Beta glycosphingolipids suppress rank expression and inhibit natural killer T cell and CD8+ accumulation in alleviating aortic valve calcification.

CD8 lymphocytes play a role in aortic valve inflammation leading to aortic valve calcification (AVC). RANK is a transmembrane protein that is important in osteoclast differentiation and calcification. Beta-glucosylceramide (beta-GC) together with beta-lactosylceramide (beta-LC), the 1:1 combination of beta- glucosylceramide and beta-lactosylceramide, designated IGL, exerts an immune modulatory effect in various inflammatory disorders in a CD8- and NKT (natural killer T cell)-dependent manner. We hypothesized that IGL may affect the inflammatory condition associated with AVC. AVC was induced in rats by oral administration of a high-adenine, high-phosphorus diet and was assessed by multislice computer tomography. Administration of this diet was associated with a marked increase in CD8 and NKT lymphocyte accumulation in the aortic valve. Administration of IGL led to marked suppression of RANK expression, associated with inhibition of both NKT and CD8 lymphocyte accumulation in the aortic valve. These effects were associated with a significant improvement in the degree of AVC in IGL-treated animals (25 and 53 by Agatston Score, in IGL-treated and controls, respectively). CD8 and NKT lymphocytes play a role in the pathogenesis of AVC, and RANK-mediated NKT inhibition by beta-glycosphingolipids can alleviate AVC.

The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients.

BACKGROUND AND AIM: Hypercholesterolaemia is a major risk factor for atherosclerosis. Cholesterol is modulated by genetic and environmental factors. An important regulatory pathway is controlled by the sterol-regulatory element-binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both SREBP-2 and SCAP are candidates to contribute to the development of atherosclerosis. We investigated the possible effects of the variability of proteins involved in this regulatory pathway on plasma lipids among familial hypercholesterolaemia patients. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped in 801 FH individuals originating from Israel, The Netherlands, and Switzerland. A linear regression model to examine the associations between SREBP-2 and SCAP isoforms and lipid and lipoprotein levels was used. In females, homozygosity either for the SREBP-2-595A or for the SCAP-796I isoform was associated with higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl, respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP-796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene-gene interaction=0.09). No such effect was observed among FH males. Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345). These effects were, however, not present when less frequent LDL receptor mutations were investigated. CONCLUSIONS: These results suggest a possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration.

The value of cine nuclear magnetic resonance imaging for assessing regional ventricular function.

Previous nuclear magnetic resonance (NMR) imaging studies to assess left ventricular function have used multiple axial planes, which are compromised by partial volume effects and are time consuming to acquire and analyze. Accordingly, an imaging approach using cine NMR and planes aligned with the true cardiac axes of the left ventricle was developed in views comparable with left ventricular cineangiography. Cine NMR imaging was used to assess regional wall motion and was validated by comparison with biplane left ventricular cineangiography. Fifty-nine patients underwent cineangiographic and NMR studies within 72 h. A poor quality NMR study precluded analysis in 4. leaving a study group of 55 patients (mean age 58 +/- 12: 17 women). Cine NMR movie loops were acquired in two long-axis planes: 1) right anterior oblique plane, parallel to the septum, and 2) four chamber orthogonal plane, perpendicular to the septum (this view is comparable to the angiographic left anterior oblique view). To assess regional wall motion, the left ventricle in both cine NMR and cineangiographic images was divided into five segments and graded on a five point grading scale from 3 for normal through 0 for akinesia and -1 for dyskinesia. Regional wall thickening was used qualitatively to aid in the analysis of wall motion. For the 275 segments compared in the right anterior oblique view, agreement was within one grade in 263 (95.6%) of 275 segments, whereas absolute agreement was observed in 171 (62%) of 275 segments. In the left anterior oblique view, of 200 segments evaluated, agreement within one grade was achieved in 184 segments (92%) and agreement was complete in 132 (66%).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term angiographic follow-up of coronary balloon angioplasty in patients with diabetes mellitus: a clue to the explanation of the results of the BARI study. Balloon Angioplasty Revascularization Investigation.

OBJECTIVES: We sought to compare the angiographic outcome of diabetic patients (treated with insulin or oral hypoglycemic agents) after successful coronary angioplasty with that in nondiabetic patients. The analysis included the outcome of the dilated (restenosis) and nondilated narrowings (disease progression). BACKGROUND: Recent data have confirmed that diabetes mellitus is an important risk factor for long-term adverse events. These adverse events are more common after balloon angioplasty than after bypass surgery (Bypass Angioplasty Revascularization Investigation [BARI]). METHODS: We examined retrospectively 353 coronary angiograms of 248 patients (55 diabetic, 193 nondiabetic) who were referred for diagnostic angiography >1 month after successful angioplasty (1.4 +/- 0.6 [mean +/- SD] repeat angiograms/patient). Restenosis and disease progression/regression were compared between groups by means of quantitative angiography. RESULTS: Baseline clinical and angiographic characteristics were similar in both groups. There was a nonsignificant trend for a higher restenosis rate of dilated narrowings in diabetic patients. There were no significant changes between diabetic and nondiabetic patients in the rates of progression and regression of narrowings that were not dilated during the initial angioplasty. The main difference was in the rate of appearance of new narrowings: There was a 22% increase in the number of narrowings on the follow-up angiogram in diabetic patients (38 new, 174 preexisting narrowings) compared with 12% (86 new, 734 preexisting narrowings) in nondiabetic patients (p < 0.004). Diabetes mellitus and the performance of angioplasty in the artery had an additive risk for development of new narrowings, which were identified in 15 (16.9%) of 89 arteries with and 16 (13.2%) of 121 without angioplasty in diabetic patients and in 42 (12.7%) of 331 arteries with and 38 (7.3%) of 518 without angioplasty in nondiabetic patients (p = 0.009). CONCLUSIONS: The combination of diabetes mellitus and an artery that was instrumented during balloon angioplasty is additive and increases the risk of formation of new narrowing in that artery. This finding may explain the high adverse event rates observed in diabetic patients in the angioplasty arm of the BARI study, most of whom had angioplasty performed in at least two arteries.

Early treatment of acute myocardial infarction with intravenous streptokinase. A high-risk syndrome.

Fifty-one successive patients treated with intravenous streptokinase 1.7 +/- 0.8 (mean +/- SD) hours after onset of symptoms of acute myocardial infarction were evaluated during a three-month posthospital follow-up period. Coronary angiography was performed four to nine days after the initial hospital admission. Twenty-eight patients had a second late angiogram. Forty-one patients had successful reperfusion but only 25% of all patients were without significant clinical cardiovascular manifestations during this period. Postmyocardial infarction angina pectoris occurred in 21 patients, an abnormal stress test result was present in 28 patients, eight patients developed congestive heart failure, and five patients had reinfarction. An intervention with percutaneous transluminal coronary angioplasty or coronary artery bypass graft was performed in 15 (37%) of 41 reperfused patients. A significantly higher intervention rate was present in patients treated with streptokinase within one hour following the onset of symptoms. Early reocclusion (within three months of the infarct) was noted in patients with 60% or more residual stenosis in their infarct-related coronary artery. These patients also had a significantly greater incidence of angina pectoris. Our findings indicate that early thrombolytic therapy of acute myocardial infarction preserves myocardium, and since the infarct-related artery is patent, but narrowed, the jeopardized area is responsible for a high-risk syndrome with an increased likelihood of ischemic symptoms. An early aggressive approach may be indicated, especially for patients with greater than 60% residual stenosis in their infarct-related coronary artery.

The outcome of patients with acute myocardial infarction ineligible for thrombolytic therapy. Israeli Thrombolytic Survey Group.

PURPOSE: The aim of this study was to determine the proportion of patients with acute myocardial infarction (AMI) excluded from thrombolytic therapy on a national basis and to evaluate the prognosis of these patients by reasons of ineligibility and according to the alternative therapies that they received during hospitalization. PATIENTS AND METHODS: During a national survey, 1,014 consecutive patients with AMI were hospitalized in all the 25 coronary care units operating in Israel. RESULTS: Three hundred and eighty-three patients (38%) were treated with a thrombolytic agent and included in the GUSTO study. Ineligible patients for GUSTO were treated: (1) without any reperfusion therapy (n = 449), (2) by mechanical revascularization (n = 97), or (3) given 1.5 million units of streptokinase (n = 85) outside of the GUSTO protocol. The inhospital and 1-year post-discharge mortality rates were 6% and 2% in patients included in the GUSTO study; 6% and 5% in those mechanically reperfused; 15% and 10% in those treated with thromoblysis despite ineligibility for the GUSTO trial, and 15% and 13% among patients not treated with any reperfusion therapy. CONCLUSIONS: Ineligibility for thrombolysis among patients with AMI remains high. Patients ineligible for thrombolysis according to the GUSTO criteria, but nevertheless treated with a thrombolytic agent were exposed to an increased risk.

Late effects of dose fractionation on the mechanical properties of breast skin following post-lumpectomy radiotherapy.

PURPOSE: Late radiation-induced skin effects were studied in a multicenter project using our new sensitive noninvasive viscoelasticity skin analyzer (VESA). METHODS AND MATERIALS: Skin viscoelasticity and anisotropy were examined quantitatively in symmetric areas of both breasts in healthy women and in 110 breast cancer patients who underwent lumpectomy and radiotherapy. These parameters were evaluated by the VESA measurement of the speed of elastic wave propagation in the skin; higher VESA readings correspond to higher skin stiffness. Effect of radiation was estimated by comparison of the data recorded in the irradiated versus nonirradiated breast of the same patient. RESULTS: Skin viscoelasticity and anisotropy were similar in contralateral areas of the breasts in healthy controls as well as in the nonirradiated breasts of the patients. With age, skin viscoelasticity decreased and anisotropy increased similarly in both breasts. Radiotherapy, by a total radiation dose in the range of 45-50 Gy given with 1.8 Gy/fraction (fx) resulted in a similar minor, but still statistically significant, increase of skin stiffness relative to control. The effect was more pronounced when a dose of 50 Gy was given in a higher dose/fraction of 2.5 Gy. CONCLUSION: We found that the increase in dose of radiation per fraction had much more impact on the development of late skin effects than elevation in the total dose given.

Transradial approach for coronary angiography and angioplasty.

The transradial approach has currently been advocated as an alternative catheterization method for coronary angiography and angioplasty, due to the recent miniaturization of angioplasty equipment. The purpose of this study was to assess the practical clinical applicability of this method. From June to November 1994, 100 patients underwent coronary angiography and angioplasty with the transradial approach. Their mean age was 66.6 +/- 11.2 years, and 79 were men. In 4, radial puncture was not successful, and in 3, femoral access was necessary to complete the procedure. Coronary angioplasty was performed in 63 patients (76 lesions) with angiographic success (per lesion) of 96%. In 5 patients, a stent was successfully implanted. All patients were ambulatory on the day after the angioplasty procedure. In 98% of the patients, the introducer was taken out 1 to 4 hours after the procedure by local compression using a special custom-made device. No patient required blood transfusion. Major complications occurred in 2 patients; both had a cerebrovascular accident (1 probably not procedure-related), and both recovered. A radial pulse was palpated in 91 of the patients before discharge, and in 6 others, adequate flow could be heard with Doppler. In 2 patients, radial flow was restored within several weeks. None of the patients suffered from ischemia of the hand. Two patients had a small pseudoaneurysm successfully treated by local compression. Thus, coronary angioplasty can be performed safely using the transradial approach with relatively few vascular complications and with better patient comfort. However, the procedure is more time-consuming initially compared with the transfemoral approach due to a learning curve regarding equipment selection and catheter manipulation.

Experience with the AVE Micro stent in native coronary arteries.

Experience with implantation of 62 AVE Micro stents is described. Stents were quickly and successfully deployed in 62 of 63 attempts (98.4%), in tortuous coronary vessels, through proximally deployed stents, and under conditions of hemodynamic instability. It is therefore a very attractive choice to treat difficult anatomy during urgent situations.

Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function.

Cine nuclear magnetic resonance (NMR) imaging, as a noninvasive and high-resolution imaging modality, has been shown to be reliable for determining absolute left ventricular (LV) volumes and ejection fraction. A relatively new gradient echo cine NMR approach using 2 orthogonal long-axis planes (2- and 4-chamber) aligned with the true axes of the left ventricle has been previously developed and validated against radiographic biplane LV cineangiography. The aim of the present investigation was to determine the reproducibility of this more rapid cine NMR approach for the measurement of LV volumes and ejection fraction. Eighteen normal subjects underwent 2 cine NMR studies, on different days, using a 1.5-tesla clinical imaging system. Studies were analyzed on-line and blindly by 2 independent observers. Intraobserver error was also determined in a blinded manner. Mean values of measurements determined by this method in this group of normal subjects were end-diastolic volume (120 +/- 20 ml), end-systolic volume (39 +/- 9 ml) and ejection fraction (67 +/- 4%). Paired analysis of data revealed no significant bias between interstudy, interobserver or intraobserver measurements, except for interobserver end-diastolic volume, where the first observer measurements were slightly elevated (5.6 +/- 7.8 ml) compared with the second. This resulted in a small difference in ejection fraction (1.7 +/- 2.3%) between observers. The absolute variation between measurements (square root of variance components) was low for all interstudy, interobserver and intraobserver comparisons: end-diastolic volume was less than +/- 6.7 ml, end-systolic volume less than +/- 3.5 ml and ejection fraction less than +/- 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

One-stage coronary angiography and angioplasty.

The combination of diagnostic angiography and angioplasty as a single procedure is becoming common practice in many institutions, but the feasibility and safety of this strategy have not been reported. This report describes 2,069 patients who underwent coronary angioplasty over a 3-year period at an institution where combined angiography and angioplasty is the norm. All patients were prepared before angiography for potential immediate angioplasty. In 1,719 patients, angioplasty was performed immediately after the diagnostic angiogram, while separate procedures were performed in 350 patients. Of those 350 patients, 254 were referred for angioplasty after diagnostic angiography at other hospitals. One thousand one hundred ninety-seven patients were admitted electively for treatment of stable angina pectoris, and 872 underwent procedures during hospitalization for unstable angina or acute myocardial infarction. One thousand nine hundred seven patients (92.2%) had successful angioplasties; in 130 patients (6.3%) the lesion could not be dilated, but no complication occurred, and in 32 patients (1.5%) angioplasty ended with a major complication (0.8% death, 1.0% Q-wave myocardial infarction, 0.5% emergency coronary artery bypass surgery). There was no difference between the combined and staged groups with regard to success, major and minor complication rates or in length of hospitalization after angioplasty. We conclude that routine combined strategy for angiography and angioplasty is feasible, safe, easier for the patient, and more cost-effective than 2 separate procedures.

Influence of coronary angioplasty on the progression of coronary atherosclerosis.

This study examines the effect of coronary angioplasty on the progression and appearance of new disease in sites of the coronary tree that were not dilated by the balloon. We examined 355 pairs of coronary angiograms from 252 patients. The study consisted of consecutive patients who were referred for catheterization > 1 month after successful angioplasty. Progression/regression and the appearance of new narrowings at sites not dilated by angioplasty were determined. The life-table method was used to determine outcome, and any event (progression, regression, and new narrowing) was analyzed according to the time of occurrence. The angioplasty artery was compared with the non-angioplasty artery and the effect of restenosis was determined by comparing arteries with and without restenosis. Progression/regression rates were not significantly different in angioplasty and non-angioplasty arteries. More new narrowings were identified in the angioplasty artery (p < 0.01). With regard to narrowings located in the angioplasty artery, progression was more common, regression less common, and the appearance of new narrowings more common in arteries with restenosis than in non-angioplasty arteries or arteries without restenosis. We believe that mechanical trauma to the artery during angioplasty could accelerate disease progression and the appearance of new narrowings in angioplasty arteries, whereas normalization of flow rate and pattern, especially in arteries without restenosis, attenuates the rate of progression and the appearance of new narrowings in these arteries. The final outcome depends on the balance between these factors.

Importance of early initiation of intravenous streptokinase therapy for acute myocardial infarction.

The importance of timing of intravenous streptokinase (SK) administration in patients with acute myocardial infarction (AMI) was evaluated. Intravenous SK, 750,000 U, was administered within 4 hours of the onset of ischemic chest pain to 72 consecutive patients having their first AMI. Six days later, cardiac catheterization was performed to calculate global ejection fraction (EF), and computer-derived infarct-related regional EF and dysfunction index were also determined; electrocardiograms were recorded, from which QRS scores could be calculated to estimate infarct size. Of 19 patients who had an anterior AMI, 12 (63%) who received intravenous SK within 2 hours after onset of pain sustained only minimal damage in terms of global EF, infarct-related EF, dysfunction index and QRS score. All 10 patients who received SK 2 to 4 hours after pain onset had large infarcts (p less than 0.001). Of the former group, 11 of 12 patients (91%) whose pain was relieved within 1.5 hours of intravenous SK administration (presumably due to successful reperfusion) had a good outcome, whereas all 7 whose pain lasted longer did poorly (p less than 0.001). Furthermore, among patients with anterior AMI, 11 of 14 (79%) whose pain was relieved within 3.5 hours of onset had small infarcts, compared with none of the 12 patients whose pain lasted longer (p less than 0.0001). In inferior AMI, the critical time between onset of pain and initiation of intravenous SK was 1.5 hours (p less than 0.05). The timing of initiation of thrombolytic therapy and the total pain duration are critical in determining outcome in AMI, and time intervals vary depending on infarct localization.

Rapid assessment of aortic regurgitation and left ventricular function using cine nuclear magnetic resonance imaging and the proximal convergence zone.

In patients with aortic regurgitation (AR), knowledge of the severity of AR, and the degree of left ventricular (LV) dysfunction are important for optimal management. Previous nuclear magnetic resonance (NMR) studies to assess these parameters used multiple tomographic planes that are time-consuming to obtain and analyze, and thus not cost-effective. In addition, these studies assessed the severity of AR by looking simply at the size of the regurgitant jet, a parameter that relates only poorly to regurgitant volume. The present study evaluates a rapid, single-plane, cine NMR approach (scan time < 10 minutes), and a new grading system for AR that is based on the presence, size and persistence of not only the regurgitant jet, but also the zone of proximal signal loss. Compared with color Doppler echocardiography (n = 42), the NMR approach detected AR with a specificity of 100% and a sensitivity of 95%. NMR regurgitant jet area correlated well with color Doppler regurgitant jet area (n = 20; r = 0.81; p < 0.01), but did not discriminate well between all grades of AR as compared with x-ray contrast aortography (n = 14). Using the new NMR grading criteria, AR grade by NMR was in accordance with aortographic grade in 12 patients, differing by only 1 grade in the remaining 2 patients. NMR grade was in accordance within 1 grade of Doppler in all patients compared (n = 20). LV volumes and ejection fraction using this single-plane approach correlated well with a previously validated, NMR biplane approach (r > 0.87; n = 18).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of early invasive and conservative treatments in patients with anterior wall non-Q-wave acute myocardial infarction.

To compare the long-term prognosis of a group of patients treated by an early invasive approach after a non-Q-wave anterior wall acute myocardial infarction (AMI) with a similar group treated conservatively, data from 110 consecutive patients with non-Q-wave AMI were retrospectively obtained from 3 different hospitals: (1) a hospital with coronary angioplasty and coronary bypass facilities favoring on early invasive approach, (2) a hospital with a catheterization laboratory and no coronary angioplasty or coronary bypass facilities, and (3) a community hospital without a catheterization laboratory. Patients were divided according to the presence or absence of an early invasive approach: those who had undergone in-hospital catheterization and revascularization (n = 55) and those with a conservative approach (n = 55). The early invasive approach resulted in a significant decrease in major events. The rate of recurrent myocardial infarction was 29% in the conservative group versus 7.2% in the invasive group (p = 0.025). Survival rate curves at 3-year follow-up showed significant differences in mortality (p = 0.001), recurrent myocardial infarction (p = 0.002), recurrent angina pectoris (p = 0.001), and development of congestive heart failure (p = 0.05). Multivariate analysis disclosed the early invasive approach to be an independent predictor for decreasing the likelihood of recurrent infarction by 86% (odds ratio 0.14, confidence intervals 0.04 to 0.48, p = 0.0006), and for decreasing the likelihood of recurrent angina by 66% (odds ratio 0.34, confidence intervals 0.18 to 0.63, p < 0.005). The early invasive strategy may result in an improved outcome in the treatment of patients with non-Q-wave anterior wall AMI compared with patients treated conservatively.

Angiographic findings in the coronary arteries after thrombolysis in acute myocardial infarction.

The angiographic appearance of the coronary arteries was examined in 308 patients with acute myocardial infarction (AMI) who received high-dose intravenous thrombolytic therapy. Coronary angiography was performed on day 7 after admission to the hospital. Patients had an average of 2.4 discrete arterial narrowings or obstructions. The narrowings were proximal and related to bifurcations. Four fifths of the culprit arteries were patient; 104 (34%) had a ruptured plaque, 22 (7%) had an ulcerated plaque, and in 190 (62%) the lesions were eccentric. Patients differed from a comparable, previously studied, control series of 302 patients with chronic stable angina pectoris who had more extensive disease. They had 5.7 narrowings/patient, also located proximally and at bifurcations, but more widely distributed in the coronary tree. Patients with AMI who are suitable for thrombolysis have a unique coronary angiographic picture. The data confirm that AMI is caused by sudden rupture of a localized atheromatous plaque that initiates an obstructive thrombotic cascade.

Prehospital coronary thrombolysis. A new strategy in acute myocardial infarction.

Thirty-four patients with acute myocardial infarction were treated prospectively using a new strategy of prehospital intravenous streptokinase given by a physician-operated mobile intensive care unit. The 29 prehospital-treated patients who had experienced no previous myocardial infarction were compared to a similar group treated with streptokinase inhospital. Patients receiving streptokinase in the prehospital phase of acute myocardial infarction had smaller infarcts and better residual myocardial function than the group given streptokinase inhospital in terms of peak creatinine phosphokinase, ejection fraction, computer-derived dysfunction index, and electrocardiographic QRS score. The only difference between these groups at baseline was the duration of pain prior to initiation of streptokinase therapy. There were no major complications related to prehospital administration of streptokinase.

Acute septal myocardial infarction diagnosed by endomyocardial biopsy in a heart transplant recipient.

We describe an unusual case of acute septal myocardial infarction in a heart transplant recipient. The clinical presentation was most suggestive of acute rejection; the correct diagnosis was first made by endomyocardial biopsy and was then verified by coronary angiography. Acute myocardial infarction should be included in the differential diagnosis of acute rejection after heart transplantation and included among the possible diagnoses made by endomyocardial biopsy in these patients.

An unusual case of non-traumatic pneumococcal mediastinal abscess.

A 16-month old baby developed severe respiratory failure because of acute laryngitis and required mechanical ventilation. Intubation was complicated by aspiration and development of chemical pneumonia. Following 4 days of treatment the child was successfully extubated. Thirty six hours after extubation the patient again developed respiratory failure and on chest X-ray pneumomediastinum was seen and later evidence of a mediastinal abscess. Conservative treatment, with antibiotics, effected complete cure.

Coronary pathology predicts conduction disturbances after coronary artery bypass grafting.

Conduction disturbances after coronary artery bypass grafting may result from compromised septal blood flow. To examine this hypothesis we reviewed the preoperative coronary angiography of 55 consecutive patients undergoing coronary artery bypass grafting. Thirty-five patients had either no lesion or a discrete lesion in the left anterior descending coronary artery that did not include the septal perforator (type I anatomy). Twenty patients had a lesion of the left anterior descending coronary artery at the origin of the first septal branch, a lesion of the first septal artery, or a pair of lesions in the left anterior descending coronary artery that straddled the origin of the first septal artery; all lesions were proximal to the graft site (type II anatomy). None of the patients with type I anatomy had a major conduction disturbance after coronary artery bypass grafting. Eleven of the patients with type II anatomy had major conduction disturbances after coronary artery bypass grafting; right bundle-branch block in 1, right bundle-branch block and left anterior hemiblock in 2, left bundle-branch block in 5, and complete atrioventricular block that required pacemaker implantation in 3 (p less than 0.001). In the 20 patients with type II anatomy, the appearance of conduction disturbances correlated well with the absence of retrograde flow to the septal branches from the right coronary artery (p less than 0.01). Pathological lesions in the left anterior descending coronary artery that compromise flow in the first perforator and that do not provide an adequate circulation produce localized damage and conduction disturbances after coronary artery bypass grafting. This can be predicted from the preoperative angiographic anatomy.