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PubMed2001

Increased QT dispersion does not reflect the increased regional variation of cardiac sympathetic nervous activity in hypertrophic cardiomyopathy.

BACKGROUND: QT dispersion (QTD) reflects regional variation of ventricular repolarization. However, the relationship between QTD and the regional variation of cardiac sympathetic nerve activity in hypertrophic cardiomyopathy (HCM) is not yet elucidated. METHODS: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM by iodine 123 metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar MIBG imaging, heart and mediastinum ratios (H/M) at early (20 minutes) and delayed (3 hours) acquisition and the washout rate (WR) were calculated. Polar maps of left ventricular myocardium were divided into 20 segments. The SD of early uptake (EU-SD), delayed uptake (DU-SD), and WR (WR-SD) in 20 segments as indices of regional variation were calculated. QT intervals were corrected by use of the Bazett formula. RESULTS: Maximum QTc correlated positively with H/M early, WR, and left ventricular wall thickness (LVWT). Minimum QTc correlated positively with WR and LVWT. Corrected QTD (QTDc) correlated negatively with EU-SD, DU-SD, and WR-SD and positively with the interventricular septal thickness/posterior wall thickness ratio. Stepwise regression analysis revealed that the most powerful determinants for maximum QTc, minimum QTc, and QTDc were WR, LVWT, and EU-SD, respectively. CONCLUSIONS: QTD correlated negatively rather than positively with the regional variability index of cardiac sympathetic nerve activity. These results suggest that increased QTD in patients with HCM may not reflect increased heterogeneity of cardiac sympathetic nerve activity.

Arrhythmias, Cardiac↗

PubMed1996

Hemodynamic and regional blood flow responses to nicotine at rest and during exercise.

We hypothesized that nicotine compromises cardiovascular responses to dynamic exercise. Hemodynamic variables were measured in conscious miniswine before and at 2 min of nicotine infusion (20 micrograms.kg-1.min-1; i.a.; N = 6) during resting conditions. Mean arterial pressure elevations (MAP; 14%) and plasma nicotine concentrations (49 +/- 7 ng.ml-1) were similar to those elicited by cigarette smoking in humans. In addition, nicotine increased systemic vascular resistance (SVR; 56%), the heart rate x systolic blood pressure product (RPP; 11%), and regional vascular resistance in the left-ventricular, renal, and splanchnic circulations, while cardiac output decreased (CO; 23%) and skeletal muscle blood flow and vascular resistance were unaffected. Plasma norepinephrine and epinephrine increased by approximately 30% and 90%, respectively. On separate days, the same hemodynamic responses were measured before and at 20 min of treadmill running during vehicle or nicotine infusion for the last 2 min of exercise (N = 10). Nicotine increased MAP (6%), SVR (14%), and RPP (3%), and elevated vascular resistance in the proximal colon and pancreas. Moreover, compared to exercise + vehicle, norepinephrine and epinephrine increased by approximately 13% and 24%, respectively, during exercise + nicotine infusion. These findings suggest that the detrimental effects of nicotine observed at rest are minimized during exercise. Nicotine's effects may be reduced during exercise by competition from local vasodilators in the heart and active musculature, and/or by differing activation of sympathetic nerve activity.

Animals↗

PubMed1984

Overdrive suppression of conduction in the canine His-Purkinje system after occlusion of the anterior septal artery.

The purpose of these experiments was to determine whether overdrive suppression of conduction (OSC), i.e., transient worsening of conduction or development of atrioventricular block after cessation of rapid pacing, could be produced in the canine His-Purkinje system damaged by ligation of the anterior septal coronary artery and to investigate the responsible mechanism. We found that OSC occurred in vivo after rapid ventricular and His bundle pacing but not after atrial pacing, and that it occurred in vitro after rapid pacing from the left bundle branch but not after pacing from the proximal His bundle. OSC was related to the duration and cycle length of pacing. Lidocaine increased while verapamil reduced the duration of OSC in vivo. The mechanism responsible for the unidirectionality of OSC is not clear but is probably related to the geometry of the atrioventricular junction and the anterograde versus the retrograde activation sequence. Changes in regional myocardial blood flow, autonomic tone, hemodynamic variables, or ventricular function do not appear to be required to produce OSC, based on the demonstration of the phenomenon in vitro. The data suggest a time- and rate-dependent change in factors affecting conduction such as excitability or cell-to-cell coupling, possibly due to accumulation of intracellular cations such as calcium.

Animals↗

PubMed2002

Squamous cell carcinoma arising in an epidermal inclusion cyst.

An epidermal inclusion cyst is a widespread benign intradermal lesion and may occur anywhere in the body. Normally, it appears as a non-tender, soft mass of variable size. Dissection usually reveals grayish-white or whitish gelatinous materials and a smooth inner surface. The overlying skin almost always shows unremarkable changes. On occasion, the cyst may rupture and induce an inflammatory reaction. It rarely turns malignant or displays a firmer mass. This study reports on a rare case of squamous cell carcinoma arising from the lining cells of an epidermal inclusion cyst, which was located in the left axillary region of a 68-year-old male patient. Clinically, it is difficult to differentiate between a benign and malignant cystic lesion. Histological examination normally yields the diagnosis. Once a diagnosis is confirmed, the tumor should be widely excised with a free margin. The outcome is always excellent. We therefore emphasize that all resected skin cystic specimens should undergo further microscopic examination to avoid any unnecessary misdiagnosis.

Aged↗

PubMed1981

Patterns of regional ventilation in patients with cardiomegaly or left heart failure.

Patterns of regional ventilation have been examined in 42 patients, the majority of whom had clinical evidence of left-ventricular or left-atrial dysfunction. Regional ventilation was studied with xenon-133 and regional perfusion with Tc-99m human albumin microspheres. The presence of a cardiac defect, seen in 54.8% of the washin images, was related to the depth of lung between the posterior heart border and the posterior lung border, but not to cardiac size. Washout patterns were fairly uniform in those patients (43%) who cleared their lungs within 3 min, but were remarkably variable in those with longer washout times. The presence of râles or clinical signs of a pleural effusion, and radiographic evidence of vascular redistribution or pleural effusion, were significantly associated with prolonged washout times. These observations suggest that the prolonged washout is due to edema in the walls of the smaller bronchioles, leading to airflow obstruction.

Adult↗

PubMed1997

[A case of isolated neck extensor myopathy with parkinsonism].

We report an 84-year-old man with marked dropped head from 80 years of age. On neurologic examination, weakness was restricted to the neck extensor muscle, and the range of motility (ROM) of cervical spine was limited. He also had vascular parkinsonism. Needle electromyography indicated myogenic changes localized in the cervical paraspinal and trapezius muscles. CT and MRI of the cervical region demonstrated neck extensor muscle atrophy. Cervical paraspinal muscle biopsy revealed decreased numbers of muscle fibers which were embedded in markedly increased connective tissue. There was neither cellular infiltration nor specific changes. These findings were identical to those seen in isolated neck extensor myopathy recently proposed by Katz et al. (1996). In addition, pathological finding of the biceps muscle of the left arm suggested subclinical general myopathy because of mild fiber-size variability with moth-eaten appearance on NADH-TR straining. Neck extensor muscle weakness and limitation of ROM improved by physical therapy, and gait disturbance also improved simultaneously. To our knowledge, this is the first report isolated neck extensor myopathy in Japanese.

Aged↗

PubMed1993

Variability occurs in the inverted repeat region of genomic DNA from bovine herpesvirus 1 respiratory, genital and bovine herpesvirus 5 encephalitic isolates.

Restriction fragment length polymorphisms (RFLPs) were detected within BHV1.1, BHV1.2, and BHV5 genomes using the restriction enzyme PstI. The genomic areas of these changes has not been previously reported. Using Southern blot hybridization with DNA probes representing the entire genome of BHV1.1, areas of genomic variation were located for a respiratory isolate (BHV1.1), four vaccine isolates (BHV1.1), a genital isolate (BHV1.2), and two encephalitic isolates (BHV5). The most frequently observed RFLPs of BHV1.1 and BHV1.2 occurred within the internal repeat region and the left terminus of the unique long region. When two separate isolates of the encephalitic BHV5 were compared, RFLPs were detected in the internal and right terminal repeat regions. These are the regions of each genome from which immediate early genes are transcribed. No genomic variation was observed throughout the unique long and unique short regions for all BHV1 and 5 isolates examined.

Animals↗

PubMed1999

Thallium-201 right lung/heart ratio during exercise in patients with coronary artery disease: relation to thallium-201 myocardial single-photon emission tomography, rest and exercise left ventricular function and coronary angiography.

The aim of this study was to correlate lung thallium-201 uptake on exercise with 201Tl single-photon emission tomography (SPET) myocardial perfusion imaging, rest and exercise equilibrium radionuclide angiographic and coronary angiographic findings in patients with coronary artery disease (CAD) using a simple, reproducible lung/heart (L/H) ratio that would be easy to use in clinical practice. L/H ratio was defined on the anterior planar image obtained during exercise 201Tl SPET acquisition as the mean counts per pixel in an entire right lung field region of interest divided by the mean counts per pixel in the hottest myocardial wall region of interest. We studied 103 patients. Fifty-nine patients (group I) with <5% likelihood of CAD were used as a reference group. In 44 CAD patients (group II), L/H ratio was compared with 201Tl SPET, radionuclide angiographic and coronary angiographic variables. The group I L/H ratio of 0.35+/-0.05 (mean +/-1 SD) was significantly lower (P<0.001) than the group II L/H ratio of 0. 45+/-0.10. An L/H ratio >0.45 (mean + 2 SD in group I) was considered abnormal. In group II, L/H ratio showed a significant correlation with stress and rest 201Tl perfusion defect size (r = 0. 39 and r = 0.42, P<0.01, respectively), but not with extent of ischaemic myocardium. The mean L/H ratio was 0.41+/-0.10 in patients with one-vessel disease (n = 15), 0.46+/-0.08 in those with two-vessel disease (n = 17) and 0.47+/-0.12 in those with three-vessel disease (n = 12), but no significant difference was found between the three subgroups. L/H ratio showed a significant inverse relation with rest and exercise left ventricular ejection fraction (r = -0.37 and r = -0.50, P<0.05 and P<0.001, respectively). Using stepwise multiple regression analysis, exercise left ventricular ejection fraction and previous history of hypertension were the sole two variables independently predictive of the L/H ratio. In conclusion, although lung thallium uptake is usually found to correlate with extent and severity of CAD, increased L/H ratio should primarily be considered as a marker of exercise-induced left ventricular systolic and perhaps diastolic dysfunction, probably independent of the underlying cardiac disease.

Case-Control Studies↗

PubMed1993

Evaluation of a local microsphere injection method for measurement of blood flow in the rabbit lower extremity.

The precision of a modified microsphere technique to measure blood flow in the hind limb of the rabbit was determined. Regional (local) injections made via a catheter in the aorta and blood withdrawn through a catheter in the hind limb enabled deposition of a high concentration of microspheres in the tissues while minimizing the number of microspheres needed for accurate measurement. 95Niobium and 141cerium-labeled 16 microns diameter microspheres were used. Blood flow was measured in 15 locations of muscle and skin for simultaneous injections into the aorta and left ventricle (group A), simultaneous injections of a mixture into the left ventricle (group B), and ventricular injections given 1 h apart (group C). No significant differences in mean blood flow measurements were found. Correlation coefficients between local and ventricular injections ranged from 0.89-0.99 and between 0.994 and 0.999 for two simultaneous ventricular injections. The variability over time was greater, with correlations between the first and second injections ranging from 0.13-0.939. Precision of the local technique compared with the ventricular technique can be kept within 30% with five or six animals. The advantage of this technique over ventricular injections is in the measurement of blood flow in small tissue samples when the number of microspheres deposited from ventricular injections is insufficient.

Animals↗

PubMed1986

Hypoxia mediated binding of misonidazole in non-malignant tissue.

Binding of 3H-misonidazole in hypoxic nonmalignant tissue was investigated in the gerbil stroke model. Cerebral infarcts were produced in male Mongolian gerbils by ligating the right common carotid artery and the severity of the lesions was quantified by scoring the animals' symptoms. The uptake of [H-3]misonidazole in the right cerebral hemisphere and the ratios of right:left hemispheral uptake correlated positively with the severity of the stroke when measured 6 to 10 hours after carotid ligation. Autoradiographs of the gerbil brains with severe infarcts showed heavy label, which was uniformly distributed, on the affected side. We conclude that the gerbil stroke model is useful for studying hypoxia in vivo. There is variability between animals that closely correlates with stroke index, but more importantly the hypoxia may be more homogeneous over regions of the brain within one animal. A reliable model of homogeneous induced hypoxia in vivo will be useful for evaluating radiolabeled drugs which may be used for quantitation of hypoxia in tumors by nuclear imaging.

Animals↗

PubMed1992

Cognitive function and regional cerebral blood flow in Parkinson's disease.

In order to investigate relationships between cognition and regional brain function, we studied 20 non-demented patients with idiopathic Parkinson's disease (PD), 21 mildly demented patients with Alzheimer's disease (AD) and 24 control subjects using cognitive testing and single photon emission computerized tomographic (SPECT) measurements of relative regional cerebral blood flow (rCBF). Neuropsychological tests were grouped into clusters reflecting frontal lobe executive abilities, perseveration, memory and visuospatial ability, with a summary score summarizing performance in all four of these spheres. SPECT imaging utilized the tracer [123I]N-isopropyl-p-iodoamphetamine with a relative measure of regional tracer uptake normalized to occipital radiotracer uptake (rCBF ratios). Patients with PD performed more poorly than controls in all cognitive domains, and were intermediate to AD patients and controls in tests of memory and overall cognitive functioning. Those PD patients who performed most poorly on neuropsychological testing showed lowest rCBF ratios in left and right temporal lobes. Using a stepwise multiple regression procedure, we examined patterns of correlations between cognitive clusters and predictor variables, including rCBF ratios, in the PD patients. We found that while patient age was a strong determinant of performance on the memory cluster and the summary score, dorsolateral frontal lobe perfusion and scores on a depression inventory accounted for a greater proportion of the variance of the frontal lobe and perseveration clusters than did age. These results imply that different neural mechanisms are responsible for the different aspects of cognitive decline seen in PD patients, with overall cognitive function closely related to age and temporal perfusion, while frontal lobe abilities are more linked to frontal perfusion and the presence of depression.

Aged↗

PubMed2002

Preconditioning attenuates the shortening of recovery during coronary occlusion in isolated rabbit hearts with D-sotalol-induced long QT intervals.

The effects of 20-min ligations of the anterior branch of the left coronary artery were studied in Langendorff-perfused rabbit hearts with 92 microM D-sotalol added to the perfusate to induce long QT intervals and triggered arrhythmias. Epicardial electrograms, a left ventricular endocardial monophasic action potential, and simulated X and Y lead electrocardiograms were used to characterize ventricular conduction and recovery. In contrast to previous work showing that global ischemia eliminated triggered activity, coronary occlusion did not alter its mean incidence. Although the anatomic distribution of earliest sites of epicardial activation by triggered beats was altered, triggered beats still appeared on the epicardial surface in the nonperfused regions. Coronary occlusion had a small and variable effect on epicardial conduction velocity but caused a significantly greater percent shortening of epicardial activation-recovery intervals in the nonperfused region of hearts given D-sotalol than in control hearts. In hearts given D-sotalol, preconditioning significantly attenuated the shortening of epicardial activation-recovery intervals in response to coronary occlusion. However, preconditioning had no effect on the mean incidence of triggered activity during coronary occlusion. Thus, the persistence of triggered activity and the shortened myocardial recovery time associated with coronary occlusion could contribute to increasing the likelihood of occurrence of malignant ventricular arrhythmias. Preconditioning by attenuating the shortening of recovery would be anti-arrhythmic.

Animals↗

PubMed2003

Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions.

BACKGROUND: The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. METHODS AND RESULTS: In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch-like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks' duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. CONCLUSIONS: The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.

Adenosine↗

PubMed1997

Alexia and agraphia in posterior cortical atrophy.

A 65-year-old woman with progressive visuospatial dysfunction for 2 years complained of later-onset associated memory impairment. MRI revealed diffuse cerebrocortical atrophy, which was especially severe in both parieto-occipital regions but spared the calcarine and pericalcarine cortices. Examination 5 years after onset revealed left visual hemi-neglect, oculomotor apraxia, optic ataxia, simultanagnosia, verbal alexia, lexical and spatial agraphia, and anterograde amnesia. This patient's disorder is considered in the context of previous reports on the array of cognitive disturbances associated with posterior cortical atrophy (pCA). Special emphasis is made on her reading and writing disturbances, because their prevalence and range of individual variability have not been established in pCA. This array of neuropsychological manifestations may help to distinguish among different clinical and etiological types of pCA, and to elucidate the pathophysiology of a syndrome that has been associated with conditions as diverse as Alzheimer's disease, subcortical gliosis, and prion diseases. The parameters described in our case may thus help to address these issues in clinico-pathological studies with large numbers of patients with pCA.

Aged↗

PubMed2005

Regional variation in capture of fibrillating swine left ventricle during electrical stimulation.

INTRODUCTION: While it has been shown that electrical stimulation can capture a region of myocardium during ventricular fibrillation (VF), the ideal location to stimulate to maximize capture of the fibrillating in vivo left ventricle (LV) is not known. We previously demonstrated a mean directionality to the propagation of VF wavefronts in swine from posterior to anterior LV. We hypothesized that this directionality of VF wavefronts would affect capture of the LV epicardium while stimulating during VF. METHODS AND RESULTS: In seven open-chest swine, during different VF episodes, electrical stimulation was performed singly or simultaneously from two lines of 26 epicardial electrodes, one on the posterior LV adjacent to the posterior descending coronary artery and another on the anterior LV adjacent to the left anterior descending coronary artery. Mapping was performed between the line of stimulating electrodes with 768 recording electrodes 2-mm apart. The incidence and extent of epicardium captured by stimulation through the lines of stimulating electrodes were determined in the mapped region. Capture occurred during 67% of 78 VF episodes. Capture from the posterior LV line was achieved in 88% of the episodes and from the anterior LV line in 44% of the episodes (P = 0.001). The maximum amount of myocardium captured was also much greater for stimulating from the posterior as compared to the anterior LV line (232 +/- 168 mm(2) vs 64 +/- 124 mm(2), P = 0.003). A significant part of the variability in capture was related to the direction of the mean VF wavefront velocity vector in each animal (r = 0.84, P < 0.05). CONCLUSION: Electrical stimulation from the posterior LV resulted in a greater incidence and extent of LV capture than stimulation from the anterior LV. A significant component of the variability in capture is related to the mean direction of VF wavefronts.

Animals↗

PubMed1996

Cardiac 123I-MIBG uptake is affected by variable uptake in reference regions: implications for interpretation in clinical studies.

Cardiac 123I-meta-iodobenzyl guanidine (123I-MIBG) uptake, using the mediastinal region as a reference, is a predictor of outcome in heart failure. Constant uptake in a reference region is required when studying the pharmacotherapeutic effects on the integrity of the cardiac adrenergic system. The aim of this study was to verify the assumption of constant uptake in reference regions and their relation to established predictors of clinical outcome. Planar 123I-MIBG images were obtained in 28 patients with heart failure. The left ventricular ejection fraction correlated with the heart-to-mediastinum (H/M) ratio but not with myocardial 123I-MIBG uptake. Plasma noradrenaline correlated with the H/M ratio, the heart-to-lung (H/L) ratio, mediastinal uptake and age, but not with uptake in the myocardium and lung. Age correlated with the H/M ratio, H/L ratio, mediastinal uptake and lung uptake, but not with myocardial uptake. In a regression model, after the inclusion of age, the H/M ratio and mediastinal uptake were not related to noradrenaline. We conclude that changes in the H/M and H/L ratios are predominantly due to confounding changes in mediastinal uptake or lung uptake. In pharmacological intervention studies, myocardial 123I-MIBG uptake should be assessed using single photon emission tomography or positron emission tomography, which do not rely on reference regions in mediastinum or lung.

3-Iodobenzylguanidine↗

PubMed1999

Familial patent ductus arteriosus and bicuspid aortic valve with hand anomalies: a novel heart-hand syndrome.

The association between cardiac and limb defects, particularly those affecting the hand, has been well documented by the delineation of several heart-hand syndromes. Based on observations with a three-generation family with seven affected individuals, we describe a novel heart-hand syndrome comprising patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplasia, and brachydactyly. The inheritance pattern was consistent with autosomal dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes. Because this new syndrome closely resembled Char syndrome (patent ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor facial anomalies), multipoint linkage analysis was performed using polymorphic DNA markers spanning the recently identified Char syndrome critical region at chromosomal bands 6p12-p21.1. This analysis formally excluded this 3-cM region, documenting that the two traits are not allelic. In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as well as an ulnar ray derivative has been identified. Because the hand anomalies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait.

Alleles↗

PubMed1988

Myocardial contrast echocardiography without significant hemodynamic effects or reactive hyperemia: a major advantage in the imaging of regional myocardial perfusion.

All agents used for myocardial contrast echocardiography to date produce adverse hemodynamic effects and alter coronary blood flow. It was hypothesized that because 5% human albumin, when sonicated for use as a contrast agent, is neither hyperosmolar nor a calcium chelator, it would not have significant effects on coronary blood flow, left ventricular function or systemic hemodynamics. Albumin microbubbles of two distinct sizes (mean size 2.9 and 5.8 micron) were produced and compared with nonsonicated albumin, nonsonicated Renografin, sonicated Renografin and hand-agitated Renografin for their effects on hemodynamics, coronary blood flow and regional left ventricular systolic thickening in 15 open chest anesthetized dogs. None of the albumin solutions significantly altered left atrial, left ventricular systolic and end-diastolic and mean aortic pressures. These agents did not cause a coronary hyperemic response or alter left ventricular systolic thickening, but slightly lowered the peak positive left ventricular maximal rate of rise in pressure (dP/dt) (-4.1 +/- 5.4%, p less than 0.01). In contrast, all the Renografin solutions caused significant changes in all these variables (p less than 0.02). In six dogs. albumin solutions did not alter these variables even in the presence of critical coronary stenosis. The contrast opacification produced by 5.8 micron albumin microbubbles was equivalent to that produced by sonicated Renografin. Compared with an equivalent amount of saline and nonsonicated albumin solutions, 10 ml of sonicated albumin did not produce any evidence of infarction, embolization or hemorrhage in the myocardium, brain or kidneys of rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗