Relationship of the long thoracic nerve to the scapular tip: an aid to prevention of proximal nerve injury.

OBJECTIVE: The objective was to determine the course of the long thoracic nerve relative to the scapula as an aid to the prevention of proximal long thoracic nerve injuries. METHODS: Eighteen fresh cadavers (7 male, 11 female) were studied. Each was sequentially placed in the transaxillary and posterolateral thoracotomy positions, and the distance of the long thoracic nerve from the scapular tip and anterior scapular border was measured. The measurements were made bilaterally; the mean, standard deviation, and 99% confidence interval were calculated for each position by gender. RESULTS: Distances from the scapular tip to the long thoracic nerve are listed as mean/outer range: transaxillary thoracotomy, male 4.9/7.0 cm left, 5.2/7.5 cm right; female 4.3/5.0 cm left, 4.7/6.0 cm right; posterolateral thoracotomy, male 3.1/6.0 cm left, 4.5/5.1 cm right; female 3.2/4.5 cm left, 3.8/5.5 cm right. In all instances, the long thoracic nerve was furthest from the scapula at its tip. CONCLUSION: For patients positioned for a transaxillary thoracotomy, incision sites should be at least 7.5 and 6.0 cm anterior to the scapular tip for male and female patients, respectively. For patients in posterolateral thoracotomy positioning, incisions should be 6.0 and 5.5 cm anterior to the scapular tip for male and female patients, respectively. By using these anatomic guidelines, we believe that the incidence of iatrogenic proximal long thoracic nerve injury can be minimized.

The role of the monosialoganglioside, GM1 as a neuroprotectant in an experimental model of cardiopulmonary bypass and hypothermic circulatory arrest.

Twelve male dogs were placed on closed-chest cardiopulmonary bypass, subjected to 2 h of HCA at 18 degrees C, and rewarmed to 37 degrees C on closed-chest cardiopulmonary bypass. All animals were mechanically ventilated and monitored for 20 h before extubation and survived for 3 days. Group 1 dogs (n = 6) were pretreated with GM1, 30 mg/kg/24 h for 3 days before HCA, and received continuous infusion of GM1 during the procedure and 30 mg/kg/24 h for 3 days after HCA. Group 2 dogs (n = 6) received vehicle only. With a species-specific behavior scale that yielded a neurodeficit score ranging from 0% (normal) to 100% (brain dead), all animals were neurologically assessed every 12 h by two observers. After death at 72 h, brains were examined by glutamate receptor autoradiography and by histologic examination for patterns of selective neuronal necrosis and were scored blindly from 0 (normal) to 100 (severe injury). These results provide evidence of a role for GE in the development of HCA-induced brain injury and suggest that monosialogangliosides may have a neuroprotective effect in prolonged periods of HCA.

Monosialoganglioside GM1 inhibits neurotoxicity after hypothermic circulatory arrest.

BACKGROUND: Prolonged hypothermic circulatory arrest (HCA) causes clinical neurologic injury. This injury involves neuronal apoptosis, or programmed cell death. We have previously demonstrated that HCA causes glutamate excitotoxicity, increased nitric oxide (NO) production, and NO-mediated apoptosis. We hypothesized that monosialoganglioside GM1 inhibits NO synthase. The purpose of this study was to determine whether GM1 inhibits NO production and neuronal apoptosis after HCA. METHODS: Fourteen dogs underwent intracerebral microdialysis to measure excitatory amino acids, glutamate, aspartate, and citrulline, an equal coproduct of NO. They underwent 2 hours of HCA at 18 degrees C and were sacrificed 8 hours after HCA. Group 1 (n = 6) was pretreated with GM1, 30 mg/kg intravenously every day for 3 days, as well as before and after HCA. Group 2 control dogs (n = 8) received vehicle only. Apoptosis was scored from 0 (normal) to 100 (severe injury). RESULTS: Excitatory amino acids, aspartate and glutamate, coagonist glycine, and citrulline levels increased significantly over baseline during HCA and after HCA. GM1 pretreatment did not appreciably alter levels of glutamate, aspartate, and glycine; however, it substantially decreased citrulline and therefore NO production throughout the experiment. GM1 significantly inhibited apoptosis (group 1 vs group 2: 15.56 +/- 13.60 vs 62.92 +/- 6.17; P < .001). CONCLUSIONS: Our results provide the first direct evidence that GM1 inhibits NO synthase to reduce NO production and HCA-induced neuronal apoptosis. GM1 did not affect excitatory glutamate or aspartate levels. GM1 has been used in clinical trials of spinal cord injury and may be efficacious in reducing neurologic injury after HCA.

Training women surgeons and their academic advancement.

The responsibility for those of us involved in residency training programs is to foster the development of future leaders in thoracic surgery. Although the actual training of female surgeons is no different than training male surgeons, academic advancement after training can be more difficult for women due to a variety of reasons. The education and training of female surgeons has its origin in admission to medical school followed by recruitment into a residency program. Following completion of a residency program, the retainment of women and men faculty should be the goal of departments and divisions of thoracic surgery. Specific recommendations are made for retainment of faculty. In addition to academic promotion and financial reward, creating the proper environment is an important consideration to allow women the chance to succeed in medicine. This report addresses the training aspects involved in the thoracic residency program and the state of professional academic advancement at the Johns Hopkins University School of Medicine.

Nitric oxide mediates neurologic injury after hypothermic circulatory arrest.

BACKGROUND: Prolonged hypothermic circulatory arrest (HCA) causes neurologic injury. However, the mechanism of this injury is unknown. We hypothesized that HCA causes nitric oxide production to result in neuronal necrosis. This study was undertaken to determine whether the neuronal nitric oxide synthase inhibitor 17477AR reduces necrosis after HCA. METHODS: Thirty-two dogs underwent 2 hours of HCA at 18 degrees C. Nitric oxide synthase catalytic assay and intracerebral microdialysis for nitric oxide production were performed in acute nonsurvival experiments (n = 16). Sixteen animals survived for 72 hours after HCA: Group 1 (n = 9) was treated with 17477AR (Astra Arcus), and group 2 (n = 7) received vehicle only. Animals were scored from 0 (normal) to 500 (coma) for neurologic function and from 0 (normal) to 100 (severe) for neuronal necrosis. RESULTS: Administration of 17477AR reduced nitric oxide production in the striatum by 94% (HCA alone), 3.65+/-2.42 micromol/L; HCA and 17477AR, 0.20+/-0.14 micromol/L citrulline). Dogs treated with 17477AR after HCA had superior neurologic function (62.22+/-29.82 for group 1 versus 141.86+/-61.53 for group 2, p = 0.019) and significantly reduced neuronal necrosis (9.33+/-4.67 for group 1 versus 38.14+/-2.23 for group 2, p<0.00001) compared with untreated HCA dogs. CONCLUSIONS: Our results provide evidence that neuronal nitric oxide synthase mediates neuronal necrosis after HCA and plays a significant role in HCA-induced neurotoxicity. Pharmacologic strategies to inhibit neuronal nitric oxide synthase after the ischemic period of HCA may be clinically beneficial.

Increased intracerebral excitatory amino acids and nitric oxide after hypothermic circulatory arrest.

BACKGROUND: Prolonged hypothermic circulatory arrest (HCA) results in neurologic injury, but the mechanism of this injury is unknown. This study was undertaken to measure quantitatively intracerebral excitatory amino acids and citrulline, an equal coproduct of nitric oxide, during HCA. We hypothesized that HCA resulted in higher levels of glutamate, aspartate, glycine, causing increased intracellular calcium, and therefore, nitric oxide and citrulline. METHODS: Ten dogs underwent intracerebral microdialysis and 2 hours of HCA at 18 degrees C. Effluent was analyzed by high performance liquid chromatography with electrochemical detection. Five dogs each were sacrificed at 8 and 20 hours after HCA. Neuronal apoptosis was scored from 0 (no injury) to 100 (severe injury). RESULTS: Time course of HCA was divided into six periods. Peak levels of amino acids in each period were compared with those at baseline. Glutamate, coagonist glycine, and citrulline, an equal coproduct of nitric oxide, increased significantly over baseline during HCA, cardiopulmonary bypass, and 2 to 8 hours after HCA. Aspartate increased significantly during HCA and 8 to 20 hours after HCA. Apoptosis score was 65.56 +/- 5.67 at 8 hours and 30.63 +/- 14.96 at 20 hours after HCA. CONCLUSIONS: Our results provide direct evidence that HCA causes increased intracerebral glutamate and aspartate, along with coagonist glycine. We conclude that HCA causes glutamate excitotoxicity with subsequent nitric oxide production resulting in neurologic injury, which begins during arrest and continues until 20 hours after hypothermic circulation arrest. To provide effective cerebral protection, pharmacologic strategies to reduce glutamate excitotoxicity require intervention beyond the initial ischemic insult.

Assessing the impact of cerebral injury after cardiac surgery: will determining the mechanism reduce this injury?

BACKGROUND: Central nervous system dysfunction continues to produce significant morbidity and associated mortality in patients undergoing cardiac surgery. Using a closed-chest canine cardiopulmonary bypass model, dogs underwent 2 h of hypothermic circulatory arrest (HCA) at 18 degrees C, followed by resuscitation and recovery for 3 days. Animals were assessed functionally by a species-specific behavioral scale, histologically for patterns of selective neuronal necrosis, biochemically by analysis of microdialysis effluent, and by receptor autoradiography for N-methyl-D-aspartate (NMDA) glutamate receptor subtype expression. RESULTS: Using a selective NMDA (glutamate) receptor antagonist (MK801) and an AMPA antagonist (NBQX), glutamate excitotoxicity in the development of HCA-induced brain injury was documented and validated. A microdialysis technique was employed to evaluate the role of nitric oxide (NO) in neuronal cell death. Arginine plus oxygen is converted to NO plus citrulline (CIT) by the action of NO synthase (nNOS). CIT recovery in the cerebrospinal fluid and from canine cortical homogenates increased during HCA and reperfusion. These studies demonstrated that neurotoxicity after HCA involves a significant and early induction of nNOS expression, and neuronal processes leading to widespread augmentation of NO production in the brain. To further investigate the production of excitatory amino acids in the brain, we hypothesized the following scenario: HCA--> increased glutamate, increased aspartate, increased glycine--> increased intracellular Ca2+--> increased NO + CIT. Using the same animal preparation, we demonstrated that HCA caused increased intracerebral glutamate and aspartate that persists up to 20 h post-HCA. HCA also resulted in CIT (NO) production, causing a continued and delayed neurologic injury. Confirmatory evidence of the role of NO was demonstrated by a further experiment using a specific nNOS inhibitor, 7-nitroindazole. Animals underwent 2 h of HCA, and then were evaluated both physiologically and for NO production. 7-Nitroindazole reduced CIT (NO) production by 58.4 +/- 28.3%. In addition, dogs treated with this drug had superior neurologic function compared with untreated HCA controls. CONCLUSIONS: These experiments have documented the role of glutamate excitotoxicity in neurologic injury and have implicated NO as a significant neurotoxin causing necrosis and apoptosis. Continued research into the pathophysiologic mechanisms involved in cerebral injury will eventually yield a safe and reliable neuroprotectant strategy. Specific interventional agents will include glutamate receptor antagonists and specific neuronal NO synthase inhibitors.

Neuronal nitric oxide synthase inhibition reduces neuronal apoptosis after hypothermic circulatory arrest.

BACKGROUND: Neurologic injury, including choreoathetosis and learning and memory deficits, occurs after prolonged hypothermic circulatory arrest (HCA). Apoptosis, or programmed cell death, is a possible cause of the neurologic injury seen after HCA. However, the mechanism of apoptosis is unknown. Hypothermic circulatory arrest causes glutamate excitotoxicity, resulting in increased nitric oxide production. We therefore hypothesized that nitric oxide mediates apoptosis. The purpose of this study was to determine if neuronal nitric oxide synthase inhibition reduces neuronal apoptosis in an established canine model of HCA. METHODS: Fourteen male hound dogs (weight, 20 to 27 kg) were placed on closed-chest cardiopulmonary bypass, subjected to 2 hours of HCA at 18 degrees C, rewarmed to normothermia, and sacrificed 8 hours after HCA. Group 1 (n = 7) dogs were treated with the neuronal nitric oxide inhibitor 7-nitroindazole, 25 mg/kg intraperitoneally, before arrest and every 2 hours until sacrifice. Group 2 (n = 7) dogs received vehicle only. The brains were analyzed histopathologically. Apoptosis, identified by hematoxylin-eosin staining, was confirmed by DNA terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling assay and electron microscopy. Apoptosis was scored by a blinded neuropathologist from 0 (normal) to 100 (severe injury). RESULTS: Apoptosis occurred early after HCA in select neuronal populations, including the hippocampus, stria terminalis, neocortex, and entorhinal cortex. Apoptotic neurons showed a characteristic shrunken cytoplasm and nuclear chromatin condensation. 7-Nitroindazole significantly inhibited apoptosis (group 1 versus 2: 19.17 +/- 14.39 versus 61.11 +/- 5.41; p < .001). CONCLUSIONS: Our results provide evidence that apoptosis is associated with the neurologic injury that occurs after HCA and that nitric oxide mediates the apoptosis that occurs after HCA. Strategies for cerebral protection during HCA may include the inhibition of neuronal nitric oxide synthase.

Cerebral hemodynamics changes during retrograde brain perfusion in dogs.

The objective of this study was to examine cerebral hemodynamics changes during hypothermic circulatory arrest (HCA) with and without retrograde cerebral perfusion (RCP). Thirteen colony-bred hound dogs were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. Five dogs underwent 2 hours of HCA without RCP and 8 with RCP. The animals were then rewarmed on CPB until normothermic and weaned. Cerebral blood flow velocity (CBFV) and Gosling Pulsatility Index (PI) in the middle cerebral artery (MCA) were studied using trans-cranial Doppler ultrasound (TCD). At baseline and during pre- and postarrest CPB, there was anterograde direction of blood flow in the MCA. During HCA with RCP, there was retrograde direction of blood flow in the MCA. There was no difference in CBFV between pre-, during, and postarrest CPB in the group with RCP; however, there was significantly increased CBFV during postarrest CPB in the group without RCP compared to the dogs with RCP. Later, at 3 hours after postarrest CPB, there was decreased CBFV in all animals accompanied by increased PI (2.4 +/- 0.4 and 2.2 +/- 0.6 for animals with RCP and without RCP, respectively) and abnormal TCD waveform changes including decreased diastolic compartment and sharp systolic peak. During hypothermic circulatory arrest, RCP provides CBFV in the MCA comparable to MCA CBFV during CPB. HCA dogs without RCP showed immediate hyperemia on reperfusion. The decreased CBFV and increased PI at 1 hour after postarrest CPB could be an indicator of progressive ischemic injury due to the increased intracranial pressure despite the implementation of RCP.

Acute type A aortic dissection intimal tears by 64-slice computed tomography: a role for endovascular stent-grafting?

AIM: The goal of this study was to identify physical characteristics of primary intimal tears in patients arriving to the hospital alive with acute type A aortic dissection using 64-multislice computerized tomography (MSCT) in order to determine anatomic feasibility of endovascular stent-grafting (ESG) for future treatment. METHODS: Radiology database was screened for acute type A aortic dissection since the time of acquisition of the 64-slice CT scanner and cross-referenced with surgical database. Seventeen patients met inclusion criteria. Images were reviewed for number, location, and size of intimal tears and aortic dimensions. Potential obstacles for ESG were determined. RESULTS: Ascending aorta (29%) and sinotubular junction (29%) were the most frequent regions where intimal tears originated. Location of intimal tears in nearly 75% of patients was inappropriate for ESG, and 94% of patients did not have sufficient proximal or distal landing zone required for secure fixation. Only 71% of patients underwent surgical aortic dissection repair after imaging and 86% of entry tears detected on MSCT were confirmed on intraoperative documentation. Only one patient would have met all technical criteria for ESG using currently available devices. CONCLUSION: Location of intimal tear, aortic valve insufficiency, aortic diameter>38 mm are major factors limiting use of ESG for acute type A dissection. Available stents used to treat type B aortic dissection do not address anatomic constraints present in type A aortic dissection in the majority of cases, such that development of new devices would be required.

Hemodynamic determinants of aortic dissection propagation by 2D computational modeling: implications for endovascular stent-grafting.

AIM: Aortic dissection is a life-threatening aortic catastrophe where layers of the aortic wall are separated allowing blood flow within the layers. Propagation of aortic dissection is strongly linked to the rate of rise of pressure (dp/dt) experienced by the aortic wall but the hemodynamics is poorly understood. The purpose of this study was to perform computational fluid dynamics (CFD) simulations to determine the relationship between dissection propagation in the distal longitudinal direction (the tearing force) and dp/dt. METHODS: Five computational models of aortic dissection in a 2D pipe were constructed. Initiation of dissection and propagation were represented in 4 single entry tear models, 3 of which investigated the role of length of dissection and antegrade propagation, 1 of which investigated retrograde propagation. The 5th model included a distal re-entry tear. Impact of pressure field distribution on tearing force was determined. RESULTS: Tearing force in the longitudinal direction for dissections with a single entry tear was approximately proportional to dp/dt and L2 where L is the length of dissection. Tearing force was much lower under steady flow than pulsatile flow conditions. Introduction of a second tear distally along the dissection away from the primary entry tear significantly reduced tearing force. CONCLUSION: The hemodynamic mechanism for dissection propagation demonstrated in these models support the use of ß-blockers in medical management. Endovascular stent-graft treatment of dissection should ideally cover both entry and re-entry tears to reduce risk of retrograde propagation of aortic dissection.

Acid phosphatase in the rat prostate: comparison with other organs.

Properties of acid phosphatase in the rat ventral prostate were compared with those in seven other organs in adult male rats by the electrophoretic mobility in acrylamide gels, susceptibility to reactions with inhibitors, and by their response to castration and subsequent testosterone replacement. The enzyme in the spleen exhibited the highest values of Km and Vmax. These values in the prostate, the liver, and the kidney showed an intermediate level, while the lowest level was found in the heart, the lung, the adrenals, and the seminal vesicle. Upon electrophoresis, a total of six isoenzyme bands were resolved. Two major zones of activity were noted. They were the slow-moving anodal bands (isoenzymes 1,2, and 3) and the fast-moving cathodal bands (isoenzymes 4,5, and 6). The spleen possessed the highest number of isoenzymes (bands 1,2,4,5 and 6) and the prostate had three (bands 1,2, and 3). The heart contained only one (band 2). Two isoenzymes (bands 1 and 2) were found in remaining organs. Results of the effects of inhibitors showed that NaF inhibited all six isoenzymes, while L(+)tartrate inhibited mainly those in the anodal zone. D(-)tartrate and formaldehyde showed no significant inhibition to any of the isoenzymes. PCMB (para-chloromercuribenzoic acid) was found to be a specific inhibitor for isoenzyme 3. Upon castration in the hosts, the enzyme activity in the prostate, the liver, and the seminal vesicle was significantly reduced. This reduction in enzyme activity involved all isoenzymes in these three organs, but isoenzyme 3 in the prostate disappeared completely after castration. The activities of these isoenzymes were restored by testosterone replacement. These results indicate that acid phosphatase in rat tissues has multiple forms; each has its own electrophoretic mobility in acrylamide gels, sensitivity to inhibitors, and response to hormonal manipulation. Isoenzyme 3 is specific to the prostate and is uniquely sensitive to PCMB inhibition and to androgen stimulation.

Apoptosis detection in brain using low-magnification dark-field microscopy.

Apoptosis or programmed cell death is a feature of normal brain development and a response to brain injury. Cells undergoing apoptosis have a characteristic morphology that normally can only be appreciated at high magnification. Using dark-field transmitted light microscopy to examine Nissl-stained material, we detected groups of apoptotic cells at much lower magnifications than often were required in the two injury models we tested. This method was useful for screening entire brain sections to assess regional and global patterns of injury. We predict that this technique in which we detect the clumped chromatin associated with apoptosis can be applied to other types of tissue.

Aortic valve replacement in the elderly. Risk factors and long-term results.

OBJECTIVE: The current study was undertaken to determine long-term results of aortic valve replacement (AVR) in the elderly, to ascertain predictors of poor outcome, and to assess quality of life. SUMMARY BACKGROUND DATA: Aortic valve replacement is the procedure of choice for elderly patients with aortic valve disease. The number of patients aged 70 and older requiring AVR continues to increase. However, controversy exists as to whether surgery devoted to this subset reflect a cost-effective approach to attaining a meaningful quality of life. METHODS: This study reviews data on 247 patients aged 70 to 89 years who underwent isolated AVR between 1980 and 1995; there were 126 men (51%) and 121 women (49%). Follow-up was 97% complete (239/247 patients) for a total of 974.9 patient-years. Mean age was 76.2 +/- 4.8 years. Operative mortality and actuarial survival were determined. Patient age, gender, symptoms, associated diseases, prior conditions, New York Health Association class congestive heart failure, native valve disease, prosthetic valve type, preoperative catheterization data, and early postoperative conditions were analyzed as possible predictors of outcome. Functional recovery was evaluated using the SF-36 quality assessment tool. RESULTS: Operative mortality was 6.1% (15/247). Multivariate logistic regression showed that poor left ventricular function and preoperative pacemaker insertion were independent predictors of early mortality. After surgery, infection was predictive of early mortality. Overall actuarial survival at 1, 5, and 10 years was 89.5 +/- 2% (198 patients at risk), 69.3 +/- 3.4% (89 patients at risk), and 41.2 +/- 6% (13 patients at risk), respectively. Cox proportional hazards model showed that chronic obstructive pulmonary disease and urgency of operation were independent predictors of poor long-term survival. Postoperative renal failure also was predictive of poor outcome. Using the SF-36 quality assessment tool, elderly patients who underwent AVR scored comparably to their age-matched population norms in seven of eight dimensions of overall health. The exception is mental health. CONCLUSIONS: Aortic valve replacement in the elderly can be performed with acceptable mortality. Significant preoperative risk factors for early mortality include poor left ventricular function and preoperative pacemaker insertion. Predictors of late mortality include chronic obstructive pulmonary disease and urgency of operation. These results stress the importance of operating on the elderly with aortic valve disease; both long-term survival and functional recovery are excellent.