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F Dexter

Publications and source records attributed to F Dexter.

12 recordsLinked to original sources
PubMed1992

Analysis of vagally induced sinus arrhythmias.

Vagal stimulation at precise times in successive cardiac cycles can elicit sinus arrhythmias. Two mechanisms have been identified that can, but do not necessarily, cause these vagally induced sinus arrhythmias. First, changes in cycle length elicited by a given concentration of acetylcholine (ACh) depend on the phase of the pacemaker cell action potential when the ACh binds to muscarinic receptors. Second, acetylcholinesterase degrades ACh rapidly enough for the mean concentration of ACh per cardiac cycle to vary from cycle to cycle. We used a mathematical model of the underlying cellular physiology, to examine whether these mechanisms are responsible for arrhythmogenesis. Computer simulation showed that both mechanisms contribute to the vagally induced sinus arrhythmias.

Arrhythmias, Cardiac↗
PubMed1992

Brain blood flow and metabolism do not decrease at stable brain temperature during cardiopulmonary bypass in rabbits.

Cerebral blood flow (CBF) during human hypothermic cardiopulmonary bypass has been reported to decrease with time, suggesting that progressive cerebral vasoconstriction or embolic obstruction may occur. We tested the hypotheses: 1) that observed CBF reductions were due to continued undetected brain cooling and 2) that CBF during cardiopulmonary bypass would be stable after achievement of constant brain temperature. Anesthetized New Zealand White rabbits underwent cardiopulmonary bypass (membrane oxygenator, centrifugal pump, bifemoral arterial perfusion) and were assigned to one of three bypass management groups based on perfusate temperature and PaCO2 management: group 1 (37 degrees C, n = 8); group 2 (27 degrees C, pH-stat, n = 9); and group 3 (27 degrees C, alpha-stat, n = 8). Systemic hemodynamics, and cerebral cortical, esophageal, and arterial perfusate temperatures were recorded every 10 min for the first hour of bypass and again at 90 min. CBF and masseter blood flow (radiolabeled microspheres) were determined at 30, 60, and 90 min of bypass, while the cerebral metabolic rate for oxygen (CMRO2) was determined at 60 and 90 min. Groups were comparable with respect to mean arterial pressure, central venous pressure, hematocrit, and arterial oxygen content throughout bypass. Cortical temperature was stable in normothermic (group 1) animals, and there was no significant change in CBF between 30 and 90 min of bypass: 68 +/- 18 versus 73 +/- 20 ml.100 g-1.min-1 (mean +/- SD). In the hypothermic groups (2 and 3), cortical temperature equilibration (95% of the total change) required 41 +/- 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Central nervous system toxicity of local anesthetic mixtures in the rat.

Local anesthetics are often administered as mixtures during regional anesthesia. This study investigated whether a synergistic or antagonistic interaction between amide/amide or amide/ester local anesthetic combinations is present with respect to central nervous system toxicity. For surgical preparation, rats were anesthetized with 0.8% halothane in 30% O2/balance N2O and mechanically ventilated. Mean arterial blood pressure and the electroencephalogram were continuously monitored. After surgery, the halothane was discontinued for 15 min. An intravenous infusion of solutions containing lidocaine alone, bupivacaine alone, or any of three mixtures of the two drugs was then begun and continued at a fixed rate until seizure activity was observed on the electroencephalogram. Total administered doses of both drugs were compared by isobolographic analysis. After a similar protocol, a second experiment was performed evaluating lidocaine, tetracaine, or any of three mixtures of those two drugs. In both experiments, normocapnia, normoxia, and normothermia were maintained for all rats. For mixtures of lidocaine/bupivacaine (P = 0.40) and lidocaine/tetracaine (P = 0.24), there was no evidence that a significant degree of either synergism or antagonism was present. At the onset of seizures, mean arterial pressure was lowest in the lidocaine-alone groups in both experiments. Increasing doses of either bupivacaine or tetracaine (with correspondingly decreasing doses of lidocaine) were associated with greater mean arterial pressure values at onset of seizures. We conclude that central nervous system toxic effects of amide/amide or amide/ester anesthetic combinations, such as might occur during accidental intravascular injection, are no more than when the drugs are administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1991

Mathematical model of cellular basis for the respiratory sinus arrhythmia.

The respiratory sinus arrhythmia (RSA) is a vagally mediated oscillation in cardiac cycle length at the frequency of breathing. We developed a mathematical model that predicted the temporal and frequency dependence of the RSA. We used the mathematical model to examine the underlying cellular basis for the RSA at the level of the sinus node. We alternated efferent vagal activity between a low and a high frequency at the frequency of breathing. This oscillation caused the rate of acetylcholine (ACh) release to oscillate between a low and a high rate at the frequency of breathing. ACh degradation followed linear pharmacokinetics for physiological concentrations of ACh. Therefore, the concentration of ACh in neuroeffector junctions of the sinus node oscillated at the frequency of breathing. Membrane potential responded rapidly to changes in the concentration of ACh relative to the rate of ACh degradation. Thus, the time course of the RSA depended on the rate of ACh degradation. Membrane potential oscillated at several integer multiples of frequency of breathing and at various higher frequencies, which were integer multiples of the frequency of breathing and the frequencies of firing of the sinus node. However, computing cardiac cycle length from membrane potential eliminated the higher frequencies. Therefore, cardiac cycle length oscillated at several integer multiples of the frequency of breathing, but not at these higher frequencies.

Acetylcholine↗
PubMed1991

Cerebral blood flow response to PaCO2 during hypothermic cardiopulmonary bypass in rabbits.

Differences in cerebral blood flow (CBF) between alpha-stat and pH-stat management depend on preserved responsiveness of the cerebral vasculature to changes in arterial carbon dioxide tension (PaCO2). We tested the hypothesis that hypothermia-induced reductions in CBF would decrease the CBF response to changing PaCO2 (delta CBF/delta PaCO2). Anesthetized New Zealand white rabbits were randomly assigned to one of three temperature groups--group 1 (37 degrees C, n = 9); group 2 (31 degrees C, n = 10); or group 3 (25 degrees C, n = 10)--and were cooled using cardiopulmonary bypass. After esophageal temperature equilibration (approximately 40 min), oxygenator gas flows were serially varied to achieve PaCO2 values of 20, 40, and 60 mm Hg (temperature-corrected). All animals were studied at all three PaCO2 levels in random order. At each level of PaCO2, CBF and masseter blood flow were determined using radiolabeled microspheres. There were no significant differences between groups with respect to mean arterial pressure (approximately 80 mmHg), central venous pressure (approximately 4 mmHg), or hematocrit (approximately 22%). Prior normothermic studies have found delta CBF/delta PaCO2 to be proportional to CBF. Nevertheless, in this study, with hypothermia-induced reductions in CBF, delta CBF/delta PaCO2 was not significantly different between temperature groups. Thus, hypothermia either increased the sensitivity of the cerebral vasculature to carbon dioxide and/or increased the effective level of cerebrospinal fluid respiratory acidosis produced by each increment of temperature-corrected PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Simulation of the diffusion of acetylcholine in the neuroeffector junctions of the sinus node.

Traditionally, the diffusion of acetylcholine (ACh) from a neuron to cardiac muscle in a neuroeffector junction has been modeled as radial diffusion from a nerve ending into a spherical homogeneous medium. Various microscopic structures in the heart may or may not influence the spatial distribution of ACh within neuroeffector junctions. To determine the effect of microscopic anatomy on the diffusion of ACh in neuroeffector junctions, we simulated the diffusion of ACh in a two-dimensional inhomogeneous geometry that was based on micrographs of neuroeffector junctions in the sinus node. ACh was released at sites adjacent to a neuron. Simulations showed that the times of peak concentration after release and the peak concentrations per se were distributed symmetrically above and below and to the right and left of the neuron, but not radially about the neuron. We conclude that the diffusion of ACh in the neuroeffector junctions of the sinus node cannot be predicted well by a mathematical model that assumes radial diffusion in a spherical and homogeneous medium.

Acetylcholine↗
PubMed1989

Mathematical model of dependence of heart rate on tissue concentration of acetylcholine.

The change in sinus period elicited by vagal stimulation depends on the rate of acetylcholine (ACh) release from the nerve endings, the rate of ACh degradation in the nodal tissue, and the responsiveness of the sinus node to ACh. Vagal stimulation in anesthetized dogs prolonged sinus period. After cessation of vagal stimulation, the sinus period returned to the prestimulation period. We developed a mathematical model to analyze the dynamics of ACh degradation in the neuroeffector junction and the dependence of sinus period on the concentration of ACh. From the in vitro reaction kinetics of acetylcholinesterase, we derived an analytical expression for the rate of ACh degradation in the intact animal. Our model represents the electrical behavior of the sinus node by the electrical activity of one pacemaker cell with six membrane ionic currents. This model predicts the decline in sinus period of the intact anesthetized dog as acetylcholinesterase degrades ACh in the neuroeffector junction. The half-life of ACh after cessation of vagal stimulation was estimated to be 2.7 s. We conclude that following termination of vagal stimulation, the sinus node of the intact animal responds to ACh as if the sinus node were one oscillator.

Acetylcholine↗
PubMed1989

Muscarinic autoreceptors do not modulate kinetics of acetylcholine release in hearts.

We determined the time course of the cellular mechanism that mediates the attenuation of the chronotropic response in anesthetized dogs to decreases in the time interval (interpulse interval) between pulses of vagal stimuli. We injected propranolol, cut the cervical vagi, and repetitively stimulated the cardiac segment of the right vagus nerve with one brief burst of electrical pulses during each cardiac cycle. We recorded the initial and steady-state changes in cardiac cycle length that were induced by the phasic vagal stimulation. The decrease in the interpulse interval decreased the initial and steady-state responses. The time delay between the release of acetylcholine (ACh) from the vagal nerve endings in the heart and inhibition of the release of additional ACh was less than 4 ms. Published delays between the time of ACh release and the time of the resulting change in membrane potential, in other biological systems, are 30-12,000 ms. We conclude that the time delay was too brief for muscarinic autoreceptors to have mediated the attenuation of ACh release from postganglionic vagal nerve endings in the heart in response to decreases in interpulse interval.

Acetylcholine↗
PubMed1989

Mathematical model of the changes in heart rate elicited by vagal stimulation.

We developed a mathematical model of the underlying cellular mechanisms responsible for the changes in sinus cycle length (SCL) elicited by vagal stimulation in intact animals. The model incorporated a stimulation-mediated depletion of the releasable pool of acetylcholine (ACh) in the nerve endings, the in vitro reaction kinetics of acetylcholinesterase, and the electrical activity of a pacemaker cell with six membrane ionic currents. SCL increased linearly with the frequency of simulated vagal stimulation, as it does in animal experiments, because the concentration of ACh in the neuroeffector junction [( ACh]) saturated as the frequency of stimulation was increased and because SCL increased geometrically in response to increases in [ACh]. The dependence of SCL on the timing of vagal stimulation in the cardiac cycle resulted, in part, from the dependence of [ACh] on SCL. Simulated vagal stimulation entrained the sinus node because the rate of activation and inactivation of ACh-activated K+ channels depended only weakly on membrane potential during diastolic depolarization. SCL increased geometrically with [ACh], because 1) during diastolic depolarization, the amplitude of the ACh-activated K+ current was approximately equal to the amplitude of the sum of the other ionic currents, 2) [ACh] was low enough to saturate neither acetylcholinesterase nor the cellular system that activates the ACh-activated K+ channels, 3) the pacemaker cell membrane behaved electrotonically like a capacitor, and 4) the sum of all the ionic currents increased linearly with the amplitude of the ACh-activated K+ current.

Acetylcholine↗
PubMed1978

[A tissue bank: aspects concerning its promotion and organization (author's transl)].

In spite of continued improvement in the production of artificial tissues, there are still many instances where replacement of the damaged part by a natural tissue grafts would be preferable. It is to satisfy this requirement that tissue banding has been developed. In this paper a brief description of the preparation of tissue grafts currently being carried out in the Yorkshire Regional Tissue Bank is given and the philosophy of tissue banking from a financial and scientifical point of view is explained.

Animals↗
PubMed1975

Light and electron microscopy studies on homograft and heterograft heart valves.

Light and electron microscopical changes were studied in 23 valvular homografts and six pig aortic heterografts, which had been inserted into patients for lengths of time varying from three days to 54 months. Prior to insertion, eleven of the homografts had been sterilised by beta-propriolactone and freeze-dried, the other twelve had been sterilised by gamma-radiation. The morphological changes in the freeze-dried group were characterised by moderate to severe structural changes including gross vacuolation, fibrinoid degeneration and calcification in the absence of any significant cellular events. It is concluded that the structural changes were due to physico-chemical degradation of the collagen due to improper preservation of the graft, prior to insertion. The morphological changes in the homografts treated with gamma-radiation were fewer and less severe in that there was less vacuolation of the matrix, less fibrinoid degeneration and no examples of calcification. Clear-cut examples of graft regeneration were never observed in either group, but the significance of minor cellular infiltrates in two of the gamma-irradiated grafts is discussed in terms of abortive regeneration. The heterografts showed moderate to intense cellularity, predominantly of macrophages. It is postulated that graft rejection phenomena are responsible for the graft failure in this group.

Animals↗