Competitive NMDA receptor antagonists and spinal-cord ischemia.

Ischemic neuronal death is associated with excitatory amino acid (EAA) release. Their action is mediated by N-methyl-D-aspartate (NMDA) receptors. Blockade of the receptors before the ischemic insult can decrease neuronal damage. Accordingly, we investigated the protective effect during spinal cord ischemia of two competitive antagonists, 4-(3-phosphonopropyl)-2-piperazine-carboxylic acid (CPP) and cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS). Male Sprague-Dawley rats underwent intrathecal administration of 10 microL saline, CGS, and CPP 10 mM solutions, in a randomized blinded fashion, and were subjected to balloon occlusion of the thoracic aorta. Proximal aortic pressure was lowered to a mean of 40 mm Hg by partial exsanguination. In the acute protocol, 21 rats divided in 3 groups of 7 (saline, CPP, and CGS) were used to calculate the aortic occlusion time (AOT) resulting in paraplegia in 50% of animals (P50). In the chronic study, 24 rats divided in 4 groups of 6 (saline, CPP, CGS, sham) underwent 12-min occlusion. The chronic animals were scored daily for 28 days and submitted to histology of the cord. In the acute study, the P50 of CGS (10 min 48 s) and CPP (11 min 11 s) was longer than saline (10 min 27 s). In the chronic groups, analysis of variance of neurologic (p = .66) and histologic (p = .66) scores did not disclose differences between CGS, CPP, and saline. In conclusion, blockade of NMDA receptors with CPP or CGS may afford some protection for durations of occlusion around the P50, but it is not beneficial when ischemic injury is more protracted.

Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia and thrombosis.

Heparin-induced thrombocytopenia and thrombosis (HITT) is an immunomediated disorder induced by the administration of heparin for therapeutic purposes. The presence of this condition in patients requiring full heparinization for cardiopulmonary bypass constitutes a formidable challenge for the cardiac surgeon. In this review, the clinical and experimental experience described in the literature are discussed in the perspective of the normal coagulation and the pathophysiology of HITT and in the light of a variety of old and new alternative anticoagulants.

Retrograde perfusion of the spinal cord during aortic crossclamping: initial observations in the swine model.

BACKGROUND: Retrograde perfusion has emerged as a useful technique for the preservation of the heart and brain when arterial circulation is interrupted. Herein, this study was designed to test the hypothesis that retrograde perfusion of the azygos vein is sufficient to maintain viability of the spinal cord during aortic occlusion in the swine model. METHODS: Female swine, 17 to 22 kg, underwent left thoracotomy, creation of a shunt between the aortic arch and the azygos vein, and aortic crossclamping for 60 minutes: the shunt was open in the retrograde perfusion group (n = 5) and closed in the control group (n = 4). The animals were evaluated for neurologic function for 8 days and killed. Spinal cords were processed for histologic examination. Additional animals underwent left thoracotomy and injection of a casting solution in the azygos vein (n = 2), left thoracotomy and angiography of the azygos vein (n = 2), and a compartmentalization procedure to separate the azygos vein from the caval system followed by angiography (n = 2). RESULTS: Differences in the neurologic (2-sample t test, P =.11) and histologic (2-sample t test, P =.65) scores of retrograde perfusion and control groups were likely due to chance. Casting and angiography groups showed extensive collaterals between azygos and caval systems, only partially interrupted by compartmentalization. CONCLUSIONS: Retrograde perfusion does not protect the spinal cord from ischemic injury. The collateral network between the azygos and caval systems prevents the oxygenated blood from reaching the cord. Surgical separation between the 2 systems was only partially successful in this study.

Selective protection of gray and white matter during spinal cord ischemic injury.

BACKGROUND: Ischemic injury in the gray matter is associated with excitatory amino acid neurotransmitters (EAA) release, and in the white matter is associated with intracellular sodium accumulation. We investigated the protective effect during spinal ischemia of the EAA antagonist, 2-carboxypiperazinyl-propylphosphonic acid (CPP), and the sodium channel blocker (2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX). METHODS: Sprague-Dawley rats were randomized in four groups, received intrathecally 10 microL of saline, CPP, QX, or QX/CPP, and underwent balloon occlusion of the aorta. Proximal pressure was lowered by exsanguination. In the acute protocol, 28 rats were used to calculate the length of occlusion, resulting in paraplegia in 50% of animals (P50). In the chronic study, 60 rats underwent 11' occlusion. The chronic animals were scored daily for 28 days and submitted to cord histology. RESULTS: The P50 of QX (11'22") and QX/CPP (11'54") were longer than saline (10'39"), suggesting a beneficial effect. Neurologic scores of all treatment groups (p = 0.0001) and histologic scores of CPP (p = 0.003) and QX/CPP (p = 0.002) were better than saline. CONCLUSIONS: Protection of spinal cord during ischemia can be achieved with intrathecal administration of selective agents directed to the gray and white matter.

Primary mediastinal malignancies: findings in 219 patients.

The purpose of this study was to determine the demographics, histology, methods of treatment, and survival in primary mediastinal malignancies. We did a retrospective review of the statewide New Mexico Tumor Registry for all malignant tumors treated between January 1, 1973 and December 31, 1995. Benign tumors and cysts of the mediastinum were excluded. Two hundred nineteen patients were identified from a total of 110,284 patients with primary malignancies: 55% of tumors were lymphomas, 16% malignant germ cell tumors, 14% malignant thymomas, 5% sarcomas, 3% malignant neurogenic tumors, and 7% other tumors. There were significant differences in gender between histologies (P < 0.001). Ninety-four percent of germ cell tumors occurred in males, 66% of neurogenic tumors were in females; other tumors occurred in males in 58% of cases. There were also significant differences in ages by histology (P < 0.001). Neurogenic tumors were most common in the first decade, lymphomas and germ cell tumors in the second to fourth decades, and lymphomas and thymomas in patients in their fifth decades and beyond. Stage at presentation (P = 0.001) and treatment (P < 0.001) also differed significantly between histologic groups. Five-year survival was 54% for lymphomas, 51% for malignant germ cell tumors, 49% for malignant thymomas, 33% for sarcomas, 56% for neurogenic tumors, and 51% overall. These survival rates were not statistically different (P > 0.50). Lymphomas, malignant germ cell tumors, and thymomas were the most frequently encountered malignant primary mediastinal neoplasms in this contemporary series of patients. Demographics, stage at presentation, and treatment modality varied significantly by histology. Despite these differences, overall five-year survival was not statistically different.

Catastrophic hemorrhage on sternal reentry: still a dreaded complication?

BACKGROUND: To define the incidence of catastrophic hemorrhage (CH) during reoperations, the experience of the University of New Mexico was reviewed and compared with the practice of surgeons contacted by questionnaire. METHODS: At the University of New Mexico, 610 reoperations were reviewed and 210 deemed high risk because of multiple reoperation, aneurysm, patent grafts, chamber's enlargement, conduit or previous mediastinitis. In the questionnaire, we asked about reentry technique, occurrence and outcome of CH, and precautions for high-risk patients. RESULTS: At the University of New Mexico there were 4 CH with 1 death, and in the questionnaire there were 2,046 CH with 392 deaths. Our rate per surgeon was lower than that of the questionnaire. Rate of CH according to the saw was 2.09 for reciprocating, 2.0 for sagittal, and 1.74 for stryker in the questionnaire. Our rate was lower (0.65) with a micro sagittal saw. High-risk category predicted CH during sternotomy (p = 0.01) but only conduit (p = 0.005) was significant by univariate analysis. CONCLUSIONS: The risk of CH could be as high as 1%. The sagittal micro oscillating saw is the safest reported to date. Presence of a conduit increases the risk by 2.5 fold.

Posterior ventricular septal rupture: an anatomical reconstruction.

Rupture of the ventricular septum following posterior myocardial infarction is an uncommon, but lethal, injury that requires prompt repair. Surgical reconstruction can be complex, demanding, and unfamiliar. Conventional techniques, as described in the literature, are associated with a variety of potential pitfalls. An alternative method we have successfully used in our last four patients is presented in detail. The procedure uses two composite (felt/pericardium) patches: an internal patch to reconstruct the left ventricular geometry and an external patch to repair the subtotal infarctectomy. For maximal security, all suture lines sandwich myocardium between two continuous felt surfaces. Specific transition stitches are described, which reliably anchor the entire repair at the critical, but poorly visualized, areas where the ventricular septum makes its transition to left and right ventricular free walls. This technique offers immediate hemostasis and a more anatomical left ventricular geometry. The method also reduces the risk of systemic thromboembolism, residual VSD, and repair disruption.

Videothoracoscopic treatment of hepatic hydrothorax.

Hepatic hydrothorax occurs frequently in ascites arising from communications in the diaphragm between peritoneal and pleural cavities. Numerous treatments have been described but are of limited utility due to invasiveness and poor success rate. We describe a case of hepatic hydrothorax in which the pore in the diaphragm was documented photographically and in which successful resolution was achieved with videothoracoscopic suture ligation and talc pleurodesis.

Intrapleural fibrinolytics in management of empyema thoracis.

STUDY OBJECTIVE: To determine the success and complication rates of fibrinolytic therapy (FL) in the treatment of thoracic empyema. DESIGN AND PATIENTS: Between December 1992 and November 1994, all patients referred with empyema thoracis (ET) were offered FL. FL consisted of streptokinase (275,000 +/- 170,000 IU) or urokinase (121,000 +/- 57,000 IU) daily for a mean of 6.2 +/- 2.1 days. SETTING: The University of New Mexico Health Sciences Center and the Albuquerque Veterans Affairs Medical Center. RESULTS: Twenty-six patients were treated. Sixty-two percent (16/26) had complete resolution (CR) of symptoms, near or complete normalization of chest radiographic findings, and required no surgery or empyema tubes. Eight percent (2/26) had relief of symptoms and partial resolution (PR) of radiographic abnormalities and were discharged from the hospital with empyema tubes in place. All patients with PR had empyema tubes removed within 30 days of hospital discharge. Thirty-one percent (8/26) of patients failed to completely improve clinically or radiographically (nonresponse) and were treated with decortication or empyema tubes for greater than 30 days. Bleeding occurred in a single patient (4%). There was no mortality associated with FL use. CONCLUSIONS: The use of FL is associated with resolution of ET in 69% (18/26) of patients. This modality is safe, effective, and spares most patients with empyema the morbidity and mortality of thoracotomy.

Role of poloxamer 188 during recovery from ischemic spinal cord injury: a preliminary study.

Paraplegia following aortic surgery is not a common event. When it does occur it significantly alters the patient's outcome. Poloxamer 188 (P188) has been shown in the experimental animal to increase regional blood flow to ischemic areas. In order to investigate its protective effect during aortic cross-clamping, 23 animals were randomized to two groups (placebo n = 11, P188n = 12) and received an intravenous injection of placebo or P188 (200 mg/kg), and underwent occlusion of the thoracic aorta and both subclavian arteries for a period of 13 minutes. They were then connected to an intravenous pump delivering either placebo or P188 (250 mg/kg/hr at a rate of 0.942 ml/hour) for 48 hours. Hindlimb function was appraised, daily for 30 days, by a lesion score (0-15). Spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. Analysis of variance for repeated measures did not reveal significant difference between P188 and placebo groups (P = 0.66). Similarly, the mean histologic scores (placebo = 1.54 +/- 0.41 SE, P188 = 1.08 +/- 0.33 SE) did not differ (Wilcoxon, P = 0.43). We conclude that intravenous administration of P188 before, during, and for 48 hours after aortic cross-clamping does not prevent paraplegia or improve the long term neurologic outcome.

Percutaneous cardiopulmonary support for the management of catastrophic mechanical complications of acute myocardial infarction.

Acute papillary muscle rupture and ventricular septal rupture following myocardial infarction are associated with high mortality. We describe the use of cardiopulmonary support to resuscitate two patients, each with one of the above conditions. Early recognition and rapid deployment of CPS were critical to successful outcome.

Multiple polyposis and adenocarcinoma arising in Barrett's esophagus.

Adenomatous polyps of the esophagus are rare in comparison with those of the lower gastrointestinal tract. Like adenomatous colon polyps, they have been associated with malignancy. We describe a case of early adenocarcinoma and multiple polyposis of the esophagus arising in a Barrett's epithelium, treated with surgical resection.

Osteogenesis imperfecta and cardiovascular diseases.

Aortic and mitral valvular insufficiency in patients with osteogenesis imperfecta result from an underlying defect in connective tissue formation. The surgical cases reported in the literature have included mechanical and bioprosthetic valve replacement as well as attempts at repair and reconstruction. Despite complications related to bleeding and tissue friability, acceptable results have been obtained. In this report, we describe aortic regurgitation secondary to osteogenesis imperfecta treated with homograft replacement. The unique cardiovascular complications of osteogenesis imperfecta and the available therapeutic options are discussed in light of the literature review.

Experimental delayed postischemic spinal cord hypoperfusion after aortic cross-clamping.

BACKGROUND: As in the brain, recent evidence has suggested a defect in the microcirculation during the reperfusion period after spinal cord ischemia. This investigation was undertaken in order to delineate blood flow dynamics in the postischemic spinal cord of the rat. METHODS: Male Sprague-Dawley rats underwent cross-clamping of the aorta and subclavian arteries (XC) for 11 minutes. Spinal cord blood flow (SCBF) was measured by autoradiography in the gray and white matter of cervical (Ce), thoracic (Th) and lumbar (Lu) regions during XC, 1 h, 6 h and 24 h (XC n = 8, 1 h n = 9, 6 h n = 9, and 24 h n = 11, groups) after XC. Control groups underwent surgical manipulations and SCBF measurement but no XC (Sham 1, n = 8), or clamping of the subclavian arteries only (Sham 2, n = 8). RESULTS: In Ce cord, there was no difference between SCBF of 1 h, 6 h, 24 h and Sham 1. In Th cord, SCBF was reduced during XC (P < 0.003 vs. Sham 2), 1 h, 6 h (P < 0.04 and P < 0.01 vs. Sham 1). In Lu cord, SCBF was not detectable in XC, and depressed in 1 h (P < 0.003) and 6 h (P < 0.003). There was no difference between 24 h and Sham 1 in Ce, Th, and Lu cords. CONCLUSIONS: The study demonstrated a period of delayed postischemic hypoperfusion in the white and gray matter of Th and Lu cord segments lasting 6 h after XC. The phenomenon may play an important role in the ultimate fate of neural elements with borderline viability after ischemic injury.

Gangliosides and spinal cord ischemia secondary to aortic cross-clamping in the rat model.

Gangliosides, complex glycolipids of the nervous system cell membranes, have been found effective both in reducing the degree of ischemic injury and in stimulating neuronal regeneration during the recovery period. In order to investigate their neuroprotective effect during spinal cord ischemia, 60 male Sprague-Dawley rats underwent occlusion of the thoracic aorta and both subclavian arteries for 13 min. In the postoperative period, function of hindlimbs was appraised, daily for 30 days, by a deficit score (0-15). The animals were then killed and spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. The rats received intraperitoneal injection of placebo (n = 29) or GM-1 30 mg/kg (n = 31) daily, from 2 days prior to surgery to 15 days after. The scores of each group for each day were analyzed by repeated measures analysis of variance. The rate of recovery was better for GM-1 (P < 0.001) from the 15th to the 30th day. A trend was seen toward lower scores in the GM-1 group (P = 0.056). Mean histologic scores (placebo = 1.14 +/- 0.23 SE, GM-1 = 1.58 +/- 0.22 SE) did not differ (Wilcoxon, P = 0.17). The present data support the hypothesis that functional improvement after spinal cord ischemia due to aortic occlusion is enhanced by the administration of gangliosides. Optical microscopy could document only irreversible injury and might not be sensitive enough to detect subtle changes during recovery of neural elements.

Air embolus complicating transthoracic percutaneous needle biopsy.

Transthoracic percutaneous needle biopsy has become popular for evaluation of pulmonary nodules. However, it is a procedure with morbidity and mortality that is not negligible. In this article, we report massive air embolus complicating needle biopsy in a patient with amyloidosis. A negative biopsy does not exclude malignancy, and if surgical excision will be performed regardless of the result, preoperative assessment using this technique may not be necessary.

Internal fixation of high tracheal stents.

A technique for internal fixation of a silicone elastomer tracheal stent is described. This technique allows the use of a short stent in situations where complex stent placement otherwise would be necessary. The procedure was used successfully to manage a postresection stricture in the subglottic trachea.

Degeneration of axons in the corticospinal tract secondary to spinal cord ischemia in rats.

Occlusion of the thoracic aorta and both subclavian arteries (XC) in the rat model produces spastic paraplegia. In order to characterize the lesion of white matter, 14 male Sprague-Dawley rats underwent XC for 10.5 to 12 min, were observed for 32 days and assessed with a lesion score. A sham group of eight underwent surgical manipulations without XC. The spinal cords were studied by optical microscopy and electron microscopy. An additional group of normal animals (n = 8) underwent spinal cord blood flow measurement with the autoradiographic technique. Optical microscopy showed normal histology in sham operated rats and rats with aortic cross-clamp and lesion score = 2-4 (n = 5), rare changes in the white matter of rats with lesion score = 8 (n = 2), and demyelination of the anterior and lateral tracts of the white matter and motor neuron loss in the gray matter of rats with lesion score = 13-15 (n = 7) and spastic paraplegia. In this last group, electron microscopy disclosed severe axonal degeneration of corticospinal tracts. In the same region spinal cord blood flow was higher than the remaining white matter. This study confirms that spastic paraplegia observed in the rat model after XC is due to degeneration of the pyramidal tracts, perhaps more susceptible to injury due to the high spinal cord blood flow.

NMDA receptor blockade and spinal cord ischemia due to aortic crossclamping in the rat model.

Recent brain research proposes that, during ischemia, synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death. Their action is mediated by the receptor subtype N-methyl-D-aspartate (NMDA). The protective effect of NMDA receptor blockade with intrathecal MgSO4 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes. Male Sprague-Dawley rats, 250-300g, underwent intrathecal administration of 20 microL of normal saline (SA n = 16), MgSO4 1M (MG n = 16), or MK-801, 25 mM solutions (MK n = 16) in a randomized order. After 2 hours, the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min. An additional control group (CO n = 16) underwent occlusion for 12 minutes, without intrathecal injection. The animals were scored according to their functional performance (LS = lesion score) each day for four days by a blinded observer. Mean LS were calculated for each group at a given day. Treatment and control groups were not different at day 1 (P = 0.302). Group MG was improved from groups SA (P = < 0.0039) and CO (P = < 0.0048) at day 4. This study demonstrates that although intrathecal NMDA receptor blockade with MgSO4 or MK-801 does not prevent paraplegia due to spinal cord ischemia in the rat, it could however influence the rate of recovery after ischemic injury.