Search

Background: Myocardial cells affected by an infarction endure oxidative stress during reperfusion. It has been suggested that the induction of a heat-shock protein 70 (Hsp72) in myocardial cells counteracts oxidative stress and improves post-ischemic contractile recovery, but clinically relevant methods of inducing Hsp70 in myocardium have yet to be successfully employed. Methods: Mab 3E10 binds extracellular nucleosides, a target that is quite accessible in damaged tissues, allowing 3E10 to penetrate still viable cells through an equilibrative nucleoside salvage pathway. We have developed the scFv fragment of the cell-penetrating 3E10 as an intracellular transporter to deliver exogenous Hsp70. Primary cardiomyocytes exposed to H 2 O 2 were incubated in vitro with a 3E10 scFv-Hsp70 fusion (Fv-Hsp) to demonstrate cytoprotection against oxidative damage. In addition, rabbits were subjected to occlusion of the left coronary artery followed by reperfusion of the heart and intravenous injection of Fv-Hsp (20 mg) or a molar equivalent of a sham control. SPECT imaging and tissue gamma counting of 99m Tc-labeled annexin V was used to visualize the infarct volume and quantify cell death, respectively. Results: In vitro , 30-40% fewer dead cells were observed with Fv-Hsp treatment 30 minutes after exposure, even when 3E10 scFv was added as a competitor (p99m Tc /gram tissue) revealed Fv-Hsp-treated rabbits had less uptake compared to controls (ANOVA); 49% less in the entire area of risk (p Conclusion: Targeted accumulation of Hsp70 at infarcted tissue is achievable and worth investigating further for clinical cytoprotection post-infarction.

BACKGROUND Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. METHODS AND RESULTS Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. CONCLUSIONS We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection.

Objectives: Vulnerability of atheroma is associated with activated macrophage infiltration and apoptosis of foam cells. Activated macrophages have a high metabolic rate, and utilize exogenous glucose as their energy source. The oxidized lipid content of foam cells, is toxic and often results in apoptosis of these cells. Nuclear imaging provides at least two potential indicators to identify vulnerable plaques: 18 F-FDG as a marker of macrophage metabolism and 99m Tc-annexin A5 ( 99m Tc-AN5) as a marker of apoptosis. This study compared the macrophage infiltration and lesion histology to the uptake of each tracer in apolipoprotein E knockout (ApoE−/−) mice. Methods: Male apoE−/− mice (n=4 –5/group) were maintained on a high-fat diet after the age of 5 wks. At the age of 25 and 35 wks, 14 C-FDG and 99m Tc-AN5 were administered and aortas were harvested. Dual-tracer autoradiography, Movat pentachrome staining and Mac-2 staining were performed on serial cryostat sections (n=5– 6/mouse). Regional tracer uptake levels (ID%×kg/mm 2 ) were evaluated in relation to the morphological lesion characteristics (AHA lesion phenotypes) and degree of macrophage infiltration (Mac-2 positive areas). Results: Plaque size and intimal thickness were increased with lesion progression. Macrophage infiltration was increased from early (type I-II) to atheromatous lesions (type III-IV) but decreased in fibroatheromatous lesions (type V). 99m Tc-AN5 showed higher uptake levels in atheromatous lesions (0.49±0.20 %IDxkg/mm 2 ) than early (0.40±0.17) or fibroatheromatous (0.30±0.13) lesions, being concordant with macrophage infiltration. 14 C-FDG uptake was also the highest in atheromatous lesions (3.1±1.5 in atheromatous, 2.8±1.5 in early, and 2.3±1.4 in fibroatheromatous lesions). The uptakes of both 99m Tc-AN5 (r=0.65, p14 C-FDG (r=0.44, p Conclusion: Each tracer showed a higher uptake in atheromatous lesions (AHA type III-IV) than other more stable lesions, directly corresponding to the degree of macrophage infiltration. Unstable plaques can be imaged utilizing 18 F-FDG and 99m Tc-annexin A5, due to the presence of metabolically active and apoptotic macrophages.

Background We tested the hypotheses that prolonged, demand-induced myocardial ischemia plateaus and that on relief of stress, myocardial function remains depressed, with proportionate reductions in blood flow and oxygen consumption indicative of hibernation. Methods and Results Closed-chest swine (n=20) were prepared with an 80% coronary stenosis. Hemodynamics, myocardial blood flow, oxygen, and lactate metabolism were measured in group 1 (n=9) (1) at baseline, (2) at 10 and 30 minutes of atrial pacing plus intravenous norepinephrine infusion, and (3) in 5 of 9 (group 1a) at ≈50 minutes after stress. Group 1a had ischemia assessed with 99m Tc-labeled BMS 181321. In group 2 (n=11), myocardial function was determined with radionuclide ventriculography (n=8), and myocardial necrosis was looked for with trichlorotetrazolium chloride staining (n=7), histology (n=10), and myocardial creatine kinase concentration (n=4). Baseline stenotic-zone endocardial blood flow was reduced versus the normal zone (0.94±0.33 versus 1.38±0.27 mL·min −1 ·g −1 , mean±SD; P −1 ·g −1 ). Stenotic-zone endocardial flow was unchanged versus baseline at 10 and 30 minutes of stress, whereas epicardial flow increased (1.62±0.53 mL·min −1 ·g −1 at 10 minutes and 1.44±0.51 mL·min −1 ·g −1 at 30 minutes, both P −1 ·100 g −1 ) at 10 and 30 minutes of stress (14.9±5.2 and 13.9±4.5 mL·min −1 ·100 g −1 , both P P Conclusions Myocardial ischemia induced by a sustained increase in oxygen demand may not progress to necrosis but may instead plateau. After relief of stress, myocardial function remains depressed, with a proportionate reduction in blood flow and oxygen consumption consistent with myocardial hibernation.

Changes in ventricular function caused by activities of daily living, including standing, walking, stair climbing, and mental stress, were evaluated using a radionuclide device that recorded left ventricular function on a beat-by-beat basis. The ambulatory monitor was positioned over the patient's left ventricle after a gated blood pool scan. Monitoring revealed a 10% increase of left ventricular ejection fraction from baseline to brisk walking, an 18% increase during stair climbing, and a 6% increase with mental stress. In some subjects, however, the increase in ejection fraction during mental stress exceeded that during exercise.

In ischemic cardiomyopathy (CM) fibrosis replaces large segments of myocardium, but in idiopathic congestive CM the myocardium contains only small foci of fibrosis or is morphologically normal. As coronary disease and myocardial infarction may be clinically silent, it is not always possible to distinguish ischemic from idiopathic congestive CM during life without cardiac catheterization. To determine whether noninvasive methods, thallium 201 myocardial (Tl) imaging and technetium 99m gated cardiac blood pool scans (GCBPS), could separate the entities, we evaluated radioisotope images of the heart in 13 patients with ischemic, and eight patients with idiopathic congestive CM, and 14 patients with normal hearts. Diagnosis was setablished by cardiac catherterization and/or autopsy in each of the 35 patients. The 14 normals could be readily distinguished from CM, and ischemic could be distinguished from idiopathic dilated CM in 20 of 21 patients. All patients with myocardiopathy showed hypokinetic and dilated left ventricles, but right ventricular dilatation was evident mainly in those with idiopathic CM. Tl images in the ischemic type had defects of greater than 40% of image circumference which corresponded to segmental wall motion abnormalities on GCBPS, whereas those with the idiopathic congestive form were homogeneous or had defects of less than 20% of image circumference. Autopsy studies in 7 of 35 patients correlated Tl defects of greater than 20% of circumference with transmural myocardial fibrosis.

Twenty-two patients with a history of myocardial infarction and suspected of having a left ventricular aneurysm were evaluated by routine clinical studies, gated cardiac blood pool scanning, and contrast left ventriculography. Thirteen patients were found to have a localized left ventricular aneurysm and nine demonstrated diffuse left ventricular hypokinesis on contrast angiography. The patients with localized left ventricular aneurysms could not be separated from those with diffuse left ventricular hypokinesis on the basis of the routine clinical evaluation including the chest roentgenogram or the finding of ST-segment elevation in the electrocardiogram. Scintiphotographic studies identified the nine with diffuse hypokinesis and twelve of the thirteen with a localized left ventricular aneurysm. In one patient with a calcified left ventricular aneurysm filled with clot, the cardiac blood pool scan showed an area of akinesis which corresponded to that seen on contrast angiography, but the aneurysm could not be detected. In nineteen of the patients in whom adequate measurements were obtained, left ventricular end-diastolic volume and ejection fraction by both contrast angiography and gated cardiac blood pool scintiphotography demonstrated a good correlation, r = 0.92 and 0.87, respectively. There was also a good correlation between the extent of left ventricular akinesis seen on contrast angiography and gated scintiphotography, r = 0.97. This study demonstrates that biplane gated cardiac blood pool scans are useful in differentiating patients with localized left ventricular aneurysms from those with diffuse left ventricular hypokinesis.

Following intravenous administration, the myocardial concentration of tracer thallium-201, potassium-43, and rubidium-81 were determined in mice; thallium was present in the greatest concentration in the myocardium (2.08% compared 1.25% for potassium and 1.15% for rubidium at 10 minutes). The regional myocardial distribution of thallium-201 was determined in dogs under conditions of normal flow, and total occlusion, and compared with potassium-43 (r=0.97). The regional distribution of thallium-201 was compared to microspheres under conditions of partial occlusion and reactive hyperemia (r=0.97). Thallium-201 was evaluated in a series of phantom scans, which demonstrated that the low energy X-ray of thallium was suitable for imaging. These results suggest that thallium-201 can be used for the evaluation of the distribution of regional myocardial perfusion.

After a 4-minute i.v. dipyridamole infusion, 0.14 mg/kg/min, serial thallium-201 scans were obtained in 60 patients undergoing cardiac catheterization. Forty patients had significant (greater than or equal to 50% stenosis) coronary artery disease (CAD), and 20 patients had normal coronary arteries or trivial lesions. The images were graded qualitatively for thallium activity by three observers. Sensitivity was 93% (37 of 40) and specificity was 80% (16 of 20). The sensitivity and specificity of the thallium-201 study were not affected by the extent of CAD, the presence of Q waves, or propranolol therapy. Twenty-seven of 37 patients who had initial defects (73%) had complete thallium redistribution of one or more defects. Patient-by-patient analysis using a regression model of all patients showed that the fate of a segmental thallium defect predicted abnormal wall motion by angiography better than ECG Q waves. The presence of propranolol therapy or collaterals did not significantly affect the thallium redistribution results. We conclude that qualitative interpretation by multiple observers of thallium images after dipyridamole infusion is a highly sensitive and specific test for CAD. After dipyridamole, as with exercise stress, the extent of thallium redistribution is related to the degree of myocardial wall motion abnormality.

To determine the effect of ischemia on myocardial clearance of thallium-201 (201Tl), we studied 12 dogs with ischemia produced after the injection of Tl. Tl was given I.V. 10 minutes before left anterior descending (LAD) coronary artery ligation. 85Sr-microspheres (MS) were administered 5 minutes later, and control biopsies were obtained from the myocardium. The LAD was tied and repeat biopsies obtained from the ischemic zone (IZ) and normal zone (NZ) 15 minures and 2 hours later. 46Sc-MS were given just before the final giopsy. Tl activity in the IZ was not significantly different from that in the NZ either before LAD occlusion or 15 minutes and 2 hours later. Tl clearance at the end of 2 hours was not significantly different (27 +/- 5% vs 28 +/- 5%, IZ vs NZ respectively) between the two zones. The half-time of Tl clearance from both the IZ and NZ was calculated at 4.5 hours (consistent with previously reported normal values). This occurred despite a decrease in regional myocardial blood flow to 24 +/- 6% of control (P less than 0.01) in the IZ and an increase to 47 +/- 14% of control (P less than 0.01) in the NZ during the study. We conclude that myocardial ischemia does not alter the normal rate of Tl clearance from the myocardium.

The appearance of the right ventricular myocardium on thallium 201 myocardial perfusion images was evaluated in patients with chronic pulmonary hypertension and compared to patients without pulmonary hypertension. Four groups of patients were studied: 1) eight normals, 2) five patients with angiographically documented coronary artery disease and normal pulmonary artery pressures, 3) ten patients with moderate to severe pulmonary parenchymal or vascular disease and documented pulmonary hypertension and 4) eight patients with chronic left ventricular dysfunction and pulmonary hypertension discovered during cardiac catheterization. The right ventricular free wall was visualized on the thallium 201 myocardial perfusion image in only one of eight normals (group 1) and in only one of the five patients with coronary artery disease (group 2) and measured 0.5 cm and 0.9 cm in thickness, respectively. In patients with documented pulmonary hypertension the right ventricle was visualized on low contrast thallium 201 myocardial perfusion image in all patients. The apparent right ventricular free wall thickness measured from the ungated thallium 201 myocardial perfusion images was 1.7 +/- 0.3 cm in group 3 and 1.5 +/- 0.2 cm in group 4. Right ventricular hypertrophy was detected by electrocardiography in only five of ten patients in group 3 and only one of eight patients in group 4. Thallium 201 myocardial perfusion imaging appears to be a useful technique for assessing the effects of chronic pulmonary hypertension on the right ventricular myocardium.

A definitive diagnosis of myocarditis requires right ventricular biopsy. Despite its specificity, however, right ventricular biopsy may lack sensitivity due to the focal nature of the disease. Because indium 111-monoclonal antimyosin antibody imaging can be used to detect myocardial necrosis, this procedure was performed on 28 patients clinically suspected of having myocarditis, 25 of whom had left ventricular ejection fractions of less than 45%, and the results were compared with those of right ventricular biopsy performed within 48 hr of the scan. Antimyosin scans were positive in nine patients who had evidence of myocarditis on right ventricular biopsy, and negative in 11 who had no evidence of myocarditis by biopsy. The remaining eight had positive antimyosin scans but showed no evidence of myocarditis on right ventricular biopsy. On the basis of a right ventricular biopsy standard, the sensitivity of this method was 100%, the specificity 58%. We conclude that antimyosin antibody imaging is a reliable screening method for the evaluation of patients suspected of having myocarditis, and that a positive antimyosin scan indicates the need for right ventricular biopsy to establish the histologic diagnosis.

Factors influencing the rate of 201Tl clearance from the myocardium have not been clearly defined. This study determined the effect of an intravenous infusion of glucose-insulin-potassium (GIK) on the net 201Tl clearance rates from myocardium with and without initial 201Tl loading. Anesthetized open-chest dogs underwent 5 min of left anterior descending coronary artery occlusion and intravenous 201Tl was injected and the occlusion released 5 min later. Thirty minutes after 201Tl injection, 30 ml of either GIK (nine dogs) or saline (five dogs) was infused intravenously. The clearance rates of 201Tl from the anterior wall (without initial 201Tl loading) and from the posterior wall (with initial 201Tl loading) were monitored with miniaturized cadmium telluride detectors placed on the myocardium. Calculation of net myocardial clearance rates was performed by linear regression analysis from serial 1 min counts. Compared with saline infusion, GIK increased the net clearance of 201Tl from both myocardial regions with and without initial loading. The most marked change induced by GIK infusion was in the myocardial region without initial 201Tl loading; a net increase in 201Tl activity (72 +/- 42 cpm/30 min) was converted into a net loss (-594 +/- 228 cpm/30 min). There was no significant change in 201Tl clearance after the saline infusion. Heart rate, aortic and left atrial pressure, sonomicrometer-measured transmural myocardial wall thickness, microsphere-determined myocardial blood flow, and blood glucose and potassium concentrations did not change significantly during GIK or saline infusions. Thus, GIK infusion appears to increase net 201Tl clearance from myocardial zones with and without initial 201Tl loading.

Global ventricular function was evaluated by both multiple gated cardiac blood pool scans (MUGA) and contrast ventriculograms in a group of 17 patients with suspected coronary artery disease. The contrast ventriculograms were analyzed frame by frame to generate a volume versus time curve for each patient, while the tracer data were analyzed by two methods: 1) the standard method, in which the left ventricle is identified on the end-diastolic frame and the background corrected activity under the region of interest obtained from the entire cardiac cycle, and displayed as a time versus activity curve; and 2) by a semi-automatic method in which the computer applies a threshold detection program to define the ventricular borders, and activity in the chamber at each point in the cardiac cycle is defined after background correction. The tracer data in each patient were analyzed independently by four observers. The tracer data correlated with the contrast data on a point by point basis r = 0.87 for the standard method, and 0.93 for the semi-automatic technique. An F test of variance revealed the semi-automatic method superior to the standard approach (P less than 0.05).

The Fab fragments of antimyosin antibodies, labeled with 99mTc, were used in the scintigraphic examination of 30 patients with myocardial infarction. The ability to detect necrosis and determine its extent from the antimyosin scan were compared with the results of quantitative regional wall motion analysis by contrast ventriculography at 10 to 14 days and 99mTc-pyrophosphate imaging. Antimyosin images recorded by planar and single photon-emission computed tomography (SPECT) delineated areas of myocardial necrosis in 27 of 30 patients (90%) compared with a 91% sensitivity of pyrophosphate in 21 of 23 patients. Infarct size was determined by both antimyosin and pyrophosphate SPECT images. Results by both techniques showed a significant correlation with computer-derived hypokinetic segment length (r = .79 for both, p = .002) and peak creatine kinase (r = .9 for both, p less than .01). Although sensitivity for and correlations with markers of necrosis were similar with both techniques, infarct size by pyrophosphate SPECT was 1.7 times larger than infarct size by antimyosin SPECT (p less than .01). Certain zones in the infarct area were differentially labeled; the nature and irreversibility of injury within these zones remains to be clarified.

Ten normal volunteers and 38 patients with acute myocardial infarction were evaluated by biplane gated blood pool scanning. The mean left ventricular end-diastolic volume in those with infarction was 125 ± 41 ml/m 2 compared to 82 ± 10 ml/m 2 in the normals. The left ventricular end-systolic volume was 82 ± 35 ml/m 2 compared to 35 ± 4 ml/m 2 , and the left ventricular ejection fraction 36 ± 8% compared to 56 ± 3% in the normals. Thirty-six of the 38 patients with infarction had an area of akinesis which ranged from 15 to 59% of the left ventricular wall. Patients with acute myocardial infarction were found to have a significant increase in left ventricular end-systolic volume and decrease in ejection fraction compared to normals. The end-diastolic volume was, however, increased only in those with an elevated left ventricular filling pressure or decreased cardiac index. Follow-up studies obtained in 20 patients between one week and three months following infarction showed that in the 14 who improved clinically, left ventricular ejection fraction significantly increased from 38 to 45% ( P < 0.001) while in six who failed to show clinical improvement or worsened, left ventricular ejection fraction remained at 30%. Left ventricular ejection fraction was significantly greater and the extent of akinesis significantly less in the patients who survived compared to those who died.

The effectiveness of intra-aortic balloon pumping in augmenting ventricular performance during acute myocardial ischemic syndromes was determined by noninvasive multigated cardiac blood pool imaging. Nine patients with unstable angina refractory to medical therapy and nine patients with acute myocardial infarction complicated by congestive heart failure were studied on and off intra-aortic balloon pumping (IABP). End-diastolic and end-systolic volumes were significantly reduced by IABP in both unstable angina and myocardial infarction. Analysis of ventricular wall motion demonstrated improved segmental contraction during IABP in all seven unstable angina patients with regional wall motion abnormalities. No significant improvement in regional contraction was observed in the nine patients with acute myocardial infarction. During IABP, percent ventricular asynergy decreased significantly (28.2%; P0.01) among patients with unstable angina but demonstrated no significant fall (4.4%; P = NS) for patients with myocardial infarction. Thus, IABP enhances contraction of ischemic but not infarcted myocardium and effectively improves ventricular function by reducing end-diastolic and end-systolic volumes.

By careful selection of the study or studies performed, it is possible to obtain information about many facets of the myocardium and cardiac function. These measurements when coupled with those of the clinical evaluation, routine chemistry tests and electrocardiogram can frequently make diagnosis, confirm the site, and extent of abnormality and define if improvement has occurred following a therapeutic intervention. Radionuclide studies offer a particularly useful tool in cardiology because they measure physiological parameters, and through these measurements, give information about anatomy. In the future, specific metabolic substrates which are metabolized only in ischemic tissue may be developed, and it is not out of the realm of possibility that radiopharmaceuticals will be developed which will localize in atherosclerotic plaque and permit the identification of patients at risk of coronary disease long before they become symptomatic.

Twenty-seven patients with acute myocardial infarction not complicated by cardiogenic shock and ten normal volunteers were studied with gated cardiac blood pool scans. The ratio right vetricular area/left ventricular area (RVA/LVA) determined from the left anterior oblique end-diastolic scans was examined. The ratio was 1.11 +/- .06 in the normal volunteers. In patients with anterior infarction the ratio fell to 0.75 +/- .12 (P less than .05) due to left ventricular enlargement. In those with inferior infarction the ratio was 1.12 +/- .23 which was greater than in those with anterior infarction (P less than .05) due to enlargement of both the left and right ventricles. Six patients with cardiogenic shock, three with inferior and three with anterior infarction were studied. The three with anterior infarction had left ventricular enlargement and a decrease in the ratio of RVA/LVA to 0.62 while the three with inferior infarction had an increase in the ratio to 2.05 suggesting right ventricular dilatation and dysfunction. These studies suggest a high incidence of right ventricular dysfunction in patients with inferior myocardial infarction.

Diagnosis of rejection after cardiac transplantation is currently made by right ventricular endomyocardial biopsy. To evaluate antimyosin imaging as a noninvasive means of detecting human cardiac rejection, the Fab fragment of murine monoclonal antimyosin antibodies was labeled with indium-111 and given intravenously to 18 patients (age 45 +/- 12 years) in 20 studies 7 days to 9 years after transplantation. Endomyocardial biopsy specimens were obtained at the time of each imaging study. Eight patients had positive scans confirmed by biopsy as rejection, and eight patients had negative scans and no evidence of rejection on biopsy. Discordance was observed in four studies, two with positive scans and no rejection on biopsy and two with negative scans and positive biopsy. The sensitivity, specificity, and overall accuracy of the technique were each 80%. Imaging with radiolabeled antimyosin antibody Fab fragments may be of value in the noninvasive identification of rejection in the cardiac transplant recipient.

Abnormalities of left ventricular function and extent of myocardial infarction were studied in relation to prevalence of late ventricular premature contractions (VPCs) in 36 patients in the convalescent stage of acute myocardial infarction (MI). Left ventricular ejection fraction (EF) and percent akinesis (%A) were calculated from gated cardiac blood pool scans; myocardial infarct size was estimated from peak CPK values; and VPCs were detected by 24 hour ambulatory ECGs 2-4 weeks following hospitalization for acute MI. Twenty-two patients had either zero (class 0) or less than 30/hour unifocal VPCs (class I). Fourteen patients had greater than 30/hour unifocal (class II), multifocal (class III) or coupled VPCs (class IV), including ventricular tachycardia. Thirteen of 14 class II-IV patients had EF less than 40% compared with only 8 of 22 class 0-I patients. Class II-IV patients had significantly lower mean EF (30.5 +/- 2.3 SE to 49.6 +/- 4.0) P less than 0.01, higher mean %A (28.1 +/- 2.2 to 16.9 +/- 3.7) P less than 0.05, and higher mean peak CPK (1350 +/- 187 to 721 +/- 155) P less than 0.05 than class 0-I patients. These data suggest that VPCs may not be an independent risk factor for sudden cardiac death in the convalescent phase of MI.

SUMMARY Theeffect ofexercise-induced myocardial ischemia oncardiopulmonary blood volume was evaluated inpatients withcoronaryartery disease during upright exercise stress testing. Regional pulmonary andcardiac blood volumes weremonitored with amulticrystal positron camerapositioned overthechest duringmaximal exercise on a bicycle ergometer. Inhaled carbon monoxide (

The effects of abrupt withdrawal or continuation of beta-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a beta-blocker and randomly selected for withdrawal of beta-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with beta-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 +/- 10.9 vs 18.2 +/- 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 +/- 0.15 vs 0.47 +/- 0.16) or 10 days later (0.42 +/- 0.14 vs 0.47 +/- 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of beta-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior beta-blockade therapy (group 4). This comparison yielded similar results. These data indicate that the beta-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. beta-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equal to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. Group 1 patients also had a higher mean rest ejection fraction (0.64 +/- 0.08 vs 0.49 +/- 0.13, p less than 0.01, higher exercise ejection fraction (0.63 +/- 0.10 vs 0.40 +/- 0.18, p less than 0.01), lower end-systolic volume (38 +/- 13 vs 79 +/- 36 ml/m2, p less than 0.01) and higher peak oxygen uptake (24.9 +/- 5.1 vs 16.6 +/- 4.9 ml/kg/min, p less than 0.01) than group 2 patients. However, the two groups had similar cardiothoracic ratios, changes in ejection fractions with exercise, and rest and exercise regurgitant indexes. Using multiple regression analysis, the best correlate of the exercise PAWP was peak oxygen uptake (r = -0.78, p less than 0.01). No other measurement added significantly to the regression. When peak oxygen uptake was excluded, rest and exercise ejection fraction also correlated significantly (r = -0.62 and r = -0.60, respectively, p less than 0.01). Patients with asymptomatic or minimally symptomatic severe aortic regurgitation have a wide spectrum of cardiac performance in terms of the PAWP during exercise. The absolute rest and exercise ejection fraction and the level of exercise achieved are noninvasive variables that correlate with exercise PAWP in aortic regurgitation, but the change in ejection fraction with exercise by itself is not.

The concentration of thallium-201 in the myocardium immediately following injection of tracer is the result of both blood flow delivering tracer to the heart and extraction by the myocardium. In these studies, the extraction of thallium-201 by the canine myocardium was determined as a function of heart rate, coronary blood flow, hypoxia, changes in pH, and following administration of propranolol, insulin, and strophanthin. Under basal conditions, extraction fraction measured 88 +/- 2.1%, following pacing to a rate of 195 beats/min extraction fraction remained unchanged at 88.5%. Similar results were found with changes in pH, propranolol, insulin, and strophanthin. Hypoxia caused a significant decrease in extraction fraction to 77.9%. When coronary blood flow was increased in excess of demands by drugs, extraction fraction fell logarithmically.

One hundred and eleven patients with transmural (TMI) and 49 with nontransmural myocardial infarction (NTMI) underwent hemodynamic investigation within 24 hours of onset of symptoms. Patients with NTMI were subdivided into those with ST-segment or T-wave changes alone with a normal QRS complex (NTMI-A) and a group with QRS abnormalities that did not satisfy the criteria for TMI (NTMI-B). Those with TMI had a significantly higher peak creatine phosphokinase (CPK) than those with NTMI: 840 plus or minus 99 and 336 plus or minus 69, respectively, P smaller than 0.05. There was not difference in peak CPK between those with NTMI-A and B. The incidence of arrhythmias and cardiac failure, and routine hemodynamic findings except for left ventricular filling pressure were similar in those with TMI and NTMI. There was not significant difference in in-hospital mortality between those with TMI (22%) and NTMI (33%). There was however a significant difference in in-hospital mortality between those with NTMI-A (0%) and NTMI-B (27%, P smaller than 0.05). The late mortality in those surviving their initial hospitalization was also not different between those with TMI (18%) and NTMI (19%) during a mean follow-up period of 20.2 months. In contrast to the in-hospital mortality those with NTMI-A had a late mortality similar to those with NTMI-B and those with TMI.

Defects on resting thallium-201 (/sup 201/Tl) scans in patients who do not have evidence of acute myocardial ischemia have been thought to represent myocardial scar. Our study of 20 patients with stable but severe coronary artery disease (CAD) was undertaken to reexamine the significance of such defects. Images in each of two projections were divided into three zones, for a total of 120 zones in 20 patients. An initial defect was present in 43 zones in 15 patients, while five patients demonstrated totally normal studies. On later scans, 18 defects persisted while 25 filled in. Twelve of 18 persistent defects were associated with ECG evidence of infarction, compared with only six of 25 transient defects. Six of 12 persistent defects, compared with only one of 18 transient defects, were associated with akinesia/dyskinesia. In addition, 17 of 18 transient defects were associated with either normal left ventricular wall motion (12 defects) or hypokinesia (five defects). Finally, 23 of 25 transient defects, compared with only 41 of 77 normal zones, were associated with severe CAD. Thus, in resting patients with stable CAD: (1) serial imaging reveals that many initial defects fill in over time; (2) initial resting defects on Tl scans maymore » not indicate myocardial scar; and (3) transient defects are usually associated with severe CAD, but normal or only mildly abnormal left ventricular wall motion.« less

Myocardial thallium-201 (/sup 201/Tl) kinetics have not been precisely defined because reliable techniques to determine continuous activity in vivo have not been available. In this study, an implantable miniature cadmium telluride radiation detection device was inserted through the left ventricular apex, positioned against the endocardium, and used for continuous on-line monitoring of myocardial /sup 201/Tl activity for 260-810 minutes in 18 dogs. Blood was serially sampled and counted. Microsphere-determined myocardial blood flow was measured before administration of /sup 201/Tl and was not significantly different from that measured at the end of the experiment in 11 of 18 dogs. Thallium was administered intravenously. Myocardial and blood activity curves were analyzed using a nonlinear least-squares estimation of the decay constant lambda (min/sup -1/). The mean final blood lambda/sub 3/ was almost identical to the mean myocardial lambda. The data suggest that /sup 201/Tl washout after peak activity is reached in nonischemic myocardium is mono-exponential. The rate of /sup 201/Tl clearance from the myocardium is related to the rate of /sup 201/Tl clearance from the blood after i.v. administration of the tracer.