Interleukin 6 G-174C polymorphism influences outcome following coronary revascularization surgery.

BACKGROUND: Levels of the proinflammatory cytokine interleukin 6 (IL-6) increase after surgery. The functional polymorphism in the IL-6 promoter region, G-174C, is associated with an increased risk of coronary heart disease. We investigated the genetic predisposition in IL-6 response to coronary revascularization and studied the association between the G-174C polymorphism, IL-6 levels, and clinical outcomes of surgery. METHODS: DNA was obtained from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for the IL-6 G-174C polymorphism by means of sequence-specific primer-polymerase chain reaction analysis. IL-6 levels were measured with an enzyme-linked immunosorbent assay on serum samples taken 3 hours postoperatively. IL-6 levels and genotypes (CC, CG, and GG) were correlated with perioperative clinical data. RESULTS: The prevalences of the CC, CG, and GG IL-6 -174 genotypes were 8%, 54%, and 38%, respectively. Patients homozygous for the C allele had higher circulating levels of IL-6 postoperatively than the patients with the CG and GG genotypes (P = .09). Patients homozygous for the G allele had a significantly lower incidence of postoperative atrial fibrillation (P = .032) and a shorter hospital stay (P = .005). This result remained statistically significant following risk stratification. The severity of coronary artery disease and a higher number of bypass grafts were associated with a significant increase in IL-6 level postoperatively (P = .028, and P = .005, respectively). Higher levels of IL-6 were associated with increased blood loss postoperatively (P = .016). CONCLUSIONS: The C allele is associated with higher postoperative IL-6 levels and a less favorable clinical outcome. The G-174C polymorphism is related to the outcome after coronary revascularization.

Tumor necrosis factor alpha influences the inflammatory response after coronary surgery.

BACKGROUND: A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNFalpha gene at position G-308A has been associated with increased TNFalpha levels. The relationship between predicted TNFalpha genotype and circulating TNFalpha levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNFalpha G-308A polymorphism, TNFalpha postoperative levels, and clinical outcome after coronary revascularization surgery. METHODS: We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNFalpha G-308A polymorphism using sequence specific primer-polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of AA, AG, and GG TNFalpha-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNFalpha (p = 0.009). Higher levels of TNFalpha were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification. CONCLUSIONS: Patients of the AA-308 TNFalpha genotype showed significantly higher TNFalpha plasma levels. Higher plasma levels of TNFalpha were associated with less favorable outcome after coronary revascularization surgery. It may prove useful to utilize TNFalpha serum levels as a marker for identifying high-risk patients in the future.

Cavoatrial tumor thrombectomy using cardipulmonary bypass without circulatory arrest.

Of 29 patients with inferior vena caval tumor thrombus, 14 with supradiaphragmatic extension were deemed suitable for operation. Patients (age, 7.5 to 70 years) had renal cell carcinoma (n = 8), Wilms' tumor (n = 2), transitional cell carcinoma (n = 1), and adrenal carcinoma (n = 3). Seven patients had stage III disease, and 7 patients had stage IV disease. Two patients (group A) had unresectable disease at exploratory celiotomy, 4 patients (group B) underwent tumor thrombectomy without cardiopulmonary bypass, and cardiopulmonary bypass was employed in 8 patients (group C). Three of 8 group C patients had Budd-Chiari syndrome at diagnosis. Cardiopulmonary bypass with moderate hypothermia, and inferior vena caval interruption (clip or filter), was employed in all patients. There were no perioperative deaths. Transient neurological impairment was observed postoperatively in 2 patients. Coagulopathy developed in 1 patient who had hepatic encephalopathy and Budd-Chiari syndrome preoperatively and in another patient in whom protamine could not be administered. No patient had acute renal failure requiring hemodialysis. Median survival is 41 and 17 months in groups B and C, respectively. Some authors have advocated profound hypothermia and circulatory arrest in these patients. We find that satisfactory visualization and excision can be performed with cardiopulmonary bypass and moderate hypothermia, avoiding potential renal, hepatic, neurological, and septic complications associated with circulatory arrest.