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Biomedical subjects

R W Joyner

Publications and source records attributed to R W Joyner.

At least 19 recordsLinked to original sources
PubMed1992

Action potential conduction between guinea pig ventricular cells can be modulated by calcium current.

We used cell pairs electrically coupled with relatively high intercellular resistance to investigate the involvement of calcium current in the origin of the source current during the conduction process of the action potential (AP). Three interventions were used to reduce the calcium current: a specific calcium channel blocker [nifedipine (NIF)], premature stimulation, and increments in the frequency of stimulation of the cell. The ionic membrane current (Iion) after the peak of the AP of the stimulated cell was positive and small when the cell was uncoupled. However, when the stimulated cell was coupled to a cell model or to another cell, Iion during this period became negative and large to supply the coupling current. A rapid early repolarization of the AP occurred in the stimulated cell because of the removal of charge from the stimulated cell. NIF decreased the magnitude of the net negative Iion during this period and caused a more rapid early repolarization in the stimulated cell. NIF increased the delay between the activations of two coupled cells at a given coupling resistance (Rc) but decreased the longest delay that could be produced without conduction failure for a given cell pair. The highest Rc below which conduction of AP occurred was also decreased by NIF. Premature stimulation and an increase of the stimulation frequency also caused an increase in the extent of the early repolarization and increased the delay between two cell activations at a given Rc. Conduction block occurred with sufficient prematurity or at a sufficiently high frequency of stimulation even though activation of the stimulated cell occurred for each stimulus. The Iion that flows during the early plateau phase of the AP in the stimulated cell became negative and significantly large by coupling two cardiac cells together. This current flow is a major component needed to supply the coupling current through the intercellular resistance. The decrease of calcium current caused a decrease in the magnitude of this net inward ionic current, resulting in an increase of the rate of early repolarization and an increase in the conduction delay between two cells at a given Rc. These results suggest the involvement of calcium current in the conduction process when cells are coupled at relatively high Rc.

Action Potentials↗
PubMed1992

Developmental changes in the beta-adrenergic modulation of calcium currents in rabbit ventricular cells.

We studied the developmental changes in the beta-adrenergic modulation of L-type calcium current (ICa) in enzymatically isolated adult (AD) and newborn (NB, 1-4-day-old) rabbit ventricular cells using the whole-cell patch-clamp method. ICa was measured as the peak inward current at a test potential of +15 mV by applying a 180-450-msec pulse from a holding potential of -40 mV with Cs(+)-rich pipettes and a K(+)-free bath solution at room temperature. In control, ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells (5.5 +/- 0.2 [mean +/- SEM] pA/pF, n = 65) than in NB cells (2.6 +/- 0.1 pA/pF, n = 60). Isoproterenol (ISO, 1 nM-30 microM) increased ICa in a dose-dependent manner for both groups. The maximal effect (Emax) of ISO, expressed as percent increase in ICa over control levels, and the concentration for one half of the maximal effect (EC50) were 203% and 51 nM, respectively, for AD cells and 111% and 81 nM, respectively, for NB cells. The effect of ISO (1 microM) on ICa was decreased as the test potential was increased from -10 to +40 mV. However, the ratio of the percent increase in ICa for AD versus NB cells was almost constant (2.09-2.45) at each test potential. Dose-response curves of forskolin (FOR, 0.3-50 microM) gave Emax and EC50 of 268% and 0.74 microM, respectively, for AD cells and 380% and 1.15 microM, respectively, for NB cells. After stimulating ICa by 10 microM ISO, the addition of 10 microM FOR produced a further increase in ICa of only 12 +/- 2% in AD cells (n = 4) but a further increase of 140 +/- 41% in NB cells (n = 6). FOR (10 microM) did not produce any increase in ICa for AD and NB cells after stimulating ICa by intracellular application of 200 microM cAMP. ICa density stimulated by 10 microM ISO (17.8 +/- 1.1 pA/pF, n = 7), 10 microM FOR (21.0 +/- 1.3 pA/pF, n = 8), or 200 microM cAMP (18.0 +/- 1.3 pA/pF, n = 5) was equivalent in AD cells, whereas ICa density stimulated by 10 microM ISO (5.8 +/- 0.6 pA/pF, n = 9) was significantly lower than that stimulated by either 10 microM FOR (13.8 +/- 1.5 pA/pF, n = 7) or 200 microM cAMP (13.4 +/- 0.7 pA/pF, n = 7) in NB cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Unidirectional block between isolated rabbit ventricular cells coupled by a variable resistance.

We have used pairs of electrically coupled cardiac cells to investigate the dependence of successful conduction of an action potential on three components of the conduction process: (a) the amount of depolarization required to be produced in the nonstimulated cell (the "sink" for current flow) to initiate an action potential in the nonstimulated cell, (b) the intercellular resistance as the path for intercellular current flow, and (c) the ability of the stimulated cell to maintain a high membrane potential to serve as the "source" of current during the conduction process. We present data from eight pairs of simultaneously recorded rabbit ventricular cells, with the two cells of each pair physically separated from each other. We used an electronic circuit to pass currents into and out of each cell such that these currents produced the effects of any desired level of intercellular resistance. The cells of equal size (as assessed by their current threshold and their input resistance for small depolarizations) show bidirectional failure of conduction at very high values of intercellular resistance which then converts to successful bidirectional conduction at lower values of intercellular resistance. For cell pairs with asymmetrical cell sizes, there is a large range of values of intercellular resistance over which unidirectional block occurs with conduction successful from the larger cell to the smaller cell but with conduction block from the smaller cell to the larger cell. We then further show that one important component which limits the conduction process is the large early repolarization which occurs in the stimulated cell during the process of conduction, a process that we term "source loading."

Action Potentials↗
PubMed1991

Cellular mechanisms of delayed recovery of excitability in ventricular tissue.

It is well established that ventricular tissue, under some conditions, exhibits the phenomenon of postrepolarization refractoriness (PRR) in which the tissue excitability is depressed after an action potential. We have done parallel experiments on rabbit papillary muscles and on isolated rabbit ventricular cells to explain the cellular basis of this phenomenon, using elevated extracellular K+ concentration ([K+]o) (8 mM) to depolarize the tissue and the isolated cells. For isolated cells, we could separately measure cellular excitability (the inverse of the cellular current threshold) and the cellular responsiveness (the ability of the cell to generate inward current after excitation has occurred). We present two hypotheses that could explain the magnitude and time course of tissue PRR in terms of either changes in cellular excitability or changes in cellular responsiveness. We show that, although small changes in cellular excitability do occur, the predominant cellular mechanism for tissue PRR is the time course of recovery of the cellular responsiveness.

Action Potentials↗
PubMed1991

Developmental changes in calcium currents of rabbit ventricular cells.

We investigated the postnatal development of L-type Ca2+ current (ICa) in enzymatically isolated adult (AD) and newborn (NB) (1-3-day-old) rabbit ventricular cells using the whole-cell, patch-clamp method. ICa was recorded with Cs(+)-rich pipettes and a Na(+)- and K(+)-free bath solution at 36 degrees C to eliminate other currents. ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells than in NB cells at potential levels between 0 and +50 mV with 1.8 mM Ca2+ as the charge carrier. There was no shift in the current-voltage relation between AD and NB cells. The maximum ICa density was 9.9 +/- 2.0 pA/pF at 14 +/- 5 mV in AD cells (n = 11) compared with 5.6 +/- 2.0 pA/pF at 13 +/- 5 mV in NB cells (n = 7) (mean +/- SD). Time to half inactivation (T 1/2) showed a nearly U-shaped relation to membrane potentials from -10 to +30 mV with the shortest T 1/2 at the potential giving the maximum ICa density in both groups. T 1/2 at 0 and +10 mV was slightly but significantly longer in NB cells (16.8 +/- 4.6 and 13.5 +/- 2.4 msec, respectively) than in AD cells (12.6 +/- 3.0 and 10.6 +/0 1.5 msec).(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channels↗
PubMed1991

Experimental model of effects on normal tissue of injury current from ischemic region.

An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells, which has been termed an "injury current." We have devised an experimental model system in which an isolated rabbit ventricular cell is electrically coupled to a model depolarized cell to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell. We found that the action potential duration of the isolated cell could be reversibly altered by varying the coupling resistance such that the action potential duration was shortened by high values of coupling resistance but could be considerably prolonged by lower resistance coupling. We did not observe automaticity in the isolated cell as a consequence of coupling to the depolarized model. The changes in action potential duration were accompanied by alterations in the frequency at which the isolated cell could respond to repetitive stimuli. In addition, the depolarization of the isolated cell produced by the electrical coupling led to a significant increase in the cellular excitability. This last effect may be of particular importance in understanding the mechanisms for origination of arrhythmias in the border zone of myocardial ischemia.

Action Potentials↗
PubMed1990

Cellular mechanism of the functional refractory period in ventricular muscle.

A premature action potential elicited in ventricular muscle during the functional refractory period of a preceding action potential requires an increased stimulus intensity for successful propagation. We measured the cellular basis for these relative decreases in tissue excitability during the recovery phase by performing parallel experiments on rabbit left papillary muscle and isolated rabbit ventricular cells in addition to conducting theoretical studies with numerical simulations of action potential initiation. For each experimental preparation, the pacing protocol consisted of a train of 10 stimuli (S1) at an S1-S1 interval of 500 msec with a premature stimulus (S2) of variable S1-S2 intervals following the tenth S1 action potential. The stimulus threshold for initiation of an S2 action potential (I2) was then measured as a function of the time of occurrence of the S2 stimulus relative to the time of 95% repolarization of the tenth S1 action potential (stimulus delay [SD] time). In the tissue preparation, the I2 increased sharply for SD times less than 0 msec to a value that was 100% above the S1 stimulus threshold for SD time = -5 +/- 2.4 msec (n = 8). Similar experiments on the isolated ventricular cell showed no increases in I2 as a function of SD time but rather significant decreases in both the action potential amplitude (APA) and the maximum rate of rise of the action potential upstroke (Vmax) of the S2 action potential. The APA and Vmax for the S2 action potential were decreased to 50% of the S1 action potential values for SD time = -5.2 +/- 2.1 msec and SD time = 0.3 +/- 1.6 msec, respectively (n = 8). Both parameters reached 100% recovery by SD time = 10 msec. These results and our numerical simulations are consistent with the hypothesis that the decreases in tissue excitability that occur with premature stimulation have a cellular mechanism as a result of a decrease in cellular responsiveness (APA, Vmax) rather than an intrinsic decrease in cellular excitability.

Action Potentials↗
PubMed1990

Electrotonic influences on action potentials from isolated ventricular cells.

This work combines a theoretical study of electrical interactions between two excitable heart cells, using a variable coupling resistance, with experimental studies on isolated rabbit ventricular cells coupled with a variable coupling resistance to a passive resistance and capacitance circuit. The theoretical results show that the response of an isolated cell to an increased frequency of stimulation is strongly altered by the presence of a coupling resistance to another cell. As the coupling resistance gradually is decreased, the stimulated cell becomes able to respond successfully to more rapid stimulation, and then, at levels of coupling resistance that allow conduction between the two cells, the coupled pair of cells exhibits arrhythmic interactions not predicted by the intrinsic properties of either cell. The experimental results show that the isolated rabbit ventricular cell is extremely sensitive to even a very small electrical load, with shortening of the action potential by 50% with electrical coupling to a model cell (of similar input resistance and capacitance to the ventricular cell) as high as 1,000 M omega, even though the action potential amplitude and current threshold are very insensitive to the electrical load.

Action Potentials↗
PubMed1989

Effects of tissue geometry on initiation of a cardiac action potential.

We used rabbit ventricular papillary muscles and isolated rabbit ventricular muscle cells to compare the effects of a decrease in cardiac excitability. For the papillary muscles, we defined tissue excitability as the inverse of the current required to initiate a propagated action potential from a local stimulus. For the isolated cells, we defined cellular excitability as the inverse of the current required to initiate a membrane action potential. For papillary muscles, lidocaine with elevated extracellular K+ concentration ([K+]o) decreased maximum rate of rise of membrane potential (Vmax), decreased conduction velocity, and strongly decreased tissue excitability. For the isolated cells, lidocaine with elevated [K+]o decreased Vmax but had little effect on cellular excitability. We interpret our results on the differences of effect on tissue excitability vs. cellular excitability as a consequence of the syncytial nature of the papillary muscle. The cell-to-cell electrical connections produce an electrical load on the locally stimulated region. This electrical load makes the tissue excitability dependent on the amount of inward current that the locally excited cells and the surrounding cells can generate. We simulated these phenomena with numerical solutions of action potential initiation in an isopotential cell compared with a two-dimensional disk of excitable tissue. The simulation results recreate the basic experimental observation that the sensitivity of the current threshold to agents that lower inward current is markedly larger for multidimensional current flow from a source compared with an isopotential system.

Action Potentials↗
PubMed1989

Effects of hypoxia on atrioventricular node of adult and neonatal rabbit hearts.

We used an isolated perfused heart model to assess the effects of graded hypoxia (95, 45, 20, 10, or 0% O2, exposure for 5 min) on the adult and neonatal (0-3 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by measuring the A-H interval at a constant atrial pacing cycle length, the longest pacing cycle length resulting in Wenckebach periodicity [Wenckebach cycle length (WCL)] and the AV nodal effective refractory period (AVNERP). The A-H intervals remained stable in neonatal hearts until O2 saturation was decreased to 10%. On the other hand, the A-H intervals began to increase in adult rabbit hearts at 20% O2. In 95% O2, the AV nodal WCL was longer in adult hearts than in the neonatal hearts (165 +/- 8 ms vs. 142 +/- 7 ms). The effect of hypoxia on the AV nodal WCL was significantly greater in adult hearts than in neonatal hearts when the O2 saturation was decreased to 20% (a 54% increase in adults vs. a 14% increase in neonates, P = 0.02). The difference was greater at lower levels of O2. In 95% O2 at comparable basis driving cycle length (240 ms), the A-H intervals were equal in neonatal and adult hearts (43 +/- 3 vs. 43 +/- 7 ms), but the AVNERP of the neonates was significantly longer than that of the adults (133 +/- 21 vs. 97 +/- 19 ms, P = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Modulation of the Purkinje-ventricular muscle junctional conduction by elevated potassium and hypoxia.

Action potential transmission in the canine ventricle normally occurs from the Purkinje (P) system into the ventricular muscle (VM) at specific P-VM junction sites. Transitional (T) cells are located between the Purkinje and the ventricular (V) cells at these P-VM junction sites. It has been shown that exposure to elevated [K+]0 in combination with hypoxia produces an increase in the P-VM conduction time. To examine this increase in P-VM conduction time, simultaneous measurements of the action potential upstrokes of T cells and the activation times of the local P and V cells at P-VM junctional sites were obtained from in vitro canine papillary muscles. The effects of elevated [K+]0 and hypoxia on conduction from P cells to T cells was then compared with the conduction from T cells to V cells to assess the relative contribution of each to the increase in the P-VM conduction time. We found that this intervention has approximately equal effects on the two sequential steps involved in P-VM conduction. We then analyzed the increased delay from T cells and V cells on the basis of three hypothetical mechanisms: 1) increased coupling resistance, 2) decreased V cell excitability, and 3) decreased cellular responsiveness of the T cells. Our results show that the effects of elevated [K+]0 and hypoxia on T-VM delay can be accounted for by a decreased responsiveness of the T cells without any significant electrical uncoupling between T and V cells or decrease in VM excitability.

Action Potentials↗
PubMed1989

Developmental changes in the electrophysiologic properties of rabbit papillary muscles.

We studied the electrophysiological properties of adult (AD) and newborn (NB) rabbit papillary muscles in vitro with superfusion of normal Tyrode's solution, solutions with elevated [K+]o, and in solutions with various concentrations of tetrodotoxin. In control solutions, the NB papillary muscles had a more negative resting membrane potential (-83.6 +/- 1.2 versus -80.0 +/- 1.5 mV), a higher rate of rise of phase 0 (134 +/- 5 versus 120 +/- 5 V/S) and a higher, longer-lasting action potential plateau than the AD papillary muscles. Exposure to elevated [K+]o led to a significant post-repolarization refractoriness in AD papillary muscles that was more than that for NB papillary muscles even when NB papillary muscles were depolarized to the same resting membrane potential as the AD papillary muscles. The NB papillary muscles were comparatively resistant to tetrodotoxin in terms of percent reduction of conduction velocity and percent rise in the current threshold for excitation. The conduction velocity for AD papillary muscles in control solution (66 +/- 6 cm/s) was more than for NB papillary muscles (44 +/- 4 cm/s), which would not be expected from the data on the rate of rise of the action potential, suggesting that the cable properties of NB papillary muscles (specifically a greater surface to volume ratio of the ventricular cells) are also significantly different from the AD papillary muscles.

Action Potentials↗
PubMed1988

Comparison of the use of nalbuphine and fentanyl during third molar surgery.

In a double-blind, randomized plan of drug administration, nalbuphine, fentanyl, and a placebo were compared for efficacy in sedation and analgesia during third molar removal. Fifty-eight patients participated in this study. Using accepted intravenous sedation and surgical techniques, fentanyl and nalbuphine were found to be better than placebo for anxiety and pain control in third molar surgery. Fentanyl had a longer duration of pain relief postoperatively than did nalbuphine. The study confirmed the need for a narcotic supplement to sedation techniques for third molar surgery.

Analgesics↗
PubMed1987

Adenosine and hypoxia effects on atrioventricular node of adult and neonatal rabbit hearts.

An isolated perfused heart model was used to assess the effects of hypoxia and adenosine on the adult and neonatal (1-5 days) rabbit atrioventricular (AV) node. The AV nodal function was assessed by the A-H interval at a constant atrial pacing cycle length and by the longest pacing cycle length resulting in Wenckebach periodicity. We defined the pacing cycle length at or below which the AV node demonstrated Wenckebach periodicity as the Wenckebach cycle length. Adenosine produced a smaller dose-dependent increase in A-H interval in neonates than in adults, but the increase in Wenckebach cycle length was similar in the two age groups. When the hearts were exposed to 5 min of hypoxia the increase of Wenckebach cycle length was greater for adults than for neonates. The change in Wenckebach cycle length in adults caused by hypoxia was significantly greater than that caused by 1 mM adenosine. In addition, in adults aminophylline could partially attenuate the increase in Wenckebach periodicity caused by adenosine, but aminophylline could not attenuate the increase in Wenckebach cycle length caused by hypoxia. We conclude that in the rabbit AV node 1) the adenosine effect in neonates is similar to that in adults; 2) neonates are relatively resistant to acute hypoxia compared with adults; and 3) the response to acute hypoxia in adults cannot be totally explained by the adenosine release theory.

Adenosine↗
PubMed1987

Alterations in endocardial activation of the canine papillary muscle early and late after myocardial infarction.

Permanent coronary occlusion produces time-dependent changes in surviving subendocardial cellular properties. We compared the functional alterations in Purkinje (P) and ventricular muscle (VM) activation early (24 hr) and late (4 weeks or greater) after permanent coronary occlusion in an in vitro preparation of canine papillary muscle. High-density extracellular (1 to 2 mm resolution) and selected intracellular recordings were made in five animals early and seven animals late during stimulation of a free-running P strand. Activation patterns of P and VM layers from ischemic and unaffected papillary muscles were compared in the same animal. Average P layer conduction velocity was determined in normal and ischemic regions with the use of a linear array of recording and stimulating electrodes. Purkinje activation was altered little in the early phase of infarction, while healing was associated with a generalized 25% reduction in P layer conduction velocity and localized block and fragmentation of P waveforms. Intracellular recordings at sites of nonsynchronous P activation revealed electrotonic interaction between cell groups. At 24 hr, small groups of VM were present but with abnormal activation patterns in regions of necrosis with fragmented and delayed extracellular waveforms produced by partially uncoupled groups of cells. Local delay and block could be modulated by rate and site of stimulation. After healing, VM activation abruptly stopped at the visual infarct border, marked by a characteristic "end potential." These studies demonstrate important differences in the functional attributes of the P and VM layers studied early and late after coronary occlusion. Alterations in cell-to-cell relationships are likely very important in determining abnormalities of activation in both settings.

Animals↗
PubMed1987

Effects of hypoxia, hyperkalemia, and metabolic acidosis on canine subendocardial action potential conduction.

We have studied the individual and combined effects of elevated external potassium concentration (8 mM [K+], metabolic acidosis (pH = 6.8), and hypoxia at different stimulation 400 milliseconds) on Purkinje (P) and ventricular (V) conduction velocities and on Purkinje-ventricular junctional conduction delay (PVJ delay) in in vitro preparations from canine ventricles. Elevated [K+] had opposite effects on P and V velocities, increasing V velocity by 8% while reducing P velocity by 7%. Acidosis reduced P velocity by 9% while reducing V velocity by only 4%. Hypoxia and rapid stimulation rates had no significant effect on either P or V velocities. All test solutions (except hypoxia alone) significantly increased the PVJ delay. The magnitude of the increase in PVJ delay was much greater than the effects on either P or V velocity. In addition, hypoxia and rapid stimulation augmented the increase in PVJ delay in the presence of elevated [K+] and/or acidosis. The special features of conduction at the PV junctional sites may produce altered pathways of excitation of the ventricles during myocardial ischemia.

Acidosis↗
PubMed1987

Characteristics of junctional regions between Purkinje and ventricular muscle cells of canine ventricular subendocardium.

The normal cardiac activation sequence requires propagation of the action potential from the subendocardial Purkinje network into the underlying ventricular muscle cells. This process occurs at specific junctional sites distributed over the endocardial surface of both ventricles. At these junctional sites, action potentials can be recorded from cells that appear to be interposed between the Purkinje cells and the ventricular muscle cells. The action potential upstrokes recorded from these "transitional" cells have characteristic double phases produced by electrotonic interactions with the Purkinje cells and the ventricular muscle cells. We have shown that these junctional regions in the canine subendocardium appear to be fixed anatomic sites with locations independent of the activation sequence of the Purkinje network. In addition, the activation delay between the Purkinje cells and the ventricular muscle cells at a junctional site and the patterns of the action potential upstrokes of transitional cells at a junctional site are independent of the activation sequence of the Purkinje network. We have also demonstrated that at some locations there are multiple Purkinje activation signals recorded with a surface electrode and that these multiple activation signals represent discrete groups of Purkinje cells, some of which contribute to the junctional process while others appear to be substantially uncoupled from neighboring Purkinje cell groups and the underlying transitional cells.

Action Potentials↗