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Early administration of amrinone does not impair regional metabolism of O2 or lactate and, by improving myocardial performance, preserves myocardial blood flow in the ischemic canine heart.

The inotropic and vasodilating effects of amrinone can upset the balance of O2 supply and demand by changing those components in opposite directions simultaneously. We used a canine model of acute coronary artery occlusion to test our hypothesis that early administration of amrinone (before failure of the heart) would have beneficial effects on hemodynamic status and regional metabolism during ischemia, even before heart failure. Twenty dogs anesthetized with thiamylal were subjected to 50%, 75%, and 100% occlusion of the left anterior descending coronary artery. Half of the dogs were given a bolus injection of amrinone (0.75 mg/kg) 1-2 min before each occlusion, immediately followed by continuous infusion (10 micrograms.kg-1 x min-1) during occlusion; the other half did not receive amrinone (control). Hemodynamic and metabolic variables were measured in the ischemic area (the left anterior descending coronary artery) and in a nonischemic area (the circumflex vein). Amrinone not only decreased heart rate, left ventricular systolic and end-diastolic pressures, and mean pulmonary arterial pressure during constrictions but also maintained contractility, stroke volume index, and stroke volume index/left ventricular end-diastolic pressure before and during constrictions. Regional myocardial blood flow in ischemic areas decreased with amrinone during constrictions but was still higher than in untreated animals. Regional ischemic and nonischemic metabolic variables (metabolism of intracoronary potassium, CO2, O2, glucose, and lactate) were similar for both groups and changed to the same extent. Amrinone appears to improve left ventricular performance and increase blood flow to ischemic myocardium while not worsening regional metabolic effects during various grades of ischemia in the dog.

Amrinone↗

Changes in intramyocardial ST segment voltage and gas tensions with regional myocardial ischemia in the dog.

This study was designed to evaluate the sensitivity of changes in myocardial carbon dioxide and oxygen tensions as indicators of regional myocardial ischemia and also to determine to what extent these changes can be related to changes in intramyocardial ST segment voltage. Changes in ST segment voltage recorded in unipolar epicardial electrodes proved to be a less-sensitive indicator of underlying myocardial ischemia than were changes in ST segment voltage recorded in unipolar intramyocardial electrodes. In 9 dogs, regional ischemia was produced by placing a variable constrictor on the left circumflex coronary artery; circumflex flow was monitored. Myocardial carbon dioxide and oxygen tensions were measured using a mass spectrometer. Unipolar electrograms were recorded using a multicontact plunge electrode. With progressive degrees of proximal stenosis, ranging from a critical stenosis, which is associated with a decrease in mean flow of less than 15%, to a severe stenosis associated with and 80% decrease, ST voltage increased 21 mv and carbon dioxide tension increased 84 mm Hg, but oxygen tension decreased only 7 mm Hg. The study suggests that increases in intramyocardial ST segment voltage, an index of myocardial ischemia, are associated with parallel increases in myocardial carbon dioxide tension, each providing a more sensitive quantitative correlate of regional myocardial ischemia than do decreases in oxygen tension. The local accumulation of carbon dioxide may be an important pathophysiological mechanism in myocardial ischemia.

Animals↗

Brain perfusion assessed by 99mTc-ECD SPECT imaging in pediatric patients with neurally mediated reflex syncope.

BACKGROUND: The involvement of cardiogenic and neurogenic mechanisms in neurally mediated reflex syncope is well documented. In our previous studies in patients with neurally mediated reflex syncope, we have found evidence for differential regulation of the noradrenergic receptors in tilt-positive and tilt-negative patients. The present work concentrates on the observations of differences in regional brain perfusion using brain SPECT via injecting the patient at the completion of the tilt test. METHODS AND RESULTS: The following study was designed to assess the reduction and regional differences in cerebral blood flow by means of SPECT using technetium-99m labeled V-oxo-1,2-N1ethylenedylbisl-cysteine diethylester (ECD) in patients with an injection during tilt testing. Twenty patients with NMS were included in the study with a mean age of 12.2 years (age range; 8-16 years). HUT was positive in 10 patients and negative in 10 patients. When tilt (+) and tilt (-) were evaluated together, regional cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical areas with highest variability of perfusion index in left frontoparietal cortex. The lowest perfusion index values were observed in the left anterior frontal region followed by the left prefrontal-frontoparietal-anterior, parietal-orbito frontal, and anterior temporal regions where perfusion is predominantly supplied via the anterior and middle cerebral arteries, while these differences did not reach statistical significance in a single dominant region compared to the other regions examined using ANOVA (P > 0.05) with this sample size. Decreases in [99mTc]ECD uptake were more widespread regionally on the left hemisphere than were decreases in right side of the brain. However when tilt- and tilt+ groups were compared, perfusion was significantly lower in the right periinsular posterior parietal and temporal regions (P < 0.05) in tilt + group. CONCLUSION: These tilt induced regional differences in brain perfusion suggest the distinct roles of middle cerebral artery dominant territory-related vasodepressor compensation mechanisms in neurally mediated reflex syncope phenomena where cerebral lateralization of cardiac control and insular ischemia may play an important role.

Adolescent↗

Auditory evoked responses to single tones and closely spaced tone pairs in children grouped by reading or matrices abilities.

Long latency auditory evoked responses (AER) were formed to single tones and rapid tone pairs. Using the t-statistic SPM technique, children with poorer WIAT reading scores demonstrated group difference overlying the left parietal and frontal language regions but just for AER to tone pair stimuli. Variables derived from these regions were not significantly different when the same subjects were grouped by K-BIT Matrices scores. When the same children were regrouped by Matrices scores and compared using the SPM technique, differences were now seen over the right hemisphere, especially in the parietal and frontotemporal regions, for both single and two-tone derived AERs. Variables derived from these regions were not significantly different for children when grouped by reading score. AER data support a specific deficit in two-tone stimulation for poorer reading children over the left hemisphere and also a deficit to both single and two-tone stimulation over the right hemisphere for children with poorer Matrices scores.

Acoustic Stimulation↗

Genetic variation and multigene families in African swine fever virus.

The genome of a virulent strain (LIS57) of African swine fever virus differs from that of the Vero-cell-adapted strain (BA71V) in several deletions located in the variable regions. The region which contains the most differences is located 8-20 kb from the left end. The DNA sequence of this region was obtained from LIS57 virus DNA and compared with the overlapping sequences of BA71V virus. This comparison revealed that the changes in the variable regions result in differences in the number of genes which belong to the multigene families 360 and 110. Virus isolate LIS57 contains at least 8 genes of the multigene family 360 and 12 genes of the multigene family 110, instead of the 6 and 5 genes, respectively, found in BA71V virus strain. The position of the deletions indicates that new combinations of multigene family members in African swine fever virus DNA may arise by in-frame recombination between homologous genes. These data indicate that the evolution of the multigene families 360 and 110 in African swine fever virus DNA has involved different processes, including gene duplication, divergence of duplicated genes, and gene deletion.

African Swine Fever Virus↗

Lidocaine increases the ventricular fibrillation threshold during bupivacaine-induced cardiotoxicity in pigs.

Ventricular fibrillation (VF) is a cause of death in bupivacaine-induced cardiovascular toxicity. We have examined the therapeutic effects of lidocaine on the threshold for bupivacaine-induced VF in in situ beating swine hearts. Twenty-four animals were allocated to one of three groups: 0.25% bupivacaine, 1% lidocaine or 0.25% bupivacaine with 1% lidocaine were infused into the left anterior descending coronary artery in increasing doses of 0, 1, 2, 4, 8 and 16 ml h-1 for 15 min, respectively. ECG and haemodynamic variables were monitored continuously during infusion. Regional myocardial function in the area supplied by the left anterior descending coronary artery was assessed using the sonomicrometry technique. VF did not occur in the lidocaine group. VF developed at higher infusion rates in animals given bupivacaine with lidocaine (in one animal at an infusion rate of 8 ml h-1 and in seven at 16 ml h-1) compared with animals given bupivacaine alone (in one at an infusion rate of 4 and in seven at 8 ml h-1). Although regional myocardial function decreased with increases in the infusion rate in each group, the depressant effects of the bupivacaine solution (medial inhibitory infusion rate of systolic shortening: IR50 = 2.43 (0.43) ml h-1) were significantly greater than those of the lidocaine solution (IR50 = 5.83 (0.87) ml h-1), but did not differ from those of the bupivacaine with lidocaine solution (IR50 = 3.54 (0.56) ml h-1). This study indicates that a combination of lidocaine and bupivacaine increased the threshold for bupivacaine-induced VF without further depressing myocardial contractility.

Anesthetics, Combined↗

Effect of transthoracic shocks on left ventricular function.

Although defibrillating shocks are thought to depress ventricular function transiently, the independent effects of high strength shocks (without the metabolic sequelae of pre-shock fibrillation) have not been assessed systematically in humans. Therefore, we delivered three consecutive synchronized monophasic transthoracic shocks (200, 200 and 360 J) at 60s intervals during sinus rhythm and evaluated the effect on left ventricular chamber size and function as determined by transesophageal echocardiography in 11 patients (mean age 67+/-8 years, 9M/2F) with depressed left ventricular function (left ventricular ejection fraction: 14-37%). The shocks did not alter hemodynamics consistently. On average, the shocks did not alter stroke volume, cardiac output, left ventricular ejection fraction or regional wall thickening (all p>0.05 versus baseline). This effect was highly variable and 36% of patients experienced a >25% reduction in cardiac output by the final shock. There was a tendency for regional wall thickening to worsen in the best baseline sextant with an offsetting significant increase in thickening in the worst baseline sextant (p=0.05). Thus, repetitive defibrillation strength transthoracic shocks do not impair left ventricular function consistently in patients with cardiomyopathy. However, the effect is widely variable and potentially important depression of left ventricular function does occur in some patients.

Aged↗

Effect of nifedipine on regional O2 consumption in ischemic myocardial tissue.

The effect of intravenous (i.v.) nifedipine (5 micrograms/kg/min) on regional O2 supply/consumption variables was determined in 14 anesthetized open-chest dogs subjected to left anterior descending coronary artery (LAD) stenosis sufficient to reduce blood flow 50%. Myocardial blood flow was measured using radioactive microspheres, and regional arterial and venous O2 saturations were determined using microspectrophotometry. During LAD occlusion, blood flow and O2 consumption were decreased in the ischemic region while O2 extraction was increased. With nifedipine treatment, LAD flow (flow probe) was increased 44% as compared with the initial occluded value, with most of this increase going to the subepicardium (microspheres). Flow to the ischemic subendocardium was not changed with nifedipine treatment. Ischemic subepicardial O2 consumption increased slightly in nifedipine-treated animals as compared with saline values, whereas O2 extraction decreased slightly. In the subendocardial region, nifedipine resulted in a significant decrease in O2 extraction, with a slight decrease in O2 consumption as compared with saline controls. The O2 supply/demand ratio was significantly improved with nifedipine only in the subendocardium of the ischemic region. This suggested that nifedipine could increase O2 consumption in the ischemic subepicardium through proportional increase in O2 supply while it decreased O2 consumption in the subendocardium relative to O2 supply.

Animals↗

An insertion-deletion event in murine immunoglobulin kappa gene resembles mutations at heavy-chain disease loci.

The analysis of spontaneous somatic mutants gives insights into the regulation of gene expression. Human heavy-chain disease (HCD) is a monoclonal lymphoproliferative disorder characterized by the presence of truncated immunoglobulin (Ig) heavy chains without associated light chains. To better understand the molecular mechanisms leading to the loss of light-chain production, we have examined a murine cell line model of heavy-chain disease. R15, a spontaneous mutant of the IgA, kappa-producing myeloma cell line W3129, produces heavy chain but no light chain. The variant delta 15 derived from R15 resembles human HCD in that it secretes a shortened heavy chain with no associated light chain. Cloning and analysis of the R15 kappa light-chain gene revealed that a 358-nucleotide insertion of unknown origin replaced 22 bases of the wild-type leader-variable region (L-V) intron (IVS). Although this genomic change left the light-chain exons and known regulatory elements intact, it altered the mRNA processing pathway, yielding two alternative RNA products, neither of which encodes a functional protein. This mutant therefore provides new insights into how genomic changes can influence gene expression.

Animals↗

Plasma B-type natriuretic peptide levels are associated with early cardiac dysfunction after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Serum B-type natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), as well as in the setting of congestive heart failure and myocardial infarction. The aim of this study was to prospectively quantify the relationship between BNP levels and cardiac outcomes after SAH. METHODS: Plasma was collected for BNP measurements as soon as possible after enrollment; a mean of 5+/-4 days after SAH symptom onset. On days 1, 3, and 6 after enrollment, troponin I (cTi) was measured and 2-dimensional echocardiography was performed. The following cardiac variables were collected and treated dichotomously: left ventricular ejection fraction (LVEF), regional wall motion abnormalities (RWMA), diastolic dysfunction, pulmonary edema, and cTi. RESULTS: There were 57 subjects. The median BNP level was 141 pg/mL (range, 0.8 to 3330 pg/mL). Higher mean BNP levels were present in those with RWMA (550 versus 261 pg/mL; P=0.012), diastolic dysfunction (360 versus 44; P=0.011), pulmonary edema (719 versus 204; P=0.016), elevated cTi (662 versus 240; P=0.004), and LVEF <50% (644 versus 281; P=0.015). CONCLUSIONS: Early after SAH, elevated BNP levels are associated with myocardial necrosis, pulmonary edema, and both systolic and diastolic dysfunction of the left ventricle. These findings support the hypothesis that the heart releases BNP into the systemic circulation early after SAH.

Aged↗

Assessment of left ventricular regional wall motion by color kinesis technique: comparison with angiographic findings.

The analysis of segmental wall motion using two-dimensional (2-D) echocardiography is subjective with high interobserver variability. Color kinesis is a new technique providing a color-encoded map of endocardial motion. We evaluated the accuracy of color kinesis and 2-D for assessment of regional asynergy compared with left ventricular angiography as a reference method. Fifteen patients admitted for myocardial infarction were studied by echocardiography the day before left ventricular angiography. The left ventricle was divided into seven segments. Each segment was classified by two independent observers as normal or abnormal in 2-D and color kinesis. Accuracy of color kinesis and 2-D was evaluated and compared to left ventricular angiography. Color kinesis is significantly superior to 2-D for all seven segments (mean 0.80/0.68, P = 0.05), except for the septum (0.67/0.60, P = NS). Interobserver variability studied by chi-square statistic is lower with color kinesis (0.70) than with 2-D (0.57). We conclude that these data suggest that color kinesis is a useful method for assessing systolic wall motion in all segments, except the septum and for improving the accuracy of segmental ventricular function and interobserver variability.

Adult↗

Structure and variation of human ribosomal DNA: the external transcribed spacer and adjacent regions.

A group of human ribosomal DNA (rDNA) recombinants that include the probable site for initiation of transcription have been examined for sequence polymorphism. A detailed restriction map of one rDNA insert was constructed using plasmid subclones and end-labeled segments. Comparison of 16 similar rDNA inserts by restriction and heteroduplex analysis demonstrated striking conservation of the external transcribed spacer and 18S gene regions, but defined a region where restriction sites for the enzymes Sma I, Hpa II, and Hha I become frequent or variable. This region extends for about 400--800 base pairs (bp) at the left end of the rDNA insert and is postulated to contain nontranscribed spacer sequences. The use of cloned rDNA segments as probes for the restriction analysis of genomic rDNA has demonstrated certain fixed sites in the nontranscribed spacer that do not vary significantly among different individuals or tumor cell lines. In contrast, restriction with the enzyme Sal I reveals several variable fragments, one of which has been found only in a retinoblastoma cell line.

Base Composition↗

Specific circular organization of the neurons of human interthalamic adhesion and of periventricular thalamic region.

Interthalamic adhesion between the medial surfaces of the left and right thalamus is a variable structure and contains the midline thalamic nuclei, which are not much developed in humans. The research has been done on 6 human brains obtained during routine autopsy (age 45 to 65; 4 male and 2 female). Every tenth 10 microm thick frontal section was stained according to Klüver-Barrera method. In all cases the authors found a specific organization of certain groups of neurons within the interthalamic adhesion (IA) in form of circles on frontal sections. These circular groups were present on all sections but only 1-2 in each. The larger mean diameter of these circular arrangements was R = 229.4 microm, and smaller was r = 203.1 microm. These circular groups within the human IA were formed in average by 7.29 neurons. In periventricular region (PVR) of thalamus similar circular groups of neurons also were present in all cases as in IA. These neuronal groups in PVR were of smaller size than in the IA, with larger mean diameter R = 201.4, smaller mean diameter r = 181.2 microm and they contained fewer neurons, 6.69 on average. All three values (both diameters of circular arrangements, and number of neurons forming them) were significantly smaller in PVR (p < .01). Morphological types and sizes of neurons in both investigated structures (IA and PV) were not different. The circular neuronal groups in IA were formed in 61% of fusiform neurons and in PVR in 48% of fusiform neurons. According to their subependymal localization, size and form, these circular groups can represent in vivo correlates of neurospheres.

Aged↗

Effects of AR-L 115 BS (Sulmazol), a new cardiotonic agent, in coronary artery disease: improved ventricular wall motion, increased pump function and abolition of pacing-induced ischemia.

AR-L 115 BS (Sulmazol) is a new noncatechol, nonglycosidic cardiotonic agent. In 17 patients with significant coronary artery disease, the influence of AR-L 115 BS on hemodynamics and regional wall motion was investigated under the following conditions: 1) control, 2) the immediate postpacing period without medication, and 3) the postpacing period under the peak influence of AR-L 115 BS, 2 mg/kg intravenously. During the postpacing phase without medication, all patients developed ischemia (angina, ST segment alterations, increase of mean left ventricular end-diastolic pressure from 13 to 30 mm Hg), left ventricular pump function diminished and overall regional wall motion showed a tendency to decrease (p greater than 0.05). However, during the postpacing period with AR-L 115 BS medication, ischemia was abolished (no angina; mean left ventricular end-diastolic pressure decreased to 13 mm Hg; hemodynamic variables returned to control levels and left ventricular pump function showed some improvement while overall regional wall motion showed tendencies to improve. A comparison of alterations of hemodynamics and regional wall motion during the postpacing phase without medication with those under the influence of AR-L 115 BS shows that overall left ventricular pump function and regional wall motion improved while angina and an increase in left ventricular end-diastolic pressure were prevented. It is concluded that AR-L 115 BS improves left ventricular pump function and regional wall motion in coronary artery disease without inducing ischemia, probably by means of a reduction in extravascular resistance.

Angina Pectoris↗

Quantitative assessment of left ventricular wall motion by two-dimensional echocardiography: validation during reversible ischemia in the conscious dog.

This study was designed to test the accuracy of echocardiographic radial shortening measurements during variable degrees of regional dysfunction produced by 14 transient (less than or equal to 10 min) coronary occlusions (8 left anterior descending coronary artery, 6 left circumflex coronary artery) followed by up to 24 h of reperfusion in chronically instrumented conscious dogs. Independent measurement of regional myocardial thickening was obtained using epicardial pulsed Doppler probes and served as a standard for comparison. Radial shortening fraction was derived from two-dimensional short-axis views along 12 equidistant radii. Six reference systems from the epicardial and endocardial centers of geometry (centroids) in a fixed or a floating position were explored. In the ischemic zone, percent thickening fraction averaged 22 +/- 5% at baseline, decreased to -4 +/- 4% during occlusion and gradually returned to baseline values after reperfusion. Percent change in radial shortening correlated significantly with percent change in thickening fraction in the ischemic zone. The worst correlation was seen with the floating endocardial centroid (r = 0.68), and the best was observed with the epicardial floating reference (r = 0.91). Moreover, the epicardial floating reference provided narrower 95% confidence limits of radial shortening and less heterogeneity among radii than did fixed reference systems. Thus, compared with an independent standard, echocardiographic measurement of radial shortening from the short axis provided recognition of discrete grades of regional dysfunction induced by transient reversible ischemia. This technique may be amenable for serial assessment of regional function after interventions on the ischemic myocardium.

Animals↗

[Mutational pattern of Ig-VH genes of synovial B-lymphocytes from different anatomical locations in a rheumatoid arthritis patient].

Synovial B-lymphocytes which are a constant feature of RA synovialitis are expanded in an antigen dependent manner. To understand the nature of the antigen driving the B-cell expansion it would be interesting to know whether there exists a restricted number of antigens. Therefore the usage of germline genes and the mutational pattern of Ig-VH-genes from synovial B-cells from 3 different anatomical regions with different onsets of local disease were analysed. Together with an immunohistological study characterising the inflammatory infiltrate (CD3, CD22, CD23 and Ki-M4), RNA was prepared from tissue sections taken from the right and left peroneal tendons and right elbow of a patient with seropositive RA. The corresponding cDNA was amplified using specific VH primers and the obtained variable region sequences were compared to their closest germline counterparts on the EMBL/Genbank data base. The molecular analysis demonstrated somatically mutated VH genes (total R/S ratios in CDR 1 + 2: right peroneal tendon 7.5; left peroneal tendon 3.5 and right elbow 3.0) in all three different regions, with two clones presenting aminoacid deletions. The values of total R/S ratios correlated directly to the duration of local disease. The aminoacid sequences from the different locations exhibited strong homology among each other. This homology was of 77% for the 19 clones belonging to the VH1 family. Immunohistochemistry demonstrated in two locations a dense follicle-like infiltrate with FDC-network, the third location presented a non-follicular distribution of lymphozytes without FDC. Hence the R/S values were correlated directly with the duration of local disease, it appears that here is an ongoing antigen-dependent B-cell activation in joints probably occurring in the FDC-networks. Moreover this study suggests--due to a high homology among the VH aminoacid sequences from B-cells of different anatomical regions--that a restricted number of antigens is involved in the B-cell expansion of RA patients.

Amino Acid Sequence↗

Left ventricular regional myocyte contractility in normal and heart failure states.

Fundamental determinants of left ventricular (LV) pump performance are preload, afterload and myocyte contractility. Regional variability in LV end systolic wall stress, an important index of LV afterload, has been well defined in both control and congestive heart failure (CHF) states. The goal of this study was to examine end systolic wall stress and myocyte contractile function in three circumferential regions of the LV in both control and CHF states. Accordingly, LV end systolic wall stress and myocyte velocity of shortening were measured from the basal, mid and apical regions in control pigs (n=5) and following the induction of pacing-induced CHF (3 weeks, 240 beats/min, n=5). LV mid wall, circumferential, end systolic wall stress decreased from base to apex in both control (35+/-7 v 16+/-4 g/cm2, P<0.05) and CHF (155+/-23 v 92+/-24 g/cm2, P<0.05) states. In the CHF group, LV end systolic wall stress was elevated by 300% compared to control values in all regions. LV myocyte velocity of shortening was equivalent in the basal and mid regions of control myocytes (52+/-2 v 57+/-2 m/s), and was higher in the apical region (63+/-3 microm/s, P<0.05). In the CHF group, LV myocyte velocity of shortening was reduced by 45% compared to controls with no regional variation. beta-adrenergic stimulation increased myocyte velocity in both the control and CHF groups, however, regional variation was observed only in the CHF group. These unique results demonstrated that minimal regional variations in myocyte contractile function exist in both control and congestive heart failure states, and does not necessarily parallel patterns of regional LV end systolic wall stress.

Animals↗

Difference of regional cerebral metabolic pattern between presenile and senile dementia of the Alzheimer type: a factor analytic study.

Positron emission tomographic studies using metabolic ratios to represent the contrast between certain brain regions have shown differences of cerebral glucose metabolism between presenile and senile dementia of Alzheimer type (DAT). In this study, factors for regional variance of cerebral metabolism in 61 patients with probable Alzheimer's disease were obtained using principal component analysis (PCA). The difference between two age groups of DAT patients according to age at onset < or = 65 years (n = 30) and > 65 years (n = 31) were investigated. A PCA using nine pairs of cerebral regions normalized to cerebellum for reduction of intersubject variability identified five regional factors for cerebral metabolism: one each for the left and right temporo-parietal cortex, and the other three for frontal cortex, primary visual and sensorimotor cortex, and mesial temporal sensorimotor cortex, and mesial temporal cortex. The age groups differed significantly only in the factor for the right temporo-parietal cortex, with a more prominent metabolic reduction in presenile than senile DAT. Severity of dementia was correlated with the factors for the right and left temporo-parietal cortex. The effect of age at onset on glucose metabolism of the right temporo-parietal cortex was independent from that of dementia severity in DAT.

Age Factors↗