Potentiation of dietary restriction-induced lifespan extension by polyphenols.

Dietary restriction (DR) extends lifespan across multiple species including mouse. Antioxidant plant extracts rich in polyphenols have also been shown to increase lifespan. We hypothesized that polyphenols might potentiate DR-induced lifespan extension.

Succinylcholine use in adult anesthesia - A multinational questionnaire survey.

There are no definitive evidence based standards regarding use of succinylcholine (SCh) for anesthesia induction. However, there is a global trend toward eliminating SCh not only in elective, but also in emergency surgery in adults. The aim of the study was to survey the use of SCh in adult elective and emergency anesthesia practice in several European countries and the United States by questionnaire.

Opioid receptors on bulbospinal respiratory neurons are not activated during neuronal depression by clinically relevant opioid concentrations.

Opioids depress the activity of brain stem respiratory-related neurons, but it is not resolved whether the mechanism at clinical concentrations consists of direct neuronal effects or network effects. We performed extracellular recordings of discharge activity of single respiratory neurons in the caudal ventral respiratory group of decerebrate dogs, which were premotor neurons with a likelihood of 90%. We used multibarrel glass microelectrodes, which allowed concomitant highly localized picoejection of opioid receptor agonists or antagonists onto the neuron.

Halothane depresses glutamatergic neurotransmission to brain stem inspiratory premotor neurons in a decerebrate dog model.

Background: Inspiratory bulbospinal neurons in the caudal ventral medulla are premotor neurons that drive phrenic motoneurons and ultimately the diaphragm. Excitatory drive to these neurons is mediated by N-methyl-d-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors and modulated by an inhibitory gamma-aminobutyric acid(A) (GABA(A))ergic input. The authors investigated the effect of halothane on these synaptic mechanisms in decerebrate dogs.

Differential processing of excitation by GABAergic gain modulation in canine caudal ventral respiratory group neurons.

The discharge frequency (F(n)) patterns of medullary respiratory premotor neurons are subject to potent tonic GABAergic gain modulation. Studies in other neuron types suggest that the synaptic input for tonic inhibition is located on the soma where it can affect total neuronal output. However, our preliminary data suggested that excitatory responses elicited by highly local application of glutamate receptor agonists are not gain modulated.

Delayed cardioprotection by isoflurane: role of K(ATP) channels.

Isoflurane mimics the cardioprotective effect of acute ischemic preconditioning with an acute memory phase. We determined whether isoflurane can induce delayed cardioprotection, the involvement of ATP-sensitive potassium (K(ATP)) channels, and cellular location of the channels. Neonatal New Zealand White rabbits at 7-10 days of age (n = 5-16/group) were exposed to 1% isoflurane-100% oxygen for 2 h.

Effects of halothane and sevoflurane on inhibitory neurotransmission to medullary expiratory neurons in a decerebrate dog model.

Background: In canine expiratory bulbospinal neurons, 1 minimum alveolar concentration (MAC) halothane and sevoflurane reduced the glutamatergic excitatory drive at a presynaptic site and enhanced the overall gamma-aminobutyric acid (GABA)-mediated inhibitory input. The authors investigated if this inhibitory enhancement was mainly caused by postsynaptic effects.

Methods: Two separate anesthetic studies were performed in two sets of decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia.

Differential modulation of respiratory neuronal discharge patterns by GABA(A) receptor and apamin-sensitive K(+) channel antagonism.

The discharge patterns of respiratory neurons of the caudal ventral respiratory group (cVRG) appear to be subject to potent GABAergic gain modulation. Local application of the GABA(A) receptor antagonist bicuculline methochloride amplifies the underlying discharge frequency (F(n)) patterns mediated by endogenous excitatory and inhibitory synaptic inputs. Gain modulation can also be produced by alterations in the amplitude of spike afterhyperpolarizations (AHPs) mediated by apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK) channels.

Effects of sevoflurane on excitatory neurotransmission to medullary expiratory neurons and on phrenic nerve activity in a decerebrate dog model.

Background: Sevoflurane is a new volatile anesthetic with a pronounced respiratory depressant effect. Synaptic neurotransmission in canine expiratory bulbospinal neurons is mainly mediated by excitatory N-methyl-D-aspartatic acid (NMDA) receptor input and modulated by inhibitory gamma-aminobutyric acid type A (GABA(A)) receptors. The authors investigated the effect of sevoflurane on these mechanisms in decerebrate dogs.

Effects of halothane on excitatory neurotransmission to medullary expiratory neurons in a decerebrate dog model.

Background: The activity of canine expiratory (E) neurons in the caudal ventral respiratory group is primarily dependent on N-methyl-D-aspartic acid (NMDA) receptor-mediated excitatory chemodrive inputs and modulated by an inhibitory mechanism mediated via gamma-aminobutyric acidA (GABA(A)) receptors. In an intact canine preparation, halothane depressed the activity of these neurons mainly by reduction in overall glutamatergic excitation. A new decerebrate preparation allows comparison of the effects of halothane on these synaptic mechanisms with an anesthetic-free baseline state.

Effect of central CO(2) drive on lung inflation responses of expiratory bulbospinal neurons in dogs.

The purpose of these studies is to better understand the nature of the reflex interactions that control the discharge patterns of caudal medullary, expiratory (E) bulbospinal neurons. We examined the effect of central chemodrive inputs measured as arterial CO(2) tension (Pa(CO(2))) during hyperoxia on the excitatory and inhibitory components of the lung inflation responses of these neurons in thiopental sodium-anesthetized, paralyzed dogs. Data from slow ramp inflation and deflation test patterns, which were separated by several control inflation cycles, were used to produce plots of neuronal discharge frequency (F(n)) versus transpulmonary pressure (P(t)).

Relative magnitude of tonic and phasic synaptic excitation of medullary inspiratory neurons in dogs.

The relative contribution of phasic and tonic excitatory synaptic drives to the augmenting discharge patterns of inspiratory (I) neurons within the ventral respiratory group (VRG) was studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microejected antagonists of GABAergic, glycinergic, N-methyl-D-aspartate (NMDA) and non-NMDA glutamatergic, and cholinergic receptors. The discharge patterns were quantified via cycle-trigger histograms.

Effects of halothane on synaptic neurotransmission to medullary expiratory neurons in the ventral respiratory group of dogs.

Background: The activity of canine expiratory neurons is primarily dependent on N-methyl-D-aspartic acid (NMDA)-receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via gamma-aminobutyric acidA (GABA(A)) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism.

Methods: Experiments were performed in halothane-anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia.

Differential roles of ionotropic glutamate receptors in canine medullary inspiratory neurons of the ventral respiratory group.

The relative roles of ionotropic N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in supplying excitatory drive to inspiratory (I) augmenting pattern neurons of the ventral respiratory group were studied in anesthetized, ventilated, paralyzed, and vagotomized dogs. Multibarrel micropipettes were used to record simultaneously single-unit neuronal activity and pressure microeject the NMDA antagonist, 2-amino-5-phosphonovalerate (AP5; 2 mM), the non-NMDA antagonist 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX; 0.25 mM), and an artificial cerebrospinal fluid vehicle.

Differential effects of GABAA receptor antagonists in the control of respiratory neuronal discharge patterns.

To ascertain the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in shaping and controlling the phasic discharge patterns of medullary respiratory premotor neurons, localized pressure applications of the competitive GABAA receptor antagonist bicuculline (BIC) and the noncompetitive GABAA receptor antagonist picrotoxin (PIC) were studied. Multibarrel micropipettes were used in halothane anesthetized, paralyzed, ventilated, vagotomized dogs to record single unit activity from inspiratory and expiratory neurons in the caudal ventral respiratory group and to picoeject GABAA receptor antagonists. The moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histograms of discharge patterns.

Improved method of canine decerebration.

We describe an improved decerebration method for dogs that is suitable for studies of brain stem neurons in the absence of anesthesia. Previously reported techniques of canine decerebration often lead to respiratory and hemodynamic instability and lack of typical decerebrate rigidity. We have developed a precise, visually controlled, midcollicular brain stem transection technique that overcomes these problems.

Modulation of the synaptic drive to respiratory premotor and motor neurons.

The characteristics of GABAergic inhibitory modulation of respiratory bulbospinal neuronal activity and short-term potentiation (STP) of phrenic motoneuronal activity were studied. Extracellular unit recording and picoejection techniques in anesthetized dogs showed that both the spontaneous rhythmic and reflexly induced discharge patterns of inspiratory (I) and expiratory (E) premotor neurons were proportionately amplified by the localized application of picomole amounts of bicuculline (Bic), a competitive GABAA antagonist. Intracellular recording and paired-pulse stimulation techniques in anesthetized rats demonstrated an STP of phrenic motor output that appears to be mediated by NMDA receptors and is associated with facilitation of EPSPs and prolonged depolarization of individual phrenic motoneurons.

Dose-dependent effects of halothane on the carbon dioxide responses of expiratory and inspiratory bulbospinal neurons and the phrenic nerve activities in dogs.

Background: Expiratory bulbospinal and inspiratory bulbospinal neurons in the ventral respiratory group provide drive for thoracoabdominal expiratory and phrenic and thoracic inspiratory motor neurons. Potent inhalational agents such as halothane may have differential effects on inspiratory and expiratory neurons, but detailed studies comparing neurons at a homologous level are lacking.

Methods: The dose-dependent effects of anesthesia with 1.

Interaction between chemoreceptor and stretch receptor inputs at medullary respiratory neurons.

The interaction between afferent inputs from carotid body chemoreceptors (CCRs) and from slowly adapting pulmonary stretch receptors (PSRs) on the discharge patterns of medullary inspiratory (I) and expiratory (E) neurons was characterized in thiopental sodium-anesthetized, paralyzed, ventilated dogs. A cycle-triggered ventilator was used to produce control and test pulmonary afferent input patterns. The CCRs were stimulated by phase-synchronized bolus injections of CO2-saturated saline into the common carotid arteries.

Expiratory bulbospinal neurons of dogs. II. Laterality of responses to spatial and temporal pulmonary vagal inputs.

Pulmonary mechanoreceptors with vagal fibers produce a combination of excitation and inhibition in the majority of the expiratory bulbospinal (EBS) neurons of dogs. Both aspects of this transpulmonary pressure-dependent neuronal response appear to be slowly adapting and activated at low pressure levels, suggesting the involvement of the slowly adapting pulmonary stretch receptors (PSRs). The purpose of the present study was to determine the contribution of different afferent pathways to each of the response components and to characterize the spatial and temporal processing of ipsi-, contra-, and bilateral vagal afferent inputs by two types of EBS neurons.

Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors.

To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps.

Dose-dependent effects of isoflurane on the CO2 responses of expiratory medullary neurons and the phrenic nerve activities in dogs.

Expiratory bulbospinal neurons (EBS) neurons in the region of the nucleus retroambigualis provide a major source of drive for thoracic and abdominal expiratory motoneurons. These studies examined the dose-dependent effects of isoflurane anesthesia from 0.5-2.