Neutrophil gelatinase-associated lipocalin as emerging biomarker of acute renal failure in renal transplant patient after coronary artery bypass surgery.

Acute renal injury (AKI) is a serious complication, which increases the risk of death after cardiac surgery. Although serum Cre is typically used for diagnosis of AKI, there are disadvantages in its use as renal marker. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein of the lipocalin family and is expressed by neutrophils and other epithelial cells including segments of proximal collecting tubule (PCT). It is introduced as an excellent renal biomarker, for the early diagnosis of AKI in children and adults undergoing renal transplantation and cardiac surgery. According to literature data NGAL is detected in the very first urine sample within two hours following ischemia. It is one of the earliest and most robustly induced proteins in kidneys following ischemic and nephrotoxic insults. We present an interesting case of renal transplant patient under long-term immunosuppressive therapy. He had already renal impairment of the transplant kidney (GFR 29.3 mL/min/1.73 m(2)). He suffered from coronary artery disease without history of myocardial infraction and underwent elective coronary artery bypass grafting (CABG). Renal function was monitored also with NAGL, in order to avoid potential renal graft failure postoperatively.

Cardiac valve surgery and myocardial damage: the role of cardiac troponin I.

AIM: The study investigated the release of cardiac Troponin I (cTnI) levels in heart valve surgery and in coronary artery bypass grafting (CABG). The aims of the research were 1) to evaluate the ability of cTnI to detect the myocardial damage; and 2) to demonstrate possible causative factors of the cTnI release after valve surgery. METHODS: A prospective, single-center study. Ninety consecutive patients were operated on for different types of cardiac surgery; 45 patients underwent cardiac valve surgery - The VALVE group. 45 patients underwent CABG surgery - the CABG group. CTnI levels were measured preoperatively, on the day of operation and the 7 days postoperatively. The diagnosis of damaged myocardium classically performed through the measurement of cTnI, twelve-lead electrocardiograms (ECG) and echocardiographics according to the protocol of the study. RESULTS: Although more elevated cTnI release was noticed in valve group early after operation, no occurrence of cardiac events was found in that group. Statistically significant occurrence of cardiac events was found in CABG group (P=0.015). No relationship was shown between the peak of cTnI and the presence of cardiac events in valve group. A statistically significant correlation was observed between cardiac events and peak cTnI in CABG group (P=0.05). Possible correlations were investigated between the peak of cTnI and perioperative parameters in both two groups. CONCLUSION: The absence of cardiac events and the association of valve surgery with higher early release of cTnI compared to CABG suggest that the type of surgery strongly affects the induction of myocardial damage.

The systemic inflammatory response in coronary artery bypass grafting: what is the role of the very low ejection fraction (EF < or = 30%)?

AIM: Patients with depressed left ventricular function are more susceptible to develop postoperative complications after cardiac surgery. The aim of the present study was to examine the effect of severe left ventricular dysfunction on the activation of systemic inflammatory reaction during and after coronary artery bypass grafting (CABG). METHODS: Clinical prospective study; 32 selected patients underwent CABG; 16 patients had depressed left ventricular function before the operation (low ejection fraction [EF] <30%)--Low EF group (study group). Sixteen patients had normal left ventricular function (normal EF, >50%)--Normal EF group (control group). The levels of inflammatory mediators TNF-alpha, IL-6, IL-8 and IL-10 were measured preoperatively, during and after cardiopulmonary bypass (CPB) and 24 hours postoperatively. RESULTS: Higher levels of almost all of inflammatory mediators were detected in patients with depressed left ventricular function compared with patients of normal EF group. IL-6 levels were found statistically significant higher in Low EF group before the induction of anesthesia (P=0.039) and after the administration of protamine (P=0.02). IL-8 levels were found statistically significant higher in Low EF group before the induction of anesthesia (P=0.05), 30 min after the start of CPB (P=0.02), after the administration of protamine (P=0.015) and 24 hours after the end of the operation (P=0.05). No statistically significant differences were demonstrated between the 2 groups of study relative to TNF-alpha and IL-10. CONCLUSION: A greater activation of systemic inflammatory reaction occurred in patients with depressed left ventricular function than in patients with normal cardiac function when they underwent CABG with extracorporeal circulation.

Cardiac troponin I versus creatine kinase-MB in the detection of postoperative cardiac events after coronary artery bypass grafting surgery.

AIM: Several studies suggest that postoperarive concentrations of cardiac troponin-I (cTnI) may increase in patients undergoing aorto-coronary bypass grafting (CABG). The degree and pattern of release appears to be associated with perioperative myocardial damage. METHODS: This was a prospective observational study with serial sampling conducted at the Departments of Cardiothoracic Surgery and Anesthesiology, University Hospital of Ioannina, Ioannina, Greece. The levels of cTnI and creatine kinase-MB (CK-MB) preoperatively, upon admission to the intensive care unit and at 12, 24, 36 and 48 hours after surgery, as well as daily from postoperative days 3-7 were determined in 41 consecutive patients (33 males and 8 females, aged 64.8+/-6.1 years) who underwent CABG with cardiopulmonary bypass. The Authors compared the patterns and variation of cTnI and creatine kinase (CK)-MB after CABG in patients with or without postoperative cardiac events (PCEs). RESULTS: Eleven patients experienced a PCE (postoperative ventricular and supraventricular arrhythmia, need for intra-aortic balloon pump (IABP) for >12 hours, or postoperative myocardial infarction, [MI]). In patients without PCE the elevation of cTnI peaked at 24 hours after surgery, while in patients with PCE maximal values of cTnI occurred after 36 hours. CTnI levels correlated with CK-MB after the procedure. Receiver-operating characteristic (ROC) curve analysis indicated that cTnI is superior to CK-MB with regard to PCE diagnosis following CABG (area under the ROC curve, 0.73, 95% CI (0.53-0.93) versus 0.54, 95% CI, (0.25-0.83). CONCLUSION: CTnI seems to be more valuable compared to CK-MB in the detection of PCEs in patients undergoing coronary surgery.

Successful cardiac and cerebral resuscitation with extracorporeal circulation and mild hypothermia.

Extracorporeal circulation could be effective for cardiac resuscitation in patients who do not respond to ''Advanced cardiac life support'' (ACLS), but cannot guarantee brain survival. A case of successful cardiac and cerebral resuscitation with extracorporeal circulation and mild hypothermia, in a 48 year-old man with cardiac arrest due to cardiac tamponade, is reported. The good long term neurologic outcome of the patient is also described.

"Learning curves" of cardiac surgery in relation to risk stratification and hospital location.

AIM: The purpose of this study was to determine any significant differences in "learning curves" between private and public hospitals when the same senior surgeon was responsible during the initial phases of open-heart surgery programs development, in relation to risk stratification and hospital location. METHODS: A prospective review of 610 patients records was performed at a newly-opened cardiothoracic program in a public University Hospital (PUH) in the periphery of Greece, and a private institution (PI) with an experienced intensive care unit (ICU) in the capital city of Athens. Preoperative risk stratification, mortality and postoperative length of stay (LOS) were analysed between 1999 to 2001. RESULTS: At PUH 298 patients were operated and 312 patients at PI. There were 136 low risk (EuroSCORE 0-2) and 474 medium and high-risk patients (EuroSCORE > or =3). There was no significantly elevated mortality or learning curve in low risk surgery either at PUH (57 patients with 1 death) or PI (79 patients and 1 death). In medium and high-risk surgery at PI there was no mortality in 68 patients operated by the senior surgeon and no learning curve in all 233 such patients. In 240 medium and high-risk patients at PUH there was a learning curve despite the involvement of the same senior surgeon. In 1999 and 2000 the observed mortality (OM) in 150 patients was 15.33%, EuroSCORE 5.98, and in 2001 in 91 patients OM 3.29%, EuroSCORE 5.95 with p=0.00.8 when "experienced" ICU staff was employed. LOS was significantly reduced in 97 patients in 2001 at PUH (8.7 d +/- 2.81 vs 11.07 days +/- 7.9 in 1999 and 2000, p=0.046) confirming the existence of a learning curve at the PUH. No such change was observed at PI (8.2 days vs 7.8, p=0.45). CONCLUSION: No mortality differences or learning curve characteristics were detected for low risk operations either at PUH or PI. For medium and high risk surgery there appears to be a learning curve in PUH but not in PI despite senior surgeon involvement in both. The presence of an experienced ICU appears to play a critical role in the outcome of operations in newly opened cardiothoracic programs.

Prevention of aortic anastomotic hemorrhage. A simplified intraoperative testing technique.

BACKGROUND: Postoperative bleeding in aortic root aneurysms had represented a challenge. METHODS: Intraoperative testing of the annular or subannular aortic anastomosis, during procedures involving replacement of the aortic root, with either synthetic tube graft, a composite graft or an allograft is described. By reversing the flow of the LV vent and delivering cardioplegia into the left ventricle and thereby pressurizing the left ventricle and its outflow, this technique enables the surgeon to simulate the volume loaded heart, prior to completion of the distal anastomosis. A systematic assessment of the proximal suture line can then be undertaken. Portions of the proximal suture line, particularly the posterior aspect, are obscured if the inspection takes place after completion of both aortic anastomoses, the coronary attachments, as well as from the presence of the main pulmonary artery and by the distended aorta itself. RESULTS: The use of this method in 34 patients is described without untoward events related to this technique. CONCLUSIONS: The advantages of this technique are a rapid and safe assessment of the integrity of the proximal suture line bed.

Possible intra-aortic balloon pump "function-related" mechanism of embolic events in patient with protruding atheroma in the thoracic aorta.

A possible new functional mechanism of atheromatous embolus is presented resulting from reversed aortic blood flow during diastolic augmentation by balloon counterpulsation. This mechanism is different from mechanical disruption during insertion. Despite this, intra-aortic balloon remains an important asset in the management of hemodynamically challenged patients.

Early mortality and morbidity of bilateral versus single internal thoracic artery revascularization: propensity and risk modeling.

OBJECTIVES: We examined whether bilateral internal thoracic artery (BITA) revascularization is associated with any increased in-hospital mortality and complications compared with single internal thoracic artery (SITA) revascularization. BACKGROUND: Despite proven long-term benefits, BITA revascularization has been slow to be adopted because of fear of increased early morbidity. METHODS: We evaluated 1,697 consecutive patients undergoing BITA (n = 867) or SITA (n = 830) revascularization. We used propensity score analyses and adjusted risk models to address differences between arms. RESULTS: There were 20 (2.3%) deaths in the BITA group versus 26 (3.1%) in the SITA group (odds ratio 0.73, p = 0.30). Propensity analysis identified several parameters that affected the decision to use BITA. Adjusting for propensity score and all potential risk factors, the odds ratio for death with BITA versus SITA was practically 1. Bilateral internal thoracic artery revascularization did not increase the number of in-hospital complications with the possible exception of deep sternal wound infections (11 [1.3%] vs. 3 [0.4%], p = 0.057). In multivariate modeling BITA increased the risk of deep sternal wound infections only in emergent cases and in older patients; the excess risk was negligible among 1,206 patients (71.1% of total) who did not have emergent revascularization and were < or =70 years old (risk difference 0.3%, p = 0.74). There was no difference in length of stay after adjustment for propensity factors (mean 11.3 vs. 11.7 days, p = 0.66). CONCLUSIONS: Bilateral internal thoracic artery revascularization grafting confers no increased risk for early death and does not prolong hospital stay. The small increase in the risk of deep sternal wound infections does not affect the majority of patients.

Oxidative status and anti-oxidant enzyme activity during calcium paradox in the rat isolated heart.

1. The effect of calcium paradox on oxidative status and the activity of anti-oxidant enzymes were studied in the rat isolated heart. Glutathione status, sulphydryl group contents and lipid peroxidation in the myocardium, as well as the release of oxidized and reduced glutathione from the heart, were taken as indices of oxidative events. 2. Reperfusion with calcium after calcium-free perfusion induced a significant decrease in the myocardial content of reduced and oxidized glutathione and non-protein sulphydryl groups. At the same time, a significant release of both forms of glutathione from the heart was observed. However, the ratio of oxidized to reduced glutathione remained unchanged and was not different from control. Increased lipid peroxidation was observed only after 30 min of reperfusion with calcium. 3. Increased anti-oxidant activity during the reperfusion period was observed. Mitochondrial Mn-superoxide dismutase (SOD) activity was increased throughout the reperfusion period, while cytoplasmic Cu,Zn-SOD and glutathione peroxidase activity showed a transient increase at 5 min reperfusion. 4. The results do not support an important role of oxygen free radicals in cell damage observed during calcium paradox in the rat isolated heart. Production of oxygen free radicals may occur during the reperfusion period, but the quantity produced is insufficient to exceed the anti-oxidant capacity of the heart.

Posttraumatic coronary artery aneurysm.

A 31-year-old man sustained blunt deceleration trauma with dissection of the left anterior descending coronary artery. We repaired a posttraumatic coronary aneurysm to prevent late occlusion of the recanalized vessel. An internal mammary artery graft was applied as a precaution against postoperative thrombosis. Follow-up at 12 months showed improved left ventricular function.

Impaired platelet aggregation after cardiopulmonary bypass in man: enhancement of collagen-induced aggregation in whole blood and plasma by adrenaline ex vivo.

1. We tested the effect of intravenous adrenaline at 0.55-1.10 nmol min-1 kg-1 (for 3-8 min, at 7-10 min post bypass; n = 7) on both microaggregation in hirudinized whole blood, using platelet counting, and macroaggregation in platelet-rich plasma, using optical aggregometry. Control (n = 12) blood samples were taken before and at 10 and 20 min after bypass. 2. Post-bypass plasma adrenaline levels (nmol/l) increased slightly in controls (1.0 versus 0.7 at 10 min, medians; P = 0.05) and markedly with adrenaline infusion (36 versus 0.5 before infusion, P = 0.02). Microaggregation (percentage decrease in single platelets) in stirred blood, reflecting largely ADP-dependent 'spontaneous' aggregation, was not influenced by adrenaline infusion. In contrast, collagen (0.2 microgram/ml)-induced microaggregation in blood was enhanced by adrenaline (92% versus 41%, P = 0.02), with no change in controls (60% versus 53%, P = 0.61). 3. In controls, collagen (0.6 microgram/ml)-induced macroaggregation in platelet-rich plasma (extent of increase in light transmission, cm) was impaired at 10 min post bypass (5.3 versus 12.1 before bypass, P = 0.01), but was enhanced by adrenaline (7.0 versus 3.6 before infusion, P = 0.02). Platelet counts (x 10(9)/l) were decreased postbypass (155 versus 220, P = 0.02) and were not influenced by adrenaline infusion (167, P = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)

Deferoxamine cardioplegia reduces superoxide radical production in human myocardium.

Recent studies have demonstrated enhanced myocardial protection during ischemia using the oxygen free radical scavenger, deferoxamine. This effect of deferoxamine may be related either to its iron-chelating property or to intervention in an iron-independent mechanism. We tested the latter by determining the rate of superoxide anion production and the degree of lipid peroxidation in human myocardial tissue after including deferoxamine in cardioplegic solution. Fourteen patients who underwent aortic, mitral, or double valve replacement were included in the study. The mean value for superoxide radical production was 59.8 +/- 17.0 nmol.min-1.g-1 for the control group (group C; n = 7) and 21.3 +/- 8.1 (p < 0.001) for the deferoxamine-treated group (group D; n = 7). The mean value for thiobarbituric reactive substances was 80.00 +/- 23.4 in group C and 38.7 +/- 23.8 nmol.min-1.g-1 in group D (p < 0.01). In conclusion, deferoxamine appears to have a moderating effect on the biochemical markers of ischemia reperfusion injury. Its scavenging effect on superoxide anion could play a role in the cellular defense against oxygen radicals during cardiac operations.

Enzymatic evaluation of renal damage caused by different therapeutic procedures for kidney stone disease.

In an attempt to evaluate renal injury relative to open surgery, percutaneous nephrolithotripsy (PCN) and extracorporeal shock wave lithotripsy (ESWL) were studied in 52 patients with renal calculus disease. Preoperative and postoperative urinary levels of N-acetyl-glycosaminidase (NAG), a sensitive marker of renal tubular damage, were studied. No significant changes were noted in posttreatment urinary NAG values among patients who underwent ESWL or PCN. Although statistically nonsignificant, a constant mild increase of urinary NAG was observed after PCN, that has to be evaluated with long-term follow-up studies. The shock wave number or power in cases treated with ESWL as well as the number of renal punctures in the PCN group did not change the effect on renal tubular function. Diabetics and patients with chronic renal disease treated by ESWL did not show any significant change in posttreatment urinary NAG levels. In contrast to that, all patients treated by open surgery had significant, intense and prolonged increase of the postoperative NAG values, especially those treated by ischaemic nephrolithotomy. Comparing the three different therapeutic modalities, open surgical procedures had the most significant effect on renal function and this difference was statistically significant. We therefore suggest that ESWL does not endanger renal function, while open surgery must be reserved for selected cases.

Macroaggregation of platelets in plasma, as distinct from microaggregation in whole blood (and plasma), as determined using optical aggregometry and platelet counting respectively, is specifically impaired following cardiopulmonary bypass in man.

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin and bleeding in profoundly hypothermic perfusion.

Clinical observation led us to believe that aprotinin fails to preserve haemostatic function in patients undergoing deep hypothermic perfusion with or without circulatory arrest. A retrospective study was made of blood loss in 80 consecutive acute Type A dissection patients before and during the aprotinin era (1987-1992). After 1988 all patients were cooled below 20 degrees C pending circulatory arrest. Fourteen patients underwent aortic root replacement and 66 replacements of the ascending aorta. Age distribution (range 22-79 years) and type of operation were similar in the aprotinin and control groups. The impervious Hemashield (Meadox) graft was used for all but five patients. These underwent aortic root replacement with preclotted, valved conduits. Overall the mean blood loss for 27 patients operated without aprotinin was 837 ml per 24 h (standard error +/- 90) and for 53 patients with aprotinin 1,929 ml per 24 h (standard error +/- 90). There was a significant difference between the two groups when profoundly hypothermic perfusion was used, with greater bleeding in aprotinin-treated patients. There were six re-entries in the aprotinin group and none in the control patients. There were ten hospital deaths (11.1%). A greater incidence of bleeding and thrombosis-related deaths was recorded for the aprotinin-treated patients. In addition, four surviving aprotinin patients suffered severe coagulation defect with blood loss greater than 4,500 ml and platelets less than 50 x 10(6). We suggest that aprotinin inhibits the protease enzymes which maintain the fluid state of blood during hypothermic low flow and arrest states. Disseminated intravascular coagulation may consume platelets thereby predisposing to abnormal bleeding and potentially fatal thrombotic events. The use of aprotinin in profoundly hypothermic perfusion should be adopted cautiously.