Biomedical subjects

K B Bach

Publications and source records attributed to K B Bach.

8 recordsLinked to original sources

PubMed1998

Cervical dorsal rhizotomy enhances serotonergic innervation of phrenic motoneurons and serotonin-dependent long-term facilitation of respiratory motor output in rats.

We tested the hypothesis that spinal plasticity elicited by chronic bilateral cervical dorsal rhizotomy (C3-C5; CDR) has functional implications for respiratory motor control. Surgery was performed on rats (CDR or sham-operated) 26 d before phrenic motoneurons were retrogradely labeled with cholera toxin. Rats were killed 2 d later, and their spinal cords were harvested and processed to reveal the cholera toxin-labeled phrenic motoneurons and serotonin-immunoreactive terminals. The number of serotonin-immunoreactive terminals within 5 micrometer of labeled phrenic motoneuron soma and primary dendrites increased 2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses to hypoxia were compared among CDR, sham-operated, and control rats. Anesthetized, paralyzed, vagotomized, and artificially ventilated rats were exposed to three, 5 min episodes of isocapnic hypoxia (FiO2 = 0.11), separated by 5 min hyperoxic intervals (FiO2 = 0.5). One hour after hypoxia, a long-lasting, serotonin-dependent enhancement of phrenic motor output (long-term facilitation) was observed in both sham and control rats. After CDR, long-term facilitation was 108 and 163% greater than control and sham responses, respectively. Pretreatment of CDR rats with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v.) before episodic hypoxia prevented long-term facilitation and revealed a modest (-28 +/- 13%; p < 0.05) long-lasting depression of phrenic motor output. The results indicate that CDR: (1) increases serotonergic innervation of the phrenic motor nucleus; and (2) augments serotonin-dependent long-term facilitation of phrenic motor output. These results further suggest a form of plasticity based on changes in the capacity for neuromodulation.

Action Potentials↗

PubMed1998

Hypercapnia-induced long-term depression of respiratory activity requires alpha2-adrenergic receptors.

We investigated the effects of repeated hypercapnic episodes (inspired CO2 fraction = 0.10) on posthypercapnic respiratory nerve discharge. Anesthetized (urethan), vagotomized, and artificially ventilated rats were presented with three consecutive 5-min episodes of hyperoxic hypercapnia, separated by 5 min of hyperoxic normocapnia (inspired O2 fraction = 0.5). Respiratory nerve discharge and blood gases were recorded before and 30 and 60 min after the final hypercapnic episode. Posthypercapnia, arterial PCO2 was maintained within 1 Torr of initial baseline values. Integrated phrenic and hypoglossal burst amplitudes decreased posthypercapnia by up to 46 +/- 17 and 55 +/- 13% of baseline values, respectively, and remained reduced for at least 1 h [long-term depression (LTD)]. The protocol was repeated in rats pretreated with the alpha2-adrenergic antagonists yohimbine HCl (0.5 mg/kg; n = 7) or 2-[2-(2-methoxy-1,4-benzodioanyl)]imidazoline (RX-821002) HCl (0.25 mg/kg; n = 3). Both drugs attenuated LTD in the phrenic and hypoglossal neurograms. Results indicate that episodic hypercapnia elicits a yohimbine- and RX-821002-sensitive LTD of respiratory nerve activity in rats, suggesting that LTD requires alpha2-receptor activation.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1997

Modulation of ventilatory control during exercise.

The control of ventilatory responses to mild or moderate dynamic exercise has been the subject of considerable debate for over a century. The prevailing view has been that the ventilatory response to exercise is stereotypical and rather unmalleable. However, paradigms involving novel associations of stimulus inputs have been shown to modulate breathing in short and longer time scales. The scope of this review includes examples of modified ventilatory responses to exercise which have been investigated in terms of neural mechanisms. An attempt to synthesise the available data into a model of neuromodulation is presented.

Animals↗

PubMed1996

Hypoxia-induced long-term facilitation of respiratory activity is serotonin dependent.

Repeated isocapnic hypoxia evokes long-term facilitation (LTF) of phrenic nerve activity in rats. We wished to determine: (1) whether hypoxia-induced LTF is serotonin dependent; and (2) whether hypoxia-induced LTF is a property of upper airway motoneurons. Phrenic and hypoglossal nerve activities were recorded in urethane anesthetized, vagotomized, paralyzed and artificially ventilated rats (n = 7). Rats were exposed to three, 5-min hypoxic episodes (FIo2 = 0.10) separated by 5 min of hyperoxia (FIo2 = 0.50). One hour after the final hypoxic episode, integrated phrenic and hypoglossal amplitudes and burst frequency were increased above control values (63 +/- 17%, 78 +/- 26% and 9.6 +/- 2.1 bursts/min, respectively: p < 0.05). In rats pretreated with methysergide (n = 7; 4 mg/kg), no changes in phrenic or hypoglossal activity from pre-stimulus control values were observed at any time post-stimulation. The results indicate that hypoxia-induced LTF requires 5-HT receptors and is characteristic of both hypoglossal and phrenic motor output.

Anesthesia, General↗

PubMed1995

Phrenic responses to contralateral spinal stimulation in rats: effects of old age or chronic spinal hemisection.

Serotonin reveals ineffective spinal pathways from the C2-lateral funiculus to contralateral phrenic motoneurons in young adult rats with acute spinal hemisection. We tested the hypothesis that old age (1.5-2 years) or chronic hemisection (3-5 days) strengthens these pre-existing crossed spinal pathways. There were no consistent differences between young adult rats with acute hemisection versus young adult rats with chronic hemisection or old rat with acute hemisection except that one long-latency phrenic excitation could not be elicited in old rats. The results indicate that neither old age nor chronic hemisection strengthens crossed-spinal pathways, but that old age may selectively diminish spinal pathways involved in the neural control of breathing.

5-Hydroxytryptophan↗

PubMed1994

Serotonin reveals ineffective spinal pathways to contralateral phrenic motoneurons in spinally hemisected rats.

Serotonin reveals ineffective (subthreshold) pathways from the C2 lateral funiculus to ipsilateral phrenic motoneurons in spinalized rats. The objective of the present study was to investigate serotonergic modulation of crossed-spinal pathways to contralateral phrenic motoneurons. Rats (n = 10) were anesthetized (urethane), paralyzed, vagotomized, and artificially ventilated. The spinal cord was hemisected at C1-C2 and, on the intact side, a tungsten stimulating electrode was placed ventral to the C2 dorsal root entry zone in the dorsolateral (approximately 1.1 mm) or the ventrolateral funiculus (approximately 2.2 mm depth). Single shocks (100-750 microA, 0.1-0.5 ms, 2 Hz) elicited a short-latency (approximately 1.0 ms to peak) excitation in the ipsilateral phrenic nerve, but usually evoked little or no response in the contralateral phrenic nerve at either stimulus site. Following systemic injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) and the serotonin precursor 5-hydroxytryptophan (5-10 mg/kg), complex responses were revealed in the contralateral phrenic nerve, including: (1) spontaneous tonic activity; (2) a short-latency (approximately 1.0 ms to peak) evoked excitation; and (3) two long-latency (approximately 2.2 and 7.8 ms to peak) evoked excitations. The longest latency excitation was expressed only when the stimulating electrode was positioned in the dorsolateral funiculus. Contralateral evoked responses were blocked by systemic methysergide (2-6 mg/kg), a broad-spectrum serotonin receptor antagonist. These results indicate that serotonin converts ineffective crossed phrenic pathways in the spinal cord to effective pathways. It remains to be determined whether serotonin is both necessary and sufficient in this modulatory process, or if it is a nonspecific result of increased phrenic motoneuron excitability.

5-Hydroxytryptophan↗

PubMed1993

Serotonin is necessary for short-term modulation of the exercise ventilatory response.

The exercise ventilatory response is augmented during conditions of increased respiratory dead space (delta Vd), a phenomenon that we refer to as short term modulation (STM). To test the hypothesis that serotonin is necessary in the mechanism underlying STM, experiments were conducted on ten awake goats. Ventilation, CO2 production and PaCO2 were measured at rest and during treadmill exercise (4 km/h, 5% grade), with and without delta Vd (0.25 L), before and after systemic administration of the serotonin receptor antagonist, methysergide maleate (n = 6; 1 mg/kg, i.v.), or the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (PCPA; n = 4; 100 mg/kg, i.v.). Pre-methysergide: (1) PaCO2 decreased from rest to exercise to a similar degree with (-1.9 mmHg) and without (-1.8 mmHg) delta Vd; (2) the exercise ventilatory response increased 59% +/- 13% (P < 0.01) with delta Vd, accounting for similar exercise PaCO2 regulation and demonstrating STM; and (3) effects of delta Vd on exercise tidal volume and frequency responses were inconsistent. Post-methysergide: (1) there were no significant effects on ventilation or PaCO2 at rest or during exercise in control (mask) conditions; (2) the exercise ventilatory response was unaffected by delta Vd, thereby allowing PaCO2 to increase 4.1 +/- 3.0 mmHg from rest to exercise (P < 0.05); and (3) with delta Vd during exercise, the tidal volume response was increased, but was offset by a decreased frequency response. Following PCPA (16-24 h): (1) hyperventilation was evident at rest and during exercise; (2) the exercise ventilatory response was augmented, indicating STM; and (3) the exercise ventilatory response with delta Vd was not affected further, allowing PaCO2 to increase from rest to exercise and indicating an inability to elicit further STM. These data suggest that serotonin is necessary for short term modulation of the exercise ventilatory response with increased respiratory dead space, although the location of relevant serotonin receptors is not yet clear.

Animals↗

PubMed1993

Time-dependent phrenic nerve responses to carotid afferent activation: intact vs. decerebellate rats.

The objectives were to determine 1) respiratory responses to carotid chemoreceptor inputs in anesthetized rats and 2) whether the cerebellar vermis plays a role in these responses. A carotid sinus nerve was stimulated (20 Hz) with five 2-min trains, each separated by approximately 3 min. During stimulation, respiratory frequency (f), peak amplitude of integrated phrenic nerve activity (integral of Phr), and their product (f x integral of Phr) immediately increased. As stimulation continued, integral of Phr progressively increased to a plateau [short-term potentiation (STP)], but f and f x integral of Phr decreased [short-term depression (STD)] to a value still above control. Upon stimulus termination, integral of Phr progressively decreased but remained above control; f and f x integral of Phr transiently decreased below baseline. After the final stimulation, integral of Phr remained above control for at least 30 min [long-term facilitation (LTF)]. Repeated 5-min episodes of isocapnic hypoxia also elicited STP, STD, and LTF. Vermalectomy lowered the CO2-apneic threshold and eliminated LTF. In conclusion, carotid chemoreceptor activation in rats elicits STP and LTF similar to that in cats; the vermis may play a role in LTF. A new response, STD, was observed.

Afferent Pathways↗