Comparison of exercise perfusion and ventricular function imaging: an analysis of factors affecting the diagnostic accuracy of each technique.

Exercise thallium-201 perfusion scans and gated equilibrium blood pool scans were performed in 120 catheterized patients with a chest pain syndrome. Eighty-six patients had coronary artery disease and 34 patients did not. The effects of gender, propranolol, exercise level, exercise ischemia, history of typical angina, history of previous myocardial infarction, electrocardiographic Q waves, number of diseases vessels and extent of coronary artery obstruction on diagnostic accuracy were evaluated. The overall sensitivity and specificity of thallium scans were 76 and 68%, respectively, and those of gated blood pool scans 80 and 62% (p = not significant). Propranolol decreased the specificity of thallium scans (propranolol = 42%; no propranolol = 87%, p less than 0.05). Thallium scans and anginal history were less sensitive for detecting coronary disease in women (men: thallium = 79%; angina = 77%; women: 54 and 46%, respectively; p less than 0.05). Exercise level did not significantly affect the diagnostic accuracy of either scan. Thallium and gated scans were both highly sensitive (95%) in detecting disease in 20 patients with a prior myocardial infarction, angina and a positive electrocardiogram. The sensitivity of the thallium scan significantly decreased as the number of diseased vessels decreased. Both thallium and gated scans were less frequently positive in patients with atypical angina or no Q waves, but were not significantly influenced by electrocardiographic ischemia. The sensitivity and specificity of both scans were low in 57 patients with the combination of atypical angina, no history of infarction and equivocal stress electrocardiogram thallium = 61 and 63%, respectively; gated = 61 and 67%). When stress thallium scan evaluation included the electrocardiogram and thallium scan interpretation, the diagnostic accuracy was 81%. When all the information from gated scans (wall motion, ejection fraction, pulmonary blood volume) was combined for final gated scan evaluation, the diagnostic accuracy was 83%. When electrocardiographic data were added to all three gated scan variables, diagnostic accuracy was 77%. In conclusion, thallium perfusion and gated blood pool scans have reasonable diagnostic accuracy for coronary artery disease in a group of patients with a moderately high prevalence of disease. However, combined variables from each test are needed to provide reliable diagnostic accuracy.

Regression of left ventricular hypertrophy in human hypertension with irbesartan.

BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication.

A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of radiocolloids. For injection of the left ventricle, the catheter is introduced through the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renografin (to confirm the endocardial injection site) and radiolabeled colloid was injected in 13 animals. Ten minutes after injection, scintigraphy was begun and continued for up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method.

Use of left ventricular filling and ejection patterns in assessing severity of chronic mitral and aortic regurgitation.

To determine whether left ventricular (LV) filling and ejection patterns can be used to characterize the severity of mitral and aortic regurgitation (MR and AR), normalized volume vs time curves derived from left ventriculograms were plotted using a computer-based image analysis system. These patterns were measured in 20 normal subjects, 14 patients with MR and 21 patients with AR. In addition, time-averaged volume changes (dV/dt) and diameter changes (dD/dt), stroke or filling volume, and ejection or filling fraction were measured during systole and diastole. The patients with volume overload were separated into 4 groups based on symptoms: asymptomatic (MR, 7 patients, AR, 10 patients); congestive heart failure (CHF) (MR, 7 patients, AR, 11 patients). Ejection fraction was significantly depressed in both CHF groups, even though stroke volume index was significantly increased in all groups. The temporal pattern of diastolic filling in patients with CHF secondary to MR and AR demonstrated slower, later diastolic filling compared with normal subjects, while in asymptomatic MR, diastolic filling was more rapid than in normal subjects. Diastolic filling patterns were similar to normal in asymptomatic AR patients. Temporal systolic emptying was slower in patients with CHF secondary to AR; emptying patterns in asymptomatic MR patients were similar to those of normal subjects; late systolic emptying was accelerated in patients with asymptomatic AR. Thus, there were filling and emptying abnormalities in all stages of volume overload secondary to regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular regional wall motion and velocity of shortening in chronic mitral and aortic regurgitation.

Left ventricular regional wall motion (percent systolic shortening) and velocity of shortening were studied in patients with heart failure due to chronic volume overloads of mitral and aortic regurgitation. Biplane left ventriculograms were analyzed by computer and divided into four regions: anterior, inferior, posterolateral and septal. The study patients included 12 normal subjects; 21 patients with aortic regurgitation (10 asymptomatic and 11 with congestive heart failure); and 11 patients with mitral regurgitation (4 asymptomatic and 7 with congestive heart failure). No patient had coronary artery disease. With heart failure, ejection fraction was decreased (p less than 0.05) in both aortic and mitral regurgitation (normal 62 +/- 3 percent [mean +/- standard error of the mean], aortic regurgitation 48 +/- 3 and mitral regurgitation 51 +/- 5). In mitral regurgitation with heart failure, the percent segment shortening in anterior (normal 42 +/- 2, mitral regurgitation 27 +/- 5) and posterolateral (normal 23 +/- 3, mitral regurgitation 16 +/- 4) regions was significantly decreased (p less than 0.05), whereas this value in the inferior (normal 32 +/- 2, mitral regurgitation 28 +/- 6) and septal (normal 46 +/- 4, mitral regurgitation 47 +/- 5) regions was normal. In aortic regurgitation with heart failure, anterior (27 +/- 2), inferior (17 +/- 3) and septal (5 +/- 1) segment shortening was significantly decreased, whereas posterolateral segment shortening was significantly decreased, whereas posterolateral segment shortening was normal (24 +/- 3). In both groups with heart failure, mean shortening velocity showed regional variations similar to those of percent shortening, whereas peak instantaneous shortening velocity was not reduced in mitral regurgitation compared with normal values. In the asymptomatic group, shortening and mean shortening velocity were normal, whereas peak instantaneous shortening velocity was increased in mitral regurgitation. In aortic and mitral regurgitation with decreased left ventricular function demonstrated by a reduced ejection fraction, there are regional wall motion abnormalities that are not caused by coronary disease.

Spectrum of global left ventricular responses to supine exercise. Limitation in the use of ejection fraction in identifying patients with coronary artery disease.

Left ventricular function was evaluated with rest and supine bicycle exercise-multigated blood pool scans in 53 patients who had previously undergone coronary angiography for evaluation of a chest pain syndrome. There were 21 normal patients (less than 25% stenosis in any coronary artery, left ventricular end-diastolic pressure less than or equal to 12 mm Hg, and normal left ventriculography) and 32 patients with coronary artery disease (CAD) (greater than 50% narrowing in 1 or more major coronary arteries). Thirty-two (60%) were receiving propranolol at the time of the study. The normal patient group had a significant increase in mean ejection fraction (EF) during exercise (+0.08 +/- 0.09), while the CAD group had no increase (0 +/- 0.11; p less than 0.05). Mean end-systolic volume decreased significantly in the normal group (-5 +/- 8 ml/m2) but demonstrated no significant change in the CAD group (1 +/- 12 ml/m2; p less than 0.05 compared with normal patients). There was no significant change in mean end-diastolic volume in either group. Mean ejection rate, mean peak systolic pressure/end-systolic volume ratio, and mean pulmonary blood volume ratio also differed in the normal versus CAD patients. Despite mean differences, there was considerable overlap in both groups of individual EF responses: 8 of 21 (38%) of the normal group did not have an increase in EF of 0.05 with exercise, while 15 of 32 (47%) of the CAD group did have an increase in EF of 0.05 with exercise. However, the addition of peak systolic pressure/end-systolic volume ratio and pulmonary blood volume (exercise/rest) ratio improved the sensitivity for detecting CAD from 53 to 84% without adversely affecting specificity. Thus, there is a wide spectrum of left ventricular EF responses to supine exercise. In our patient population, EF alone was an insensitive and nonspecific marker of CAD. The addition of other parameters of global left ventricular function, which may be generated using radionuclide angiography, helps distinguish patients with CAD from normal subjects.

Mitral valve replacement for isolated mitral regurgitation: analysis of clinical course and late postoperative left ventricular ejection fraction.

One hundred five patients underwent mitral valve replacement for relief of isolated mitral regurgitation between 1974 and 1979. There were 4 in-hospital deaths (4 percent) and 12 late deaths giving an 82 percent predicted 5 year survival rate. An age of 60 years or more at the time of surgery and a preoperative left ventricular ejection fraction of less than 0.40 were the only variables that correlated with decreased survival at 3 to 5 years after operation (p less than 0.05). Postoperatively, 87 (98 percent) of 89 long-term survivors were in New York Heart Association functional class I or II (68 in class I and 19 in class II). Survival did not differ between patients with porcine versus mechanical valve replacement, but patients with a mechanical valve had a greater incidence of postoperative cerebrovascular accident (8.6/100 patient years) than did patients with a porcine valve (2.8/100 patient years) (p less than 0.002). Ejection fraction at rest was determined with multigated cardiac imaging 12 to 75 months postoperatively in 34 of 89 long-term survivors. The mean preoperative ejection fraction was 0.62 +/- 0.09 (mean +/- 1 standard deviation) and the mean postoperative ejection fraction was 0.50 +/- 0.15 (p less than 0.001). When the preoperative value was compared with the postoperative value at rest the ejection fraction increased by 0.10 or more in 1 patient (3 percent), remained within +/- 0.09 of the preoperative value in 12 patients (35 percent) and decreased by 0.10 or greater in 21 patients (62 percent). Sixteen (94 percent) of 17 patients whose postoperative ejection fraction was greater than 0.50 were in functional class I postoperatively compared with 11 (65 percent) of 17 patients whose postoperative ejection fraction was 0.50 or less (p less than 0.05). No preoperative factor, including preoperative ejection fraction or cardiothoracic ratio, predicted the postoperative ejection fraction. A postoperative exercise ejection fraction was obtained in 29 patients, and an abnormal ejection fraction change with exercise (increase less than 0.05) was observed in 20 patients (69 percent). Patient age at the time of study correlated inversely with the change in ejection fraction from rest to exercise; no other variables were predictive. It is concluded that, in addition to age, only preoperative left ventricular function as measured by ejection fraction predicts survival in patients undergoing mitral valve replacement for isolated mitral regurgitation. Clinical recovery is good even though the majority of long-term survivors have a postoperative decrease in ejection fraction.

Successful management of right ventricular failure with the ventricular assist pump following aortic valve replacement and coronary bypass grafting.

Right ventricular failure is an infrequent but potentially lethal complication of cardiac surgical procedures. We have successfully treated a patient with right ventricular failure with the use of a right ventricular assist pump (RVAP). This patient had aortic stenosis and coronary artery disease involving the circumflex and right coronary arteries. He also had chronic obstructive pulmonary disease with mild pulmonary hypertension (mean pulmonary artery pressure of 26 mm Hg) and evidence of mild right ventricular failure (right ventricular pressure of 40/14 mm Hg). Gated radionuclide angiography, performed preoperatively, showed that the right ventricle had normal wall motion. Right ventricular failure prevented discontinuation of cardiopulmonary bypass despite use of an intra-aortic balloon pump. The right atrial pressure was 20 mm Hg with a left atrial pressure of 8 to 10 mm Hg. Bypass was readily discontinued following implantation of the RVAP. Recovery of the patient's right ventricle was evaluated with serial determinations of right ventricular work. The RVAP was removed on the fifth postoperative day and the patient made a complete recovery. Postoperatively, gated radionuclide angiography demonstrated moderate recovery of right ventricular function. We suspect that the perioperative right ventricular failure was a result of unsatisfactory myocardial protection due to total occlusion of the proximal right coronary artery, which resulted in a maldistribution of the cardioplegic solution. This case demonstrates that right ventricular function can be restored following circulatory support with a mechanical assist device.

Anatomic features of the eye disclosed with nuclear magnetic resonance imaging.

Nuclear magnetic resonance (NMR) imaging of the eye and paraorbital areas was performed in 35 volunteers and in four patients with ocular pathology. Two- and three-dimensional images were performed with saturation recovery (SR), inversion recovery (IR), and spin echo (SE) pulse sequences. Fat was brighter than surrounding tissue on images obtained with all pulse sequences, while muscle and optic nerve were of decreased intensity. The optic chiasm and vitreous were of decreased intensity compared with orbital fat on SR. The lens had even less signal intensity than the vitreous on SR and IR images and blended into the surroundings on SE images. A melanoma of the ciliary body and a lymphoma of the lacrimal gland were identified. In conclusion, NMR images can be used to identify normal and pathologic orbital and eyeball anatomy. Image contrast is provided by high intensity fat, which is interspersed throughout other orbital structures.

Cardiovascular monitoring during elective aortic surgery.

We designed a prospective study to determine whether cardiac ejection fraction as measured noninvasively could isolate a subset undergoing aortic surgery for whom central venous pressure (CVP) predicted pulmonary artery wedge pressure (PAWP). Sixteen patients were studied. Simultaneous values of PAWP and CVP were analyzed, using linear regression analysis. A significant correlation between CVP and PAWP was found for the entire patient population and for each of four time periods: preoperative, before and after aortic cross-clamping, during aortic cross-clamping, and postoperative. A significant correlation between PAWP and CVP was found during the entire perioperative period for 14 of the 16 patients. However, the slope of the regression line, or the sensitivity of the CVP in reflecting changes in PAWP, was greater than 0.5 in only seven of the 16 patients. There was no correlation between the preoperative ejection fraction and the CVP/PAWP. We conclude that the CVP is an insensitive indicator of left ventricular filling pressure in most patients accepted for elective infrarenal aortic surgery, and monitoring of the PAWP is recommended.

Magnetic resonance imaging in leukodystrophies of childhood.

Magnetic resonance imaging (MRI) is particularly valuable in the diagnosis of childhood brain disorders with abnormal myelination because MRI may identify lesions not always seen with x-ray CT scans. We report the clinical and magnetic resonance findings of six children with leukodystrophy. T2 weighted (spin-echo) images disclosed striking asymmetric involvement of cerebral white matter, particularly in periventricular white matter and visual radiations. Calculated T1 values were significantly elevated in the children with leukodystrophy.

Adenosine improves cardiomyocyte respiratory efficiency.

The role of adenosine on the regulation of mitochondrial function has been studied. In order to evaluate this the following experiments were done in isolated rat cardiomyocites and mitochondria using polarographic techniques. Cardiomyocyte oxygen consumption (MVO2) and mitochondrial respiratory function (State 3 and State 4, respiratory control index, and ADP/O ratio) were evaluated after exposure to adenosine. Cardiomyocyte MVO2 was significantly lower in cells previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) than in cells not exposed to adenosine (control). Addition of dipyridamole (10 microM) or 8-(p-Sulfophenyl) theophylline (50 microM) to cardiomyocytes before adenosine incubation prevented the adenosine-induced changes in MVO2. Mitochondria obtained from isolated perfused beating heart previously perfused with adenosine (10 microM, 30 min heart perfusion) also resulted in significant increases in ADP/O and respiratory control index compared to matching control. Mitochondria isolated from cardiomyocytes previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) resulted in a significant increase in mitochondrial ADP/O ratio compared to control. Adenosine-induced decrease in cardiomyocyte MVO2 may be related to an increase in efficiency of mitochondrial oxidative phosphorylation, and more economical use of oxygen, which is necessary for survival under ischemic stress.

Metabolic regulation of in vivo myocardial contractile function: multiparameter analysis.

To gain insight into the mechanisms of myocardial regulation as it relates to the interaction of mechanical and metabolic function and perfusion, intact animal models were instrumented for routine physiological measurements of mechanical function and for measurements of metabolism (31P NMR, NADH fluorescence (redox state)) and perfusion (2H NMR and Laser doppler techniques). These techniques were applied to canine and cat models of volume and/or pressure loading, hypoxia, ischemia and cardiomyopathic states. Data generated using these techniques indicate that myocardial bioenergetic function is quite stable under most loading conditions as long as the heart is not ischemic. In addition, these data indicate that there is no universal regulator and that different biochemical regulators appear to mediate stable function under different physiological and pathophysiological conditions: for example; during hypoxia, NADH redox state appears to play a regulatory role; and in pressure loading, ADP, phosphorylation potential and free energy of ATP hydrolysis as well as NADH redox state appear to be regulatory.

Sodium flux and bioenergetics in the ischemic rat liver.

Concurrent 23Na and 31P nuclear magnetic resonance spectroscopy has been employed to study the effects of ischemia upon the high-energy phosphagens and sodium ion concentration within the in vivo rat liver. High-energy phosphates in the form of ATP were depleted within 10 min of the onset of ischemia when measured by NMR. However, similar liver samples subjected to analytical biochemistry retained 27 +/- 12% of their ATP after a similar 10-min ischemic insult. Time-dependent 23Na NMR measurements, obtained in the presence of the shift reagent Dy(TTHA) to distinguish intracellular from extracellular sodium, revealed a rapid rise in the intracellular sodium when the liver was made ischemic. Intracellular and extracellular sodium concentrations approached equilibrium with an exponential time constant of 14.7 +/- 7 min. The initial rate of sodium influx was calculated to be 1.50 meq.l-1.min-1. The results indicate that the ischemic liver has a high passive sodium permeability and that NMR detectable 31P signals reflect the actual availability of cytosolic high-energy phosphates to enzymes, in this instance the membrane-bound [Na+, K+]-ATPase.

Nuclear magnetic resonance imaging characterization of a rat mammary tumor.

Intradermal injection (1 X 10(6) cells) of rat mammary adenocarcinoma (13762A) was made in the back skin in 12 rats. Tumor growth and characterization was followed with nuclear magnetic resonance imaging (NMRI) in 9 rats (3 rats died before completion of the study) at 3, 4, and 5 weeks after injection, using spin echo, inversion-recovery, and calculated T1 techniques. Three rats were sacrificed after each of the three imaging periods for histological studies designed to distinguish solid tumor mass from necrosis. Qualitative NMR imaging T1 values increased as the tumors increased in size as evidenced by a progressive decrease in image intensity compared to the surrounding tissues on the T1 weighted images. Calculated T1 values also increased as the tumors aged (Week 3 = 0.3 +/- 0.11; Week 4 = 0.45 +/- 0.07; Week 5 = 0.42 +/- 0.03). Planimetry of tumor areas on histological sections showed that as tumors increased in size, the ratio of necrotic area to solid tumor area increased (Week 3 = 0.3 +/- 0.11; Week 4 = 0.45 +/- 0.07; Week 5 = 0.51 +/- 0.05). These findings indicate that the progressive increase in T1 observed on NMR images may be secondary to the increasing degree of necrosis, with a resultant change in water content and state. Thus, the range of T1 values observed in tumors of similar type may be due to change in tumor physiology and anatomy as tumor growth progresses. In conclusion, careful correlation of histological data with NMR image data is necessary before NMR imaging can be used to provide reliable noninvasive histological information concerning tumor pathology.

Temporal relationships between eating behavior and liver adenine nucleotides in rats treated with 2,5-AM.

Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) elicits eating behavior in rats by its action in the liver. To evaluate whether the decrease in liver ATP levels produced by injection of 2,5-AM plays a role in the eating response, we examined the relationship between changes in eating behavior and liver adenine nucleotide levels over time in rats given 2,5-AM. Liver ATP concentrations decreased within 15 min after injection of 2,5-AM (300 mg/kg ip), remained low for up to 90 min postinjection, and returned to control (saline injection) levels by 4 h after treatment. Rats fed ad libitum initiated eating between 15 and 45 min after 2,5-AM treatment, after liver ATP levels had declined. Rats given food 1 h after 2,5-AM treatment increased food intake, but if access to food was delayed for 4 h after 2,5-AM injection the eating response was attenuated or absent. Whereas liver AMP and ADP levels were also altered by injection of 2,5-AM, changes in food intake did not consistently track changes in these nucleotides. The results support the hypothesis that the eating response to 2,5-AM is triggered by a decrease in liver ATP level.

Hepatic phosphate trapping, decreased ATP, and increased feeding after 2,5-anhydro-D-mannitol.

The mechanism by which the fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) elicits feeding behavior was investigated by studying its metabolism and biochemical effects in liver. Thin-layer chromatography of liver extracts from rats given 2,5-AM containing 14C-labeled 2,5-AM showed that the analogue is phosphorylated in vivo with a time course that parallels the eating response. In vivo 31P nuclear magnetic resonance spectroscopy of rat liver during intravenous infusion of 2,5-AM and high-resolution nuclear magnetic resonance analyses of liver extracts showed that 2,5-AM is rapidly phosphorylated in liver, trapping hepatic phosphate and decreasing ATP, inorganic phosphate, and phosphate diesters. These changes occurred in a time frame in which the feeding response is elicited in conscious animals given the same dose of 2,5-AM by the same route. During an interval in which 2,5-AM increased eating, it also increased urinary uric acid excretion, implicating enhanced adenosine degradation in the reduction in hepatic ATP. These results provide the first direct evidence that changes in a high-energy phosphate-carrying compound in liver may provide a signal to initiate eating behavior.