Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved.

Electromechanical synchronization of the heterotopic and native heart by dual atrial stimulation following heart transplantation.

After heterotopic heart transplantation, a 59-year-old woman presented with remarkable symptoms of breathlessness and fatigue, despite excellent donor heart function. Asynchrony of donor and native heart provoked haemodynamic instability. Dual atrial pacemaker implantation lead to linkage and synchronization of atrial and ventricular contraction in both the donor and native heart with the faster organ executing the synchronization. Remarkable relief of symptoms has been evident during the long-term follow-up.

Predictors of perioperative mortality after coronary artery bypass grafting in the elderly.

BACKGROUND: Coronary artery bypass grafting (CABG) is associated with higher operative risk in the elderly compared to younger patients. The aim of this study was to evaluate risk factors for perioperative mortality after CABG in the elderly. METHODS: We investigated 325 consecutive patients aged 75 or over undergoing isolated CABG at our institution. We analyzed the patients' characteristics and perioperative outcome. Patients were divided into survivors and non-survivors; risk factors and complications were compared. Based on this, we performed a multivariate logistic regression analysis to determine independent risk factors for perioperative mortality. RESULTS: Non-survivors of CABG more often suffered from concomitant extracardiac atherosclerosis (non-survivors, 62.2 %; survivors, 40.6 %; p = 0.013) as well as from renal insufficiency preoperatively (non-survivors, 35.1 %; survivors 8.0 %; p < 0.0001). A trend towards higher incidences of impaired left ventricular function (non-survivors, 37.8 %; survivors, 29.9 %; p = 0.105) and a history of recent myocardial infarction (non-survivors, 29.7 %; survivors, 17.0 %; p = 0.061) were found in non-survivors compared to survivors. Furthermore, non-survivors more often underwent CABG with cardiopulmonary bypass (CPB non-survivors, 96.1 %; survivors 70.6 %; p = 0.0005). Multivariate logistic regression analysis revealed that preoperatively impaired renal function (OR: 2.857, p < 0.0001), use of CPB (OR: 5.952, p = 0.0175), extracardiac atherosclerosis (OR: 1.581, p = 0.0228), and recent myocardial infarction (OR: 1.574, p = 0.0405) were independent risk factors for perioperative mortality. Comparison of patients undergoing CABG with or without CPB reveals that patients operated without CPB had a higher preoperative risk than patients undergoing CABG with CPB. CONCLUSION: These results show that besides impaired renal function, extracardiac atherosclerosis, and history of recent myocardial infarction, the use of CPB is a major risk factor for CABG in the elderly. Perioperative mortality and morbidity can be significantly reduced if CPB is avoided.

The impact of diabetes mellitus at the time of heart transplantation on long-term survival.

AIMS/HYPOTHESIS: To analyse the impact of diabetes mellitus (DM) at the time of heart transplantation on long-term survival and incidence of transplant coronary artery disease (TxCAD). METHODS: We analysed 773 consecutive adult heart transplant recipients who underwent primary heart transplantation from May 1986 until December 2000. The cohort consisted of 140 patients with diabetes mellitus (with DM, men 82%) and 633 patients without (wo DM, men 84%) diabetes mellitus at the time of transplantation. The patients were documented as to survival and incidence of TxCAD. RESULTS: Patients with diabetes mellitus were older compared to those without diabetes mellitus (with DM 54.9+/-6.8a vs wo DM 49.7+/-10.8a; p=0.0001), they had a higher incidence of ischaemic cardiomyopathy prior to transplantation (with DM 52% vs wo DM 30%; p=0.0001), but reduced long-term survival (10 year survival: with DM 40% vs wo DM 58%; log-rank=0.025). Surprisingly, the incidence of transplant coronary artery disease (TxCAD) was comparable at 10 years (with DM 28% vs wo DM 22%; log-rank=0.625). In multivariate Cox proportional hazard analysis, diabetes mellitus present at the time of heart transplantation (HR 1.594; 95%CI 1.009-2.518; p=0.045), but not age (HR 0.990; 95%CI 0.965-1.014; p=0.404) was an independent predictor affecting long-term survival. CONCLUSION/INTERPRETATION: The presence of diabetes mellitus at the time of heart transplantation adversely affects long-term patient survival, but does not predict the occurrence of transplant coronary artery disease. The definite mechanisms of adverse survival primarily seem to relate to generally impaired global organ function. Despite a less favourable long-term outcome, our data still justify heart transplantation in end-stage heart failure patients with diabetes mellitus.

Target vessel revascularization without cardiopulmonary bypass in elderly high-risk patients.

BACKGROUND: Coronary artery bypass grafting in patients over 75 years is associated with high operative risk. Target vessel revascularization without cardiopulmonary bypass is a promising option for highly selected, older patients. However, the outcome remains uncertain. METHODS: We investigated 44 patients over 75 years, matched for preoperative risk and left ventricular function, who underwent coronary artery bypass grafting either with or without cardiopulmonary bypass (CPB). We analyzed patients characteristics, Parsonnet score, EuroSCORE, short as well as midterm outcome and quality of life (freedom from recurrence of angina, anti-anginal therapy, sf36 test). RESULTS: Perioperative mortality was higher in the patient group operated with CPB (15.9) as compared to patients operated without CPB (4.5%, p = 0.0226). Patients operated with cardiopulmonary bypass received more grafts (3.1 +/- 0.1) than patients operated without cardiopulmonary bypass (1.6 +/- 0.1, p = 0.0001) and and were more likely to undergo complete revascularization (with CPB 100%, without CPB 63.6%, p = 0.0010). Perioperative complications were more frequent and midterm survival was worse in the patient group operated with CPB (log rank p = 0.0228). Quality of life was comparable in both groups. CONCLUSIONS: The concept of incomplete target vessel revascularization of the culprit lesion seems to be a promising option for selected high-risk patients, predominantly due to lower perioperative mortality.

Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: The feasibility of complete revascularization on the beating heart without cardiopulmonary bypass (CPB) as compared with the standard operation with CPB in elective low-risk patients with multivessel disease has not been clearly demonstrated in a prospective trial. METHODS: Eighty selected low-risk patients were enrolled. In preoperative study with coronary angiography, the decision was made whether complete revascularization without CPB could be performed. Patients were randomly assigned to receive CABG either with (n = 40) or without CPB (n = 40). Randomization criteria were age, sex, and left ventricular ejection fraction. Completeness of revascularization as well as short- and mid-term clinical outcome in a 13.4 +/- 6.5 month follow-up period were monitored. RESULTS: Twenty-six of 40 (65%) patients undergoing CABG without CPB underwent complete revascularization. In 5 of these patients (12.5%) suitable vessels were discarded for technical reasons and 9 patients (22.5%) were switched to CABG with CPB owing to the deeply intramyocardial course of target vessels (n = 5) or to hemodynamic instability (n = 4). In the group of patients operated on with CPB, 34 of 40 patients (85%) received complete revascularization. In 6 patients (15%) suitable vessels were discarded for technical reasons. Mean number of bypass grafts was 3.1 +/- 0.8 with CPB and 2.6 +/- 0.5 without CPB (p = 0.043). Clinical outcome and hospital stay were comparable in both groups. No patient died during the study period. No myocardial infarction was observed. Three patients undergoing CABG without CPB underwent successful PTCA 3 months after surgery. CONCLUSIONS: CABG without the use of CPB is effective for complete revascularization in the majority of selected low-risk patients. Nevertheless, it has to be stated that the rate of incomplete revascularization in this early series of CABG without CPB is higher, and compromises the basic principle of complete revascularization.

Cardiopulmonary bypass affects cognitive brain function after coronary artery bypass grafting.

BACKGROUND: The causes for cognitive impairment after coronary artery bypass grafting (CABG) have long been a topic for debate. METHODS: We prospectively followed 308 consecutive, unselected survivors of CABG at our institution. In addition to determination of clinical measurements, cognitive brain function was measured objectively by P300 auditory-evoked potentials before CABG, at 7-day and at 4-month follow-up. Standard psychometric tests (Trail Making Test A, Mini Mental State Examination) were also performed. RESULTS: At 7-day follow-up cognitive P300 auditory-evoked potentials were significantly impaired compared with preoperative levels (peak latencies: 376 +/- 40 ms versus 366 +/- 37 ms, p = 0.0001). P300 measurements were almost normalized at 4-month follow-up (peak latencies: 369 +/- 33 ms, p = NS versus preoperative). Standard psychometric tests failed to detect this subclinical cognitive impairment. Multiple regression analysis revealed that use of cardiopulmonary bypass was the only independent predictor of impaired cognitive brain function at 7-day (p < 0.0001) and 4-month follow-up (p = 0.0008). The presence of diabetes mellitus (p = 0.0135) or concomitant repair of significant carotid artery stenosis (p = 0.0049) was predictive of late improvement of cognitive brain function at 4-month follow-up. CONCLUSIONS: Objective cognitive P300 auditory-evoked potential measurements demonstrate that the use of cardiopulmonary bypass is the only predictor of short- and long-term cognitive brain dysfunction after CABG. Interestingly, the presence of diabetes mellitus and concomitant repair of a significant carotid artery stenosis were predictive for long-term cognitive benefit.

Enhanced peroxynitrite formation is associated with vascular aging.

Vascular aging is mainly characterized by endothelial dysfunction. We found decreased free nitric oxide (NO) levels in aged rat aortas, in conjunction with a sevenfold higher expression and activity of endothelial NO synthase (eNOS). This is shown to be a consequence of age-associated enhanced superoxide (.O(2)(-)) production with concomitant quenching of NO by the formation of peroxynitrite leading to nitrotyrosilation of mitochondrial manganese superoxide dismutase (MnSOD), a molecular footprint of increased peroxynitrite levels, which also increased with age. Thus, vascular aging appears to be initiated by augmented.O(2)(-) release, trapping of vasorelaxant NO, and subsequent peroxynitrite formation, followed by the nitration and inhibition of MnSOD. Increased eNOS expression and activity is a compensatory, but eventually futile, mechanism to counter regulate the loss of NO. The ultrastructural distribution of 3-nitrotyrosyl suggests that mitochondrial dysfunction plays a major role in the vascular aging process.

Normothermic cardiopulmonary bypass is beneficial for cognitive brain function after coronary artery bypass grafting--a prospective randomized trial.

BACKGROUND: Hypothermic and normothermic cardiopulmonary bypass (CPB) have resulted in apparently contradictionary cardiac and neurologic outcome. Cerebrovascular risk and cognitive dysfunction associated with normothermic CPB still remain uncertain. MATERIALS AND METHODS: In a prospective randomized study, we measured the effects of mildly hypothermic (32 degrees C, n=72) vs. normothermic (37 degrees C, n=72) CPB on cognitive brain function. All patients received elective coronary artery bypass grafting (mean age 62.1+/-6.3 years, mean ejection fraction 60.4+/-13%). Cognitive brain function was objectively measured by cognitive P300 auditory-evoked potentials before surgery, 1 week and 4 months after surgery, respectively. Additionally, standard psychometric tests ('trailmaking test A', 'mini-mental state') were performed and clinical outcome was monitored. RESULTS: Patients, operated with mild hypothermia, showed a marked impairment of cognitive brain function. As compared with before surgery (370+/-45 ms), P300 evoked potentials were prolonged at 1 week (385+/-37 ms; P<0.001) and even at 4 months (378+/-34 ms, P<0.001) after surgery, respectively. In contrast, patients operated with normothermic CPB, did not show an impairment of P300 peak latencies (before surgery 369+/-36 ms, 1 week after surgery 376+/-38 ms, n.s.; 4 months after surgery 371+/-32 ms, n.s.). Group comparison revealed a trend towards prolonged P300 peak latencies in the patient group undergoing mildly hypothermic CPB (P=0.0634) 1 week after surgery. Four months postoperatively, no difference between the two groups could be shown (P=n.s.) Trailmaking test A and mini mental state test failed to discriminate any difference. Five patients died (mild hypothermia n=3, normothermia n=2) postoperatively (cardiac related n=3, sepsis n=2). None of the patients experienced major adverse cerebrovascular events. CONCLUSIONS: Objective cognitive P300 auditory evoked potential measurements indicate, that subclinical impairment of cognitive brain function is more pronounced in patients undergoing mildly hypothermic CPB as compared with normothermic CPB for CABG.

Lack of nuclear apoptosis in cardiomyocytes and increased endothelin-1 levels in a rat heart model of myocardial stunning.

OBJECTIVE: Reperfusion injury may affect the cardiac NO and endothelin production. We investigated whether 20 min of total ischemia followed by 40 min of reperfusion can induce apoptosis in a Langendorff model of retrogradely perfused rat hearts (37 degrees C; paced at 300/'), and we attempted to correlate these findings with measured tissue NO and ET-1 levels. METHODS: An apoptosis detection system was utilized which catalytically incorporates fluorescein-12-dUTP at the 3'-OH DNA ends using the principle of the TUNEL assay, with direct visualization of the labeled DNA. ET-1 was measured by radioimmunoassay and NO3/NO2 by ion pairing HPLC on C18 reverse phase columns. RESULTS: None of the postischemic (n = 6) nor of the control perfused (90 min, n = 6) hearts showed signs of apoptosis, while those exposed to longer ischemia (40 min) and reperfusion (2 h) confirmed the presence of apoptotic cells. Myocardial ET-1 concentrations were 4.8 +/- 1.0 versus 8.3 +/- 2.5 pg/100 mg (control vs. ischemic hearts, respectively; mean +/- SD; p < 0.05). Myocardial NO contents showed no differences. CONCLUSION: These data suggest that the time window of apoptosis with detectable DNA fragmentation exceeds 20 min of global total ischemia and 40 min of reperfusion, a model frequently used for inducing myocardial stunning. While NO was not increased in postischemic hearts, increased ET-1 levels indirectly argue for a role of ET-1 as inducer of apoptosis, but only at a later stage of reperfusion.

Inflammatory response and myocardial injury following coronary artery bypass grafting with or without cardiopulmonary bypass.

OBJECTIVE: In coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) the inflammatory response is suggested to be minimized. Coronary anastomoses are performed during temporary coronary occlusion. Inflammatory response and myocardial ischaemia need to be studied in a randomized study comparing CABG in multivessel disease with versus without CPB. METHODS: Following randomization 30 consecutive patients received CABG either with (n=16) or without CPB (n=14). Primary study endpoints were parameters of the inflammatory response (interleukin (IL)-6, interleukin-10, ICAM-1, P-selectin) and of myocardial injury (myoglobin, creatine kinase-MB (CK-MB), troponin I) (intraoperatively, 4, 8, 16, 24 and 48 h after surgery). The secondary endpoint was clinical outcome. RESULTS: The incidence of major (death: CABG with CPB n=1, not significant (n.s.)) and minor adverse events (wound infection: with CPB n=2, without CPB n=1, n.s. ; atrial fibrillation: with CPB n=3, without CPB n=2, n.s.) was comparable between both groups. The release of IL-6 was comparable during 8 h of observation (n.s.). Immediately postoperatively IL-10 levels were higher in the operated group with CPB (211.7+/-181.9 ng/ml) than in operated patients without CPB (104.6+/-40.3 ng/ml, P=0.0017). Thereafter no differences were found between both groups. A similar pattern of release was observed in serial measures of ICAM-1 and P-selectin, with no difference between both study groups (n.s.). Eight hours postoperatively the cumulative release of myoglobin was lower in operated patients without CPB (1829.7+/-1374. 5 microg/l) than in operated patients with CPB (4469.8+/-4525.7 microg/l, P=0.0152). Troponin I release was 300.7+/-470.5 microg/l (48 h postoperatively) in patients without CPB and 552.9+/-527.8 microg/l (P=0.0213). CK-MB mass release was 323.5+/-221.2 microg/l (24 h postoperatively) in operated patients without CPB and 1030. 4+/-1410.3 microg/l in operated patients with CPB (P=0.0003). CONCLUSIONS: This prospective randomized study suggests that in low-risk patients the impact of surgical access on inflammatory response may mimic the influence of long cross-clamp and perfusion times on inflammatory response. Our findings indicate that multiregional warm ischaemia, caused by snaring of the diseased coronary artery, causes considerably less myocardial injury than global cold ischaemia induced by cardioplegic cardiac arrest.

Complement C6 deficiency protects against diet-induced atherosclerosis in rabbits.

Low-density lipoprotein (LDL) can be transformed to an atherogenic moiety by nonoxidative, enzymatic degradation. Enzymatically degraded LDL induces macrophage foam cell formation, provokes release of cytokines, and also activates complement. To determine whether complement activation may contribute to atherogenesis, 6 pairs of homozygous C6-deficient rabbits and their non-C6-deficient heterozygous siblings were fed a cholesterol-rich diet for 14 weeks. Cholesterol levels and plasma lipoprotein profiles of the animals in the C6-competent and C6-deficient groups did not significantly differ, and the high density lipoprotein and LDL cholesterol ratios at the end of the experiment were 0.07+/-0.01 and 0.08+/-0.01 (SEM), respectively. However, differences in atherosclerotic plaque formation were discernible macroscopically, with extensive aortic lesions being visible in all C6-competent animals and absent in all C6-deficient animals. Aortas were sectioned from thorax to abdomen, and 10 sections were stained from each aorta. Quantification of atherosclerotic lesions and lumen stenosis with the use of computer-based morphometry documented a dramatic protective effect of C6 deficiency on the development of diet-induced atherosclerosis. We conclude that the terminal complement sequence is centrally involved in atherosclerotic lesion progression.