Do you need to clamp a patent left internal thoracic artery-left anterior descending graft in reoperative cardiac surgery?

BACKGROUND: Dogma suggests optimal myocardial protection in cardiac surgery after prior coronary artery bypass graft surgery (CABG) with patent left internal thoracic artery (LITA) pedicle graft requires clamping the graft. However, we hypothesized that leaving a patent LITA-left anterior descending (LAD) graft unclamped would not affect mortality from reoperative cardiac surgery. METHODS: Data were collected on reoperative cardiac surgery patients with prior LITA-LAD grafts from July 1995 through June 2006 at our institution. With the LITA unclamped, myocardial protection was obtained initially with antegrade cardioplegia followed by regular, retrograde cardioplegia boluses and systemic hypothermia. The Society of Thoracic Surgeons National Database definitions were employed. The primary outcome was perioperative mortality. Variables were evaluated for association with mortality by bivariate and multivariate analyses. RESULTS: In all, 206 reoperations were identified involving patients with a patent LITA-LAD graft. Of these, 118 (57%) did not have their LITA pedicle clamped compared with 88 (43%) who did. There were 15 nonsurvivors (7%): 8 of 188 (6.8%) in the unclamped group and 7 of 88 (8.0%) in the clamped group (p = 0.750). Nonsurvivors had more renal failure (p = 0.007), congestive heart failure (p = 0.017), and longer perfusion times (p = 0.010). When controlling for independently associated variables for mortality, namely, perfusion time (odds ratio 1.014 per minute; 95% confidence interval: 1.004 to 1.023; p = 0.004) and renal failure (odds ratio 4.146; 95% confidence interval: 1.280 to 13.427; p = 0.018), an unclamped LITA did not result in any increased mortality (odds ratio 1.370; 95% confidence interval: 0.448 to 4.191). Importantly, the process of dissecting out the LITA resulted in 7 graft injuries, 2 of which significantly altered the operation. CONCLUSIONS: In cardiac surgery after CABG, leaving the LITA graft unclamped did not change mortality but may reduce the risk of patent graft injury, which may alter an operation.

Cardiac injury during resternotomy does not affect perioperative mortality.

BACKGROUND: Cardiac injury at the time of resternotomy is a complication faced by all cardiac surgeons, although little is known about its effects on morbidity and mortality. This study was designed to address these questions. STUDY DESIGN: Resternotomies performed at the University of Virginia from 1996 to 2005 were identified. Operative notes were reviewed, and any injury during resternotomy to the heart, great vessels, or bypass grafts was recorded. Perioperative complications and mortality were recorded using the Society of Thoracic Surgeons National Database. RESULTS: In the 11-year period studied, 612 resternotomies were performed out of 7,872 total adult cardiac procedures (7.8%). Fifty-six patients (9.1%) had an injury sustained during resternotomy and initial dissection. Injury to grafts was most common (46.4%), with mammary arteries comprising 21% of the total and vein grafts, 25%. The right ventricle was the second most commonly injured structure (21.4%). There were no significant differences in overall nonadjusted mortality in the injured group compared with that in the noninjured group (8.9% versus 10.2%, p=0.66). Multivariate analysis demonstrated third-time resternotomy to be an independent risk factor for cardiac injury (p=0.04). CONCLUSIONS: Cardiac injury at the time of resternotomy is not associated with an increase in perioperative morbidity or mortality. Third-time resternotomy is an independent risk factor for cardiac injury, so vigilance and adequate preparation are paramount in these patients.

Additive protection against lung ischemia-reperfusion injury by adenosine A2A receptor activation before procurement and during reperfusion.

OBJECTIVE: Adenosine A2A receptor activation during reperfusion improves lung ischemia-reperfusion injury. In this study we sought to determine whether pretreatment of rabbits with a potent and selective adenosine A2A receptor agonist, ATL-313, before transplantation or whether adding ATL-313 to the preservation solution results in equivalent or additional protection compared with ATL-313 added during reperfusion. METHODS: An isolated, ventilated, ex vivo blood-perfused rabbit lung model was used. All groups underwent 2 hours of reperfusion after 18 hours of cold ischemia (4 degrees C). ATL-313 was administered 1 hour before ischemia intravenously, with the preservation solution, and/or during reperfusion. RESULTS: Both pretreatment of donor animals with ATL-313 or adding ATL-313 just during reperfusion improved pulmonary function, but significantly greater improvement was observed when pretreatment and treatment during reperfusion were combined (all P < .05). Myeloperoxidase levels, bronchoalveolar lavage tumor necrosis factor alpha levels, and pulmonary edema were all maximally decreased in the combined treatment group. The administration of an equimolar amount of the potent and highly selective adenosine 2A receptor antagonist, ZM 241385, along with ATL-313, resulted in the loss of protection conferred by ATL-313. CONCLUSIONS: Adenosine A2A receptor activation with ATL-313 results in the greatest protection against lung ischemia-reperfusion injury when given before ischemia and during reperfusion. Improved pulmonary function observed with adenosine A2A receptor activation was correlated with decreased bronchoalveolar lavage tumor necrosis factor alpha and decreased lung myeloperoxidase. The loss of protection observed with the concurrent administration of the adenosine A2A receptor antagonist, ZM 241385, supports that the mechanism of ATL-313 protection is specifically mediated via adenosine A2A receptor activation.

Adenosine A2A activation attenuates nontransplantation lung reperfusion injury.

BACKGROUND: Lung reperfusion injury is a significant problem in cardiothoracic surgery. Previous studies have demonstrated that an adenosine A(2A) agonist can attenuate lung reperfusion injury in a lung transplantation model. There has been little work, however, examining its effects in the setting of nontransplant ischemia reperfusion. Our hypothesis was that an A(2A) agonist would attenuate lung reperfusion injury in a warm ischemia hilar clamping model. STUDY DESIGN: Sprague Dawley rats underwent 90 min of left hilar clamping followed by 4 h of reperfusion. Group 1 (n = 13) received an intravenous infusion of 0.06 ug/kg/min of ATL-146e, which was started 10 min before reperfusion. Group 2 (n = 16) received an equivalent saline infusion. A third sham group (n = 14) received the same protocol as Group 2 but no lung ischemia. RESULTS: Animals receiving ATL-146e showed significant improvements in oxygenation (Group 1: 447 +/- 26.02 mmHg versus Group 2: 223 +/- 24.46 mmHg (P < 0.001) as well as ventilation (pCO2 Group 1: 48.78 +/- 3.88 versus Group 2: 63.56 +/- 4.80 (P = 0.009)). Total protein in the bronchoalveolar lavage was significantly higher in the saline group compared with the adenosine as well as a higher proportion of neutrophils. Histological analysis demonstrated a significantly higher number of neutrophils in the IR group compared with the adenosine group. CONCLUSIONS: ATL-146e, an adenosine analogue that is a specific agonist for the A(2A) receptor, attenuates reperfusion injury in an in vivo rat lung model. Arterial blood gas measurements demonstrate a statistically significant increase in oxygenation and improved ventilation.

Pulmonary macrophage inhibition and inhaled nitric oxide attenuate lung ischemia-reperfusion injury.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is postulated to occur biphasically. Donor pulmonary macrophages mediate early injury, and neutrophil-dependent injury predominates in the later phase of LIRI. We hypothesized that the biphasic response to LIRI would be attenuated by the administration of gadolinium, a known pulmonary macrophage inhibitor, and inhaled nitric oxide (NO), a pulmonary vasodilator that also interferes with neutrophil chemotaxis. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, study groups (n = 10 per group) underwent two hours of reperfusion after 18 hours of cold ischemia (4 degrees C). Lungs received gadolinium alone, or inhaled NO in the presence or absence of macrophage inhibition with gadolinium. RESULTS: Compared with control animals, pulmonary macrophage inhibition with the concurrent administration of inhaled NO increased lung compliance (p < 0.01) and oxygenation (p = 0.03), while also decreasing pulmonary artery pressure (p < 0.01), myeloperoxidase content by 63% (p < 0.01), wet to dry ratios by 23% (p < 0.01), and lung tissue (p < 0.01) and bronchoalveolar lavage tumor necrosis factor-alpha (TNF-alpha) protein levels (p < 0.01). CONCLUSIONS: The severity of LIRI was most significantly reduced by the inhibition of pulmonary macrophages and the concomitant use of inhaled NO. Pulmonary macrophages, likely through the elaboration of proinflammatory cytokines such as TNF-alpha, not only cause early injury themselves but also prime cells such as neutrophils to injure lungs in the later stages of LIRI. The LIRI was effectively blunted by the reduction of macrophage-dependent injury by gadolinium while inhaled NO also attenuated injury by reducing pulmonary hypertension and minimizing neutrophil sequestration.

Attenuation of lung reperfusion injury by modified ventilation and reperfusion techniques.

BACKGROUND: High ventilation and perfusion pressures after lung transplantation may have deleterious effects. We hypothesized that using combined protective approaches for ventilation and perfusion would be optimal for reducing injury and improving function after ischemia-reperfusion. METHODS: Using an isolated, blood-perfused, rabbit lung model, lungs underwent 120 minutes of reperfusion either immediately (Sham) or after 18 hours of cold ischemia (IR). Groups Sham-P and IR-P underwent protective ventilation and reperfusion, and Groups Sham-C and IR-C underwent conventional ventilation and reperfusion. Protective ventilation involved gradually increasing the flow rate during 5 minutes to 1.8 liters/min, and conventional ventilation entailed immediate initiation of flow at 1.8 liters/min. Protective reperfusion involved gradually increasing perfusion during 5 minutes to 60 ml/min, and conventional reperfusion entailed immediate perfusion at 60 ml/min. Two other groups underwent either protective ventilation with conventional perfusion or vice versa. Airway pressure, pulmonary artery pressure, and arterial blood gases were measured throughout reperfusion. Wet/dry weight, highest oxygenation index, and bronchoalveolar lavage (BAL) protein were also measured. RESULTS: Protective ventilation and perfusion after ischemia (IR-P) resulted in significant improvements in lung function as measured by increased Po(2) and decreased Pco(2), airway pressure, and highest oxygenation index compared with conventional reperfusion (IR-C). Injury was significantly reduced in IR-P lungs as measured by reduced edema (wet/dry weight) and vascular leakage (BAL protein). In most cases, IR-P lungs performed better, with less injury than protective ventilation or perfusion alone. CONCLUSIONS: This protective approach of ventilation and perfusion after ischemia may improve lung function after transplantation, a simple method that could easily be applied clinically.

Early repair of complete atrioventricular septal defect is safe and effective.

BACKGROUND: Surgical repair of complete atrioventricular septal defect (CAVSD) is a well-established procedure performed on young children. Our hypothesis is that with modern techniques, the current risks of CAVSD repair in children aged younger than 3 months and in children older than 3 months are equal. METHODS: This was a retrospective review of 65 infants and children with a mean age of 10.9 months (range, 1 month to 15.5 years) who underwent CAVSD repair from 1990 to 2004. Twenty-six repairs (40%) were done on or before 3 months of age (group A) and 39 repairs (60%) were done after 3 months of age (group B). In all patients, the ventricular septal defect was repaired with an individualized approach according to each patient's specific anatomy: direct suturing without a patch, interposition of a small pericardial patch with a running suture, or both. The atrioventricular commissure was closed with interrupted sutures, and all atrial defects were closed with a pericardial patch. Data were analyzed using the chi2 analysis and the Fisher exact test. RESULTS: Three hospital deaths occurred (<30 days), 2 in group A and 1 in group B (7.7% vs 2.6%, respectively, p = 0.33). One death in group A occurred during another noncardiac surgery. Early reoperation (<1 year of initial surgery) for residual ventricular septal defect or significant mitral regurgitation, or both, occurred in 3 group A patients and in 4 group B patients (11.5% versus 10.3% respectively, p = 0.68). CONCLUSIONS: These results suggest that repair of CAVSD defects in children 3 months of age or younger had similar outcomes compared with those who underwent surgical repair after 3 months of age.

Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism.

BACKGROUND: ATL-146e protects the spinal cord from ischemia/reperfusion injury, presumably via adenosine A(2A) receptor activation, but this relationship remains unproven. We hypothesized that spinal cord functional and cytoarchitectural preservation from ATL-146e would be lost with simultaneous administration of the specific adenosine A(2A) antagonist ZM241385 (ZM), thus proving that adenosine A(2A) receptor activation is responsible for the protective effects of this compound. METHODS: New Zealand White rabbits underwent 45 minutes of infrarenal aortic cross-clamping. Groups (n = 10) included sham, ischemia, ischemia plus ATL-146e (ATL-146E), ischemia plus ZM, or ischemia with both compounds (agonist-antagonist). Tarlov scores were recorded every 12 hours. After 48 hours, the spinal cord was fixed for histology and microtubule-associated protein 2 immunohistochemistry. RESULTS: Tarlov scores at 48 hours were significantly better in the sham and ATL-146E groups (5.0 and 3.9, respectively) compared with the other three groups (all < or =1.3; P < .001). On hematoxylin and eosin, neuronal viability was higher in the sham, ATL-146E, and agonist-antagonist groups compared with the control and ZM groups (P < .05). Microtubule-associated protein 2 expression was preserved in the sham and ATL-146E groups but was lost in the ATL + ZM, ZM241385, and control groups. CONCLUSIONS: ATL-146e preserves the spinal cord in terms of both cytoarchitecture and function after reperfusion of the ischemic spinal cord, but this preservation is not completely blocked by competitive adenosine A(2A) receptor antagonism. Although ATL-146e does seem to partially function through activation of the adenosine A(2A) receptor, the neuroprotective mechanism may not be limited to this particular receptor.

A comparison of adenosine A2A agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits.

OBJECT: Steroid agents remain the lone pharmacological treatment in widespread use for acute spinal cord injury (SCI), although their utility remains in dispute in the neurotrauma literature. Adenosine A2A receptor activation with ATL-146e, a selective A2A agonist, has shown potential benefit in treating SCI; however, it has not been compared with the gold standard, methylprednisolone. The authors of this study evaluated ATL-146e and methylprednisolone for their ability to preserve neuronal viability and motor function in experimental SCI. METHODS: New Zealand White rabbits sustained SCI or sham injury via the Allen weight-drop technique. Ten minutes postinjury, animals received ATL-146e (ATL group, 0.06 microg/kg/min intravenously for 3 hours), methylprednisolone (steroid group, 30 mg/kg intravenously), or saline (trauma control group). Hindlimb motor function was recorded every 12 hours using the Tarlov motor grading scale (0, paralysis-5, normal hop). At 48 hours, fixed spinal cord tissue was evaluated for neuronal viability. Hindlimb motor function in animals treated with ATL-146e was equivalent to that of sham-injured animals and was significantly better than that of trauma control animals at all time points and that of steroid-treated animals at 12 hours (p = 0.05). Motor function in steroid-treated animals was worse than in those given ATL-146e and better than that of trauma control animals at later time points, but was not statistically significant (both p > 0.05). Neuronal viability (measured in neurons/hpf) was significantly higher in both treatment groups compared with the trauma control group (12.1 +/- 1.4 neurons/hpf for the ATL and 13.3 +/- 1.4 neurons/hpf for the steroid group compared with 7.5 +/- 1.5 neurons/hpf for the trauma control group; both p < 0.04). Neuronal viability did not differ among ATL-146e-treated, steroid-treated, and sham-injured groups. CONCLUSIONS: The use of ATL-146e is at least as effective as methylprednisolone in preserving function and is equivalent to methylprednisolone in preserving the structure of spinal cord tissue after blunt SCI. Adenosine A2A receptor activation may be an effective treatment for acute SCI while avoiding the adverse effects of steroid agents.

Comparison of systemic and retrograde delivery of adenosine A2A agonist for attenuation of spinal cord injury after thoracic aortic cross-clamping.

BACKGROUND: Paraplegia remains a devastating complication of thoracic aortic surgery, which has been attenuated by retrograde adenosine and systemic adenosine A2A receptor activation. We hypothesized that despite retrograde spinal perfusion of an adenosine A2A agonist (ATL-146e), systemic therapy produces superior spinal cord protection with reduced inflammation. METHODS: Forty pigs underwent 30-minute thoracic aortic cross-clamping. Pigs received: no therapy (control); retrograde saline (retrograde control); retrograde ATL-146e; systemic ATL-146e; systemic ATL-146e with retrograde saline; or systemic and retrograde ATL-146e. Retrograde therapies were given during ischemia. Systemic ATL-146e (0.06 microg.kg(-1).min(-1)) was given intravenously for 3 hours at reperfusion. At 24 hours, motor function was assessed using the Tarlov scale. Tissue was analyzed for neuronal viability, microtubule-associated protein-2 expression, and neutrophil sequestration (myeloperoxidase activity). RESULTS: Four pigs received retrograde barium showing both radiographic and histologic spinal cord perfusion. Tarlov scores at 24 hours were significantly improved versus both control groups in all ATL groups except the combined ATL-146e group (all p < 0.05). Neuronal viability by hematoxylin and eosin stain was significantly preserved in systemic ATL groups compared with both control groups (all p < 0.05). Microtubule-associated protein-2 expression was significantly preserved compared with both control groups in all systemic ATL groups. Systemic ATL significantly lowered myeloperoxidase activity versus both control groups (p < 0.01). CONCLUSIONS: Both retrograde and systemic ATL-146e therapies attenuate ischemic spinal cord injury, but combining the two routes was less effective. Given comparable results between the two routes and the simplicity of systemic delivery, peripheral venous ATL-146e at reperfusion should be preferred for spinal cord protection in thoracic aortic surgery.

Computational design and experimental testing of a novel axial flow LVAD.

Thousands of cardiac failure patients per year in the United States could benefit from long-term mechanical circulatory support as destination therapy. To provide an improvement over currently available devices, we have designed a fully implantable axial-flow ventricular assist device with a magnetically levitated impeller (LEV-VAD). In contrast to currently available devices, the LEV-VAD has an unobstructed blood flow path and no secondary flow regions, generating substantially less retrograde and stagnant flow. The pump design included the extensive use of conventional pump design equations and computational fluid dynamics (CFD) modeling for predicting pressure-flow curves, hydraulic efficiencies, scalar fluid stress levels, exposure times to such stress, and axial fluid forces exerted on the impeller for the suspension design. Flow performance testing was completed on a plastic prototype of the LEV-VAD for comparison with the CFD predictions. Animal fit trials were completed to determine optimum pump location and cannulae configuration for future acute and long-term animal implantations, providing additional insight into the LEV-VAD configuration and implantability. Per the CFD results, the LEV-VAD produces 6 l/min and 100 mm Hg at a rotational speed of approximately 6300 rpm for steady flow conditions. The pressure-flow performance predictions demonstrated the VAD's ability to deliver adequate flow over physiologic pressures for reasonable rotational speeds with best efficiency points ranging from 25% to 30%. The CFD numerical estimations generally agree within 10% of the experimental measurements over the entire range of rotational speeds tested. Animal fit trials revealed that the LEV-VAD's size and configuration were adequate, requiring no alterations to cannulae configurations for future animal testing. These acceptable performance results for LEV-VAD design support proceeding with manufacturing of a prototype for extensive mock loop and initial acute animal testing.

Hyperoxic ventilation exacerbates lung reperfusion injury.

OBJECTIVE: It is well known that hyperoxia can be potentially harmful to the ventilated patient, although little is known about the potential effects in the setting of lung reperfusion. We hypothesized that hyperoxic ventilation at the time of reperfusion could worsen the effects of lung reperfusion injury. METHODS: Using an ex vivo, blood perfused, isolated rabbit lung system, we evaluated the effects of hyperoxic (fraction of inspired oxygen = 100%, n = 10) versus normoxic (room air, n = 10) ventilation after 18 hours of cold ischemia. Lungs were ventilated and perfused for 2 hours. A control group was immediately perfused and ventilated with a fraction of inspired oxygen of 100%. RESULTS: Lung wet/dry ratios demonstrated lower tissue edema in the normoxic group compared with in the hyperoxic group (6.72 +/- 0.89 vs 7.62 +/- 1.14 [mean +/- standard error of the mean], P = .04). Lung ventilation was also significantly better in the normoxic group versus the hyperoxic group (PCO2 = 28.96 +/- 2.01 vs 36.68 +/- 3.20 mm Hg, P = .04). Conversely, lung oxygenation after 2 hours of reperfusion (normoxic group ventilated for the last 15 minutes on 100% fraction of inspired oxygen) was not significantly different between groups (PO2 = 590.2 +/- 50.1 vs 499.6 +/- 67.5 mm Hg, P = .25). CONCLUSIONS: Ventilating lungs with 100% fraction of inspired oxygen at the time of reperfusion could increase the risk of lung reperfusion injury at the time of transplantation. Thus the patient should be ventilated with as low a fraction of inspired oxygen as possible to achieve adequate oxygen saturations during this critical reperfusion period.

Acute sleep deprivation in the thoracic surgical resident does not affect operative outcomes.

BACKGROUND: There is an increasing trend toward work hour restrictions for doctors world wide. These reforms have been inspired, in part, by the assertion by some that the fatigued physician is more prone to making errors. Interestingly, there is very little in the way of objective data with regard to the effects of sleep deprivation on patient outcomes. We have recently studied this in attending surgeons. The present study focused on thoracic surgical residents. Our hypothesis was that acute sleep deprivation would not lead to an increase in operative times or complications. METHODS: A retrospective review of all cases performed by thoracic surgical residents at the University of Virginia from January 1994 to March of 2004 was done. Complication rates of cases performed by "sleep deprived" (SD) residents were compared with cases done when the residents were "not sleep deprived" (NSD). A resident was deemed sleep deprived if he or she performed a case the previous evening that started between 10 pm and 5 am or ended between the hours of 11 pm and 7:30 am. RESULTS: A total of 7,323 cases were recorded in the STS database over the 10-year period examined. Two hundred and twenty-nine of these cases (3%) were performed by SD residents. Mortality rates for coronary artery bypass operations showed no significant differences (2.1% [SD = 3 of 141 patients] vs 3.1% (NSD = 143 of 4452 patients), p = 0.63). A comparison of operative, neurologic, renal, infectious, and pulmonary complications as well as cardiopulmonary bypass times, cross-clamp times, the use of blood products, and length of stay also demonstrated no significant differences between groups. CONCLUSIONS: Acute sleep deprivation in thoracic surgical residents does not affect operative efficiency, morbidity, or mortality in cardiac surgical operations.

Adenosine A2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation.

BACKGROUND: Reperfusion injury continues to significantly affect patients undergoing lung transplantation. Isolated lung models have demonstrated that adenosine A 2A receptor activation preserves function while decreasing inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e during the initial reperfusion period preserves pulmonary function and attenuates inflammation in a porcine model of lung transplantation. METHODS: Mature pig lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of cold ischemia before transplantation and 4 hours of reperfusion. Animals were treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05 microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With occlusion of the opposite pulmonary artery, the animal was maintained for the final 30 minutes on the allograft alone. Recipient lung physiology was monitored before tissue evaluation of pulmonary edema (wet-to-dry weight ratio), myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme-linked immunosorbent assay. RESULTS: When the ATL group was compared with the IR group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1 vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7 vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e-treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P < .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/- 4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The ATL group demonstrated significantly less inflammation on histology. CONCLUSION: Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.

Evaluation of an absorbable cyanoacrylate adhesive as a suture line sealant.

BACKGROUND: Previous formulations of cyanoacrylate, though very effective, proved to have too high a tissue reactivity to be used internally. A novel cyanoacrylate compound with less tissue reactivity was recently developed. The objective of this study was to assess this novel cyanoacrylate compound for the use as vascular suture line sealant. MATERIALS AND METHODS: Twelve adult female sheep received a 6 mm PTFE interposition graft in each iliac artery, for a total of 24 grafts. Using oxidized cellulose (Surgicel) as a control, two formulations of a new cyanoacrylate compound (named "compound A" and "compound B") were assessed during this trial. Hemostatic efficiency was measured at the time of operation by the assessment of bleeding time and amount of blood loss. Long-term graft patency was assessed angiographically at 4, 6, and 18 months. Tissue reaction at 2 weeks, 1, 6, and 18 months was assessed grossly by vascular surgeons and microscopically by a blinded pathologist. RESULTS: Average time to hemostasis was 37.6, 50.6, and 219 s in group A, group B, and oxidized cellulose control groups, respectively (P

Adenosine A2A receptor agonist improves cardiac dysfunction from pulmonary ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) injury negatively impacts patient outcome in lung transplantation. Clinically, we observed that lung transplant patients with ischemia-reperfusion injury tend to have cardiac dysfunction. Previous studies have shown that ATL-146e (4-{3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester), a selective adenosine A2A receptor agonist, reduces lung inflammation after ischemia-reperfusion. We hypothesized that pulmonary ischemia-reperfusion causes secondary heart dysfunction and ATL-146e will improve this dysfunction. METHODS: We utilized an in vivo rabbit lung ischemia-reperfusion model. The Sham group underwent 120 minutes single lung ventilation. The IR and ATL groups underwent 90 minutes right lung ischemia with 30 minutes right lung reperfusion. The ATL-146e was given intravenously to the ATL group during reperfusion. Cardiac output and arterial blood gases were monitored, and neutrophil sequestration was measured by myeloperoxidase activity. RESULTS: Upon reperfusion, cardiac output (mL/min) significantly dropped in the IR and ATL groups. By 15 minutes reperfusion, cardiac output in the ATL group improved significantly over the IR group and remained significant thereafter. Lung myeloperoxidase activity was significantly reduced by ATL-146e. Although never hypoxemic, arterial oxygenation was lower in the IR and ATL groups while central venous pressures and mean arterial pressures were similar among groups. A separate experiment demonstrated that reperfusion with the antioxidant N-(2-mercaptopropionyl)glycine prevented cardiac dysfunction. CONCLUSIONS: Pulmonary ischemia-reperfusion causes cardiac dysfunction independent of preload, afterload, and oxygenation. The ATL-146e improves this dysfunction presumably by the antiinflammatory effects of adenosine A2A receptor activation on neutrophils. One likely mechanism involves the release of oxidants from the ischemic lung upon reperfusion, which has immediate negative effects on the heart.

The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A2A receptor activation.

OBJECTIVE: Spinal cord ischemia/reperfusion injury involves multiple factors that may be modulated by adenosine A 2A receptor activation. This study defines injury progression in terms of function, cytoarchitecture, and inflammation and assesses whether adenosine A 2A receptor activation by ATL-146e limits injury progression. METHODS: Mature swine were divided into 3 groups: sham thoracotomy, IR (30 minutes of ischemia followed by reperfusion), and ATL (ischemia/reperfusion with ATL-146e administration for the first 3 hours of reperfusion). Subgroups were killed at 0, 3, 6, 12, 24, and 48 hours after reperfusion. Function was followed up with Tarlov scores. Spinal cord tissue was evaluated for neuronal viability, microtubule-associated protein-2 immunohistochemistry, and neutrophil sequestration (myeloperoxidase assay). Spinal cord tissue, cerebrospinal fluid, and serum were evaluated for tumor necrosis factor-alpha by enzyme-linked immunosorbent assay. RESULTS: Function was significantly impaired at 24, 36, and 48 hours in the IR group compared with the sham and ATL groups ( P < .05). Neuronal viability and microtubule-associated protein-2 staining were significantly preserved in the sham and ATL groups compared with the IR group at 24 and 48 hours ( P < .05). Spinal cord myeloperoxidase levels were significantly higher in the IR group than in the sham and ATL groups at 24 and 48 hours. Although negligible in serum and cerebrospinal fluid, tumor necrosis factor-alpha levels in the spinal cord peaked significantly higher in the IR group compared with the sham and ATL groups at 6 and 24 hours ( P < .05). CONCLUSIONS: Spinal cord ischemia/reperfusion induced changes in neutrophil sequestration, microtubule-associated protein-2 expression, and neuronal viability within 24 hours of reperfusion. Spinal cord tumor necrosis factor-alpha increased significantly by 6 to 12 hours after reperfusion. Adenosine A 2A receptor activation attenuates spinal cord inflammation, which may be critical for the preservation of neuronal function and cytoarchitecture after ischemia/reperfusion.

Sleep deprivation does not affect operative results in cardiac surgery.

BACKGROUND: There has been an increasing trend towards the mandatory reduction in work hours for physicians because of the fear that sleep-deprived (SD) surgeons are more prone to make mistakes. We hypothesized that sleep deprivation would not be associated with increased morbidity or mortality in cardiac operations. METHODS: A retrospective review was done of all cases performed by all attending cardiac surgeons from January 1994 to April 2003. Complication rates of cases performed by SD surgeons were compared with cases done when the surgeons were not sleep-deprived (NSD). A surgeon was deemed sleep deprived if he or she performed a case the previous evening that started between 10:00 pm and 5:00 am, or ended between the hours of 11:00 pm and 7:30 am. RESULTS: A total of 6,751 cases were recorded in the Society of Thoracic Surgeons database over the 9-year period examined. Of these, 339 cases (5%) were performed by SD surgeons, and 6,412 (95%) cases were performed by NSD surgeons. Mortality rates for coronary artery bypass operations showed no significant differences (1.7% [SD = 4/223] vs 3.1% [NSD = 133/4206)] p = 0.34). Operative (p = 0.47), pulmonary (p = 0.60), renal (p = 0.93), neurologic (p = 0.11), and infectious (p = 0.87) complications of all cases also failed to show any statistically significant differences in any group. Perfusion times, cross-clamp times, and the use of blood products were also similar between groups. CONCLUSIONS: Sleep deprivation does not affect operative morbidity or mortality in cardiac surgical operations. These data do not support a need for work hour restrictions on surgeons.

Adenosine A2A analogue reduces long-term neurologic injury after blunt spinal trauma.

BACKGROUND: ATL-146e is an adenosine A(2A) agonist that has recently been demonstrated to improve neurological outcome in spinal cord injury in animals. In the current study, we extended the treatment paradigm and tested neurobehavioral functioning out to 1 week after injury to assess if early neurological improvement is sustained long term by an adenosine analogue. MATERIALS AND METHODS: New Zealand White rabbits (3.0-3.5 kg) sustained mid-thoracic blunt spinal cord injury using a weight-drop model (10 g weight dropped from 6 cm directly onto dura). Animals received either (1) 3 h iv infusion of saline carrier (Trauma, N = 21); (2) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus of 10.8 microg/kg ATL-146e at 3 h postinjury (ATL, N = 14); or (3) 3 h iv infusion of 0.06 microg/kg/min ATL-146e followed by intraperitoneal bolus injection of 10.8 microg/kg ATL-146e at 3, 12, and 24 h postinjury (ATL-PLUS, N = 11). Fourteen animals underwent sham injury. Hemodynamic parameters were monitored and hind limb motor functioning was assessed by Tarlov scores (0 = paralyzed to 5 = normal hop) for 7 days after injury. RESULTS: ATL-146e significantly improved Tarlov scores of ATL-146e groups compared with saline-treated controls (P < 0.01 12, 24, 36, and 48 h). Control animals, severely neurologically impaired at 48 h (Tarlov 1.61 +/- 0.35), were euthanized early due to ethical concerns, thus not permitting later statistical comparisons. Early neurological improvements in both ATL-146e-treated groups were sustained longer term (7 day mean Tarlov, SHAM 4.9 +/- 0.30, ATL 5.0 +/- 0, ATL-PLUS 4.25 +/- 0.31). CONCLUSIONS: ATL-146e given immediately after blunt spinal cord trauma significantly improves neurological outcome, which is sustained through 7 days. Early adenosine A2A receptor agonism may be critical since additional IP administration afforded no further neurological improvement. The current data further support the potential clinical utility of adenosine A(2A) agonists in the treatment of spinal cord injury.

Mitral repair is superior to replacement when associated with coronary artery disease.

OBJECTIVE: To compare the outcomes of mitral repair and replacement in revascularized patients with ischemic mitral regurgitation. SUMMARY BACKGROUND DATA: Combined coronary bypass (CABG) and mitral procedures have been associated with the highest mortality (>10%) in cardiac surgery. Recent studies have suggested that mitral valve replacement (MVR) with sparing of the subvalvular apparatus had comparable results to mitral repair when associated with CABG. METHODS: Over the past 7 years, 54 patients had CABG/mitral repair versus 56 who had CABG/MVR with preservation of the subvalvular apparatus. The groups were similar in age at 69.2 years in the replacement group versus 67.0 in the repair group. We compared these 2 groups based on hospital mortality, incidence of complications including nosocomial infection, neurologic decompensation (stroke), pulmonary complication (pneumonia, atelectasis, and prolonged ventilation), and renal complications (acute renal failure or insufficiency). RESULTS: The mitral repair group had a hospital mortality of 1.9% versus 10.7% in the replacement group (P = 0.05). Infection occurred in 9% of repairs compared with 13% of replacements (P = 0.59). The incidence of stroke was no different between groups (2 of 54 repairs vs. 2 of 56 replacements, P = 1.00). Pulmonary complication rate was 39% in repairs versus 32% in replacements (P = 0.59). Worsening renal function occurred in 15% of repairs versus 18% of replacements (P = 0.67). CONCLUSIONS: Mitral repair is superior to mitral replacement when associated with coronary artery disease in terms of perioperative morbidity and hospital mortality. Although preservation of the subvalvular apparatus with MVR has a theoretical advantage in terms of ventricular function, mitral repair clearly adds a survival benefit in patients with concomitant ischemic cardiac disease.