Differentiation of reperfused-viable (stunned) from reperfused-infarcted myocardium at 1 to 3 days postreperfusion by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy.

Thrombolytic therapy has increased the need for a technique to assess the viability of recently reperfused myocardium. This study examined the ability of in vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy to distinguish reperfused-viable (stunned) from reperfused-infarcted myocardium at 6, 30, and 54 hours following coronary artery occlusion in a canine model. A 15-minute occlusion produced reperfused-viable myocardium in five animals and a 360-minute occlusion produced reperfused-infarcted myocardium in six animals. Postreperfusion risk zone myocardial phosphocreatine (PCr) concentration measured by P-31 NMR spectroscopy was significantly depressed throughout the 3-day study period in infarcted but not in viable myocardium (p less than 0.01 between groups, all time points). The postreperfusion ratio of inorganic phosphate (Pi) to PCr concentration, as determined by NMR spectroscopy, was elevated throughout the study period in infarcted but not in viable reperfused myocardium (p less than 0.01 between groups, all time points). Postreperfusion Pi concentration was elevated at 6 hours but not subsequently in reperfused-infarcted myocardium, and was not elevated in reperfused-viable myocardium. Logistic regression models selected PCr concentration and the Pi/PCr ratio as providing the best discrimination between reperfused-viable and reperfused-infarcted myocardium. The accuracy of P-31 NMR variables selected by logistic regression analysis for determining myocardial viability ranged from 97% to 100%.

Effect of brief regional ischemia followed by reperfusion with or without superoxide dismutase and catalase administration on myocardial sarcoplasmic reticulum and contractile function.

The effect of reperfusion with and without free radical scavengers on sarcoplasmic reticulum and contractile function was examined in a canine model of 15-minute coronary artery occlusion followed by reperfusion. Dogs were reperfused with (n = 13) or without (n = 16) superoxide dismutase and catalase or were killed at 15 minutes of ischemia (n = 17). Superoxide dismutase and catalase were administered as a bolus (20,000 and 12,500 U/kg, respectively) beginning 1.25 minutes before reperfusion followed by infusion of 16,000 and 12,500 U/kg/hr, respectively. Sarcoplasmic reticulum function was evaluated from the rate of calcium uptake of unfractionated subepicardial, subendocardial, and transmural homogenates determined with and without ruthenium red to close the calcium release channel. Mechanical function was evaluated by means of sonomicrometry. Fifteen minutes of ischemia significantly (p less than 0.05) depressed the sarcoplasmic reticulum calcium uptake rate only in the subendocardium (from 25 +/- 2 to 14 +/- 1 nmol/min/mg without ruthenium red and from 60 +/- 3 to 49 +/- 3 nmol/min/mg with ruthenium red). Reperfusion with or without superoxide dismutase and catalase restored homogenate calcium uptake rates to normal, although severe contractile dysfunction persisted. This indicates that damage to the sarcoplasmic reticulum may not be the major cause of postreperfusion contractile dysfunction. Ischemia-reperfusion caused a decrease in systolic shortening from 19 +/- 2% to 1 +/- 2% with and from 18 +/- 1% to 4 +/- 1% without free radical scavengers (p = NS between groups). Thus administration of superoxide dismutase and catalase beginning shortly before reperfusion had no effect on postreperfusion contractile dysfunction or sarcoplasmic reticulum function.

Effect of variation in heart size on quantitative thallium SPECT.

Quantitative single-photon emission tomographic (SPECT) thallium 201 (201Tl) cardiac studies are frequently used to improve test accuracy. One common technique uses polar mapping of relative tracer distribution to compare patient data to emplates from "normal" patient data. Commercial software does not correct for cardiac size variations. This study's purpose was to determine the effect of uncorrected variations in heart size on the variance of the normal population, which is the basis of template significance levels. Twenty-one male volunteers with low probability (less than 5%) for coronary disease underwent SPECT-Tl stress test. Data analysis with and without size correction was performed. Data were corrected for size by use of a three-dimensional compression/expansion algorithm. Quantitative data were generated by radial search to maximum activity in short-axis reconstructions. The mean activity and its variance was calculated from 288 points encompassing the myocardium. Mean and variance differences were analyzed by paired t test. There was no difference in activity means (pT greater than .9), indicating that size correction does not distort the data. The corrected data had, however, significantly lower variance (pT less than .0001). This shows that ventricular size variation contributes significantly to "normal" template variance and may adversely affect diagnostic accuracy in the absence of volume correction.

Magnetic resonance imaging of cardiac rhabdomyosarcoma. Quantifying the response to chemotherapy.

This report illustrates the use of cardiac magnetic resonance imaging (MRI) to quantify the initial extent of a cardiac rhabdomyosarcoma and, more importantly, its response to chemotherapy. Image slices spanning the heart and adjacent structures were analyzed using Simpson's rule applied to the image slices to estimate the tumor volume initially, then after 5 weeks, and again after 4 months of chemotherapy. A substantial, progressive reduction in tumor volume during chemotherapy was shown. After chemotherapy was discontinued, an increase in tumor volume was shown. It is suggested that, in addition to being useful in patient care, the technique may be useful in clinical investigations by providing an objective, quantitative measure of tumor response to therapy.

Comparison of atrial contribution to cardiac hemodynamics in patients with normal and severely compromised cardiac function.

The importance of atrial contribution to cardiac function in patients with congestive heart failure is controversial. Ten patients with severe congestive failure (Group A) and 10 patients with normal ventricular function (Group B) were studied during atrial and ventricular pacing. Left ventricular ejection fraction, baseline pulmonary capillary wedge pressure, and baseline cardiac index were different between Group A and Group B patients: 22 +/- 10 vs. 65 +/- 11 (p less than 0.01); 21 +/- 5 vs. 8 +/- 4, (p less than 0.01); and 2.8 +/- 0.5 vs. 3.5 +/- 1.0 (p = 0.05). Compared with atrial pacing, cardiac index decreased from 2.8 +/- 0.6 to 2.2 +/- 0.5 (p less than 0.01) in Group A and from 3.6 +/- 0.7 to 2.9 +/- 0.5 (p less than 0.01) in Group B, during ventricular pacing. Pulmonary capillary wedge pressure increased by similar amounts in both groups during ventricular pacing. The change in cardiac index, % change in cardiac index, and change in pulmonary capillary wedge pressure from atrial to ventricular pacing, were not different between Group A and Group B patients. By logistic regression analysis, no association was found between the % change in cardiac index and the following variables: left ventricular ejection fraction, left ventricular end-diastolic volume, baseline pulmonary capillary wedge pressure, change in pulmonary capillary wedge pressure, and baseline cardiac index. The atrial contribution to resting steady-state cardiac function is similar between patients with severe congestive failure and those with preserved ventricular function.

Enzyme kinetics and relaxation measurements with surface coils.

A pulse sequence which produces the inversion of magnetization at a selected chemical shift for in vivo surface coil spectroscopy is proposed. The sequence uses a shaped, complex sech inversion pulse and "depth pulse" phase alternation. The sequence can be used for both in vivo inversion transfer and inversion recovery experiments.

Reperfused-viable and reperfused-infarcted myocardium: differentiation with in vivo P-31 MR spectroscopy.

The ability of in vivo phosphorus-31 magnetic resonance (MR) spectroscopy to permit accurate distinction between reperfused-viable and reperfused-infarcted myocardium was examined in a canine model of acute coronary occlusion. In vivo myocardial pH and phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were measured at baseline and for the first 90 minutes after reperfusion of a total coronary artery occlusion producing either predominantly viable (nine animals) or infarcted (nine animals) myocardium in the region of metabolic study. Myocardial viability was assessed in each animal by means of postmortem triphenyltetrazolium chloride staining. Tissue was characterized from the in vivo P-31 MR data by means of logistic regression analysis. The accuracy of using the P-31 MR data for distinguishing reperfused-viable from reperfused-infarcted myocardium was 100% (69 of 69 data points, 18 of 18 animals). Results of the logistic regression procedure indicated that phosphocreatine was the metabolic variable enabling most effective separation of reperfused-viable and reperfused-infarcted myocardium. Thus, metabolic data obtained with P-31 MR spectroscopy permit effective separation of reperfused-viable from reperfused-infarcted myocardium.

Angiographic observations and clinical relevance of coronary thrombus in unstable angina pectoris.

To assess the mechanisms of unstable angina, the coronary angiographic studies in 69 patients with severe unstable angina (prolonged pain or pain at rest) and in 20 patients with stable angina were blindly reviewed to assess the coronary morphologic changes in these syndromes. Coronary angiography was performed an average of 1.7 days from admission and an average of 24 hours from last symptoms of chest pain in patients with unstable angina. Angiographic studies were analyzed for evidence of coronary thrombus (intraluminal filling defects) at significant stenoses in patent vessels or thrombus at sites of total occlusion) and for coronary lesion morphology suggesting a complex or acute lesion (irregular or ill-defined margins, inhomogeneity, haziness or ulceration). Angiographic evidence of coronary thrombus was present in 40 of 69 patients (58%) with unstable angina: 31 (45%) had intraluminal filling defects and 9 (13%) had thrombotic total occlusion with well-developed collaterals present. Only 1 of 20 patients (5%) with stable angina had evidence of thrombus (p less than 0.001). Complex lesions were present in 18 other unstable patients (26%) and in 2 other patients (10%) with stable angina who did not have angiographic evidence of thrombus. Overall, 58 of 69 patients (84%) with unstable angina had morphologic findings suggesting an acute process (thrombus or complex lesion) compared with 3 of 20 patients (15%) with stable angina, p less than 0.0001. Thus, unstable angina is associated with a high prevalence of angiographic coronary thrombus and complex lesions suggesting an acute process, in contrast to stable angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary artery thrombus detection by magnetic resonance imaging.

We report a patient in whom cardiac magnetic resonance imaging detected a clinically unsuspected pulmonary artery thromboembolus. Follow-up MRI after surgical removal of the thromboembolus showed normal pulmonary arteries. This case illustrates the potential utility of MRI in the detection and follow-up of central pulmonary artery thromboembolism.

Thallium-201/technetium-99m-RP-30A disparity in the course of myocardial infarction after attempted reperfusion.

Recent reports have established that 201Tl may be taken up in areas of recent myocardial infarction after myocardial blood flow is re-established. In addition, there is accelerated 201Tl "washout" from these regions producing a pattern of "reverse redistribution." We present a case in which these phenomena may have contributed to a disparity of findings between a 201Tl stress imaging study and a repeat stress imaging study performed with a [99mTc] isonitrile (99mTc-RP-30A).

Effective separation of normal, acutely ischemic, and reperfused myocardium with P-31 MR spectroscopy.

The ability of phosphorus-31 magnetic resonance (MR) spectroscopy to accurately characterize myocardium as normal, ischemic, or reperfused but viable was examined in the canine model of acute coronary artery occlusion. P-31 MR measurements of in vivo myocardial pH, phosphocreatine, adenosine triphosphate, and inorganic phosphate levels were made at baseline and for 6 hours after sustained coronary occlusion (ten animals) or coronary occlusion reperfused after 60 minutes (12 animals). Ten control animals were studied in parallel fashion, without coronary occlusion. Myocardial tissue characterization derived from the P-31 MR spectroscopy data by logistic regression analysis had an overall accuracy of 89%. Overall accuracy was unaffected by duration between coronary occlusion and P-31 MR study. Thus, metabolic data obtained with P-31 MR spectroscopy effectively separate normal, acutely ischemic, and reperfused but viable myocardium.

Association between extent of coronary artery disease and ventricular premature beat frequency after myocardial infarction.

Severe coronary artery disease (CAD) and frequent ventricular premature beats (VPBs) on ambulatory ECG monitoring in the late hospital phase after myocardial infarction are independent predictors of prognosis. To study the relationship between extent of CAD and VPB frequency, 128 consecutive (91 men, 37 women) patients surviving 6 days after myocardial infarction underwent 24-hour ECG, coronary angiography, and left ventriculography. CAD was graded as zero to one-, two-, and three-vessel (V), and also by a previously validated "jeopardy score" with 0 to 12 as grades of incremental CAD severity. Average VPB frequency was significantly correlated with CAD by V, CAD by jeopardy score, and by left ventricular ejection fraction (p less than 0.01 for all three). With the use of a multivariate ordinal logistic regression model, both VPB frequency and left ventricular ejection fraction were found to have independent association with CAD. The median VPB frequency was 1/hr, 0.6/hr, and 6/hr in zero to one-, two-, and three-V CAD, respectively (zero to one- and two-V CAD vs three-V CAD p less than 0.01, one-V CAD vs two-V CAD p = NS). In conclusion, frequent VPBs following myocardial infarction are associated with extensive CAD and are independent of left ventricular ejection fraction. Therefore, the prognostic value of frequent VPBs may be related to severe underlying ischemic disease.

Intracellular myocardial pH measured in vivo with sustained and reperfused coronary occlusion.

Intracellular pH provides an important measure of the adequacy of local tissue perfusion. The purpose of this study was to measure regional intracellular myocardial pH (impH) in the ischemic zone in vivo during experimental canine coronary occlusion, with and without coronary reperfusion. Twenty adult dogs were studied. Ten dogs underwent permanent ligation of the proximal anterior left descending coronary artery (group L), five dogs had coronary reperfusion after 1 hour of total coronary occlusion (group R), and five dogs did not undergo ligation and served as controls (group C). Intracellular myocardial pH was measured by 31phosphorus nuclear magnetic resonance spectroscopy at baseline and then at 15-minute intervals for 6 hours after coronary occlusion (or after sham occlusion in group C). Baseline impH did not differ among groups (group C, 7.22 +/- 0.12 mean +/- standard error of mean; group L, 7.17 +/- 0.07; group R, 7.22 +/- 0.09). During hour 1 of total occlusion, the impH of both groups L (6.58 +/- 0.05) and R (6.55 +/- 0.08) was significantly reduced as compared with the impH of group C (7.3 +/- 0.12; p less than 0.05). At 0 to 1, 1 to 3, and 3 to 5 hours of reperfusion, the impH of group R (7.34 +/- 0.08, 7.27 +/- 0.07, and 7.29 +/- 0.06, respectively for these times) did not differ from group C (7.26 +/- 0.11, 7.21 +/- 0.07, and 7.25 +/- 0.10). At these same times, the impH of group L (6.47 +/- 0.05, 6.57 +/- 0.04, and 6.75 +/- 0.04) was significantly reduced as compared with both groups R and C (p less than 0.05). Thus a severe, persistent regional intracellular myocardial acidosis occurs in the ischemic zone with coronary occlusion but is rapidly corrected by reperfusion within 1 hour.

Contrast injection bradycardia during coronary angiography: effects in the denervated human heart.

To assess the contribution of cardiac innervation toward understanding the mechanisms of bradycardia during contrast coronary angiography, heart rate (HR) responses in eight patients after heart transplantation were compared with 10 normal patients (control), 10 patients with coronary artery disease (CAD) and normal ventricular function, and 10 patients with congestive cardiomyopathy and normal coronary arteries. The longest P-P interval was measured beat to beat before (HR 1) and after (HR 2) coronary angiography. The coronary vessel perfusing the sinus node did not influence HR 2 responses within each group. HR 1 was significantly different from HR 2 (p less than 0.05) in the control and CAD groups but was not different in the transplant and cardiomyopathy groups. Compared with the control group, the percent decrease in HR was significantly less in transplant patients than in patients with cardiomyopathy. Thus contrast injection bradycardia is absent in denervated patients after heart transplant, and this response is markedly blunted in cardiomyopathy patients who are known to have diminished vasodepressor reflexes. These findings suggest that the bradycardia response is probably a neurally mediated phenomenon.

Thrombosis in unstable angina: angiographic aspects.

Angiographic studies in patients with unstable angina indicate that intracoronary thrombus is present in a substantial proportion of patients with unstable angina who have early angiography and that these patients often have distinctive coronary lesion morphology that may represent a marker for instability. These studies, in conjunction with recent histopathologic studies demonstrating plaque defects and overlying thrombosis in patients with unstable ischemia and sudden death, suggest a common mechanism for unstable angina and myocardial infarction and strongly support the rationale for antithrombotic therapy with heparin and with aspirin in the management of patients with unstable angina.

Nuclear magnetic resonance study of high-energy phosphate stores in models of adriamycin cardiotoxicity.

Previous studies have suggested that one of the mechanisms of adriamycin (ADR) cardiomyopathy is depletion of high-energy phosphate stores (HEP). To examine this hypothesis, we used 31P nuclear magnetic resonance to assess the adenosine triphosphate-to-phosphocreatine ratio (ATP-to-PCr ratio) in Langendorff-perfused rabbit hearts. Using either an acute (5 days of therapy at 5 mg/kg/day) or chronic model (7 to 10 weeks of therapy at 1.2 or 1.5 mg/kg twice a week), we compared isovolumetric LV systolic pressure, heart rate, ATP-to-PCr ratios, and histologic lesions between the treated and control animals in each model. In the acute model, there was a significant increase in the ATP-to-PCr ratio (P less than 0.02), without significant changes in myocardial function. Despite significant hemodynamic and histologic alterations in the chronic model, compared to controls, we were unable to identify significant differences in ATP-to-PCr ratios. We conclude that there appear to be differences in energy metabolism between the acute cardiotoxicity and the chronic cardiomyopathy of ADR in the rabbit model and the mechanism of the chronic cardiomyopathy from ADR therapy does not appear to be related to progressive impairment of cellular high-energy phosphate metabolism as measured by the ATP-to-PCr ratio.

Detection and localization of recent myocardial infarction by magnetic resonance imaging.

The potential of magnetic resonance imaging (MRI) to detect and localize acute myocardial infarction (AMI) in 27 patients a mean interval of 15 days after AMI was evaluated. Eighteen asymptomatic volunteers were also studied to determine the specificity of the observations. The diagnosis of AMI was established by conventional criteria; the infarct was localized by electrocardiography in all patients, technetium pyrophosphate scintigraphy in 19 and necropsy in 1 patient. MRI detected increased myocardial signal intensity in 88%, cavitary signal in 74% and regional wall thinning in 67% of the patients. At least 1 of these 3 features was seen in the area of the infarct in each patient. The sensitivity of these MRI observations was not influenced by location of the infarct or presence of Q waves. Asymptomatic volunteers also had increased myocardial signal in 83%, cavitary signal in 94% and wall thinning in 11% of cases. Some patients had these findings in myocardial segments not suspected of being involved by recent or remote AMI. It is concluded that AMI can be detected by MRI performed an average of 15 days after infarction. However, the hearts of normal volunteers and apparently normal myocardial segments of patients with AMI may have the MRI findings previously associated with AMI. Of these findings, wall thinning was the most predictive of and specific for AMI.

Improved in vivo magnetic resonance imaging of acute myocardial infarction after intravenous paramagnetic contrast agent administration.

Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), a paramagnetic relaxation agent, has been used in vitro to improve the detection of acute myocardial infarction (MI) by magnetic resonance imaging (MRI). In this study, the ability of Gd-DTPA to improve in vivo magnetic resonance imaging of MI was examined. Ten dogs with MI caused by left anterior descending coronary artery ligation were imaged 1 to 5 days after infarction. Imaging was performed before and for 2 hours after intravenous administration of 0.34 mmol/kg Gd-DTPA. One to 2 days after MI, Gd-DTPA improved visualization of the infarct in 3 of 4 dogs. This effect was more prominent in dogs imaged 4 to 5 days after MI, when 6 of 6 dogs showed substantially improved infarct definition after Gd-DTPA. At both times the intensity ratio, an objective measure of contrast between infarcted and normal tissue that is defined by the ratio of image intensity of infarcted area to that of noninfarcted area, was significantly better after Gd-DTPA administration. The intensity ratio at 24 to 48 hours after infarction was 1.4 +/- 0.2 (mean +/- standard deviation) before Gd-DTPA, and 1.7 +/- 0.6 after Gd-DTPA (p = 0.03). The intensity ratio at 4 to 5 days after infarction was 1.5 +/- 0.3 before Gd-DTPA, and 1.8 +/- 0.5 after Gd-DTPA (p less than 0.001). Thus, Gd-DTPA administration improves in vivo visualization of MI by MRI.