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.

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)

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.

Quantitation of regional myocardial function by cine computed tomography: pharmacologic changes in wall thickness.

To determine the capability of high speed computed transmission tomography to quantitate regional wall thickening dynamics over a wide range of physiologic states, left ventricular wall thickening was studied in nine anesthetized mongrel dogs in the control state and during separate infusions of dobutamine (10 micrograms/kg per min) and phenylephrine (25 micrograms/kg per min). After an intravenous bolus of contrast medium the heart was imaged from base to apex with serial transverse images in eight short-axis cine computed tomographic planes. In each dog during each experimental condition, 50 ms scans spanning the cardiac cycle were acquired at each anatomic level. Left ventricular epicardial and endocardial boundaries were identified on end-diastolic and end-systolic images at the equatorial left ventricular planes by an objective threshold contour method validated in a series of experiments performed on ex vivo anatomic specimens. End-diastolic and end-systolic frames were automatically realigned by superposition of epicardial centers of gravity and then rotated using a cross correlation function. The left ventricular wall thickness was measured manually at 16 points around the circumference by two independent observers. For the group of dogs the average percent wall thickening was 40.5 +/- 28.2% and varied among segments from 18 to 70% in the control state. After dobutamine was administered, significant increases in heart rate and cardiac output (p less than or equal to 0.01) were accompanied by an increase in the average wall thickening (73.6 +/- 51.2%; p less than or equal to 0.001) in the left ventricle; the average wall thickening among segments ranged from 46 to 97%. After phenylephrine administration, significant increases in mean blood pressure and cardiac output (p less than or equal to 0.01) were noted along with a significant increase in average left ventricular wall thickening (60.3 +/- 52.5%; p less than or equal to 0.001). Despite an overall increase in the percent wall thickening, no statistically significant changes in segmental contraction pattern between control and drug intervention states were observed. The wall thickness measurements were highly reproducible between the two independent readers (reliability coefficient = 0.99). Cine computed tomography-derived measurements can potentially be used for quantitative assessment of left ventricular wall thickening dynamics of a single heartbeat during acute interventions, such as the administration of drugs.

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.

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.

Phase image characterization of ventricular contraction in left and right bundle branch block.

The phase image is a computer-derived functional image, based on the analysis of the time versus radioactivity curve in each pixel location of the multiple gated blood pool scintigram. Within the ventricular regions of interest, the phase angle is roughly equivalent to the time of onset of counts reduction or to the time of onset of ventricular contraction and is expressed in degrees from 0 to 360 degrees. A gray scale-coded image of such a regional phase angle, the phase image, can be looked on as a map of sequential contraction. This method was applied in 33 patients without severe contraction abnormality including 16 patients with normal conduction, 9 with right bundle branch block and 8 with left bundle branch block. In patients with normal conduction the pattern of phase angle distribution, representing the pattern of ventricular contraction, was homogeneous and symmetric in both the left and right ventricles. Analysis in this normal group indicated a slight but significant difference between the mean (+/- standard deviation) phase angle of the left ventricle (8.5 +/- 11.8 degrees) and that of the right ventricle (13.6 +/0 12.9 degrees, p = 0.01). There was a slight, but nonsignificant difference between mean intrapatient left and right ventricular phase angle onset (1.9 +/- 6.5 degrees). The mean phase angle of the right ventricle in patients with right bundle branch block (27.6 +/- 14.2 degrees) and of the left ventricle in those with left bundle branch block (21.9 +/- 14.0 degrees) was delayed compared with that in patients with normal conduction (p less than 0.05 for both). The mean intrapatient difference between left and right ventricular mean phase angles in patients with normal conduction (-5.2 +/- 6.8 degrees) was significantly different from that in patients with right (-21.8 +/- 10.3 degrees, p less than 0.001) or left (21.8 +/- 6.8 degrees, p less than 0.001) bundle branch block. The mean intrapatient difference between onset of left and right ventricular phase angles was also significantly different from normal in patients with right (-10.6 +/- 7.5 degrees, p less than 0.005) or left (18.7 +/- 8.3 degrees, p = 0.01) bundle branch block. Although phase imaging is not without artifactual error, this study demonstrates that the phase image can characterize familiar conduction abnormalities. It presents the potential for application as a general noninvasive tool in the investigation of the timing and sequence of ventricular contraction in patients with normal or abnormal ventricular activation.

The etiology and implications of dense cavitary "photopenia" on myocardial perfusion scintigraphy.

Dense cavitary "photopenia" was observed on 21 of 200 consecutive stress perfusion scintigrams. A prominent finding in many cases, it sometimes occupied only a portion of the region overlying the ventricular cavity, was often seen in some projections and not others, and was frequently adjacent to myocardial perfusion defects. To distinguish an etiology among reduced cavitary radioactivity, relatively increased background radioactivity, or reduced radioactivity in overlying myocardium, quantitative analysis of cavitary, lung and myocardial radioactivity was performed in patients with dense cavitary "photopenia," with and without lung uptake, and compared with results from studies showing increased lung uptake without cavitary photopenia and with normal studies. The results showed that dense cavitary photopenia was related to reduced radioactivity in overlying myocardium. Correlative imaging studies performed with echocardiography and contrast ventriculography confirmed this relationship to myocardial scar in 15 of 21 patients in whom associated akinesis or dyskinesis was seen. Hence, dense cavitary photopenia on stress perfusion scintigraphy is due to a dense myocardial perfusion abnormality, and is often indicative of related scar and an associated severe contraction abnormality.

Basal interventricular septal thallium-201 defects: real or artifact?

Misinterpretation of reversible defects at the base of the interventricular septum is perhaps among the greatest single causes of false positive TI-201 myocardial perfusion images. This is a report of a patient with angiographically documented ischemia at the base of the septum and corresponding reversible defects as seen using TI-201 imaging. Illustrated are two different forms of malalignment artifact that duplicate this patient's findings in a patient with normal perfusion.