Biomedical subjects

K W Hewett

Publications and source records attributed to K W Hewett.

At least 19 recordsLinked to original sources

PubMed2000

The rate and anisotropy of impulse propagation in the postnatal terminal crest are correlated with remodeling of Cx43 gap junction pattern.

BACKGROUND: Disruptions to intermyocyte coupling have been implicated in arrhythmogenesis and development of conduction disturbances. At present, understanding of the relationship between the microscopic organization of intercellular coupling and the macroscopic spread of impulse in the normal and diseased heart is largely confined to theoretical analyses. METHODS AND RESULTS: The abundance and arrangement of gap junctions, as well as conduction properties, were assessed in terminal crest preparations isolated from the atria of neonate, weanling, and adult rabbits. We report that the connexin composition of terminal crest was uncomplicated, with Cx43 being the most prominent isoform detectable by Western blotting and immunostaining. Terminal crest myocytes showed little change in total Cx43-gap junction per cell during postnatal growth as assessed by stereology. However, marked non-uniformities emerged in the sarcolemmal distribution of Cx43-gap junctions. Cx43-gap junction area at myocyte termini increased 3.5-fold from birth to adulthood. Correlated with this change in Cx43, impulse propagation velocity parallel to the myofiber axis, as assessed by multi-site optical mapping using voltage-sensitive dye (di-4-ANEPPS), increased 2.4-fold. Conversely, the amount of Cx43-gap junctions on myocyte sides, and the conduction velocity transverse to the myofiber axis, remained relatively invariant during maturation. Hence, the increasing electrical anisotropy of maturing terminal crest was wholly accounted for by increases in conductance velocity along the bundle. This increase in longitudinal conduction velocity was correlated with changes in the sarcolemmal pattern, but not the overall density, of Cx43-gap junctions. CONCLUSIONS: This study provides the first correlative structure/function analysis of the relationship between the macroscopic conduction of impulse and the microscopic cellular organization of gap junctions in a differentiating cardiac bundle. Confirmation is provided for theoretical predictions which emphasize the importance of the cell-to-cell geometry of coupling in determining the spread and pattern of myocardial activation.

Analysis of Variance↗

PubMed2000

A new framework for echocardiographic assessment of left ventricular mechanics: sensitivity to heart failure.

A recent report describes an approach to ventricular mechanics that employs mean end-systolic fiber stress and an exact mathematical strain index based on wall thickness referenced to myocardial mass. We used echocardiography and mean arterial pressures to determine the strain index and wall stress in (1) normal hearts from patients and swine, (2) swine with pacing-induced congestive heart failure, and (3) patients with dilated cardiomyopathy. Pigs were also studied under afterload variation with phenylephrine. Paired values of stress and strain index from control hearts (both swine and human) were tightly clustered. Values from animals and patients with congestive heart failure deviated from this cluster. Excellent separation (sensitivity 83%, specificity 94%) was displayed between control and paced pigs, despite confounding effects of varying afterload. We conclude that these variables display little change over a large range of normal cardiac mass, but deviate from this range during heart failure.

Adolescent↗

PubMed1999

Inducible lethal ventricular arrhythmias in swine with pacing-induced heart failure.

INTRODUCTION: Rapid pacing-induced heart failure provides an excellent animal model for the study of heart failure. We studied the development of ventricular tachyarrhythmias using programmed stimulation in a pacing-induced heart failure model. We also studied action potential characteristics and the relationship between action potential and heart rate. METHODS AND RESULTS: Ten pigs were instrumented and were studied before the onset and every week after rapid pacing was instituted. Weekly echocardiograms and programmed stimulation were done in a sedated state. In vitro electrophysiologic studies were done on left ventricular myocardium in 4 heart-failure animals and 4 controls. All animals developed progressive heart failure with left ventricular dilatation and reduced percentage fractional shortening. No arrhythmias were induced at baseline or the first and second weeks. Ventricular fibrillation was induced in one animal on the third week and 4 animals on week 4, while there was no appreciable worsening in echocardiographic indices of ventricular dysfunction between weeks 3 and 4. Ventricular effective refractory period was unchanged during the 4 weeks. In vitro studies showed action potential prolongation in heart failure myocardium. However, action potential duration at pacing rates >100 bpm were similar to controls. No early or delayed afterdepolarizations were observed. CONCLUSION: This study demonstrated an increased susceptibility to ventricular fibrillation with the development of heart failure which was not related to the degree of ventricular dysfunction. Also, the normalization of action potential duration at higher heart rates suggests that the increased incidence of inducible ventricular fibrillation in this model may not be solely due to prolonged action potential duration.

Animals↗

PubMed1999

Wall thickness referenced to myocardial volume: a new noninvasive framework for cardiac mechanics.

Dimensional variables measured for study of left ventricular mechanics are subject to errors arising from difficulty in determining zero-stress dimensions for use as a reference. Based on a method validated for measurements within individuals, we have devised an approach that facilitates comparison between individuals while minimizing random scatter. We define an exact mathematical index of strain, ln(h(0)/h), using wall thickness (h) referenced to extrapolated wall thickness at zero-luminal volume (h(0)). Noninvasive data from rabbits, pigs, and humans all yielded highly similar myocardial stress, ln(h(0)/h), and work values. The stress-ln(h(0)/h) relationship during afterload variation was constant among individual pigs with a twofold variation in ventricular mass. Stress-ln(h(0)/h) data from our analysis displayed lower scatter than either pressure-volume data normalized to myocardial mass or stress-ln(h(0)/h) data referenced to end-diastolic dimensions. A Frank-Starling-like curve with high correlation (r(2) = 0.96) was constructed from single points from different pigs, suggesting a low level of size and intersubject scatter. This method offers high precision for noninvasive characterization of ventricular and myocardial mechanics and for comparisons between subjects and between species.

Animals↗

PubMed1998

Changes in L-type calcium channel abundance and function during the transition to pacing-induced congestive heart failure.

OBJECTIVE: The development of congestive heart failure (CHF) is accompanied by left ventricular (LV) and myocyte contractile dysfunction. However, time-dependent cellular and ionic events which contribute to the initiation and progression of CHF remain unclear. This study tested the central hypothesis that changes in L-type Ca2+ channel current (ICa) and abundance (Bmax) are early events in the transition to CHF. METHODS: LV fractional shortening by echocardiography, isolated LV myocyte shortening velocity by videomicroscopy, ICa by voltage-clamp, and Bmax by [3H]nitrendipine binding were determined at each week during the progression of pacing-induced CHF in pigs (240 bpm; n = 6/week for 3 weeks). Myocyte and L-type Ca2+ channel function were determined under basal conditions and after beta-adrenergic receptor stimulation with 25 nM isoproterenol. RESULTS: After 1 week of pacing, myocyte and L-type Ca2+ current responses to beta-adrenergic receptor stimulation were reduced by 20% from control values and was accompanied by over a 210% increase in plasma catecholamine levels. After 2 weeks of pacing, reductions in LV fractional shortening and myocyte shortening velocity from control values (20 +/- 1 vs. 34 +/- 2% and 36.7 +/- 2.9 vs. 50.6 +/- 2.4 microns/s, respectively, P < 0.05) were paralleled by decreased ICa (2.47 +/- 0.10 vs. 3.63 +/- 0.25 pA/pF, P < 0.02) and Bmax (149 +/- 16 vs. 180 +/- 12 fmol/mg, P < 0.03). After 3 weeks of pacing, LV fractional shortening was reduced by over 50%, myocyte shortening velocity by 37%, and ICa and Bmax were reduced by over 25% from control values. Furthermore, after 3 weeks of pacing, the ICa/Bmax ratio was reduced from control values (16.2 +/- 0.9 vs. 20.6 +/- 1.2 [fA/pF]/[fmol/mg], P < 0.03), which suggests functional defects in the remaining L-type Ca2+ channels. CONCLUSIONS: An early event during the transition to pacing-induced CHF was diminished beta-adrenergic receptor augmented L-type Ca2+ current, which was followed by an absolute loss of steady-state L-type Ca2+ current and channel abundance. The development of severe CHF was accompanied by a loss of Ca2+ carrying capacity through residual channels. These unique findings suggest that a contributory molecular mechanism for the initiation and progression of CHF is changes in the structure and function of the L-type Ca2+ channels.

Adrenergic beta-Agonists↗

PubMed1998

Differential developmental effects of acute hypoxia on the rabbit atrioventricular conduction axis.

The differential developmental effects of hypoxia on antegrade fast and slow and retrograde conduction through the atrioventricular junction are unknown. This study describes the effects of hypoxia on fast and slow antegrade atrioventricular node, infra-Hisian and retrograde conduction in immature and mature hearts during premature pacing protocols in excise, perfused adult and neonatal rabbits. The results are: (1) antegrade conduction delay through the atrioventricular node is the same developmentally, but delay through the His-Purkinje system is greater in adults; (2) hypoxia reduces the extra delay in the His-Purkinje system in adults; (3) fast atrioventricular node conduction is more sensitive to hypoxia in neonates than in adults, and slow atrioventricular node conduction is more sensitive to hypoxia in adults than in neonates, and (4) retrograde atrioventricular node conduction is more resistant to hypoxia in neonates than in adults.

Aging↗

PubMed1997

Myocardial electrophysiological properties in the presence of an AT1 angiotensin II receptor antagonist.

INTRODUCTION: Blockade of the AT1 angiotensin II (Ang II) receptor has been shown to provide anti-hypertensive effects. However, whether AT1 Ang II receptor antagonists influence myocardial electrophysiological properties remains unclear. METHODS AND RESULTS: Accordingly, atrial and ventricular myocardial electrophysiological properties were examined in adult rat (n = 13) and guinea pig (n = 9) myocardial preparations in the presence of the specific AT1 Ang II receptor antagonist, valsartan (CGP 48933; 0.5, 5, or 500 mumol/L). These concentrations reflect up to 100 fold higher drug concentrations than those observed in clinical trials. Transmembrane potential data were recorded using standard microelectrode techniques at baseline and following superfusion with valsartan. The lower concentrations of valsartan (0.5 and 5 mumol/L) had minimal effects on myocardial electrophysiology. In the presence of 500 mumol/L of valsartan, resting membrane potential increased from baseline in both rat (-82.3 +/- 4.1 vs -76.8 +/- 5.8 mV, p < 0.05) and guinea pig (-81.6 +/- 2.9 vs -76.9 +/- 2.0 mV, p < 0.05) atrial myocardium. Action potential duration at 90% repolarization was increased in guinea pig atrial (91.7 +/- 1.4 vs 80.0 +/- 5.6 ms, p < 0.05) and ventricular (131.1 +/- 8.1 vs 118.7 +/- 8.3 ms, p < 0.05) myocardium following exposure to 500 mumol/L of valsartan. In a separate series of experiments, Ang II (1.0 mumol/L) had no effect on atrial or ventricular action potential characteristics in either species. CONCLUSION: Thus, the effects of valsartan, which were observed only at concentrations 100 fold higher than those reported in clinical trials, may be due to non-specific drug interactions with the myocyte sarcolemma.

Angiotensin Receptor Antagonists↗

PubMed1997

Different effects of flecainide on atrioventricular conduction properties in the adult and immature rabbit heart.

The influence of flecainide (0.1, 0.5, 1.0, and 2.0 micrograms/mL) on atrioventricular (AV) conduction was studied in neonatal and adult perfused rabbit hearts using extracellular bipolar surface electrograms and premature atrial and ventricular pacing. Flecainide produced a concentration and rate-related increase in the steady-state nodal conduction (AHmin) and an increase in slow AH conduction (AHmax) in both age groups. The drug produced significant increases in the refractory periods of the atrium, AV node, His-Purkinje system, and ventricular myocardium. The neonatal refractory periods were significantly greater at lower or the same drug concentrations than those of the adult. The neonatal Wenckebach cycle length was significantly greater with a lower concentration of drug (0.5 microgram/mL) than was the adult Wenckebach cycle length. The His-Purkinje system steady-state conduction time (HVmin) was increased by a lower concentration of drug in the neonate (0.5 microgram/mL) as compared with 2.0 micrograms/mL in the adult. These data show that across a wide range of AV conduction parameters, the neonatal preparations responded to a lower concentration of flecainide than did the adult preparations. These findings may, in part, be the basis for the reported greater efficacy of the drug in children than in adults.

Aging↗

PubMed1996

Changes in atrioventricular conduction properties with refractory-period modulation.

Dofetilide, clofilium, and risotilide, three drugs known to prolong cardiac action potentials and refractory periods, were studied by using a perfused isolated rabbit heart preparation with intermittent premature pacing and bipolar surface electrograms. The rate-related effects of these drugs on atrioventricular (AV) conduction were tested by pacing at a long (400 ms) and a short (250 ms) basic cycle length (BCL). All three drugs increased refractory periods in a concentration-dependent manner in most segments of the AV axis. The maximal atrio-His (AH) conduction interval (AHmax) and delta AH (AHmax - AHmin) produced by premature pacing was decreased by the highest concentration of each drug at the 400-ms BCL, whereas only clofilium reduced AHmax and delta AH at the 250-ms BCL. Changes in delta AH correlated best with changes in the atrial functional refractory period. The His-Purkinje system conduction interval (HV), represented by delta HV, was unaffected by any drug at either BCL. These results show that if atrial or nodal refractory periods are increased sufficiently, AHmax but not AHmin was decreased at the 400-ms BCL. Because dofetilide and risotilide did not affect AHmax at the 250-ms BCL, these drugs may be less effective at preventing AV nodal reentrant tachycardias than a drug such as clofilium that displays less rate dependency.

Animals↗

PubMed1996

Developmental effects of d-sotalol on anterograde and retrograde atrioventricular conduction in the rabbit.

INTRODUCTION: These experiments investigate the developmental effects of d-sotalol on standard electrophysiologic parameters of anterograde and retrograde AV conduction in the rabbit. METHODS AND RESULTS: Using bipolar electrograms and standard pacing techniques, the effects of graded concentrations of d-sotalol on anterograde and retrograde conduction in mature and immature perfused rabbit hearts were compared. Also, a quantitative assessment of the drug's effects on a rate-dependent property of anterograde AV node (AVN) conduction, termed the "recovery process," was compared in mature and immature rabbit hearts. The main developmental electrophysiologic findings of this investigation are: (1) in both the mature and immature rabbit heart, d-sotalol increases the anterograde conduction time and prolongs refractoriness of the AVN, yet the minimal concentrations of d-sotalol that produce these changes are lower in the neonate; (2) d-sotalol increases the anterograde refractory period of the His-Purkinje system in both age groups, but increases anterograde infra-Hisian conduction only in the neonate; (3) 1 x 10-4 M d-sotalol significantly changes the time constant of the AVN recovery process in the neonate, but not in the adult; (4) for retrograde conduction, slow conduction through the AVN (HAmax) and infra-Hisian region (VHmax) are increased by d-sotalol in the neonate, but not in the adult. CONCLUSIONS: The findings of this study illustrate that d-sotalol has different effects on parameters of the developing AV conduction system. This implies that there may be maturational changes in the ionic currents that are responsible for anterograde and retrograde AVN and His-Purkinje conduction.

Aging↗

PubMed1995

Myocyte electrophysiological properties following the development of supraventricular tachycardia-induced cardiomyopathy.

Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction, diminished myocyte contractile function, and abnormalities in sarcolemmal receptor systems. We hypothesized that changes in myocyte action potential characteristics and L-type Ca2+ channel (Ca2+ channel) function, which are major determinants of myocyte contractile processes, would occur with SVT cardiomyopathy. LV function and isolated myocyte contractile function were examined in 11 pigs with SVT cardiomyopathy (pace 240 bpm; 3 weeks) and 11 control pigs. With chronic SVT, LV fractional shortening fell and myocyte shortening velocity was reduced compared to controls (11 +/- 2 v 37 +/- 2%, P < 0.0001; and 32.5 +/- 1.2 v 55.7 +/- 1.6 microns/s, P < 0.0001, respectively). Isolated myocyte action potential upstroke velocity and amplitude were reduced with SVT cardiomyopathy compared to controls (92.8 +/- 4.8 v 129.5 +/- 3.1 V/s, P < 0.0001; and 98.2 +/- 2.2 v 110.3 +/- 1.3 mV, P < 0.0001, respectively). the duration of the myocyte action potential, defined as the time to 90% repolarization, was prolonged with SVT cardiomyopathy compared to controls (201.7 +/- 5.9 v 169.1 +/- 6.8 ms, P = 0.002). These specific abnormalities in the indices of myocyte contractile function and action potential characteristics which occurred with SVT cardiomyopathy were not normalized following beta-adrenergic receptor stimulation. In order to determine a potential mechanism for the changes in myocyte contractile function and action potential characteristics with SVT cardiomyopathy, Ca2+ channel function was examined in control and SVT myocytes. In SVT myocytes, peak L-type Ca2+ current (ICa) normalized to membrane capacitance and the Ca2+ channel inactivation time constant were reduced compared to controls (-2.30 +/- 0.24 v -3.79 +/- 0.28 pA/pF, P = 0.0001; and 104.0 +/- 10.8 v 199.9 +/- 27.4 ms, P = 0.005, respectively). The abnormalities in Ca2+ channel function with SVT cardiomyopathy persisted in myocytes with equivalent membrane capacitances and were not normalized with beta-adrenergic receptor stimulation. In conclusion, findings from the present study suggest that fundamental abnormalities in myocyte electrical events (action potential) and ionic flux (Ca2+ channel function) are contributory mechanisms for the depressed myocyte contractile function with SVT cardiomyopathy.

Action Potentials↗

PubMed1995

Image-based display of activation patterns derived from scattered electrodes.

Presentation of electrophysiologic data, such as activation patterns, can take many forms, the most common of which are hand- or machine-drawn isochronal maps. We present an image-based method which provides accurate matching between electrophysiologic data and the anatomic sites from which the data were derived. This method is linear, simple, and straightforward to implement, and presents results in a format which is easy to understand and interpret.

Algorithms↗

PubMed1994

Effect of beta-adrenergic stimulation on the QT interval of children with syncope.

The effect of intravenous bolus doses (0.25, 0.5, 1.0 microgram) of isoproterenol on the QT and RR intervals was reviewed in a group of 34 children undergoing autonomic testing for syncope. Twenty-one patients had a positive orthostatic test and 13 were negative. The two groups (positive and negative) were compared. Baseline QT and RR intervals were similar. The RR interval was shortened by isoproterenol in both groups. Isoproterenol shortened the QT interval in the negative group (as seen in normal persons), but produced QT prolongation in the positive group, although neither reached statistical significance when compared to baseline within the respective group. Comparing the values for RR and QT at each dose of isoproterenol (including baseline) between the two groups showed a significant difference in the QT interval after the 1.0-microgram dose of isoproterenol. Thus children with orthostatic positive neurocardiogenic syncope showed a different QT response to beta-adrenergic stimulation. This lends support to the theory of altered beta-adrenergic sensitivity being present in children with neurocardiogenic syncope.

Adolescent↗

PubMed1994

Developmental electrophysiology of encainide and its major metabolites on the Purkinje fiber action potential.

OBJECTIVE: With clinical data suggesting that neonates may be more prone to developing electrophysiologic side effects from encainide, this study investigates the in vitro developmental electrophysiologic effects of encainide and its major metabolites on the action potential parameters of the canine cardiac Purkinje fiber. METHODS: With standard microelectrode techniques, the in vitro tonic and rate-related effects of encainide, and its major metabolites (3-methoxy-4-hydroxy encainide, MODE, and O-dimethyl encainide, ODE) were investigated using mature and immature canine cardiac Purkinje fibers. RESULTS: The significant developmental differences in the effects of these compounds on the canine Purkinje fiber illustrated in this study are: (1) 1 x 10(-6) M encainide depresses Vmax in neonatal Purkinje fibers, yet not in the adult. (2) 1 x 10(-6) M MODE lengthens APD90 in the neonate, yet it has no substantial effect in the adult. (3) 1 x 10(-6) M ODE shortens APD90 in the adult, yet it has no appreciable effect on the neonate. (4) Rate-related effects of encainide and ODE are more pronounced in adult Purkinje fibers. CONCLUSION: In contrast to other in vitro studies on class I antiarrhythmic agents, neonatal canine Purkinje fibers seem to be more sensitive than the adult to the tonic depolarization depressant effect of encainide. This in vitro sensitivity parallels clinical experience with the drug in neonatal patients. Although encainide is no longer available for clinical use, these findings highlight the fact that the immature conduction system may show markedly different sensitivities to different class I agents despite the fact that these agents share similar qualitative pharmacologic properties.

Action Potentials↗

PubMed1994

The direct effects of protamine sulfate on myocyte contractile processes.

The use of protamine sulfate in patients has been associated with circulatory collapse and is suspected to directly depress left ventricular function. However, the cellular basis for these changes that occur after protamine administration are unknown. Accordingly, the first objective of this study was to determine the direct effects of protamine on isolated myocyte contractile function. Myocytes were isolated from porcine hearts and contractile function was examined at baseline and then after the administration of protamine in concentrations of 20, 40, or 80 micrograms/ml. These concentrations were chosen because they reflect the serum concentrations of protamine commonly obtained in patients. The presence of protamine resulted in a dose-dependent decline in myocyte contractile function. For example, in the presence of a 20 microgram/ml concentration of protamine myocyte contractile function did not change significantly from baseline values, whereas an 80 microgram/ml protamine concentration caused myocyte percent and velocity of shortening to fall by more than 35% from baseline values. In light of the fact that protamine directly depressed myocyte contractile function, a second objective of this study was to examine potential cellular mechanisms responsible for this effect. Accordingly, in the next series of experiments, the effects of protamine on the myocyte sarcolemmal beta-adrenergic receptor system were examined by measuring myocyte contractile function with the beta-adrenergic agonist isoproterenol (25 nmol/L), as well as with the concomitant addition of protamine and isoproterenol. In the presence of protamine, myocyte beta-adrenergic responsiveness was significantly reduced. For example, in the presence of an 80 microgram/ml dose of protamine, both myocyte percent and velocity of shortening fell by greater than 50% when compared with isoproterenol alone values (p < 0.05). To determine the reversibility of these protamine effects, we performed additional experiments in the presence of heparin. Incubation with heparin before protamine addition prevented the negative effects of protamine on myocyte function. However, the addition of heparin after protamine incubation failed to reverse the negative effects of protamine on myocyte function. In a final set of experiments, the effects of protamine on isolated myocyte electrophysiologic properties were examined using microelectrode techniques at baseline and with either 40 or 80 micrograms/ml doses of protamine. Myocyte resting membrane potential changed from baseline with the addition of a 40 micrograms/ml dose of protamine (-79.2 +/- 0.5 versus -75.2 +/- 0.8 mV (p < 0.05), with no further change at an 80 micrograms/ml dose of protamine (-73.0 +/- 1.3 mV).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1993

Cell and sarcomere contractile performance from the same cardiocyte using video microscopy.

The relationship between whole cell and sarcomere contractile performance from within the same myocyte remains unclear. In the present study, the dynamic properties of whole cell and sarcomere contractile performance were examined from the same myocyte by computer-assisted video microscopy. Isolated canine left ventricular myocytes were field stimulated at 1 Hz, and whole cell and sarcomere contractile performance was measured in the unloaded unattached state (n = 16) and after attachment to a basement membrane substrate (n = 18). Whole cell and sarcomere contractile measurements were obtained immediately on initiation of electrical stimulation as well as at steady state, after which measurements were repeated in the presence of 25 nM isoproterenol. Video-microscopic images of whole cell and sarcomere contractions were obtained at final magnifications of x1,100 and x5,500, respectively. By use of a 240-Hz high-scan-rate charge-coupled device camera and a video-based edge-detection system synchronized with the camera video output, the myocyte and sarcomere motion data were digitized. Steady-state percentage and velocity of shortening for whole cells and sarcomeres were 4.75 +/- 0.30% and 56.50 +/- 2.37 microns/s and 8.63 +/- 0.60% and 2.24 +/- 0.46 microns/s, respectively, for the attached myocytes and 8.63 +/- 0.48% and 71.38 +/- 6.14 microns/s and 11.73 +/- 3.22% and 2.72 +/- 0.62 microns/s, respectively, for the unattached myocytes. With the initiation of electrical stimulation, the extent of the shortening-velocity of relengthening relationship increased in a linear fashion for the attached (whole cell, r = 0.87; sarcomere, r = 0.90; both P < 0.001) and unattached myocytes (whole cell, r = 0.83; sarcomere, r = 0.88; both P < 0.001). In all experiments, isoproterenol significantly increased the slope of these linear relationships (P < 0.01). Furthermore, the relationship between whole cell and sarcomere velocity of shortening was highly linear (r > 0.91, P < 0.001). In summary, this study demonstrated that the video-based edge-detection technique could be adapted to measure cell and sarcomere contractile performance from the same myocyte. Furthermore, a significant linear relationship exists between whole cell and sarcomere contractile dynamics with alterations in both load and inotropic state.

Animals↗

PubMed1992

The developmental electrophysiologic effects of moricizine HCl on the canine cardiac Purkinje fiber.

Using standard microelectrode techniques, the developmental cellular electrophysiologic effects of moricizine HCl on adult and neonatal canine Purkinje fibers were studied. Steady state and rate-related changes in the transmembrane action potentials produced by moricizine HCl in both age groups were characterized and compared. Also, the rate of barium-induced abnormal automaticity before and after drug was also investigated in neonatal and adult Purkinje fibers. The major findings of this study are as follows. (1) The steady state and rate-related depressant effects of moricizine HCl on Vmax were similar in both age groups. (2) Moricizine HCl shortened APD90 in the adult fibers to a greater extent than in the neonate. (3) The concentration of moricizine HCl required to significantly reduce the rate of abnormal automaticity was less in the neonate than in the adult. The effect of moricizine HCl on APD90 of individual Purkinje fibers is influenced both by their control APD90 value as well as by maturational factors. It is less clear whether developmental differences in the effects of moricizine HCl on abnormal automaticity are solely a result of differences in control rates of abnormal automaticity between the two age groups.

Action Potentials↗

PubMed1992

Developmental cellular electrophysiologic effects of propafenone on the rabbit atrioventricular node.

Transmembrane recordings and surface electrograms were used to evaluate the influence of propafenone on the cellular electrophysiology of isolated neonatal and adult rabbit atrioventricular node (AVN) preparations. An automatic interval of 863 +/- 82 ms (mean +/- SEM, n = 14) in neonates was found to be significantly shorter than the 1510- +/- 205-ms (n = 12) automatic interval observed in adults. Propafenone in a concentration of 5 x 10(-6) M significantly increased the automatic interval of neonatal pacemakers but not that of the adult preparations. These changes in automaticity produced by propafenone were not dependent on the adrenergic receptor-blocking action of the drug. The pacemaker escape time after overdrive pacing was also shorter in the neonate than in the adult. Propafenone prolonged the escape time of the neonatal tissues but not those of the adult. AVN refractory period, A-H interval, and antegrade Wenckebach rate were comparably increased in a concentration-dependent manner in both age groups. The maximum diastolic potential was decreased by propafenone in the neonatal atrionodal tissue but not in other regions of the AVN and not in any region of the adult AVN. Action-potential duration was increased in all regions of the AVN in both age groups. Action-potential amplitude and maximum upstroke velocity were decreased by propafenone in both age groups. Unlike other excitable tissues of the heart, the action-potential duration of AVN nodal cells increased with decreasing pacing intervals as the pacing interval approached the Wenckebach interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗