Search PubMed⌕ Search

Biomedical subjects

J A Armour

Publications and source records attributed to J A Armour.

At least 19 recordsLinked to original sources
PubMed2006

Mechanism of smart baroreception in the aortic arch.

A mechanism is proposed by which the patch of baroreceptors along the inner curvature of the arch of the aorta can sense hemodynamic events occurring downstream from the aortic arch, in the periphery of the arterial tree. Based on a solution of equations governing the elastic movements of the aortic wall, it is shown that the pressure distribution along the patch of baroreceptors has the same functional form as the distribution of strain along the patch. The significance of these findings are discussed, particularly as they relate to the possibility of a neuromechanical basis of essential hypertension.

Animals↗
PubMed2006

Preemptive, but not reactive, spinal cord stimulation mitigates transient ischemia-induced myocardial infarction via cardiac adrenergic neurons.

Our objective was to determine whether electrical neuromodulation using spinal cord stimulation (SCS) mitigates transient ischemia-induced ventricular infarction and, if so, whether adrenergic neurons are involved in such cardioprotection. The hearts of anesthetized rabbits, subjected to 30 min of left anterior descending coronary arterial occlusion (CAO) followed by 3 h of reperfusion (control), were compared with those with preemptive SCS (starting 15 min before and continuing throughout the 30-min CAO) or reactive SCS (started at 1 or 28 min of CAO). For SCS, the dorsal C8-T2 segments of the spinal cord were stimulated electrically (50 Hz, 0.2 ms, 90% of motor threshold). For preemptive SCS, separate groups of animals were pretreated 15 min before SCS onset with 1) vehicle, 2) prazosin (alpha(1)-adrenoceptor blockade), or 3) timolol (beta-adrenoceptor blockade). Infarct size (IS), measured with tetrazolium, was expressed as a percentage of risk zone. In controls exposed to 30 min of CAO, IS was 36.4 +/- 9.5% (SD). Preemptive SCS reduced IS to 21.8 +/- 6.8% (P < 0.001). Preemptive SCS-mediated infarct reduction was eliminated by prazosin (36.6 +/- 8.8%) and blunted by timolol (29.4 +/- 7.5%). Reactive SCS did not reduce IS. SCS increased phosphorylation of cardiac PKC. SCS did not alter blood pressure or heart rate. We conclude that preemptive SCS reduces the size of infarcts induced by transient CAO; such cardioprotection involves cardiac adrenergic neurons.

Animals↗
PubMed2006

Stochastic behavior of atrial and ventricular intrinsic cardiac neurons.

To quantify the concurrent transduction capabilities of spatially distributed intrinsic cardiac neurons, the activities generated by atrial vs. ventricular intrinsic cardiac neurons were recorded simultaneously in 12 anesthetized dogs at baseline and during alterations in the cardiac milieu. Few (3%) identified atrial and ventricular neurons (2 of 72 characterized neurons) responded solely to regional mechanical deformation, doing so in a tightly coupled fashion (cross-correlation coefficient r = 0.63). The remaining (97%) atrial and ventricular neurons transduced multimodal stimuli to display stochastic behavior. Specifically, ventricular chemosensory inputs modified these populations such that they generated no short-term coherence among their activities (cross-correlation coefficient r = 0.21 +/- 0.07). Regional ventricular ischemia activated most atrial and ventricular neurons in a noncoupled fashion. Nicotinic activation of atrial neurons enhanced ventricular neuronal activity. Acute decentralization of the intrinsic cardiac nervous system obtunded its neuron responsiveness to cardiac sensory stimuli. Most atrial and ventricular intrinsic cardiac neurons generate concurrent stochastic activity that is predicated primarily upon their cardiac chemotransduction. As a consequence, they display relative independent short-term (beat-to-beat) control over regional cardiac indexes. Over longer time scales, their functional interdependence is manifest as the result of interganglionic interconnections and descending inputs.

Action Potentials↗
PubMed2004

"Smart" baroreception along the aortic arch, with reference to essential hypertension.

Beat-to-beat regulation of heart rate is dependent upon sensing of local stretching or local "disortion" by aortic baroreceptors. Distortions of the aortic wall are due mainly to left ventricular output and to reflected waves arising from the arterial tree. Distortions are generally believed to be useful in cardiac control since stretch receptors or aortic baroreceptors embedded in the adventitia of the aortic wall, transduce the distortions to cardiovascular neural reflex pathways responsible for beat-to-beat regulation of heart rate. Aortic neuroanatomy studies have also found a continuous strip of mechanosensory neurites spread along the aortic inner arch. Although their purpose is now unknown, such a combined sensing capacity would allow measurement of the space and time dependence of inner arch wall distortions due, among other things, to traveling waves associated with pulsatile flow in an elastic tube. We call this sensing capability--"smart baroreception." In this paper we use an arterial tree model to show that the cumulative effects of wave reflections, from many sites far downstream, have a surprisingly pronounced effect on the pressure distribution in the root segment of the tree. By this mechanism global hemodynamics can be focused by wave reflections back to the aortic arch, where they can rapidly impact cardiac control via smart baroreception. Such sensing is likely important to maintain efficient heart function. However, alterations in the arterial tree due to aging and other natural processes can lead in such a system to altered cardiac control and essential hypertension.

Animals↗
PubMed2004

Control of cardiac function and noise from a decaying power spectrum.

Evidence is presented that adds to the debate surrounding the question: To what extent does neural control of cardiac output exploit noise? The transduction capability of cardiac afferent neurons, situated in and adjacent to the heart, is vital to feedback in control of cardiac function. An analysis of in situ cardiac afferent activity shows evidence of independent and exponentially distributed interspike intervals. An anatomical basis for such memoryless interspike intervals ultimately derives from the fact that each afferent neuron is associated with a field of sensory neurites, or bare nerve endings, that transduce local chemical and mechanical stimuli in a many-to-one fashion. As such, cardiac afferent neurons and their sensory neurite inputs are respectively modeled here by the Hodgkin-Huxley equations forced by "red" noise (decaying power spectrum) perturbing an otherwise constant subthreshold input. A variable barrier competition model is derived from these equations in order to address the question: How are noisy inputs being processed by sensory neurons to cause each spike? It is found that ion channels are responsible for significant input "whitening" (increased spectral power at higher frequency) through differentiation of the inputs. Such whitening is a means to distinguish low-frequency control signals from otherwise red noise fluctuations. Furthermore, spiking occurs when backward moving averages of the whitened inputs, over a window of the order of the sodium activation time scale, exceed an approximately constant barrier.

Action Potentials↗
PubMed2004

Cell transplantation for treatment of acute myocardial infarction: unique capacity for repair by skeletal muscle satellite cells.

An adult heart injured by an ischemic episode has a limited capacity to regenerate. We administered three types of adult guinea pig cells [cardiomyocytes (CMs), cardiac fibroblasts (CFs), and skeletal myoblasts (Mbs)] to compare their suitability for repair of acute myocardial infarction. We used confocal fluorescent microscopy and a variety of specific immunomarkers and echocardiography to provide anatomic evidence for the viability of such cells and their possible functional beneficial effects. All cells were transfected with adenovirus-containing beta-galactosidase gene so that migration from the injection sites could be traced. Both freshly isolated CMs as well as CFs were found concentrated in the infarcted zone; these cells survived for at least 2 wk posttransplantation. Transplanted CMs were regularly striated and grew long projections that could form gap junctions with native CMs, which was evidenced by connexin43 labeling. In addition, CM transplantation resulted in increased angiogenesis in the infarcted areas. In contrast, transplanted CFs did not appear to make any gap junctional contacts with native CMs nor did they enhance local angiogenesis. Mbs cultured for 7 days and transfected Mbs were identified 7 days posttransplantation in the infarcted area. During that time and thereafter, Mbs proliferated and differentiated into myotubes that formed new, regularly striated myofibers that occupied most (50-70%) of the infarcted area by 2-3 wk. These newly formed myofibers maintained their Mb skeletal muscle origin as evidenced by their capacity to express myogenin and fast skeletal myosin. This skeletal phenotype appeared to downregulate with time, and Mbs partially transdifferentiated into a cardiac phenotype as indicated by labeling for cardiac-specific troponin T and cardiac myosin heavy chain. By the third week posttransplantation, new myofibers formed apparent contacts with the native CMs via putative gap junctions that expressed connexin43. Myocardial performance of animals that were successfully transplanted with Mbs was improved.

Age Factors↗
PubMed2003

Porcine intrinsic cardiac ganglia.

The gross, light, and electron microscopic anatomies of the porcine intrinsic cardiac nervous system were investigated in 26 pigs to facilitate functional studies in this model. Gross anatomy: Numerous ganglia and interconnecting nerves (ganglionated plexuses) were found to be concentrated in epicardial fat in five atrial and six ventricular regions. The five atrial ganglionated plexuses identified were (1) the ventral right atrial, (2) the right vena cava-right atrial, (3) the dorsal atrial, (4) the interatrial septal, and (5) the left superior vena cava-left atrial ones. Six ventricular ganglionated plexuses were identified in close proximity to the (1) roots of the aorta and pulmonary artery (craniomedial), extending along the left main coronary artery to the (2) ventral interventricular and (3) circumflex coronary arteries. (4) A ganglionated plexus was identified around the origin of the dorsal interventricular coronary artery, as well as the (5) right main and (6) right marginal coronary arteries. Isolated neurons were identified scattered throughout the cranial interventricular septum. Microscopic anatomy: Approximately 3,000 neuronal somata were estimated to compose this intrinsic cardiac nervous system. Some ganglia contained more than 100 neurons. Neuronal somata had dimensions of roughly 33.1 (short axis) by 46.3 (long axis) microm. Most were multipolar, a small population of unipolar neurons being identified in atrial and ventricular tissues. At the electron microscopic level, asymmetrical axodendritic synapses with small clear, round vesicles were identified, some containing large dense-cored vesicles. In summary, porcine intrinsic cardiac neurons are concentrated in 11 distinct atrial and ventricular ganglionated plexuses. These extensive plexuses, along with fewer scattered neurons, display varied neuronal morphology and synaptology that represent the anatomical substrate for complex information processing within the intrinsic cardiac component of the porcine cardiac neuronal hierarchy. These anatomical data provide a framework for physiological analyses of the porcine intrinsic cardiac nervous system.

Animals↗
PubMed2003

Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.

The intrinsic cardiac nervous system is the final common integrator of regional cardiac function. The ischemic myocardium modifies this nervous system. We sought to determine the role that intrinsic cardiac neuronal P(1) purinergic receptors play in transducing myocardial ischemia and the subsequent reperfusion. The activity generated by ventricular neurons was recorded concomitant with cardiac hemodynamic variables in 44 anesthetized pigs. Regional ventricular ischemia was induced by briefly occluding (30 s) the ventral interventricular coronary artery distal to the arterial blood supply of identified ventricular neurons. Adenosine (100 microM) was administered to these neurons via their local arterial blood supply during or immediately after transient coronary artery occlusion. Occlusion was also performed following local administration of adenosine A(1) [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] or A(2) [3,7-dimethyl-1-propargylxanthine (DMPX)] receptor blocking agents. The activity generated by ventricular neurons was modified by transient coronary artery occlusion and the subsequent reperfusion (||Delta|| 112 +/- 14 and 168 +/- 34 impulses/min, respectively; P < 0.01 vs. preischemic states). Locally administered adenosine attenuated neuronal responses to reperfusion (-75%; P < 0.01 compared with normal reperfusion) but not ischemia. The neuronal stabilizing effects that adenosine elicited during reperfusion persisted in the presence of DMPX but not DPCPX. It is concluded that activation of neuronal adenosine A(1) receptors stabilizes the intrinsic cardiac nervous system during reperfusion.

Adenosine↗
PubMed2002

Long-term modulation of the intrinsic cardiac nervous system by spinal cord neurons in normal and ischaemic hearts.

Electrical excitation of the dorsal aspect of the rostral thoracic spinal cord imparts long-term therapeutic benefits to patients with angina pectoris. Such spinal cord stimulation also induces short-term suppressor effects on the intrinsic cardiac nervous system. The purpose of this study was to determine whether spinal cord stimulation (SCS) induces long-term effects on the intrinsic nervous system, particularly in the presence of myocardial ischaemia. The activity generated by right atrial neurons was recorded in 10 anesthetized dogs during basal states, during prolonged (15 min) occlusion of the left anterior descending coronary artery, and during the subsequent reperfusion phase. Neuronal activity and cardiovascular indices were also monitored when the dorsal T1-T4 segments of the spinal cord were stimulated electrically (50 Hz; 0.2 ms) at an intensity 90% of motor threshold (mean 0.32 mA) for 17 min. SCS was performed before, during and after 15-min periods of regional ventricular ischaemia. Occlusion of a major coronary artery, one that did not perfuse investigated neurons, resulted in their excitation. Ischaemia-induced neuronal excitatory effects were suppressed (-76% from baseline) by SCS. SCS suppression of intrinsic cardiac neuronal activity persisted during the subsequent reperfusion period; after terminating 17 min of SCS, at least 20 min elapsed before intrinsic cardiac neuronal activity returned to baseline values. It is concluded that populations of intrinsic cardiac neurons are activated by inputs arising from the ischaemic myocardium. Ischaemia-induced activation of these neurons is nullified by SCS. The neuronal suppressor effects that SCS induces persist not only during reperfusion, but also for an extended period of time thereafter. These long-term effects may account, in part, for the fact that SCS imparts clinical benefit to patients with angina of cardiac origin not only during its application, but also for a time thereafter.

Action Potentials↗
PubMed2002

Role of P(1) purinergic receptors in myocardial ischemia sensory transduction.

OBJECTIVES: To characterize the role that cardiac sensory P(1) purinergic (adenosine A(1) or A(2)) receptors play in transducing myocardial ischemia. METHODS: Porcine nodose ganglion cardiac sensory neuron adenosine A(1) or A(2) receptor function was studied in situ during control states as well as in the presence of the peptides bradykinin and substance P or focal ventricular ischemia. The responses of porcine nodose ganglion cardiac and non-cardiac afferent neuronal somata to adenosine were also studied in vitro. RESULTS: Local application of A(1) or A(2) adenosine receptor agonists modified the activity generated by ventricular sensory neurites associated with 70 and 74% of identified nodose ganglion cardiac afferent somata in situ, respectively, exciting most neurons. In contrast, adenosine reduced the excitability of nodose ganglion cardiac afferent neuronal somata in vitro. Bradykinin and substance P affected 56 and 63%, respectively, of tested afferent neurons. The capacity of ventricular sensory neurites to transduce signals relating to these peptides was virtually eliminated by the presence of P(1) purinergic receptor antagonists. So was their capacity to transduce focal ventricular ischemia. Since most cardiac sensory neurites responded differently to adenosine in vivo than did cardiac afferent neuronal somata in vitro, it appears that the transduction properties of cardiac afferent neurons need to be characterized in situ. CONCLUSIONS: Most ventricular sensory neurites associated with nodose ganglion afferent neurons possess adenosine A(1) and/or A(2) receptors that play a primary role in transducing myocardial ischemic events to central neurons. These data support clinical observations implicating cardiac sensory purinoceptors in transducing myocardial ischemic events.

Adenosine↗
PubMed2001

Transmyocardial laser revascularization remodels the intrinsic cardiac nervous system in a chronic setting.

BACKGROUND: Prospective trials have demonstrated that transmyocardial laser revascularization (TMLR) imparts symptomatic relief to patients with refractory angina. Because peak clinical effectiveness of TMLR is usually delayed by several months, it has been proposed that ventricular denervation is one mechanism whereby TMLR imparts symptomatic relief. We have demonstrated that TMLR does not denervate the heart in the acute setting, nor does it modify the intrinsic cardiac nervous system (ICNS) in the acute setting. However, the long-term effects of TMLR on the ICNS remain unknown. METHODS AND RESULTS: A holmium:yttrium-aluminum-garnet laser created 20 channels through the anterolateral left ventricular free wall of 10 dogs. Four weeks later, the function of cardiac sensory inputs to the ICNS was studied by applying veratridine (7.5 micromol/L) to ventricular sensory fields. Chronotropic and inotropic responses elicited by cardiac sympathetic or parasympathetic efferent neurons stimulated electrically (10 Hz, 4 V, 4 ms) or chemically (nicotine 5 to 20 microgram/kg IV) were also assessed. Chemical activation of epicardial sensory neurites with veratridine elicited expected ICNS excitatory responses. Electrical stimulation of sympathetic and parasympathetic efferent neurons induced expected altered cardiac responses. In contrast, the responsiveness of the ICNS to systemically administered nicotine was obtunded. CONCLUSIONS: Although chronic TMLR does not affect cardiac afferent or extracardiac efferent neuronal function, it does "remodel" the ICNS so that its responsiveness to a known potent chemical agonist (ie, nicotine) becomes obtunded. Remodeling of the ICNS may account in part for the delayed symptomatic relief that TMLR imparts to patients with refractory angina.

Action Potentials↗
PubMed2001

Responsiveness of intrinsic cardiac neurons to left atrial and hypothalamic cardioactive peptides.

This study was designed to investigate whether cardioactive peptides derived from left atrial tissue or the hypothalamus modulate neurons within the intrinsic cardiac nervous system. Peptides derived from left atrial or left auricular tissues with known coronary artery dilator properties were administered (0.1 ml; 100 microM dose) individually over 10-s periods into the arterial blood supply of ventral ventricular neurons in 11 anesthetized pigs (19-28 kg). Similarly, three hypothalamic protein-hormonal complexes that express coronary artery vasodilator properties, protein-hormone complexes C, G and K, were studied. Each peptide modified the activity generated by some of the neurons identified in a locus of the ventral ventricular ganglionated plexus of each animal. The hypothalamic peptides elicited primarily excitatory responses, whereas the atrial ones induced more suppressor than excitatory responses. Cardiovascular indices remained unchanged overall, indicating that observed neuronal effects were not secondary to cardiodynamic alterations. These data indicate that intrinsic cardiac neurons are sensitive to left atrial and hypothalamic peptides that exhibit coronary artery dilator properties.

Action Potentials↗
PubMed2001

Neuromodulation therapy does not influence blood flow distribution or left-ventricular dynamics during acute myocardial ischemia.

OBJECTIVES: Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). METHODS: In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. RESULTS: SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. CONCLUSIONS: SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

Acute Disease↗
PubMed2001

Competition model for aperiodic stochastic resonance in a Fitzhugh-Nagumo model of cardiac sensory neurons.

Regional cardiac control depends upon feedback of the status of the heart from afferent neurons responding to chemical and mechanical stimuli as transduced by an array of sensory neurites. Emerging experimental evidence shows that neural control in the heart may be partially exerted using subthreshold inputs that are amplified by noisy mechanical fluctuations. This amplification is known as aperiodic stochastic resonance (ASR). Neural control in the noisy, subthreshold regime is difficult to see since there is a near absence of any correlation between input and the output, the latter being the average firing (spiking) rate of the neuron. This lack of correlation is unresolved by traditional energy models of ASR since these models are unsuitable for identifying "cause and effect" between such inputs and outputs. In this paper, the "competition between averages" model is used to determine what portion of a noisy, subthreshold input is responsible, on average, for the output of sensory neurons as represented by the Fitzhugh-Nagumo equations. A physiologically relevant conclusion of this analysis is that a nearly constant amount of input is responsible for a spike, on average, and this amount is approximately independent of the firing rate. Hence, correlation measures are generally reduced as the firing rate is lowered even though neural control under this model is actually unaffected.

Animals↗
PubMed2001

Transduction capabilities of neonatal ventricular afferent neurons in vivo.

We sought to determine the capacity of ventricular sensory nerve endings (neurites) associated with neonatal nodose ganglion afferent neurons to transduce mechanical and chemical stimuli in situ. Spontaneous activity generated by 17 nodose ganglion cardiac afferent neurons was identified in 8 anesthetized neonatal pigs (10-21 days old) using extracellular recording recording techniques. The activity generated by afferent neurons was studied when their ventricular sensory neurites were exposed to local mechanical or chemical stimuli, following systemic administration of specific chemicals or during brief periods of apnea. Gentle mechanical distortion of their ventricular sensory fields enhanced the activity generated by 6 spontaneously active afferent neurons, while suppressing the activity generated by another 3 neurons. Afferent neuronal activity was either enhanced or suppressed when the following chemicals were applied to identified ventricular epicardial sensory fields: the sodium channel modifier veratridine (92% of tested neurons); the P1-purinoceptor agonist adenosine (92%); the neuropeptides angiotensin II (100%), bradykinin (90%) and substance P (90%); and the nitric oxide donor S-nitroso-N-acetylpenicillamine (100%). Epicardial application of isoproternol or nicotine induced modest neuronal responses. Cardiac afferent neurons were also affected when these chemicals were administered systemically. Apnea of 60-100 s duration modified (enhanced, n = 2; suppressed, n = 5) the activity generated by most identified afferent neurons. The estimated average conduction velocity of afferent axons associated with these neurons was 1.0 +/- 0.2 m/s. It is concluded that neonatal nodose ganglion cardiac afferent neurons respond to many of the chemicals known to modify adult cardiac afferent neurons. That cardiac afferent neurons are capable of sensing the mechanical and chemical milieu of the neonatal heart should be taken into account when considering altered neonatal cardiovascular status such as occurs during apnea.

Action Potentials↗
PubMed2001

A highly variable segment of human subterminal 16p reveals a history of population growth for modern humans outstide Africa.

We have sequenced a highly polymorphic subterminal noncoding region from human chromosome 16p13.3 flanking the 5' end of the hypervariable minisatellite MS205, in 100 chromosomes sampled from different African and Euroasiatic populations. Coalescence analysis indicates that the time to the most recent common ancestor (approximately 1 million years) predates the appearance of anatomically modern human forms. The root of the network describing this variability lies in Africa. African populations show a greater level of diversity and deeper branches. Most Euroasiatic variability seems to have been generated after a recent out-of-Africa range expansion. A history of population growth is the most likely scenario for the Euroasiatic populations. This pattern of nuclear variability can be reconciled with inferences based on mitochondrial DNA.

Africa↗
PubMed2001

Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using multiprobe telomeric FISH and the new MAPH telomeric assay.

Subtelomeric chromosomal abnormalities are emerging as an important cause of human genetic disorders. The scope of this investigation was to screen a selected group of children with idiopathic mental retardation for subtelomeric anomalies using the multiprobe telomeric FISH method and also to develop and test a new assay, the MAPH telomeric assay, in the same group of patients. The new MAPH telomeric assay uses the recently published MAPH methodology that permits the measurement of locus copy number by hybridisation with a specifically designed set of probes located at the end of human chromosomes. Seventy patients with idiopathic mental retardation have been screened using the established multiprobe telomeric FISH assay and the new MAPH telomeric assay, for all telomeres. One patient with de novo 8p subtelomeric deletion was identified. The new MAPH telomeric assay confirmed the same results in both normal and abnormal samples. This is the first description of the use of MAPH methodology to detect chromosomal imbalances near the telomeres in idiopathic mentally retarded patients. The new MAPH telomeric assay offers a new, fast, accurate and cost effective diagnostic tool to detect chromosomal imbalances near telomeres in mentally retarded patients, as well as the characterisation of known chromosomal abnormalities, spontaneous recurrent miscarriages, infertility, hematological malignancies, preimplantation genetic diagnosis, and other fields of clinical and research interests.

Adolescent↗