Inflammatory lung injury after cardiopulmonary bypass is attenuated by adenosine A(2A) receptor activation.

OBJECTIVE: Cardiopulmonary bypass has been shown to exert an inflammatory response within the lung, often resulting in postoperative pulmonary dysfunction. Several studies have shown that adenosine A(2A) receptor activation attenuates lung ischemia-reperfusion injury; however, the effect of adenosine A(2A) receptor activation on cardiopulmonary bypass-induced lung injury has not been studied. We hypothesized that specific adenosine A(2A) receptor activation by ATL313 would attenuate inflammatory lung injury after cardiopulmonary bypass. METHODS: Adult male Sprague-Dawley rats were randomly divided into 3 groups: 1) SHAM group (underwent cannulation + heparinization only); 2) CONTROL group (underwent 90 minutes of normothermic cardiopulmonary bypass with normal whole-blood priming solution; and 3) ATL group (underwent 90 minutes of normothermic cardiopulmonary bypass with ATL313 added to the normal priming solution). RESULTS: There was significantly less pulmonary edema and lung injury in the ATL group compared with the CONTROL group. The ATL group had significant reductions in bronchoalveolar lavage interleukin-1, interleukin-6, interferon-gamma, and myeloperoxidase levels compared with the CONTROL group. Similarly, lung tissue interleukin-6, tumor necrosis factor-alpha, and interferon-gamma were significantly decreased in the ATL group compared with the CONTROL group. There was no significant difference between the SHAM and ATL groups in the amount of pulmonary edema, lung injury, or levels of proinflammatory cytokines. CONCLUSION: The addition of a potent adenosine A(2A) receptor agonist to the normal priming solution before the initiation of cardiopulmonary bypass significantly protects the lung from the inflammatory effects of cardiopulmonary bypass and reduces the amount of lung injury. Adenosine A(2A) receptor agonists could represent a new therapeutic strategy for reducing the potentially devastating consequences of the inflammatory response associated with cardiopulmonary bypass.

Timing of stroke after cardiopulmonary bypass determines mortality.

BACKGROUND: Stroke is an important complication of cardiopulmonary bypass (CPB). This study determined if the timing of stroke events after CPB predicted stroke-related mortality or rehabilitation needs at hospital discharge. METHODS: We performed a retrospective review of 7201 consecutive cardiac surgical patients during a 10-year period and identified 202 strokes. Postoperative stroke after CPB was classified as early (< or = 24 hours) or late (> 24 hours). Data were collected on patient characteristics, intraoperative variables and outcomes, postoperative course, stroke severity, and discharge status, including death from stroke. Logistic regression analysis was used to assess the relationship between the timing of stroke and discharge status after adjusting for clinically relevant factors. RESULTS: The stroke incidence was 2.8%. Postoperative strokes occurred within 24 hours in 22.8% (46 of 202) and after 24 hours in 77.2% (156 of 202). Factors found in logistic regression analysis to be independently associated with stroke-related death included stroke within 24 hours postoperatively (odds ratio [OR], 9.16; p < 0.0001), preoperative chronic renal insufficiency (OR, 4.46; p = 0.01), and National Institute of Health Stroke Scale (NIHSS) score (OR, 1.16 per NIHSS point increase; p < 0.0001). Among survivors, early stroke was associated with greater rehabilitation needs (p < 0.001). CONCLUSIONS: Early stroke after CPB is independently associated with higher stroke-related death and is associated with increased need for skilled rehabilitation at discharge. Neuroprotective strategies aimed at reducing early postoperative stroke may positively impact death and neurologic disability after CPB.

Cutaneous metastases in patients with rectal cancer: a report of six cases.

Cutaneous metastases from rectal cancer are rare manifestations of disseminated disease and uniformly represent dismal survival. A retrospective review of six patients with rectal cancer metastatic to the dermis was performed. The diagnosis of rectal cancer was made concurrently with the diagnosis of the dermal metastases in all six patients. A 100 per cent histopathologic concordance existed between the tissue of the dermal metastases and primary rectal tumor. The progression of systemic metastatic disease was the cause of death in 83.3 per cent of patients (5/6). No patient survived more than 7 months from the time of diagnosis. Recognition of suspicious skin lesions as possible harbingers of undiagnosed visceral malignancy is important in managing patients both with and without a history of previous cancer.

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.

A change in perspective: results for ischemic mitral valve repair are similar to mitral valve repair for degenerative disease.

BACKGROUND: Although the benefits of mitral valve repair for degenerative disease are well established, many consider surgery for functional ischemic mitral regurgitation (MR) less amenable to operative treatment. We hypothesized that mitral valve repair for ischemic MR results in outcomes similar to those for mitral valve repair for degenerative MR. METHODS: Retrospective review of nonemergent mitral valve repairs for an 8-year period revealed 105 patients with functional ischemic MR, of whom 39 were treated for severe tethering (ischemic group), and 245 patients with degenerative MR (degenerative group). RESULTS: Patients in the ischemic group had more comorbidities (p < 0.01) and worse preoperative left ventricular dysfunction (ejection fraction < or = 0.29) compared with patients in the degenerative group; (ischemic, 37.1% [39 of 105] versus degenerative, 2.0% [5 of 245]; p < 0.01). Immediate postrepair transesophageal echocardiogram revealed a 0 to 1+ MR in all patients in both groups (not significant). The hospital mortality rate was 1.9% (2 of 105) in the ischemic group and 1.2% (3 of 245) in the degenerative group (p = 1.00). The 5-year survival rate was 83.9% in the ischemic group and 94.3% in the degenerative group (p < 0.01). Five-year freedom from reoperation for recurrent MR was 100% and 97.5% in the ischemic and degenerative groups, respectively (p = 0.14). Postoperative renal failure and stroke rates were similar between both groups (not significant). The incidence of moderate or greater MR after more than 1 year of follow-up was similar between groups (not significant). CONCLUSIONS: Despite the multiple comorbidities that afflict patients with ischemic MR, mitral valve repair for ischemic and degenerative disease produces comparable and satisfactory outcomes. An aggressive approach to repair of functional ischemic MR, including treatment of tethering, leads to durable results.

A simplified approach to degenerative disease: triangular resections of the mitral valve.

BACKGROUND: Only 40% of patients with mitral valve (MV) regurgitation undergo operative repair rather than replacement. Quadrangular resection combined with ring annuloplasty has been the most common method of repair for degenerative posterior leaflet disease. Techniques such as sliding annuloplasty and artificial chord usage have increased the complexity of repair. These techniques have been perceived to be difficult and have possibly reduced the incidence of MV repair. We present our experience with a simplified approach to MV repair utilizing a triangular resection and larger rings. METHODS: Retrospective review of all MV repairs over a 7-year period (1999 to 2006) revealed 154 patients who underwent triangular resection for degenerative disease. Patients who underwent ring annuloplasty without leaflet resection and patients who had artificial chords or quadrangular resections were excluded. RESULTS: Of 154 patients who underwent triangular resection, isolated posterior leaflet resection was performed on 130 patients. Isolated anterior and combined anterior and posterior leaflet triangular resections were performed on 16 and 8 patients, respectively. Thirty-day postoperative mortality was 0%. Five-year freedom from reoperation for recurrent mitral regurgitation was 99.0%. No patients who had intended leaflet resection were converted to MV replacement. Intraoperative transesophageal echocardiogram revealed trace to 1+ mitral regurgitation. Mild systolic anterior motion was noted in 7.1% of cases initially, but resolved with volume loading in all. CONCLUSIONS: Triangular leaflet resection of the mitral valve produces durable results and can be safely and efficiently performed with minimal morbidity and mortality. This technique should allow increased utilization of MV repair for degenerative disease.