Myocardial fatty acid utilisation during exercise induced ischemia in patients with coronary artery disease.

AIM: Reversible or irreversible myocardial damage due to ischemia correlates with altered membrane functions of the cells. To compare myocardial free fatty acid (FFA) metabolism and flow during exercise induced ischemia we studied ten patients with coronary artery disease but without previous myocardial infarction. METHODS: A series of post-exercise single-photon emission computed tomography (SPECT) measurements was performed after injection of 123I labelled heptadecanoic acid (HDA). Myocardial perfusion was estimated from the separately performed exercise-redistribution thallium study. Fatty acid metabolic rate, thallium uptake and washout were calculated for anterior, lateral, posterior and septal segments. RESULTS: The more reduced post-exercise FFA metabolic rate (-63 +/- 18%, mean +/- 1 SD) compared to flow (-36 +/- 16%) was related to the severity of myocardial ischemia and wall motion abnormalities. CONCLUSION: In this small group of patients, the reduced post-exercise FFA metabolic rate tentatively suggests a parsimonious workload of the exercising myocardium by reducing oxygen consumption in patients with coronary artery disease.

Multislice MRI in assessment of myocardial perfusion in patients with single-vessel proximal left anterior descending coronary artery disease before and after revascularization.

BACKGROUND: Our purpose was to use multislice MRI for detection of reversible myocardial ischemia and assessment of the effect of revascularization on tissue perfusion in patients with coronary artery disease. METHODS AND RESULTS: Eleven patients with single-vessel proximal left anterior descending coronary artery disease were studied with MRI and thallium scintigraphy before and 3 months after revascularization. All patients had a reversible perfusion defect by scintigraphy before treatment. With a 1.5-T MR imager, IR-prepared turboflash images were acquired in three left ventricular short-axis planes during 0.05 mmol/kg Gd-DTPA bolus at rest and with dipyridamole-induced stress. Before treatment, stress increased enhancement slope in normal (6.4+/-4.4 to 7.4+/-5.0 s(-1), P<.04) and decreased it in underperfused (5.4+/-3.7 to 2.6+/-1.4 s(-1), P<.02) regions, resulting in a contrast-to-noise ratio of 6.87+/-3.09 in underperfused myocardium. Revascularization normalized enhancement patterns of the formerly underperfused myocardium and decreased defect size both in scintigraphy (66+/-53 degrees to 8+/-12 degrees, P<.001) and MRI sections (49+/-41 degrees to 9+/-8 degrees, P<.001). Agreement of 85% in detection and correlation of 0.86 (SEE, 21 degrees, P<.001) in sizing perfusion defects was found between MRI and scintigraphy. CONCLUSIONS: Multislice contrast-enhanced MRI can be used to detect myocardial perfusion defects in patients with coronary artery disease and in assessment of the effect of treatment on myocardial perfusion.

HDLs containing apolipoproteins A-I and A-II (LpA-I:A-II) as markers of coronary artery disease in men with non-insulin-dependent diabetes mellitus.

BACKGROUND: Abnormalities in HDL and an increased risk of coronary artery disease (CAD) coexist in non-insulin-dependent diabetes mellitus (NIDDM). HDLs can be separated by their apolipoprotein (apo) content into particles containing apoA-I but not apoA-II (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). The LpA-I particles have been suggested to be more effective in conferring protection against CAD than the LpA-I:A-II particles. However, data are sparse, and no studies have defined the role of these two classes of particles in NIDDM. METHODS AND RESULTS: LpA-I and LpA-I:A-II particles were quantified by a differential electroimmunoassay in four groups of men with similar age and body mass index (BMI) distributions. Group 1 consisted of 50 patients with NIDDM and angiographically verified CAD; group 2, 50 men with CAD but no diabetes; group 3, 50 men with NIDDM but no CAD; and group 4, 31 healthy men. Serum apoA-I and apoA-II concentrations were measured by immunoturbidimetry, and HDL2 and HDL3 were separated by ultracentrifugation. Concentrations of LpA-I:A-II particles in group 1 were 13.8%, 18.3%, and 26.9% lower than in groups 2 through 4, respectively. In a two-by-two factorial ANOVA, adjusted for age and BMI, the differences were significant for both CAD (P < .001) and NIDDM (P < .001), with no interaction between the factors. These results were confirmed by comparable differences in the serum concentrations of apoA-I and apoA-II. LpA-I particles were related to the presence or absence of CAD (P = .013), but the difference was lost in a multivariate analysis. A low HDL3 cholesterol concentration characterized both CAD (P = .002) and NIDDM (P = .024). HDL2 cholesterol differed significantly with regard to the presence of NIDDM (P = .033) but only borderline with respect to CAD (P = .073). CONCLUSIONS: ApoA-II-containing lipoproteins and HDL3 cholesterol are powerful markers of CAD in men with NIDDM.

High density lipoprotein subfractions in non-insulin-dependent diabetes mellitus and coronary artery disease.

High density lipoprotein (HDL) subfractions (2b, 2a, 3a, 3b, and 3c) separated by gradient gel electrophoresis (GGE) and defined by Gaussian summation analysis, and the compositions of HDL2 and HDL3, separated by preparative ultracentrifugation, were studied in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD): group 1 (DM+CAD+, n = 50); group 2 (DM-CAD+, n = 50); group 3 (DM+CAD-, n = 50); and group 4 (DM-CAD-, n = 31). HDL GGE subfraction distributions, available in 125 subjects, were not significantly different among the groups. In contrast, dividing the whole study population into quartiles of serum triglyceride (TG) concentration showed that high TG levels were significantly associated with low HDL2b and high HDL3b concentrations. In a multivariate linear regression model, postheparin plasma hepatic lipase (HL) activity, and fasting serum insulin and TG concentrations were all associated independently and inversely with low HDL2b, but lipoprotein lipase or cholesteryl ester transfer protein activities were not correlated with HDL2b concentrations. Group 1 tended to have the smallest mean particle sizes in the HDL subfractions, significantly (P < 0.03, CAD vs. non-CAD) for HDL2b and for HDL2a. These differences were independent of TG, insulin and HL, but lost their significance when adjusted for beta-blocker therapy. Both HDL2 and HDL3 particles in group 1 were significantly depleted of unesterified cholesterol, and their HDL2 was TG-enriched (P = 0.053). A high HL activity, hyperinsulinemia and hypertriglyceridemia are independently associated with low levels of HDL2b and generally small HDL particle size. HDL particles in subjects with NIDDM and CAD are small-sized and have a low free cholesterol content. Both these characteristics may be markers of impaired reverse cholesterol transport.

Exclusion of coronary artery disease by exercise thallium-201 tomography in patients with aortic valve stenosis.

In many patients with valvular aortic stenosis (AS), management decisions may be possible without invasive studies if coexistent coronary artery disease (CAD) can be ruled out noninvasively. The use of thallium-201 single-photon emission computed tomography to the exclusion of CAD was studied in 44 patients aged 41 to 78 years with AS. In addition to cardiac catheterization and selective coronary angiography, patients underwent a cardiac ultrasound study and thallium-201 myocardial perfusion imaging at rest and after bicycle ergometer exercise. Two thirds of the patients had critical AS (valve area index less than or equal to 0.5 cm2/m2) but none had left ventricular systolic dysfunction. Twenty-one patients had angiographically significant CAD (greater than or equal to 50% diameter stenosis in greater than or equal to 1 coronary artery), whereas 23 had either a fully normal angiogram (n = 17) or mild (less than 50%) stenoses (n = 6). Each patient with significant CAD had an abnormal thallium-201 tomogram, either a strictly segmental perfusion defect (n = 19), or a patchy nonsegmental abnormality (n = 2); however, 10 of 23 patients free of significant CAD had similar results. Thus, the sensitivity and specificity of an abnormal scintigram were 100 and 57%, respectively. If only segmental perfusion defects typical of CAD had been considered abnormal, then the sensitivity of the test would have been 90% and the specificity 70%. Patients with false abnormal scintigrams had more severe AS and more angiographically nonsignificant CAD than those with true normal findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary collateral circulation.

The occurrence and influence of coronary collateral circulation and obstruction of the supplying coronary arteries on left ventricular contractility, prevalence of myocardial infarction, and bicycle exercise ergometer test were studied in a random sample of 286 patients with angiographically documented coronary artery disease. Collaterals appeared increasingly in all three main coronary arteries with grade of obstruction. The highest prevalence of collaterals occurred in stenosis of the right coronary artery (60%), followed by the left descending artery (45%); they occurred least in the left circumflex artery (21%) (p less than 0.001). The frequency of intra-arterial collateral circulation was 42%, 11%, and 12%, respectively (p less than 0.001). With total occlusion of the left anterior descending coronary artery, 22% of the patients had normokinetic anterior and apical left ventricular wall when collaterals were present. More often, the inferior wall showed normal contraction with total occlusion of the right coronary artery and collaterals [52%, p less than 0.001 compared with left anterior descending artery (LAD)]. The prevalence of inferior myocardial infarction was 39%, with collateral circulation to the totally occluded right coronary artery. The respective prevalence of anterior infarction and total occlusion in the left coronary artery was 58% (p less than 0.02). The presence or absence of collaterals had no obvious influence on ST-segment response during bicycle ergometer test. In triple-vessel disease, peak work capacity was better when collaterals to LAD were not jeopardized (427 kpm) than when jeopardized (321 kpm) (p less than 0.02).

Angiographic findings in patients exhibiting ischemia after oral dipyridamole.

We have assessed the angiographic features of a group of 37 patients given oral dipyridamole and 37 patients given matching placebo. Both groups represented severe coronary arterial disease and were studied prior to bypass surgery. Six patients (16%) had angina and 13 patients (35%) had electrocardiographic changes after dipyridamole. All the patients in the control group were nonresponders. In the group given dipyridamole the patients responding with angina had significantly more compromised collaterals than the patients without chest pain (P = 0.021). The same applied to the patients with electrocardiographic changes versus those with no electrocardiographic changes (P = 0.034). No differences between responders and nonresponders could be found in terms of the severity of coronary arterial disease, severity of anginal symptoms, exercise tolerance, antianginal medication, number of past myocardial infarctions, and left ventricular ejection fraction. In conclusion, the data strongly suggest that ischaemic responses to dipyridamole originate from myocardial steal accentuated by compromised flow in collateral vessels.

Studies on ergometer exercise testing. II. Effect of previous myocardial infarction, digoxin, and beta-blockade on exercise electrocardiography.

The results of exercise electrocardiography were studied in a random sample of 317 subjects with clinical suspicion of coronary artery disease. In 278 patients with coronary artery disease the rate of false negative tests was 18% with and 12% without previous myocardial infarction. If ST elevation was considered a negative response, the corresponding values were 25% and 13%, respectively, p less than 0.01. The greatest prevalence of negative tests was seen after anterior myocardial infarction: 27% or 42% when ST elevation was not included into positive responses. The sensitivity of exercise-induced ST depression for the presence of multivessel disease was lower after anterior infarction (67%) than in other patients with previous infarction (86%), p less than 0.01. The corresponding specificities were 71% and 22%, respectively, p less than 0.005. If ST elevation was included into positive responses these differences were abolished. In subjects without myocardial infarction the sensitivity was 89% and specificity 43%. Digitalized patients had somewhat higher sensitivity in the exercise electrocardiogram than those without digoxin, 90% vs. 81% (p less than 0.05), but the difference was not seen with exclusion of ST elevation. The specificity was not influenced by digitalis. beta-blockade had no effect on the sensitivity or specificity, but the prevalence of postexercise ST evolution was lower with (11%) than without (30%) beta-blockade. The prevalence of slowly ascending ST depression was reduced by three factors: the presence of digitalis in patients without previous myocardial infarction, infarction itself, and the extent of coronary artery disease. We conclude that exercise electrocardiography has only a limited value in prediction of multivessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on ergometer exercise testing. I. Significance of the type of ST-segment response, sex, and chest pain.

Ergometer exercise electrocardiographic (EECG) data were surveyed in a series of 328 patients (277 men and 51 women) subjected to coronary arteriography. The sensitivity and specificity of EECG for coronary artery disease (CAD) were 84% and 54%, respectively. The predictive accuracy of a positive test for CAD was 95% in men and 81% in women. The predictive accuracy of a negative test was 25% in men and 62% in women. When slowly ascending ST depression was considered insignificant, the sensitivity of EECG declined to 71%, with an increase in specificity to 64%. CAD was present in 89% of the patients with slowly ascending ST depression and 65% of them had a multivessel disease. Seventy-two subjects had postexercise ST-segment elevation. The predictive value of this sign for CAD was 94%. Exercise-induced chest pain had quite a similar diagnostic significance as EECG. The prevalence of CAD in patients with a history of typical angina was 94% in both sexes. Atypical chest pain was associated with normal coronary arteriography in 59% of males and 100% of females.

Pacemaker infections--treatment with total or partial pacemaker system removal.

During the years 1977 to 1983, 1,458 pacemakers were implanted or reimplanted in our clinic. Seventy-nine patients were treated during the same period for pacemaker system infections. The time interval between the preceding surgical maneuver and the manifest infection was 11.9 +/- 10.2 months in the catheter fistulas and 12.2 +/- 11.5 months in the pacemaker pocket infections. Forty-one of 79 infections (52%) occurred following the first generator implantation. In 33/43 (76.7%) patients with partial pacemaker system removal, recurrent infection occurred 19.6 +/- 17.2 months later. The infection was treated with similar surgical maneuvers resulting in subsequent infections in 9 patients after 9.8 +/- 7.2 months. In the patients with total pacemaker system removal infection developed in 2/25 (8%). The infection resulted in septicemia in 9 patients. Major surgical intervention was necessary for removal of the infected endocardial electrode in 7 patients. According to our experience there are no grounds for partial removal of the pacemaker system if infection occurs. The primary results may be satisfactory but re-infection will appear in the majority of the patients after a period of several months.

Evidence of myocardial ischaemia in patients with chest pain syndromes and normal coronary angiograms.

Patients with chest pain syndromes and normal coronary angiograms were studied with a new set of methods that included thermodilution coronary sinus blood flow and coronary dye dilution curves with special computer analysis, oxygen and lactate determinations, thallium scannings, atrial pacing and dipyridamole tests. The following observations and conclusions were made: Patients with cardiac hypertrophy have a reduced circulating coronary blood volume in relation to the left ventricular mass; this may play a role in patients' vulnerability to ischaemia. During pacing-induced angina a significant imbalance between oxygen supply and demand can be demonstrated in patients with "syndrome X". Dipyridamole-induced chest pain as a result of myocardial ischaemia seems to occur in patients with normal coronary arteries. Marked ischaemia evidenced by a regional intensity reduction of 25% or more in thallium scans results in a significant increase in coronary volume. This is obviously due to mobilization of reserve vasculature as a response to ischaemia. A reduction in the ratio of myocardial oxygen supply to demand was demonstrated even in connection with milder defects, the regional intensity reduction being as low as 12.5%.

Marked relief of acute exacerbation of congestive cardiomyopathy by intravenous practolol--report of a case.

This paper reports a case of severe low output cardiac failure due to congestive (alcoholic) cardiomyopathy which was unresponsive to dopamine infusion, but which improved rapidly on intravenous practolol therapy. The therapeutic range of beta-blockade turned out to be quite narrow.

Flow-volume relations in coronary circulation and distribution of coronary flow into nutritional and non-nutritional compartments.

Simultaneous assessment of coronary flow and flow-volume relation makes it possible to evaluate the dilatatory responses of coronary vasculature. A new set up of methods for investigation of the coronary circulation was employed to study the nature of the coronary flow and volume responses to dipyridamole in dogs. The turnover rate of coronary blood, the reciprocal value of the mean transit time, can be accurately determined by computer simulation analysis of coronary dye dilution curves. After intravenous dipyridamole (0.5 mg/kg) both coronary turnover rate and electromagnetically assessed blood flow were observed to increase in parallel and to the same degree (+55%). This indicates that no increase in the coronary vascular volume and, accordingly, no significant overall coronary dilatation takes place. The effective coronary blood flow in relation to the myocardial oxygen consumption, i.e. the nutritional flow, and the myocardial oxygen consumption decreased by 25% concomitant to a corresponding fall in myocardial oxygen requirements. Thus, the increase in total coronary flow after dipyridamole is useless for myocardial metabolism, and may properly be denoted as luxury perfusion or throughput flow.

The microbial colonization due to medical devices in intensive care patients with special emphasis on Candida albicans.

Incidence of microbial colonization related to medical devices was prospectively studied in 101 consecutive patients treated in intensive care unit ICU. Following endotracheal intubation 50% of patients had positive bacterial culture in the trachea within 24 hours irrespective of the use of antibiotics. Positive urine cultures occurred in 33% of patients with indwelling urinary catheters. Colonization of the trachea and the urinary tract with Candida albicans usually followed a few days after the bacterial colonization. However, septic Candida albicans infections seem to be rare in intensive care patients in spite of abundant colonization in the mucous membranes. Simultaneous growth of Candida albicans in the trachea and the urinary tract was associated with poor prognosis.

Chest pain and rate-dependent left bundle branch block in patients with normal coronary arteriograms.

A triad of exertional chest discomfort, transient rate-dependent left bundle branch block (LBBB), and normal coronary arteries is presented in seven consecutive patients. Although the clinical symptoms resembled effort angina, qualities atypical of classic angina pectoris were commonly noted: 1) the onset was always abrupt; and 2) the pain was local, never radiating; 3) palpitation; and 4) "walk through" phenomenon were often present. The abrupt pain took place simultaneously with the appearance of LBBB induced by physical exercise in all seven patients. Atrial pacing or spontaneous resting heart rate changes produced similar sensations and LBBB in four of the five patients examined in this way. Similarly, in the same four patients kinetocardiographic recordings disclosed a sudden occurrence of paradoxic cardiac movement at the moment LBBB and chest pain appeared. The paradoxic systolic motion disappeared at reversion to normal conduction.