What is expected from positron emission tomography in the quantitation of regional myocardial perfusion in man.
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Biomedical subjects
Publications and source records attributed to O Parodi.
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Silent ischaemia has been widely investigated limiting the diagnostic approach to the left ventricle. To date, no systematic study on silent ischaemia in patients with demand-induced right ventricular dysfunction has been reported. The occurrence of painless ischaemic episodes was evaluated by atrial pacing and radionuclide angiography in 20 consecutive patients with single right coronary artery stenosis and without previous myocardial infarction. At the peak pacing rate all patients showed transient myocardial dysfunction (reduction of ejection fraction and/or development of wall-motion abnormalities) localized to the right, the left, or to both ventricles in 9, 1 and 10 patients, respectively. Eight patients experienced chest pain (group 1) and 12 were asymptomatic (group 2) at the maximal pacing rate. Basal left ventricular ejection fraction (55 +/- 4% vs. 55 +/- 5%), basal right ventricular ejection fraction (48 +/- 4% vs. 46 + 8%), peak pacing left (52 +/- 9% vs. 50 +/- 11%) and right (38 +/- 7% vs. 37 +/- 9%) ventricular ejection fractions, and maximal pacing pressure rate product (17,289 +/- 2880 vs. 19,244 +/- 3806) were not significantly different in the two groups. This study demonstrates a high prevalence of silent ischaemia in patients with single right coronary artery stenosis and pacing-induced dominant right ventricular dysfunction. Painful episodes do not appear to be related to the magnitude of changes in ejection fraction.
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In ischemic heart disease, the left ventricle has been considered the main target of an imbalance between myocardial oxygen supply and demand. Accordingly, the approach to ischemia has been directed at the evaluation of the left ventricle. The aim of this study was to assess the relative involvement of the left and right ventricle in patients with isolated right coronary artery stenosis. We studied 20 patients with a clinical history of effort angina (15 male, 5 female, mean age 54.1 +/- 6.2) using radionuclide angiography and atrial pacing. Findings were compared with those of 6 normal subjects that were paced at the maximal heart rate of 150 beats/min. Atrial pacing was interrupted because of diagnostic ST segment depression in 8 patients, Wenckebach type atrioventricular block in 1, chest pain without electrocardiographic changes in 4 and the achievement of the maximal prefixed heart rate of 150 beats/minute in 7. With respect to control conditions, during atrial pacing right ventricular ejection fraction declined from 46.8 +/- 6.8% to 37.4 +/- 8.1% (p less than 0.001), while no significant change was observed in left ventricular ejection fraction values (55.2 +/- 4.5% and 51.1 +/- 10.2% respectively). During atrial pacing, left ventricular peak filling rate increased from 1.77 +/- 0.53 to 4.71 +/- 1.8 end-diastolic volumes/second (p less than 0.0001). Qualitative analysis of regional wall motion showed a right ventricular dysfunction in 19/20 patients; this was prevalent in 9 and involving also the left ventricle in 10; an isolated impairment of the left ventricle was observed in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously demonstrated that enhanced glucose utilization in reperfused myocardium as assessed by F-18 2-deoxyglucose (FDG) and positron tomography predicts functional recovery. In this study, we compared segmental uptake of F-18 FDG with that of Tl-201 and Tc-99m (Sn) pyrophosphate (Tc-99m PPi) as conventional markers of tissue viability in seven dogs after a 3-hour intracoronary balloon occlusion and 20 hours of reperfusion. Myocardial blood flow was determined with microspheres. Regional retention fractions were calculated from tracer tissue concentrations, the arterial input function, and blood flow. Ischemic injury was assessed by triphenyltetrazolium chloride (TTC) staining and histologic analysis. At 24 hours, blood flow was 22% lower in reperfused than in control myocardium (p less than 0.05). Uptake of Tl-201 was related linearly to blood flow (r = 0.92), while glucose utilization and Tc-99m PPi were 2.9 (p less than 0.01) and 4.7 (p less than 0.05) times higher in reperfused than in control myocardium. Retention fractions of Tc-99m PPi increased with the degree of ischemic injury, while F-18 FDG uptake was highest in segments with mild cell injury. Thus, in ischemically injured myocardium, Tl-201 primarily reflects blood flow. F-18 FDG as a marker of glucose utilization identifies ischemically injured but viable tissue. The admixture of necrotic cells can be determined with Tc-99m PPi. Our results indicate that a dual tracer approach might best characterize the presence and extent of reversibly and of irreversibly injured tissue in a given myocardial region.
UNLABELLED: In the past ten years we studied 80 patients with angina at rest by 201-Thallium perfusion scintigraphy. According to ECG changes during episodes of transient ischemia at rest, the patients were divided into three groups. Thirty six patients showed transient ST segment elevation (Group 1); 33 ST segment depression (Group 2) and 11 normalization of negative T waves (Group 3). 201-TI scintigraphy was performed during spontaneous or ergonovine induced episodes of ischemia and at redistribution. Group 1 showed localized and severe perfusion defects, well correlated to the site of ECG changes. Group 2 showed more diffuse and less severe perfusion defects, less correlated to the site of ECG changes. Group 3 showed perfusion defects similar to those observed in Group 1 and associated in 54% with basal perfusion defects due to previous myocardial infarction. IN CONCLUSION: A) three main perfusion patterns are associated with the three types of ECG changes; B) relative to ECG, myocardial scintigraphy provides a more accurate definition of the site and extension of ischemia, particularly in Group 2 patients.
The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of various doses of intracoronary verapamil on the diameter of angiographically normal left coronary artery segments was investigated in 22 patients with and without coronary atherosclerosis by quantitative angiography. Very low doses (50 micrograms) were given in 3 patients; doses of 250 micrograms, 350 micrograms and 500 micrograms were administered in 7, 6 and 13 patients, respectively. A single dose was administered in 15 patients, while two increasing doses of verapamil were tested in 7. The effect of verapamil was compared in each patient with that of nitroglycerin (NG; 0.6 mg), administered sublingually in all as the last step of the study. An additional group of 8 patients served as the control. These patients received 4 intracoronary injections of contrast medium without drugs and a fifth injection following 0.6 mg of sublingual NG. In the control group no significant changes in coronary artery diameter were observed following the four control injections of contrast medium, while a 18 +/- 9% increase in vascular diameter was observed following NG. When verapamil was injected a dose-dependent vasodilation was observed, which began to be significant with doses higher than 250 micrograms. Mean percent variations of coronary artery diameter relative to control were -0.2 +/- 3.6%, 4.6 +/- 5.5%, 11.4 +/- 7.5% and 19.9 +/- 10.7%, in response to verapamil doses of 50, 250, 350 and 500 micrograms, respectively. Subsequent nitroglycerin induced a 21.5 +/- 10.7% mean percent coronary artery dilation (NS vs verapamil 500 micrograms and vs NG in the control group). Thus, verapamil induced a dose-dependent coronary vasodilation which at a dose of 500 micrograms was comparable to that induced by NG. Both with verapamil and NG the smallest vessels exhibited the greatest vasodilation. It is concluded that at the doses used in this study, injection of verapamil into the left coronary artery is safe and markedly decreases tone in the large coronary arteries. This finding supports the use of verapamil in clinical conditions in which the role of coronary vasoconstriction is proven or thought to be relevant.
The availability of mobile gamma cameras or the nearness of nuclear medicine devices to the coronary care unit make the assessment of transient myocardial ischemia by radioisotopic techniques practical. Nuclear cardiology provides information on the presence, site and extent of ischemia and helps the clinician in the evaluation of myocardial functional impairment and recovery. Monitoring of myocardial wall motion by radionuclide ventriculography demonstrates that during angina at rest; global ejection fraction is not always sensitive to regional ischemia; episodes of angina with undetectable electrocardiographic signs of ischemia can be associated with severe myocardial dysfunction; separate left and right phase analysis of radionuclide ventriculography is a sensitive tool to assess segmental dyssynergy localized to the left or the right ventricle; a prevalent right ventricular impairment during ischemia, not measurable by Thallium scintigraphy, is possible; the recovery of function after ischemia is usually fast and apparently complete. In addition, useful diagnostic information can be derived by left ventricular injection of radioactive microspheres during cardiac catheterization followed by gated acquisitions of the intramyocardial radioactivity. Gated microsphere acquisitions, providing diastolic and systolic images, avoid blurring of images due to cardiac motion and enhance contrast between myocardium and background: the overall result is an improved detection and definition of small perfusion defects. Furthermore, this technique permits simultaneous assessment of regional perfusion and wall motion. An appraisal of potential mismatches between flow and function after revascularization procedures can be recognized by this approach. The development of technology is improving the performance of nuclear medicine instrumentation, hampered, at present, by limited spatial and temporal resolution.(ABSTRACT TRUNCATED AT 250 WORDS)
Information on the anatomical site of myocardial ischemia and infarction is commonly derived from the 12-lead electrocardiogram; however, correspondence between an electrocardiogram lead, showing ischemic changes and actual location of ischemia is not always present. In our experience, a good correspondence between the electrocardiogram and perfusion defects was found in patients with angina at rest and anterior ST segment elevation or normalization of negative T wave while patients with transient ST segment depression showed perfusion defects which correlated less with electrocardiographic changes. In addition, patients with ischemic episodes at rest and with inferior ST segment elevation, right or left ventricular ischemia were indistinguishable on the basis of the electrocardiogram as documented by Thallium-201 scintigraphy and radionuclide ventriculography. In effort angina, the site and extension of ST segment depression, even in patients with single vessel disease, failed to localize the actual anatomical location of myocardial ischemia. In patients with persistent ST segment depression and/or negative T waves, and clinically documented myocardial necrosis, transmural and non-transmural persistent perfusion defects were found in spite of absence of Q waves. In these patients, late normalization of the electrocardiogram did not correspond to normalization of flow. In conclusion, electrocardiographic changes do not always provide correct information regarding the presence, location and extent of myocardial ischemia and a multiparametric approach is often required in order to characterize ischemic and/or necrotic areas.
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Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.
This study describes the clinical experience with four patients with variant angina caused by spasm of the right coronary artery who were assessed for evidence of right ventricular involvement. The patients were suspected of having predominant right ventricular ischemia on the basis of normal thallium-201 scans, left ventricular ejection fraction, regional wall motion assessed by equilibrium radionuclide angiography (RNA), two-dimensional echocardiographic findings, and left ventricular hemodynamics; all procedures were performed during transient ST segment elevation in the inferior leads. Right ventricular ischemia was documented in four patients by first-pass radionuclide studies and phase analysis of RNA, and in three patients by simultaneous right and left hemodynamic monitoring. The clinical findings from these four patients are compared with those from four other patients with similar electrocardiographic changes, coronary anatomic distribution, and documented right coronary spasm but with evidence of left ventricular involvement as documented by abnormal thallium-201 scintigraphy, RNA, two-dimensional echocardiography, and left hemodynamics during ischemic episodes. Although preliminary, these data indicate the existence of prevalent right ventricular ischemia during variant angina caused by right coronary vasospasm. This condition should be suspected whenever typical anginal symptoms and/or ischemic electrocardiographic changes are accompanied by normal thallium-201 scintigraphic findings and/or normal left ventricular function as assessed by RNA, echocardiography, and left hemodynamic monitoring. Among noninvasive procedures, first-pass radionuclide study and phase analysis of RNA represent suitable techniques for detecting transient right ventricular dysfunction.
Possible effects of regional wall motion abnormalities on apparent regional myocardial tracer concentrations on emission tomographic images were evaluated in six open chest dogs. Each dog was studied twice: In Run 1, 13N ammonia and microspheres were injected during a 6 min coronary occlusion, and serial images acquired by positron emission tomography during occlusion and reperfusion. In Run 2, 1 h later, 13N ammonia and microspheres were reinjected at control, and serial images recorded at control, during a repeat 6 min coronary occlusion, and after reperfusion. Segmental function was monitored with ultrasonic crystals, and 13N tissue concentrations determined in vivo from the tomographic images and postmortem by well counting. In Run 1, fractional shortening in ischemic segments fell by 89 +/- 16% SD from control. The ischemic versus control segment ratio for 13N activity concentrations averaged 0.29 +/- 0.08 and for microspheres 0.20 +/- 0.15. In Run 2 the ischemic versus control segment ratio was at control 0.77 +/- 0.12 for 13N tissue activity and 0.85 +/- 0.07 for microspheres. Fractional shortening fell during occlusion by 131 +/- 29% from control, returned to control early, and fell again by 11 +/- 16% late during reperfusion. These changes were paralleled by changes in apparent regional 13N tissue concentrations of the prelabeled myocardium. Compared with control, they were 37 +/- 9% lower during occlusion and rose to 94 +/- 20% early and to 89 +/- 16% at control late during reperfusion. In vitro determined tissue concentration ratios of ischemic to control myocardium were similar for 13N and microsphere activity (0.83 and 0.85), which ruled out loss of 13N ammonia from tissue during occlusion or reperfusion. Our results indicate that regional wall motion abnormalities cause artifactual segmental defects in tracer concentrations on emission tomographic images of the heart, which must be considered for qualitative and quantitative analysis of regional tracer tissue concentrations.
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