Decreased DNA Disruption in the Porcine Neocortex with Erythromycin Preconditioning during Prolonged Hypothermic Circulatory Arrest: Evidence for Neuroprotection.

BACKGROUND AND AIM OF THE STUDY: We have previously reported that the neocortex is selectively vulnerable to injury in an acute porcine model of hypothermic circulatory arrest (HCA) at 18°C. In view of recent evidence showing that pharmacologic preconditioning with a single dose of erythromycin induces tolerance against transient global cerebral ischemia in rats, we hypothesized that erythromycin would reduce the number of apoptotic neurons in the neocortex in an acute porcine model of HCA at 18°C. METHODS: Fourteen piglets underwent 75 min of HCA at 18°C following pretreatment with erythromycin (25 mg/kg, IV) (n = 8) or vehicle (Normal Saline 0.9%) (n = 6), applied 12 hr before arrest. Three served as normal controls. After gradual rewarming to a temperature of 36°C, treatment animals were sacrificed and brains were perfusion-fixed and cryopreserved. Neuronal apoptosis after HCA was observed morphologically with hematoxylin and eosin staining, and characterized by in situ DNA fragmentation using terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry. RESULTS: Pre-ischemic conditioning with a single dose of the antibiotic erythromycin reduced neuronal apoptosis in the neocortex of the porcine brain. TUNEL-positive cells indicating DNA fragmentation and neuronal injury were significantly greater in the neocortex of animals treated with 18°C HCA (2.55 ± 1.17) compared to animals undergoing HCA after erythromycin preconditioning (1.76 ± 0.91) (p ≤ 0.001). CONCLUSIONS: These results suggest that cerebral protection during HCA may be achieved with erythromycin pharmacological preconditioning in the porcine model.

Atypical pattern of lung involvement in pacemaker endocarditis.

Pacemaker endocarditis has a high rate of morbidity and mortality and is associated with substantial health-care cost. To maximize the effectiveness of treatment, diagnosis of pacemaker endocarditis should be made as early as possible. Medical treatment alone is not successful, and the removal of the entire artificial pacing system is often required. We present a case of a female patient with a permanent transvenous pacemaker, recurring episodes of fever and chills, general malaise, and a computed tomography image of a solitary tumor-like lesion indicating pneumonia. The symptoms subsided with empirical antibiotics but without improvement in the radiologic images. A wedge resection of the lesion by thoracotomy was performed, revealing a necrotic lung lesion compatible with pulmonary infarct. Transesophageal echocardiography showed a mass that was adherent to the pacemaker lead. The therapeutic approach consisted of surgical removal of the complete pacing system along with long-term antibiotic therapy and implantation of a new device with an epicardial lead. Serial follow-up echocardiograms for a 1-y period did not show any recurrence, and the subsequent course was uneventful.

Aortic root aneurysm in an adult patient with aortic coarctation: a single-stage approach.

Coarctation of the aorta is a common congenital defect that may be undiagnosed until adulthood. Moreover, coarctation is associated with congenital and acquired cardiac pathology that may require surgical intervention. The management of an adult patient with aortic coarctation and an associated cardiac defect poses a great technical challenge since there are no standard guidelines for the therapy of such a complex pathology. Several extra-anatomic bypass grafting techniques have been described, including methods in which distal anastomosis is performed on the descending thoracic aorta, allowing simultaneous intracardiac repair. We report here a 37-year old man who was diagnosed with an aortic root aneurysm and aortic coarctation. The patient was treated electively with a single-stage approach through a median sternotomy that consisted of valve-sparing replacement of the aortic root and ascending-to-descending extra-anatomic aortic bypass, using a 18-mm Dacron graft. Firstly, the aortic root was replaced with the Yacoub remodelling procedure, and then the distal anastomosis was performed to the descending aorta, behind the heart, with the posterior pericardial approach. The extra-anatomic bypass graft was brought laterally from the right atrium and implanted in the ascending graft. Postoperative recovery was uneventful and a control computed tomographic angiogram 1 month after complete repair showed good results.

Noninvasive ventilation for post-pneumonectomy severe hypoxemia.

ARDS remains a lethal complication after major lung resections. The reported mortality ranges from 50% to 100%, with increased incidence and mortality rates in pneumonectomy patients. The pathogenesis of early ARDS is still not fully understood, and the majority of patients will require mechanical ventilation. A review of the literature reveals that the role of noninvasive ventilation (NIV) in ARDS after lung resection is unclear, in contrast to its well established benefits in other types of respiratory failure. NIV is a technique of augmenting alveolar ventilation delivered by face mask, without introducing an endotracheal tube. NIV may reduce the need for endotracheal mechanical ventilation and improve clinical outcome in patients with acute respiratory failure after lung resection, avoiding complications related to intubation. We present a case of early ARDS following left-sided pneumonectomy, where bi-level positive airway pressure ventilation prompted a successful outcome.

Total circulatory arrest: a life-saving procedure for mediastinoscopic major hemorrhage.

Acute hemorrhage during mediastinoscopy is a life-threatening complication. Although rare, iatrogenic damage of the thoracic great vessels is probable during mediastinoscopic biopsy. We report two cases of iatrogenic massive mediastinoscopic bleeding from the aortic arch and innominate artery managed initially by simple packing and controlled finally by cardiopulmonary bypass and repair under total circulatory arrest.

Modified staged surgical approach to coexisting severe coronary artery disease and large abdominal aortic aneurysm.

Surgical management of coexisting severe coronary artery disease and large or symptomatic abdominal aortic aneurysm may be required in patients who are unsuitable candidates for minimally invasive interventions. Although several options have been proposed, the optimal timing to deal with both entities, in order to achieve the best outcome, is still debatable. This report presents a modified approach based on a two-stage treatment in a single anesthetic session.

Hypothermia at 10 degrees C reduces neurologic injury after hypothermic circulatory arrest in the pig.

BACKGROUND: We have previously reported that sensory, motor neocortex, and hippocampus are selectively vulnerable to injury in an acute porcine model of HCA at 18 degrees C. This study was undertaken to assess whether further cooling to 10 degrees C can reduce neurological injury during HCA. METHODS: Twelve piglets underwent 75 minutes of HCA at 18 degrees C (n = 6) and 10 degrees C (n = 6). Four served as normal controls. After gradual rewarming and 80 minutes of reperfusion, treatment animals were sacrificed and brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after HCA were characterized by in situ DNA fragmentation using TUNEL histochemistry. Hematoxylin and eosin histology was used to characterize cell damage morphologically. TUNEL-positive cells were scored on a scale of 0 to 5. Grade 0: no TUNEL-positive cells; Grade 1: < 10%; Grade 2: 10% to 25%, Grade 3: 25% to 50%, Grade 4: 50% to 75%; and Grade 5: > 75%. RESULTS: TUNEL-positive cells indicating DNA fragmentation were scored in the motor and sensory neocortex, hippocampus, cerebellum, thalamus, and medulla of animals treated with 18 degrees C and 10 degrees C HCA and were significantly greater than in normal controls. Profound cooling to 10 degrees C resulted in a significant reduction of neuronal injury in the neocortex and hippocampus. CONCLUSIONS: This data support that cerebral protection may be better at very cold temperatures compared to 18 degrees C hypothermia. Regions selectively vulnerable to neuronal injury are offered more neural protection by profound hypothermia. These affects are observed in the acute state, suggesting activation of the apoptotic mechanisms at early stages can be inhibited by profound hypothermia.

Temporary adrenal dysfunction with descending thoracic aortic occlusion.

BACKGROUND: We sought to determine whether descending thoracic aortic occlusion (DTAOC) induced ischemia results in adrenal dysfunction. METHODS: Eight pigs underwent DTAOC for 45 min. Six control pigs underwent a sham procedure. Serum cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline, at the end of DTAOC, 30 and 60 min after restoration of flow, and 24 hours later. Statistical analysis was performed using repeated measures ANOVA and t-test. RESULTS: In the study group, cortisol levels decreased during DTAOC (p=0.048) and 30 min after flow restoration (p=0.004). In the control group there was no change in serum cortisol levels. In the study group the drop in serum cortisol was associated with an increase in ACTH levels during DTAOC (p=0.040) and 30 minutes after flow restoration (p=0.070). The increase in ACTH was also significant when compared to the controls during DTAOC (p=0.030) and 30 min after blood flow restoration (p=0.040). CONCLUSIONS: There is a transient period of adrenal dysfunction associated with DTAOC that results in stimulation of the pituitary-adrenal axis.

Effect of profound hypothermia during circulatory arrest on neurologic injury and apoptotic repressor protein Bcl-2 expression in an acute porcine model.

OBJECTIVES: We reported that the neocortex and hippocampus are selectively vulnerable to injury in an acute porcine model of hypothermic circulatory arrest at 18 degrees C. We hypothesize that further cooling to 10 degrees C could reduce neurologic injury in these regions. To further elucidate the mechanisms of neurologic injury and protection, we assessed the expression of the anti-apoptotic protein Bcl-2. METHODS: Twelve piglets underwent 75 minutes of hypothermic circulatory arrest at 18 degrees C (n = 6) and 10 degrees C (n = 6). After gradual rewarming and reperfusion, animals were put to death and brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after hypothermic circulatory arrest were characterized by in situ DNA fragmentation with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) histochemistry. Bcl-2 protein expression was characterized with immunohistochemistry. Statistical comparisons were made by t test, analysis of variance, and Mann-Whitney U test, as appropriate. RESULTS: Concentrations of TUNEL(+) cells were significantly lower after profound hypothermia at 10 degrees C compared with 18 degrees C hypothermia in the sensory and motor neocortex and hippocampus (t test, P < .0001; P < .006; P < .006, respectively). Positive Bcl-2 immunostaining was observed only in the motor and sensory neocortex and hippocampus after 18 degrees C hypothermic circulatory arrest. Profound cooling to 10 degrees C resulted in a significant increase in Bcl-2 immunostaining in the motor and sensory cortex as compared with 18 degrees C (Mann-Whitney U test, P < .05). CONCLUSIONS: Deep hypothermia at 10 degrees C protects the neocortex and hippocampus from insult during hypothermic circulatory arrest as suggested by significantly reduced TUNEL(+) staining in these areas. Although a concomitant increase in Bcl-2 expression was observed in the neocortex at 10 degrees C, it remains unclear whether profound hypothermia deters from neuronal injury by activation of the anti-apoptotic protein Bcl-2.

Endovascular repair for thoracic aortic disease: tertiary single-center experience in northwestern Greece.

The purpose of this article is to report the initial experience with endovascular repair of thoracic aortic disease in a single tertiary vascular unit in northwestern Greece. Between 2003 and 2005, 16 patients were treated with endovascular techniques for various pathologies of the descending thoracic aorta. Twelve patients were treated electively and four emergently. Operative and follow-up data for a mean time of 18.4 months were retrospectively collected and analyzed. Primary technical success was obtained in 14 (87.5%) cases. No early or late deaths occurred, and there was no major operation-related complication. No paraplegia was observed in our patients. Stent graft-related complications occurred in 18.75% (one type 2 and two type 3 endoleaks), but they all had a favorable outcome. No further problems have been reported in any of our patients. Endovascular stent graft repair for diseases of the thoracic aorta seems to be a promising alternative to open surgery, especially for high-risk patients. Long-term results are needed to confirm the early benefit of this treatment option with regard to morbidity and mortality rates. The potential of this technique to be applicable even in relatively small, tertiary vascular centers might be of great benefit to patients.

Endovascular stent-graft repair as a late secondary procedure after previous aortic grafts.

Thoracic and abdominal aortic endovascular procedures as alternatives to aortic reoperations were studied in three different cases. An anastomotic aneurysm after previous thoracic aortic graft for coarctation, a second-stage elephant trunk repair (descending thoracic aortic aneurysm), and a secondary aneurysm proximal to a previous abdominal aortic graft were successfully treated with endovascular stent-grafts. During the follow-up period no lethal events or major aortic or graft-related complications were observed, except a type II endoleak in the anastomotic aortic aneurysm case. An endovascular stent-graft can be safely deployed into a previously implanted vascular graft, avoiding repeat surgery.

Acute regional neuronal injury following hypothermic circulatory arrest in a porcine model.

OBJECTIVES: Although deep hypothermic circulatory arrest (HCA) is routinely used to interrupt normal perfusion of the brain and prevent subsequent cerebral ischemic injury during cardiac surgery, it is associated with various forms of neurologic disturbances. Neurologic sequelae after prolonged HCA include motor, memory and cognitive deficits. The present study was designed to assess acute regional neuronal injury after HCA in an animal model. METHODS: Six piglets underwent 75 min of HCA at 18 degrees C. Four piglets served as normal controls. After gradual rewarming and reperfusion, treatment animals were killed and their brains were perfusion-fixed and cryopreserved. Regional patterns of neuronal apoptosis after HCA was characterized by in situ DNA fragmentation using terminal deoxyneucleotidyl-transferase-mediated biotin-dUTP nick end-labeling (TUNEL) histochemistry. Hematoxylin and eosin histology was used to characterize cell damage morphologically. TUNEL-positive cells were scored on a scale of 0 to 5. Grade 0: no TUNEL-positive cells; Grade 1: <10%, Grade 2: 10-25%, Grade 3: 25-50%, Grade 4: 50-75%; and Grade 5: >75%. RESULTS: TUNEL-positive cells indicating DNA-fragmentation were scored in the precentral gyrus (motor neocortex), postcentral gyrus (sensory neocortex), hippocampus, cerebellum, thalamus and ventral medulla of HCA treated animals and were significantly greater than in normal controls (P

Superiority of early relative to late ischemic preconditioning in spinal cord protection after descending thoracic aortic occlusion.

OBJECTIVE: We previously showed that ischemic preconditioning significantly reduced spinal cord injury caused by 35-minute aortic occlusion. In this study we investigated the effect of ischemic preconditioning on spinal cord injury after 45-minute aortic occlusion. METHODS: Thirty-two pigs were divided as follows: group 1 (n = 6) underwent sham operation, group 2 (n = 6) underwent 20 minutes of aortic occlusion, group 3 (n = 6) underwent 45 minutes of occlusion, group 4 (n = 6) underwent 20 minutes of occlusion and 48 hours later underwent an additional 45 minutes, and group 5 (n = 8) underwent 20 minutes of occlusion and 80 minutes later underwent an additional 45 minutes. Aortic occlusion was accomplished with two balloon occlusion catheters placed fluoroscopically after the origin of the left subclavian artery and at the aortic bifurcation. Neurologic evaluation was by Tarlov score. The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin-eosin staining. The number of neurons was counted, and the inflammation was scored (0-4). Statistical analysis was by Kruskal-Wallis and 1-way analysis of variance tests. RESULTS: Group 5 (early ischemic preconditioning) had better Tarlov scores than group 3 ( P < .001) and group 4 (late ischemic preconditioning, P < .001). The histologic changes were proportional to the Tarlov scores, with the least histologic damage in the animals of group 5 relative to group 3 (number of neurons P < .001, inflammation P = .004) and group 4 (number of neurons P < .001, inflammation P = .006). CONCLUSION: Early ischemic preconditioning is superior to late ischemic preconditioning in reducing spinal cord injury caused by the extreme ischemia of 45 minutes of descending thoracic aortic occlusion.

Early ischemic preconditioning without hypotension prevents spinal cord injury caused by descending thoracic aortic occlusion.

OBJECTIVE: Postoperative neurologic deficits after thoracic aortic reconstruction vary widely. Our previous study showed that delayed ischemic preconditioning could prevent spinal cord injury caused by occlusion of the descending thoracic aorta in pigs. We investigated early ischemic preconditioning in the same model. METHODS: Twenty-eight pigs were divided into 4 groups: group 1 (n = 6) underwent a sham operation, group 2 (n = 6) underwent aortic occlusion for 20 minutes, group 3 (n = 8) underwent aortic occlusion for 35 minutes, and group 4 (n = 8) underwent aortic occlusion for 20 minutes and underwent aortic occlusion 80 minutes later without hypotension for 35 minutes. Aortic occlusion was accomplished by using 2 balloon occlusion catheters placed fluoroscopically at T6 to T8 above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to the Tarlov scale (0-4). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin-and-eosin stain. Histologic results (number of neurons and grade of inflammation) were scored (0-4) and were similarly analyzed. Statistical analysis was by means of the Kruskal-Wallis test. RESULTS: Group 4 had a better neurologic outcome at 24, 48, and 120 hours in comparison with group 3 (P <.001). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in animals of group 3 (number of neurons, P <.001; grade of inflammation, P <.001). CONCLUSION: Early ischemic preconditioning without hypotension protects against spinal cord injury after aortic occlusion, as confirmed by using the Tarlov score and histopathology.

Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion?

OBJECTIVE: Ischemic preconditioning has been found to protect various organs from a subsequent longer ischemic insult. We investigated whether the late phase of ischemic preconditioning reduces spinal cord injury from occlusion of the descending thoracic aorta. METHODS: Twenty-four pigs (27 to 30 kg) were randomly divided in four groups: group I (n = 4) underwent a sham operation, group II (n = 4) underwent aortic occlusion for 20 minutes, group III (n = 8) underwent aortic occlusion for 35 minutes, and group IV (n = 8) underwent aortic occlusion for 20 minutes and, 48 hours later, aortic occlusion for 35 minutes. Aortic occlusion was accomplished with two balloon occlusion catheters placed fluoroscopically at T(6) to T(8) above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to Tarlov's scale (0 to 4, with 4 as normal). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin and eosin stain. Histologic results (number of neurons and grade of inflammation) were scored 0 to 4 (4, intact spinal cord; 0, no neurons and high inflammation) and were similarly analyzed. Results were expressed as the mean +/- the standard error of the mean, and statistical analysis used the Kruskal-Wallis test. RESULTS: Group IV had a better neurologic outcome at 24, 48, and 120 hours in comparison with group III (P <.001), although 120 hours after the end of the experiment, the neurologic outcome in group IV was worse than at 24 hours (P =.014). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in the animals of group III (number of neurons, P <.001; and grade of inflammation, P <.001). CONCLUSION: Ischemic preconditioning (late phase, 48 hours after the first occlusion) reduces spinal cord injury after aortic occlusion, as estimated with Tarlov's score and histopathology.

Is vitamin C superior to diltiazem for radial artery vasodilation in patients awaiting coronary artery bypass grafting?

OBJECTIVES: We aimed to measure the vasodilating effects of vitamin C on the radial arteries of healthy subjects and to assess whether vitamin C is superior in this regard to diltiazem, a commonly used vasodilator in coronary artery bypass using radial conduits. METHODS: In a case-control study (study 1) oral single-dose vitamin C (2 g) was given to 15 healthy nonsmokers and 15 matched otherwise healthy smokers. In a randomized double-blind study (study 2) oral single-dose vitamin C (2 g, n = 15) and diltiazem (180 mg, n = 15) were compared in preoperative patients with coronary artery disease. We examined the dilation of the radial artery with high-resolution ultrasonography and measurement of the lumen surface and color Doppler images of the nondominant radial artery just before and 2 hours after drug administration. RESULTS: In study 1 both smokers and nonsmokers showed a significant increase in the lumen surface at 2 hours compared with at baseline (P <.001 and P =.013, respectively). The increase was larger in smokers (median, 37.5% vs 14.3%; P =.004). In study 2 both groups showed statistically significant increases in the lumen surface at 2 hours compared with at baseline (P <.001 and P =.008 for vitamin C and diltiazem, respectively). Vitamin C achieved a larger increase than diltiazem (median, 33.3% vs 18.2%; P =.016). In multivariate modeling the increase in lumen surface was independently predicted by use of vitamin C over diltiazem (+21.2%, P =.007), diabetes mellitus (+14.5%, P =.085), increased cholesterol (+26.2%, P =.001), and smoking history (+20.8%, P =.017). CONCLUSIONS: Vitamin C is a potent acute vasodilator in both smokers and nonsmokers and is superior to diltiazem in preoperative coronary patients who need protection from vasospasm of the radial conduit.