Areas of the heart which are supposedly absent of myocardial viability due to persistent thallium defect in exercise thallium myocardial scintigraphy some-times recover ventricular wall motion through coronary revascularization. To avoid such underestimation of myocardial viability, a "re-injection method" was developed. At the peak of supine ergometer exercise in 51 patients with coronary artery disease, 111 MBq thallium was injected. Conventional exercise and 3 h-delay images were then obtained using single photon emission computed tomography. Subsequently, 55 MBq thallium was injected and a re-injection image was obtained 1 h later. Each image was divided into 12 segments and compared by left ventriculography and coronary angiography. Redistribution was found in 36 patients (71%) on the delayed images and in 44 patients (86%) on either the delayed or the re-injection images (p<0.05). There were 127 re-distribution segments (38%) on the delayed images and 163 (49%) on the re-injection images out of 336 defects on the exercise images (p<0.001). In normokinetic segments with significant coronary stenosis and in hypokinetic segments, redistribution was found in 42% and 45% of the defects, respectively, on the delayed images, and in 65% and 62% of the defects, respectively, on the re-injection images (p<0.01). However, no significant differences were observed between the delayed and either the delayed or re-injection images in the akinetic segments. These results suggest that the re-injection method is useful for avoiding underestimation of myocardial viability.

View full abstract

We have investigated the relationship between plasma endothelin (ET) concentrations and several clinical characteristics in 31 patients with acute myocardial infarction (MI). ET levels were also measured in 10 age-matched healthy subjects, 9 patients with unstable angina, and 20 patients with chronic heart disease. In patients with MI, although no significant relationship was observed between plasma ET concentrations and measured hemodynamic parameters, plasma levels were higher in patients with pulmonary congestion than in those without this complication (1.61±0.29 vs 1.21±0.33 fmol/ml; p<0.01). No significant difference in plasma ET levels was found between cardiac and peripheral sampling sites (pulmonary artery; 1.07±0.28, right atrium; 1.02±0.28, peripheral artery 1.12±0.23 peripheral vein; 1.14±0.38 fmol/ml: N.S.), or among patients with uncomplicated MI, unstable angina (1.000.32 fmol/ml), and healthy subjects (1.01 0.29 fmol/ml). Increased level were observed in patients with decompensated heart failure due to chronic heart disease, but were not found in patients without pulmonary congestion (1.62±0.60 vs 1.11± fmol/ml; p<0.01). These observations suggest that plasma ET concentrations are elevated in the presence of congestive heart failure or severe ventricular depression, but are not persistently increased by myocardial ischemia per se.

View full abstract

To examine whether measurements of lung thallium-201 (Tl-201) uptake with single photon emission computed tomography (SPECT) following exercise or dipyridamole infusion provide complementary information as reported in planar imaging, we examined 140 patients undergoing exercise or dipyridamole Tl-201 SPECT and coronary arteriography for the diagnosis of coronary artery disease (CAD). On the reconstructed coronal tomographic image, regions of interest were placed over the left upper lung field and the left ventricular myocardium. Lung to heart ratio (L/H ratio) was calculated as a fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. An L/H ratio of larger than a value of mean+2 standard deviation, derived from patients without significant coronary stenosis, was considered as abnormal. The patients with abnormal L/H ratio on exercise Tl-201 SPECT had larger extent and severity scores of Tl-201 defects on the initial image, lower left ventricular ejection fraction, higher end-diastolic pressure and higher incidence of multi-vessel CAD than those with the normal ratio. However, in dipyridamole studies, abnormal L/H ratio did not relate to scintigraphic or hemodynamic severity. These data confirmed that increased lung Tl-201 uptake after exercise suggested the presence of extensive CAD or left ventricular dysfunction. However, L/H ratio might be less useful in dipyridamole studies. Thus, quantitative measure-ments of L/H ratio with exercise but not dipyridamole SPECT could provide additional information related to the involved cardiac pump performance in CAD.

View full abstract

We investigated smooth muscle cell proliferation associated with restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 8 arteries with fragmented internal elastic, lamina obtained at autopsy in 7 patients who died between 2 months to 2 years 11 months after coronary angioplasty. The internal elastic lamina fragmentation, measured longitudinally along the blood vessels, measured 6.6±6.9 mm. Smooth muscle cell proliferation was concentrated around the fragmented internal elastic lamina, extending longitudinally even to unfragmented areas. The proliferation of smooth muscle cells extended for 1.8±2.2 mm in the proximal portion of the fragmentation, and for 2.0±2.9 mm in the distal portion. The possibility of new stenoses resulting from smooth muscle cell proliferation at sites adjacent to those subjected to PTCA should be borne in mind when PTCA of the proximal segments of the left anterior descending coronary artery is contemplated.

View full abstract

Previous studies have demonstrated that the long-term prognosis after acute myocardial infarction in patients whose infarct-related artery remains occluded is worse than that in those with anterograde flow. To determine how to identify patients with occluded infarct-related arteries noninvasively, 143 consecutive patients after a first myocardial infarction underwent exercise testing and dipyridamole thallium scintigraphy. The incidence of total occlusion was higher in inferior/posterior infarction than in anterior infarction (29/53 vs 28/90; p = 0.005). In patients with inferior/posterior infarction, discriminant analysis revealed a sensitivity of 79%, a specificity of 88% and an accuracy of 83% (p=0.0005) in identifying those with an occluded infarct-related artery. In patients with anterior infarction, the analysis showed a sensitivity of 68%, a specificity of 85% and an accuracy of 79% (p<0.0001) in identifying those with an occluded artery. These results indicate that noninvasive study may be useful in the evaluation of total occlusion of the infarct-related coronary artery.

View full abstract

Among 125, 000 patients who underwent coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988, 128 (0.1%) were found to have 50-99% stenosis of one or both coronary ostia. A11 cases were associated with minimal or no obstruction in the distal coronary arteries. Thirty-six percent were males and 64% were females. Fifty percent had ostial narrowing of the left main trunk, 41% had ostial narrowing of the right coronary artery, and 9% had bilateral ostial stenosis. Based on angiographic appearance, the patients were categorized into three groups: 1) atherosclerotic (77%), 2) primary (unknown etiology) (13%), and 3) secondary to aortic valve disease (10%). Compared with the other groups, primary solitary coronary ostial stenosis was commonly found in middle-aged premenopausal or postsurgical menopausal females who had few coronary risk factors and were experiencing severe angina symptoms. At autopsy, most cases were atherosclerotic, however, fibromuscular dysplasia may be found in primary solitary ostial stenosis. This rate entity is difficult to diagnose, and is associated with increased risk during cardiac catheterization and bypass surgery. Solitary ostial stenosis should be included in the differential diagnosis of ischemic heart disease, especially in young or middle-aged female patients.

View full abstract

Hemodynamic and neurohumoral responses to supine bicycle exercise were evaluated in 16 patients with congestive heart failure (New York Heart Association functional class II-III) and in 8 normal controls. We determined cardiac output by the dye-dilution method, and forearm hemodynamics by plethysmography. The patients had lower resting cardiac and stroke indexes (p<0.05) than the normal controls. During exercise, the increase in the cardiac index due to an increase in heart rate, was less than that in the controls. Resting and exercise systemic vascular resistance indices were higher in the patients (p<0.05). The patients had lower resting forearm blood flow and higher forearm vascular resistance (p<0.05), and the increases during exercise were comparable in the 2 groups. However, forearm venous tone and venous pressure increased more in the patients (p<0.05). Exercise duration was shorter in the patients (p<0.01). Resting plasma angiotensin 11 and norepinephrine were similar in the 2 groups, but plasma 6-keto-prostaglandin F_1α and atrial natriuretic peptide were higher in the patients. During exercise, all of these neurohumoral parameters rose more in the patients than in the controls (p<0.05). Thus, the patients exhibited impaired central and peripheral hemodynamics both at rest and during exercise. The excessive exercise responses of all of the neurohumoral factors suggest that both vasoconstrictor and vasodilator systems are activated in heart failure.

View full abstract

To determine the common morphological characteristics of hypertrophic cardiomyopathy (HCM) by ventriculography from a right anterior oblique projection, diaphragmatic and free wall configurations were analyzed in 15 patients with obstructive HCM (HOCM), 32 patients with nonobstructive HCM (HUNCH) and 17 controls. There was a convexity extending into the left ventricle in the right anterior oblique projection due to hypertrophy of the interventricular septum (IVS) in all patients with HCM. The peak convexity, where septal thickness was maxi-mal (M point), was closer to the base in HOCM than in HNCM. Due to this convexity, the left ventricle showed a catenoid-shaped distortion at the M point. The distortion was severer in HOCM than in HNCM. Left ventricular free wall (LVFW) thickness was measured at the base and near the apex. LVFW thickness in HOCM decreased toward the apex, similar to that in controls, but in 17 of 32 HNCM (53%) LVFW thickness increased toward the apex. Cardiac index and stroke index in HCM were significantly smaller than those in controls. There was a significant correlation between the position of the M point and stroke index in HCM. These results indicate that a common morphological characteristic of HCM on the diaphragmatic side is the existence of a convexity extending into the left ventricle, and that cardiac performance in HCM is greatly influenced by the nature of the convexity. Myocardial abnormality seems to exist primarily at the base of the IVS in HOCM, and primarily in the lower part of the IVS and LVFW in HNCM.

View full abstract

We investigated the role of β-adrenoceptors at postganglionic sympathetic nerve endings in noradrenaline release in rabbits with cardiomyopathic congestive heart failure produced by adriamycin (1 mg/kg, I.V., twice a week for 8 weeks). Plasma noradrenaline levels were measured before, 30 min after, and 60 min after the start of continuous intravenous administration of adrenaline (0.06μg/kg/min) in adriamycin-treated and vehicle-treated rabbits in anesthetized condition and pithed condition with electrically stimulated sympathetic outflow (3 Hz, 1 ms square wave pulse, 90 V). In both the anesthetized and pithed conditions, adrenaline increased plasma noradrenaline levels in vehicle-treated rabbits. However, in the adriamycin-treated rabbits, adrenaline had no effect on the plasma noradrenaline level. Pretreatment with propranolol (0.2 mg/kg, bolus I.V. + 0.1 mg/kg/hr, continuous infusion) almost completely abolished the rise in plasma noradrenaline associated with adrenaline infusion in vehicle-treated rabbits. These results suggest that in rabbits with adriamycin-induced cardiomyopathy, the noradrenaline release from the sympathetic nerve endings via the activation of presynaptic β-adrenoceptors is reduced. This might be due to down-regulation of presynaptic β-adrenoceptors caused by the elevated plasma noradrenaline due to cardiac failure. However, other possibilities such as reduced affinity or impaired signal transduction cannot be excluded.

View full abstract

To determine how collagen is remodeled in the heart during the development of cardiac hypertrophy, the collagen concentration and the proportions of types I, III, and V collagen were analyzed in the hearts of 10-, 20-, 32-, and 40-week-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The collagen concentration was calculated after the hydroxyproline content was measured and the proportions of types I, III, and V collagen were determined by non-interrupted SDS-polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the collagen concentrations in 10-week-old SHR and WKY. At 20 weeks, the collagen concentration in the hearts of the SHR had decreased significantly (p< 0.01) when compared to that in the WKY, at 40 weeks, this concentration in SHR had increased significantly (p<0.05) when compared to that in the WKY. Type V collagen in WKY increased with age and type I collagen in the 20- and 40-week-old WKY de-creased significantly (p<0.05) when compared to that in the 10-week-old WKY. However, the proportion of type I collagen in the 20-week-old WKY did not differ from that of the 40-week-old WKY. There was no significant difference between the proportions of the various types of collagen in 10-week-old SHR and those in age- and sex-matched WKY. However, the proportion of type V collagen in the 20- and 40-week-old SHR was significantly (p<0.01) higher than that in age- and sex-matched WKY. Moreover, the proportion of type I collagen in the 40-week-old SHR was significantly (p<0.01) lower than that in age- and sex-matched WKY. The III/I ratio of the 40-week-old SHR was significantly higher than that of age-matched WKY (p< 0.05). These results show qualitatively and quantitatively that collagen is remodeled as cardiac hypertrophy develops and that there is a prominent increase in type V collagen. This suggests that type V collagen is involved in the pathogenesis of cardiac hypertrophy in SHR.

View full abstract

We studied the relative synthetic phase (S-phase) ratio of cardiac myocytes of spontaneously hypertensive rats (SHR) utilizing monoclonal antibody to 5-bro-mo 2'-deoxyuridine (BrdU), a halogen derivative of thymidine. BrdU was administered intraperitoneally to SHR and Wistar Kyoto rats at 66.7 mg/kg/day for 3 consecutive days. The rats were sacrificed I week after the first injection of BrdU. Using anti-BrdU antibody, myocardial tissue was stained by the avidin biotinylated peroxidase complex method. We assessed the ability of the nuclei to synthesize DNA. The percentage of BrdU-labeled myocyies was higher in SHR than in control rats at 9 weeks. The hyperplastic phase of heart growth in rats was presumed to occur about 3 weeks after birth. From these results, the ability of the myocardial cell to synthesize DNA is probably enhanced under the load of high blood pressure in the early hypertrophic phase following hyperplasia.

View full abstract

To investigate the role of abnormal Ca²⁺ metabolism in the diminished contractile function of diabetic myocardium, we measured the Ca²⁺ transients and cell contraction of diabetic rat myocytes. Isolated diabetic (8 weeks after 40 mg/kg streptozotocin, i.v.) and normal myocytes were loaded with acetoxymethyl ester of indo-1 (indo-1/AM). Ca²⁺ transients and cell circumferential shortening were measured simultaneously, using high temporal resolution video image analysis. The diastolic base and systolic peak of Ca²⁺ transients were significantly lower in diabetic myocytes than in normal myocytes (peak ratios: 0.49±0.02 vs 0.56±0.01, p<0.05; base ratios: 0.43±0.01 vs 0.48±0.01, p<0.01, Mea±SE). The cell circumferential shortening of diabetic myocytes was also significantly lower than that of normal myocytes (2.9±0.3% vs 5.2±0.9%, p<0.05). Although isoproterenol (10-8 and 10-7 M) increased the peak of Ca²⁺ transients in both diabetic and normal myocytes, the peak value of Ca²⁺ transients in the diabetic group was significantly lower than that in the normal group. The decreased Ca²⁺ transients may be responsible for the decreased contractile function in diabetic myocardium.

View full abstract

In previous studies, magnetic resonance imaging (MRI) using contrast agents was found to be useful in distinguishing reperfused infarcts from nonreperfused infarcts. However, there have been only a few detailed studies using consecutive MR images for the assessment of myocardial reperfusion during an acute myocardial infarction and also no studies have been performed using a percutaneous transluminal coronary occlusion model (closed chest model). We induced acute myocardial infarction in dogs by occluding and then reperfusing the coronary artery with a balloon catheter. ECG-gated MR images were taken using the spin-echo technique before and after Gd-DTPA injection during both coronary artery occlusion and after reperfusion. We defined the intensity ratio (IR) as the signal intensity at the ischemic area divided by that at the nonischemic area on MR images and compared each image by the IR. Without Gd-DTPA, there was no difference between infarcted and normally perfused myocardium. Infarcted myocardium had a low signal intensity (IR=0.68±0.14) soon after Gd-DTPA injection. This difference diminished with time. After reperfusion the infarcted myocardium had a high signal intensity (IR:1.76±0.34). We conclude that Gd-DTPA- enhanced MRI can distinguish reperfused from nonreperfused infarcts soon after Gd-DTPA administration.

View full abstract

This report presents a case of aortic valvular dysfunction and right coronary artery disease following radiation therapy on the mediastinum. A 61-year-old woman had received mediastinal radiation for the treatment of right mammary cancer 20 years previously. She developed symptoms of congestive heart failure 6 months ago. The patient was found to have aortic valvular dysfunction and proximal stenosis of the right coronary artery. Surgical aortic valve replacement improved cardiac status, and vasodilator treatment reduced ischemia due to right coronary artery stenosis.

View full abstract

Coronary spasm was observed in two sisters. Neither of them had significant atheromatous stenosis in the coronary arteries. The 41-year-old elder sister presented with resting morning angina. The stress electrocardiogram showed marked depression of the ST-segment in precordial leads. Diffuse vasospasm in the left anterior descending artery was induced by the intracoronary administration of acetylcholine. The 38-year-old younger sister suffered from acute inferior myocardial infarction after taking methylergonovine following an abortion. Emergent coronary angiography disclosed a thrombus in the proximal right coronary artery which was dissolved with intracoronary administration of urokinase. There was no residual stenosis in the culprit vessel. Although the sisters do have risk factors for coronary spasm, an inherited factor may contribute to the mechanism of the spasm.

View full abstract