Myocardial kinetics of thallium-201 after dipyridamole infusion in normal canine myocardium and in myocardium distal to a stenosis.

The purpose of the present study was to define myocardial and blood thallium-201 (Tl-201) kinetics after infusion of dipyridamole in normal canine myocardium and in myocardium distal to a coronary artery stenosis. Miniature radiation detector probes were implanted in the left ventricle in 39 open-chest dogs. A balloon constrictor was placed around the proximal left circumflex coronary artery. Electromagnetic flow probes were positioned proximally around both the left circumflex and left anterior descending coronary arteries. In five control dogs (group 1) the balloon occluder was not inflated; in 12 dogs (group 2) a mild stenosis was created such that resting flow was not reduced, yet the hyperemic response after 10 s of total occlusion was partially attenuated; in nine dogs (group 3) a moderate stenosis was created such that resting flow was not reduced, yet the hyperemic response was completely eliminated; and in 13 dogs (group 4) a severe stenosis was created such that resting flow was reduced. After intravenous dipyridamole (0.08 mg/kg . min-1 x 4 min), 1.5 mCi Tl-201 was injected intravenously and probe counts were collected continuously for 4 h. The mean 4-h fractional myocardial Tl-201 clearance for nonstenotic zones was 0.35, 0.27 for group 2 stenotic zones, 0.19 for group 3 stenotic zones, and 0.05 for group 4 stenotic zones (P less than 0.0001). After reaching peak activity, myocardial Tl-201 activity cleared biexponentially with a final decay constant lambda 2 = 0.0017 +/- 0.0001 min-1 (SE) for nonstenotic zones, 0.0011 +/- 0.0001 min-1 for group 2 stenotic zones, and 0.0006 +/- 0.0001 min-1 for group 3 stenotic zones (P less than 0.01). Group 4 stenotic zone Tl-201 clearances were negligible (decay constant essentially zero). Blood Tl-201 activity decayed triexponentially with a final blood lambda 3 = 0.0018 +/- 0.0001 min-1, which was almost identical to the final myocardial lambda 2 decay constant. Thus, the rate of myocardial Tl-201 clearance can distinguish between coronary stenoses of graded hemodynamic severity. These results may be applicable to quantitative techniques for determining myocardial Tl-201 clearance rates on serial clinical images after dipyridamole administration.

1H-NMR spectroscopy can accurately quantitate the lipolysis and oxidation of cardiac triacylglycerols.

Triacylglycerol metabolism in isolated, perfused hearts from rats fed a diet containing 20% rapeseed oil (RSO) was studied using 1H-NMR spectroscopy. RSO-induced elevation in cardiac triacylglycerols is associated with an increase in the peak area of fatty acid 1H-NMR resonances. The ratio of methyl, gamma-methylene or methylene protons adjacent to a carbon-carbon double bond to the number of methylene protons in these hearts measured by 1H-NMR spectroscopy gives values similar to those derived from previously reported chemical analyses. In addition, the triacylglycerol content of these hearts determined by chemical analysis directly correlates with their content of 1H-NMR visible fatty acid resonances. This quantitative relationship allows the real-time measurement of the rates of cardiac triacylglycerol lipolysis using 1H-NMR spectroscopy. Rates of triacylglycerol lipolysis measured using 1H-NMR spectroscopy are similar to those previously measured by chemical methods. Triacylglycerol lipolysis measured using 1H-NMR spectroscopy occurs at a significantly faster rate in hearts perfused in the presence or absence of glucose when compared to hearts perfused with glucose and acetate or medium-chain fatty acids. Finally, the rate of triacylglycerol lipolysis in glucose perfused hearts is linearly related to work output. These results demonstrate that 1H-NMR spectroscopy can accurately quantitate triacylglycerol content and metabolism in the rapeseed oil-fed rat model. 1H-NMR spectroscopic or imaging techniques may be useful in the real-time evaluation of cardiac triacylglycerol content and metabolism.

Effect of decreased blood flow and ischemia on myocardial thallium clearance.

To determine the effect of reduced coronary blood flow on myocardial thallium-201 clearance over a range of flows, miniature radiation detectors were inserted into the left ventricular apex and positioned against the anterior and posterior endocardial walls in 21 dogs. Thallium was administered intravenously and myocardial tracer activity was monitored continuously for 1 hour in both walls. A balloon occluder was then partially inflated around the left anterior descending coronary artery in 19 dogs, producing a range of anterior wall blood flow reductions as assessed by the microsphere technique. Thallium activity was monitored continuously for 3 hours in both walls. Two dogs served as control animals and had no coronary artery occlusion at 1 hour. At the end of the 4 hour experiment, the dogs were sacrificed and the hearts counted in a well counter. The 19 dogs with coronary artery stenosis were divided into three groups (mild, moderate and severe flow reduction groups) on the basis of their poststenosis anterior/posterior wall regional myocardial blood flow ratios. The two control dogs had similar thallium clearances in the anterior and posterior left ventricular walls during the 3 hour period, as assessed by the radiation detectors, and by a final anterior/posterior wall thallium ratio near unity. All three groups of dogs with coronary stenosis had comparable fractional thallium clearances from the anterior and posterior walls before and after the balloon occluder inflation. The final anterior/posterior left ventricular wall thallium ratios were not significantly different than unity for all three groups of dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative split dose thallium-201 imaging with exercise: a technique for obtaining rest and exercise perfusion images in one setting and markedly reducing the study time.

In the current study, a technique for performing serial thallium imaging after two separate tracer injections was applied to exercise thallium imaging, thus allowing the acquisition of rest and exercise images within 1 hour. Twenty-four patients with and 10 patients without significant coronary artery disease were studied. One mCi of thallium-201 was injected intravenously and imaging was performed at rest in three projections. The patient was then stressed and an additional 1 mCi of thallium injected during exercise. Images in the same three projections were collected. After computer realignment, the rest image was subtracted from the exercise image to produce an image representing perfusion during exercise. All 24 patients with coronary artery disease had a positive study, while 9 of 10 without disease had a negative study. The images were then interpreted using a computer method designed to quantitate regional myocardial thallium distribution and redistribution. With quantitative interpretation, 23 of 24 patients with coronary disease had a positive study, while only 1 without disease had a positive study. With qualitative interpretation, 39 (89%) of 44 stenosed coronary arteries demonstrated thallium defects in corresponding myocardial segments, while 54 (93%) of 58 nonstenosed coronary arteries did not. With quantitative interpretation, 38 (86%) of 44 stenosed coronary arteries demonstrated thallium defects in corresponding myocardial segments, while 53 (91%) of 58 nonstenosed coronary arteries did not. A split dose thallium imaging technique that allows imaging before and immediately after exercise, thus markedly reducing the study time, has been validated.

Proton nuclear magnetic resonance relaxation times in severe myocardial ischemia.

Contrast produced by differences in regional proton relaxation times (T1 and T2) provides the potential to assess the extent of myocardial infarction using nuclear magnetic resonance (NMR) imaging. Previous laboratory studies have shown that longitudinal (T1) and transverse (T2) relaxation times are prolonged in acute myocardial infarction, and these prolongations have been attributed entirely to increases in tissue water content. The present study seeks to evaluate the relation between both T1 and T2 and regional myocardial perfusion and water content throughout a wide range of blood flow reduction. The left anterior descending coronary artery and collateral vessels supplying a region of the anterior wall of the left ventricle were ligated in 10 dogs for 4 hours until they were killed. Both water proton and bulk proton relaxation times of myocardial samples from ischemic and control zones were measured at 200 and 20 MHz, respectively. Regions of severe ischemia (flow less than 5% of control) demonstrated no significant alteration in T1 compared with nonischemic myocardium. Greatest T1 and T2 elevations were observed in moderately ischemic myocardium (flow = 5 to 50% of control). The water relaxation behavior differed with the severity of the flow reduction and was not totally dependent on changes in water content. These data suggest that relaxation time alterations are more complex than previously reported in myocardial ischemic insult. In the future, using T1 weighted imaging methods, myocardial ischemic insults associated with severe reductions in blood flow would be anticipated to demonstrate a doughnut pattern with an area of abnormal intensity in the peripheral zone surrounding a central ischemic zone with normal intensity.

Regional variability in the myocardial clearance of thallium-201 and its importance in determining the presence or absence of coronary artery disease.

There are several limitations in using absolute myocardial clearance of thallium-201 for the detection of coronary artery disease. Noncardiac factors such as peak exercise heart rate and blood level of thallium can affect its absolute myocardial clearance. However, because all myocardial segments in a given heart are exposed to the same noncardiac factors, a relative difference in myocardial clearance of thallium between segments could reflect the presence of coronary artery disease. Accordingly, myocardial clearance of thallium was analyzed in 370 patients. Patients in Group I (n = 45) had less than 1% probability of having coronary artery disease, patients in Group II (n = 44) had normal coronary arteries and patients in Group III (n = 281) had coronary artery disease. Although mean myocardial clearance of thallium in 15 myocardial segments in three views in Group I subjects was 3.4 +/- 0.7 hours, the variability between the slowest and fastest clearing segments in the same subject was as much as 98%. This variability was systematic, suggesting technical reasons associated with imaging as the cause of the variability: 78% of the slowest clearing segments were basal whereas 53% of the fastest clearing segments were apical (p less than 0.01). When Group II and III patients were compared based on Group I values, the absolute myocardial clearance of thallium had a sensitivity and specificity of 92 and 16%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

A noninvasive radiographic technique for evaluation of exercise-induced changes in cardiac function.

An electrocardiographic-triggered radiographic technique for obtaining a single image of the heart at both end-systole and end-diastole was used in conjunction with upright bicycle exercise to detect stress-induced changes in 1) systolic and diastolic cardiac transverse diameter, and 2) regional motion of the free left ventricular wall. Twenty-one patients were studied; 10 had normal coronary arteries and 11 had significant coronary artery disease. Twenty patients (10 with normal coronary arteries and 10 with coronary artery disease) also had multigated radionuclide blood pool scans at rest and with exercise. All patients without coronary disease showed a decrease in systolic cardiac transverse diameter with exercise and a slight increase in amplitude of motion of the left ventricular free wall. Eight (73%) of the 11 patients with coronary artery disease showed an increase in systolic transverse cardiac diameter with exercise (p less than 0.001), and 5 developed either new regional left ventricular asynergy or deterioration of segments with rest asynergy. Eight of the 10 patients with coronary artery disease who had rest and exercise radionuclide scans had an abnormal ejection fraction response to exercise. However, only 4 of the 10 control patients who had multigated scans had a normal ejection fraction response, although all showed normal regional wall motion with exercise. This new approach is inexpensive and easily performed. These preliminary data suggest that it may be a useful adjunct to cardiac stress testing and is worthy of further study.

Contrast echocardiography in acute myocardial ischemia: I. In vivo determination of total left ventricular "area at risk".

Myocardial contrast echocardiography has been shown recently to accurately assess the "area at risk" for necrosis after acute coronary occlusion in the experimental model. Risk area quantitation, however, has been studied primarily from single tomographic planes. Because the three-dimensional extent of myocardial necrosis depends on the total volume of myocardium at risk, the total left ventricular "area at risk" was determined in 11 dogs (Group A) with either left anterior descending or left circumflex artery occlusion using contrast echocardiography and compared with risk area determined by technetium autoradiography. An excellent correlation was found between the two methods (r = 0.96%, y = 0.91x + 1.5, p less than 0.001, SEE = 3.17). A comparison of risk area for individual levels of the left ventricle using both methods, however, showed some variation in the degree of correlation, with the poorest fit being apparent at the apex. To identify the source of the variation, errors caused by data registration were minimized in six additional dogs (Group B) by implanting epicardial markers at a single level and measuring "area at risk" at this level using both methods. When no registration error was present, the correlation between the two methods was excellent (r = 0.99, y = 0.92x + 2.6, p less than 0.001, SEE = 0.55). In conclusion, the "area at risk" for infarction after acute coronary occlusion can be determined accurately for the entire left ventricle as well as for a single tomographic slice using myocardial contrast echocardiography. This was validated using technetium autoradiography, which is an established method of determining "area at risk" in the experimental setting.

Right ventricular ejection fraction response to exercise in patients with coronary artery disease: influence of both right coronary artery disease and exercise-induced changes in right ventricular afterload.

To determine the influence of proximal right coronary artery disease and right ventricular afterload on right ventricular ejection fraction response to exercise, 64 patients were studied at rest and after supine exercise with gated equilibrium radionuclide angiography and coronary angiography. Right ventricular afterload response to exercise was estimated from determinations of exercise-induced changes in pulmonary blood volume, previously shown to correlate with exercise-induced changes in pulmonary capillary wedge pressure. Values for right ventricular ejection fraction decreased from rest to exercise (48 +/- 5% to 42 +/- 9%, p less than 0.001) in patients with an elevated pulmonary blood volume ratio. Values were unchanged in patients with isolated proximal right coronary artery disease (rest 49 +/- 3%, exercise 47 +/- 7%), decreased in patients with combined right and left coronary disease (rest 48 +/- 6%, exercise 39 +/- 10%, p less than 0.001) and increased (rest 47 +/- 5%, exercise 52 +/- 6%, p less than 0.001) in patients with isolated left coronary artery disease. To determine the coinfluence of coronary anatomy and changes in pulmonary blood volume, patients were classified by pulmonary blood volume ratio. Among patients with a normal pulmonary blood volume ratio, right ventricular ejection fraction did not change significantly in those with proximal right coronary artery disease during exercise, but increased significantly in patients with isolated left coronary disease. Among patients with an elevated pulmonary blood volume ratio, right ventricular ejection fraction during exercise increased significantly in those with proximal right coronary artery disease but was unchanged in patients with isolated left coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Quantitation of myocardial infarct size from thallium-201 images: validation of a new approach in an experimental model.

A new computer-based method has been developed to quantitate myocardial infarct size from the size of the regional thallium-201 deficit. The operator outlines the left ventricular myocardial activity with an ellipse. The program then plots the background-corrected activities of the highest mean value in a 3 pixel myocardial band perpendicular to and within the ellipse. The approach uses a new interpolative background correction. To determine the accuracy of this approach in assessing regional thallium deficit size, acute myocardial infarction was produced in six dogs by 24 hour occlusion of the proximal left anterior descending coronary artery. Infarct size was assessed from planar thallium images of the dog heart in three views, each with the chest opened and closed and with the heart excised and placed in a cradle. Before removal of the heart, triphenyltetrazolium chloride was infused to delineate normal from infarct tissue. Transverse slices of left ventricle were made and thallium images of the slices acquired. Infarct size delineated by triphenyltetrazolium chloride staining was expressed as a percent of the total left ventricular slice surface area (planimetric infarct size). Infarct size from whole heart and left ventricular slice thallium images was expressed as a percent of the total length of the left ventricular perimeter (perimetric infarct size). This was determined from points below a certain percent of normalized peak thallium activity in the computer-generated thallium activity curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Demonstration of increased myocardial lipid with postischemic dysfunction ("myocardial stunning") by proton nuclear magnetic resonance spectroscopy.

Histopathologic studies have demonstrated accumulation of lipid droplets in myocardium subjected to greater than or equal to 6 h of ischemic insult. Proton nuclear magnetic resonance (NMR) spectroscopy can provide a noninvasive means to evaluate changes in tissue lipid and, potentially, to characterize the ischemic insult. To determine whether lipids accumulate with a brief ischemic insult, myocardial lipid content was evaluated by 1H NMR spectroscopy of ex-vivo samples from seven dogs in a model of postischemic dysfunction created by 15 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Regional myocardial function was assessed by measuring segment length shortening with use of a pair of ultrasonic crystals placed in the ischemic zone and in the control zone. During the occlusion, all dogs had significant ischemia of the occlusion zone as measured by radiolabeled microspheres (0.08 +/- 0.08 versus 0.88 +/- 0.09 ml/g per min for the control zone), and all dogs developed systolic stretching of the ischemic zone segment. Myocardial lipid content was significantly elevated in the samples from the coronary occlusion zone (p less than 0.02). The increase in lipid signal may result from the ischemia-induced decrease in beta oxidation and resultant accumulation of fatty acyl esters (for example, fatty acids, triglycerides and acylcarnitines). In conclusion, this study shows that myocardium subjected to a brief (approximately 15 min) coronary occlusion followed by 3 h of reperfusion demonstrates a significant increase in NMR-detectable lipid content.

Quantitative analysis of dipyridamole-thallium images for the detection of coronary artery disease.

To determine if the detection of coronary artery disease by dipyridamole-thallium imaging is improved by quantitative versus qualitative analysis, and combining quantitative variables, 80 patients with chest pain (53 with and 27 without coronary artery disease) who underwent cardiac catheterization were studied. Segmental thallium initial uptake, linear clearance, monoexponential clearance and redistribution were measured from early, intermediate and delayed images acquired in three projections. Normal values were determined from 13 other clinically normal subjects. When five segments per view were used for quantitative analysis, sensitivity and specificity were 87 and 63%, respectively, for uptake, 77 and 67% for linear clearance, 60 and 60% for monoexponential clearance and 62 and 56% for redistribution. Of the four variables, uptake and linear clearance were the most sensitive (p less than 0.01) and specificity did not differ significantly. Using three segments per view, the specificity of uptake increased (p less than 0.05) to 78% without a significant change in sensitivity (85%). With this approach, sensitivity and specificity did not differ from those of qualitative analysis (85 and 78%, respectively). Stepwise logistic regression analysis demonstrated that the best quantitative thallium correlate of the presence of coronary artery disease was a combination variable of "either abnormal uptake or abnormal linear clearance, or both." Using five segments per view, the model's specificity (85%) was greater than that of uptake alone (p less than 0.02), with similar sensitivity (92%). Using three segments per view, the model's specificity (93%) was greater than that of uptake alone (p less than 0.05) and of qualitative analysis (p less than 0.05), with similar sensitivity (85%).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of the quantitative thallium imaging variables that optimize detection of coronary artery disease.

Although quantification of exercise thallium images has been previously reported, the relative value of different imaging variables for detection of coronary artery disease has not been analyzed in a large group of patients with cardiac catheterization data. Regional initial thallium uptake, redistribution and clearance on thallium study were measured in 325 patients also undergoing cardiac catheterization (281 patients with and 44 patients without coronary artery disease). Normal values were defined in 55 other clinically normal subjects. When five myocardial segments were analyzed in each view, the respective values for sensitivity and specificity were 95 and 50% for initial thallium uptake, 60 and 87% for redistribution and 74 and 66% for clearance. Initial thallium uptake was the most sensitive but least specific (p less than 0.001), whereas redistribution was the least sensitive and most specific (p less than 0.001). Using stepwise logistic regression analysis, the best correlate of coronary artery disease was initial thallium uptake. Addition of redistribution to a mathematical model of the probability of coronary artery disease did not alter sensitivity, but increased specificity from 50 to 70% (p less than 0.001). Once initial uptake and redistribution were considered, myocardial thallium clearance provided no additional improvement in the correlation. Excluding the two basal segments in each view from the analysis increased the specificity from 70 to 80% (p less than 0.001) without affecting sensitivity. Of the 15 patients (5%) with coronary disease not detected using this approach, none had left main disease and 10 (67%) had one vessel disease. A combination of variables derived from quantification of exercise thallium images provides a superior sensitivity and specificity for the detection of coronary artery disease compared with the use of a single variable.

Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain.

Accurate prognostic information is important in determining optimal management of patients presenting for evaluation of chest pain. In this study, the ability of exercise thallium-201 myocardial imaging to predict future cardiac events (cardiovascular death or nonfatal myocardial infarction) was correlated with clinical, coronary and left ventricular angiographic and exercise electrocardiographic data in 139 consecutive, nonsurgically managed patients followed-up over a 3 to 5 year period (mean follow-up, 3.7 +/- 0.9), using a logistic regression analysis. Among patients without prior myocardial infarction (100 of 139), the number of myocardial segments with transient thallium-201 defects was the only statistically significant predictor of future cardiac events when all patient variables were evaluated. Among patients with myocardial infarction before evaluation (39 of 139), angiographic ejection fraction was the only significant predictor of future cardiac events when all variables were considered. This study suggests an approach to evaluate the risk of future cardiac events in patients with possible ischemic heart disease.

Monitoring the bioenergetics of cardiac allograft rejection using in vivo P-31 nuclear magnetic resonance spectroscopy.

Monitoring human cardiac allograft rejection is currently accomplished by endomyocardial biopsy. Available noninvasive methods for identifying rejection have lacked the necessary sensitivity or specificity, or both, for routine clinical application. In vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy has been used for monitoring phosphorus metabolism in both animal models and humans. In the present study this technique was employed as a noninvasive means to assess the bioenergetic processes that occur during cardiac allograft rejection in a rat model. Brown Norway rat hearts were transplanted subcutaneously into the anterior region of the neck of Lewis rat recipients (allografts). Control isografts employed Lewis donors and recipients. Phosphocreatine to inorganic phosphate (PCr/Pi), phosphocreatine to beta-adenosine triphosphate (PCr/ATP beta), beta-adenosine triphosphate to inorganic phosphate (ATP beta/Pi) ratios and pH of the transplanted hearts were monitored using surface coil P-31 NMR spectroscopy (at 4.7 tesla) daily for 7 days. To allow recovery from the compromise induced by the surgical procedure, the measurements obtained on day 2 were taken as a baseline. PCr/Pi was unchanged or increased in the isografts but decreased continually in allografts, with the difference becoming significant by day 4 when compared with levels in day 2 allografts (p less than 0.005) and by day 3 when compared with levels in the isograft group (p less than 0.05). PCr/ATP beta in isografts did not change throughout the study; however, allografts demonstrated a significant decrease as early as day 3 (p less than 0.01), although a significant difference between isografts and allografts did not become manifest until day 4 (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

OBJECTIVE: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. METHODS: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg.kg-1) and propranolol (2 mg.kg-1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. RESULTS: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg.s-1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased -dP/dtmax of -1705(369) mm Hg.s-1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

Quantification of myocardial infarction by computer-assisted positron emission tomography.

The accuracy of three-dimensional transverse section positron emission imaging for quantification of myocardial infarction size was validated and compared with the accuracy of two dimensional planar positron imaging. After induction of acute anterior myocardial infarction in anaesthetised dogs, gallium-68 albumin microspheres were injected into the left atrium. Planar and transverse section images of the thorax were obtained with a multicrystal positron camera. After staining with tetrazolium tetrachloride injected intravenously, the hearts were excised, sectioned manually, and planar imaging repeated. Each myocardial infarction was clearly delineated by transverse section imaging with high contrast ratios (mean 0.68 +/- 0.02 SEM); planar imaging identified seven of nine infarcts but with lower contrast ratios (0.24 +/- 0.04; P < 0.001). The volume of infarcted myocardium determined from transverse section images correlated well with true infarct volume (r = 0.94); whereas planar images poorly predicted infarct size (r = 0.63). Thus, computer-assisted transverse section positron imaging provides in vivo localisation of microsphere distribution for improved radioisotopic quantification of myocardial infarction.

Observations on autoregulation in skeletal muscle: the effects of arterial hypoxia.

Autoregulation of blood flow in skeletal muscle, as manifested by steady-state resistance changes, has been shown to be present in the low range of perfusion pressure but has been demonstrated by some observers to be lacking at higher perfusion pressures. Transient responses have often been neglected or observed only qualitatively in analyses of autoregulation. The present study was undertaken (1) to determine the relative importance of steady-state and transient responses in flow in demonstrating autoregulation of blood flow over a broad range of perfusion pressures, (2) to establish a means of quantitating autoregulation, and (3) to observe the effect of hypoxia on autoregulation. In isolated, perfused canine gracilis muscle, perfusion pressure was increased and subsequently returned to baseline (9.7 +/- 0.13 kPa [73 +/- 1 mmHg]) during perfusion with normally oxygenated blood (PO2 = 9.3-13.3 kPa [70-100 mmHg]), and mildly (PO2 = 6.1-9.2 kPa [46-69 mmHg]), moderately (PO2 = 4.5-6.0 kPa [34-45 mmHg]), or severely (PO2 = 2.7-4.4kPa [20-33 mmHg]) hypoxic blood. Consistent with other studies canine gracilis muscle was often found to possess passive vascular responses when only steady-state parameters were considered. However, quantitation of the transient response in flow with step increases in perfusion pressure demonstrated substantial transient responses under conditions of normal oxygenation, and progressive attenuation of flow transients with increasing hypoxia.