Roberto Zamparelli

The −174G/C Interleukin-6 Polymorphism Influences Postoperative Interleukin-6 Levels and Postoperative Atrial Fibrillation. Is Atrial Fibrillation an Inflammatory Complication?

Background—It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the −174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results—In 110 primary isolated coronary artery bypass patients the −174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P <0.001 for difference between the area under the curve). Conclusion—The −174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization.

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization.

Genetic control of postoperative systemic inflammatory reaction and pulmonary and renal complications after coronary artery surgery.

BACKGROUND Although some data suggest that the individual genetic predisposition for developing major or minor degrees of postoperative systemic inflammatory reaction may influence postoperative morbidity, this hypothesis has not been clinically tested to date. Methods and results The -174 G/C polymorphism of the promoter of the interleukin 6 gene was determined preoperatively in 111 consecutive patients submitted to primary isolated coronary artery bypass. The results of the genetic analysis were then correlated with the postoperative interleukin 6 levels and the development of postoperative renal and pulmonary complications. G homozygotes had significantly higher interleukin 6 levels postoperatively (P <.0001 for the difference between areas under the curve). These patients also had worse postoperative pulmonary and renal function. The mean perioperative difference in serum creatinine, potassium, and nitrogen was 0.82 +/- 0.34, 0.99 +/- 0.44, and 10.1 +/- 7.8 mg/dL versus 0.18 +/- 0.14, 0.15 +/- 0.48, and 2.6 +/- 4.1 mg/dL for GG versus non-GG carriers (P <.0001), respectively. The mean respiratory index at 6 and 12 hours was 2.9 +/- 0.8 and 2.8 +/- 0.3 versus 2.1 +/- 0.5 and 1.3 +/- 0.1, respectively (P <.0001). The mean duration of mechanical ventilation was 22.5 +/- 2.1 versus 12.7 +/- 6.7 hours (P <.01). A correlation was found between postoperative interleukin 6 levels and renal and pulmonary complications. CONCLUSION The interleukin 6 -174 G/C polymorphism modulates postoperative interleukin 6 levels and is associated with the degree of postoperative renal and pulmonary dysfunction and in-hospital stay after coronary surgery.

4G/5G PAI-1 Promoter Polymorphism and Acute-Phase Levels of PAI-1 Following Coronary Bypass Surgery: A Prospective Study

AbstractBackground and objective: The 4G/5G plasminogen activator inhibitor-1 (PAI-1) promoter polymorphism has been associated with basal PAI-1 levels, with ischemic heart disease, and with adverse prognosis in critically ill patients. We hypothesized it might also influence the acute-phase levels of PAI-1 following coronary bypass surgery. Methods: In 111 consecutive patients undergoing elective coronary bypass surgery, 4G/5G genotyping and serial plasma PAI-1 activity and antigen levels were prospectively measured before surgery, daily up to 72 h, and at discharge. The inflammatory reaction was additionally assessed by white cell count, fibrinogen, interleukin-6, and C-reactive protein levels. Results: PAI-1 activity and antigen concentrations increased approximately two-fold after surgery, peaking at 48 hours. Carriers of the 4G-allele, compared with 5G/5G homozygotes, showed approximately 20% higher PAI-1 activity and antigen both preoperatively (P = 0.007 and P = 0.035) and after surgery. White cell count, fibrinogen, interleukin-6, and C-reactive protein values did not differ significantly according to genotypic groups. In multivariate analysis, the 4G/5G genotype was the only significant modulator of postoperative PAI-1 activity (P = 0.003) and the main significant modulator of postoperative PAI-1 antigen (P = 0.013). No significant interaction was found between the effects of time and genotype on postoperative PAI-1. This indicates that the association between 4G/5G and acute-phase PAI-1 levels is secondary to the genotype-related difference of baseline PAI-1. Conclusions: Postoperative PAI-1 concentrations of patients undergoing elective coronary bypass surgery are higher in carriers of the 4G-allele than in 5G/5G homozygotes as a result of higher baseline values. Knowledge of 4G/5G status may be useful to predict acute-phase PAI-1 concentrations.

A pump-prime aprotinin dose in cardiac surgery: Appraisal of its effects on the hemostatic system

OBJECTIVES To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN A prospective randomized study. SETTING A university hospital. PARTICIPANTS Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

A case of myocardial infarction effectively treated by emergency coronary stenting soon after a Bentall–De Bono aortic surgery

Postoperative ischemia may complicate cardiac surgery, despite myocardial protection and recent technical developments. Its medical management in the intensive cardiac care unit is usually efficient, although sometimes it requires the revision of the surgical site. In other cases, urgent coronary angiography and subsequent coronary stenting may resolve the situation. Ostial stenosis of coronary anastomoses is a well-known uncommon but dramatic complication after aortic surgery causing myocardial ischemia. Cases of effort angina have been described several months after surgery, but in some cases, acute myocardial infarction may occur days or weeks after intervention. We here describe an anteroseptal ST-elevation myocardial infarction soon after a Bentall aortic root replacement due to compression of the left main ostium by surgical glue, which has been effectively treated by emergency coronary stenting. This case highlights the importance of a joint management of acute myocardial ischemia after cardiac surgery by the cardiac surgeon and the interventional cardiologist.

Pulsatile normothermic cardiopulmonary bypass and plasma catecholamine levels

The aim of the study was to assess plasma catecholamine levels in patients undergoing myocardial revascularization and relate them to pulsatile (P) and nonpulsatile (NP) normothermic cardiopulmonary bypass (CPB). Twenty-eight patients were randomly assigned to different CPB management: 15 patients were assigned to group ‘P’, 13 patients to group ‘NP’. During normothermic extracorporeal circulation, group ‘P’ received pulsatile perfusion, while group ‘NP’ received nonpulsatile perfusion. Levels of epinephrine and norepinephrine were evaluated during the operation and in the intensive care unit (ICU), at seven time points. Haemodynamic assessment was performed at four time points in the same period. Demographic and surgical data were collected, and the postoperative course was analysed. Epinephrine levels were markedly increased during CPB in both groups, while norepinephrine increased more in group NP in comparison with group P. No significant difference was found in fluid administration, transfusion, drugs usage, or postoperative complications. Normothermic pulsatile CPB seems to achieve reduced levels of norepinephrine. A clinical beneficial effect of this finding was not demonstrated during the study.

Ultrasound artifacts mimicking pleural sliding after pneumonectomy

STUDY OBJECTIVE To determine the presence of pleural sliding on chest ultrasonography (US) in a series of patients admitted to a surgical intensive care unit (SICU). DESIGN Prospective, observational study. SETTING 16-bed SICU of a University hospital. PATIENTS 8 patients (7 men, 1 woman), aged 64 - 73 years (mean 67.5 yrs). Seven patients underwent pneumonectomy for pulmonary neoplasms; one patient underwent an atypical lung resection after having undergone a pneumonectomy one year before. INTERVENTIONS None. MEASUREMENTS Chest ultrasounds were performed during mechanical ventilation and spontaneous ventilation after endotracheal tube removal. In both examinations, pleural sliding was searched bilaterally in brightness mode (B-mode) and motion mode (M-mode) on the anterior thoracic wall in the least gravitationally dependent areas. RESULTS During mechanical ventilation, pleural sliding was always absent on the side of the pneumonectomy and present on the other side. During spontaneous ventilation, some artifacts mimicking pleural sliding were noted on the side of the pneumonectomy both in B-mode and M-mode (presence of the seashore sign) in all patients, except for the one patient who had undergone a pneumonectomy one year earlier. Those artifacts became more pronounced during deep breaths. CONCLUSIONS Ultrasound artifacts mimicking pleural sliding may be observed in the absence of the lung and may originate from the activity of intercostal muscles since they become more evident during deep breathing.

Magnesium metabolism in open-heart surgery

The levels of magnesium in serum, urine and erythrocytes were studied in 22 patients undergoing cardiac surgery for valvular prosthesis. Magnesium values were correlated with serum albumin and non-esterified fatty acids (NEFA). Data were collected before anesthesia, 10 min after sternotomy, heparinization and declamping of the aorta and in the 1st postoperative day. A slight decrease in magnesemia was observed before extracorporeal circulation (ECC) and was mainly due to haemodilution. The correlation of magnesium with NEFA was significant only after heparinization. The use of the St Thomas solution as cardioplegia fully corrected the hypomagnesemia previously reported during ECC as well as in the 1st postoperative day. A moderate hypermagnesemia was observed at the end of ECC, but no patient reached dangerous levels of serum magnesium. Urinary losses increased during and after ECC. Red blood cell magnesium showed a slight increase before ECC, followed by a significant reduction at the end of ECC.

Early postoperative obstructive prosthetic mitral valve thrombosis in a patient double heterozygous for factor V Leiden and prothrombin G20210A mutation.

Early postoperative obstructive prosthetic mitral valve thrombosis in a patient double heterozygous for factor V Leiden and prothrombin G20210A mutation -