volume in 1 second. Six-minute walk distance increased from 913 +/- 310 feet before the lung reduction operation to 1202 +/- 274 feet 6 months after the operation (p < 0.001). Maximal inspiratory and expiratory pressures were significantly increased in 16 patients after lung reduction surgery. Perceived dyspnea was significantly improved. Exercise pulse oximetry demonstrated that 83% of patients met American Thoracic Society criteria for supplemental oxygen use before lung reduction surgery. After the operation, 70% of patients continued to meet American Thoracic Society criteria for supplemental oxygen use. Notably, 10 patients with exertional desaturation while breathing room air discontinued supplemental oxygen use because of a reduction in dyspnea. CONCLUSIONS: These findings demonstrate significant subjective and functional improvements related to lung reduction surgery. Exercise-induced hypoxia was not reversed by lung reduction surgery. Discontinuance of supplemental oxygen use owing to reduction in dyspnea and improved physical performance may not be warranted in lieu of continued exertional desaturation.

Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia.

Profound hypothermia induced with cardiopulmonary bypass has a protective effect on spinal cord function during operations on the thoracoabdominal aorta. The mechanism of this protection remains unknown. It has been proposed that the release of excitatory amino acids in the extracellular space plays a causal role in irreversible neuronal damage. We investigated the changes in extracellular neurotransmitter amino acid concentrations with the use of in vivo microdialysis in a swine model of spinal cord ischemia. All animals underwent left thoracotomy and right atrium-femoral artery cardiopulmonary bypass with additional aortic arch perfusion. Lumbar laminectomies were then done and microdialysis probes were inserted stereotactically in the anterior horn of the second and fourth segments of the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min and 15-minute samples were assayed by high-performance liquid chromatography. Group 1 animals (n = 6) underwent aortic clamping distal to the left subclavian artery and proximal to the renal arteries for 60 minutes at normothermia (37 degrees C) and group 2 animals (n = 5) were cooled to a rectal temperature of 20 degrees C before application of aortic clamps, maintained at this level during cardiopulmonary bypass until the aorta was unclamped, and then slowly rewarmed to 37 degrees C. Seven amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and five putative inhibitory neurotransmitters (glycine, gamma-aminobutyric acid, serine, adenosine, and taurine). Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. The increase in aspartate concentration was not significant. The extracellular concentrations of glycine and gamma-aminobutyric acid also increased significantly during ischemia and reperfusion. Hypothermia uniformly prevented the release of amino acids in the extracellular space. Glutamate levels remained significantly decreased even after rewarming to normothermia whereas glycine levels returned to baseline values. These results are consistent with a role for excitatory amino acids in the production of ischemic spinal cord injury and suggest that the mechanism of hypothermic protection may be related to decreased release of these amino acids in the ischemic spinal cord.

Hypothermic bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta.

BACKGROUND: Hypothermic cardiopulmonary bypass with intervals of circulatory arrest is a useful adjunct during operations on the descending thoracic aorta and distal aortic arch when severe aortic disease precludes placement of clamps on the aorta. Hypothermia also has a marked protective effect on spinal cord function during periods of aortic occlusion. METHODS: Fifty-one patients (age range, 22 to 79 years) with descending thoracic or thoracoabdominal aortic disease had resection and graft replacement of the diseased aortic segments using hypothermic cardiopulmonary bypass and intervals of circulatory arrest in situations where the location, extent, or severity of disease precluded placement of clamps on the proximal aorta (8 patients) or (in 43 patients) when extensive thoracic (11) or thoracoabdominal (32) aortic disease was present and the risk for development of spinal cord ischemic injury and renal failure was judged to be increased. Patent intercostal (below T-6) and upper lumbar arteries were attached to the graft whenever possible. RESULTS: Thirty-day mortality was 9.8% (5 patients). Paraplegia occurred in 2 and paraparesis in 1 of the 46 30-day survivors (6.5%). Among the 27 operative survivors with thoracoabdominal aneurysms, paraplegia occurred in 1 of 12 with Crawford type I (8%), 0 of 10 with type II, and 1 of 5 with type III aneurysms (20%). Paraplegia occurred in none of the 12 patients with aortic dissection and in 2 of the 15 patients with degenerative aneurysms. Renal failure requiring dialysis occurred in 1 (2.2%) of the 46 30-day survivors. CONCLUSIONS: Hypothermic circulatory arrest is a valuable adjunct for the treatment of complex aortic disease involving the aortic arch and thoracoabdominal aorta. In patients with thoracoabdominal aneurysms, its use has been associated with a low incidence of renal failure and an incidence of paraplegia/paraparesis in traditionally high-risk subsets (type I and II aneurysms, aortic dissection), which may be less than that observed with other surgical techniques.

Anterior septal coronary artery infarction in the canine: a model of ventricular tachycardia with a subendocardial origin. Ablation and activation sequence mapping.

BACKGROUND: In humans, chronic ventricular tachycardia (VT) is usually associated with myocardial infarcts that involve the interventricular septum. In an effort to more closely mimic the anatomic substrate that gives rise to chronic VT in humans, we developed a canine model of VT in which the anterior septal coronary artery was ligated. The site of earliest activation, the subsequent activation sequence, and the mechanism of VT associated with the resultant ventricular septal infarct was then evaluated to determine if this model accurately reflected the characteristics of human VT. METHODS AND RESULTS: Seventeen dogs underwent occlusion-reperfusion ventricular septal infarcts. Four to 7 days later, electrophysiological studies were performed. VT was initiated by programmed electrical stimulation and terminated by pacing at a cycle length of 50% to 75% of the VT cycle length. Electrophysiological studies were performed using a 256-channel mapping system. A total of 15 VT morphologies were mapped in 9 animals. Fourteen of 15 morphologies had septal subendocardial sites of earliest activation and 1 had a septal midwall site of earliest activation. VT ablation was performed using a nitrous oxide cryoprobe and confirmed the site of earliest activation by subsequently rendering VT noninducible. Electrophysiological studies demonstrated four distinct VT activation sequences: (1) circular reentrant (n = 7), (2) concentric spread (n = 5), (3) figure-of-eight (n = 2), and (4) septal midwall (n = 1). CONCLUSIONS: This canine model of ventricular septal infarction produces VTs with sites of earliest activation and activation sequences similar to those in humans. A reentrant mechanism as the basis of these arrhythmias is supported by the following observations: (1) all VT was initiated and terminated with programmed electrical stimulation; (2) VT activation sequences were consistent with reentry; and (3) precise interruption of the sequence terminated the VT and rendered it noninducible.

Dextrorphan inhibits the release of excitatory amino acids during spinal cord ischemia.

The release of excitatory amino acids, particularly glutamate, into the extracellular space plays a causal role in irreversible neuronal damage after central nervous system ischemia. Dextrorphan, a noncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to provide significant protection against cerebral damage after focal ischemia. We investigated the changes in extracellular neurotransmitter amino acid concentrations using in vivo microdialysis in a swine model of spinal cord ischemia. After lumbar laminectomies were performed, all animals underwent left thoracotomy and right atrial-femoral cardiopulmonary bypass with additional aortic arch perfusion. Microdialysis probes were then inserted stereotactically into the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid and 15-minute samples were assayed using high-performance liquid chromatography. Group 1 animals (n = 9) underwent aortic clamping distal to the left subclavian and proximal to the renal arteries for 60 minutes. Group 2 animals (n = 7) were treated with dextrorphan before application of aortic clamps, and during aortic occlusion and reperfusion. Five amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and three putative inhibitory neurotransmitters (glycine, gamma-amino-butyric acid, and serine). Somatosensory-evoked potentials and motor-evoked potentials were monitored. Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. In animals treated with dextrorphan, glutamate concentrations decreased to one-third of baseline levels before aortic clamping and remained unchanged during ischemia and reperfusion. There was early loss of somatosensory-evoked potentials and motor-evoked potentials during ischemia in group 1 animals.(ABSTRACT TRUNCATED AT 250 WORDS)