Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

OBJECTIVES: We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents. BACKGROUND: It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension. METHODS: Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery. RESULTS: Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not. CONCLUSIONS: The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Recovery of contractility of viable myocardium during inotropic stimulation is not dependent on an increase of myocardial blood flow in the absence of collateral filling.

OBJECTIVES: The purpose of this study was to determine whether contractile recovery induced by dobutamine in dysfunctioning viable myocardium supplied by nearly occluded vessels is related to an increase in blood flow in the absence of collaterals. BACKGROUND: Dobutamine is used to improve contractility in ventricular dysfunction during acute myocardial infarction. However, it is unclear whether a significant increase in regional blood flow may be involved in dobutamine effect. METHODS: Twenty patients with 5- to 10-day old anterior infarction and > or =90% left anterior descending coronary artery stenosis underwent 99mTc-Sestamibi tomography (to assess myocardial perfusion) at rest and during low dose (5 to 10 microg/kg/min) dobutamine echocardiography. Rest echocardiography and scintigraphy were repeated >1 month after revascularization. Nine patients had collaterals to the infarcted territory (group A), and 11 did not (group B). RESULTS: Baseline wall motion score was similar in both groups (score 15.9+/-1.3 vs. 17.4+/-2.0, p = NS), whereas significant changes at dobutamine and postrevascularization studies were detected (F[2,30] = 409.79, p < 0.0001). Wall motion score improved significantly (p < 0.001) in group A both at dobutamine (-5.3+/-2.2) and at postrevascularization study (-5.5+/-1.9), as well as in group B (-3.9+/-2.8 and -4.5+/-2.4, respectively). Baseline 99mTc-Sestamibi uptake was similar in both groups (62.9+/-9.7% vs. 60.3+/-10.4%, p = NS), whereas at dobutamine and postrevascularization studies a significant change (F[2,30] = 65.17, p < 0.0001) and interaction between the two groups (F[2,30] = 33.14, p < 0.0001) were present. Tracer uptake increased significantly in group A both at dobutamine (+ 10.9+/-7.9%, p < 0.001) and at postrevascularization study (12.1+/-8.7%, p < 0.001). Conversely, group B patients showed no change in tracer uptake after dobutamine test (-0.4+/-5.8, p = NS), but only after revascularization (+8.8+/-7.2%, p < 0.001). CONCLUSIONS: The increase in contractility induced by low dose dobutamine infusion in dysfunctional viable myocardium supplied by nearly occluded vessels occurs even in the absence of a significant increase in blood flow.

Immunodetection of human atherosclerotic plaque with 125I-labeled monoclonal antifibrin antibodies.

To test the affinity of a new F(ab')2 monoclonal antibody (TRF1) against human fragment D dimer of cross-linked fibrin for atherosclerotic plaques free of detectable thrombi, 6 atherosclerotic segments of carotid and femoral artery, and as a control 5 segments of atherosclerosis-free internal mammary artery, were drawn from 11 male patients undergoing bypass surgery. All segments were carefully washed in order to remove possible endoluminal thrombi, and cut to obtain pairs of intimal fragments of similar weight, containing either plaques (n = 16), or fatty streaks (n = 12), or normal endothelium (n = 20). Each fragment underwent a direct binding test to TRF1, or to a non-specific antibody, both labeled with 125I. The activity in each fragment was measured after 3 h of incubation at 37 degrees C, and after washing the fragments every hour for 3 h. TRF1 binding (as percentage of initial activity) was significantly higher (P < 0.001) in atherosclerotic than in normal fragments (26% +/- 11.5%, vs. 9.2% +/- 3.9% in fatty streaks, and 1.9% +/- 0.6% in normal endothelium), and indirect immunofluorescence confirmed TRF1 uptake within the plaque wall. By contrast, the non-specific antibody did not show any significant binding. These preliminary results demonstrate the high specific affinity of TRF1 for atherosclerotic plaques, probably due to the hemorheologic phenomena that activate platelets and provoke the formation of fragment D dimers of cross-linked fibrin on the plaque surface.

Immunoscintigraphy of atherosclerotic uncomplicated lesions in vivo with a monoclonal antibody against D-dimers of insoluble fibrin.

To test the effectiveness of a new F(ab')2 monoclonal antibody against human fragment D-dimer of cross-linked fibrin in the detection of uncomplicated atherosclerotic lesions of the carotid vessel previously documented at echo-color-Doppler and selective arteriographic study, 8 patients underwent a scintigraphic study including dynamic and early and delayed (3 h later) static imaging of the neck after injection of a bolus of 99mTc-labeled monoclonal antibody, and were subsequently operated. Vessel specimens and blood samples were drawn at operation and counted. No adverse reaction occurred after administration of the monoclonal antibody. The atherosclerotic lesion appeared as a focal area of asymmetrical tracer uptake, already visible at early images in four patients, and at delayed images in five. The average tracer uptake ratio between pathological and normal vessels was 1.40+0.24 (P < 0.05) at time-activity curves derived from dynamic images, 2.17+/-0.97 (P < 0.05) at early static images and 2.05+/-0.98 (P < 0.05) at delayed static images, respectively. Mean vessel to blood uptake rate of specimens obtained at operation was 2.22+/-0.59 (P < 0.001). The study shows that the 99mTc-labeled antibody was found to be safe and capable of detecting atherosclerotic plaques in humans.

Differences of regional coronary flow reserve assessed by adenosine thallium-201 scintigraphy early and six months after successful percutaneous transluminal coronary angioplasty or stent implantation.

This study assesses regional coronary flow reserve using adenosine thallium-201 scintigraphy early and 6 months after angiographically successful percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Seventeen consecutive men with a significant isolated left anterior descending coronary artery stenosis were scheduled for repeat coronary angiography and adenosine-planar thallium-201 scintigraphy within 24 hours and 6 months after successful PTCA (n = 8) or stent implantation (n = 9). After background subtraction, left ventricular segmental uptake was semiquantitatively assessed on thallium images. The perfusion defect severity was scored from 0 (normal) to 3. Coronary angiograms were analyzed using an automated edge contour detection computer analysis system. Data are expressed as mean value +/- 1 SD, and proportions as percentage. The residual narrowing was 17 +/- 8% after PTCA and 9 +/- 2% after stent implantation (p = 0.02). Twenty-four hours after the procedure, hypoperfused segments were detected in all patients (100%) and in 4 patients (44%) (p = 0.05), respectively. The total number of hypoperfused segments was greater after PTCA than after stent implantation (16 [40%] vs 7 [16%], p = 0.001, respectively) as was the perfusion defect severity (4.4 +/- 3.1 vs 1 +/- 1.2, p = 0.006). Six months after the procedure, 3 of the 5 patients who had undergone PTCA without restenosis still had reversible perfusion defects. None of the stent-treated patients had restenosis or reversible perfusion defects (p = 0.05). Among PTCA-treated patients without restenosis, the total number of hypoperfused segments and the perfusion defect severity were 9 of 25 (36%) and 0.8 +/- 0.8, respectively. Thus, a regional reduction in coronary flow reserve, occasionally observed early after successful stent implantation, is probably due to a transient alteration of small coronary vessels, as was also supported by the absence of perfusion defects 6 months after the procedure. The more severe impairment of regional coronary flow reserve observed early after successful PTCA is probably also due to angiographic underestimation of the residual stenosis, as suggested also by the persistence of reversible perfusion defects 6 months after the procedure in a few patients.

Isometric handgrip exercise increases endothelin-1 plasma levels in patients with chronic congestive heart failure.

This study demonstrated an immediate and short-lasting endothelin-1 release in the circulation of patients with severe chronic congestive heart failure during isometric handgrip exercise, but not in normal subjects. Our data suggest that endothelin-1 levels may increase transiently during daily physical activity, thus contributing to progressive deterioration of left ventricular function.

Peak exercise left ventricular performance in normal subjects and in athletes assessed by first-pass radionuclide angiography.

The role of Frank-Starling law of the heart in determining the increase in cardiac output during exercise in humans is still controversial (e.g., the mechanisms responsible for the enhancement of left ventricular [LV] filling during the shortened diastolic interval). Ten weight lifters, 12 swimmers and 12 sedentary subjects who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed both at rest and at peak exercise using a multicrystal gamma camera. Compared with resting values, heart rate and cardiac index at peak exercise increased by 101 +/- 16 beats/min (p less than 0.001) and 6.7 +/- 2.8 liters/min/m2 (p less than 0.001) in weight lifters, by 96 +/- 9 beats/min (p less than 0.001) and 9.5 +/- 2 liters/min/m2 (p less than 0.001) in swimmers, and by 103 +/- 9 beats/min (p less than 0.001) and 7.3 +/- 1.8 liters/min/m2 (p less than 0.001) in sedentary subjects. Stroke volume increased by 20.5 +/- 9.8 ml/m2 (p less than 0.001) in swimmers only. End-diastolic volume at peak exercise did not change in weight lifters and in swimmers; it decreased by 8.2 +/- 8.6 ml/m2 (p less than 0.01) in sedentary subjects. A significant correlation was found between the decrease in end-systolic volume and the increase in peak rapid filling rate at peak exercise in all 3 groups (r = 0.65, p less than 0.05 in weight lifters; r = 0.59, p less than 0.05 in swimmers; r = 0.67, p less than 0.05 in sedentary subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular volumes during exercise in normal subjects and patients with dilated cardiomyopathy assessed by first-pass radionuclide angiography.

During isotonic exercise, left ventricular (LV) suction and the Frank-Starling law of the heart may have important roles in the enhancement of early LV diastolic filling and in the increase of myocardial contractility, respectively. It remains controversial whether these mechanisms operate in normal subjects or patients with dilated cardiomyopathy. Ten healthy subjects and 10 patients with idiopathic dilated cardiomyopathy who underwent maximal upright bicycle exercise testing were studied. First-pass radionuclide angiography was performed at both rest and peak exercise using a multicrystal gamma camera. In normal subjects, LV end-systolic volume at peak exercise was smaller than during baseline (17 +/- 7 vs 30 +/- 15 ml/m2; p < 0.05), whereas rapid filling volume was greater (52 +/- 16 vs 38 +/- 8 ml/m2; p < 0.01). In patients with dilated cardiomyopathy, both end-systolic (108 +/- 34 to 123 +/- 53 ml/m2; p = NS) and rapid filling (24 +/- 6 to 28 +/- 9 ml/m2; p = NS) volumes did not change from rest to peak exercise. A significant correlation was found between the changes in end-systolic volume at peak exercise and in peak rapid filling rate in normal subjects (r = 0.6; p < 0.05), but not in patients with dilated cardiomyopathy (r = 0.3; p = NS). In normal subjects, end-diastolic volume at peak exercise was similar to that during baseline (78 +/- 14 and 85 +/- 15 ml/m2, respectively; p = NS), whereas in patients with dilated cardiomyopathy, it was greater (164 +/- 50 vs 146 +/- 33 ml/m2; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina and normal epicardial coronary arteries: radionuclide features and pathophysiological implications at long-term follow-up.

BACKGROUND: The aim of this study was to identify specific characteristics associated with modifications of symptoms and to evaluate the presence of a pathophysiological link between radionuclide abnormalities and delayed run-off of coronary contrast dye in patients with angina and normal coronary arteries. METHODS: We followed up 53 patients (21 men and 32 women, mean age: 52 +/- 10 years) with angina and angiographically normal epicardial coronary arteries, 21 of whom (40%) displayed a pattern of slow contrast dye run-off from coronary vessels, on visual assessment using a semiquantitative empirical score. Exercise tests showed ECG abnormalities in 29 patients (55%). RESULTS: All patients were alive 92 +/- 44 months after catheterization (140 +/- 79 months after beginning of symptoms). However, 30 patients (57%), who reported worsening or no change of symptoms, presented with a non-significant higher prevalence of conduction abnormalities at rest ECG (27 versus 17%), pathological exercise tests (57 versus 52%), and delayed run-off (47 versus 30%). Regional left ventricular function and perfusion were then simultaneously assessed at rest and peak exercise with 99mTc-sestamibi. Exercise-induced radionuclide abnormalities were detected in 27 patients (51%), who also presented with a non-significant higher prevalence of pathological exercise tests (63 versus 43%) and no improvement of symptoms (63 versus 46%). However, exercise-induced functional and perfusional abnormalities were simultaneously present in 29 out of 42 (69%) coronary territories supplied by vessels with delayed run-off, versus 21 out of 117 (17%) normal territories (P = 0.00032). CONCLUSIONS: Despite a good prognosis, some patients with angina and normal coronary arteries presented no improvement of symptoms at follow-up, and had functional and perfusional abnormalities in coronary territories supplied by vessels showing delayed contrast dye run-off.

Nitroglycerin-induced changes in myocardial sestamibi uptake to detect tissue viability: radionuclide comparison before and after revascularization.

BACKGROUND: Nitroglycerin (NTG) is known to increase the blood supply to the myocardium, and would thus increase the delivery of a perfusional tracer such as sestamibi (MIBI) to the tissue. The latter, in turn, would take up and concentrate the tracer to a greater extent than in basal conditions only if energy-dependent mechanisms were still available-that is, only if the cells were still viable. METHODS: We evaluated the changes that intravenous administration of NTG induced on the uptake of MIBI by akinetic myocardial areas, using tomographic perfusional imaging in 23 patients with previously ascertained anterior myocardial infarction who were undergoing myocardial revascularization procedures. Changes in uptake were compared with echocardiographic and perfusional changes occurring after operation. RESULTS: The improvement of MIBI uptake after NTG correctly identified 12 of the 16 patients (75%) showing postoperative wall motion improvement; they comprised 12 of the 14 (86%) patients with NTG-induced increase in MIBI uptake who showed improved wall motion after operation. A close correlation (r = 0.88, P < 0.001) was found between the increase in myocardial MIBI uptake induced by NTG infusion and that induced by revascularization. The presence of collaterals to the akinetic area was associated with a significantly (P < 0.01) greater increase in MIBI uptake both during NTG infusion and after operation. CONCLUSIONS: The results of this study suggest that MIBI perfusional myocardial scintigraphy during infusion of NTG is capable of detecting viable but chronically hypoperfused myocardium, predicting postoperative wall motion and perfusional improvement, and reflecting the postoperative pattern of perfusion. The best results were achieved in patients with evidence of collateral circulation supplying the infarcted area.

Immunoscintigraphy of venous thrombi: clinical effectiveness of a new antifibrin D-dimer monoclonal antibody.

Safety and thrombus imaging capabilities of the 99mTc-labeled form of a new F(ab')2 monoclonal antibody (MoAb) against fragment D dimers from cross-linked human fibrin, previously shown to be effective labeled to 131I in detecting venous thrombi in the rabbit, were investigated. Sixteen patients (seven men, mean age: 60+/-7 years) with deep (n = three) and superficial (n = 13) venous thromboses of the lower limbs documented at echo-Doppler study underwent, 24 hours before saphenous vein stripping, a scintigraphic study after IV injection of the 99mTc-MoAb (1,129+/-275 MBq/mL), acquiring dynamic images, as well as early and delayed static images of lower limbs. Tracer activity was compared in normal and pathologic areas. At the operation, vessel wall including the thrombotic lesion was isolated, weighed, and counted. Blood radioactivity and MoAb concentration were also measured. No adverse reaction was observed after MoAb administration. Thrombus site appeared as a focal area (hot spot) of asymmetrically increased tracer uptake, already detectable at early images in all patients. All thrombi detected at echo-Doppler study (n=25) were confirmed at scintigraphic study, which showed four additional hot spots subsequently confirmed to represent thrombi at operation. Average percent ratio between pathologic and normal regions was 1.51+/-1.34 (p < 0.05) at time-activity curves, 2.27+/-1.1 (p < 0.05) at early static images, and 2.15+/-1.2 (p < 0.05) at delayed images, respectively. Thrombus-to-blood uptake ratio was 4.3+/-0.9 (p < 0.01). The F(ab')2 MoAb proved to be safe, and low levels of antimouse antibodies were detected in response, although further studies are needed to assess tolerance and effectiveness in case of a second administration in the same patient. The 99mTc-labeled MoAb was very effective in identifying venous thromboses both at deep and superficial localizations, although its sensitivity and specificity need be evaluated in a more numerous group, including also patients with different and clinically more relevant localizations, such as caval thromboses. However, the possibility of obtaining high-quality images within 4 hours of MoAb administration is clinically relevant, and carries also therapeutic implications, especially in pulmonary thromboembolism.

99mTc anti-D-dimer MoAb detects venous thrombi in man.

Authors' work is based on the ability of a 99mTc labelled antibody (MoAb) against D-Dimer (D-D) to visualize thrombi in man. D-Dimer is a specific epitope created during the cross-linking process of fibrin strains. Five normal volunteers and 5 patients with leg varices were given 10 mCi of 99mTc anti-D-Dimer MoAb (research approved by our Ethical Committee). Each patient gave his informed consent. Scintigraphic images were taken at 5, 60, 180 min. No adverse reaction was observed. Two patients underwent saphenous stripping 3 hrs after injection, in the other 4 patients scintigraphic images were acquired at 6 and 8 hrs. Twelve hot spots were visualized. Of these, 5 were localized during operation with a pencil-like probe and exsected. Specific activity of exsected thrombi, saphenal walls and blood samples was measured. Thrombus to vein wall ratio of 2.2 +/- 0.6 and a thrombus to blood of 3.1 +/- 0.8 was measured. In non operated patients the best scintigraphic images were obtained between 60 and 180 min. 99mTc anti-D-Dimer MoAb is a promising agent for localization of thrombi.

Detection of early systolic dysfunction in ischemia by sequential radionuclide imaging of ejection rates.

The effectiveness of sequential imaging of early regional left ventricular contraction in the detection of ischemic abnormalities was assessed in 47 patients (15 with previous infarction) with angiographically proven coronary artery disease, and 11 normal volunteers, undergoing first pass radionuclide angiography with a multielement gamma camera at rest and at peak exercise. Global left ventricular hemodynamic parameters, and functional images of regional ejection fraction and ejection rate were compared to 6 pairs of sequential rate images showing the decrease and the increase of regional left ventricular volume during a time-interval of 80-280 ms (at rest) and 50-175 ms (at stress) from end-diastole. Diagnostic accuracy of sequential images (67-91%) was higher than that of ejection rate image (71-72%), and of global hemodynamic parameters (33-60%), in the detection of coronary patients. Regional sensitivity of stress sequential increase and decrease image achieved 77% and 100%, respectively. During early systole sensitivity of stress sequential increase and decrease images approached 100% even at rest, subsequently decreasing because of normalizing contraction. Thus, the analysis of early systolic dysfunction provided by dynamic sequential functional images of ejection rates proved to be an effective diagnostic tool in the detection of myocardial ischemic dysfunction.

What is the most appropriate stimulation mode in patients with sinus node dysfunction?

Sinus node disease (SND) has caused many controversies about the appropriate stimulation mode. We compared the advantages and disadvantages of VVI, AAI, DDD, and DDI mode. In an additional study, left ventricular function at rest (R) and during exercise (E) was investigated in dual chamber and ventricular stimulation mode with a stimulation rate of 70 ppm (R) and 110 ppm (E). A total of 223 patients (pts) was investigated (67 AAI, 87 VVI, 69 DDI). Hemodynamic disadvantages in VVI mode resulted in a 55% actuarial incidence of atrial fibrillation after five years. In AAI mode, we found another 25% complication rate due to impaired AV conduction (n = 9) or a bradyarrhythmia (n = 6) with slow ventricular response. DDI mode implies the possibility of sustaining a pacemaker mediated tachycardia. Single ventricular stimulation with a high stimulation rate (110 ppm) under E showed a worse left ventricular performance as compared to dual chamber stimulation. DDI mode shows none of the aforementioned disadvantages. To sum it up: Until a dual chamber rate responsive pacemaker becomes available, the DDI mode represents the best stimulation mode for patients with a SND.

[Exponential analysis of the relationship between ST segment depression and heart rate during exercise in patients with ischemic cardiopathy]. / Analisi esponenziale del rapporto fra sottolivellamento del tratto ST e frequenza cardiaca durante sforzo in pazienti con cardiopatia ischemica.

ST segment displacement sensitivity and specificity during exercise in the detection of myocardial ischemia are controversial, even when using mathematical approaches such as a linear regression analysis of ST/heart rate slope. In an attempt to see whether an exponential fit (ST = A-B*exp (-K*RR] of ST/heart rate relation during exercise could increase the diagnostic accuracy of exercise test in the detection of myocardial ischemia, we studied 165 patients (141 men and 24 women, mean age: 56 +/- 10 years) undergoing a simultaneous radionuclide assessment of regional ventricular function and myocardial perfusion at rest and at peak exercise in 4 hours by means of 2 injections of 99mTc-MIBI. Normal radionuclide findings were found in 4 subjects, whereas exercise-induced myocardial ischemia was detected in 90 patients with no evidence of previous myocardial infarction, and in 71 patients with previous myocardial infarction. ST segment depression was present at peak exercise in no normal subject, and in 52.2% and 60.4% of ischemic and infarcted patients, respectively, achieving a sensitivity of 55.9%, a specificity of 100% and a diagnostic accuracy of 57%. A, B and K coefficients of exponential analysis showed a wide variability among patients; however, the algebraic sign of K coefficient was negative in 50% of normal subjects versus 9.9% of patients (chi 2-test: p less than 0.02), thus achieving a sensitivity of 90.1%, a specificity of 50% and a diagnostic accuracy of 89.1% in the detection of exercise-induced myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Improvement in the accuracy of diagnosis of ischemic heart disease with simultaneous radioisotope evaluation of regional myocardial function perfusion and an exercise test]. / Incremento di accuratezza nella diagnosi di cardiopatia ischemica mediante valutazione radioisotopica simultanea della funzione e della perfusione miocardica regionali ed unico test ergometrico.

The recently developed myocardial agent methoxy-isobutyl-isonitrile (MIBI), labelled to 99mTc, allows one to evaluate global and regional ventricular function as well as myocardial perfusion by means of a single exercise stress test, significantly increasing diagnostic accuracy for coronary artery disease. Between September 1988 and March 1989, 407 patients with either suspected or already ascertained coronary artery disease underwent simultaneous assessment of regional ventricular function with first pass radionuclide angiography, and of myocardial perfusion with single photon emission computerized tomography, by means of 2 injections of 99mTc-MIBI at rest and at peak of the same exercise test. Out of these patients, 56 (52 men and 4 women, whose mean age was 57 +/- 7 years) underwent coronary angiography within 6 months of radionuclide examination and were included in the study. There were 13 1-vessel, 26 2-vessel and 17 3-vessel disease patients. Thirty-six of them had had a previous (greater than 6 months old) myocardial infarction, on the anterior wall in 16 patients, on the inferior wall in 20. In all patients a computerized bicycle stress test was performed; interruption criteria were ST segment depression greater than or equal to 1 mm in 27 patients (48%), the achievement of a heart rate greater than 85% of maximal age-predicted heart rate in 12 patients (22%) and fatigue in 17 patients (30%). Scintigraphic results were compared to angiographic findings: global sensitivity and specificity of the simultaneous evaluation were 82% and 81%, respectively, vs 95% and 56% of functional results and 85% and 71% of perfusion results, respectively. Regional analysis was also performed, by dividing scintigraphic images into the territories supplied by the 3 main coronary vessels, i.e., left anterior descending artery (LAD), left circumflex artery (LCx) and posterior descending artery (PD). On LAD territory the simultaneous evaluation achieved a sensitivity of 88% and a specificity of 63%, vs 98% and 38% of functional analysis and 88% and 50% of perfusional analysis, respectively. On LCx territory sensitivity and specificity were respectively 71% and 96%, vs 91% and 64% of function, and 77% and 96% of perfusion alone. On PD territory sensitivity was 85%, vs 94% and 91%, respectively; specificity was 73%, vs 55% and 55%, respectively. Combined functional and perfusional analysis achieved a 68% sensitivity in identifying less than or equal to 75% coronary narrowings, and a 90% sensitivity for greater than 90% narrowings.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute oral trimetazidine administration increases resting technetium 99m sestamibi uptake in hibernating myocardium.

BACKGROUND: Trimetazidine is an antiischemic drug protecting the myocardium from ischemic damage through the preservation of mitochondrial oxidative metabolism, without any hemodynamic effect. 99mTc-sestamibi is accumulated by myocytes according to mitochondrial function. As mitochondrial metabolism is thought to be present in hibernating myocardium, the aim of the study was to investigate trimetazidine effects on infarcted and eventually hibernating myocardial areas by means of 99mTc-sestamibi perfusional scintigraphy, comparing them to postoperative recovery of wall motion. METHODS AND RESULTS: Twelve patients with previous myocardial infarction underwent 2 perfusion imaging tomographic studies at rest with 99mTc-sestamibi, receiving placebo or trimetazidine (60 mg orally), and subsequently underwent revascularization procedures. An echocardiographic study was carried out before and >3 months after revascularization. At polar map analysis of placebo scan, infarcted vascular territories (wall motion score index: 2.65 +/- 0.31) showed 73.7% +/- 10.4% of the territory with activity <2.5 SD from the mean of normals, for a severity (expressed as the sum of the standard deviations below average normal values in all abnormal pixels) of 833.8 +/- 345.7. Polar map analysis of the trimetazidine scan showed tracer uptake increased significantly in 11 of them, by 8.2% +/- 3.0% (p < 0.001) and by 180.3 +/- 111.0 SD (p < 0.001), respectively. Postoperative wall motion score index improved significantly in 9 of these territories (-0.9 +/- 0.4, p < 0.001). CONCLUSIONS: Trimetazidine-associated increase in 99mTc-sestamibi uptake in infarcted but viable myocardial areas is probably related to an improvement in mitochondrial oxidative metabolism that is essential to 99mTc-sestamibi retention. Additionally, coupling trimetazidine administration to 99mTc-sestamibi perfusional scintigraphy may represent a means of detecting viable myocardium.