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Biomedical subjects

N H West

Publications and source records attributed to N H West.

At least 19 recordsLinked to original sources

Facial immersion bradycardia in teenagers and adults accustomed to swimming.

We compared heart rate and breath-hold duration during facial immersion in teenagers, 11-14 years (N = 6), 15-18 years (N = 6) and adults, 33-48 years (N = 11). The subjects were members of a competitive swimming club, and were familiar with facial immersion. In contrast to the results of a previous study (J. Appl. Physiol. 63 (1987) 665) in which naïve subjects were used, the 11-14 group were able to breath-hold as long as adults (mean +/- SE, 47+/-6 vs. 46+/-4 s). This allowed time for the full development of bradycardia. Pre-immersion heart rate was significantly higher in young teens than in adults (100+/-4 vs. 78+/-3 b.p.m.). Heart rate after 30 s of head immersion was statistically identical (young teens, 65+/-5 b.p.m.; adults, 64+/-3 b.p.m.). Therefore, both the percentage reduction from pre-immersion rate and rate of fall in heart rate were greater in 11-14-year-olds than in adults. Oxygen loading increased breath-hold time in all groups, and slowed the onset of bradycardia in adults and older teens, but not in the 11-14-year-old group, during the first 10 s after immersion. We conclude that breath-hold time in teenagers is influenced by familiarity with underwater breath-holding. The resulting cardiovascular adjustments in 11-14-year-olds are intrinsically at least as intense as those in adults and seem to have a faster onset.

Adolescent↗

Pulmonary vagal modulation of ventilation in toads (Bufo marinus).

This study examined the role of pulmonary vagal feedback on hypercapnic chemosensitivity and breathing pattern formation in cane toads (Bufo marinus). Decerebrate, paralysed toads were uni-directionally ventilated with air, 2.5% CO(2) or 5.0% CO(2) with the lungs inflated or deflated, before and after pulmonary vagotomy. Motor output from the mandibular branch of the trigeminal nerve served as an index of fictive breathing. As respiratory drive was increased, breathing frequency increased and breaths were clustered into discrete episodes separated by periods of apnea. Lung deflation tended to enhance episodic breathing while inflation biased the system towards apnea at low levels of respiratory drive and a pattern of continuous, small breaths at higher levels of respiratory drive. Following bilateral pulmonary vagotomy there was no increase in ventilation during hypercapnia and lung inflation/deflation had no effect on breathing pattern. In isolated brainstem-spinal cord preparations from the same animals, all variables associated with fictive breathing were unaffected by changes in superfusate pH from 8.0 to 7.6. The breathing pattern from the in vitro preparations was highly variable. This study demonstrates a crucial role for vagal feedback in modulating respiration and the respiratory responses to hypercapnia in B. marinus.

Animals↗

Relative distribution of blood flow in rats during surface and submerged swimming.

The relative distribution of blood flow was investigated in conscious rats with a radiological imaging technique that utilizes technetium-99m ethyl cysteinate dimer (99mTc-ECD). The objective of the study was to determine the effects of locomotory activity on the distribution of blood flow during a dive response. We compared the relative distribution of systemic flow in rats at rest, surface swimming and during periods of voluntarily initiated underwater swimming. The pattern of blood flow differed considerably between the three groups of rats. In resting controls, blood flow was widely distributed throughout the whole body with the thoraco-abdominal region receiving the largest fraction of cardiac output. During surface swimming blood shifted towards the exercising limbs, while during underwater swimming systemic blood flow was largely restricted to the head and thorax. However, the active front and hind limbs were not rendered totally ischemic. This suggests that the demands of exercising skeletal muscle partially over-ride the peripheral vasoconstriction during asphyxic diving in conscious rats. Furthermore, relative blood flow to the head increased during underwater swimming, which supports the view that there is a preferential maintenance of blood flow to the brain.

Abdomen↗

Contribution of hypercapnia and trigeminal stimulation to cerebrovascular dilation during simulated diving.

We investigated the relative contribution of humoral (carbon dioxide) and neural (trigeminal stimulation) inputs in the cerebrovasodilatory response to simulated diving in the rat. The cerebral hemodynamic profile of rats was determined using the brain blood flow tracer N-[14C]isopropyl-p-iodoamphetamine. During a simulated dive response, cerebral vascular resistance (CVR) decreased 63.1%, resulting in a 1.5-fold increase in cerebral blood flow (CBF). To investigate the contribution of hypercapnia to the decrease in CVR during simulated diving, we measured CBF during simulated diving in rats with preexisting hypocapnia. To investigate the contribution of trigeminal input, we measured CBF during periods of trigeminal stimulation alone with continued ventilation. Preexisting hypocapnia abolished the cerebrovasodilatory response to simulated diving. Trigeminal stimulation alone did not produce a significant increase in CBF from control values in any brain region, suggesting that trigeminal input does not contribute to the cerebrovascular response to simulated diving in rats. These results suggest that the cerebrovasodilatory response observed during diving in small mammals is driven primarily by progressive hypercapnia associated with asphyxia.

Animals↗

The role of angiotensin in arterial blood pressure regulation in the toad Bufo marinus.

Little is known about the role of the renin-angiotensin system in anuran amphibians, although they appear to possess the functional components of such a system. We investigated the role of angiotensin (ANG) in arterial blood pressure regulation in the conscious toad Bufo marinus using the angiotensin-converting enzyme blocker captopril. We found that conversion of endogenous ANG I to ANG II made a significant contribution to mean arterial pressure in undisturbed animals. The vascular tone contributed by ANG II was not mediated via &agr ; adrenergic mechanisms because increases in pressure in response to ANG infusion were unaffected by the presence of the &agr ; antagonist phentolamine. Angiotensin-induced vasoconstriction was shown to be an important mechanism in arterial blood pressure regulation in the face of an acute hypotensive perturbation of pressure brought about by sodium nitroprusside. Blockade of the conversion of ANG I to ANG II significantly delayed the recovery of mean arterial pressure after sodium nitroprusside-induced hypotension. This suggests that the renin-angiotensin system may play an important role in the initial responses to hypotension in anurans, whether brought about by haemorrhage or dehydration.

Angiotensin II↗

Distribution of regional cerebral blood flow in voluntarily diving rats.

The distribution of regional cerebral blood flow (rCBF) was examined in conscious, voluntarily diving rats using the brain blood flow tracer N-[14C]isopropyl-p-iodoamphetamine and quantitative autoradiography. A detailed examination of the regional distribution of cerebral blood flow revealed that almost all brain regions were hyperperfused during diving. During diving, rCBF increased by an average of 1.7-fold in 29 of the 33 brain regions examined, despite a 69.2 % decrease in cardiac output. Only some regions of the basal ganglia (caudate-putamen and globus pallidus) and limbic areas (hippocampus and amygdala) did not increase rCBF significantly during diving. We determined that the increase in rCBF during diving is primarily due to a corresponding 20.9 % decrease in cerebrovascular resistance. A significant increase in perfusion pressure during diving also potentially contributed to the increase in rCBF. Because some brain regions did not increase flow significantly during diving, these results suggest that not all brain regions participate equally in the global cerebrovascular response to diving. This study provides evidence to support the view that the brain is preferentially perfused during conscious voluntary diving in the rat. The mechanism(s) that probably produce the cerebrovascular changes during diving are discussed.

Animals↗

Trigeminal and chemoreceptor contributions to bradycardia during voluntary dives in rats.

This study investigates the importance of chemoreceptive and trigeminal information during voluntarily initiated diving in rats. The heart rate responses to simulated diving are unaffected by chemoreceptor drive [McCulloch, P.F., and N. H. West. Am. J. Physiol. 263 (Regulatory Integrative Comp. Physiol. 32): R1049-R1056, 1992] but are reversibly eliminated by infusion of glutamate receptor antagonists into the spinal trigeminal nuclei [McCulloch, P. F., I. A. Paterson, and N. H. West. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R669-R677, 1995]. To investigate the role of chemoreceptor drive in conscious dives, rats were made hypercapnic, hyperoxic, or hypoxic predive. The role of trigeminal input was explored by infusing the glutamatergic antagonists D-2-amino-7-phosphoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione into the region of the trigeminal nuclei. The alteration of arterial blood gases predive had no effect on diving bradycardia. Trigeminal blockade reduced the intensity of the bradycardia but did not abolish it. Chemoreceptor input does not play a significant role in determining heart rate during conscious diving in rats. The attenuation, rather than abolition, of bradycardia on trigeminal blockade suggests either that we achieved incomplete blockade or that an additional spectrum of sensory inputs not present in simulated diving is important in determining the underwater heart rate during conscious diving in rats.

Animals↗

An intact glutamatergic trigeminal pathway is essential for the cardiac response to simulated diving.

Nasal water flow plus concomitant expiratory apnea in anesthetized (Innovar-Vet), paralyzed, and artificially ventilated rats produces immediate bradycardia. To investigate the origin of this response, four procedures were used to block the trigeminal pathway. 1) Trigeminal receptors within the nasal passages were anesthetized by infusing local anesthetic through the external nares. 2) Trigeminal nerves that innervate the nasal passages were sectioned bilaterally as they passed through the orbit. 3) The trigeminal neural pathway was blocked within the brain stem by either electrolytically lesioning or infusing local anesthetic into the spinal trigeminal nucleus interpolaris (Sp5I). 4) Synaptic transmission within Sp5I was prevented by infusing glutamate receptor antagonists D-2-amino-7-phosphonoheptanoic acid and 6,7-dinitroquinoxaline-2,3-dione. After each of the procedures was completed, the cardiovascular responses to nasal water flow plus apnea were either attenuated or eliminated. The major conclusion of this study is that an intact glutamatergic trigeminal pathway is required for manifestation of the cardiovascular responses to nasal stimulation. Evidence also suggests that N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors are both required for synaptic neurotransmission within Sp5I.

Animals↗

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cardiovascular responses to nasal water flow in rats are unaffected by chemoreceptor drive.

Peripheral chemoreceptors generally play a limited role in the initial development of diving bradycardia in mammals. However, T.F. Huang and Y.I. Peng (Jpn. J. Physiol. 26: 395-401, 1976) reported that peripheral chemoreceptors are very important for manifestation of the diving response in conscious rats. The objectives of this study were to reinvestigate those findings and determine whether the cardiovascular responses to simulated diving in the rat were potentiated during preexisting hypoxia or hypercapnia. Responses to simulated diving were elicited by nasal water flow with concurrent apnea in paralyzed, artificially ventilated Sprague-Dawley rats anesthetized with Innovar. The experiments show that nasal stimulation in the rat results in rapid bradycardia and hypotension and that these responses are not due to laryngeal stimulation. The data also suggest that chemoreceptors do not play a role in the initiation of the responses to simulated diving in rats and that preexisting chemoreceptor drive does not alter the cardiovascular responses. Additionally, we found that concomitant expiratory apnea is necessary to sustain the profound initial cardiovascular changes induced by nasal water flow.

Animals↗

Factors terminating nonventilatory periods in the turtle, Chelydra serpentina.

PaO2, PaCO2 and pHa were measured via an extracorporeal loop in conscious snapping turtles (Chelydra serpentina) breathing air or hypoxic (10, 15% O2), hyperoxic (30% O2), or hypercapnic (2% CO2) gases. Turtles breathed into an inverted funnel ventilated with the test gas. Breathing was recorded with a differential pressure transducer. In all turtles, nonventilatory periods were interrupted by breathing episodes containing multiple breaths. In normoxia, PaO2 at the end of nonventilatory periods ranged from 22-128 mm Hg, although PaCO2 showed a less than 5 mm Hg variation about the mean. There was a positive correlation between PaCO2 at the end of the nonventilatory period and the number of breaths in the succeeding period of ventilation. PaCO2 at the end of nonventilatory periods did not change significantly in hyperoxia, although mean PaO2 was significantly increased. In hypoxia, on the other hand, mean PaO2 was significantly reduced and PaCO2 at the end of the nonventilatory period was slightly, but significantly lower. Nonventilatory periods were shorter when turtles breathed 15% O2 (9.3 +/- 1.2 min) or 10% O2 (5.5 +/- 0.3 min) than when they breathed air (17.6 +/- 3.4 min). The results indicate that, in undisturbed turtles, the most important stimulus triggering a breathing episode is the rise in PaCO2 to a critical value during the preceding nonventilatory period. An increase in hypoxic drive shortens the nonventilatory period. However, in normoxia, PaO2 at the end of many nonventilatory periods probably does not fall sufficiently to stimulate O2-sensitive chemoreceptors.

Animals↗

Cardiovascular responses to denervation of pulmocutaneous baroreceptors in toads.

Toad pulmocutaneous arterial baroreceptors are connected to afferent fibers carried in the recurrent laryngeal nerves (rLNs). Bilateral rLN denervation in conscious toads (Bufo marinus) caused 34 and 78% increases in heart rate (Fh) and systemic arterial blood pressure (Pa) within 10-15 min, respectively. The variance of Pa was significantly increased 2 days after denervation, but Pa and Fh were not. In additional chronic experiments, 5 of 17 baroreceptor-denervated toads died within the 2-wk recovery period. No deaths occurred in sham-operated toads. The mean Pa, Fh, and cardiac interval (Ic), the mean variance of Pa, Fh, and Ic, and Pa and Fh responses to stress, plasma composition, and the dry-to-wet weight ratio of skeletal muscle and lung were not statistically different in denervated and sham-operated toads. However, the sensitivity of Ic to changes in Pa, exposed by intra-arterial injections of phenylephrine and nitroprusside, was attenuated in denervated toads. Postmortem examination revealed occasional pulmonary lesions, the incidence of which appeared correlated with causes of pulmonary hypertension: baroreceptor denervation and phenylephrine injections. We conclude that pulmocutaneous arterial baroreflex is tonically active but is not essential for the long-term maintenance of Pa in conscious undisturbed toads.

Animals↗

Measurement of signal period on a personal microcomputer and its application to the analysis of cardiac interval and blood pressure.

Personal microcomputers interfaced with analog-digital converters are capable of analyzing almost any biological signal, yet are limited in their ability to directly measure a signal's period/frequency. We describe a short program which measures the interval between periodic events up to 3.5 Hz. In addition, an expanded program which calculates the frequency distribution, distribution statistics, and cross regressions of cardiac interval and blood pressure is described.

Analog-Digital Conversion↗

Hypoxemic threshold for lung ventilation in the toad.

The relationship between the activity of the buccal force pump, expressed as the time integral of positive buccal pressure, and PaO2 was investigated in conscious toads, Bufo marinus, unidirectionally ventilated at a high flow rate (240-260 ml/min). The high ventilatory flow rate meant that PaO2 was largely independent of the animal's ventilatory activity so that the relationship between pulmonary ventilation and PaO2 was effectively open-loop. The hypoxemic threshold (PaO2) for lung ventilation was 54.2 mm Hg in hypocapnia (PaCO2 = 4.7 +/- 0.3 mm Hg), 82.6 mm Hg in normocapnia (PaCO2 = 11.6 +/- 0.2 mm Hg), and 137.9 mm Hg in hypercapnia (PaCO2 = 20.1 +/- 0.1 mm Hg). Unidirectional ventilation with 20% O2 in N2, a condition in which the toads were normoxic but hypocapnic, stopped pulmonary ventilation cycles. Taken with existing evidence that hyperoxia stops pulmonary ventilation even under conditions in which PaCO2 is elevated this suggests that hypoxic and hypercapnic stimuli summate to drive lung ventilation in the toad. Bilateral denervation of the carotid labyrinths decreased pulmonary ventilation in absolute terms, but did not reduce the proportionate increase in pulmonary ventilation in response to normocapnic hypoxia, suggesting that chemoreceptors within the carotid labyrinth may contribute to, but are not solely responsible for, the hypoxemic ventilatory drive.

Animals↗

Responses to circulatory pressures, and conduction velocity, of pulmocutaneous baroreceptors in Bufo marinus.

1. Baroreceptor activity was recorded within the recurrent laryngeal branch of the toad vagus in forty-four preparations. The receptive fields of the receptors were located in the pulmocutaneous artery (p.c.a.), generally within 5 mm of its separation from the truncus. However, the most easily recorded afferents in this nerve were mechanoreceptors which responded to punctate stimulation of the lip of the glottis. 2. The conduction velocities of p.c.a. baroreceptor and mechanoreceptive glottal afferents recorded in the recurrent laryngeal nerve ranged from 0.3-0.7 (0.5 +/- 0.1) m s-1 and 2.2-14.0 (6.8 +/- 0.8) m s-1 respectively, which suggests that baroreceptor afferent fibres are non-myelinated and that glottal afferent fibres are myelinated. 3. The p.c.a. baroreceptor discharge was largely confined to a period of systole in which systemic and p.c.a. arterial pressure profiles were identical. The maximum discharge frequency, number of spikes per cycle, and the duration of discharge increased, and the discharge latency decreased, as p.c.a. pressures were elevated. The latency of the discharge was pronounced at low p.c.a. pressures, and could be partially accounted for by the conduction time of the baroreceptor afferents to the electrodes (up to 100 ms). 4. Carotid and aortic arterial baroreceptor and pharyngeal afferents were recorded in two pharyngeal branches of the vagus nerve which were closely associated with the carotid and aortic arterial arches. 5. It is suggested that baroreceptor populations with their receptive fields in the third- (carotid) and sixth- (p.c.a. or pulmonary) arch arteries should be considered homologous in anurans and mammals, but that those of the fourth- (aorta) arch artery should not, since the vagal branches in which their afferents are carried do not appear to be equivalent in anurans and mammals.

Action Potentials↗

Response characteristics of pulmocutaneous arterial baroreceptors in the toad, Bufo marinus.

1. Response characteristics of baroreceptors with receptive fields in the pulmocutaneous artery (p.c.a.) were determined in pithed toads by applying pressure steps, ramps, sine waves, and volume infusions into the vascularly isolated and perfused p.c.a. 2. The baroreceptors exhibited phasic and tonic discharge thresholds (30.3 +/- 2.3 and 36.2 +/- 2.8 mmHg respectively) which were above mean arterial pressure values reported for conscious undisturbed toads. They are comparable, in this respect, to non-myelinated mammalian arterial baroreceptors. 3. The maximum-phasic and minimum-adapted discharge frequencies of the p.c.a. baroreceptors were low (30 and 2-3 spikes s-1, respectively), but resembled those reported for mammalian non-myelinated baroreceptors when an adjustment was made for the difference in the temperature of mammalian and amphibian preparations. 4. The sensitivity of the baroreceptor discharge frequency to pressure (delta F/delta P) was estimated from pressure-step and pressure-ramp stimuli. Both estimates were greater than those reported for mammalian systemic arterial baroreceptors after the values were normalized to the maximum discharge frequency of the receptors. delta F/delta P and saturation discharge frequency values estimated from ramp stimuli increased with the dP/dt of pressure ramps. 5. The diameter of the p.c.a. was measured by sonomicrometry in toads anaesthetized with urethane. The diameter pulsation was 7.7 +/- 0.3% of the mean diameter (3.5 +/- 0.1 mm) at a mean pulse pressure of 22 +/- 1 mmHg, and Peterson's pressure-strain modulus was calculated to be 4.0 X 10(5) +/- 0.3 X 10(5) dyn cm-2, which suggests that the p.c.a. is highly compliant, and in this respect is comparable to the pulmonary artery, but not to systemic arteries, in mammals. Baroreceptor discharge began near the point of peak dynamic compliance (dV/dP) and continued as dV/dP decreased. Increasing the rate of infusion reduced the peak dV/dP, but increased the baroreceptor discharge frequency. 6. The response to sinusoidal oscillating pressure stimuli was distorted by rectification. Increasing the frequency of sinusoidal stimulation over the range 0.05-1.0 cycles s-1 reduced the number of spikes per cycle, but increased the mean discharge frequency.

Action Potentials↗