Biomedical subjects

L W Dickerson

Publications and source records attributed to L W Dickerson.

13 recordsLinked to original sources

PubMed2000

The effect of sodium bicarbonate on propranolol-induced cardiovascular toxicity in a canine model.

STUDY OBJECTIVE: To evaluate the potential utility of sodium bicarbonate in an established model of acute propranolol toxicity. METHODS: Two minutes after the completion of a propranolol infusion (10 mg/kg), a bolus of 1.5 mEq/kg of sodium bicarbonate solution (1 mEq/mL) followed by an infusion of 1.5 mEq/kg over the next 26 minutes (n = 6) or an equivalent timing and volume of 5% dextrose solution (n = 6) was administered in each dog. Targeted cardiovascular parameters included heart rate, mean arterial pressure, left ventricular dP/dtmax, and QRS interval. RESULTS: Propranolol infusion significantly depressed heart rate (p < 0.0001), mean arterial pressure (p < 0.0001), dP/dtmax (p < 0.0001) and prolonged the QRS interval (p < 0.0001). Sodium bicarbonate failed to significantly improve these targeted parameters when compared to control animals. CONCLUSION: In this canine model of propranolol toxicity, intravenous sodium bicarbonate appears to be an ineffective single therapy. Furthermore, these results may suggest a different mechanism of sodium channel blockade for propanolol than that of type IA antiarrhythmic agents.

Animals↗

PubMed1999

Cocaine-induced cardiovascular effects: lack of evidence for a central nervous system site of action based on hemodynamic studies with cocaine methiodide.

It has been suggested that cocaine acts directly in the brain to enhance central sympathetic outflow. However, some studies suggested that the cardiovascular effects of cocaine are related to a peripheral action. To characterize further the site of cocaine's cardiovascular effect, we compared the hemodynamic effects of cocaine (2 mg/kg, i.v. bolus) with those observed after administration of an equimolar dose (2.62 mg/kg, i.v. bolus) of cocaine methiodide, a quaternary derivative of cocaine that does not penetrate the blood-brain barrier, by using sufentanil-sedated dogs. Cocaine produced significant (p < 0.05) increases in heart rate (+37+/-11 beats/min), mean arterial pressure (+55+/-11 mm Hg), left ventricular end-diastolic pressure (+5.3+/-1.0 mm Hg), and cardiac output (+2.4+/-0.9 L/min). Cocaine methiodide produced increases in heart rate (+57+/-11 beats/min), mean arterial pressure (+45+/-11 mm Hg), left ventricular end-diastolic pressure (+3.4+/-1.0 mm Hg), and cardiac output (1.1+/-0.9 L/min), which were not significantly different from those observed with cocaine. Because opiate sedation potentially might have attenuated central sympathetic outflow, we further confirmed the qualitative similarity of the actions of cocaine and cocaine methiodide on heart rate and blood pressure in unsedated, conscious dogs. Our data suggest that the cardiovascular effects of cocaine result primarily from a peripheral site of action.

Anesthetics, Intravenous↗

PubMed1998

Control of negative inotropic vagal preganglionic neurons in the dog: synaptic interactions with substance P afferent terminals in the nucleus ambiguus?

Previous research from this laboratory has shown that substance P-immunoreactive (SP) terminals synapse upon negative chronotropic vagal preganglionic neurons (VPNs), but not upon negative dromotropic VPNs, of the ventrolateral nucleus ambiguus (NA-VL). Moreover, SP agonists injected into NA-VL cause bradycardia without decreasing AV conduction. In the current study, we have: (1) defined the electron microscopic characteristics of the SP neurons of NA-VL in dog; and (2) tested the hypothesis that SP nerve terminals synapse upon negative inotropic VPNs of NA-VL, retrogradely labeled from the cranial medial ventricular (CMV) ganglion. Numerous SP terminals and a few SP neurons were observed in the vicinity of retrogradely labeled neurons. SP terminals were observed forming synapses with unlabeled dendrites and with SP dendrites, but never with the retrogradely labeled neurons. Together, these results and earlier findings suggest that SP agonists may be able to induce bradycardia without decreasing AV conduction or ventricular contractility.

Animals↗

PubMed1998

Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by catecholaminergic afferents to the NA-VL.

Animals↗

PubMed1998

Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility.

We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P < 0.05). Next, the ganglionic blocker trimethaphan (0.3-1.0 ml of a 50 microg ml(-1) solution) was injected into the CMV fat pad. Then vagal stimulation was repeated, which now produced a relatively small 5% (N.S., P > 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.

Adipose Tissue↗

PubMed1997

Stimulation of dog RVLM and A5 area changes sympathetic outflow to vascular beds without effect on the heart.

Studies were conducted in anesthetized, vagotomized dogs while blood pressure; blood flows in femoral, renal, mesenteric, and left circumflex coronary arteries; electrocardiogram; and regional cardiac contractile force were monitored. The ventral surface of the medulla was exposed, and pressor sites in the rostral ventrolateral medulla (RVLM) were mapped by microinjections of L-glutamate. L-Glutamate activation of the RVLM evoked selective effects on different components of the cardiovascular system. Increases of 20-130 mmHg in blood pressure were accompanied by vascular conductance decreases in the femoral (-48 +/- 4%), renal (-30 +/- 4%), and mesenteric (-38 +/- 3%) arterial beds. These effects were without any obvious topography within the RVLM. There were only small or negligible changes in heart rate (HR), cardiac contractile force, and coronary vascular conductance. Thus stimulation of the canine RVLM increased sympathetic tone selectively to structures other than the heart. Stimulation of the ventral medulla in a region that lay rostral to the RVLM and ventromedial to the facial nucleus selectively increased femoral vascular conductance by 103 +/- 33% and decreased vascular conductance in the renal (-20 +/- 5%) and mesenteric (-15 +/- 4%) arterial beds. There was no increase in HR, and the increases in blood pressure were relatively small. Immunohistochemical data led us, tentatively, to identify this rostral area as overlapping part of the A5 area.

Animals↗

PubMed1993

Relationship between coronary hemodynamic changes and the phasic events of rapid eye movement sleep.

Previous studies in dogs showed dramatic increases in coronary blood flow associated with episodes of sinus tachycardia during rapid eye movement (REM) sleep. The present study demonstrates that 90% of these surges in heart rate and coronary flow are concentrated during periods of phasic REM sleep and only 10% in tonic REM sleep. Intensely phasic REM was distinguished from moderately phasic REM sleep by the degree of phasic eye movement. The surges were three times more frequent during intensely phasic REM than in moderately phasic REM sleep. However, the magnitudes of heart rate (37% +/- 3%) and coronary flow (25% +/- 3%) surges were unaffected by the specific substage of REM sleep. The incidence of surge events was almost eleven times greater in epochs of phasic REM that also contained a muscle twitch than in those that did not. During REM sleep, muscle twitches accompanying surges were not associated with any additional elevations in coronary flow or myocardial demand. Our data indicate that the sinus tachycardia-associated surges in coronary flow represent integrated autonomic responses intrinsic to phasic periods of REM sleep in dogs.

Animals↗

PubMed1993

Primary coronary vasodilation associated with pauses in heart rhythm during sleep.

We observed 162 episodes of pause in heart rhythm in chronically instrumented dogs primarily during transitions from deep slow-wave sleep to other stages of sleep. These pauses lasted 1.1-8.0 s and were followed by increases in coronary blood flow (CBF) averaging 30% and ranging up to 84%. The postpause surges in CBF do not appear to be mediated by local metabolic factors because the flow surges occurred without significant changes in the heart rate x systolic blood pressure (HRxSBP) product, a standard index of cardiac metabolic activity. Enhanced vagal tone is suggested by the background of marked respiratory sinus arrhythmia, low average heart rates, and the hallmark event, the pause in heart rhythm. In a series of experiments in alpha-chloralose-anesthetized dogs, we demonstrated that direct vagus nerve stimulation can induce both the pause in heart rhythm and the postpause increase in CBF in a pattern similar to that observed during sleep. This response was markedly attenuated after pericoronary denervation. These observations provide suggestive evidence but not definitive proof that enhanced vagal activity may be involved in the increase in CBF after spontaneous pauses in heart rhythm during sleep.

Animals↗

PubMed1992

Long-latency auditory-evoked potentials: role of polysensory association cortex in the cat.

The objective of this study has been to define the role of polysensory association cortex in the generation of "wave NA" and of "wave C," long-latency auditory-evoked potentials recorded from the vertex of conscious cats as, respectively, a marked negative potential of latency 30-48 msec followed by a broad positive wave of latency 50-75 msec. Wave C may represent the feline analogue of the longer latency human auditory-evoked potential wave P2, insofar as both waveforms are very large amplitude, long duration positivities characterized by long recovery cycles. Based on previous studies of wave C and the generators of other middle-latency evoked potentials, we hypothesized that both wave NA and wave C might reflect, at least in part, the cortical culmination of a nonlemniscal line auditory association system arising in reticulothalamic projections to intralaminar and associated ventral thalamic regions. Relays from these thalamic areas are known to project to polysensory association cortex, including pericruciate gyrus, anterolateral gyrus, and medial suprasylvian gyrus. Therefore we implemented a series of lesion experiments to characterize the role of each of these cortical areas in the production of wave NA and wave C. Our results indicate that all three polysensory association areas contribute significantly to both waves NA and C, although the largest effects followed ablation of the pericruciate area alone. Thus, the generator substrates of waves NA and C appear to involve a long-recovery cycle system which functionally incorporates activation of association cortex.

Acoustic Stimulation↗

PubMed1992

Behavioral states and sudden cardiac death.

Remarkable progress has been made both experimentally and clinically in defining the influence of behavioral states on susceptibility to life-threatening arrhythmias. Biological models have been developed to emulate anger and fear and have permitted detailed study of the intermediary mechanisms involved in stress-induced ischemia and ventricular fibrillation. The studies highlight the importance of adrenergic factors and the pathological significance of the poststress state. Clinically, the role of daily stresses in inducing silent myocardial ischemia and arrhythmias has been extensively characterized, and standardized behavioral stress tests have become available. Certain sleep states have been found to provoke ischemic episodes and arrhythmias. In particular, phasic rapid eye movement (REM) sleep has been shown both in animals and humans to conduce to perfusion abnormalities and propensity to fibrillation. Episodic surges in sympathetic nervous system activity appear to be the underlying basis. These conceptual and practical advances illustrate the promise of behavioral cardiology in the diagnosis and treatment of individuals at risk for sudden cardiac death.

Anger↗

PubMed1991

Midlatency auditory-evoked responses: effect of scopolamine in the cat and implications for brain stem cholinergic mechanisms.

The objective of this study has been to define the role of cholinergic mechanisms in the generation of "wave A," a middle latency auditory-evoked potential recorded as a positivity with a 20-25 ms peak latency from the vertex of conscious cats. Wave A and its generator system have particular significance as an experimental model of the human middle latency component "P1." Both the feline wave A and the human P1 are characterized by a long recovery cycle, disappearance during slow wave sleep, and reappearance during rapid eye movement (REM) sleep and during wakefulness. The orchestration of several phenomena of REM sleep are known to involve muscarinic cholinergic mechanisms in the brain stem. Therefore, middle latency auditory-evoked potentials were studied in awake cats before and after injection of a cholinergic antagonist, scopolamine. Wave A and the successive negative potential were abolished by scopolamine in a dose-dependent fashion. This effect occurred within 5-15 min and was spontaneously reversible within a few hours. Although individual subjects were differentially susceptible to lower doses of the drug, all six subjects in this study demonstrated a well-defined statistically significant response at higher doses of the drug. In addition, careful parametric baseline studies were performed in each cat to strengthen the evidentiary linkage between wave A as recorded from the vertex in these experiments and previous studies describing the origin and trajectory of wave A in the brainstem reticular formation and several regions of thalamus, including the intralaminar nuclei. Thus, we conclude that the production of wave A depends substantially on the postsynaptic activation of muscarinic cholinergic receptors whose cells of origin lie within the brainstem reticular formation.

Animals↗

PubMed1991

Autonomic nervous system and coronary blood flow changes related to emotional activation and sleep.

Experimental models have been developed to investigate the influences of anger, fear, and sleep on coronary blood flow. Studies of anger in dogs with coronary stenosis indicate that the postarousal phase is particularly conducive to myocardial ischemia. Specifically, a delayed coronary vasoconstrictor response has been observed within 1-3 minutes after cessation of behavioral arousal. The response is prevented by bilateral stellectomy and can be elicited in anesthetized animals by electrical stimulation of the right or left stellate ganglion. The latter effect is averted by alpha-adrenergic blockade with prazosin. Although the basis for the protracted nature of the delayed vasoconstriction remains to be clarified, the current hypothesis is that the phenomenon results from a time-dependent imbalance between the vasoconstrictor effects of adrenergic input and the vasodilator influences of coronary pressure and/or cardiac metabolic activity. A behavioral model emulating the fear state has also been developed. When dogs that fail to exhibit anger are placed in a food-access confrontation protocol, the animals demonstrate a fearlike state evidenced by a cowering posture and somatic tremor. There is a distinct plasma catecholamine profile that is characterized by a predominant increase in epinephrine compared with norepinephrine. This is in contrast to the pattern observed during anger, in which a prevalent increase in norepinephrine is observed. Fear results in significant increases in heart rate, arterial blood pressure, and coronary arterial flow. Sleep is also associated with substantial alterations in coronary hemodynamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Anger↗

PubMed1990

Cat-P300 present after association cortex ablation.

The cat-P300 is a positive endogenous potential, larger to a stimulus when rare than when frequent, with a latency of 200-500 msec. The role of polysensory association cortex, postulated to be important in human P300 generation, was assessed in the cat. EEG was recorded in 13 awake cats from a skull screw at the vertex. Stimuli included frequent (P = 0.80) 1 kHz and rare (P = 0.10) 2 kHz tone pulses with probabilities counterbalanced across 260-trial blocks. After 12 preoperative sessions, bilateral ablations were made of pericruciate cortex (4 cats), anterior lateral and medial suprasylvian gyri (4 cats) and all 3 areas (5 cats). Postoperatively, all 13 cats showed a P300 across 12 recording sessions. Thus polysensory association cortex is not essential for generation of the cat-P300.

Acoustic Stimulation↗