Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding.

The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity. Ability of the myocardial cell to bind tritiated ouabain in vivo was assessed after 1, 2, and 6 h of coronary occlusion followed by 45 min of reperfusion, and correlated with measurements of in vitro (Na+ + K+)-ATPase activity and in vitro [3H]ouabain binding after similar periods of ischemia. Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related. Anterior wall infarction was produced in 34 dogs by snaring of confluent branches of the left coronary system. Epicardial electrograms delineated ischemic and border zone areas. Coronary reperfusion after 2 and 6 h of occlusion was associated with impaired reflow of blood and markedly impaired uptake of [3H]ouabain in ischemic myocardium. In both groups, in vivo [3H]ouabain binding by ischemic tissue was reduced out of proportion to the reduction in flow. Despite near-complete restoration of flow in seven dogs occluded for 1 h and reperfused, [3H]ouabain remained significantly reduced to 58 +/- 9% of nonischemic uptake in subendocardial layers of the central zone of ischemia. Thus, when coronary flow was restored to areas of myocardium rendered acutely ischemia for 1 or more hours, ischemic zones demonstrated progressively diminished ability to bind ouabain. To determine whether ischemia-induced alteration in myocardial (Na+ + K+)-ATPase might underlie these changes, (Na+ + K+)-ATPase activity and [3H]ouabain binding were measured in microsomal fractions from ischemic myocardium after 1, 2, and 6 h of coronary occlusion. In animals occluded for 6 h, (Na+ + K+)-ATPase activity was significantly reduced by 40% in epicardial and by 35% in endocardial layers compared with nonischemic myocardium. Comparable reductions in in vitro [3H]ouabain binding were also demonstrated. Reperfusion for 45 min after occlusion for 6 h resulted in no significant restoration of enzyme activity when compared to the nonreperfused animals. In six animals occluded for 2 h, a time at which myocardial creatine phosphokinase activity remains unchanged, (Na+ + K+)-ATPase activity was reduced by 25% compared with nonischemic enzyme activity. In five dogs occluded for 1 h, (Na+ + K+)-ATPase activity in ischemic myocardium was unchanged from control levels. We conclude that reduced regional myocardial blood flow, local alterations in cellular milieu, and altered glycoside-binding properties of (Na+ + K+)-ATPase all participate in the reduction of cardiac glycoside binding observed after reperfusion of ischemic myocardium. In addition, after 2 or more hours of severe ischemia, myocardial (Na+ + K+)-ATPase catalytic activity is significantly reduced despite incubation in the presence of optimal substrate concentrations.

Localization of cardiac myosin-specific antibody in myocardial infarction.

Specific localization of purified antibody against cardiac myosin has been demonstrated in areas of altered myocardial membrane permeability after experimental myocardial infarction. Intravenously administered radioiodine-labeled antimyosin was selectively localized in infarcted myocardium of seven dogs 24 h after coronary occlusion. The mean ratio (+/-SE) of antimyosin antibody in infarcted to normal myocardium in the center of the infarct was 4.2+/-0.4 for endocardial and 2.9+/-0.3 for epicardial layers. By utilizing (Fab')2 fragments of antimyosin obtained by pepsin digestion of purified antibody, the ratio of uptake was increased in eight dogs to 6.1+/-0.6 in the endocardial and 3.3+/-0.4 in the epicardial layers at the infarct center 24 h after occlusion. These ratios were further increased in the infarct center to 13.8+/-1.2 in the endocardial and 7.3+/-0.8 in the epicardial layers when eight dogs were sacrificed 72 h after coronary occlusion. The specificity of antimyosin (Fab')2 localization in infarcted myocardium was demonstrated in four dogs by simultaneous intravenous administration of 125I-labeled antimyosin (Fab')2 and 131I-labeled normal rabbit gamma globulin (Fab')2. Nonspecific trapping of normal rabbit IgG (Fab')2 was observed to be about 38% of total antimyosin (Fab')2 uptake in the central zone of infarction. Regional blood flow was related to antimyosin (Fab')2 uptake in infarcted myocardium by utilizing simultaneous administration of 85Sr-labeled microspheres. An inverse exponential relationship between antimyosin (Fab')2 uptake and regional blood flow was observed (r=0.85). The specific localization of antimyosin antibody or its (Fab')2 components in infarcted myocardium suggests a conceptually new approach to myocardial infarct localization and sizing.

Myocardial uptake of (99m)Tc-N-NOET and (201)Tl during dobutamine infusion. Comparison with adenosine stress.

BACKGROUND: The myocardial uptake of (99m)Tc-sestamibi is attenuated by dobutamine stress, resulting in underestimation of ischemia. N-Ethyl-N-ethoxy-dithiocarbamato-N-(99m)Tc ((99m)Tc-N-NOET) is a new (99m)Tc-labeled perfusion agent that is highly extracted by the myocardium by a mechanism different from that defined for (99m)Tc-sestamibi. We therefore hypothesized that (99m)Tc-N-NOET uptake would not be attenuated by dobutamine and that (99m)Tc-N-NOET uptake would be comparable to (201)Tl uptake during dobutamine stress. METHODS AND RESULTS: In 28 open-chest dogs, after placement of a stenosis in the left anterior descending coronary artery that reduced flow reserve by >50%, adenosine (300 microgram. kg(-1). min(-1); n=15) or dobutamine (2.5 to 30 microgram. kg(-1). min(-1); n=13) was infused. During adenosine stress, the stenotic-to-normal activity ratio for (99m)Tc-N-NOET was 0.55+/-0.05. The stenotic-to-normal flow ratio was 0.33+/-0.04 at the time of (99m)Tc-N-NOET injection. During dobutamine stress, the stenotic-to-normal (99m)Tc-N-NOET activity ratio was 0.63+/-0.04, comparable to the (201)Tl activity ratio of 0.59+/-0.04. The stenotic-to-normal flow ratio was 0.47+/-0.04 at the time of (99m)Tc-N-NOET and (201)Tl injection. The relationship between (99m)Tc-N-NOET uptake and blood flow was comparable for adenosine and dobutamine stress, with no evidence of attenuation of (99m)Tc-N-NOET extraction by dobutamine. Conclusions-In the presence of coronary stenoses that reduced regional flow reserve, the myocardial uptake of (99m)Tc-N-NOET and (201)Tl are closely proportional to blood flow during both adenosine and dobutamine stress, suggesting that the adverse effect of dobutamine on (99m)Tc-sestamibi uptake is a tracer-specific phenomenon rather than a generalized effect. The clinical implication of this finding is that (99m)Tc-N-NOET might be preferable to (99m)Tc-sestamibi when used with dobutamine stress for detection of coronary stenoses.

Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection.

BACKGROUND: Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. METHODS AND RESULTS: In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)). CONCLUSIONS: ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

99mTc-N-NOET myocardial uptake reflects myocardial blood flow and not viability in dogs with reperfused acute myocardial infarction.

BACKGROUND: N-Ethoxy-N-ethyl-dithiocarbamato-nitrido-(99m)Tc ((99m)Tc-N-NOET) is a new neutral lipophilic (99m)Tc-labeled myocardial perfusion agent with a high first-pass extraction fraction and delayed redistribution kinetics after transient ischemia comparable to what is observed with (201)Tl. It is unknown whether the uptake of this tracer reflects myocardial viability or just reperfusion flow in the setting of a reperfused myocardial infarction. METHODS AND RESULTS: In 13 anesthetized open-chest dogs, the left anterior descending coronary artery was occluded for 180 minutes, followed by 180 minutes of reperfusion. (201)Tl and (99m)Tc-N-NOET were injected after either 60 (group 1, n=9) or 175 (group 2, n=4) minutes of reperfusion. Myocardial blood flow was measured by radioactive microspheres, and (201)Tl and (99m)Tc-N-NOET tissue activities were determined by gamma-well counting. Normalized myocardial blood flow in the central infarct zone fell from 0.80+/-0. 03 (SEM) and 0.89+/-0.01 at baseline to 0.18+/-0.04 and 0.13+/-0.02 during the occlusion in groups 1 and 2, respectively. Normalized (201)Tl activity in these segments was 0.39+/-0.04 and 0.43+/-0.04 and reflected myocardial viability rather than reperfusion flow (P<0. 001). Normalized (99m)Tc-N-NOET activity in the same segments was 0. 84+/-0.08 and 0.64+/-0.03, respectively (P<0.01 versus (201)Tl; P=NS versus reperfusion flow) and more accurately reflected reperfusion flow (0.99+/-0.17 and 0.70+/-0.04) than residual viability. CONCLUSIONS: The myocardial uptake of (99m)Tc-N-NOET reflects reperfusion myocardial blood flow and not viability in a canine model of reperfused acute myocardial infarction. The clinical use of early (99m)Tc-N-NOET imaging to assess the success of coronary reperfusion in patients with acute myocardial infarction should be investigated.

Early dipyridamole (99m)Tc-sestamibi single photon emission computed tomographic imaging 2 to 4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events: comparison with submaximal exercise imaging.

BACKGROUND: Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI. METHODS AND RESULTS: Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole (99m)Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise (99m)Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI. CONCLUSIONS: Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.

Role of myocardial perfusion imaging in evaluating thrombolytic therapy for acute myocardial infarction.

Myocardial thallium-201 scintigraphy is being increasingly employed as a method for assessing the efficacy of coronary reperfusion in acute myocardial infarction. New thallium uptake after intracoronary tracer administration after successful recanalization indicates that nutrient blood flow has been successfully restored. One may also presume that some myocardial salvage occurred if thallium administered in this manner is transported intracellularly by myocytes with intact sarcolemmal membranes. However, if one injects thallium by way of the intracoronary route immediately after reperfusion, the initial uptake of thallium in reperfused myocardium may predominantly represent hyperemic flow and regional thallium counts measured may not be proportional to the mass of viable myocytes. When thallium is injected intravenously during the occlusion phase the degree of redistribution after thrombolysis is proportional to the degree of flow restoration and myocardial viability. When thallium is injected for the first time intravenously immediately after reperfusion, an overestimation of myocardial salvage may occur because of "excess" thallium uptake in the infarct zone consequent to significant hyperemia. Another approach to myocardial thallium scintigraphy in patients undergoing thrombolytic therapy is to administer two separate intravenous injections before and 24 hours or later after treatment. Clinical studies have demonstrated that the improvement in defect size on serial images predicts improvement in regional function and patency of the infarct-related vessel. Finally, patients with acute myocardial infarction who receive intravenous thrombolytic therapy are candidates for predischarge exercise thallium-201 scintigraphy for risk stratification and detection of residual ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

A comprehensive analysis of myocardial infarction due to left circumflex artery occlusion: comparison with infarction due to right coronary artery and left anterior descending artery occlusion.

Forty consecutive patients with creatine kinase-MB confirmed myocardial infarction due to circumflex artery occlusion (Group 1) were prospectively evaluated and compared with 107 patients with infarction due to right coronary artery occlusion (Group 2) and 94 with left anterior descending artery occlusion (Group 3). All 241 patients underwent exercise thallium-201 scintigraphy, radionuclide ventriculography, 24 h Holter electrocardiographic (ECG) monitoring and coronary arteriography before hospital discharge and were followed up for 39 +/- 18 months. There were no significant differences among the three infarct groups in age, gender, number of risk factors, prevalence and type of prior infarction, Norris index, Killip class and frequency of in-hospital complications. Acute ST segment elevation was present in only 48% of patients in Group 1 versus 71 and 72% in Groups 2 and 3, respectively (p = 0.012), and 38% of patients with a circumflex artery-related infarct had no significant ST changes (that is, elevation or depression) on admission (versus 21 and 20% for patients in Groups 2 and 3, respectively) (p = 0.001). Abnormal R waves in lead V1 were more common in Group 1 than in Group 2 (p less than 0.003) as was ST elevation in leads I, aVL and V4 to V6 (p less than or equal to 0.048). These differences in ECG findings between Group 1 and 2 patients correlated with a significantly higher prevalence of posterior and lateral wall asynergy in the group with a circumflex artery-related infarct. Infarct size based on peak creatine kinase levels and multiple radionuclide variables was intermediate in Group 1 compared with that in Group 2 (smallest) and Group 3 (largest). During long-term follow-up, the probability of recurrent cardiac events was similar in the three infarct groups. When patients with a circumflex artery-related infarct were stratified according to the presence or absence of abnormal R waves in lead V1 or V2, the abnormal R wave group had more admission ST elevation (p = 0.025), a larger infarct (p less than 0.05) and more extensive coronary artery disease (p = 0.027). In fact, all patients with a circumflex artery-related infarct and an abnormal R wave in lead V1 had multivessel disease. An abnormal R wave in lead V1 had a 96% specificity for circumflex versus right coronary artery-related infarction but a sensitivity of only 21%. Discriminate function analysis of all admission historical and ECG variables identified inferior and lateral ST elevation as independent predictors of circumflex artery-related infarction...

Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis.

Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of "no reflow." Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs. Infarct size (percent of left ventricle) determined with triphenyltetrazolium chloride was similar in all groups (Group I, 24 +/- 4%; Group II, 29 +/- 4%; Group III, 25 +/- 4%). Thus, in this experimental canine model, 3 hours of coronary occlusion followed by either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis resulted in little delayed thallium-201 redistribution or myocardial salvage as assessed histologically, despite significant recovery of regional flow.

Effects of nitroglycerin-induced hypotension on myocardial blood flow in a two vessel occlusion-stenosis anesthetized canine model.

The effects of acute occlusion of the left anterior descending coronary artery on regional blood flow (microspheres) to the remote bed supplied by either an unstenosed or a stenosed circumflex coronary artery were assessed during the infusion of intravenous nitroglycerin in 11 open chest barbiturate-anesthetized mongrel dogs. Left anterior descending coronary artery occlusion in the presence of an unstenosed left circumflex artery during nitroglycerin infusion caused systolic aortic and distal circumflex pressure to decrease significantly from 98 +/- 4 to 91 +/- 3 and from 99 +/- 4 to 92 +/- 3 mm Hg, respectively. Remote circumflex bed flow was unchanged. The infusion of intravenous nitroglycerin in the presence of a left circumflex stenosis (gradient 31 +/- 3 mm Hg) reduced systolic aortic and distal circumflex pressure to 98 +/- 2 (p = 0.001) and 71 +/- 4 mm Hg (p = 0.001), respectively, and lowered remote circumflex bed endocardial flow from 1.00 +/- 0.08 to 0.79 +/- 0.07 ml/min per g (p = 0.001). When the left anterior descending coronary artery was occluded under these conditions, systolic aortic and distal left circumflex pressure decreased to 89 +/- 3 (p = 0.005) and 62 +/- 4 mm Hg (p = 0.08), respectively. Remote circumflex artery bed endocardial and transmural flow were significantly reduced to 0.58 +/- 0.07 (p = 0.01) and 0.65 +/- 0.07 ml/min per g (p = 0.03), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of and variables associated with silent myocardial ischemia on exercise thallium-201 stress testing.

The prevalence of silent myocardial ischemia was prospectively assessed in a group of 103 consecutive patients (mean age 59 +/- 10 years, 79% male) undergoing symptom-limited exercise thallium-201 scintigraphy. Variables that best correlated with the occurrence of painless ischemia by quantitative scintigraphic criteria were examined. Fifty-nine patients (57%) had no angina on exercise testing. A significantly greater percent of patients with silent ischemia than of patients with angina had a recent myocardial infarction (31% versus 7%, p less than 0.01), had no prior angina (91% versus 64%, p less than 0.01), had dyspnea as an exercise test end point (56% versus 35%, p less than 0.05) and exhibited redistribution defects in the supply regions of the right and circumflex coronary arteries (50% versus 35%, p less than 0.05). The group with exercise angina had more ST depression (64% versus 41%, p less than 0.05) and more patients with four or more redistribution defects. However, there was no difference between the two groups with respect to mean total thallium-201 perfusion score, number of redistribution defects per patient, multi-vessel thallium redistribution pattern or extent of angiographic coronary artery disease. There was also no difference between the silent ischemia and angina groups with respect to antianginal drug usage, prevalence of diabetes mellitus, exercise duration, peak exercise heart rate, peak work load, peak double (rate-pressure) product and percent of patients achieving greater than or equal to 85% of maximal predicted heart rate for age. Thus, in this study group, there was a rather high prevalence rate of silent ischemia (57%) by exercise thallium-201 criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of intravenous digoxin in patients with severe heart failure initially treated with diuretics and vasodilators.

The purpose of this study was to assess the hemodynamic effects of intravenous digoxin in patients with New York Heart Association class IV heart failure, who had never previously been treated with digitalis drugs, and who were initially treated only with diuretics and systemic vasodilators to clinical end points of compensation. Eleven male patients, 5 with idiopathic and 6 with ischemic cardiomyopathy, had sinus rhythm and were hospitalized with congestive heart failure not precipitated by an acute ischemic event. All 11 patients were treated with intravenous furosemide and various vasodilators without invasive hemodynamic monitoring for a mean period of 4.3 +/- 2.1 days. This therapy resulted in subjective and objective improvement in all patients as reflected by a significant decrease in heart failure score from 9.5 +/- 2.2 to 2.7 +/- 2.3 (p less than 0.001). When compensation was achieved by clinical criteria, the patients were instrumented and hemodynamics obtained before and serially thereafter for 6 hours after the intravenous administration of digoxin given in two 0.5 mg doses 2 hours apart. In response to digoxin, cardiac index increased from 2.6 +/- 0.7 liters/min per m2 to a peak of 3.3 +/- 0.6 liters/min per m2 (p less than 0.005); left ventricular stroke work index (g X m/m2) increased from 27 +/- 16 to 43 +/- 23 (p less than 0.005) and the ejection fraction (eight patients) increased from 21 +/- 13% to 29 +/- 11% (p less than 0.04). Mean pulmonary capillary wedge pressure decreased from 24 +/- 7 to a minimum of 17 +/- 4 mm Hg (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of ischemia and postischemic dysfunction on myocardial uptake of technetium-99m-labeled methoxyisobutyl isonitrile and thallium-201.

The myocardial uptake of a new technetium-99m-labeled myocardial perfusion agent, methoxyisobutyl isonitrile (Tc-99m MIBI), and thallium-201 was correlated with microsphere flow in an open chest canine model of low coronary flow and postischemic dysfunction. Eighteen dogs were given an injection of thallium-201 (0.5 mCi) and Tc-99m MIBI (5 mCi) either after 40 min of partial left anterior descending artery occlusion (Group I, 10 dogs) or during reperfusion after 15 min of left anterior descending artery occlusion (Group II, 8 dogs). Regional dysfunction was documented during injection in both groups by quantitative two-dimensional echocardiography. Regional blood flow was assessed by radiolabeled microspheres. The heart was excised 15 min after radionuclide injection and the left ventricle divided into 96 segments for gamma well counting. Among Group I dogs, central ischemic thallium-201 and Tc-99m MIBI activity (expressed as a percent of the activity in the corresponding nonischemic zone) was comparable, respectively, for endocardial (54 +/- 17% and 52 +/- 17%), mid-wall (71 +/- 20% and 69 +/- 17%) and epicardial (89 +/- 13% and 94 +/- 9%) segments and increased proportionally with flow. There was a good linear correlation among these endocardial segments between flow and both thallium-201 (r = 0.78) and Tc-99m MIBI (r = 0.85) activity. Among Group II dogs, central ischemic endocardial flow (59 +/- 14%) was comparable to thallium-201 (70 +/- 18%) and Tc-99m MIBI (74 +/- 12%) activity. Similarly, relative endocardial flow in the intermediate ischemic region (71 +/- 11%) was comparable to thallium-201 (77 +/- 11%) and Tc-99m MIBI (81 +/- 10%) activity. Thus, myocardial uptake of Tc-99m MIBI and thallium-201 is comparable under conditions of low coronary flow and postischemic dysfunction and closely parallels flow alterations.

Do false positive thallium-201 scans lead to unnecessary catheterization? Outcome of patients with perfusion defects on quantitative planar thallium-201 scintigraphy.

OBJECTIVES: We postulated that artifactually abnormal thallium-201 scans are well identified at the time of initial clinical interpretation by experienced readers and do not lead to unnecessary coronary angiography. BACKGROUND: Exercise thallium-201 scintigraphy employing quantitative imaging techniques has yielded sensitivity and specificity values of 80% to 90%. There are image artifacts, such as breast shadows, and variants of normal that, if not correctly identified, can lead to a high false positive rate for detection of coronary artery disease. METHODS: Data from 338 consecutive patients with one or more focal thallium-201 defects on quantitative planar images were reviewed. All patients had undergone symptom-limited exercise scintigraphy and were classified as having either artifactual or nonartifactual thallium-201 defects after review of clinical reports. RESULTS: Of the 265 patients with defects judged to be nonartifactual on clinical readings, 167 underwent coronary angiography, which demonstrated significant coronary artery disease (> or = 50% stenosis) in 161 (96%) and normal findings in 6. Four of the latter six had documented prior myocardial infarction. The remaining 73 patients (85% female) had thallium-201 defects deemed to be artifactual on clinical readings, chiefly as a result of breast (66%) and diaphragmatic (8%) attenuation or variants of normal (26%). Only 4 (5%) of the 73 patients underwent subsequent coronary angiography; none had coronary artery disease. One had aortic stenosis and two had variant angina. Follow-up (mean 20 +/- 2 months) of the 69 patients in this group who did not undergo coronary angiography revealed no deaths and one nonfatal non-Q wave myocardial infarction. CONCLUSIONS: Artifactual defects on quantitative planar thallium-201 scintigraphy are well recognized by experienced interpreters and do not result in a high false positive rate leading to unnecessary cardiac catheterization. The incidence of coronary artery disease is high in patients with thallium-201 defects judged to be nonartifactual, and many patients with perfusion defects and angiographically normal coronary arteries have organic heart disease.

Left ventricular hyperkinesia at rest and during exercise in normotensive patients 2 to 27 years after coarctation repair.

The short- and long-term results of effective surgical repair of coarctation of the aorta on left ventricular mass and function in 48 patients were evaluated using echocardiography and stress-gated radionuclide angiography. Thirty-two of the 48 patients who had no additional cardiac problems and had technically adequate radionuclide angiograms form the basis for this report. Among these, three had mild systolic hypertension and none had significant aortic valve dysfunction. Age at the time of study ranged from 6.5 to 59 years (mean 27). Age at the time of surgery ranged from 3 months to 34 years (mean 12 years). Duration from surgery to the time of noninvasive study ranged from 2 to 29 years (mean 15). In the 32 patients, left ventricular mass was 120 +/- 20 g/m2, compared with a control value of 87 +/- 10 g/m2. Mean left ventricular ejection fraction was elevated to 69.2 +/- 1.6% at rest (control 60 +/- 1.3%) and 78.8 +/- 1.3% during exercise (control 70 +/- 1.7%) (p less than 0.01). The systolic ejection rate was significantly increased (p less than 0.01) and end-systolic volume significantly decreased (p less than 0.01) compared with values in control patients. There was no correlation between ejection fraction and either age at the time of surgery or years since surgery. These findings of hyperdynamic left ventricular function and increased left ventricular mass without apparent cause many years after coarctation repair raise important questions as to mechanisms, extension to other forms of afterload stress that have been surgically or medically relieved and long-term outcome.

Effects of dipyridamole and aminophylline on hemodynamics, regional myocardial blood flow and thallium-201 washout in the setting of a critical coronary stenosis.

Experiments were performed to characterize the interaction of intravenous dipyridamole and aminophylline on thallium-201 transport kinetics, regional myocardial blood flow and systemic hemodynamics in the presence of a critical coronary artery stenosis. In 12 dogs with a critical left anterior descending coronary artery stenosis, arterial pressure decreased from a mean value (+/- SEM) of 107 +/- 6 to 94 +/- 3 mm Hg (p less than 0.05) and distal left anterior descending artery pressure decreased from 70 +/- 7 to 55 +/- 4 mm Hg (p less than 0.05) after intravenous administration of dipyridamole (0.25 mg/kg body weight). In the left anterior descending perfusion zone, the endocardial/epicardial flow ratio decreased from 0.70 to 0.36 and the intrinsic thallium washout rate was significantly prolonged. Intravenous aminophylline (5 mg/kg) reversed the dipyridamole-induced systemic hypotension and transmural coronary steal and restored the thallium washout rate to baseline values. In six other dogs, aminophylline alone resulted in no alterations in systemic and coronary hemodynamics or regional myocardial blood flow. As expected, dipyridamole-induced vasodilation and coronary steal were prevented by aminophylline pretreatment. These data show that in a canine model of partial coronary stenosis, systemic hypotension, adverse regional flow effects (coronary steal) and prolonged thallium-201 washout consequent to intravenously administered dipyridamole are promptly reversed by intravenous aminophylline administration. Aminophylline alone had no significant hemodynamic and coronary flow effects. This study provides further insight into the altered thallium kinetics occurring as a consequence of dipyridamole-induced vasodilation and suggests that the prompt reversal of symptoms and signs of ischemia with aminophylline in patients receiving intravenous dipyridamole for clinical imaging studies probably reflects the reversal of transmural coronary steal.

Effects of successful intravenous reperfusion therapy on regional myocardial function and geometry in humans: a tomographic assessment using two-dimensional echocardiography.

This study tested the hypothesis that reperfusion therapy might provide benefit at two levels: 1) by arresting infarct migration at the endocardial level, such that partial or complete recovery of regional function occurs; and 2) if the former is not achieved, by preventing complete or near complete transmural migration and subsequent infarct expansion. To test this hypothesis, 24 patients who received intravenous streptokinase therapy within 4 h of chest pain were studied prospectively. All patients underwent two-dimensional echocardiography at the time of admission and 1, 2, 3 and 10 days later. The patients also underwent coronary angiography 2 h after completion of streptokinase therapy. Although 18 (75%) of the 24 patients had a patent infarct-related artery, only 8 (45%) of the 18 patients with this finding showed improvement in regional function. Improvement was not evident until 3 to 10 days after streptokinase therapy. In addition to the presence of an open infarct-related artery, the interval between chest pain and onset of streptokinase therapy (2.5 +/- 0.5 versus 3.2 +/- 0.7 h, p = 0.02) differed significantly between patients who did or did not show improved regional function. Of the 15 of 16 patients with no improvement in regional function, 4 showed infarct expansion, and all had a closed infarct-related artery compared with only 2 of the 11 not showing expansion (p = 0.01). In conclusion, intravenous streptokinase given within 4 h of chest pain results in improvement in regional function in about 33% of the patients, presumably by arresting the infarction within the endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative diagnostic accuracy of Tl-201 and Tc-99m sestamibi SPECT imaging (perfusion and ECG-gated SPECT) in detecting coronary artery disease in women.

OBJECTIVES: This prospective study was conducted in 115 women to directly compare the sensitivity and specificity of thallium-201 (Tl-201), technetium-99m (Tc-99m) sestamibi perfusion and Tc-99m sestamibi electrocardiographic (ECG)-gated single-photon emission computed tomographic (SPECT) studies for detection of coronary artery disease (CAD). BACKGROUND: Data on the comparative diagnostic accuracy of Tl-201 and Tc-99m sestamibi perfusion imaging for the detection of CAD, specifically in women, are very limited. METHODS: Eighty-five patients with suspected CAD, scheduled for coronary angiography, and 30 volunteers with a pretest likelihood of < or = 5% for CAD were evaluated. Within 1 week, each patient underwent Tl-201 and Tc-99m sestamibi SPECT imaging procedures (both perfusion and gated SPECT imaging). Treadmill stress testing was used in 78 patients and dipyridamole in the remaining 37 patients. All images were interpreted by three observers in a blinded manner (consensus reading). Technetium-99m sestamibi SPECT studies were read without and then with ECG gating. Technetium-99m sestamibi gated SPECT studies were used to differentiate scar tissue from soft tissue attenuation artifact. RESULTS: The overall sensitivities for detecting > or = 50% and > or = 70% stenoses were 75.0% and 84.3%, respectively, for Tl-201, and 71.9% and 80.4%, respectively, for Tc-99m sestamibi perfusion studies (p = 0.48). The specificity for lesions > or = 50% was 61.9% for Tl-201 and 85.7% for Tc-99m sestamibi perfusion (p = 0.07), whereas for lesions > or = 70% it was 58.8% for Tl-201 and 82.4% for Tc-99m sestamibi perfusion (p = 0.01). When the 34 patients with a normal coronary angiogram were added to the group of 30 normal volunteers, the "specificity" for lesions > or = 70% was 67.2% for Tl-201, 84.4% for Tc-99m sestamibi SPECT perfusion (p = 0.02) and 92.2% for Tc-99m sestamibi gated SPECT (p = 0.0004). CONCLUSIONS: Both Tl-201 SPECT and Tc-99m sestamibi SPECT perfusion studies had a similar sensitivity for the detection of CAD in women. However, Tc-99m sestamibi SPECT perfusion imaging shows a significantly better specificity, which is further enhanced by the use of ECG gating.

Response to incremental doses of dobutamine early after reperfusion is predictive of the degree of myocardial salvage in dogs with experimental acute myocardial infarction.

OBJECTIVES: We sought to determine whether the inotropic response to dobutamine might be useful for estimating the extent of viable myocardium soon after reperfusion. BACKGROUND: Early identification of viable myocardium in the presence of severe left ventricular dysfunction after reperfusion is important for clinical decision making. METHODS: Nine open-chest dogs had left anterior descending coronary artery occlusion for 40 to 180 min, followed by gradual reperfusion. The systolic thickening response to incremental dobutamine doses was measured with ultrasonic crystals and regional flow by microspheres. RESULTS: Dogs were divided into two groups based on triphenyl tetralozium chloride infarct size (group 1: 9.3 +/- 3.0% risk area; group 2: 51.1 +/- 4.8%). In group 2 dogs with larger infarcts, regional flow during peak dobutamine was lower than it was in group 1 in endocardial (1.15 +/- 0.22 vs. 2.64 +/- 0.33 mL x min(-1) x g(-1)) and midwall (1.47 +/- 0.32 vs. 2.92 +/- 0.36 mL x min(-1) x g(-1)) layers, and endocardial flow in group 2 failed to increase from baseline (0.96 +/- 0.07 vs. 1.15 +/- 0.22 mL x min(-1) x g(-1)). Group 1 dogs demonstrated a dose dependent increase in systolic thickening with dobutamine versus a blunted response in group 2. The inotropic response to only 10 microg x kg(-1) x min(-1) of dobutamine was predictive of the degree of myocardial salvage. CONCLUSIONS: In the early postischemic stunning phase of reperfusion, the inotropic response to dobutamine is predictive of the degree of myocardial salvage and ultimate infarct size. The ability to distinguish between stunned versus necrotic myocardium early after reperfusion was most likely due to the presence of subendocardial flow reserve during dobutamine in dogs with predominantly salvaged myocardium.

Comparison of rest thallium-201 imaging and rest technetium-99m sestamibi imaging for assessment of myocardial viability in patients with coronary artery disease and severe left ventricular dysfunction.

OBJECTIVES: We prospectively compared myocardial uptake of thallium-201 (201Tl) at rest with rest technetium-99m (99mTc) sestamibi uptake in the same patients, using quantitative singlephoton emission computed tomography (SPECT). BACKGROUND: Because of only slightly delayed redistribution, 99mTc-sestamibi uptake at rest may be less than 201Tl uptake, thereby underestimating the extent of viability. METHODS: Twenty patients (2.25 stenoses per patient) with a mean left ventricular ejection fraction of 33 +/- 2% underwent early and 3-h delayed rest 201Tl SPECT, rest 99mTc-sestamibi SPECT and two-dimensional echocardiography. RESULTS: The 280 scan segments were classified as either a normal, mild reduction in viability, defined as delayed 201Tl uptake < or = 75% and > or = 5%, or a severe reduction in viability, defined as delayed 201Tl uptake < 50%. Mild and severe defects were further classified as fixed or having rest 201Tl redistribution. Comparisons by patients were made using repeated measures analysis of variance and Dunnett's multiple comparisons test to compare 99mTc-sestamibi with initial rest 201Tl and delayed 201Tl uptake. Twenty patients had at least one mild fixed defect (95 total segments). The average percent uptake in these defects for initial 201Tl, delayed 201Tl and 99mTc-sestamibi was 62.5 +/- 2.7%, 63.1 +/- 7.1% and 67.3 +/- 9.7%, respectively (p = NS). Twelve patients (27 segments) had mild redistribution defects on serial rest 201Tl imaging. The average percent uptake was 61.6 +/- 5.2% for initial 201Tl, 67.0 +/- 9.1% for delayed 201Tl and 67.7 +/- 12.4% for 99mTc-sestamibi defects. Technetium-99m sestamibi uptake was not significantly different than that for delayed 201Tl but was significantly greater than initial 201Tl uptake. Seventeen patients (52 segments) had severe fixed 201Tl defects. The average percent uptake was 38.9 +/- 7.3% for initial 201Tl, 38.3 +/- 12.2% for delayed 201Tl and 42.7 +/- 14.2% for 99mTc-sestamibi defects in these patients (p = NS). Ten patients (19 segments) had severe redistribution defects on rest 201Tl imaging. The average percent uptake was 37.0 +/- 8.5% for initial 201Tl, 42.9 +/- 8.6% for delayed 201Tl and 44.5 +/- 11.3% for 99mTc-sestamibi defects. As was seen for mild 201Tl redistribution defects, 99mTc-sestamibi uptake was significantly higher than initial 201Tl uptake, but not significantly different than delayed 201Tl uptake in these severe defects. CONCLUSIONS: Technetium-99m sestamibi uptake after injection at rest is comparable to 201Tl uptake after injection at rest in patients with severe coronary artery disease and left ventricular dysfunction, suggesting comparable worth for viability assessment.