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Biomedical subjects

A A Grace

Publications and source records attributed to A A Grace.

At least 91 records · Page 5Linked to original sources
PubMed1995

The significance of paced electrogram fractionation in hypertrophic cardiomyopathy. A prospective study.

BACKGROUND: Increased duration of paced right ventricular (RV) electrograms in hypertrophic cardiomyopathy has been shown in 37 patients to correlate with the risk of ventricular fibrillation (VF). The changes in electrogram duration with pacing stimulus prematurity discriminated patients into three groups: VF survivors, an intermediate group with either non-sustained ventricular tachycardia (NSVT) on ambulatory monitoring or a family history of sudden death (FHSD), and those with none of these risk factors (noRF) for sudden death (SD). The consistency of these original groups has been tested prospectively in a further 64 patients. METHODS AND RESULTS: Of 64 patients with hypertrophic cardiomyopathy, 3 had documented VF, 1 had witnessed SD and is assumed to have had VF, 25 had NSVT, 21 had FHSD, and 14 had noRF. Nineteen patients had syncope. They were studied by pacing one RV site with a decremental sequence and recording high-pass filtered electrograms from three other RV sites. The delay of each fractionated potential in the electrogram was determined relative to a pacing stimulus of increasing prematurity. These measurements were repeated by pacing each ventricular site in turn. The electrograms were characterized by two parameters: the extrastimulus coupling interval (S1S2) at which delay increased by more than 0.75 ms/20 ms decrease in S1S2 interval and the change in electrogram duration between an S1S2 of 350 ms and ventricular effective refractory period. The 4 VF patients had a mean increase in electrogram duration of 16.1 ms and an increase in delay at a mean S1S2 of 368 ms. Three VF patients were within the original VF group, while only 6 of 60 non-VF patients were within this group, discriminating between VF patients and the remainder (P < .007). The 14 noRF patients had a mean change in electrogram duration of 4.5 ms and an increase in delay at a mean S1S2 of 301 ms. Eleven patients were within the original noRF group, and only 8 of the remaining 50 patients also were within the noRF group, discriminating between the noRF patients and the remainder (P < .0005). Most of the NSVT and FHSD patients were between the original VF and noRF groups, with 5 of 25 NSVT and 1 of 31 FHSD patients in the original VF group. There was no relation between syncope and electrophysiological characteristics. Programmed electrical stimulation (PES) was performed in the first 15 patients of this study. Of the total 52 patients from the original and current studies, PES identified 2 out of 6 VF patients, and there was no correlation between VF inducibility and intraventricular conduction delay. CONCLUSIONS: These data are consistent with the original VF and noRF groups. Most patients with FHSD or NSVT were between these groups. Pooled data from the original and current groups (n = 101) allow definition of a new VF group, which includes all patients with VF (n = 9), 8 of 30 patients with VT, and 3 of 31 patients with FHSD. This new group may be used as a criterion for implantable cardioverter-defibrillator implantation in a prospective trial of the technique for the prediction of SD.

Adult↗
PubMed1995

Different effects of subchronic clozapine and haloperidol on dye-coupling between neurons in the rat striatal complex.

Atypical antipsychotic drugs, such as clozapine, are distinguished from classical antipsychotics (e.g. haloperidol) by their lower liability for producing motor side-effects. Although initial studies suggested that the clinical efficacy of antipsychotic drugs is related to their affinity for the D2 dopamine receptor, the delayed onset of both the therapeutic effects and the extrapyramidal symptoms associated with these drugs implicates a more complex mechanism of action. In this study, we found that continuous (but not acute) treatment of rats with either drug caused an increase in dye coupling between neurons in the limbic component of the rat striatal complex (i.e. the shell region of the nucleus accumbens) after withdrawal of the drugs. Furthermore, continuous treatment with haloperidol, but not clozapine, also increased dye coupling in the motor-related part of the striatal complex (i.e. the dorsal striatum). Thus, both therapeutically effective drugs show a delayed effect on dye coupling between neurons in the accumbens shell, whereas only the drug associated with motor side effects altered coupling between cells in the dorsal striatum. Antipsychotic drugs may therefore alleviate the profound disturbances in cognitive function of schizophrenics by producing sustained alterations in the way signals from the cortex are integrated within these brain regions.

Animals↗
PubMed1995

The tonic/phasic model of dopamine system regulation: its relevance for understanding how stimulant abuse can alter basal ganglia function.

The changes in dopamine system regulation occurring during stimulant administration are examined in relation to a new model of dopamine system function. This model is based on the presence of a tonic low level of extracellular dopamine that is released by the presynaptic action of corticostriatal afferents. In contrast, spike-dependent dopamine release results in a phasic, high concentration of dopamine in the synaptic cleft that is rapidly inactivated by reuptake. Tonic dopamine has the ability to down-modulate spike-dependent phasic dopamine release via stimulation of the very sensitive dopamine autoreceptors present on dopamine terminals. Stimulants are known to elicit locomotion and stimulate reward sites by releasing dopamine from terminals in the nucleus accumbens, which is followed by a rebound depression. It is proposed that the initial activating action of stimulants is caused by increasing the release of dopamine into the synaptic cleft to activate the phasic dopamine response. However, by interfering with dopamine uptake, stimulants also allow dopamine to escape the synaptic cleft, thereby depressing subsequent spike-dependent phasic dopamine release by increasing the tonic stimulation of the autoreceptor. In contrast, repeated stimulant administration is proposed to cause long-term sensitization by pharmacological disruption of a cascade of homeostatic compensatory processes. Upon drug withdrawal, the fast compensatory systems that were blocked by stimulants rapidly restore homeostasis to the system at a new steady-state level of interaction. As a consequence, the slowly changing but potentially more destabilizing compensatory responses are prevented from returning to their baseline conditions. This results in a permanent change in the responsivity of the system. Homeostatic systems are geared to compensate for unidimensional alterations in a system, and are capable of restoring function even after massive brain lesions or the continuous presence of stimulant drugs. However, the system did not evolve to deal effectively with repetitive introduction and withdrawal of drugs that disrupt dopamine system regulation. As a consequence, repeated insults to a biological system by application and withdrawal of drugs that interfere with its homeostatic regulation may be capable of inducing non-reversible changes in its response to exogenous and endogenous stimuli.

Amphetamines↗
PubMed1995

The serum concentration of active transforming growth factor-beta is severely depressed in advanced atherosclerosis.

Recent evidence has led us to propose that transforming growth factor-beta (TGF-beta) is a key inhibitor of atherosclerosis. We show here that a population of patients with advanced atherosclerosis all have less active TGF-beta in their sera than patients with normal coronary arteries, with a fivefold difference in average concentration between the two groups. This correlation with atherosclerosis is much stronger than for other known major risk factors and it may therefore have important diagnostic and prognostic significance. Aspirin medication correlates with an increase in active TGF-beta concentration, indicating that therapeutic interventions for TGF-beta are possible.

Aged↗
PubMed1995

Repeated treatment with haloperidol and clozapine exerts differential effects on dye coupling between neurons in subregions of striatum and nucleus accumbens.

The delayed onset of action of antipsychotic drugs (APDs) during the treatment of schizophrenia has been hypothesized to temporally correlate with the induction of depolarization block in rat mesencephalic dopamine (DA) cell groups. Nevertheless, it is unknown whether these drugs also exert a delayed action on the dopaminoceptive postsynaptic target cells in the striatal complex. Using in vivo intracellular recording and dye labeling techniques, the effects of APDs on dye coupling were examined in subregions of the striatal complex defined by double staining for calbindin immunoreactivity. Rats treated repeatedly with APDs were found to exhibit a 66-71% higher incidence of coupling that occurred in a drug- and a region-specific manner, that is, both drug treatments increased dye coupling in the limbic-associated accumbens shell region whereas only haloperidol increased dye coupling in the motor-related striatal matrix and accumbens core regions. In addition, cells located in regions in which dye coupling was altered also showed significantly higher input resistance. These changes were not observed in response to DA receptor blockade by acute drug administration or when haloperidol was administered for a period sufficient to induce DA receptor supersensitivity but not DA cell depolarization block (i.e., 2 weeks). Therefore, alteration in dye coupling appears to be correlated temporally with the induction of DA cell depolarization block. The finding that both APDs exert a common action on neurons in the accumbens shell region is consistent with its identification as the site of therapeutic drug actions, whereas the capacity of haloperidol to also affect cells in the motor-related matrix and core regions correlates with its high propensity to induce extrapyramidal side effects.

Animals↗
PubMed1995

Activation of dopamine cell firing by repeated L-DOPA administration to dopamine-depleted rats: its potential role in mediating the therapeutic response to L-DOPA treatment.

The administration of L-dihydroxyphenylalanine (L-DOPA) to patients with Parkinson's disease is known to produce acute effects that include the reduction of rigidity as well as delayed therapeutic actions involving the resumption of complex motor behavior. In order to examine the potential role of dopamine (DA) cell activity in mediating these responses, the effects of acute and repeated L-DOPA administration on the electrophysiological activity of the residual dopamine (DA) neurons were examined in rats that had received partial 6-hydroxydopamine (6-OHDA)-induced DA lesions. DA cell activity was assessed along three dimensions: (1) the relative proportion of DA neurons exhibiting spontaneous spike firing, (2) their basal firing rate, and (3) their firing pattern. Following 6-OHDA-induced DA depletion, rats were treated for 1 month with saline or L-DOPA. In addition, rats from each group received either an acute injection of L-DOPA or saline on the day of recording. In rats receiving repeated saline treatment, the DA neurons recorded following acute L-DOPA administration were firing at significantly slower basal firing rates and exhibited less burst firing when compared to saline-pretreated rats given acute saline. In contrast, DA cells recorded from rats that had received repeated L-DOPA administration for 4 weeks followed by an acute saline injection did not exhibit any significant differences from DA cells of intact control rats with respect to basal firing rate or firing pattern; however, there was a substantial increase in the proportion of DA neurons exhibiting spontaneous spike firing after correcting for 6-OHDA-induced cell loss. In addition, in rats receiving repeated L-DOPA treatment, the DA cells recorded following acute administration of L-DOPA showed significantly less of a reduction in firing rate when compared to the cells recorded following acute L-DOPA in the saline treatment group. These results show that: (1) acute L-DOPA administration appears to exert its actions by DA autoreceptor stimulation, whereas (2) repeated L-DOPA administration increases the proportion of spontaneously active DA neurons in partially lesioned rats. As a result, repeated L-DOPA administration would be expected to cause an increase in spike-dependent DA release as a consequence of the greater proportion of DA cells showing spontaneous activity. This may be the major factor underlying the delayed therapeutic benefits of L-DOPA therapy in the treatment of Parkinson's disease.

Animals↗
PubMed1995

Synaptic interactions among excitatory afferents to nucleus accumbens neurons: hippocampal gating of prefrontal cortical input.

The interactions among excitatory inputs arising from the prefrontal cortex, amygdala, and hippocampus, and innervating nucleus accumbens neurons were studied using in vivo intracellular recording techniques. Neurons recorded in the accumbens displayed one of three activity states: (1) silent, (2) spontaneously firing at low, constant rates, or (3) a bistable membrane potential, characterized by alternating periods of activity and silence occurring in concert with spontaneous transitions between two steady-state membrane potentials (average, -77.3 +/- 7.1 mV base, -63.0 +/- 7.4 mV plateau). These neurons also exhibited a high degree of convergence of responses elicited by stimulation of each of the three excitatory inputs tested. Activation of hippocampal afferents, but not cortical, amygdaloid, or thalamic afferents, induced bistable cells to switch to the depolarized (active) state. In contrast, no bistable cells were encountered in the nucleus accumbens following an acute transection of the fornix. Furthermore, microinjection of lidocaine in the vicinity of the hippocampal afferents at the level of the fornix caused a reversible elimination of the plateau phase in bistable cells. These data suggest that hippocampal input is necessary for accumbens neurons to enter a depolarized, active state. Furthermore, activation of prefrontal cortical inputs fail to evoke spike firing in accumbens neurons unless they are in this active state. Consequently, the hippocampus appears to be capable of gating prefrontal corticoaccumbens throughput.

Action Potentials↗
PubMed1994

Tonic D2-mediated attenuation of cortical excitation in nucleus accumbens neurons recorded in vitro.

The effects of dopamine D1 and D2 selective drugs on the responses evoked in accumbens neurons by stimulation of cortical afferents were studied in an in vitro brain slice preparation. The D2-specific antagonist sulpiride (1-10 microM) increased, whereas the D2 agonist quinpirole (1-20 microM) occasionally attenuated the amplitude of stimulation-evoked EPSPs recorded in accumbens neurons. Administration of the D1 agonist SKF 38393 (3-10 microM) or the D1 antagonist SCH 23390 (10 microM) did not alter the EPSP amplitude, although an apparent change in the time course of the EPSP was often observed. In slices obtained from dopamine (DA)-depleted animals, sulpiride failed to induce changes in the amplitude of the EPSPs, whereas quinpirole produced a highly significant suppression of EPSP amplitude that was only occasionally observed in control slices. These results indicate that DA modulates the response of accumbens neurons to cortico-accumbens fiber stimulation via D2 receptors. Furthermore, these D2 receptors appear to be located presynaptically on the cortical afferent terminals, since this action of DA was not accompanied by changes in membrane potential, input resistance, or time constant, and was not modified by changes in the membrane potential. These data provide evidence for a tonic basal level of D2 receptor stimulation in the accumbens slice preparation.

Animals↗
PubMed1994

Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats: I. Basic physiology and response to corticostriatal fiber stimulation.

The electrophysiological characteristics of two subtypes of striatal neurons, identified by their distinct patterns of response to paired impulse stimulation of corticostriatal afferents, were compared using in vivo intracellular recordings in rats. As observed in previous extracellular recording studies, the majority of neurons (73%) were found to be of the Type II class, with the remaining cells exhibiting the Type I response pattern. For all cells, cortical stimulation elicited 5-30 mV EPSPs at latencies ranging from 2.0-5.3 msec. Increasing the stimulating current intensity caused a progressive increase in the amplitude of the evoked EPSPs without altering their latencies, suggesting that the EPSPs are monosynaptically mediated. Both the average amplitude and duration of the evoked EPSPs at spike threshold in Type I neurons (9.8 +/- 1.7 mV, 11.8 +/- 2.8 msec; mean +/- SEM) were significantly smaller than those of Type II cells (20.3 +/- 1.4 mV, 22.7 +/- 2.1 msec). Although the average latency to the onset of the EPSP was similar for both cell classes (Type I cells: 2.3 +/- 0.3 msec; Type II cells: 2.2 +/- 0.2 msec), the EPSPs in Type I cells reached peak amplitude and the spikes were triggered at significantly longer latencies than in the Type II cells (peak I: 11.2 +/- 2.5 msec vs. II: 7.6 +/- 0.7 msec; spike I: 8.0 +/- 1.2 msec vs. II: 5.7 +/- 0.4 msec). Striatal neurons had a comparatively hyperpolarized resting membrane potential (-70.2 +/- 2.1 mV) and had an average input resistance of 35.4 +/- 7.6 M omega. Overall, striatal neurons exhibited low levels of spontaneous activity (0.6 +/- 0.7 Hz) with 50% of the neurons being quiescent. Type I cells exhibited significantly higher firing rates (3.2 +/- 0.8 Hz) than Type II cells (0.8 +/- 0.3 Hz), although their resting membrane potentials were not significantly different. Spontaneously occurring spikes had an average amplitude of 72.7 +/- 3.4 mV and spike thresholds of -50.1 +/- 1.5 mV. Irregularly occurring depolarizing plateau potentials, which typically gave rise to spike discharge, were frequently observed in both spontaneously firing and quiescent neurons. A small proportion of the cells recorded (3/55) exhibited a Type I response pattern but had unique physiological characteristics that were similar to those described by others as arising from large, aspiny striatal neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Identification and characterization of striatal cell subtypes using in vivo intracellular recording in rats: II. Membrane factors underlying paired-pulse response profiles.

Two subtypes of neurons in the striatum have been defined on the basis of their different response patterns to paired-impulse stimulation of corticostriatal afferents, with type I cells showing a longer spike latency, facilitation at short intervals, and inhibition at long intervals, and type II cells defined by the facilitation occurring at long interstimulus intervals. Nevertheless, the companion report has shown that this distinction of cell types cannot be accounted for by differences in the basic physiological properties of these cells, but instead is likely to be due to differences in their synaptic connectivity. The experiments performed in this study were directed at examining in detail the membrane factors and synaptic responses that may contribute to these distinct response patterns. When pairs of stimuli were delivered to the corticostriatal fibers at 10-30 ms interstimulus intervals, the EPSPs elicited in type I neurons exhibited a temporal summation, resulting in a facilitation of spike firing to the second stimulus relative to the first. In contrast, type II cells showed decreased EPSP amplitude at short intervals, and in cells showing a short-interval inhibition, there was a significant increase in spike threshold (+5.3 +/- 1.4 mV) during the second response. All type II neurons recorded with KCl-filled microelectrodes showed short-interval facilitation with little or no change in spike threshold. Although the use of KCl electrodes did not alter the facilitation at short intervals in type I neurons it did increase the rate of rise of the EPSP, causing spikes to be triggered at a latency similar to that of type II cells. Paired stimuli delivered at 75-150 ms interstimulus intervals showed inverse effects on type I and type II cells with respect to the probability of spike firing. In type I cells, the evoked EPSP was followed by a long-latency membrane hyperpolarization that prevented the second EPSP from reaching spike threshold. In contrast, the smaller-amplitude hyperpolarization evoked in type II cells enabled the second stimulus to activate an EPSP at the same membrane potential as the first stimulus, resulting in a facilitation of spiking.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1994

Identification and characterization of striatal cell subtypes using in vivo intracellular recording and dye-labeling in rats: III. Morphological correlates and compartmental localization.

In the first two reports of this series, in vivo intracellular recording techniques were used to characterize the electrophysiological properties of two types of striatal neurons that had been identified by their distinct response patterns to stimulation of corticostriatal afferents. In this paper, we examined whether cells showing Type I or Type II response patterns also differed with respect to their morphology or compartmental localization by combining intracellular recording and Lucifer yellow staining with immunocytochemical localization of calbindin 28 kd immunoreactivity. In the majority of cases, both Type I and Type II neurons exhibited similar morphological characteristics, with 80% of the Type I cells (13/16) and all of the Type II cells (n = 40) being small or medium spiny neurons. In each case where the morphological class of the cell was different than the spiny cell class, the cell exhibited a Type I response pattern. These spiny neurons had somata that averaged 17.1 +/- 1.3 microns in diameter and gave rise to between four and eight primary dendrites. The axons typically arose from cell bodies (7/13 for Type I and 25/40 for Type II cells) and emitted extensive local axonal collaterals. However, the axons of Type I cells more frequently originated from the dorsal surface of the somata (9/13; 69%), whereas Type II axons more frequently arose from the ventral surface of the somata (25/35; 71%), which may account for their different extracellular waveforms. In coronally sectioned tissue (n = 18), the axons always projected laterally when the somata were located in the medial striatum and projected medially when the somata were in the lateral striatal region. In a subset of experiments (N = 22), Lucifer yellow-stained neurons were localized with respect to their position within the patch and matrix compartments of the striatum using subsequent staining for calbindin 28 kd immunoreactivity. Of the 20 labeled medium spiny neurons examined (Type II: N = 13; Type I: N = 7), 19 were located in the calbindin-positive matrix compartment. The only neuron localized to the patch compartment was a medium spiny cell that exhibited a Type II paired impulse response pattern. In addition, of the two aspiny neurons from this group with beaded dendrites, one was localized to the border between adjacent patch and matrix compartments, whereas the other was located completely within the matrix compartment. Therefore, despite their distinct paired impulse response patterns, the majority of both Type I and Type II neurons were medium spiny cells located in the matrix compartment of the striatum.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Modulation of dorsal thalamic cell activity by the ventral pallidum: its role in the regulation of thalamocortical activity by the basal ganglia.

The actions mediated by limbic system output projections of the basal ganglia were investigated by studying the effects of ventral pallidum (VP) stimulation on the activity of neurons in thalamic target nuclei, including several of the dorsal thalamic nuclei and the nucleus reticularis, using in vivo intracellular recordings in rats. Intracellular injection of Lucifer yellow was used in a subset of experiments to identify the neurons recorded and to confirm their location with respect to the specific thalamic nuclei targeted. Stimulation of the VP evoked ipsps in 79% of the mediodorsal cells recorded. In the reticular nucleus, 73% of the neurons tested responded with evoked ipsps. In contrast, in other dorsal thalamic nuclei VP stimulation evoked depolarizations in 58% of the cells recorded. The latency to onset of the ipsps in the mediodorsal nucleus and in the reticular nucleus were not substantially different (1.7 +/- 1.1 msec vs. 2.7 +/- 1.1 msec), whereas the depolarizing response evoked in dorsal thalamic nucleus neurons typically occurred at longer and more variable latencies (3.5 +/- 2.7 msec). These experiments support a dual functional role for limbic system output from the basal ganglia in the regulation of thalamocortical activity: a) a direct inhibitory projection from the VP to the mediodorsal nucleus and b) an indirect disinhibition of neurons in other dorsal thalamic nuclei that occurs via a direct inhibitory projection to the reticular nucleus of the thalamus. Such an anatomical arrangement may be relevant to the presence of hypofrontality and the breakdown of cognitive filtering observed in schizophrenics.

Animals↗
PubMed1994

Early complications after dual chamber versus single chamber pacemaker implantation.

This study was performed to compare the frequency of early complications after single chamber versus dual chamber permanent pacemaker implantation. Early complication was defined as one occurring in the 6-week period following implantation. We prospectively analyzed consecutive pacemaker implantation from January 1987 to June 1993 at our regional center. All complications were also analyzed for the relationship to operator experience, the venous access route, and the presence of temporary pacing wire at the time of implantation of the permanent pacing system. A total of 2019 new pacemaker units were implanted during this period. 1733 patients (85.8%) received a VVI pacemaker and 286 (14.2%) a DDD unit. Wound infection occurred in 11 (0.6%) VVI patients and 6 (2.1%) DDD patients. Lead displacement occurred in 18 (1%) VVI patients and 15 (5.2%) DDD patients (11 [3.8%] atrial and 4 [1.4%] ventricular). There were 10 (0.6%) pneumothoraces, 9 (0.5%) hematomas requiring drainage, 1 (0.06%) chylocele, and 2 (0.1%) deaths in the VVI group. There were 2 (0.7%) pneumothoraces, 2 (0.7%) hematomas, and no deaths in the DDD group. There was no significant increase in complications for experienced infrequent implanters (< 12 systems per year). In both groups the subclavian approach was associated with a risk of pneumothorax when compared to the cephalic approach. The rate of wound infection was higher in patients who had a temporary pacing wire in place. The use of prophylactic antibiotics does not appear to affect the incidence of wound infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Maze 3 for atrial fibrillation: two cuts too few?

The Maze procedure has been developed as a surgical approach to the management of patients with atrial fibrillation refractory to medical treatment. The recent modification of the technique (Maze 3) achieves good rate control with coordinated AV contractions. However, the procedure involves cuts that completely isolate a block of left atrial (LA) wall, including the four ostia of the pulmonary veins. The electrical and mechanical activity of this isolated LA block are dissociated from the rest of the atrium, and the area may, in fact, continue to fibrillate. This may provide a nidus for the development of mural thrombus. The weight and endocardial surface area of the LA block and of the entire LA were estimated in ten formalin fixed hearts from trauma victims with no evidence of cardiac disease. In these samples, the LA block represented 35% of the endocardial surface area of the entire LA and 29% of the weight. The LA block is of sufficient size to allow macroreentrant circuits to form and has the potential to fibrillate if isolated from the rest of the atrium. We modified the Maze 3 procedure to recruit the otherwise isolated LA block by using two additional cuts around each pair of pulmonary veins as they enter the LA. The first patient who underwent the modified procedure demonstrated sinus rhythm on Holter monitoring postoperatively and remained in sinus rhythm following burst atrial pacing at 300 and 420 beats/min each for 30 seconds. In addition, atrial contractions were found to contribute 19% of the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1994

Ambulatory assessment of the QT interval in patients with hypertrophic cardiomyopathy: risk stratification and effect of low dose amiodarone.

This study aims to assess the dynamics of the QT interval in patients with hypertrophic cardiomyopathy (HCM). Three consecutive QT intervals and the preceding RR intervals were measured on 24 hour ambulatory electrocardiograms at 30-minute intervals in ten high risk patients with HCM (sudden cardiac death [SCD] and/or documented ventricular fibrillation), aged 29 +/- 17 years, compared with ten age and sex matched low risk patients with HCM (no syncope, no adverse family history, and no ventricular tachycardia on Holter monitoring), and ten normal subjects. Another ten patients who were on amiodarone therapy (200-mg daily) were also studied. Patients with intraventricular conduction defects were excluded. There were 4,424 pairs of QT intervals and their preceding RR intervals were measured in this study. A nonsignificant prolongation in the QT interval and a significant prolongation in QTc values (Bazett's and Fridericia's formulas) were demonstrated in patients with HCM compared with normals. There were no significant differences in the QT and QTc between high and low risk patients. The slope of regression line for the QT against RR interval was significantly different between normals and HCM (0.1583 +/- 0.040 vs. 0.2017 +/- 0.043, P < 0.05), but not between high and low risk patients. Amiodarone significantly prolonged the QT and QTc without significantly altering the slope of the regression line (0.2017 +/- 0.043 vs 0.2099 +/- 0.037, NS). Our findings support the observations that there is a prolonged QT interval in patients with HCM and that there is no significant use dependent effect of amiodarone on ventricular repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Intracellular pH recovery during respiratory acidosis in perfused hearts.

Na(+)-H+ exchange and Na(+)-dependent HCO3- influx both contribute to recovery of intracellular pH (pHi) after an acidosis induced by using the NH4Cl prepulse technique in mammalian and avian cardiac tissue. We have investigated the relative contributions of these mechanisms to pHi recovery during respiratory acidosis in the Langendorff-perfused ferret heart with and without correction of extracellular pH (pHo). pHi was measured from the chemical shift of the exogenous 31P nuclear magnetic resonance pH indicator 2-deoxy-D-glucose 6-phosphate. Intrinsic intracellular buffering capacity, calculated from the change in intracellular HCO3- concentration after a change in CO2, was reduced from approximately 33 (no inhibitors of acid extrusion present) to 19 +/- 5 mM when H+ extrusion during the acid loading phase was inhibited. During respiratory acidosis (pHo approximately 6.95), the proton efflux rate (JH) calculated at pHi 6.85 was 0.30 +/- 0.04 mmol.l-1.min-1 (n = 9). When pHo was corrected by increasing external HCO3- concentration to 60 mM during respiratory acidosis (pHo approximately 7.33), JH was 1.11 +/- 0.11 mmol.l-1.min-1 (n = 7), and when pHo was partially corrected by the addition of 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid to the perfusion solution (pHo approximately 7.1), JH was 0.64 +/- 0.08 mmol.l-1.min-1 (n = 6). In all three groups Na(+)-H+ exchange and HCO3- influx each contributed approximately 50% to acid-equivalent efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Dye coupling between rat striatal neurons recorded in vivo: compartmental organization and modulation by dopamine.

1. The presence of dye coupling between striatal neurons was investigated using in vivo intracellular recording and dye injection in adult rats. In 17% of the cases in which a single striatal neuron was injected with Lucifer yellow, more than one labeled neuron was recovered. In control rats, this dye coupling was observed only between single pairs of medium spiny neurons and only when the neuron injected exhibited the Type II response profile as defined by paired-pulse stimulation of corticostriatal afferents. 2. After intravenous administration of the D1/D2 agonist apomorphine at a behaviorally effective dose (i.e., 0.1-0.3 mg/kg), an increase in the incidence (from 17% to 82% of injected cells) and extent (from 2 cells to 3-7 cells labeled per injection) of dye coupling was observed. This effect was mediated by D2 receptor stimulation because administration of the D2 agonist quinpirole caused similar alterations in the incidence and extent of dye coupling (66% coupled). In contrast, administration of the D1 agonist SKF 38393 or the D1 antagonist SCH 23390 did not result in any significant alteration in dye coupling. 3. In control rats, the entire somatodendritic regions of dye-coupled neurons were found to be localized within single matrix compartments of the striatum. However, after intravenous administration of apomorphine or quinpirole, clusters of dye-coupled neurons were found to extend across the patch/matrix boundary. Moreover, dye coupling was observed after injecting cells exhibiting either the Type I or the Type II response profile. 4. In response to D2 receptor stimulation, both the extent and the pattern of coupling between striatal neurons is altered, resulting in direct coupling between neurons that are otherwise functionally and anatomically segregated in the control animal.

Afferent Pathways↗