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Biomedical subjects

Alexander Wahba

Publications and source records attributed to Alexander Wahba.

14 recordsLinked to original sources

Heparin resistance and increased platelet activation in coronary surgery patients treated with enoxaparin preoperatively.

OBJECTIVE: Patients with unstable coronary disease have changes in the hemostatic system. These patients are often treated with low molecular weight heparin. In patients who are accepted for coronary artery bypass grafting, treatment with low molecular weight heparin is frequently continued until surgery. We hypothesized that in coronary artery bypass grafting, the hypercoagulable state seen in unstable patients persists into the intra- and postoperative phase despite preoperative treatment with low molecular weight heparin. The aim of this study was to explore and describe the perioperative hemostatic process in patients with unstable coronary artery disease undergoing coronary artery bypass grafting. METHODS: Thirty-two patients with unstable coronary disease treated preoperatively with enoxaparin, and 32 stable control patients not treated with enoxaparin, were included. All patients were taking low dose aspirin until the day before surgery. Before cardiopulmonary bypass, all patients were given tranexamic acid as a bolus injection. Blood samples for analysis of platelet counts, international normalized ratio, activated partial thromboplastin time, fibrinogen, protein S, protein C, prothrombin fragment 1 + 2, thrombin-antithrombin complex, antithrombin, plasmin-antiplasmin complex, D-dimer, neutrophil-activating peptide 2, platelet-monocyte complexes, and heparin concentrations were drawn preoperatively, after 30 min on cardiopulmonary bypass, and 30 min, 3 h, and 20 h postoperatively. Heparin was given during cardiopulmonary bypass to maintain an activated clotting time above 480 s. RESULTS: Patients in the enoxaparin group needed more heparin to maintain an activated clotting time above 480 s, and had higher heparin concentrations and lower antithrombin values compared with control patients. Neutrophil-activating peptide 2 concentrations were higher in the enoxaparin group. CONCLUSIONS: Patients treated with enoxaparin before coronary artery bypass grafting showed signs of heparin resistance intraoperatively. Enoxaparin-treated patients also had increased perioperative platelet activation. Reasons for the observed difference in platelet activation remain unclear.

Aged↗

Health-related quality of life three years after coronary surgery: a comparison with the general population.

OBJECTIVES: To assess health-related quality of life (HRQOL) in patients three years after coronary artery bypass grafting (CABG) compared to the general Norwegian population, with emphasis on age and gender-differences. DESIGN: A cross-sectional postal survey of patients who underwent CABG in 2000. HRQOL was assessed using the Short Form 36 (SF-36). Subgroup analyses were performed according to age (<70 versus =70 years) and gender. RESULTS: Of 233 eligible patients 203 responded (mean age 67.6 years, 17% females). Patients reported better scores on bodily pain than the general population (p=0.008), but did not differ on other subscales of SF-36. Younger patients tended to score lower, older patients higher than the general population on HRQOL. Female patients reported lower HRQOL than the general female population and reported significantly lower scores than male patients on 3 of 8 subscales. CONCLUSIONS: Three years after CABG the HRQOL is comparable to the general Norwegian population even in older patients. The older patients reported less pain than the general population.

Age Factors↗

Increased fibrinolysis and platelet activation in elderly patients undergoing coronary bypass surgery.

Reexploration for hemorrhage after cardiac surgery is associated with increased morbidity and mortality. Elderly cardiac surgical patients have an increased risk of excessive bleeding and reexploration. In the present study we investigated the perioperative hemostatic function in elderly patients compared with younger patients undergoing coronary artery bypass grafting. Twenty-five elderly (75 yr and older) and 25 younger (younger than 60 yr) patients were included in the study. Blood samples for the analysis of platelet counts, international normalized ratio, activated partial thromboplastin time, fibrinogen, d-dimer, antithrombin, prothrombin fragment 1 + 2, thrombin-antithrombin complex, plasmin inhibitor, neutrophil-activating peptide 2, and platelet-monocyte complexes were drawn preoperatively, 30 min, and 3 h postoperatively and approximately 20 h postoperatively. Elderly patients had an increased activation of the hemostatic system. In particular, elderly patients showed a more pronounced increase in fibrinolysis and platelet activation postoperatively compared with younger patients.

Adult↗

Effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery.

OBJECTIVE: The aim of the study was to evaluate the effect of clopidogrel on midterm graft patency following off-pump coronary revascularization surgery. DESIGN: Ninety-four consecutive patients who underwent off-pump coronary artery bypass grafting between 1997 and 2002 were studied (58 men, 36 women; 61.7 +/- 9.8 years). The initial 36 patients (control group) received 75 to 160 mg acetyl salicylic acid (ASA) as an antiplatelet agent, whereas the consecutive 58 patients (clopidogrel group) received 75 mg clopidogrel postoperatively in addition to ASA. Intraoperatively, graft flow was assessed with transit-time flowmetry in all patients and the peripheral anastomoses were assessed with epicardial ultrasound in 28 patients. Sixty-two patients underwent angiography after a mean of 185 +/- 92 days. A total of 82 grafts were evaluated angiographically. Grafts with TIMI flow 2 and 3 were assessed as patent. RESULTS: At angiographic follow-up, the overall graft patency rate was 84% (31/37) in the control group and 93% (42/45) in the clopidogrel group (P value was not significant [ns]). Graft patency rates for left internal mammary artery (LIMA) grafts were 92% (23/25) versus 96% (28/29) (ns), and for saphenous vein grafts were 66% (7/11) versus 87% (14/16) (ns), respectively. CONCLUSION: The observed trend toward higher patency rates in patients treated with clopidogrel did not reach statistical significance. Further larger studies are necessary to confirm these preliminary results.

Clopidogrel↗

On-pump versus off-pump coronary artery bypass grafting: more heat-shock protein 70 is released after on-pump surgery.

OBJECTIVES: The use of cardiopulmonary bypass in coronary artery bypass grafting (CABG) may contribute to the postoperative inflammatory response. The molecular chaperone heat-shock protein (HSP) 70 may be induced by ischemia, and has been detected both in the myocardium and in the circulation after CABG. In vitro, extracellular HSP70 may activate both innate and adaptive immunity. Hypothesizing that use of cardiopulmonary bypass (CPB) leads to more circulating HSP70, we explored the release of it in 10 patients undergoing CABG with the use of CPB, and in 10 patients undergoing off-pump surgery CABG (OPCAB). METHODS: Blood samples were taken preoperatively, twice peroperatively, 2 and 6 h postoperatively and the next day. Serum analyses were performed by means of immunoassays. RESULTS: We detected a significant difference in postoperative circulating HSP70 between on-pump and off-pump patients (median peaks of 2849 and 756 pg/ml, respectively, P < 0.01 2 h postoperatively). Interleukin-6 and -8 increased in all patients, without significant differences between the groups. Serum interleukin-10 increased at the end of the operation in 7 of 10 patients operated with cardiopulmonary bypass (median 51.7 pg/ml), but in none of the off-pump patients. Furthermore, in the first group, interleukin-10 correlated with the HSP70 concentration at the end of the operation, r = 0.75, P < 0.05. Serum markers of myocardial damage were higher in conventional than off-pump patients on day 1 postoperatively: median cardiac Troponin T was 0.358 and 0.126 microg/l, respectively, P < 0.01. Correspondingly, median creatine kinase-MB was 23.6 and 7.8 microg/l in on-pump and off-pump patients, respectively, P < 0.001. Peak HSP70 correlated with both Troponin T and creatine kinase-MB measured on day 1. CONCLUSIONS: Significantly more HSP70 was released into the circulation following conventional than following off-pump CABG. Circulating HSP70 may indicate cellular stress or damage. Furthermore, HSPs are suggested as immunoregulatory agents, and may be important in the host defence postoperatively.

Aged↗

Prophylactic treatment with desmopressin does not reduce postoperative bleeding after coronary surgery in patients treated with aspirin before surgery.

UNLABELLED: The synthetic vasopressin analog desmopressin has hemostatic properties and may reduce postoperative bleeding after coronary artery bypass grafting (CABG). A study on the effects of recent aspirin ingestion on platelet function in cardiac surgery showed a greater impairment of platelet function in patients treated with aspirin <2 days before the operation. We evaluated the effects of desmopressin on postoperative bleeding in CABG patients who were treated with aspirin 75 or 160 mg until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel group trial. One-hundred patients were included and divided into two groups. One group received desmopressin 0.3 micro g/kg and the other received placebo (0.9% NaCl) after the neutralization of heparin with protamine sulfate. Postoperative blood loss was recorded for 16 h. The mean (SD) bleeding was 606 (237) mL in the desmopressin group and 601 (301) mL in the placebo group (P = 0.93), representing no significant difference (95% confidence interval, -107 to 117 mL). We conclude that desmopressin does not reduce postoperative bleeding in CABG patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of desmopressin to these patients after the neutralization of heparin with protamine sulfate does not reduce postoperative bleeding.

Aged↗

Heart surgery with extracorporeal circulation leads to platelet activation at the time of hospital discharge.

OBJECTIVE: Heart surgery with extracorporeal circulation has a marked effect on platelet function and coagulation accounting for abnormal blood loss and allegedly a low incidence of thromboembolic complications. Little is known about platelet function at the time of hospital discharge of routine patients. METHODS: Blood samples from 91 patients undergoing elective heart surgery were drawn before surgery and prior to discharge. Thirty-seven patients underwent coronary artery surgery and 54 an aortic valve implantation. The mean age of patients was 69+/-9 years. Fifty patients were male and 41 female. Platelet function was evaluated using plasma beta-thromboglobulin quantification in enzyme-linked immunosorbent assay. In addition, flow cytometric analysis of platelet-monocyte conjugates and platelet-neutrophil conjugates was performed. RESULTS: The platelet count before discharge was significantly increased (265+/-86 vs. 212+/-61 x 10(9)/l preoperatively). beta-Thromboglobulin was significantly increased (176+/-127 vs. 79+/-70 ng/ml preoperatively) and flow cytometry proved a significant increase in monocyte-platelet aggregates (8.3+/-5.4% vs. 5.3+/-2.6% preoperatively) indicating platelet activation at the time of hospital discharge. There were no significant differences among the three subgroups coronary surgery, mechanical valve insertion and biological valve insertion. CONCLUSIONS: Heart surgery with extracorporeal circulation leads to significant platelet activation and a reactive increase in platelet count before discharge. This is in contrast to the reduced platelet function immediately postoperatively.

Adult↗

Single-dose tranexamic acid reduces postoperative bleeding after coronary surgery in patients treated with aspirin until surgery.

UNLABELLED: Tranexamic acid reduces postoperative bleeding after coronary artery bypass grafting. We evaluated the effects of a single dose of tranexamic acid given immediately before cardiopulmonary bypass (CPB) in patients treated with aspirin until the day before surgery. The study was a prospective, randomized, double-blinded, placebo-controlled, parallel-group trial. Eighty patients were included and divided into two groups: one group received tranexamic acid 30 mg/kg, and one group received placebo (0.9% NaCl) as a bolus injection before CPB. Postoperative blood loss was recorded for 16 h. Transfusions of blood products were recorded for the whole hospital stay. Transfusions of packed red cells were given when the hematocrit value was less than 20% during CPB and less than 25% after surgery. The patients in the tranexamic acid group had significantly less postoperative bleeding compared with the patients in the placebo group (mean [SD]) (475 [274] mL versus 713 [243] mL; P < 0.001). An effective inhibition of fibrinolysis was found in patients receiving tranexamic acid. Tranexamic acid reduces postoperative bleeding in coronary artery bypass grafting patients treated with aspirin until the day before surgery. IMPLICATIONS: Continuation of aspirin medication until the day before coronary artery bypass grafting may increase postoperative bleeding. The administration of a single dose of tranexamic acid (30 mg/kg) immediately before cardiopulmonary bypass significantly reduced postoperative bleeding and inhibited fibrinolysis in these patients.

Aged↗

Guiding surgical cannulation of the inferior vena cava with transesophageal echocardiography.

UNLABELLED: We studied 150 adult cardiac surgery patients to assess visualization of the venous cannula and the venous system by intraoperative transesophageal echocardiography and to register the incidence of cannulation of hepatic veins. The quality of images, the dimensions of the venous system, the position of the venous cannula, and the adequacy of venous return were registered. Acceptable image quality of the inferior vena cava and the right hepatic vein (RHV) was obtained in 95% and 87% of cases, respectively. Considerable individual variations were found in the dimensions of the venous system. The cannula position could be determined in 99% of the cases. Ten percent of venous cannulae were primarily placed in the RHV. A short distance between the eustachian valve and the RHV possibly predisposes to cannulation of the RHV. No other patient-related factors were associated with cannula position. Placement of the cannula deep in the inferior vena cava was associated with reduced venous return and may be a more important cause of reduced return than a cannula positioned in a hepatic vein. IMPLICATIONS: Correct positioning of the venous cannula draining blood to the cardiopulmonary bypass circuit is important. Intraoperative transesophageal echocardiography allows satisfactory determination of the cannula position in nearly all patients. Ten percent of venous cannulae are primarily positioned in the right hepatic vein and not in the inferior vena cava as intended.

Adult↗

Intraoperative color Doppler ultrasound assessment of anastomoses of the left internal mammary artery to the left anterior descending coronary artery during off-pump coronary artery bypass surgery correlates with angiographic evaluation at the 8-month follow-up.

OBJECTIVE: This study was performed to evaluate the correlation between intraoperative color Doppler ultrasound assessment of anastomoses of the left internal mammary artery (LIMA) to the left anterior descending coronary artery (LAD) performed on the beating heart and the angiographic assessment after 8 months. METHODS: Twenty patients (M/F ratio, 14:6; mean age, 62 +/- 8 years) underwent epicardial color Doppler ultrasound imaging with a 10-MHz linear array GE Vingmed transducer combined with a GE Vingmed System FiVe. Transit-time flowmetry was used as intraoperative control. Follow-up coronary angiography after a median of 245 days (range, 128-320 days) allowed assessment of thrombolysis in myocardial infarction (TIMI) flow and FitzGibbon grading in all patients. Detailed quantitative coronary angiography was performed in 10 patients with an emphasis on comparing the LAD diameter at the toe of the anastomosis (D1) and in the downstream LAD (D2). RESULTS: Intraoperative ultrasound analysis revealed 19 patent LIMA-LAD anastomoses (95%). A >50% stenosis was detected in 1 anastomosis (5%), which was subsequently revised successfully. Follow-up angiographic evaluation showed TIMI-III flow and FitzGibbon grade A in 18 of 20 anastomoses (90%). One anastomosis was occluded, and one had FitzGibbon grade B stenosis. The D1/D2 ratios of the LAD measurements assessed with intraoperative ultrasound and follow-up quantitative coronary angiography were significantly correlated (r2 = 0.62; P < .01). CONCLUSION: Intraoperative color Doppler ultrasound allows a detailed evaluation of LIMA-LAD anastomoses during off-pump surgery, and the results correlate significantly with those of angiographic evaluation after 8 months. The present study shows that epicardial ultrasound is a promising tool for verification of LIMA-LAD anastomoses performed on the beating heart and may reduce the risk of impaired graft flow caused by technical errors.

Coronary Angiography↗

[Coronary surgery--arterial grafts instead of venous grafts?].

BACKGROUND: Recurrence of symptoms and the need for repeat interventions remains a clinical challenge following coronary artery bypass surgery, despite excellent early results. Saphenous vein graft failure has been identified as a main contributing factor to unsatisfactory long-term results. The use of multiple arterial grafts instead of venous grafts appears to be a promising treatment modality. This article describes our own experience with arterial revascularisation and gives a critical review of the literature. MATERIAL AND METHODS: Extended arterial revascularisation was performed in 30 patients at our institution between 1998 and 2001. Clinical follow-up was performed in all patients; re-angiography was done in six patients. 23 patients were operated on with bilateral mammary arteries; 11 patients received radial artery grafts. RESULTS: The median follow up was 12 months. All patients are alive, none suffered a new myocardial infarction. Our results are in accordance with the published literature. INTERPRETATION: Arterial grafting is a valuable tool in the armamentarium of modern coronary artery bypass surgery. Large randomised trials are required to clarify the role of extended arterial grafting in routine coronary bypass surgery.

Aged↗

Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4.

BACKGROUND: Coronary artery bypass grafting with the use of cardiopulmonary bypass is known to mediate an inflammatory response. The stress-inducible heat-shock protein (HSP) 70 has been detected in myocardial cells after CABG, and toll-like receptors (TLRs) are suggested as putative signaling receptors for the HSPs, mediating synthesis of inflammatory cytokines. The main aims of our study were to explore the release of HSP70 and the regulation of monocyte TLR-2 and TLR-4 expression after CABG. METHODS AND RESULTS: Twenty patients referred for elective CABG were included in this study. Using immunoassays, we detected HSP70 in plasma after CABG, with peak concentration immediately after surgery. Interleukin-6 in plasma reached peak concentration 5 hours after surgery. Monocyte CD14, TLR-2, and TLR-4 expression, as analyzed by flow cytometry, was initially downregulated. On day 1, CD14 expression normalized, whereas TLR-2 and TLR-4 expression was upregulated. TLR-4 was significantly upregulated even on postoperative day 2. Additional experiments revealed that peritoneal macrophages from control (C3H/HeN) mice responded to HSP70 with release of tumor necrosis factor, whereas macrophages from mutated TLR-4 (C3H/HeJ) mice were unresponsive. In vitro, human adherent monocytes responded to recombinant HSP70 with interleukin-6 and tumor necrosis factor release. CD14 and TLR-4 monoclonal antibodies inhibited the cytokine response. CONCLUSIONS: In this study, we observed an immediate release of HSP70 into the circulation and a modulation of monocyte TLR-2 and TLR-4 expression after CABG. TLR-4 and CD14 appear to be involved in an HSP70-mediated activation of innate immunity.

Aged↗