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Biomedical subjects

M R Hodges

Publications and source records attributed to M R Hodges.

At least 19 recordsLinked to original sources
PubMed2006

CO2/H+ chemoreceptors in the cerebellar fastigial nucleus do not uniformly affect breathing of awake goats.

Our objective in this study was to test the hypothesis that focal acidosis (FA) in the cerebellar fastigial nucleus (CFN) of awake goats arising from global brain acidosis induced by increasing inspired CO2 will increase breathing. FA was created by reverse microdialysis of mock cerebral spinal fluid, equilibrated with 6.4, 25, 50, or 80% CO2 through chronically implanted microtubules (cannula). Dialysis with 6.4% CO2 had no significant effects on any physiological parameters. However, microdialysis at higher levels of CO2 increased pulmonary ventilation (V(I)) in one group of studies and decreased V(I) in a second group and the difference between the groups was significant (t = 9.16, P < 0.001). In one group of studies (n = 8), FA with 50 and 80% CO2 significantly increased (P < 0.05) Vi by 16 and 12%, respectively, and significantly increased (P < 0.05) heart rate by 13 and 9%, respectively. In contrast, in another group of studies (n = 6), FA with 25 and 50% CO2 significantly decreased (P < 0.05) Vi by 7 and 10%, respectively. In this group oxygen consumption was decreased during dialysis with 80% CO2. On the basis of histology, we estimate that the increased and decreased responses were associated with FA primarily in the rCFN and cCFN, respectively. We conclude that there are CO2/H+-sensitive neurons in the CFN that do not uniformly affect breathing. In addition, the significant changes in heart rate and oxygen consumption during FA indicate that the CFN can also influence non-respiratory-related control systems.

Acidosis, Respiratory↗
PubMed2005

Homing in on the specific phenotype(s) of central respiratory chemoreceptors.

To some it may seem that we now know less about respiratory chemoreception than we did 20 years ago. Back then, it was widely accepted that the central respiratory chemoreceptors (CRCs) were located exclusively on or near the surface of the ventrolateral medulla (VLMS). Now, instead, it is generally believed that there are widespread sites of chemoreception, and there is little agreement on when and how each of these sites is involved in respiratory control. However, those in the field know that this actually is progress, primarily because we have gone from simply identifying candidate regions, to identifying specific neuronal subtypes that may be the sensors. In this invited review, we have been asked to discuss some of the current controversies in the field. First, we define the minimal requirements for a cell to be a CRC, and what assumptions can not be made without more data. Then we review the evidence that two neuronal subtypes, serotonergic neurones of the midline raphe and glutamatergic neurones of the retrotrapezoid nucleus, are chemoreceptors. There is evidence supporting a role in respiratory chemoreception for both types of neurone, as well as the other candidates, but there is also information that is missing. Future work will need to focus on which of the candidates are indeed chemoreceptors, what percentage of the overall response each one contributes, and how this percentage varies under different conditions.

Animals↗
PubMed2004

Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe.

Our aim was to determine the effects of carotid body denervation (CBD) on the ventilatory responses to focal acidosis and ibotenic acid (IA) injections into the medullary raphe area of awake, adult goats. Multiple microtubules were chronically implanted into the midline raphe area nuclei either before or after CBD. For up to 15 days after bilateral CBD, arterial PCO2 (PaCO2) (13.3 +/- 1.9 Torr) was increased (P < 0.001), and CO2 sensitivity (-53.0 +/- 6.4%) was decreased (P <0.001). Thereafter, resting PaCO2 and CO2 sensitivity returned (P <0.01) toward control, but PaCO2 remained elevated (4.8 +/- 1.9 Torr) and CO2 sensitivity reduced (-24.7 +/- 6.0%) > or =40 days after CBD. Focal acidosis (FA) at multiple medullary raphe area sites 23-44 days post-CBD with 50 or 80% CO(2) increased inspiratory flow (Vi), tidal volume (Vt), metabolic rate (VO2), and heart rate (HR) (P <0.05). The effects of FA with 50% CO2 after CBD did not differ from intact goats. However, CBD attenuated (P <0.05) the increase in Vi, Vt, and HR with 80% CO2, but it had no effect on the increase in VO2. Rostral but not caudal raphe area IA injections increased Vi, BP, and HR (P < 0.05), and these responses were accentuated (P <0.001) after CBD. CO2 sensitivity was attenuated (-20%; P <0.05) <7 days after IA injection, but thereafter it returned to prelesion values in CBD goats. We conclude the following: 1) the attenuated response to FA after CBD provides further evidence that the carotid bodies provide a tonic facilitory input into respiratory control centers, 2) the plasticity after CBD is not due to increased raphe chemoreceptor sensitivity, and 3) the "error-sensing" function of the carotid body blunts the effect of strong stimulation of the raphe.

Acidosis↗
PubMed2004

Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats.

The major objective of this study was to gain insight into whether under physiological conditions medullary raphe area neurons influence breathing through CO(2)/H(+) chemoreceptors and/or through a postulated, nonchemoreceptor modulatory influence. Microtubules were chronically implanted into the raphe of adult goats (n = 13), and breathing at rest (awake and asleep), breathing during exercise, as well as CO(2) sensitivity were assessed repeatedly before and after sequential injections of the neurotoxins saporin conjugated to substance P [SP-SAP; neurokinin-1 receptor (NK1R) specific] and ibotenic acid (IA; nonspecific glutamate receptor excitotoxin). In all goats, microtubule implantation alone resulted in altered breathing periods, manifested as central or obstructive apneas, and fractionated breathing. The frequency and characteristics of the altered breathing periods were not subsequently affected by injections of the neurotoxins (P > 0.05). Three to seven days after SP-SAP or subsequent IA injection, CO(2) sensitivity was reduced (P < 0.05) by 23.8 and 26.8%, respectively, but CO(2) sensitivity returned to preinjection control values >7 days postinjection. However, there was no hypoventilation at rest (awake, non-rapid eye movement sleep, or rapid eye movement sleep) or during exercise after these injections (P > 0.05). The neurotoxin injections resulted in neuronal death greater than three times that with microtubule implantation alone and reduced (P < 0.05) both tryptophan hydroxylase-expressing (36%) and NK1R-expressing (35%) neurons at the site of injection. We conclude that both NK1R- and glutamate receptor-expressing neurons in the medullary raphe nuclei influence CO(2) sensitivity apparently through CO(2)/H-expressing chemoreception, but the altered breathing periods appear unrelated to CO(2) chemoreception and thus are likely due to non-chemoreceptor-related neuromodulation of ventilatory control mechanisms.

Animals↗
PubMed2004

Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats.

To gain insight into why there are chemoreceptors at widespread sites in the brain, mircrotubules were chronically implanted at two or three sites in the medullary raphe nuclei of adult goats (n = 7). After >2 wk, microdialysis (MD) probes were inserted into the microtubules to create focal acidosis (FA) in the awake state using mock cerebral spinal fluid (mCSF) equilibrated with 6.4% (pH = 7.3), 50% (pH = 6.5), or 80% CO(2) (pH = 6.3), where MD with 50 and 80% CO(2) reduces tissue pH by 0.1 and 0.18 pH unit, respectively. There were no changes in all measured variables with MD with 6.4% at single or multiple raphe sites (P > 0.05). During FA at single raphe sites, only 80% CO(2) elicited physiological changes as inspiratory flow was 16.9% above (P < 0.05) control. However, FA with 50 and 80% CO(2) at multiple sites increased (P < 0.05) inspiratory flow by 18.4 and 30.1%, respectively, where 80% CO(2) also increased (P < 0.05) tidal volume, heart rate, CO(2) production, and O(2) consumption. FA with 80% CO(2) at multiple raphe sites also led to hyperventilation (-2 mmHg), indicating that FA had effects on breathing independent of an increased metabolic rate. We believe these findings suggest that the large ventilatory response to a global respiratory brain acidosis reflects the cumulative effect of stimulation at widespread chemoreceptor sites rather than a large stimulation at a single site. Additionally, focal acidification of raphe chemoreceptors appears to activate an established thermogenic response needed to offset the increased heat loss associated with the CO(2) hyperpnea.

Acidosis, Respiratory↗
PubMed2004

Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex area induces abnormal breathing periods in awake goats.

In awake rats, >80% bilateral reduction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Bötzinger complex (pre-BötzC) resulted in hypoventilation and an "ataxic" breathing pattern (Gray PA, Rekling JC, Bocchiaro CM, Feldman JL, Science 286: 1566-1568, 1999). Accordingly, the present study was designed to gain further insight into the role of the pre-BötzC area NK1R-expressing neurons in the control of breathing during physiological conditions. Microtubules were chronically implanted bilaterally into the medulla of adult goats. After recovery from surgery, the neurotoxin saporin conjugated to substance P, specific for NK1R-expressing neurons, was bilaterally injected (50 pM in 10 microl) into the pre-BötzC area during the awake state (n = 8). In unoperated goats, 34 +/- 0.01% of the pre-BötzC area neurons are immunoreactive for the NK1R, but, in goats after bilateral injection of SP-SAP into the pre-BötzC area, NK1R immunoreactivity was reduced to 22.5 +/- 2.5% (29% decrease, P < 0.01). Ten to fourteen days after the injection, the frequency of abnormal breathing periods was sixfold greater than before injection (107.8 +/- 21.8/h, P < 0.001). Fifty-six percent of these periods were breaths of varying duration and volume with an altered respiratory muscle activation pattern, whereas the remaining were rapid, complete breaths with coordinated inspiratory-expiratory cycles. The rate of occurrence and characteristics of abnormal breathing periods were not altered during a CO2 inhalation-induced hyperpnea. Pathological breathing patterns were eliminated during non-rapid eye movement sleep in seven of eight goats, but they frequently occurred on arousal from non-rapid eye movement sleep. We conclude that a moderate reduction in pre-BötzC NK1R-expressing neurons results in state-dependent transient changes in respiratory rhythm and/or eupneic respiratory muscle activation patterns.

Animals↗
PubMed2004

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats.

In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex (pre-BötzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BötzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-BötzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/- 10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately 60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (approximately 90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-BötzC area were lesioned in these goats. We conclude that, in the awake state, the pre-BötzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-BötzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.

Animals↗
PubMed2003

Effects on breathing in awake and sleeping goats of focal acidosis in the medullary raphe.

Our aim was to determine the effects of focal acidification in the raphe obscurus (RO) and raphe pallidus (RP) on ventilation and other physiological variables in both the awake and sleep states in adult goats. Through chronically implanted microtubules, 1) a focal acidosis was created by microdialysis of mock cerebrospinal fluid (mCSF), equilibrated with various levels of CO2, and 2) medullary extracellular fluid (ECF) pH was measured by using a custom-made pH electrode. Focal acidosis in the RO or RP, by dialyzing either 25 or 80% CO2 (mCSF pH approximately 6.8 or 6.3), increased (P < 0.05) inspiratory flow by 8 and 12%, respectively, while the animals were awake during the day, but not at night while they were awake or in non-rapid eye movement sleep. While the animals were awake during the day, there were also increases in heart rate and blood pressure (P < 0.05) but no significant change in metabolic rate or arterial Pco2. Dialysis with mCSF equilibrated with 25 or 80% CO2 reduced ECF pH by the same amount (25%) or three times more (80%) than when inspired CO2 was increased to 7%. During CO2 inhalation, the reduction in ECF pH was only 50% of the reduction in arterial pH. Finally, dialysis in vivo only decreased ECF pH by 19.1% of the change during dialysis in an in vitro system. We conclude that 1) the physiological responses to focal acidosis in the RO and RP are consistent with the existence of chemoreceptors in these nuclei, and 2) local pH buffering mechanisms act to minimize changes in brain pH during systemic induced acidosis and microdialysis focal acidosis and that these mechanisms could be as or more important to pH regulation than the small changes in inspiratory flow during a focal acidosis.

Acidosis↗
PubMed2003

Do genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to regulation of breathing?

As part of a large scale, high through-put physiologic genomics study, we sought to determine whether genes on rat chromosomes 9, 13, 16, 18, and 20 contribute to phenotypic differences in the control of breathing between two inbred rat strains (SS/Mcw and BN/Mcw). Through a chromosomal substitution breeding strategy, we created 5 consomic rat strains (SS.BN9, SS.BN13, SS.BN16, SS.BN18, and SS.BN20), which were BN/Mcw homozygous at only one chromosome and SS/Mcw homozygous at all other chromosomes. Standard plethsmography was used to assess eupneic breathing and ventilatory responses to CO(2) (FI(CO(2))=0.07) and hypoxia (FI(CO(2))=0.12), and Pa(CO(2)) during treadmill exercises provided the index of the exercise hyperpnea. There were no robust differences in eupneic breathing between any strains. The ventilatory response to CO(2) was 150% greater (P<0.001) in the SS/Mcw rats than in the BN/Mcw rats and all consomic strains had the SS/Mcw phenotype. Hyperventilation during hypoxia did not differ between the parental and the consomic strains, but ventilation during hypoxia was greater (P<0.001) in the SS/Mcw than in the BN/Mcw, and the SS.BN9, and SS.BN18 appeared to acquire this BN/Mcw phenotype. The hyperventilation during treadmill walking was greater (P<0.006) in the BN/Mcw and the SS.BN18 rats than in the SS/Mcw rats. Finally, the duration of the apnea following an augmented breath (post sigh apnea, PSA) was greater (P<0.001) in the BN/Mcw and the SS.BN9 rats than all other strains. We conclude that the robust difference between the parental strains in ventilatory CO(2) sensitivity is not due to genotypic differences on the 5 chromosomes studied to date, but genotypic differences on chromosomes 9 and 18 contribute to differences in ventilatory responses to hypoxia, exercise, and/or to the differences in the PSA.

Animals↗
PubMed2001

Herpes simplex virus dermatitis in patients using latanoprost.

PURPOSE: To describe the possible association of latanoprost with herpetic dermatitis of the periocular skin. METHOD: Interventional case reports. A 79-year-old woman with open-angle glaucoma developed a vesicular dermatitis of the left lower eyelid 14 months after starting latanoprost therapy. An 84-year-old man with pigmentary glaucoma developed a vesicular dermatitis of the right upper lid after 2 months of treatment with latanoprost and 8 days of treatment with tobramycin/dexamethasone for presumed bacterial conjunctivitis. In both cases, the dermatitis was characteristic of a herpetic infection. RESULTS: Latanoprost was discontinued in both cases. The woman was treated with vidarabine 3% ointment, and the man was not treated with antiviral agents. In both patients, the dermatitis healed uneventfully. The lesions of the man were cultured, and a biopsy was performed; herpes simplex virus type 1 was recovered from the culture and confirmed by immunofluorescence testing. CONCLUSION: Latanoprost, which has been associated with reactivation of herpetic keratitis, may also cause reactivation of herpetic dermatitis of the periocular skin.

Aged↗
PubMed2001

Relaxation of postoperative astigmatism after lens implantation through a 6.25 mm scleral wound in children.

PURPOSE: To investigate the evolution of postoperative astigmatism in children having cataract extraction with intraocular lens (IOL) implantation through a 6.25 mm superior scleral tunnel wound. SETTING: A university clinical practice. METHODS: A retrospective chart review of all pediatric patients having cataract extraction and IOL implantation in the practice of 1 surgeon from 1995 to 2000 was performed. Statistical comparisons were performed using the Student t test for nonpaired data. RESULTS: Ten eyes of 9 children were included. Six cataracts were due to corneal or corneoscleral lacerations, 3 were idiopathic, and 1 occurred after blunt trauma. Eight eyes could not be refracted preoperatively because of mature cataract. The mean cylindrical correction of all refractions performed 1 to 15 days after surgery (n = 6) was 6.71 diopters (D) +/- 1.63 (SD); of those performed at 16 to 30 days (n = 6), 2.71 +/- 2.09 D; and of those performed at 31 to 45 days (n = 7), 1.93 +/- 1.48 D. The mean spherical equivalent of the final (dispensed) refraction was -0.21 +/- 1.79 D; the mean cylindrical correction of this refraction was 1.13 +/- 0.79 D. The difference between the cylindrical correction of the final prescription and the corneal astigmatism in fellow eyes was not statistically significant (P =.29). CONCLUSIONS: Relaxation of large amounts of suture-induced astigmatism occurs in children having cataract extraction. Surgeons should not hesitate to secure scleral wounds meticulously in children for fear of a permanent undesirable refractive outcome.

Adolescent↗
PubMed1994

Accuracy of pulse oximetry during hypoxemia.

To determine the accuracy of four pulse oximeters during mild and moderate arterial hypoxemia, we produced stepwise arterial blood desaturation in 25 healthy, nonsmoking volunteers by adjusting the inhaled oxygen concentration. At plateaus of < 80%, 85% to 90%, 90% to 95%, and 95% to 100%, pulse oximetry saturation (SpO2) was measured with the four different monitors: Dinamap Plus Model 8700, Oxyshuttle, Ohmeda 3700, and MiniOx IV. Arterial blood samples were analyzed with a co-oximeter and the arterial oxyhemoglobin saturation (SaO2) was compared with the SpO2 readings at each plateau. Significant deterioration in the accuracy of pulse oximeters was observed as SaO2 decreased. In 14 instances of hypoxemia (SaO2 < 90%), subjects exhibited SpO2 values greater than 90%. In conclusion, the accuracy of pulse oximetry deteriorates as hypoxemia worsens. Confirmation of arterial blood oxyhemoglobin saturation by co-oximetry is necessary when precise determination of arterial oxyhemoglobin level is critical.

Adult↗
PubMed1993

Influence of posture on arm exercise tolerance and physiologic responses in persons with spinal cord injured paraplegia.

This study compared metabolic and cardiopulmonary responses to incremental supine and upright sitting arm crank ergometry (ACE) in nine men with spinal cord injured paraplegia ranging from T1-T5. Both tests consisted of continuous graded ACE from rest to volitional fatigue on a modified electronically braked cycle ergometer with the work rate increased by 8.2 W.min-1. No significant differences (P > 0.05) existed for peak ACE power output (W), oxygen uptake, pulmonary ventilation, respiratory exchange ratio, and O2 pulse between the two tests. Heart rate and O2 pulse responses at six submaximal work rates representing 0-58% peak W were also not significantly different between postures. These data indicate that ACE tolerance in persons with high-lesion paraplegia was not enhanced when ACE was performed in the supine posture.

Adult↗
PubMed1988

Continuous monitoring of gas exchange and oxygen use with dual oximetry.

The utility of integrated pulse and pulmonary artery oximetry, known as dual oximetry, was evaluated by monitoring 10 critically ill surgical patients for a total of 208 patient hours. The ventilation-perfusion index (VQI), an estimate of venous admixture, and the oxygen extraction index (O2EI), an estimate of tissue oxygen utilization coefficient, previously described, were calculated on-line from arterial and mixed venous oxyhemoglobin saturations using a computer. Effective monitoring was accomplished 85% of the total time. The dual oximetry device was nonfunctional owing to equipment failure only 15% of the time, even though no undue attention was given to instructing the staff on operation of the oximeters. Accuracy of VQI and O2EI was reconfirmed by this study. Drift in the saturations, VQI, and O2EI during the 6-h period between calibrations was negligible. The 95% range of random variability was +/- 2% for SaO2, +/- 3% for SvO2, +/- 5% for VQI, and +/- 0.04 for O2EI. Thirty-six episodes of arterial blood desaturation below 90% were detected by continuous oximetry. In contrast, 74 routine arterial blood samples revealed only four such episodes. Dual oximetry appears to be a technically reliable and accurate method of monitoring pulmonary gas exchange and tissue oxygen utilization. The equipment provided stable readings for at least six hours without recalibration. Random variability is sufficiently small to allow early detection of alterations in pulmonary and circulatory function without blood sampling.

Anesthesia, General↗
PubMed1988

Oxygen supplementation during electroconvulsive therapy.

The effects of ventilation with 30% and 100% oxygen were investigated on the circulatory and electrocardiographic response to electroconvulsive therapy (ECT) in 12 patients during 40 treatments. Administration of 30% oxygen resulted in a 25% decrease in seizure duration compared with 100% oxygen (P less than 0.0125). Hypoxaemia, defined as SaO2 less than 90%, occurred during five of 20 treatments with 30% oxygen and during two of 20 treatments with 100% oxygen (ns), and was associated invariably with loss of airway control. Heart rate, arterial pressure, and the incidence of cardiac arrhythmias were not affected significantly by oxygen supplementation. Inspired oxygen concentration has a significant effect on seizure activity and should be of a consistent value if a reproducible seizure is to be produced during ECT. Breathing 100% oxygen does not appear to affect adversely the cardiovascular response to ECT. However, arterial hypoxaemia may develop rapidly during or after the seizure, regardless of oxygen supplementation, if adequate control of airway and ventilation is not maintained.

Adult↗