Clinical validation of the planar radionuclide ventriculography in patients with right ventricular dysfunction.

OBJECTIVES: Gated radionuclide ventriculography (RNV) may be used for the evaluation of the right ventricular function. However, the accuracy of the method should be clinically validated in patients suffering from diseases with specific pathology of the right ventricle (RV) and with possible left ventricular (LV) interaction. METHODS: Three groups of 15 patients each, diagnosed with arrhythmogenic right ventricular dysplasia (ARVD), pulmonary artery hypertension (PAH) or atrial septal defect (ASD) were compared to a group of normal subjects. The parameters for both ventricles were evaluated separately (ejection fractions: LVEF and RVEF, and intraventricular synchronism quantified as phase standard deviation: LVPSD and RVPSD) as well as the relation or interdependence of the right to left ventricle (RV/LV volume ratio, LV/RV ejection fraction and stroke volume ratios, and interventricular synchronism). All the variables as a whole were analyzed to identify groups of patients according to their functional behaviour. RESULTS: Significant differences were found between the patients and control group for the RV function while the LV function remained mostly within normal limits. When the RV function was considered, the control group and ASD patient group showed differences regarding the ARVD and PAH patients. On evaluating the RV/LV ratios, differences were found between the control group and the ASD group. In the PAH patients, LV function showed differences in relation to the rest of the groups. CONCLUSION: RNV is a reliable clinical tool to evaluate RV function in patients with RV abnormality.

Preconditioning during coronary angioplasty: no influence of collateral perfusion or the size of the area at risk.

AIMS: It is unclear whether the protection observed in human heart following repetition of brief episodes of ischaemia is due to opening of coronary collaterals or to ischaemic preconditioning. We investigated whether the improvement in ST segment change following repeated episodes of brief ischaemia during coronary angioplasty is due to preconditioning when the size of the area at risk and the collateral flow are taken into account. METHODS AND RESULTS: Thirty-six patients underwent percutaneous transluminal coronary angioplasty. Intracoronary ST segment changes were measured throughout the procedure and used as an endpoint. The size of the area at risk and the collateral perfusion within the ischaemic bed were measured using single photon emission computerized tomography (SPECT). Mean ST segment shift observed in all patients significantly decreased from 11.0+/-2.6 mm during the first balloon inflation to 8.5+/-2.3 mm during the second inflation. This protective effect occurred in the absence of any change in the size of the area at risk (mean: 46+/-5% of LV) and of the collateral perfusion to the ischaemic zone (mean: 23+/-4% of flow in the non-ischaemic zone). CONCLUSION: These results suggest that ischaemic preconditioning does occur during repeated brief coronary artery occlusion in the human heart.

Non-invasive testing of acquired long QT syndrome: evidence for multiple arrhythmogenic substrates.

BACKGROUND: Although well-defined clinically and electrocardiographically, Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic point of view. An increasingly accepted hypothesis is that it represents an attenuated form of Congenital Long QT Syndrome. To test this hypothesis further, we investigated patients with Acquired LQTS, using various investigations that are known to give information in patients with Congenital LQTS. METHODS: All the investigations were performed in patients with a history of Acquired Long QT Syndrome, defined by marked transient QT lengthening (QT>600 ms) and/or torsades de pointes. Measurement of the QT interval dispersion, the interlead difference for the QT interval on a 12-lead ECG, was performed in 18 patients and compared with 18 controls, matched for age and sex. To assess sympathetic myocardial innervation, I-123 Meta-iodobenzylguanidine (I-123-MIBG) scintigraphy was performed in 12 patients, together with Thallium scintigraphy, to rule out abnormal myocardial perfusion. Time-frequency analysis of a high-resolution ECG using a wavelet technique, was made for nine patients and compared with 38 healthy controls. Finally, genetic studies were performed prospectively in 16 consecutive patients, to look for HERG, KCNE1, KCNE2 and KCNQ1 mutations. The functional profile of a mutated HERG protein was performed using the patch-clamp technique. RESULTS: Compared with the control group, a significant increase in QT dispersion was observed in the patients with a history of Acquired LQTS (55+/-15 vs. 33+/-9 ms, P<0.001). In another group of patients with Acquired LQTS, 123 I-MIBG tomoscintigraphy demonstrated a decrease in the sympathetic myocardial innervation. Time--frequency analysis using wavelet transform, demonstrated an abnormal frequency content within the QRS complexes, in the patients with Acquired LQTS, similar to that found in Congenital LQTS patients. Molecular screening in 16 consecutive patients, identified one patient with a missense mutation on HERG, one of the LQTS genes. Expression of the mutated HERG protein led to altered K(+) channel function. CONCLUSION: Our results suggest that Acquired and Congenital Long QT Syndromes have some common features. They allow the mechanism of the clinical heterogeneity, found in both syndromes, to be understood. Further multi-facet approaches are needed to decipher the complex interplay between the main determinants of these arrhythmogenic diseases.

In vivo measurement of myocardial oxidative metabolism and blood flow does not show changes in cancer patients undergoing doxorubicin therapy.

PURPOSE: The aim was to investigate in patients receiving doxorubicin whether any alteration in myocardial oxidative metabolism or blood flow as assessed by positron emission tomography (PET) could be observed either after the first dose of the drug, or during its chronic administration. METHODS: Six female non-heart-failure cancer patients treated with doxorubicin were included in a longitudinal study. Resting radionuclide cineangiography and PET scanning with carbon-11 acetate were performed the day before the initiation of doxorubicin treatment at a dosage of 50 mg/m2 every 3 weeks, and 3 weeks after the cumulative administration of 300 mg/m2 (chronic toxicity). In addition, PET was performed 24 h after the first administration of doxorubicin (evaluation of acute toxicity). Myocardial oxidative metabolism and blood flow were assessed by PET (acute and chronic toxicity), and left ventricular ejection fraction was measured by radionuclide angiography (chronic toxicity). RESULTS: Using PET for both acute and chronic toxicity evaluations, no significant effect of doxorubicin was observed either on the flux through the tricarboxylic acid (TCA) cycle or on myocardial blood flow. However, systolic left ventricular function showed a small but significant impairment after the administration of 300 mg/m2 of doxorubicin. CONCLUSIONS: Other hypotheses should be explored to better explain the predominant mechanisms of the cardiotoxicity of anthracyclines in humans.

Severity and extent of perfusion defects provoked by transient coronary occlusion compared with myocardial damage observed after infarction.

A peripheral perfusion tracer injection at the time of coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA) may delineate the myocardial 'area at risk' related to a given artery. To evaluate the location, size and severity of the corresponding scintigraphic defects, we conducted a prospective study of 36 patients who received a 99Tcm-sestamibi injection during single-vessel coronary angioplasty (PTCA = 18 LAD, 16 RCA and 2 LCX) followed by SPET. For comparison, a reference group of 36 successive patients examined during the early phase of myocardial infarction (MI), matched for the same vascular territories (18 anterior, 16 inferior and 2 lateral), were analysed in the same way after standard stress/reinjection 201Tl SPET. The imaging characteristics of both groups showed excellent agreement as well degree of uptake defects, in terms of topography and extent. A defect index, taking into account both size and severity, was in the same range for PTCA and MI patients (mean +/- standard deviation): for LAD vs anterior = 28.4 +/- 13.5% (PTCA), 27.1 +/- 12.2% (MI-stress) and 24.2 +/- 10.0% (MI-reinjection); for RCA vs inferior = 15.5 +/- 10.2% (PTCA), 14.7 +/- 9.7% (MI-stress) and 13.2 +/- 8.2% (MI-reinjection). Sectoral correlations between PTCA and MI groups were also highly significant.

Three-dimensional automatic image warping in cardiac SPECT.

This study presents a new tool for the visualization and analysis of three-dimensional (3-D) cardiac single-photon emission computed tomography (SPECT). The first step consisted of computing the 3-D pseudo-skeleton of a binarized myocardium and, using the skeleton points, to design a bullet model (half ellipsoid prolonged by a cylinder). Afterwards, this model was used to drive the warping of the 3-D myocardium, initially egg-shaped, into a thick, flat disc using the thin-plate splines as deformation method. Hence, instead of achieving several rotations of the initial egg-shaped volume to have an idea on the myocardial outer face (epicardial) only, the whole myocardium is seen by looking either on top of the disc-shaped transformed myocardium (epicardial surface) or underneath for the inner face (endocardial). This new shape permitted us to localize any type of defect and to evaluate its extent and depth just by a single glance. A detailed analysis, achieved after stripping away this shape in about 10 layers, allowed us to evaluate the defect extent layer by layer and to determine whether the defect involves the totality of the myocardium layers. Finally, its flattening following the ventricular long-axis led to a summed bull's eye.

Gated blood-pool SPECT evaluation of changes after radiofrequency catheter ablation of accessory pathways: evidence for persistent ventricular preexcitation despite successful therapy.

OBJECTIVES: This study was designed to prospectively evaluate the effects of radiofrequency ablation in Wolff-Parkinson-White (WPW) syndrome by scintigraphic analysis. BACKGROUND: The functional changes triggered by radiofrequency current ablation of atrioventricular accessory pathways are not fully known. METHODS: Forty-four patients with WPW syndrome were consecutively investigated before and 48 h after radiofrequency therapy. Fourteen patients had right sided atrioventricular pathways and 30 patients had left sided bypass-tracts. Planar gated imaging and gated blood pool tomography were performed in all of these patients. RESULTS: A significant increase in the left ventricular ejection fraction (LVEF) was demonstrated in patients with left preexcitation (62.2+/-7.9% before ablation against 64.4+/-6.3% after ablation, p = 0.02) but not for those with right sided anomalous pathway. Phase analysis only gave significant differences following ablation of right sided pathways (left-to-right phase difference = 14.4+/-13.8 degrees before ablation versus 7.5+/-7.2 degrees after ablation, p<0.05). Early abnormal ventricular contraction persisted in 12 patients with right accessory pathways and in 8 patients with left accessory pathways despite the complete disappearance of any abnormal conduction as proven electrophysiologically. CONCLUSIONS: Following catheter ablation of atrioventricular accessory pathways: 1) an improvement of left ventricular function may be seen, particularly in patients with left sided accessory pathways, and 2) unexpected persistence of local ventricular preexcitation at the site of successful ablation may be detected.

Two-year assessment by exercise thallium scintigraphy of myocardial revascularization using bilateral internal mammary and gastroepiploic arteries.

OBJECTIVE: To assess the blood flow supply offered to the myocardium by surgical revascularization using bilateral internal mammary (IMAs) and gastroepiploic (GEA) arteries. METHODS: Two-year assessment by exercise thallium myocardial scintigraphy without medical treatment was performed in 122 patients (mean age 61 +/- 9 years) who underwent coronary artery bypass grafting (CABG) with exclusive use of IMAs and GEA. Usually, the right IMA was used to bypass the left anterior descending coronary artery, and the left IMA to bypass the diagonal and the marginal arteries as a sequential graft if required. The GEA was used to bypass the right coronary artery (RCA) in 50 patients and its posterior branches in 72 patients. RESULTS: During maximal or submaximal exercise stress testing, 119 patients (98%) were asymptomatic and 26 patients (21%) exhibited moderate ischemic ECG modifications which were correlated (P < 0.01) with incomplete revascularization and with the use of GEA to bypass the RCA. A third of patients had moderate ischemic thallium defects on exercise reversible after redistribution (anterior, 10; lateral, 2; inferior, 28). Silent residual myocardial ischemia detected by thallium scintigraphy was correlated (P < 0.001) with ECG modifications and incomplete revascularization; and inferior thallium defects were more frequent when GEA bypassed the RCA (P < 0.05). However, 26% of patients had residual ischemia despite a complete revascularization, and in at least 18% of cases for GEA and 8% for right IMA, arterial graft blood flow was insufficient at maximum exercise level and caused silent residual myocardial ischemia detected by thallium scintigraphy. CONCLUSIONS: Myocardial revascularization using bilateral IMAs and GEA offers a satisfactory myocardial perfusion in the majority of cases; however silent residual myocardial ischemia was detected in a third of patients and was related to incomplete revascularization and to insufficient blood flow supply probably due to small diameter of the arterial grafts.

Effects of lipid-lowering drugs on left ventricular function and exercise tolerance in dyslipidemic coronary patients.

Previous studies suggested that certain lipid-lowering drugs such as statins suppress ubiquinone, affect mitochondrial function, and may have deleterious effect on skeletal or cardiac muscles with potentially serious clinical consequences, especially in patients with established coronary heart disease and left ventricular dysfunction. In this double-blind study, we assessed the effects of 20 mg simvastatin (S, n = 32) or 200 mg micronized fenofibrate (F, n = 32, control group) on rest and exercise left ventricular function in hypercholesterolemic survivors of a previous Q-wave acute myocardial infarction. Left ventricular radionuclide imaging was performed at rest and during submaximal exercise and global and segmental (nine segment regional wall-motion score) ejection fractions were measured before treatment and 12 weeks later. Serum ubiquinone was reduced after treatment (p = 0.03) in the S but not the F group, whereas total and low-density lipoprotein (LDL) cholesterol were significantly reduced in both groups. Before treatment, mean global ejection fraction was 52.1+/-12.2% and 49.3+/-11.8% at rest in F and S patients, respectively, and increased (56.0+/-13.7% in F and 52.1+/-12.9% in S) at peak exercise (no difference between groups). After treatment, the increase in ejection fraction tended to be lower in S (0) than in F (+3.8%) but not significantly. However, ejection fraction at rest increased after treatment in S (p = 0.009) but not in F. Subgroup analyses indicated that the improvement in rest ejection fraction in S was essentially observed in patients with ejection fraction <40% (n = 8, +6%), whereas it was stable in patients with ejection fraction >40% (+1.8%). Finally, the numbers of akinetic or hypokinetic segments at rest and during exercise were not different in the two groups before and after treatment. Mean maximal exercise load (113+/-23 watts in F vs. 104+/-27 W in S before treatment) was not modified by the treatment (111+/-21 and 104+/-27 W). Thus a 12-week lipid-lowering treatment with either S or F did not negatively alter left ventricular function during exercise in dyslipidemic patients with established coronary heart disease and did not affect their ability to exercise. The improvement in left ventricular function at rest after simvastatin in patients with left ventricular dysfunction warrants confirmation in further studies with large sample size.

Does the extended use of arterial grafts compromise the myocardial recovery after coronary artery bypass grafting in left ventricular dysfunction?

OBJECTIVE: To assess the prognostic factors of myocardial recovery expected after coronary bypass surgery and the impact of surgical technique used, a prospective non-randomized study including a 1-year postoperative evaluation of left ventricular function was performed in patients with left ventricular dysfunction (left ventricular ejection fraction (LVEF) < 0.40). METHODS: From 1993 to 1996, 110 patients (mean age 61+/-11 years) were included in the study. The mean LVEF was 31+/-6%. All patients had preoperative radionuclide investigations based on the combination of stress/reinjection thallium single photon emission computed tomography (SPECT) and planar evaluation of LVEF; 88% of patients had reversible ischemic thallium defects. Two surgical technique were used: 53 patients received the left internal mammary artery with associated sequential vein graft, and 57 patients received only arterial grafts, internal mammary and gastroepiploic arteries. The mean number of distal anastomoses was 3.2+/-0.8 and 54% of patients had complete revascularization. At 1 year, all survivors had clinical evaluation and the same radionuclide investigations. RESULTS: The early mortality was 2.7%. At 1 year, 100 patients were surviving; on average, NYHA class decreased 1.9+/-0.8 to 1.4+/-0.6 (P < 0.01) and CCS class from 2.8+/-0.6 to 1+/-0.3 (P < 0.01). The mean LVEF increase from 31+/-9 to 34+/-10% (P < 0.01) and the mean LV end-diastolic volume decreased from 317+/-112 to 285+/-108 ml (n.s.). The postoperative improvement in LV function was higher in patients in NYHA class 3 or 4 before surgery (P < 0.05), when associated sequential vein graft had been used (P < 0.01), and in patients with low preoperative LVEF (P < 0.01). The postoperative LVEF improvement observed was significantly correlated with the improvement in left ventricular end-diastolic (LVED) volume and the improvement in redistribution/reinjection thallium uptake. Multivariate analysis showed that the surgical technique used and the preoperative LVEF were independent prognostic factors of the postoperative myocardial function recovery, with a significant positive impact of the vein use. CONCLUSION: This study confirms the excellent clinical results of coronary artery bypass grafting (CABG) in patients with coronary artery disease and LV dysfunction; improvement in LV function can be documented objectively and is correlated with reperfusion of hibernating myocardium. However, the extended use of arterial grafts does not allow to achieve the significant myocardial recovery observed with the use of one internal mammary artery (IMA) and associated sequential vein graft; it seems to be related to the preoperative selection of patients, but a direct negative impact of arterial grafts was documented and leads to be cautious in patients with severe LV dysfunction.

Theoretical model for myocardial functional characterization: application to a group of patients evaluated before and after surgical revascularization.

BACKGROUND: The functional improvements resulting from coronary revascularization (CABG) in patients with depressed ventricular function may be described by the use of a model combining global or local quantification of myocardial perfusion, viability, and contraction. An illustration of this model, with data provided by conventional radionuclide studies as they are performed routinely in many centers, is presented and the limitations of this approach for predicting the results of CABG are discussed. METHODS AND RESULTS: The model is based on three independent variables, which can be approximated in this preliminary study by parameters derived from standard stress and redistribution/reinjection thallium-201 single-photon emission computed tomography (SPECT) acquisitions with quantification of the tracer uptake defects and from a planar gated blood pool left ventricular ejection fraction (LVEF) measurement: Perfusion is assumed to correspond to 100-stress defect (in percentage), viability is 100-redistribution/reinjection defect, and contraction is 100(LVEF/70), assuming that a normal 70% LVEF corresponds to 100% contraction. In a group of 30 patients prospectively evaluated with this protocol and included in the study on the basis of a pre-CABG LVEF <40%, a significant improvement in LVEF was demonstrated (28.2% +/- 8.5% before CABG vs 35.8% +/- 7.3% after CABG), which is accompanied by a significant decrease of the stress thallium defects (34.8% +/- 13.8% vs 25.6% +/- 10.6%), whereas the average (but not the individual) redistribution/reinjection defects remain almost stable (27.7% +/- 10.9% vs 25.7% +/- 10.1%). As reported in the three-dimensional model, pre-CABG and post-CABG representative points clearly demonstrate the functional improvements for the main variables, but there is a large spectrum of responses to revascularization. It appears that the border between reversible and nonreversible thallium defects does not match the limit between ischemic myocardium (with no contraction alteration and therefore without contraction improvement potential) and hibernating myocardium, which is able to recover mechanical function and therefore is responsible for the improvement of global LVEF. CONCLUSIONS: Thallium SPECT is far from ideal for use as an independent characterization of perfusion and viability because hibernating myocardium may be present in both the fixed and reversible parts of thallium defects. Prediction of functional recovery is conditioned by an accurate identification of viable but underperfused and noncontracting myocardium. In the future, with the use of adequate study protocols that are able to measure viability without interference of perfusion and perfusion independent of viability, the proposed model may be able to characterize regional function as a cluster of representative points for each territory and to delineate areas of the theoretical volume corresponding to a potentially recoverable situation.

Assessment of left ventricular stiffness and compliance.

Invasive and non-invasive methods exist to assess left ventricular compliance (LVC). This work has two parts, one experimental and one clinical. We estimated left chamber stiffness in dogs by using volume data from radionuclide ventriculography (RNV) and left ventricular pressure data, synchronized with a gating system to the intraventricular dp/dt max to obtain volume and pressure data from a mean cardiac cycle. In five dogs after acute experimental ischaemia, the modulus chamber stiffness Kp rose from 30.2 +/- 4.4 to 55.4 +/- 5.9 (P < 0.01). In 10 dogs with experimental infarction after intra-aortic balloon pumping, Kp decreased from 33.7 +/- 5.0 to 15.5 +/- 3.9 (P < 0.01) and in five dogs with experimental infarction, after intravenous infusion of sodium nitroprusside, Kp decreased from 41.4 +/- 5.5 to 22.2 +/- 2.8 (P < 0.01). In eight normal volunteers and in 20 postmyocardial infarction patients, we estimated a parameter reflecting the LVC by using volume data with blood flow velocity at the mitral valve annulus. Assuming that the mitral flow-velocity variation reflects LV pressure changes, the formula LVC = (dv/dt)/(dp-dt) becomes (dv/dt)/(df/dt) = dv/df. Values obtained in normals were 0.841 +/- 0.295 m-1s and after myocardial infarction 0.331 +/- 0.10 m-1s. Both methods allow clear separation in groups of animals or patients according to the expected changes in LVC or stiffness.

[Role of isotope methods in the evaluation of cardiac function in intensive care]. / Place des méthodes isotopiques pour l'évaluation de la fonction cardiaque aux soins intensifs.

Radioisotopic cardiac investigation techniques still have a limited role in intensive care units, mainly due to cumbersome traditional equipment, even if in some cases favourable local circumstances exist, such as the proximity of a nuclear medicine unit or the availability of a mobile gamma camera. Nevertheless, nuclear techniques show a number of interesting features, mainly related to the fact that measurements of cardiac chamber volumes and of their variations can be directly derived from activity counts, without any geometrical hypothesis as it is necessary for other methods such as contrast angiography or echocardiography. The whole cardiac cycle (its systolic part as well as its diastolic part) can therefore be evaluated. In addition, since the blood pool labelling remains stable for a long period after a single tracer injection, continuous monitoring of critically ill patients becomes possible. In this case it is no longer the gamma camera imaging system which may be used but rather a very sensitive miniature detector associated with a computerized data acquisition system, allowing beat-by-beat assessment of cardiac activity. The development of this device raises specific problems related to detection geometry, elimination of extracardiac background and stability of the probe positioning on the patient's thorax, but it is clear that such a system merits its place in an intensive care unit in the near future.

Clinical experience with technetium-99m teboroxime scintigraphy in patients referred for myocardial perfusion evaluation.

A series of 30 patients (25 males, 5 females, age = 28-73 years) with a clinical indication of thallium-201 stress/4 hours redistribution scintigraphy has been studied using stress/rest (n = 7) or rest/stress (n = 23) protocols with technetium-99m teboroxime (CARDIOTEC, Squibb Diagnostics) in order to assess the clinical usefulness of this new molecule and to compare it to thallium. In all cases coronary artery disease was known or highly suspected, with a history of myocardial infarction in 18 cases (subacute n = 6, remote n = 12) and/or previous by-pass surgery or PTCA in 5 cases. Medical treatment was not discontinued at the time of stress testing. Coronary angiography was available for 27 patients. Exercise tests for both tracers were carried out on an ergometric bicycle during the same day and the levels of exercise achieved for the thallium studies were very similar to those achieved for teboroxime. Imaging was performed in three planar projections and sudies were evaluated using a model with 4 territories: septal and anterior assumed to correspond to the LAD artery, lateral and latero-posterior (= LCX), inferior and posterior (= RCA) and apex. Classification of results was: normal, ischemic, infarcted and infarcted with ischemia. With reference to the thallium-201 results, agreement was found in 86% (37/43) of normal regions and in 82% (63/77) of abnormal regions. Relative to documented coronary artery lesions (27 patients) sensitivity and specificity of thallium and teboroxime for exact correspondence between arteries and territories were, respectively: thallium, se = 71%, sp = 64%, teboroxime, se = 67%, sp = 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Technetium-99m teboroxime scintigraphy. Clinical experience in patients referred for myocardial perfusion evaluation.

In order to evaluate the clinical value of a new myocardial perfusion tracer, a series of 30 patients (25 male, 5 female, mean age 56 years) referred for thallium 201 stress/redistribution scintigraphy has been studied using stress/rest (n = 7) or rest/stress (n = 23) protocols with technetium 99m teboroxime (Cardiotec SQUIBB). In all cases coronary artery disease was known or highly probable, with a history of myocardial infarction in 18 cases. Medical treatment was not discontinued at the time of stress testing, and coronary angiography was available in 27 patients. Exercise tests for both tracers were carried out on a bicycle ergometer during the same day, and the levels of exercise achieved for the 201Tl study were very similar to those achieved for 99mTc-teboroxime. Studies performed in three planar projections were evaluated using a model with four territories: septal and anterior assumed to correspond to the left anterior descending artery, lateral and latero-posterior (left circonflex), inferior and posterior (right coronary artery) and apex. Classification of results was: normal, ischaemic, infarcted and infarcted with ischaemia. On comparison with the 201Tl results, agreement was found in 86% (37/43) of normal regions and in 82% (63/77) of abnormal regions. Relative to documented coronary artery lesions (27 patients), sensitivity and specificity of 201Tl and 99mTc-teboroxime for exact correspondence between arteries and territories were respectively: 201Tl: sensitivity 64%, specificity 60%; 99mTc-teboroxime: sensitivity 62%, specificity 77%.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of chest pain by nuclear cardiology techniques.

This article reviews the nuclear cardiology techniques which can be used to assess chest pain. Nuclear techniques can potentially give valuable information on the location and extent of myocardial perfusion abnormalities, the assessment of myocardial viability, and/or presence of myocardial necrosis and the effects, both regional and global, of myocardial ischemia on myocardial function. The article reviews specific tests available and their indications and indicates the usefulness of these techniques for the clinician managing myocardial ischemia.

A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements.

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. 123I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.

Influence on the myocardial and blood activity course of the characteristics of the labelled fatty acid injected i.v. into mice.

In order to choose a labelled fatty acid (FA) for the external study of myocardial metabolism, FAs that are different in chain length, saturation, nature and position of the radioactive label, are injected i.v. into mice. Myocardial and blood activities are measured at various times p.i. It appears that hexadecanoic and hexadecenoic acids, iodine labelled in omega position, have the highest maximal myocardial activity among all the FAs studied. Furthermore, the myocardial and blood time-activity course is similar for both FAs. As unsaturated FAs have apparently a higher myocardial fixation in man than the saturated ones, 123I 16 iodo-9 hexadecenoic acid has been selected and seems well suited for the study of myocardial metabolism.