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Biomedical subjects

M W Dae

Publications and source records attributed to M W Dae.

At least 19 recordsLinked to original sources
PubMed2001

Effects of reduced sympathetic activity on myocardial metaiodobenzylguanidine (MIBG) washout.

1. Increase in myocardial sympathetic activity contributes markedly to the pathophysiology of conditions such as congestive heart failure and is also associated with myocardial infarction. However, measurement of myocardial sympathetic activity in vivo is difficult. 2. The present study assesses the effectiveness of metaiodobenzylguanidine (MIBG) imaging to characterize modulation of sympathetic activity, as induced by dexmedetomidine, a highly specific alpha-2 adrenoceptor agonist. 3. We imaged washout of [125I]-MIBG from rabbit heart before and during two consecutive 45-min intravenous infusions of dexmedetomidine (10 microg kg(-1) followed by 16 microg kg(-1)) (n=9) or of saline (n=9). 4. Heart rate (HR), and mean blood pressure (BP) were measured before and at the end of each study period. Plasma noradrenaline (NA) was measured before and after study drug infusion. The hearts were then excised and biopsied for MIBG tissue concentration [MIBG] (% kg-dose g(-1)). 5. Relative to saline controls, dexmedetomidine significantly decreased HR, BP, plasma NA and MIBG washout. There was an inverse correlation between MIBG washout and residual [MIBG] in the myocardium (r= -0.75, P < 0.01). 6. These data suggest that a reduction of sympathetic nervous system activity causes a decrease in myocardial MIBG washout in vivo in rabbits, and confirms the usefulness of MIBG scintigraphy as a non-invasive tool to measure changes in myocardial sympathetic activity.

3-Iodobenzylguanidine↗
PubMed2001

Absolute quantification of regional myocardial uptake of 99mTc-sestamibi with SPECT: experimental validation in a porcine model.

UNLABELLED: We have evaluated a method for absolute in vivo quantification of 99mTc-sestamibi uptake in a porcine model of myocardial perfusion. METHODS: Correlated CT and radionuclide images were obtained from eight adult pigs using a combined CT-SPECT imaging system. In each case, the CT image is used to generate an object-specific attenuation map that is incorporated into an iterative algorithm for reconstruction and attenuation correction of the radionuclide image. Anatomic information available from the correlated CT image is used to correct the radionuclide image for partial-volume errors by mathematically modeling the radionuclide imaging process. A volume of interest, or template, that approximates the geometric extent of the myocardium is defined from the CT image. Once defined, the template is assigned unit activity and is mathematically projected using a realistic physical model of the radionuclide imaging process including nonideal collimation and object-specific attenuation. The template is then reconstructed from these projections to obtain a pixel-by-pixel partial-volume correction for the myocardium in the radionuclide image. The CT image is also used to delimit the anatomic boundaries of the myocardium for quantification of the radionuclide images. The pixel intensities in the corrected radionuclide image are calibrated in units of activity concentration (MBq/g) and compared with the ex vivo activity concentration measured directly from the excised myocardium. RESULTS: Without corrections, the measured in vivo activity concentration in the porcine myocardium was only 10% of the true value. Correcting for object-specific attenuation improved the accuracy of this measurement but resulted in values that were still only 42% of the true value. By correcting for both attenuation and partial-volume errors, we were able to achieve absolute quantification with an accuracy error near 10%. CONCLUSION: We have shown that, by applying object-specific attenuation corrections and suitable partial-volume corrections, absolute regional activity concentration can be measured accurately in the porcine myocardium.

Animals↗
PubMed2000

Impact of a home-based walking and resistance training program on quality of life in patients with heart failure.

Patients with heart failure (HF) often have profound activity limitations and diminished quality of life (QOL) due to symptoms of dyspnea and fatigue. Although recent studies demonstrate positive physiologic and psychological benefits of low to moderate intensity, supervised, aerobic exercise training performed 3 to 5 days/ week for 20 to 40 minutes' duration, in a monitored setting, the efficacy of a home-based exercise program combining endurance and resistance exercise on symptoms and QOL, are unknown. This randomized controlled study examined the efficacy, safety, and adherence rates of a 3-month home-based combined walking and resistance exercise program on symptoms and QOL in 40 women and men aged 30 to 76 years with New York Heart Association class II to III HF. Baseline and 3-month evaluations consisted of a chronic HF questionnaire to assess symptoms and QOL and exercise capacity by symptom-limited treadmill exercise test with respiratory gas analysis. The exercise intervention improved fatigue (p = 0.02), emotional function (p = 0.01), and mastery (p = 0.04). Overall exercise adherence was excellent (90%) and there were no reported adverse events. A moderate intensity home-based combined walking and resistance program for patients with class II to III HF is safe and effective in reducing symptoms and improving QOL.

Adult↗
PubMed2000

Long-term estrogen replacement therapy is associated with improved exercise capacity in postmenopausal women without known coronary artery disease.

BACKGROUND: Short-term estrogen administration improves vasodilation and has been shown to improve exercise capacity. However, it is unknown whether long-term estrogen replacement therapy is associated with improved exercise capacity in postmenopausal women without known coronary artery disease. METHODS AND RESULTS: We studied 248 postmenopausal women without known coronary artery disease (mean age 63.5 years); 158 (64%) were current or past hormone replacement therapy (HRT) users and 108 (44%) were current users of HRT. Attributes potentially affecting exercise capacity and cardiac risk factors were carefully measured. These included duration of estrogen replacement therapy, all variables in the Framingham risk index, physical activity level, body mass index, waist-to-hip ratio, presence of osteoporosis, and family history of heart disease. We measured maximal oxygen uptake (MVO (2)) and anaerobic threshold as objective markers of exercise capacity. The relation between exercise capacity and use of HRT was analyzed with the use of logistic regression, controlling for confounding variables. We found that fitness, as measured by MVO (2) and anaerobic threshold, was significantly greater in women who had used HRT currently or in the past compared with women who had never used HRT. This difference in fitness was not confounded by age or physical activity level. CONCLUSIONS: Estrogen replacement therapy is associated with increased exercise capacity as measured by MVO (2) and anaerobic threshold in postmenopausal women without coronary artery disease. This finding is consistent with the beneficial effect of short-term estrogen administration on improved endothelium-dependent and endothelium-independent vasodilation.

Aged↗
PubMed2000

Reperfused rat myocardium subjected to various durations of ischemia: estimation of the distribution volume of contrast material with echo-planar MR imaging.

PURPOSE: To estimate and compare the fractional distribution volume (fDV) of gadodiamide injection and technetium 99m-diethylenetriaminepentaacetic acid (DTPA) in the reperfused myocardium of rat hearts subjected to various durations of ischemia. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and autoradiography were performed in rats subjected to 20, 30, 40, or 60 minutes of regional ischemia followed by 1 hour of reperfusion. The fDVs of gadodiamide injection and (99m)Tc-DTPA were measured and compared by using inversion-recovery echo-planar imaging and autoradiographic phosphor imaging, respectively. RESULTS: The mean fDV of both tracers (gadodiamide and (99m)Tc-DTPA) in normal myocardium was 18% +/- 1, whereas that in the entire area at risk increased significantly (P <.05) with 20, 30, 40, and 60 minutes of ischemia to 32% +/- 1, 57% +/- 4, 66% +/- 2, and 68% +/- 2, respectively. The fDV was significantly (P <.05) greater in the core of infarction-78% +/- 4, 89% +/- 5, and 88% +/- 5 with 30, 40, and 60 minutes of ischemia, respectively-than in the normal myocardium or in the area at risk. CONCLUSION: The fDV of MR contrast material in the periinfarcted rim was significantly (P <. 05) greater than that in the normal myocardium, but significantly less than that in the core of infarcted myocardium.

Analysis of Variance↗
PubMed1999

Measurement of the distribution volume of gadopentetate dimeglumine at echo-planar MR imaging to quantify myocardial infarction: comparison with 99mTc-DTPA autoradiography in rats.

PURPOSE: To measure the fractional distribution volume of gadopentetate dimeglumine in normal and reperfused infarcted myocardium at magnetic resonance (MR) imaging by using the fractional distribution volume of technetium 99m-diethylenetriaminepentaacetic acid (DTPA) as an independent reference. MATERIALS AND METHODS: Rats were subjected to 1 hour of coronary artery occlusion and 1 hour of reperfusion before inversion-recovery echo-planar imaging or autoradiography. Regional change in relaxation rate (delta R1) ratios for myocardium over blood were compared with radioactivity ratios for myocardium over blood after the injection of 99mTc-DTPA. RESULTS: Both delta R1 and radioactivity ratios demonstrated equilibrium distribution and hence represent partition coefficients (lambda). The fractional distribution volumes were greater in infarcted myocardium (0.90 +/- 0.05 for gadopentetate dimeglumine and 0.89 +/- 0.04 for 99mTc-DTPA) than in normal myocardium (0.23 +/- 0.02 for gadopentetate dimeglumine and 0.16 +/- 0.01 for 99mTc-DTPA). Area at risk at autoradiography was not significantly different from that at histomorphometry. The infarction size defined by using triphenyltetrazolium chloride was 13% +/- 4 smaller than that defined by using autoradiography. CONCLUSION: The fractional distribution volumes of gadopentetate dimeglumine and 99mTc-DTPA are similar and indicate extracellular distribution in normal myocardium and intracellular as well as extracellular distribution in reperfused infarction. Because the failure of cells to exclude these agents is indicative of necrosis, contrast medium-enhanced MR imaging may be useful to quantify myocardial infarction.

Animals↗
PubMed1998

Is there any advantage to the acquisition of 24-hour thallium images, in the presence of persistent perfusion defects at 4 h after reinjection?

We determined the incidence of delayed 24-h reversibility post thallium-201 reinjection and imaging at 4 h, as well as the prognostic and significance of such delayed reversibility. We studied 46 consecutive patients with persistent thallium-201 perfusion or incompletely reversible single-photon emission tomography (SPET) perfusion defects acquired within 10 min after reinjection performed 4 h after stress. In 38 of 46 patients (82%) 24-h images showed no further reversibility beyond the post-reinjection 4-h study (group A). Eight of 46 patients (17%) demonstrated reversibility on 24-h imaging (group B). Of these eight, three patients showed no improvement compared with the post-stress images, with a mean perfusion score of the abnormal segments of 1. 25+/-0.50 on the 4-h images, and of 3.00 on the 24-h images, where normal is 4. Four patients presented with nine mixed regions. Four of these regions showed an improvement in the mean perfusion score of 2.50+/-0.58 on 4- and 24-h images. Two of them, with moderate/severe defects, demonstrated complete reversibility at 4-h post-reinjection imaging. In addition, five other regions presented no improvement at 4-h imaging, but showed an improvement in the mean perfusion score from 0.80+/-0.84 at 4-h to 3.30+/-0.89 at 24-h imaging. Two of these regions in one patient showed a severe perfusion score of 0 at 4 h, and complete reversibility at 24 hours, with a mean score improvement of 4. Another patient had three severe perfusion defects; two of them redistributed partially at 4 h and completely at 24 h. The remaining segment with a perfusion score of 0 at 4 h, presented complete reversibility with a score of 4 at 24 h. Two (4%) patients revealed significant reversibility at 24 h in a region that was severely underperfused after post-reinjection imaging at 4 h. Among group B patients, 75% (6/8) had recent acute ischemic syndrome, compared with only 13% (5/38) in group A (P = 0. 001). Among 11 patients with unstable angina, six (55%) had evidence of delayed 24-h reversibility, compared with 2 of 35 (6%) patients without clinically acute ischemia (P = 0.001). On follow-up, there were seven (17%) cardiac deaths among the 38 group A patients but three (38%) among the eight group B patients (P = 0.3). These findings suggest that although the presence of delayed 24-h 201Tl, post-reinjection reversibility is infrequent, it has potential clinical importance. Thus, delayed 24-h imaging should be considered in the context of unstable angina or other acute coronary syndromes.

Aged↗
PubMed1998

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.

Albumins↗
PubMed1997

Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death.

BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.

3-Iodobenzylguanidine↗
PubMed1997

Myocardial perfusion imaging with a combined x-ray CT and SPECT system.

UNLABELLED: We evaluated a novel combined x-ray CT and SPECT medical imaging system for quantitative in vivo measurements of 99mTc-sestamibi uptake in an animal model of myocardial perfusion. METHODS: Correlated emission-transmission myocardial images were obtained from 7- to 10-kg pigs. The x-ray CT image was used to generate an object-specific attenuation map that was incorporated into an iterative ML-EM algorithm for reconstruction and attenuation correction of the coregistered SPECT images. The pixel intensities in the SPECT images were calibrated in units of radionuclide concentrations (MBq/g), then compared against in vitro 99mTc activity concentration measured from the excised myocardium. In addition, the coregistered x-ray CT image was used to determine anatomical boundaries for quantitation of myocardial regions with low perfusion. RESULTS: The accuracy of the quantitative measurement of in vivo activity concentration in the porcine myocardium was improved by object-specific attenuation correction. However, an additional correction for partial volume errors was required to retrieve the true activity concentration from the reconstructed SPECT images. CONCLUSION: Accurate absolute SPECT quantitation required object-specific correction for attenuation and partial volume effects. Additional anatomical information from the x-ray CT image was helpful in defining regions of interest for quantitation of the SPECT images.

Algorithms↗
PubMed1996

Deconvolution: a novel signal processing approach for determining activation time from fractionated electrograms and detecting infarcted tissue.

BACKGROUND: Two important signal processing applications in electrophysiology are activation mapping and characterization of the tissue substrate from which electrograms are recorded. We hypothesize that a novel signal-processing method that uses deconvolution is more accurate than amplitude, derivative, and manual activation time estimates. We further hypothesize that deconvolution quantifies changes in morphology that detect electrograms recorded from regions of myocardial infarction. METHODS AND RESULTS: To determine the accuracy of activation time estimation, 600 unipolar electrograms were calculated with a detailed computer model using various degrees of coupling heterogeneity to model infarction. Local activation time was defined as the time of peak inward sodium current in the modeled myocyte closest to the electrode. Deconvolution, minimum derivative, and maximum amplitude were calculated. Two experienced electrophysiologists blinded to the computer-determined activation times marked their estimates of activation time. F tests compared the variance of activation time estimation for each method. To evaluate the performance of deconvolution to detect infarction, 380 unipolar electrograms were recorded from 10 dogs with infarcts resulting from ligation of the left anterior descending coronary artery. The amplitude, duration, number of inflections, peak frequency, bandwidth, minimum derivative, and deconvolution were calculated. Metrics were compared by Mann-Whitney rank-sum tests, and receiver operating curves were plotted. CONCLUSIONS: Deconvolution estimated local activation time more accurately than the other metrics (P < .0001). Furthermore, the algorithm quantified changes in morphology (P < .0001) with superior performance, detecting electrograms recorded from regions of myocardial infarction. Thus, deconvolution, which incorporates a priori knowledge of electrogram morphology, shows promise to improve present clinical metrics.

Algorithms↗
PubMed1995

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.

3-Iodobenzylguanidine↗
PubMed1995

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.

3-Iodobenzylguanidine↗
PubMed1995

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.

Coronary Disease↗
PubMed1994

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.

3-Iodobenzylguanidine↗