The relationship of myocardial contraction and electrical excitation--the correlation between scintigraphic phase image analysis and electrophysiologic mapping.

BACKGROUND: Phase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation. OBJECTIVES: We sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both. METHODS: In 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites. RESULTS: In each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups. CONCLUSIONS: A noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences.

Modulation of molecular conductance induced by electrode atomic species and interface geometry.

We present a systematic theoretical investigation of the interaction of an organic molecule with gold and palladium electrodes. We show that the chemical nature of the electrode elicits significant geometrical changes in the molecule. These changes, which are characteristic of the electrode atomic species and the interface geometry, are shown to occur at distances as great as 10 Angstrom from the interface, leading to a significant modification of the inherent electronic properties of the molecule. In certain interface geometries, the highest occupied molecular orbital (HOMO) of the palladium-contacted molecule exhibits enhanced charge delocalization at the center of the molecule, compared to gold. Also, the energy gap between the conductance peak of the lowest unoccupied molecular orbital (LUMO) and the Fermi level is smaller for the case of the palladium electrode, thereby giving rise to a higher current level at a given bias than the gold-contacted molecule. These results indicate that an optimal choice of the atomic species and contact geometry could lead to significantly enhanced conductance of molecular devices and could serve as a viable alternative to molecular derivatization.

Heterogeneous sympathetic innervation influences local myocardial repolarization in normally perfused rabbit hearts.

BACKGROUND: Heterogeneity of sympathetic innervation is thought to contribute to the potential for fatal arrhythmia. However, little is known about the effects of heterogeneous innervation on repolarization. METHODS AND RESULTS: To assess this relationship, we measured activation recovery intervals (ARIs) from 64 epicardial sites in 11 rabbits studied 2 weeks after regional denervation produced by phenol and 4 sham-operated rabbits. ARI results were compared with the distribution of sympathetic innervation measured from 3D reconstructions of serial autoradiographs of [(125)I]metaiodobenzylguanidine and (99m)Tc-sestamibi. ARIs were recorded during baseline sinus rhythm, norepinephrine (NE) infusion (0.1 microg. kg(-1). min(-1)), and left stellate ganglion stimulation (SS). NE shortened ARI in 98% of electrodes in the denervated region. The degree of ARI shortening and dispersion increased (P<0.001 and P<0.01, respectively) as denervation became more severe. SS shortened ARI in 30% of electrodes in the denervated area, with increased shortening and dispersion related to increased severity of denervation (P<0.01). SS prolonged ARI in 70% of electrodes in the denervated area, with no correlation with severity of denervation. CONCLUSIONS: The magnitude and dispersion of local repolarization responses are related to the severity of denervation, as well as the type of stimulation: neural (SS) versus humoral (NE). The differences may relate to the concentration of NE released.

Effect of transmural versus nontransmural myocardial infarction on inducibility of ventricular arrhythmias during sympathetic stimulation in dogs.

Transmural myocardial infarction interrupts sympathetic nerves and denervates viable muscle distal to myocardial infarction. The effect of sympathetic stimulation on responses to programmed ventricular stimulation was studied in dogs without myocardial infarction (Group I: n = 5), with transmural anterior wall myocardial infarction (Group II: n = 6) and with nontransmural anterior wall myocardial infarction (Group III: n = 9). Ventricular effective refractory period during sympathetic stimulation decreased by 16 +/- 18, 1 +/- 2 and 12 +/- 8 ms (mean +/- SD) in viable muscle of the inferoapical left ventricle in Groups I, II and III, respectively, suggesting efferent sympathetic denervation by transmural myocardial infarction only. Sustained ventricular tachycardia or fibrillation was induced more easily during sympathetic stimulation in six of the six dogs with transmural infarction, but in only two of the nine dogs with nontransmural infarction (p less than 0.01). It is concluded that the partial sympathetic denervation produced by transmural myocardial infarction enhances the ease of induction of ventricular tachycardia and fibrillation during sympathetic stimulation. A similar mechanism may lead to increased risk for lethal arrhythmias during periods of high sympathetic tone in patients with transmural myocardial infarction.

Interaction of "supplementary" scintigraphic indicators of ischemia and stress electrocardiography in the diagnosis of multivessel coronary disease.

Lung uptake, ventricular cavitary dilation and basal myocardial uptake represent abnormalities that have been associated with myocardial ischemia on stress thallium-201 images, but that are supplementary to the conventional assessment of perfusion distribution. These "supplementary" indicators of ischemia were related to the coronary distribution of perfusion abnormalities, the results of electrocardiographic stress testing and to the findings on coronary angiography in 73 patients. Forty patients had multivessel coronary disease; 19 of these had three vessel disease. Perfusion abnormalities were seen in 39 of these 40 patients but were indicative of multivessel coronary disease in only 28 and of three vessel disease in only 6. However, supplementary indicators were present in 33 of 40 patients with multivessel disease and in 15 of 19 with three vessel disease. Furthermore, they were seen in 16 of 22 patients with multivessel disease in whom conventional perfusion abnormalities underestimated the extent of disease, but in only 4 of 12 patients in whom the extent of disease was overestimated. The presence of either perfusion abnormalities in a multivessel distribution or supplementary indicators identified 38 (95%) of 40 patients with multivessel disease. A markedly positive electrocardiographic treadmill test was a less sensitive indicator of multivessel disease, appearing in only 15 of 40 patients. However, it was present in only 4 of 33 patients without multivessel coronary disease and was more specific for that diagnosis than were supplementary scintigraphic indicators (88 versus 67%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure.

To assess the potential utility of piroximone (MDL-19,205), an investigational inotrope-vasodilator agent, in severe heart failure, 15 patients with severe left ventricular failure refractory to conventional agents were enrolled in an acute hemodynamic study. After incremental intravenous dosing (mean total dose 1.8 +/- 0.4 mg/kg body weight), cardiac index increased (1.7 +/- 0.3 to 2.6 +/- 0.6 liters/min per m2; p less than 0.001) and left ventricular filling pressure decreased (25 +/- 7 to 19 +/- 7 mm Hg; p less than 0.001). Also decreasing significantly were right atrial pressure (13 +/- 6 to 7 +/- 5 mm Hg; p less than 0.005) and systemic vascular resistance (1,633 +/- 394 to 1,183 +/- 278 dynes.s.cm-5; p less than 0.001). Heart rate and mean arterial pressure did not change, whereas stroke work index increased significantly (13.3 +/- 4.3 to 21.6 +/- 7.3 g.m/m2; p less than 0.005). The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone. Similar responses were obtained after incremental doses of piroximone in oral solution. After oral doses of piroximone tablets, cardiac index also increased significantly (2.1 +/- 0.6 to 2.4 +/- 0.5 liters/min per m2; p less than 0.05), although this magnitude of increase was comparatively low. In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01).

Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction.

To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.

Phase image evaluation of patients with ventricular pre-excitation syndromes.

To localize bypass pathways, left and right ventricular regions were analyzed at rest by phase image analysis in 18 patients with ventricular pre-excitation syndromes. These were compared with image findings in 18 normal subjects. In each of 17 patients with pre-excitation, the site localized on electrophysiologic study correlated closely with the region of earliest ventricular phase angle. This site could be objectively separated from that in normal subjects in each of eight patients with an active left-sided pathway and in both patients with a right-sided pathway. Those with a septal pathway revealed earliest septal phase angle, but could not be separated from normal subjects. In the eight patients with an active left bypass tract, the onset, upstroke and peak of the left ventricular phase histogram preceded those of the right ventricular histogram. Those with a left-sided pathway demonstrated a mean left ventricular phase angle, a difference between mean left and mean right ventricular phase angle and a difference between earliest left and right ventricular phase angles which was significantly less than that in normal subjects (p less than 0.05). These variables presented characteristic converse changes in those with a right-sided pathway. Sequential phase changes in 10 studies suggested "fusion" of normal septal with lateral bypass fronts. Electrocardiographic and electrophysiologic localization of the bypass pathway agreed in only 8 of 14 patients with a recognized delta wave. The phase image represents a new, noninvasive method of evaluating ventricular pre-excitation. The method may provide useful information complementary to that of electrocardiographic and electrophysiologic analysis.

Phase image characterization of localized and generalized left ventricular contraction abnormalities.

To evaluate their phase image characteristics, 61 patients with varying left ventricular contraction abnormalities were studied. In 16 normal patients, the left ventricular phase image revealed a homogeneous pattern, a narrow bell-shaped histogram and an orderly spatial progression of phase angle (phi). In 16 patients with segmental abnormalities, the left ventricular phase image showed a region of uniformly delayed phase angle corresponding to the site of segmental abnormality, a discrete secondary histogram peak and a discontinuous, but orderly, spatial progression of phase angle. The mean phase angle (phi) (23.6 +/- 15.7 degrees) and its standard deviation (17.6 +/- 7.2 degrees) differed from the normal group (7.6 +/- 11.1 degrees, p less than 0.002 and 8.9 +/- 2.8 degrees, p less than 0.001). The percent of end-diastolic volume involved in the segmental abnormality, calculated using phase data in 13 of these and in 11 additional patients with a left ventricular aneurysm on ventriculography, correlated well with the percent akinetic segment on scintigraphic (r = 0.78) and angiographic (r = 0.84) study. In 18 patients with generalized abnormalities, the left ventricular phase image revealed multiple regions of inhomogeneous phase angle, a grossly irregular histogram and a disorderly spatial progression of phase angle. The mean phase angle (56.4 +/- 23.9 degrees) and standard deviation (27.3 +/- 7.1 degrees) differed from values in the normal group and from patients with segmental contraction abnormalities (both p less than 0.001). The mean phase angle and its standard deviation in scattered regions with abnormally prolonged phase angle differed significantly from abnormal regions in patients with segmental abnormalities (both p less than 0.001). These patterns of left ventricular phase angle demonstrate characteristics that may help differentiate between ventricles with segmental and generalized contraction abnormalities. Their relation to underlying pathophysiology and potential clinical implications should be considered.

The scintigraphic characteristics of ventricular pre-excitation through Mahaim fibers with the use of phase analysis.

The phase image pattern of blood pool scintigrams was blindly assessed in 11 patients exhibiting conduction through Mahaim pathways, including 6 nodoventricular and 5 fasciculoventricular. These patterns were compared with the phase image findings in normal subjects, patients with left and right bundle branch block in the absence of pre-excitation and patients with pre-excitation through atrioventricular (AV) connections. In all patients with a Mahaim pathway, the site of earliest phase angle was septal or paraseptal. Phase progression was asymmetric and the pre-excited ventricle demonstrated the earliest mean ventricular phase angle in 10 of 11 patients. This pattern, and the associated ventricular phase difference, appeared to vary from that in normal subjects and in those with a septal AV connection, in whom phase progression is generally symmetric. Scintigraphic phase analysis provided localizing information and presented patterns consistent with Mahaim pathways. Although not able to differentiate among Mahaim pathway subtypes, these phase patterns differed from those in normal subjects, those with right and left lateral free wall pathways and most patients with a septal AV pathway. However, the phase pattern of patients with a Mahaim pathway may not differ from that of patients with a septal AV connection displaying an asymmetric pattern of phase progression, or those with left and right bundle branch block in the absence of pre-excitation. Objective, yet imperfect phase measurements supported these differences. Such image findings may complement the often complex electrophysiologic evaluation of patients presenting with pre-excitation.

Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk.

The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed.

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation.

OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

Microvascular injury in reperfused infarcted myocardium: noninvasive assessment with contrast-enhanced echoplanar magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to measure the accumulation of labeled albumin and to visualize its distribution pattern in reperfused infarcted myocardium as a function of time between onset of reperfusion and administration of the tracer. BACKGROUND: Myocardial microvascular injury leads to leakage of albumin from the intravascular space. Quantitative measurements of GdDTPA-albumin with inversion recovery echoplanar imaging (IR-EPI) may allow noninvasive monitoring of microvascular injury. METHODS: After 1 h of coronary artery occlusion, 56 rats were injected with GdDTPA-albumin or 123I-GdDTPA-albumin either immediately before reperfusion or 1/2, 1 or 24 h after reperfusion. GdDTPA-albumin in blood, normal myocardium and reperfused infarction was dynamically measured with IR-EPI during 1 h postinjection (PI). Autoradiograms were obtained at 15 min PI. Accumulation of labeled albumin in myocardium was expressed as the ratio of myocardial to blood content. RESULTS: In normal myocardium, the ratio of changes of relaxation rate-ratio (deltaR1-ratio) was 0.12+/-0.01 and did not change over 1 h. In reperfused infarction, however, the deltaR1-ratio increased after administration. Animals given GdDTPA-albumin before reperfusion exhibited fastest accumulation (deltaR1-ratio 15 min PI: 0.56+/-0.03) and essentially homogeneous distribution. The accumulation was slower when administered at 1/2, 1 and 24 h after reperfusion (deltaR1-ratios 15 min PI: 0.39+/-0.03; 0.31+/-0.04; 0.16+/-0.01; p < 0.001 compared to administration before reperfusion). Moreover, the tracer accumulated predominantly in the periphery of the injury zone. CONCLUSIONS: Amount and distribution pattern of labeled albumin in reperfused infarction are modulated by duration of reperfusion. The accumulation of GdDTPA-albumin can be quantified by IR-EPI. Thus, IR-EPI may be useful to noninvasively monitor myocardial microvascular injury in reperfused infarction.

Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology.

OBJECTIVES: The purpose of this study was to better understand the effects of long-term right ventricular pacing on left ventricular perfusion, innervation, function and histology. BACKGROUND: Long-term right ventricular apical pacing is associated with increased congestive heart failure and mortality compared with atrial pacing. The exact mechanism for these changes is unknown. In this study, left ventricular perfusion, sympathetic innervation, function and histologic appearance after long-term pacing were studied in dogs in an attempt to see whether basic changes might be present that might ultimately be associated with the adverse clinical outcome. METHODS: A total of 24 dogs were studied. Sixteen underwent radiofrequency ablation of the atrioventricular (AV) junction to produce complete AV block. Seven of these underwent long-term pacing from the right ventricular apex (ventricular paced group), and nine had atrial and right ventricular apical pacing with AV synchrony (dual-chamber paced group). A control group of eight dogs had sham ablations with normal AV conduction. These dogs had atrial pacing only. Regional perfusion and sympathetic innervation were studied in all dogs by imaging with thallium-201 and [I123]metaiodobenzylguanidine, respectively. The degree of innervation was also determined by assay of tissue norepinephrine levels. Left ventricular function was assessed by radionuclide ventriculography. Cardiac histology was studied with both light and electron microscopy. RESULTS: Mismatching of perfusion and innervation in the ventricular paced group was noted, with perfusion abnormalities of both the septum and free wall. Regional [I123]metaiodobenzylguanidine distribution was homogeneous. Tissue norepinephrine levels were elevated in both the ventricular and dual-chamber paced groups compared with the control group. No light or electron microscopic findings were noted in any groups. In the dual-chamber paced group, diastolic dysfunction was noted, with normal systolic function. CONCLUSIONS: Ventricular pacing resulted in regional changes in tissue perfusion and heterogeneity between perfusion and sympathetic innervation. Both ventricular and dual-chamber pacing were associated with an increase in tissue catecholamine activity. The abnormal activation of the ventricles via right ventricular apical pacing may result in multiple abnormalities of cardiac function, which may ultimately affect clinical outcome.

Modulation of the electronic structure of semiconducting nanotubes resulting from different metal contacts.

Examined in this paper is the role of the metal electrode influencing the structure and electronic properties of semiconducting carbon nanotubes near the interface at low bias. Specifically, we present quantum-chemical calculations of finite sections of a (8,0) semiconducting single wall nanotube contacted with gold and palladium clusters. The calculations at the density functional level of theory, which included full geometry optimizations, indicate the formation of bonds between the metal atoms of the electrode and the carbon atoms of the nanotube. The local work function of the metal electrode can be expected to exhibit significant variations as a result of this bond formation. Compared to the gold-contacted nanotubes, the palladium-contacted nanotubes have a small but interesting increase in both length and diameter. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the gold-contacted nanotube are shown localized at the edges. In contrast, the HOMO and LUMO of the palladium-contacted nanotube are extended over the entire nanotube and the metal cluster contacted to it, providing thereby a better conduction path in the contact region of the electrode and the nanotube. The involvement of the highly directional d orbitals in the interactions involving the palladium cluster leads to an enhanced pi electron density in the nanotube. This enhanced pi electron density is synonymous with an improved electron transmission.

Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content.

OBJECTIVES: The sympathetic nervous system has profound influences on myocardial function, particularly during ischemia. There is controversy, however, as to whether myocardial ischemia results in damage to myocardial sympathetic nerves coursing through the ischemic territory. To further evaluate these issues, we assessed the acute and chronic effects of transient myocardial ischemia on sympathetic nerve function and morphology. METHODS: A total of 20 dogs were studied. For acute studies (n = 9), we performed serial dynamic imaging of I-123 metaiodobenzylguanidine (MIBG) washout during coronary occlusion and reperfusion, and assessed residual myocardial perfusion with thallium-201. For chronic studies (n = 11), we assessed sympathetic innervation and perfusion 11 days following a transient intracoronary balloon occlusion. Imaging results were correlated with electrocardiographic responses, histology, and tissue norepinephrine (NE). RESULTS: In the acute studies, regional MIBG washout increased more than 2-fold in the ischemic territory compared to the control region during coronary occlusion (14.2 +/- 2.3 vs. 5.9 +/- 1.2%, P < 0.01). Tissue NE was reduced in the ischemic territory compared to the non-ischemic territory (335 +/- 162 vs. 751 +/- 190 ng/g, P < 0.01). Myocardial perfusion was normal. In the chronic studies, 9/11 dogs showed ischemic ECG changes during balloon occlusion, and developed ventricular arrhythmias. On follow-up imaging, 5/11 dogs showed reduced MIBG uptake relative to thallium, in viable myocardium overlying necrotic subendocardium, reduced NE (226 +/- 77 vs. 733 +/- 82 ng/g in control regions, P < 0.01), decreased nerve density, and a larger extent of denervation than scar (25.5 +/- 3.7 vs. 8.2 +/- 2.7%, P < 0.02). Six of 11 dogs showed normal innervation patterns. CONCLUSIONS: These studies suggest that the sympathetic nerves are acutely affected in regions of myocardial ischemia as detected by enhanced regional washout of MIBG. In addition, chronic sympathetic nerve denervation can occur in the absence of transmural myocardial necrosis; however, the occurrence of transient ischemia does not predict the development of chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The severity of ischemia, as evidenced by the extent of the related necrosis, does appear to predict chronic denervation. The mechanisms leading to chronic denervation of sympathetic nerves in the absence of transmural infarction remain to be defined.

Analysis of thallium-201 "washout" from parametric color coded images.

We developed a parametric washout image which color codes regional washout, and blindly compared enhanced perfusion images in multiple projections with regional washout graphs and images in 25 patients. Washout images permitted true spatial and anatomic assessment of regions viewed en face as well as those seen in tangent, making possible the exclusion of non-coronary irregularities and permitting evaluation of washout over the apparent cavity. "Cavitary" washout was abnormal in 10 of 12 patients with apparent cavitary dilation on the post stress image, but in none without this finding. The distribution and rotation of washout abnormalities seen over the cavity when viewed en face, and the long delay between the termination of stress and post-exercise image acquisition, suggest that apparent cavitary dilation is often related to improved visibility of the 201T1 deficient blood pool due to relative ischemia of the overlying myocardial wall.

A quantitative assessment of patient motion and its effect on myocardial perfusion SPECT images.

Patient motion during image acquisition is a frequent cause of SPECT perfusion image artifacts. We sought to determine the relationship between patient motion and the resultant image artifact. The effect of patient motion on 201Tl SPECT scintigrams was assessed with computer simulation to create 66 new image sets with artifactual vertical, horizontal and combined patient motion introduced over a broad range in six normal studies. Visual analysis of regional radioactivity in these simulated images, as well as quantitative analysis of the resultant polar coordinate display was performed. The presence and extent of "motion" artifacts varied with the number and location of the projection images affected, as well as the extent of their displacement. Although the extent of the defect varied with the frames affected, they were not necessarily more extensive when related to vertical displacement in the center of the orbit. The location of induced defects varied with direction of displacement and the location of frames affected. Vertical and horizontal motion created additive defects. Defect size grew with incremental vertical displacement but subsequently decreased with yet increasing displacement. Both the irregular, "lumpy" distribution of radioactivity, often with opposing "defects", as well as curvilinear extraventricular radioactivity, were visual clues suggesting SPECT defects related to motion artifact. A clinical case review revealed that approximately 25% of studies demonstrate such motion during acquisition but only 5% contribute to visible image deterioration. While detection is important, postacquisition attempts to correct such artifacts are incomplete and optimally, they must be prevented.

Metaiodobenzylguanidine as an index of atrioventricular nodal adrenergic activity.

UNLABELLED: Despite its importance, little is known about the uptake, storage and release of catecholamines in the atrioventricular (AV) node and His bundle. Previous in vitro studies have been limited by metabolism of norepinephrine. Metaiodobenzylguanidine (MIBG) shares many transport properties with norepinephrine and is considered a functional marker of adrenergic activity. METHODS: We used [125I]MIBG +/- 99mTc-sestamibi (99mTc-MIBI) and [123I]MIBG +/- 201TI] to evaluate regional differences in adrenergic activity between cardiac conductive and contractile elements in rats. Histological localization of the AV node and His bundle was performed using stains for acetylcholinesterase. RESULTS: Densitometric evaluation of autoradiographs, obtained from 20-mu thick sections of hearts from rats injected with either [125I]MIBG +/- 99mTc-MIBI (n = 4) and [123I]MIBG +/- 201TI (n = 6), revealed that there was approximately 30% more MIBG uptake in the AV node and His bundle compared to atrial or ventricular muscle (p < 0.05). Color-coded functional maps, generated by computer to simultaneously display 123I or [125I]MIBG and perfusion markers, revealed that the heterogeneous distribution of MIBG was independent of myocardial blood flow. CONCLUSION: When used as a selective functional marker of adrenergic activity in the cardiac conduction system, 123I- or [125I]MIBG autoradiography demonstrates increased adrenergic activity in the AV node and His bundle compared with the left ventricle. MIBG imaging provides a new research technique to probe in vivo modulation of AV nodal and His bundle sympathetic activity.

Variability of normal coronary anatomy: implications for the interpretation of thallium-SPECT myocardial perfusion images in single-vessel disease.

UNLABELLED: Standard criteria for assigning perfusion defects to a specific vascular territory often result in mistaken identification of the affected coronary artery due to the normal variability of coronary anatomy. A retrospective study was performed to determine the frequency of this type of error and to identify the most common perfusion patterns associated with specific coronary lesions. METHODS: Records were reviewed of all patients with single-vessel coronary artery disease (CAD) who had exercise or dipyridamole thallium SPECT myocardial perfusion studies since 1987. Patients with coronary artery bypass grafts and an interval between the two studies greater than 6 wk or interval change in medical status were excluded. Ninety-three studies were available for review. The size, severity and location of all perfusion defects were noted by three observers who had no knowledge of the angiographic data. Significant CAD was defined as luminal diameter stenosis greater than 50%. RESULTS: The diseased vessel was correctly identified in 85% of positive studies. Thallium SPECT, however, mistakenly predicted additional vessel involvement in 29% of those studies. Another 15% correctly predicted single-vessel disease but identified the wrong artery. Using standard criteria, thallium SPECT correctly predicted the arteriogram findings in only 56% of studies. Most of these findings could be correlated with variations in individual coronary anatomy. CONCLUSION: The accurate localization of coronary stenoses by thallium SPECT imaging requires close correlation with arteriography owing to the significant variability in normal coronary anatomy.