Emmeran Gams

Functional and Biochemical Evaluation of Platelet Aspirin Resistance After Coronary Artery Bypass Surgery

Background—Aspirin inhibits platelet activation and reduces atherothrombotic complications in patients at risk of myocardial infarction and stroke. However, a sufficient inhibition of platelet function by aspirin is not always achieved. The causes of this aspirin resistance are unknown. Methods and Results—Patients undergoing coronary artery bypass grafting (CABG) have a high incidence of aspirin resistance. To evaluate functional and biochemical responses to aspirin, platelet-rich plasma was obtained before and at days 1, 5, and 10 after CABG. Thromboxane formation, aggregation, and &agr;-granule secretion were effectively inhibited by 30 or 100 &mgr;mol/L aspirin in vitro before CABG, but this inhibition was prevented or attenuated after CABG. Whereas the inhibition of thromboxane formation and aggregation by aspirin in vitro partly recovered at day 10 after CABG, oral aspirin (100 mg/d) remained ineffective. The inducible isoform of cyclooxygenase in platelets, COX-2, has been suggested to confer aspirin resistance. In fact, immunoreactive COX-2 was increased 16-fold in platelets at day 5 after CABG, but the COX-2 selective inhibitor celecoxib did not alter aspirin-resistant thromboxane formation. By contrast, the combined inhibitor of thromboxane synthase and thromboxane receptor antagonist terbogrel equally prevented thromboxane formation of platelets obtained before (control) and after CABG. Conclusions—Platelet aspirin resistance involves an impairment of both in vivo and in vitro inhibition of platelet functions and is probably due to a disturbed inhibition of platelet COX-1 by aspirin.

Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.

INTRODUCTION Cell transplantation for myocardial regeneration has been shown to have beneficial effects on cardiac function after myocardial infarction. Most clinical studies of intramyocardial cell transplantation were performed in combination with coronary artery bypass grafting (CABG). The contribution of implanted stem cells could yet not be clearly distinguished from the effect of the CABG surgery. Our current phase 1 clinical study has focused on the safety and feasibility of CD133+-enriched stem cell transplantation without CABG and its potential beneficial effect on cardiac function. METHOD AND RESULTS Ten patients with end-stage chronic ischemic cardiomyopathy (ejection fraction <22%) were enrolled in the study. Bone marrow (up to 380 mL) was harvested from the iliac crest. CD133+ cells were purified from bone marrow cells using the CliniMACS device with purities up to 99%. Autologous bone marrow CD133+ cells (1.5-9.7 X 106 cells) were injected into predefined regions. Cardiac functions prior to and 3, 6, and 9 months after cell transplantation were assessed by cardiac magnetic resonance imaging. Stem cell transplantation typically improved the heart function stage from New York Heart Association/Canadian Cardiovascular Society class III-IV to I-II. The mean preoperative and postoperative ventricular ejection fractions were 15.8 +/- 5% and 24.8 +/- 5%, respectively. CONCLUSION CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Pulmonary embolism: a frequent cause of acute fatality after lung resection

Between 1975 and 1993, lung resections were performed in 1735 patients because of malignancies, with an early postoperative mortality of 7.2% (125 patients). Early postoperatively acute cardiorespiratory failure was experienced by 32 patients (1.85%), of whom 26 died despite immediate resuscitation measures. In 20/26 patients autopsy was performed revealing central pulmonary embolism as the cause of death in 19 of them. In one patient a rupture of the free posterior left ventricular wall following transmural myocardial infarction was found. Two patients who could be resuscitated successfully were operated on with extracorporeal circulation after pulmonary angiography had been performed to confirm the diagnosis; however they died 2 days later of right heart failure. Of the survivors three cases had myocardial infarctions, one patient had arrhythmias of unknown etiology. Immediate embolectomy with the use of extracorporeal circulation was performed in two patients, only on the ground of suspected pulmonary embolism and without further diagnostic measures. Both patients survived. Of the 23 cases, with proven pulmonary embolism 17 were still under postoperative prophylaxis with heparin. Six patients were already fully mobilized. We conclude that massive pulmonary embolism is a frequent early postoperative fatal complication after lung resections, which cannot be safely prevented by postoperative heparinization. The only successful life-saving measure in the case of central pulmonary embolism is immediate pulmonary embolectomy, if necessary without further diagnostic measures.

Flow cytometry analysis of platelet cyclooxygenase‐2 expression: induction of platelet cyclooxygenase‐2 in patients undergoing coronary artery bypass grafting

Summary. There are conflicting reports about the expression of cyclooxygenase (COX)‐2 in human platelets. The present study describes a flow cytometric method for the measurement of platelet COX. Both COX‐1 and COX‐2 were shown to be expressed in platelets from patients undergoing a coronary artery bypass graft. There was a significant increase in COX‐2 expression at day 5 as compared with pre‐surgery values (mean fluorescence 12·31 ± 0·88 versus 9·15 ± 0·88; means ± SEM, n = 7, P < 0·05), whereas COX‐1 levels did not change (13·45 ± 1·11 versus 12·38 ± 1·41; n = 7, P > 0·05).

Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX).

PURPOSE Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections. METHODS Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls). RESULTS In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV). CONCLUSIONS These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

Impact of prior percutaneous coronary intervention on the outcome of coronary artery bypass surgery: A multicenter analysis

OBJECTIVES Do prior percutaneous coronary interventions adversely affect the outcome of subsequent coronary artery bypass grafting? We investigated this effect on a multicenter basis. METHODS Eight cardiac surgical centers provided outcome data of 37,140 consecutive patients who underwent isolated first-time coronary bypass grafting between January 2000 and December 2005. Twenty-two patient characteristics and outcome variables were retrieved. Three groups of patients were analysed for in-hospital mortality and in-hospital major adverse cardiac events: patients without a previous percutaneous coronary intervention, with 1 previous intervention, and with 2 or more previous percutaneous coronary interventions before bypass grafting. A total of 29,928 patients with complete information for prior percutaneous coronary intervention underwent final analysis. Unadjusted univariate and risk-adjusted multivariate logistic regression analysis as well as computed propensity score matching were performed, based on 14 major risk factors to correct for and minimize selection bias. RESULTS A total of 10.3% of patients had 1 previous percutaneous coronary intervention, and 3.7% of patients had 2 or more previous interventions. Risk-adjusted multivariate logistic regression analysis revealed a significant association of 2 or more previous percutaneous coronary interventions with in-hospital mortality (odds ratio [OR], 2.0; confidence interval [CI], 1.4-3.0; P = .0005) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0013). After propensity score matching, conditional logistic regression analysis confirmed the results of adjusted analysis. A history of 2 or more previous percutaneous coronary interventions was significantly associated with in-hospital mortality (OR, 1.9; CI, 1.3-2.7; P = .0016) and major adverse cardiac events (OR, 1.5; CI, 1.2-1.9; P = .0019). CONCLUSIONS Multicenter analysis confirms that a history of multiple previous percutaneous coronary interventions increases in-hospital mortality and the incidence of major adverse cardiac events after subsequent coronary artery bypass grafting. Critical discussion of the treatment strategy in these patients is warranted.

Predictors and outcome of ICU readmission after cardiac surgery.

OBJECTIVE Readmission to the intensive care unit (ICU) after cardiac surgery is associated with higher costs and may be correlated with an increased mortality. We wanted to evaluate predictors of ICU readmission and to analyze the outcome of those patients. METHODS 3523 patients who underwent CABG and/or valve surgery between 2004 and 2007 were reviewed retrospectively. The reasons for readmission and the postoperative course were analyzed. Furthermore, perioperative risk factors for readmission were determined by multivariate regression analysis. RESULTS Of the 3374 patients discharged from the ICU, 5.9 % (198) of patients required a second stay in the intensive care (group r). The readmission rate was 4.8 % following CABG and 8.9 % following valve +/- CABG ( P < 0.05). The mean interval from ICU discharge to readmission was 3.3 +/- 6.2 days. Of the patients who were not readmitted, 1.3 % died in hospital, compared to 14.4 % in group r ( P < 0.05). After readmission, the mean length of stay in the ICU and in hospital was 7.1 +/- 5.9 and 21.3 +/- 11.1 days (3.1 +/- 1.2 and 13.1 +/- 5.1 days for all other patients [ P < 0.05]). Main reasons for readmission were respiratory failure (59 %), cardiovascular instability (25 %), renal failure (6.5 %), cardiac tamponade/bleeding (6 %), gastrointestinal complications (2 %) and sepsis (1.5 %). Multivariate logistic regression analysis revealed that preoperative renal failure, mechanical ventilation > 24 h, reexploration for bleeding and low cardiac output state were independent predictors for readmission. CONCLUSIONS Patients after valve/combined surgery are more likely to require readmission to the ICU. Respiratory complications were the most common reasons for readmission. To reduce the readmission rate, it is necessary to treat cardio-respiratory problems early, particularly in patients showing predictive risk factors.

Increased preoperative C-reactive protein (CRP)-values without signs of an infection and complicated course after cardiopulmonary bypass (CPB) – operations

OBJECTIVE C-Reactive protein (CRP) is known to be a sensitive indicator of infection. Since it is also involved in the acute phase reaction, it is of great interest, whether an isolated preoperative increase of CRP without further signs of infection is of any prognostic value for postoperative outcome after cardiac surgery with cardiopulmonary bypass (CPB), which itself is possibly causing a systemic inflammatory response syndrome (SIRS). METHODS Fifty patients with an isolated CRP-elevation (>5 mg/l) (from 6.2 to 93.3 mg/l) were operated using CPB (group A). A control group (group B) consisted of 50 cardiac surgery patients, matched in the patterns of age, gender and kind of disease. No preoperative CRP-elevation (from 0 to 4.8 mg/l) occurred in this group. RESULTS The postoperative course of both groups showed significant differences. Septic complications were seen more often in group A (20%) than in the controls (2%) (P < 0.01). Microbiology (blood culture, cultures from nose, tracheal aspirate and urine) was positive only in 10% of these patients. Catecholamine support (epinephrine, norepinephrine and/or doses of dopamine or dobutamine of more than 3 microg/kg per min) was needed in 26% of group A cases, whereas it was only needed in 10% of group B (P < 0.05). A significantly longer respiratory support was also necessary in patients with elevated CRP (25.2 +/- 6.4 h vs. 6.6 +/- 0.8 h) (P < 0.01). Furthermore there was a significant difference in the duration of intensive care (4.6 +/- 0.8 days vs. 2.6 +/- 0.3 days) (P < 0.05). CONCLUSIONS These data show that patients without apparent infection or inflammation, who had elevated CRP-values preoperatively, face an increased risk of septic complications after extracorporeal circulation. As microbiology tests are negative in most cases, it may be speculated that the majority of septic complications are due to a SIRS.

Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases.

We report 2 cases in which patients with coronary heart disease not amenable for conventional revascularization underwent transmyocardial laser revascularization (TMLR) and implantation of AC133+ bone-marrow stem cells. The reason for using TMLR in combination with stem cell application is to take advantage of the synergistic angiogenic effect. The local inflammatory reaction induced by TMLR should serve as an informational platform for stem cells and may trigger their angiogenic differentiation. Functional analysis of myocardial performance after treatment in these 2 cases revealed dramatic improvement of the wall motion at the site of the TMLR and stem cell application. Because TMLR does not enhance myocardial contractility and there was no angiographic evidence of major collaterals to the ischemic region in either patient, we assume that the synergistic effect of stem cells and TMLR-induced angiogenesis occurred; however, our assumption is of a speculative nature. We think that TMLR in combination with stem cell transplantation might become a novel revascularization therapy for ischemic myocardium.

Heart-type fatty acid binding protein (hFABP) in the diagnosis of myocardial damage in coronary artery bypass grafting

OBJECTIVES Heart-type fatty acid binding protein (hFABP) is an intracellular molecule engaged in the transport of fatty acids through myocardial cytoplasm and has been used as a rapid marker of myocardial infarction. However, its value in the evaluation of perioperative myocardial injury has not yet been assessed. METHODS 32 consecutive patients undergoing coronary artery bypass grafting were included in a prospective, randomized study using standardized operative procedures and myocardial protection. Three patients with perioperative myocardial infarction were added. Serial blood samples were taken preoperatively, before ischemia, 5 and 60 min after declamping, 1 and 6 h postoperatively and on postoperative days 1, 2 and 10 and were tested for hFABP, creatine kinase isoenzyme MB (CKMB) and troponin I (TnI). RESULTS Hospital mortality was zero. The kinetics of the biochemical parameters revealed a typical pattern for each marker. In routine patients, hFABP levels peaked as early as 1 h after declamping, whereas CKMB and TnI peaked only 1 h after arrival in the intensive care unit. Patients with perioperative infarction displayed peak levels some hours later in all marker proteins. Peak serum levels of hFABP correlated significantly with peak levels of CKMB (r=0.436, P=0.011) and TnI (r=0.548, P=0.001), indicating the degree of myocardial damage. CONCLUSIONS hFABP is a rapid marker of perioperative myocardial damage and peaks earlier than CKMB or TnI. The kinetics of marker proteins in serial samples immediately after reperfusion is more suitable for the detection of perioperative myocardial infarction than a fixed cut-off level.