Magnetic resonance cholangiopancreatography for the accurate diagnosis of biliary complications after liver transplantation: comparison with endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography - long-term follow-up.

Biliary complications after liver transplantation remain a serious cause of morbidity and mortality. Direct invasive cholangiographic techniques, endoscopic retrograde cholangiography (ERCP) or percutaneous transhepatic cholangiography (PTC), have procedure-related complications. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive, safe, and accurate. The aim of this study was to evaluate MRCP in detecting biliary complications following liver transplantation and comparing findings with ERCP and PTC. Twenty-seven consecutive liver transplant recipients who presented with clinical and biochemical, ultrasonographic, or histological evidence of biliary complications were evaluated with MRCP. Patients were followed up for a median period of 36 months. The presence of a biliary complication was confirmed in 18 patients (66.6%): anastomotic biliary stricture in 12 (66.6%); diffuse intrahepatic biliary stricture in 5 (27.7%): ischemic (n = 3), recurrence of primary sclerosing cholangitis (n = 2), and choledocholithiasis in one. In nine patients (33.3%), MRCP was normal. Six patients underwent ERCP, and eight PTC. There was a statistically significant correlation between the MRCP and both ERCP and PTC (p = 0.01) findings. The sensitivity and specificity of the MRCP were 94.4% and 88.9%, respectively, and the positive and negative predictive values, 94.4% and 89.9%, respectively. MRCP is an accurate imaging tool for the assessment of biliary complications after liver transplantation. We recommend that MRCP be the diagnostic imaging modality of choice in this setting, reserving direct cholangiography for therapeutic procedures.

Colorectal cancer in young patients in Israel: a distinct clinicopathological entity?

PURPOSE: This study was designed to characterize the entity of colorectal cancer (CRC) in young patients and to evaluate whether it has any unique epidemiological or clinicopathological features. METHODS: The study population consisted of all consecutive young (≤50 years old at diagnosis) patients with CRC who were diagnosed during the years 1997-2007 and were treated at our institution, and a matching group of patients (>50 years at diagnosis). The medical files of these patients were reviewed, and the epidemiological, clinical, and pathological features of both groups were compared. RESULTS: There were 406 patients: 203 in each group. The features of the older group were typical for patients with CRC, but the younger group showed female predominance, different ethnic composition, prevalence of family history of cancer and hereditary CRC syndromes, and lower incidence of polyps. The incidence of left-sided tumors and advanced stages (III-IV) at diagnosis was higher in the younger patients. Mucinous/signet ring histology, grade, stage, lymphatic and vascular invasion were all predictive of survival, whereas age was not. CONCLUSIONS: Colorectal cancer in young patients was found to display a cluster of unique characteristics but fewer than previously reported and young age by itself was not found to impact patient outcome.

Anti-Saccharomyces cerevisiae antibodies in Behçet's disease--a familial study.

OBJECTIVE: To evaluate the rate and clinical correlations of antibodies against saccharomyces cerevisiae (ASCA) among healthy family members of patients with Behçet's disease (BD). METHODS: Twenty-one BD patients and 52 healthy family members (HFM) were studied. Data from medical files and from patients' interviews was collected, regarding the entire spectrum of disease manifestations. Each family member was personally interviewed and a questionnaire composed of BD symptoms and their temporal relation was compiled. IgA- and IgG-ASCA levels, determined by ELISA, were studied in all BD patients and their family members, the results were compared to a group of 23 healthy controls (HC). RESULTS: Eight (38.1%) BD patients were ASCA positive, compared to five among HFM (9.6%) and none among healthy unrelated controls (p=0.001). Mean IgG and IgA-ASCA levels were significantly higher in BD patients compared with HFM and HC groups (p = 0.002 and p = 0.03, respectively). No correlation was found between positive ASCA tests and any of BD-related manifestations. Mean IgG-ASCA levels were significantly lower in HFM compared to BD patients (p = 0.03), yet IgA-ASCA levels were similar in HFM and BD. Mean IgG and IgA-ASCA levels were higher in HFM compared with healthy unrelated controls (p=0.09 and p=0.03). No difference was found in ASCA rates between relatives of BD patients who had positive or negative ASCA tests, or between spouses of BD patients and genetically related relatives. In HFM with recurrent oral ulcers there was a positive correlation between titers of IgA-ASCA and the yearly number of oral ulcers episodes (p = 0.01), and mean ulcers healing time (p = 0.01). IgG-ASCA titers correlated with yearly number of aphtae episodes (p = 0.03). CONCLUSION: The results of this study confirm our previous observation on a high prevalence of ASCA in BD. ASCA levels are also increased in healthy family members of BD patients, and are probably influenced by genetic as well as environmental factors. ASCA in HFM were significantly associated with a more severe oral ulcer disease. The role of ASCA as a marker for predisposition to develop future BD remains to be evaluated.

Radiation treatment for ductal carcinoma in situ (DCIS): is a boost to the tumor bed necessary?

The aim of the presented study was to evaluate the long-term outcome of breast-conserving surgery and radiation for the treatment of ductal carcinoma in situ (DCIS) and the role of the radiation boost to the tumor bed. The files of 75 women with DCIS treated by breast-conserving surgery followed by definitive radiation from 1988 to 1997 were reviewed for demographic data, prognostic variables, radiation dose, radiation boost, recurrence, and outcome. Total radiation dose was 5000 cGy delivered in 25 fractions. Twenty patients (26.7%) received an additional boost to the tumor bed of 1000 cGy in 5 fractions. Median follow-up time was 81.5 months (range, 22-145). Pearson correlation coefficient and its significance was calculated between the variables. Log rank test was used to analyze differences in local recurrence rates between patients who did or did not receive a boost, and a Cox regression model was fitted to the data to predict recurrence. Ten patients (13%) had local recurrence; one patient showed lymphatic spread. Histopathologic examination revealed DCIS in 6 cases (60%) and invasive duct carcinoma in 4 (40%)(one minimally invasive). The recurrence group included 3 of the 20 patients who received a radiation boost (15%) and 7 of the 55 who did not (12.7%) (p=0.7). Correlation analysis of patient characteristics, prognostic factors, and treatment was significant only between mastitis as the presenting symptom (n=4) and longer time to recurrence (p=0.02). The recurrence rate in the present study was similar to other series of conservative treatment for DCIS of the breast. No additional value was found for the radiation boost. Larger controlled randomized studies are needed to confirm these findings.

Neutrons and sudden cardiac death (SCD) codes 121-125 ICD 10.

Recent studies have shown that (1) monthly neutron activity (NA) (imp/min) correlates with monthly number of acute myocardial infarction (AMI); (2) NA is higher on days of automatic implantable cardioverter defibrillators (AICD) discharges for VT, VF. Here we checked the level of NA in relation to timing and type of sudden cardiac death (SCD) patients [n=848 (579, 68.28% male)] obtained from the Kaunas registry for the years 2002-2004. All underwent Forensic Medicine post mortem examination and classification according to ICD10 by code 121-125. Daily NA data were obtained from Oulu U-ty, Finland and Moscow Monitoring Station of the Russian Academy of Sciences. No difference in NA was found on days with or without SCD. In men < 65, SCD occurred on days with higher NA than in women of the same age (p = 0.01) or in > 65 y old men (p = 0.045). Days of SCD with myocardial ruptures showed the highest level of NA, significantly higher than on all days (n = 669) of SCD (p = 0.037) and all 1096 days of the study (p = 0.0048). Three groups were accompanied by significantly higher NA: repeated AMI, myocardial ruptures (codes122, 123), and coronary atherothrombosis without AMI, related to electrical heart instability. The mechanism of possible neutron role in pathophysiology needs special studies.

Importance of the conal branch of the right coronary artery in patients with acute anterior wall myocardial infarction: electrocardiographic and angiographic correlation.

OBJECTIVES: This study assessed prospectively the correlation between the conal branch of the right coronary artery and the pattern of ST segment elevation in leads V1 and V3R during anterior wall acute myocardial infarction (AMI). BACKGROUND: The traditional electrocardiographic (ECG) definition of anteroseptal AMI-ST segment elevation in leads V1 to V3-has recently been challenged. The significance of ST segment elevation in lead V1 during anterior wall AMI is unclear. METHODS: The admission 12-lead ECG with additional lead V3R and the coronary angiograms performed within 10 days of hospital admission were evaluated in 28 consecutive patients (mean age +/- SD 62 +/- 9 years) admitted to the coronary care unit with anterior wall AMI. Patients were classified into two groups according to the magnitude of ST segment elevation in lead V1: group A (elevation > or = 1.5 mm, n = 12) and group B (elevation < 1.5 mm, n = 16). Two types of conal branch were identified: small (not reaching the interventricular septum [IVS]) and large (reaching the IVS). RESULTS: ST segment elevation in lead V3R was found in 11 (92%) and 6 (37%) patients from group A and group B, respectively (p < 0.001); a small conal branch was seen in 10 (83%) and 3 (19%) patients, respectively (p < 0.001). Ten patients (all from group B) had a large conal branch. CONCLUSIONS: ST segment elevation in lead V1 in the admission ECG of patients with anterior wall AMI is strongly related to ST segment elevation in lead V3R and is associated with a small conal branch. Our findings suggest that lead V1 reflects the right paraseptal area supplied by the septal branches of the left anterior descending coronary artery (LAD), alone or together with the conal branch. The absence of ST segment elevation in lead V1 during anterior AMI suggests that the IVS is protected by a large conal branch in addition to the septal branches of the LAD (double circulation).

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.

Suicide-homicide temporal interrelationship, links with other fatalities, and environmental physical activity.

UNLABELLED: Homicide and suicide are extremes in human behavior. The aim of this study is to investigate the connection by time between suicide and homicide, between them and other fatalities, and their links with the level of cosmophysical activity. METHODS: Using the national database of Lithuania (1990-2002) we found that 547,875 deaths, 4,638 homicides (3,374 male) and 19,527 (16,019 male) suicides were registered in that period. Their temporal distribution over 156 months was compared with solar and cosmic-ray activity. Pearson correlation coefficients and their probabilities were established. RESULTS: There was a correlation between monthly rates of homicide and male groups. Female suicide rates correlated with male and total homicide numbers. Both homicide and suicide rates were inversely correlated with solar and cosmic-ray activity. Suicide numbers, but not homicides, were inversely related to geomagnetic activity. Suicide rates were inversely correlated with total, cardiovascular, traffic accident, and sudden deaths; homicide with total, traffic accident, and sudden deaths. CONCLUSION: Temporal distribution of homicide and suicide is significantly interrelated. Both are linked to parameters of cosmophysical activity. The influence of cosmic rays deserves special attention.

Plasma neurotransmitter profile during different phases of the ovulatory cycle.

The influence of the different phases of the menstrual cycle on platelet-poor plasma norepinephrine (NE) and serotonin (5HT) was examined in 17 normal volunteers. The examinations were performed consecutively during 3 phases of the ovulatory cycle: 1) follicular phase, 2) ovulation, and 3) luteal phase. This investigation was initiated after a preliminary study in 51 volunteers showed wide and consistent variations of plasma NE and 5HT during the different phases of the cycle. Since in this first group the determinations had not been performed consecutively in the same subjects, and the changes observed in the different phases of the cycle could reflect interpersonal variations, the determinations were performed consecutively in a second group, concomitantly with serum estradiol (E2) and LH measurements. The results showed a decrease in plasma 5HT from the follicular phase [144.3 +/- 69.3 nmol/L (+/- SD)] to ovulation (55.7 +/- 41.4; P less than 0.001) and a subsequent increase in the luteal phase (141.3 +/- 96.4; P less than 0.01). The nadir in plasma 5HT showed an inverse correlation with serum LH (r = -0.07). Plasma NE increased from the follicular phase (1226.5 +/- 475.1 pmol/L) to ovulation (1694.0 +/- 564.4; P = 0.027) and reached a maximum in the luteal phase (2335.0 +/- 728.2; P = 0.0034). This rise correlated positively with serum E2. In conclusion, plasma 5HT and NE vary with the different phases of the menstrual cycle. Plasma NE rises during ovulation and seems to to correlate positively with serum E2 levels. Plasma 5HT reaches a nadir during ovulation and correlates inversely with serum LH.

Ovarian angiotensin-converting enzyme activity in humans: relationship to estradiol, age, and uterine pathology.

The present study was designed to measure angiotensin-converting enzyme (ACE) activity in the human ovary and in serum and to relate this activity to age, serum estradiol levels, and uterine and endometrial pathology. ACE activity was determined in 56 females by a radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. Ovarian ACE activity, but not serum ACE, was found to increase with age (P < 0.01) and was significantly greater in postmenopausal subjects (n = 31; 1.35 +/- 0.05 nmol/mg.min) than in subjects with active ovaries (n = 21; 0.65 +/- 0.2 nmol/mg.min; P = 0.0033). Ovarian ACE activities in fertile women in the preovulatory phase (n = 14) and the postovulatory phase (n = 7) were not statistically different (0.66 +/- 0.23 and 0.63 +/- 0.17 nmol/mg.min, respectively). Serum ACE activities were similar in females with active and nonactive ovaries (87.6 +/- 5.0 vs. 81.7 +/- 5.3 nmol/mL-min, respectively). Serum estradiol levels in fertile women were significantly higher than those in postmenopausal women (P = 0.0023). Serum estradiol levels were negatively correlated with age (r = -0.46; P = 0.0041) and were not correlated with either serum ACE activity (r = 0.080; P = NS) or ovarian ACE activity. In summary, human ovarian ACE activity, but not serum ACE, is positively correlated with age. Serum estradiol levels decrease with age, but are not correlated with either ovarian or serum ACE activity. Endogenous serum estradiol levels had no apparent effect on ovarian or serum ACE activity. The presence of uterine pathology affects ovarian ACE activity. The cause of the increased ovarian ACE activity is not clear, but may be related to the aging process.

Season of birth and autistic disorder in Israel.

OBJECTIVE: Variations in month of birth were examined in patients with infantile autism to test the hypothesis that birth in a particular month may be a risk factor for this disorder. METHOD: Data for autistic patients registered with the National League for Autism in Israel (N = 188) during the years 1964-1986 were compared with data on monthly distribution of live births in Israel for the corresponding period. RESULTS: After risk ratio estimates were computed for children born with infantile autism for each month, a significant increase was observed for children born in March and August. This association was true for each year throughout the study. An additional finding was a significantly higher rate of birth of autistic children in the years 1970-1976. CONCLUSIONS: This study, although made in a different climatic area than three earlier studies, further emphasizes the earlier findings that March and August births are a risk factor for development of autistic disorder.

Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines.

The possible relationship between body weight, food preferences, and plasma neurotransmitters was investigated in 96 healthy volunteers. The volunteers were divided into groups according to sex, body mass index, and food preferences. In all groups fasting platelet-poor plasma (PPP) norepinephrine and serotonin (5-HT) were examined. PPP-5-HT was low in obese individuals (mean +/- SD: 51.7 +/- 34.6 nmol/L) in comparison with lean individuals (94.31 +/- 85.2 nmol/L; P < 0.01), in lean male carbohydrate cravers (22.7 +/- 16.4 nmol/L) in comparison with protein cravers (132.9 +/- 80.6 nmol/L; P < 0.005) and noncravers (64.7 +/- 51.7 nmol/L; P < 0.05), and in obese male carbohydrate cravers (34 +/- 22.7 nmol/L) in comparison with obese male protein cravers (98.8 +/- 28.4 nmol/L; P < 0.001). In conclusion, PPP-5-HT might be seen as a peripheral indicator of processes linked with food consumption and food preferences.

Dipyridamole first-pass radionuclide ventriculography: prediction of future cardiac events.

Dipyridamole thallium myocardial perfusion imaging is a useful alternative to stress testing in the diagnostic and prognostic assessment of patients with coronary artery disease. The diagnostic use of dipyridamole radionuclide ventriculography is much more controversial, but no long-term prognostic studies have been reported. Imaging results of 159 consecutive patients who were referred for dipyridamole first-pass radionuclide ventriculography were correlated with subsequent cardiac events over a mean follow-up period of 11 months. An abnormal response to dipyridamole infusion (any reduction in wall motion or absolute decrease in global left ventricular ejection fraction of > or = 5 ejection fraction units) was associated with an increased incidence of nonfatal myocardial infarction (4.5% vs 0%, p < 0.05) and cardiac-related death (9% vs 1%, p < 0.001). The sensitivity, specificity, and negative predictive value of dipyridamole first-pass radionuclide ventriculography in predicting future cardiac events were 86%, 71%, and 98%, respectively, with a relative risk of 15 (confidence interval 12.06 to 18.1). In conclusion, dipyridamole first-pass radionuclide ventriculography demonstrated significant prognostic value in a large unselected patient population. This technique may provide a widely applicable and useful alternative to dipyridamole thallium perfusion imaging in the assessment of cardiac risk in patients with coronary artery disease.

Usefulness of dobutamine radionuclide ventriculography for prediction of left ventricular function improvement after coronary artery bypass grafting for ischemic cardiomyopathy.

Ventricular function may improve after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy depending on the amount of contractile myocardial reserve. Based on the studies using dobutamine echocardiography to predict regional wall improvement after revascularization, we investigated the benefit of low-dose dobutamine radionuclide ventriculography for assessing functional contractile reserve in this population. The study group included 56 patients with ischemic cardiomyopathy (mean left ventricular [LV] ejection fraction [EF] of 23 +/- 5%) and multivessel disease, who were referred for viability assessment. All underwent radionuclide ventriculography before and during infusion of 5 and 10 microg/kg/min of dobutamine. An increase in global LVEF from rest to dobutamine was calculated, and 10% was considered the cutoff value to predict ventricular improvement after CABG. Of the 35 patients who underwent CABG 1 month later, 29 were available for repeated radionuclide ventriculography after 12 +/- 5 months. Of these, 15 showed improvement (delta LVEF > or = 5%, mean 10 +/- 5%) and 14 did not (delta LVEF < 5%, mean -1 +/- 3%). The increase in EF with dobutamine had the highest univariate predictive value of all parameters evaluated. The sensitivity, specificity, and positive and negative predictive values of dobutamine radionuclide ventriculography were 67%, 93%, 91%, and 72%, respectively. We conclude that dobutamine radionuclide ventriculography is a useful method to assess contractile reserve and predict ventricular functional improvement after CABG in patients with ischemic cardiomyopathy.

Long-term prognosis of 210 patients who underwent coronary angiography before 40 years of age.

We report on a follow-up of 210 patients who underwent coronary angiography before age 40. We found that young patients with normal coronary arteries have an excellent prognosis, whereas those with single-vessel disease have an unfavorable outcome resembling that of patients with multivessel disease.

Prognostic significance of maximal precordial ST-segment depression in right (V1 to V3) versus left (V4 to V6) leads in patients with inferior wall acute myocardial infarction.

This study examines whether patients with inferior wall acute myocardial infarction (AMI) and maximal ST-segment depression in left precordial leads are at higher risk for in-hospital mortality. The charts of patients (n = 213) with inferior wall AMI and an initial electrocardiogram that displayed peaked, tall T waves or ST-segment elevation with upright T waves in inferior leads were reviewed, after excluding patients with inverted T waves in inferior leads (n = 75). ST-segment deviation from baseline was measured for all leads. Patients were classified into 3 types: I = no precordial ST-segment depression; II = sum of ST-segment depression in leads V1 to V3 equal to or more than the sum of ST-segment depression in leads V4 to V6; and III = maximal precordial ST-segment depression in leads V4 to V6. Thirty-six patients (17%) died in the hospital. In-hospital mortality rates for patients with types I and II were 12% and 10%, respectively, compared with 41% for those with type III (p < 0.0001). Mortality rates in surviving patients were similar for all types up to 1 year after infarction. Multivariate logistic regression models for in-hospital mortality by ST-segment depression type adjusted for age, previous AMI, diabetes mellitus, and thrombolytic therapy revealed that type III pattern was a strong predictive factor for in-hospital mortality (odds ratio = 4.9, p = 0.0008, 95% confidence interval 1.93 to 12.26). Thus, patients with inferior wall AMI and maximal precordial ST-segment depression in leads V4 to V6 are at high risk for in-hospital mortality.

Importance of left anterior hemiblock development in inferior wall acute myocardial infarction.

Of the 87 consecutive patients admitted with first inferior wall acute myocardial infarction, 17 had acute left anterior hemiblock. The appearance of left anterior hemiblock identified a specific group with more extensive coronary artery disease and suggests disease of the left anterior descending coronary artery.

Renal outcome and vascular morbidity in systemic lupus erythematosus (SLE): lack of association with the angiotensin-converting enzyme gene polymorphism.

OBJECTIVES: The angiotensin-converting enzyme (ACE) gene polymorphism has been associated with worse outcome in various chronic glomerular disorders and in hypertension. Because nephritis and vascular morbidity are prominent determinants of outcome in systemic lupus erythematosus (SLE), we studied the distribution and prognostic effect the ACE genotype might have on the outcome of SLE. METHODS: Fifty-six consecutive Israeli SLE patients and 48 (sex and ethnic origin matched) healthy individuals were evaluated for the ACE genotype by a polymerase chain reaction-based assay. The clinical and laboratory parameters of the patients as well as the SLE disease activity index (SLEDAI) and the presence of hypertension, diabetes mellitus, ischemic heart disease, congestive heart failure, and stroke were correlated with the ACE genotype. RESULTS: The distribution of the ACE genotype D/D, D/I, and I/I in the lupus group was 59%, 36%, and 5%, respectively, similar to the distribution in the control group (54%, 31%, and 15%, respectively). We failed to find any significant association between the ACE genotype and disease manifestations, SLEDAI, renal function, or cardiovascular and cerebrovascular morbidity. The clinical and laboratory parameters associated with renal outcome and vascular morbidity in our cohort are described. CONCLUSIONS: No difference was found between the distribution of the ACE genotype in lupus patients and the general population in Israel. Renal function as well as cardiovascular and cerebrovascular morbidity among Israeli patients with SLE are disease-related and independent of the ACE gene polymorphism.

Expression of the apoptosis-related oncogenes bcl-2, bax, and p53 in Merkel cell carcinoma: can they predict treatment response and clinical outcome?

Chemotherapy and radiation therapy act predominantly through the induction of apoptosis in malignancies. Merkel cell carcinoma, an aggressive malignancy with prominent apoptosis, has proved to be sensitive to both modes to a certain degree. We used immunohistochemical methods to examine 25 Merkel cell carcinomas and 8 of their lymph node metastases to assess the status of the antiapoptotic gene bcl-2 and 2 proapoptotic genes, wild-type p53 and bax. All tumors showed prominent bax immunopositivity; 76% were positive for bcl-2, and only 28% were positive for p53, the latter presumably reflecting mutated p53. No statistically significant relationship was found between tumor immunopositivity and therapy response or survival. The widespread bax immunopositivity and the apparently low rate of p53 mutations, as suggested by the low rate of p53 immunopositivity, may be related to the presence of prominent apoptosis in Merkel cell carcinoma. The finding of bcl-2 immunopositivity in 76% of the tumors suggests that some of the tumor cells may be resistant to apoptosis-inducing agents.

Is the heart a source for elevated circulating endothelin levels during aorta-coronary artery bypass grafting surgery in human beings?

Reports have shown increased systemic levels of endothelins during coronary artery bypass grafting in human beings. It was not known whether increased endothelin levels during coronary artery bypass grafting reflect a general systemic response to the surgical procedure or increased myocardial production of endothelins in response to ischemia and reperfusion. We therefore measured endothelin levels in the right atrium and proximal aorta of 15 patients undergoing coronary artery bypass grafting for anginal syndrome immediately before aortic crossclamping and again after cessation of cardiopulmonary bypass. In five patients, we also measured coronary sinus levels of endothelins during cardiopulmonary bypass circulation. We found that endothelin levels were elevated throughout the surgical procedure. Right atrial endothelin levels were significantly elevated after cessation of cardiopulmonary bypass circulation with respect to values immediately before aortic crossclamping (11.1 +/- 3.1 vs 14.2 +/- 3.7 pg/ml, p = 0.008), whereas endothelin levels in the proximal aorta did not rise significantly (10.5 +/- 2.3 vs 11.6 +/- 2.4 pg/ml, p > 0.5). Coronary sinus endothelin levels tended to decline temporarily during cardiopulmonary bypass circulation (11.1 +/- 2.1 pg/ml before aortic crossclamping, 7.9 +/- 1.9 1 minute after release of aortic crossclamp, and 9.9 +/- 2.1 pg/ml after release of partial aortic crossclamping, p = 0.06). We conclude that the rise in right atrial endothelin levels during coronary artery bypass grafting reflects systemic production and secretion of endothelins, probably by vasculature or organs distal to the proximal aorta, and is not the result of increased myocardial production and secretion of endothelins.