Search

Noninvasive imaging strategies will be critical for defining the temporal characteristics of angiogenesis and assessing efficacy of angiogenic therapies. The alphavbeta3 integrin is expressed in angiogenic vessels and represents a potential novel target for imaging myocardial angiogenesis. We demonstrated the localization of an indium-111-labeled ((111)In-labeled) alphavbeta3-targeted agent in the region of injury-induced angiogenesis in a chronic rat model of infarction. The specificity of the targeted alphavbeta3-imaging agent for angiogenesis was established using a nonspecific control agent. The potential of this radiolabeled alphavbeta3-targeted agent for in vivo imaging was then confirmed in a canine model of postinfarction angiogenesis. Serial in vivo dual-isotope single-photon emission-computed tomographic (SPECT) imaging with the (111)In-labeled alphavbeta3-targeted agent demonstrated focal radiotracer uptake in hypoperfused regions where angiogenesis was stimulated. There was a fourfold increase in myocardial radiotracer uptake in the infarct region associated with histological evidence of angiogenesis and increased expression of the alphavbeta3 integrin. Thus, angiogenesis in the heart can be imaged noninvasively with an (111)In-labeled alphavbeta3-targeted agent. The noninvasive evaluation of angiogenesis may have important implications for risk stratification of patients following myocardial infarction. This approach may also have significant clinical utility for noninvasively tracking therapeutic myocardial angiogenesis.

Context: Current management of patients with unstable angina and non-Q wave myocardial infarction generally consists of intensive medical therapy, with angiography and revascularization sometimes limited to those who fail such therapy., Aim: To determine if certain baseline characteristics are predictive of patients who fail medical therapy, since such patients could then be expeditiously directed to a more invasive strategy in a cost-effective manner., Methods: The study cohort consisted of the 733 patients in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB study who were randomized to conservative strategy. Patients were to be treated with bedrest, anti-ischaemic medications, aspirin, and heparin, and were to undergo risk-stratifying tests, consisting of an exercise test with ECG and thallium scintigraphy, scheduled to be performed within 3 days prior to, or 5 days after, hospital discharge and 24 h Holter monitoring scheduled to begin 2-5 days after randomization. Baseline clinical and ECG characteristics were compared between patients who 'failed' medical therapy and those who did not 'fail'. Failure was defined using clinical end-points (death, myocardial infarction, or spontaneous ischaemia by 6 weeks after randomization) or a strongly positive risk-stratifying test. For each test an ordered failure profile of results was calculated and consisted of death, myocardial infarction, or rest ischaemia occurring prior to performance of the test, a markedly abnormal test result, and no abnormality., Results: Clinical end-points occurred in 241 (33%) patients and were more likely to occur in patients who at presentation were older, had ST-segment depression on the qualifying ECG, or were being treated with heparin or aspirin. Characteristics independently predictive of developing a clinical event or an abnormal exercise treadmill test included: ST-segment depression on the qualifying ECG, history of prior angina, family history of premature coronary disease (i.e. onset <55 years of age), prior use of heparin or aspirin, and increasing age. By combining these baseline risk characteristics for each outcome the incidence of developing a clinical event ranged from 8% if none was present to 63% if all six were present, and of developing a markedly abnormal risk stratifying test from 8-21% if none were present to approximately 90% if all six were present., Conclusions: Baseline characteristics associated with developing a clinical event or a markedly abnormal risk stratifying test were similar: rest anginal episode accompanied by ST-segment depression and occurring despite treatment with aspirin and heparin, a history of angina, older age, and family history of coronary disease. Patients with these characteristics are appropriate candidates for expeditious cardiac catheterization and consideration for revascularization, while patients without them may be suitable for medical management alone., (Copyright 1999 The European Society of Cardiology.)

Current protocols for use of tissue-type plasminogen activator in acute myocardial infarction include heparin estimated by the activated partial thromboplastin time (aPTT). Recent reports indicate a risk of recurrent ischemic events with long aPTT values. Longer aPTT values in the Thrombolysis in Myocardial Infarction-II (TIMI II) Trial, obtained within the first 48 hours, were associated with patency at 18 to 48 hours and better left ventricular function at discharge (average 9.6 days), but also with emergency catheterizations within the first 48 hours and, weakly, with recurrent ischemia during the first 18 hours. A moderate decrease in fibrinogen, compared with a "small" decrease, was also associated with patency, but a "large" decrease was associated with hemorrhagic events. Patency was associated with higher fibrinogen values and higher plasminogen values at baseline. The aPTT results support frequent monitoring during the first 24 to 48 hours to ensure optimal clinical outcome. The coagulation factor results suggest that there may be an optimum window for fibrinogenolysis in this setting.

Objectives: This study sought to determine the significance of abnormal thallium-201 (Tl-201) lung uptake on stress imaging in the absence of perfusion abnormalities., Background: Abnormal Tl-201 lung uptake, represented by an increased lung/heart ratio (LHR), on stress imaging is a marker of stress-induced left ventricular dysfunction and poor prognosis in patients with coronary artery disease., Methods: We evaluate 1,271 patients from the Thrombolysis in Myocardial Infarction (TIMI)-IIIB trial (86% of TIMI-IIIB cohort) with unstable angina or non-Q wave myocardial infarction, who underwent predischarge exercise (92%) or dipyridamole stress (8%) Tl-201 imaging. An increased LHR (> or = 0.50) was related to perfusion abnormalities and adverse cardiac events at 1 year., Results: Of 1,271 patients, there were 762 (60%) with and 509 (40%) without perfusion abnormalities. An increased LHR was seen in 227 patients (18%) (173 [23%] with, 54 [11%] without perfusion abnormalities). Patients with an increased LHR had a lower left ventricular ejection fraction, higher body weight, lower exercise capacity and a higher prevalence of angina on exercise than patients with a normal LHR. In the two groups with increased LHR, there was no difference in age, hypertension, previous myocardial infarction, total exercise time, frequency of angina and ST segment depression on exercise. However, the group with an increased LHR and normal myocardial perfusion had a preponderance of women (65% vs. 30%, p < 0.001). At 1-year follow-up, patients with an increased LHR had a higher cardiac event rate than those with a normal LHR (18% vs. 10%, respectively, p = 0.001) despite a higher revascularization rate (28% vs. 15%, p < 0.001). An increased LHR was associated with increased adverse cardiac events, irrespective of the presence or absence of perfusion abnormalities., Conclusions: An increased LHR continues to be associated with higher adverse cardiac events in the current era of aggressive interventional management of coronary artery disease. An increased LHR in the absence of myocardial perfusion abnormality is seen mostly in women and overweight patients. However, despite the apparent absence of perfusion abnormalities, an increased LHR in this group is also associated with a higher rate of adverse cardiac events.

Previous studies have shown an association between distortion of the terminal portion of the QRS (QRS[+] pattern: emergence of the J point > or = 50%. of the R wave in leads with qR configuration or disappearance of the S wave in leads with an Rs configuration) on admission and in-hospital mortality in acute myocardial infarction (AMI). However, the mechanism for this association is not known. We assessed the relation between QRS(+) pattern and coronary angiographic findings, infarct size, and long-term prognosis in the Thrombolysis In Myocardial Infarction 4 trial. Patients were allocated into 2 groups based on the presence (QRS[+], n = 85) or absence (QRS[-], n = 293) of QRS distortion. The QRS(+) patients were older (mean +/- SD: 61.1 +/- 10.6 vs 57.5 +/- 10.6 years, p = 0.004), had more anterior AMI (49% vs 37%, p = 0.04), and less previous angina (42% vs 54%, p = 0.05). QRS(+) patients had larger infarct size as assessed by creatine kinase release over 24 hours (209 +/- 147 vs 155 +/- 129, p = 0.003), and predischarge sestamibi (MIBI) defect (17.9 +/- 15.9% vs 11.2 +/- 13.4%, p <0.001). When adjusting for difference in baseline characteristics, p values for the differences in 24-hour creatine kinase release were 0.03 and 0.64 for anterior and nonanterior AMI, respectively, and for MIBI defect size 0.03 and 0.02, respectively. One-year mortality (18% vs 6%, p = 0.03) was higher and the weighted end point of death, reinfarction, heart failure, or left ventricular ejection fraction <40% (0.33 +/- 0.37 vs 0.24 +/- 0.32, p = 0. 13), tended to be higher in the anterior AMI patients with QRS(+). No difference in clinical outcome was found in patients with non-anterior AMI. These findings suggest that this simple electrocardiographic definition of presence of QRS(+) pattern on admission may provide an early estimation of infarct size and long-term prognosis, especially in anterior AMI.

Objectives: This study sought to determine the prognostic value of rest and exercise left ventricular ejection fraction in patients receiving thrombolytic therapy as part of the Thrombolysis in Myocardial Infarction (TIMI) trial., Background: In the prethrombolytic era, ejection fraction at rest as well as during exercise was an important prognostic index in patients recovering from acute myocardial infarction. The prognostic value of these measurements in the thrombolytic era is not clear., Methods: As part of the TIMI II protocol, we obtained radionuclide left ventricular ejection fraction at rest and during symptom-limited submaximal supine exercise. Measurements were related to 1-year all-cause as well as cardiac mortality. In addition, the relation between ejection fraction obtained at rest and 1-year cardiac mortality in this study was compared with the relation established previously in the prethrombolytic era by the Multicenter Postinfarction Research Group., Results: A distinct relation was noted between left ventricular ejection fraction at rest and all-cause mortality. The highest mortality rate (9.9%) was noted in patients with an ejection fraction < 30%. Those not undergoing a study had a 1-year mortality rate of 6.2%. Peak exercise ejection fraction provided prognostic information similar to that of rest ejection fraction. Likewise, change in ejection fraction from rest to exercise did not appreciably improve prognostic impact., Conclusions: Rest left ventricular ejection fraction is an important prognostic index in patients receiving thrombolytic therapy. Peak exercise ejection fraction and the change in ejection fraction from rest to exercise do not provide appreciable prognostic data beyond those obtained at rest. Patients unable to exercise or those not having a rest study have a poor prognosis. When compared with the Multicenter Postinfarction Research Group data, there was strong evidence of a difference in survival in the two studies. At any level of ejection fraction, mortality was lower in TIMI II patients than in patients in the prethrombolytic era.

To ascertain whether the outcome of patients with suspected myocardial infarction differs when chest pain is still present at initiation of thrombolytic therapy, participants in the Thrombolysis in Myocardial Infarction Phase II study, all of whom presented within 4 hours of symptoms onset, were retrospectively divided into 2 groups: (1) those with chest pain present at onset of intravenous thrombolysis, n = 3,000; and (2) those who were free of chest pain on beginning intravenous thrombolytic therapy, n = 337. Patients free of chest pain were older (58 vs 57 years, p = 0.01), more often women (23 vs 17%, p = 0.01), had fewer electrocardiographic leads with ST elevation (3.8 vs 4.1, p < 0.001), and the presenting event was confirmed less often as myocardial infarction than as chest pain without infarction (88 vs 96%, p < 0.001). There were no significant differences between the 2 groups for in-hospital death, reinfarction, recurrent ischemic events, stroke, overall hemorrhagic complications, coronary angioplasty or bypass surgery. At 6-weeks follow-up, more pain-free patients had resting ejection fraction > 0.55 (35 vs 31%, p = 0.001) and fewer developed congestive heart failure (12 vs 20%). At 1-year follow-up, fewer pain-free patients developed congestive heart failure (15 vs 21%, p = 0.009), but no differences existed between the 2 groups in frequency of death, reinfarction, coronary angioplasty, bypass surgery or anginal class. Thus, there are several observations in patients who were free of chest pain at onset of lytic therapy. (1) The majority developed enzymatic or electrocardiographic evidence of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives: The purpose of this study was to compare the assessment of myocardial area at risk in patients with coronary artery stenosis by coronary angiography and quantitative myocardial perfusion imaging with technetium-99m sestamibi., Background: Decisions concerning patient management frequently rely on semiquantitative angiographic estimation of the myocardial area at risk, although this approach has not been well validated. Technetium-99m sestamibi is a perfusion imaging agent with little redistribution after initial myocardial uptake. This characteristic allows for injection during angioplasty and later imaging for visualization and quantitation of the nonperfused area at risk., Methods: Thirty-nine patients referred for coronary angioplasty were studied. Technetium-99m sestamibi was injected intravenously during angioplasty balloon inflation. Planar (33 patients) or tomographic (6 patients) imaging was performed after completion of angioplasty. Imaging was repeated 24 to 48 h later. Myocardial risk area (perfusion defect on angioplasty image) was quantified as an integral using circumferential count distribution profiles and normal reference. Angiographic risk area was assessed using five scoring methods., Results: The scintigraphic risk area was 14 +/- 15 on planar images and 39 +/- 16 on tomography. Scintigraphic risk area of patients with infarction was larger than in patients without (22 +/- 17 versus 7 +/- 8, p = 0.003). The left anterior descending coronary artery had a larger mean risk area than other vessels (22 +/- 15 versus 7 +/- 11, p = 0.002). The presence of angiographic collateral channels was associated with smaller risk areas. Angiographic risk scores correlated only moderately with the technetium-99m sestamibi risk area (r = 0.54 to 0.65), with considerable spread of data., Conclusions: Area at risk estimated from coronary angiography does not correlate well with that from quantitative myocardial perfusion imaging with technetium-99m sestamibi. These findings emphasize that the functional significance of coronary artery disease is not predicted by coronary anatomy alone.

To determine the effect of thrombolytic therapy on the frequency of right ventricular (RV) dysfunction, and whether RV dysfunction is a risk factor for morbidity and mortality after discharge from the hospital, 1,110 patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial with acute inferior wall left ventricular myocardial infarction were studied. RV dysfunction was defined as an RV wall motion abnormality on equilibrium radionuclide ventriculography performed a mean of 9 days after admission to the hospital. Fifty-eight patients (5%) had RV dysfunction. Baseline clinical characteristics among patients with and without RV dysfunction were similar. However, patients with RV dysfunction had a lower mean left ventricular ejection fraction (51.2 +/- 1.2% vs 55.5 +/- 0.3%; p < 0.001) and a greater frequency of in-hospital complications. Angiographic data from patients undergoing protocol catheterization 18 to 48 hours after hospital admission show that the infarct-related artery was more likely to be occluded in those with RV dysfunction (48% [15 of 31] vs 14% [68 of 495]; p < 0.001). There was no difference in the frequency of multivessel disease between the 2 groups. In patients with RV dysfunction in whom radionuclide ventriculography was repeated 6 weeks after hospital discharge, RV wall motion abnormalities persisted in only 18% (8 of 45). Mortality in the year after discharge was 3.5% (2 of 58) among patients with RV dysfunction compared with 1.7% (18 of 1,052; p = NS) among those without RV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

The ability of technetium (Tc)-99m sestamibi myocardial perfusion imaging at rest to evaluate myocardial infarction and first-pass ejection fraction was studied in a trial involving 18 institutions. Protocol I compared regional perfusion with occurrence of infarction by Q wave or by gated blood pool scan wall motion abnormality in 146 patients. Protocol II assessed first-pass right and left ventricular ejection fraction in 85 patients. In protocol I, Tc-99m sestamibi images were abnormal in 104 of 111 patients (94%) with both a Q wave and a gated scan wall motion abnormality and was normal in 23 of 25 patients (92%) in whom both were normal. Therefore, concordance existed in 105 (94%) patients. Of 115 patients with a Q wave, 107 (93%) had an abnormal Tc-99m sestamibi study. Of 115 patients with a gated scan wall motion abnormality, 108 (94%) had an abnormal Tc-99m sestamibi study. Tc-99m sestamibi imaging showed corresponding perfusion abnormalities in 81% of 69 anterior Q-wave infarcts, 73% of 55 inferior Q-wave infarcts and 88% of 8 posterior infarcts. Specificity in normal regions on electrocardiography and wall motion was 91, 100 and 100%, respectively, for anterior, inferior and posterior regions, respectively, between wall motion and perfusion. Of 17 myocardial segments per patient, there was concordance in 74% of patients. First pass Tc-99m sestamibi imaging of ejection fraction agreed well with conventional first-pass imaging for the right and left ventricle. It is concluded that Tc-99m sestamibi myocardial imaging at rest reliably diagnoses and localizes infarction and assesses ejection fraction by first-pass imaging.

Global and regional left ventricular performances were evaluated with equilibrium radionuclide angiocardiography in patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial at the time of hospital discharge. Studies at rest were available in 1,162 (69%) of the invasive and 1,150 (69%) of the conservative strategy patients, and exercise studies in 1,133 (67%) of the invasive and 1,145 (69%) of the conservative patients. Repeat studies were performed at the time of 6-week follow-up. Global and regional ejection fraction at rest were both comparable in patients assigned to each of the treatment strategies. However, at the time of hospital discharge patients in the invasive strategy had normal exercise responses more frequently (29.7 vs 25.8% p = 0.01), greater peak exercise LV ejection fraction (54.8 +/- 13.8% vs 53.1 +/- 14.1%, p = 0.004), greater exercise--rest change in LV ejection fraction (3.7 +/- 6.7% vs 2.7 +/- 7.2%, p less than 0.001) and greater peak exercise infarct zone regional ejection fraction (53.2 +/- 31.1% vs 50.3 +/- 33.0%, p less than 0.001) than patients assigned to the conservative strategy. At 6-week follow-up these differences between treatment strategies were no longer evident. When data were restricted to those collected at comparable work loads, similar differences in hospital discharge exercise performance between invasive vs conservative strategy patients were observed. Thus, there is a small transient difference in exercise global and regional LV performance associated with an invasive as opposed to conservative strategy after thrombolytic therapy. These differences are noted at the time of hospital discharge but not at 6 weeks, and are unlikely to confer clinical benefit.

To investigate prospectively the occurrence and significance of postinfarction transient left ventricular dysfunction, 33 ambulatory patients who underwent thrombolytic therapy after myocardial infarction were monitored continuously for 187 +/- 56 min during normal activity with a radionuclide left ventricular function detector at the time of hospital discharge. Twelve patients demonstrated 19 episodes of transient left ventricular dysfunction (greater than 0.05 decrease in ejection fraction, lasting greater than or equal to 1 min), with no change in heart rate. Only two episodes in one patient were associated with chest pain and electrocardiographic changes. The baseline ejection fraction was 0.52 +/- 0.12 in patients with transient left ventricular dysfunction and 0.51 +/- 0.13 in patients without dysfunction (p = NS). At follow-up study (19.2 +/- 5.4 months), cardiac events (unstable angina, myocardial infarction or death) occurred in 8 of 12 patients with but in only 3 of 21 patients without transient left ventricular dysfunction (p less than 0.01). During submaximal supine bicycle exercise, only two patients demonstrated a decrease in ejection fraction greater than or equal to 0.05 at peak exercise; neither had a subsequent cardiac event. These data suggest that transient episodes of silent left ventricular dysfunction at hospital discharge in patients treated with thrombolysis after myocardial infarction are common and associated with a poor outcome. Continuous left ventricular function monitoring during normal activity may provide prognostic information not available from submaximal exercise test results.

In summary, myocardial perfusion scintigraphy with either thallium or the isonitriles has added substantially to electrocardiographic definition of both myocardial infarction and acute and chronic myocardial ischemia. Using perfusion scintigraphy, one can define infarct zones, risk zones, and the presence of reperfusion following thrombolytic therapy. When perfusion scintigraphy is combined with physiologic or pharmacologic stress, myocardial ischemia can be documented, irrespective of electrocardiographic documentation of the phenomenon. Delayed imaging may be important for defining viability even in the presence of significant Q waves. Myocardial perfusion scintigraphy provides prognostic evaluation of patients with both acute and chronic coronary syndromes. When the current cumulative experience is looked at critically, it is clear that myocardial perfusion scintigraphy has helped in the development of an understanding of the limitations of electrocardiography in the diagnostic and functional categorization of patients with acute and chronic coronary disease.

The regional myocardial concentration of lidocaine after intravenous bolus administration was studied in the setting of myocardial infarction in 27 dogs utilizing a 24 hour old infarct model. Myocardial levels of lidocaine measured by gas chromatography were related to regional myocardial blood flow measured by radioactive microspheres in the same sample. A highly significant positive linear relation was noted between relative regional myocardial blood flow and lidocaine tissue concentration in animals killed 1 and 3 minutes after the injection of lidocaine (R2 = 0.81 and 0.85, respectively). This positive linear relation was no longer evident at 5 or more minutes after injection of lidocaine. This lack of linear relation resulted from dramatic reductions in myocardial lidocaine concentration in normally perfused zones with much lesser reductions in lower flow zones. Thus the initial distribution of lidocaine after bolus injection is directly proportional to myocardial blood flow within the first 3 minutes of injection. Thereafter, the washout of lidocaine appears to be the dominant factor in myocardial distribution.

We evaluated dual imaging with thalium-201 (201TI) and technetium-99m (99mTc) pyrophosphate in 80 patients with documented acute myocardial infarction (55 transmural, 25 nontransmural infarction). Color-coded isocount display of 201TI images was essential for interpretation in 16 patients. Combined 201 TI and 99mTc-pyrophosphate imaging for infarct detection was 100% sensitive; however, either was falsely negative in 12 of 80 patients. False-negative individual 201TI or 99mTc-pyrophosphate infarct images were most common in patients with small infacts or left ventricular hypertrophy. Thallium-201 images correctly localized the site of acute transmural infarction in all 51 patients with a positive image, while 99mTc-pyrophosphate localized the site of infarction in 49 of 53 with an abnormal image. Comparison of the size of the imaged infarct region revealed size discordance in 25 of 49 patinets, with 99mTc-pyrophosphate larger in 21 of 49 and 201TI larger in only four of 49. Thus dual radionuclide imaging provides definition of the presence and location of acute myocardial infarction.

The spontaneous changes in left ventricular ejection fraction (LVEF) during the first 24 hours of a first transmural infarction were assessed in 34 patients by serial gated cardiac blood pool imaging. Major therapeutic interventions with a view to limit infarct size were not used. Four determinations of LVEF were performed. Study 1 was performed as soon as possible after admission to the hospital. Studies 2 and 3 were performed 2 and 4 hours, respectively, after study 1. Twenty-four patients (70%) had study 1 within 6 hours after the onset of acute chest pain and 10 had it 6-12 hours after the onset of chest pain. Study 4 was performed 24 hours after the onset of chest pain. Compared with study 1, 19 of 34 patients (56%) had spontaneous changes in LVEF in at least one of the subsequent studies, exceeding the expected variability in stable patients. The changes ranged from a 32% increase to 14% absolute decrease. LVEF improved in 11 patients and deteriorated in eight. These spontaneous changes in left ventricular performance indicate that a single assessment of LVEF during the early hours of transmural myocardial infarction may not properly characterize cardiac performance in an individual patient and may not be the most appropriate reference against which to compare subsequent evolution of left ventricular function. These data may have implications for studies of the effects of early therapeutic interventions on LVEF.

To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02). The leakage of tracers from liposomes may result from destabilization or destruction of liposomes in the ischemic myocardium by the action of phospholipases, catabolites, and local environmental changes. This effect is less marked for negative liposomes. The use of liposomes improved the regional distribution of the tracer in infarcted tissue. However, the absolute amount of tracer delivered to the myocardium is less than that achieved with the free form.

Fifty-seven patients with acute myocardial infarction were observed for early postmyocardial infarction angina and associated transient ST-segment changes. Nine patients had postinfarction angina with transient ST-segment elevation (group 1), seventeen patients had postinfarction angina with ST-segment depression or no ST-segment changes (Group 2), and 31 patients had no postinfarction angina (Group 3). The patients in Group 1 had a statistically significant increased incidence of early reinfarction and death, when compared with the other two groups, singly or combined. There was no significant difference in the incidence of reinfarction and death when Group 2 is compared with Group 3. Patients with transient ST-segment elevation associated with early postmyocardial infarction angina may be an appropriate group in whom to consider newer, more aggressive modes of postinfarction management.

The relation of degree of regional wall motion abnormality by equilibrium radionuclide angiocardiography to the presence and mural extent of regional necrosis or scar at autopsy was evaluated in 23 autopsy patients who had a history of myocardial infarction and had equilibrium radionuclide angiocardiography within 40 days of death. Of the 228 regions evaluated by equilibrium radionuclide angiocardiography, 135 had abnormal regional wall motion and 102 (76%) of these 135 regions had evidence of myocardial infarction at autopsy. The overall sensitivity, specificity and predictive values of regional wall motion abnormality for regional necrosis or scar were 69, 59 and 76%, respectively. Of the 33 false positive regions, 20 (61%) had severe narrowing of the coronary artery supplying that region, 13 (39%) were adjacent to a region with a myocardial infarction and almost half (16 [48%]) were in the lateral wall. Eighty-three (36%) of the 228 regions were akinetic or dyskinetic, 52 (23%) were hypokinetic and 93 (41%) were normal. Sixty-three (76%) of the 83 akinetic/dyskinetic segments had transmural myocardial infarction at autopsy, 14 (17%) had nontransmural myocardial infarction and only 6 (7%) contained no necrosis or scar. In contrast, 14 (27%) of 52 hypokinetic segments had transmural myocardial infarction, 11 (21%) had nontransmural myocardial infarction and 27 (52%) were normal. Thus, the most severe regional wall motion abnormality (akinesia/dyskinesia) almost always indicates regional myocardial infarction which is usually transmural whereas less severe dysfunction (hypokinesia) is not necessarily associated with regional necrosis or scar. The severity of regional dysfunction must be considered if equilibrium radionuclide angiocardiography is used to evaluate the presence and mural extent of myocardial infarction within a region.

The effect of direct current (DC) countershock upon myocardial technetium-99m stannous pyrophosphate (PYP) uptake was studied in 22 dogs. All eight dogs imaged had positive abnormal PYP scintigrams that were usually indistinguishable from experimental infarction. In three animals, additional areas of radionuclide uptake were seen in overlying noncardiac tissue. Left and right ventricular myocardial PYP uptake averaged (+/- SEM) 23 +/- 5 times control and 24 +/- 6 times control, respectively. These activity ratios occurred without reduction in regional myocardial blood flow (RMBF), and were associated with histologic evidence of necrosis. The necrosis was usually epicardial, corresponding to the transmural site of greatest PYP uptake. The magnitude of PYP accumulation and the weight of damaged tissue increased with increasing applied energy. Thus, PYP uptake following DC countershock could result in false-positive interpretation of acute ischemic myocardial infarction. Since RMBF is normal in regions of PYP uptake, the major determinant of radionuclide accumulation is the extent of cellular damage.

Right ventricular myocardial infarction has been reported to occur exclusively in association with inferior left ventricular infarction. To determine the frequency of right ventricular myocardial infarction in association with anterior left ventricular myocardial infarction, all hearts with anterior myocardial infarction studied over a 3-year period were examined for evidence of right ventricular necrosis or scar. Of 97 hearts with anterior myocardial infarction, 13 (13%) had anterior right ventricular myocardial infarction. The right ventricular infarcts involved from 10% to 50% (mean 28%) of the circumference of the right ventricular free wall from base to apex. The associated left ventricular infarcts were all anteroseptal and large and involved from 36% to 67% (mean 50%) of the total area of the left ventricular free wall and septum. Nine of the 13 patients underwent equilibrium radionuclide angiography and six had demonstrable right ventricular regional and global dysfunction. Thus, right ventricular myocardial infarction does occur with anterior wall left ventricular infarction, and right ventricular dysfunction may be demonstrable by radionuclide angiography. Further investigation is needed to define the hemodynamic characteristics, clinical importance, and therapeutic implications of anterior right ventricular myocardial infarction.

In summary, a variety of nuclear techniques may be used to investigate the effects of thrombolytic therapy and myocardial reperfusion. Assessments of global and regional ventricular function, myocardial perfusion, and metabolic integrity are available and appear to add substantially to conventional assessment. Timing of studies appears to be critical. Complementary data can be obtained in both the acute and convalescent phase of myocardial infarction.

Repeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-99m pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P less than 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in Mp dogs, resulting in accelerated urinary excretion of PYP (46.9+/-3.6 vs 35.8+/-2.4 percent injected dose in one hour, P less than 0.01), and reduced blood PYP. Thus MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data.

To evaluate the quantitative relationships between resting potassium-43 (43K) myocardial imaging and left ventricular segmental contraction abnormalities, 15 patients were studied by both radionuclide and contrast angiographic techniques at least two months following transmural myocardial infarction. The ECG location of infarction involved the anterior wall alone in six patients, inferior wall alone in three patients, both anterior and inferior walls in five patients, and in one patient ECG-anatomic correlation was obscured by newly developed left bundle branch block. 43K defects were noted in all patients. Anterior wall 43K defects were noted in all patients with previous anterior infarction and seven of nine inferior infarcts. These 43K defects were associated with a quantifiable decrease in regional radioactivity of at least 20% of normal appearing zones, and their location correlated with the angiographic site of akinesis or dyskinesis. The extent of the 43K defect (% 43K HP [% potassium 43 hypoperfusion]) was measured by planimetry and averaged 49% of the anterior view image (range 25-66%), 43% of the left anterior oblique image (range 0-58%), with the mean of both views being 47% (range 17-62%). The mean total area of the anterior image was 58 cm2 (range 40-101 cm2). The extent of the 43K defect (% 43K HP) was related to the extent of segmental contraction abnormality (% ACS). Correlations between % ACS and anterior view % 43K HP (r = 0.67), left anterior oblique % 43K HP (r = 0.54), and mean % 43K HP (r = 0.77) were found. The total size of the anterior view image correlated with left ventricular end-diastolic volume (r = 0.79). Thus, in this initial group of patients following transmural infarction, potassium-43 imaging can be accurately and quantitatively correlated with the site and extent of regional ventricular dysfunction as it is assessed by quantitative left ventricular angiography.

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.

The uptake of liposomes bearing positive, negative, or no net charge on their membrane and containing a radioactive tracer, [99mTc]diethylenetriamine pentaacetic acid, was studied in 12 intact dogs 24 hours after the induction of myocardial infarction, and compared to the relative regional myocardial blood flow determined from radioactive microspheres. Positively charged and neutral liposomes concentrate in infarcted regions against a flow gradient, while negative liposomes are passively distributed according to regional blood flow. Because positively charged and neutral lipisomes concentrate in infarct areas and have the ability to incorporate pharmacologic agents in their aqueous or lipid phase, they may serve as vehicles for drug delivery to infarct zones of low flow.

Balloon inflation performed during percutaneous transluminal coronary angioplasty causes transient total occlusion of the coronary artery and thus provides a model for evaluation of the regional myocardial responses to transient ischemia. Twenty patients with normal left ventricular function undergoing angioplasty of isolated stenosis of the proximal left anterior descending coronary artery were studied. In group A (14 patients) analysis of one inflation-deflation sequence per patient was performed. Group B (six patients) had multiple (greater than 5) inflations; the first and last sequences were analyzed. Assessment included continuous two-dimensional echocardiography with computerized quantitative analysis of regional left ventricular wall motion, and continuous 12 lead electrocardiographic recordings. The mean duration of inflation in group A was 62 +/- 6 seconds (mean +/- SD). The onset of regional left ventricular dysfunction was 12 +/- 5 seconds after inflation. Profound dysfunction was noted in all patients. After 60 seconds of balloon occlusion of the coronary artery, 29% of patients had severe hypokinesia of the ischemic region and 71% had akinesia or dyskinesia. With deflation there was prompt recovery of regional function, with full recovery at 43 +/- 17 seconds. Comparison of data from first and last inflations in group B revealed no significant differences in time to onset of dysfunction, magnitude of dysfunction or time to complete recovery of function. The onset of ischemic electrocardiographic changes lagged behind the onset of wall motion abnormalities, with only 64% of patients showing evidence of ischemia on 12 lead electrocardiograms at 20 seconds of inflation. After 60 seconds, 86% had ischemia detectable by electrocardiography. Thus, balloon inflation during coronary angioplasty leads to profound but reversible regional left ventricular dysfunction. Repeated occlusions of the coronary artery during angioplasty do not have a cumulative ischemic effect. It may be hazardous to apply these findings to patients who have underlying major left ventricular dysfunction and in whom the reversibility of dysfunction and lack of cumulative ischemic effect may not be assured.

In Thrombolysis in Myocardial Infarction (TIMI) Phase I,290 patients with acute myocardial infarction were randomized to either intravenous recombinant tissue-type plasminogen activator (rt-PA) or intravenous streptokinase. Two hundred twenty-nine patients had radionuclide ventriculograms at discharge for assessment of global and regional left ventricular ejection fraction. Among these 229 patients 185 had totally occluded infarct-related arteries, and angiographic reperfusion of the infarct-related artery occurred in 69% of patients treated with rt-PA and 28% of patients treated with streptokinase (p less than 0.001). Mean global left ventricular ejection fraction was not different for rt-PA-treated patients compared with streptokinase-treated patients (0.46 versus 0.45). However, the average regional ejection fraction of the regions subtended by the infarct-related artery showed a trend toward better average infarct region ejection fraction in patients treated with rt-PA than in patients treated with streptokinase (0.40 versus 0.36; 0.05 less than p less than 0.06). Analysis of data according to perfusion status of the infarct-related artery showed no difference in mean global left ventricular ejection fraction between patients with sustained versus nonsustained reperfusion (0.47 versus 0.44). However, there was better average regional ejection fraction of the region subtended by the infarct-related artery in patients with sustained reperfusion (0.40 versus 0.36; p less than 0.01). Thus, quantitation of regional left ventricular function by radionuclide techniques provides a noninvasive means for evaluating the effects of thrombolysis. This study suggests a direct relation between improvement of regional left ventricular function and the greater infarct-related artery patency rate achieved by rt-PA compared with streptokinase.

Ventricular performance was evaluated sequentially in 31 patients with uncomplicated acute transmural myocardial infarction (13 anterior and 18 inferior). Left ventricular ejection fraction, ejection rate, regional wall motion, and right ventricular ejection fraction were ascertained using first-pass radionuclide angiocardiography on four occasions during hospitalization. Inferior infarction resulted in a greater reduction in right ventricular ejection fraction than anterior infarction (mean +/- SEM; 48 +/- 2 versus 56 +/- 2%, P less than 0.01). In contrast, in anterior infarction there was greater depression of left ventricular ejection fraction than in inferior infarction (34 +/- 3 versus 50 +/- 3%, P less than 0.01). From initial to discharge studies, there was no significant change in global performance or regional wall motion in either group. These data show that the location of transmural infarction has a profound effect upon the magnitude of right and left ventricular dysfunction. In addition, ventricular systolic performance remains relatively stable during the hospital phase of uncomplicated transmural myocardial infarction.

Before commencing the randomized Thrombolysis in Myocardial Infarction phase II (TIMI II) study, 370 patients were administered intravenous recombinant tissue plasminogen activator (rt-PA) within 4 hours of onset of acute myocardial infarction (AMI) and assigned to 2-hour (immediate) percutaneous transluminal angioplasty (n = 33), 18- to 48-hour (delayed) angioplasty (n = 288) or no angioplasty (n = 49) in a nonrandomized, observational pilot study. Left ventricular ejection fraction at rest and during exercise was assessed by gated equilibrium radionuclide ventriculography at hospital discharge and again at 6 weeks. At hospital discharge, ejection fraction averaged 50% at rest and 56% at peak exercise. At 6-week follow-up, ejection fraction averaged 50% at rest and 53% at peak exercise. At 6-week follow-up, resting ejection fraction average 49% in the 2-hour angioplasty group, 49% in the 18- to 48-hour angioplasty group and 55% in the no-angioplasty group. Variables independently predicting "good functional outcome" at 6-week follow-up (survival with resting ejection fraction greater than equal to 50% and no decrease with exercise) in the 18- to 48-hour angioplasty group were fewer leads with ST-segment elevation greater than or equal to 0.1 mV, younger age, rapid normalization during rt-PA infusion of ST segments or dramatic relief of chest pain, absence of arrhythmias within the first 24 hours of treatment initiation, no prior infarction and not a cigarette smoker at entry. Thus, the TIMI II pilot study demonstrates that most patients with AMI of less than or equal to 4-hour duration treated with rt-PA have good ventricular function after AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

In summary, nuclear techniques have important roles in both the acute and convalescent phase of MI. Acutely, both myocardial perfusion and ventricular function may be assessed. In patients treated with thrombolytic therapy, perfusion imaging, and metabolic imaging using PET may be able to delineate ischemic myocardium. These techniques are being developed to accurately quantify salvaged myocardium for assessing the efficacy of an acute intervention, and to characterize (functionally) the remaining myocardium for possible further intervention. In the convalescent phase, prognostic information is obtained from both rest and exercise evaluation of ventricular function and reserve, ambulatory monitoring, as well as from the presence of exercise-induced ischemia as documented by quantitative thallium imaging. The results of these studies can be used to determine appropriate management strategies.

To assess the clinical and prognostic importance of the early appearance of a functional left ventricular aneurysm after myocardial infarction, we used equilibrium radionuclide angiocardiography to study 51 patients with an initial anterior infarction. A functional aneurysm was defined as an area of systolic akinesis or dyskinesis with a distinct diastolic deformity and preserved adjacent wall motion. Functional aneurysms developed in 18 patients (Group 1). Left ventricular ejection fraction was comparable in this group and in the 33 patients without aneurysm (Group 2) (27.3 +/- 10 vs. 31.4 +/- 12 per cent). One-year mortality was markedly different, with 11 deaths (61 per cent) in Group 1 and 3 (9 per cent) in Group 2 (P less than 0.001). Six (55 per cent) of the deaths in Group 1 were sudden. Patients with a functional aneurysm appearing within 48 hours had the highest risk of dying (8 of 10). Thus, early formation of a functional aneurysm occurs frequently after anterior myocardial infarction and carries a high risk of death within one year that is independent of ejection fraction. In addition, the absence of a functional aneurysm identifies a large group with a low one-year mortality despite a markedly impaired ejection fraction.

Twenty-three surviving patients who were weaned from cardiopulmonary bypass with intraaortic balloon pump assistance returned for follow-up radionuclide left ventricular (LV) function and thallium 201 perfusion studies at a mean of 23 +/- 3 months following operation. It was found tat despite profound intraoperative myocardial depression requiring intraaortic balloon assistance, 13 patients had no change (within 10%) in the resting LV ejection fraction compared with the preoperative measurement. Among all 23 patients, there was no difference between mean (+/- standard error of the mean) preoperative and postoperative resting LV ejection fraction (48 +/- 4 vs 46 +/- 4%, p = not significant [NS]). Only 11 patients had perioperative myocardial infarction documented by new Q waves in the electrocardiogram, by elevation of creatine kinase-MB fraction, or by defects on thallium 201 imaging not explained by documented myocardial infarction before operation. Overall, postoperative resting LV ejection fraction was not different from the preoperative value in patients with perioperative myocardial infarction (44 +/- 7 vs 47 +/- 5%, p = NS). Postoperative resting LV ejection fraction rose by greater than 10% compared with preoperative values in 4 patients (3 with aortic valve replacement), remained within the 10% limit in 9 patients, and fell by greater than 10% in 10 patients (7 with perioperative myocardial infarction). Only 4 out of 16 patients studied at follow-up with exercise radionuclide studies demonstrated a normal LV response to exercise (greater than 5% increase in LV ejection fraction). Thus, among survivors requiring intraaortic balloon pump assistance for weaning from cardiopulmonary bypass, LV performance at rest is frequently preserved. In addition, 11 of the 23 patients had evidence of perioperative myocardial infarction, indicating a component of reversible intraoperative LV dysfunction.

The feasibility of imaging the inflammatory response to acute transmural myocardial infarction in man using biologically active indium-111 (111In)-labeled autologous leukocytes was assessed in 36 patients. Indium-111 leukocytes (approximately 500 microCi) were injected i.v. 18-112 hours after the onset of chest pain. Cardiac imaging was performed 24 hours later with a mobile gamma camera. Twenty-one patients had positive images and 15 had negative images. The percent of positive images increased as the interval between infarction and 111In-leukocyte injection shortened; all patients injected within 24 hours of infarction had positive images. Patients with positive images were injected with 111In leukocytes earlier after infarction (mean +/- SEM, 43 +/- 4 vs 63 +/- 7 hours; p less than 0.05) and were younger (53 +/- 2 vs 65 +/- 3 years; p less than 0.05) than those with negative images. Several other parameters that could possibly have affected the imaging results were examined and were not significantly different in patients with positive and negative images. These included peak serum creatine kinase, location of infarction, incidence of pericarditis, use of antiinflammatory drugs (aspirin and indomethacin) or membrane-active antiarrhythmic drugs (lidocaine and procainamide), peripheral leukocyte count and cell labeling efficiency. The function of the labeled cell was similar in patients with positive and negative images. Six patients with acute infarction serving as controls and given free 111In oxine and six patients with stable coronary artery disease given 111In leukocytes all had negative cardiac images.

Technetium-99m isonitrile myocardial perfusion imaging was employed in a patient undergoing thrombolytic therapy with recombinant tissue plasminogen activator for acute anteroseptal myocardial infarction. Technetium-99m isonitrile does not demonstrate significant myocardial redistribution after intravenous injection. The imaging agent was administered in the emergency room, prior to the initiation of thrombolytic therapy. The initial area at risk for infarction was visualized on images obtained after the patient had been effectively treated. Imaging performed 5 days later, after repeat injection of [99mTc]isonitrile, showed a smaller myocardial perfusion defect indicating salvage of myocardium. Thus, this technique offers promise as a noninvasive means of assessing the area at risk, the success of reperfusion, and the presence of salvaged myocardium, early in the course of acute myocardial infarction.

A multicenter study of rest and exercise thallium-201 myocardial imaging in 190 patients from five centers was performed. Exercise images were obtained after graded treadmill or bicycle stress with use of five different gamma camera models and were interpreted by the originating investigator without knowledge of other clinical data. Of 42 patients with less than 50 percent coronary stenosis, 4 (10 percent) had a resting image defect, 1 (2 percent) a new exercise defect and 5 (12 percent) either a resting or an exercise image defect, or both. Of 148 patients with coronary stenosis of 50 percent or greater, 64, (45 percent) had an image defect in the study at rest, 90 (61 percent) had new or increased defects after exercise, and 115 (78 percent) had resting or exercise defects, or both. New exercise image defects were more common than exercise S-T depression (90 of 148 [61 percent] versus 62 of 148[42 percent]; P less than 0.01). In a second group of 111 patients with acute myocardial infarction studied at three centers, 90 patients (81 percent) had image defects compared with 71 (64 percent) two had new electrocardiographic Q waves (P less than 0.01). Smaller infractions, as assessed with serum enzyme values, and diaphragmatic infarctions were less commonly detected than larger or anterior infarctions. These findings suggest that myocardial imaging complements the electrocardiographic identification of acute myocardial infarction of exericse-induced myocardial ischemia.

The external imaging patterns and the kinetics of infiltration of indium-111 labeled polymorphonuclear leukocytes (PMNs) occurring in the course of the inflammatory response associated with myocardial infarction were studied in dogs subjected to closed-chest anterior wall infarction. The effects of infarct age and regional residual myocardial blood flow upon PMN infiltration were investigated and quantified, and the capacity of indium-111 PMNs to image the experimental infarction was evaluated qualitatively. The epicardial accumulation of indium-111 PMNs occurred primarily in infarct zones with residual blood flow of 0.6 times normal and was maximal (14.8 +/- 3.8 times normal) in the lowest blood flow zone (less than 0.1 times normal). PMN accumulation in the endocardial infarct zones occurred in the regions with blood flow less than 0.6 times normal and was maximal (26.8 +/- 4.9 times normal) in the lowest blood flow zone. However, contrary to the maximal epicardial infiltration period, which occurred within the first 24 hours after infarction, the maximal endocardial infiltration occurred at 72 hours after infarction. In both endocardium and epicardium, PMN uptake was minimal at 120 hours after infarction. In vivo cardiac images were abnormal and revealed discrete, anatomically distinct areas of increased myocardial radioactivity uptake in the anterior wall of all dogs studied within 24--96 hours after infarction. All images obtained 120 hours after infarction were negative. Thus, indium-111 PMNs provide a noninvasive means of in vivo imaging of the inflammatory response to myocardial infarction and allow quantification of this response at a tissue level.

The regional concentration of lidocaine using a double constant infusion technique (250 micrograms/kg/min x 15 minutes followed by 35 micrograms/kg/mg/min x 120 minutes) was studied immediately (2 hours) in seven dogs and 24 hours (six dogs) after myocardial infarction. Tissue levels were determined by gas chromatography and related to regional myocardial blood flow as determined by the radioactive microsphere technique in multiple samples. At 2 hours after infarction a significantly higher lidocaine concentration (4.1 +/- 0.42 micrograms/g) was found in zones with greatly reduced blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that (2.6 +/- 0.19 micrograms/g) in zones with normal blood flow (regional myocardial blood flow greater than 0.8 ml/min per g) (p less than 0.01). In contrast, in the 24 hour model the opposite situation was observed. Although the concentration of lidocaine in the infarct zone was substantial, a significant decline in lidocaine tissue concentration was found in the zones of lowest blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that in normal zones (1.76 +/- 0.21 versus 3.38 +/- 0.21 micrograms/g, p less than 0.001). In addition, no significant differences in lidocaine concentrations were found between endocardium and epicardium in any of the groups other than those related to regional myocardial blood flow. Thus, with the double constant infusion technique, lidocaine reached normal and ischemic myocardium in concentrations equivalent to therapeutic plasma concentrations, even in lower infarct blood flow zones, with no significant differences between endocardium and epicardium. Of perhaps greater significance, the age of the ischemic insult is an important determinant of lidocaine tissue distribution in infarcted myocardium.

Thallium-201 ((201)T1) myocardial perfusion imaging allows definition of zones of myocardial infarction and ischemia. The temporal changes in sequential quantitative (201)T1 infarct imaging was studied 4 and 24 hours in dogs subjected to closed-chest anterior wall myocardial infarction. A temporal decrease in (201)T1 imaged infarct areas was noted in 10 of 13 animals. In no animal did the infarct area increase. The imaged infarct area decreased by an average of 30% from 12.9 ± 6.2 cm(2) at 4 hours to 9.1 ± 5.1 cm(2) at 24 hours (p < 0.001), and involved 34 ± 16% of the total (201)T1 left ventricular distribution at 4 hours and 22 ± 14% at 24 hours (p < 0.001). The magnitude of temporal change in imaged infarct area was not predicted by initial image defect or final histopathologic infarct size. Thus, the results of (201)T1 infarct imaging in the early period of infarction are clearly dependent upon the time at which the procedure is performed.

The pathophysiological correlates of thallium-201 (201TI) myocardial uptake were studied in a 24-hour-old closed-chest canine infarct model. Reduction in regional 201Tl uptake correlated well with the magnitude of tissue creatine phosphokinase depletion and microsphere estimates of transmural blood flow. In low flow endocardial regions 201Tl occasionally under-estimated the magnitude of flow reduction. Even slight reductions of 201Tl uptake (less than 0.86 of normal) were associated with histopathological and histochemical evidence of necrosis.