Search PubMed⌕ Search

Biomedical subjects

P A Low

Publications and source records attributed to P A Low.

At least 19 recordsLinked to original sources
PubMed1997

Chronic constriction model of rat sciatic nerve: nerve blood flow, morphologic and biochemical alterations.

We evaluated the nerve blood flow (NBF), light and electron microscopy, and adrenergic innervation of rat sciatic nerve at 2-45 days after the application of four loose ligatures. Ischemia developed at the lesion edge, creating an endoneurial dam. Calcitonin gene-related peptide, norepinephrine and NBF were increased within the lesion. Morphologic alterations consisted of early endoneurial edema, followed by myelinated fiber degeneration, with relative sparing of small myelinated and unmyelinated nerve fibers, and leukocyte adhesion to microvessels. Axonal degeneration predominated over demyelination. At 45 days, profuse regeneration of small myelinated fibers was seen. The mechanism of lesional sensitization is discussed.

Animals↗
PubMed1996

Postural tachycardia syndrome: time frequency mapping.

Orthostatic tachycardia is common but its specificity remains uncertain. Our preliminary work suggested that using autonomic function testing in conjunction with time-frequency mapping (TFM), it might be possible to characterize a subset of the postural tachycardia syndrome (POTS), that is due to a restricted autonomic neuropathy. We describe 20 patients (17 women and 3 men, aged 14-43 years) with florid POTS and 20 controls (14 women and 6 men, aged 20-41 years). Autonomic failure was quantified by its distribution (cardiovagal, adrenergic and sudomotor) and severity, a symptom profile was generated, and spectral indices, based on modified Wigner distribution during rest and head-up tilt (80 degrees) were evaluated. During tilt-up POTS patients differed from controls by an excessive heart rate (> 130 bpm) (P < 0.001), and higher diastolic pressure (P < 0.01). During rest, cardiovagal oscillations (at respiratory frequencies [RF]) and slow rhythms at nonrespiratory frequencies (NONRF) (from 0.01 to 0.07 Hz) in R-R intervals (RRI) (P < 0.01) were reduced. Both RF and NONRF rhythms in RRI were further blunted with tilt-up (P < 0.001). Slow adrenergic vasomotor rhythms in blood pressure (BP) (approximately 0.07 Hz) surged with tilt-up and returned to normal levels afterwards. The index of sympatho-vagal balance (NONRF-Systolic BP (SBP)/RF-RRI) was dramatically increased in POTS (P < 0.001). Distal postganglionic sudomotor failure was observed, and impairment of the BP responses to the Valsalva maneuver (phase II) suggested peripheral adrenergic dysfunction. Persistent orthostatic dizziness, tiredness, gastrointestinal symptoms and palpitations were common in POTS patients. It is possible to identify a subset of POTS patients who have a length-dependent autonomic neuropathy, affecting the peripheral adrenergic and cardiovagal fibers, with relative preservation of cardiac adrenergic fibers.

Adolescent↗
PubMed1996

Efficacy of limb cooling on the salvage of peripheral nerve from ischemic fiber degeneration.

Since peripheral nerve has a large ischemic safety factor, hypothermia, by reducing metabolic demands, is potentially an efficacious technique to rescue nerve from ischemic fiber degeneration (IFD). We therefore evaluated the influence of temperature on the severity of IFD resulting from a standard ischemic stress. Ischemia to the left sciatic nerve in the rat was produced by embolization of 2 x 10(6) microspheres (14 microns) into its supplying arteries. The limb was embolized at three temperatures, 37 degrees C, 32 degrees C, and 28 degrees C and was maintained at each temperature for an additional 4 h. End points, evaluated 7 days after embolization, for the embolized limb were: (1) behavioral scores, 0-11 in increasing limb function; (2) compound nerve action potential of sciatic-tibial nerve; (3) sciatic nerve blood flow (NBF, in mL/100 g/min); and (4) histologic grade, expressed as percentage of fibers undergoing IFD (0 = < 5%; 1 = 5-25%; 2 = 26-50%; 3 = 51-75%; 4 = > 75%). NBF was reduced in all groups, varying with temperature, and all indices of nerve structure and function were significantly improved with hypothermia. We conclude that hypothermia, easily achievable in a limb nerve, is highly efficacious in the rescue of nerve from IFD. These findings are of clinical relevance.

Animals↗
PubMed1996

Ischemic reperfusion causes lipid peroxidation and fiber degeneration.

Although the neuropathology of ischemic fiber degeneration (IFD) is relatively well known, its pathogenesis is poorly understood. One putative mechanism of IFD is oxidative stress, causing a breakdown of the blood-nerve barrier (BNB) and lipid peroxidation. We evaluated the effect of ischemic reperfusion of rat sciatic-tibial nerve seeking biochemical and pathologic evidence of BNB disruption and lipid peroxidation. Ischemia, caused by the ligation of the supplying arteries to sciatic-tibial nerve, was maintained for 3 h, followed by reperfusion. Reperfusion resulted in an increase in nerve lipid hydroperoxides, greatest at 3 h, followed by a gradual decline over the next month. Nerve edema and IFD consistently became more severe with reperfusion, indicating that oxidative stress impairs the BNB (edema) and causes IFD. Reduced reperfusion was greatest over distal sciatic nerve and midtibial nerve at day 7. The most ischemic segment (midtibial), of nonreperfused ischemic nerves (duration 3 h), underwent both edema and IFD that was as pronounced as those of other segments after reperfusion, and underwent a smaller increase with reperfusion, suggesting that ischemia alone can also cause IFD and edema. The type of fiber degeneration was that of axonal degeneration.

Animals↗
PubMed1996

Certain cardiovascular indices predict syncope in the postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) represent a patient population with orthostatic intolerance; some are prone to syncope, others are not. The underlying neurocardiovascular mechanisms are not completely understood. The current study was undertaken to assess if certain cardiovascular indices are predictive of syncope in POTS. We compared the response to tilt-up and the Valsalva maneuver in four groups: POTS patients who fainted (POTS-f; n = 11;31 +/- 11 years): POTS patients who did not faint (POTS-nf; n = 9; 29 +/- 9 years); normal controls (NLS; n = 13; 39 +/- 11 years); patients with generalized autonomic failure with orthostatic hypotension and syncope (n = 10; 59 +/- 14 years). Beat-to-beat heart rate (HR), systolic arterial pressure, diastolic arterial pressure (DAP) and pulse pressure (PP) were monitored using Finapres. Cardiac output, stroke volume (SV) and end-diastolic volume (EDV), and calculated total peripheral resistance (TPR) were recorded using thoracic electrical bioimpedance. An autonomic reflex screen which quantitates the distribution and severity of autonomic failure was also done. With the patient supine, all POTS patients (POTS-nf; POTS-f) had increased HR (p < 0.001) and reduced SV/EDV (p < 0.001) when compared with NLS. On tilt-up, POTS-f patients were significantly different from both NLS and POTS-nf patients; the most consistent alteration was a fall instead of an increase in TPR; other changes were a greater reduction in PP, a reduction (instead of an increment) in DAP, and a different pattern of changes during the Valsalva maneuver (excessive early phase II, attenuated or absent late phase II). Our results suggest alpha-adrenergic impairment with increased pooling or hypovolemia in POTS-f patients. We conclude that it is possible to identify the mechanism of syncope in POTS patients, and perhaps other patients with orthostatic intolerance and an excessive liability to syncope.

Adult↗
PubMed1996

Adenosine: potential modulator for vasovagal syncope.

OBJECTIVES: This study examined the hypothesis that adenosine could provoke a vasovagal response in susceptible patients. Mechanisms of the vasovagal response were further explored by studying the adenosine-mediated reactions. BACKGROUND: Increased sympathetic activity is frequently observed before vasovagal syncope. Recent studies have demonstrated that adenosine, in addition to its direct bradycardiac and vasodilatory effects, can increase sympathetic discharge by activating cardiovascular afferent nerves. METHODS: The effects of adenosine and head-up tilt-table testing with or without isoproterenol were prospectively evaluated in 85 patients examined for syncope after negative results of electrophysiologic testing (51 men and 34 women, mean [+/- SD] age 61 +/- 17 years). Adenosine bolus injections of 6 mg and 12 mg were sequentially administered to patients in the upright position. The same protocol was implemented in 14 normal control subjects (7 men and 7 women, mean [+/- SD] age 38 +/- 10 years). RESULTS: Transient hypertension or tachycardia was observed in 57 (67%) and 20 (24%) patients after administration of 6 mg and 12 mg of adenosine, respectively, during the immediate phase (first 15 s), suggesting direct sympathetic activation. Hypotension and reflex tachycardia were observed in all patients during the delayed phase (15 to 60 s after adenosine injection), suggesting baroreceptor unloading. A vasovagal response was induced in 22 (26%) and 29 (34%) patients after adenosine administration and during tilt-table testing. Inducibility of a vasovagal response by these two methods was comparable (p = 0.12). Of the control subjects, one (7%) had a vasovagal response after adenosine administration and one (7%) had a positive response during tilt-table testing. CONCLUSIONS: These observations support the idea that adenosine is an endogenous modulator of the cardiac excitatory afferent nerves. Sympathetic activation by adenosine can be direct (i.e., cardiac excitatory afferent nerves) and indirect (i.e., vasodilation and reflex sympathetic activation). Adenosine could be an important modulator in triggering a vasovagal response in susceptible patients during examination for syncope.

Adenosine↗
PubMed1996

Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy.

Nerve lipid peroxidation is increased in experimental diabetic neuropathy, and alpha-lipoic acid will prevent the deficits in nerve blood flow, oxidative stress, and distal sensory conduction. Because these alterations can occur by mechanisms other than augmenting lipid peroxidation in vivo, and because both pro-oxidant and antioxidant effects of the agent have been reported, we undertook studies of in vitro lipid peroxidation of brain and sciatic nerve using an in vitro lipid peroxidation model with an ascorbate-iron-EDTA system. We evaluated the effectiveness of the R(+)-, S(-)-enantiomers, and racemate of alpha-lipoic acid in reducing thiobarbituric acid reactive substances (TBARS) generation in rat brain and sciatic nerve. Studies were also done in an incubation medium containing 20 mM glucose, which increased lipid peroxidation up to fourfold. A dose-dependent and statistically significant reduction in lipid peroxidation was seen with both tissues with similar potencies for both enantiomers. This effect was unassociated with any reduction in the loss of alpha-tocopherol.

Animals↗
PubMed1996

Extreme vasoreactivity of rat epineurial arterioles to vasopressin.

Vasopressin is a potent vasoconstrictor to most blood vessels but is a vasodilator to some. The role of vasopressin in the regulation of nerve blood flow (NBF) is not known. We undertook a dose-effect study of vasopressin on NBF and evaluated its interactions with alpha-adrenoreceptors and its effect on ischemic conduction failure. NBF was measured using microelectrode hydrogen polarography. Vasopressin was administered topically (to epineurium). Topical epineurial application of vasopressin caused a concentration -dependent reductin of NBF (EC 50 = 6.6 x 10(-9) M; asymptote = 73.9% NBF reduction). The topical application of subthreshold concentrations of vasopressin and norepinephrine alone resulted in no change in NBF, but combined application resulted in a dramatic reduction in NBF (72.3%). The ratio of amplitudes of muscle compound action potential evoked on proximal to distal stimulation was used as an index of the presence of an ischemic conduction block. This ratio was significantly reduced following the combined topical application of supramaximal concentrations of vasopressin and norepinephrine. These findings suggest that vasopressin is a potent neural vasoconstrictor and that vasoconstriction caused by combined vasopressin and norepinephrine can produce partial conduction block of sciatic-tibial nerve [corrected].

Administration, Topical↗
PubMed1996

Levodopa and deprenyl treatment effects on peripheral indices of oxidant stress in Parkinson's disease.

The oxidant stress theory of Parkinson's disease (PD) hypothesizes that levodopa treatment may be potentially harmful and this is supported by studies demonstrating levodopa toxicity to cultured dopaminergic neurons. These in vitro experiments, however, lack the physiologic protective mechanisms present in vivo. Oxyradical damage to cell membranes liberates malondialdehyde, which we measured in the serum of 27 PD patients just before and after levodopa (with carbidopa) administration. We also measured plasma products of the two routes by which levodopa potentially generated oxyradicals: (1) 5-S-cysteinyl-dopa (derived from levodopa autoxidation), and (2) 3,4-dihydroxyphenylacetic acid (DOPAC), produced by monoamine oxidase (MAO) metabolism of dopamine. Following levodopa/carbidopa administration, both of these plasma products were markedly increased; however, the mean serum malondialdehyde concentration was unchanged and remained similar to the normal control group (N=15) value. Chronic treatment with the MAO-B inhibitor, deprenyl (N=16), was not associated with any differences in serum malondialdehyde or plasma 5-S-cysteinyl-dopa concentrations compared with those not treated with deprenyl (N=11). The post-levodopa rise of plasma DOPAC was only slightly attenuated with deprenyl therapy, consistent with a predominant MAO-A effect in the circulation and peripheral organs. Thus, in contrast to in vitro studies, we did not detect evidence of oxidative damage in the circulation following levodopa administration, despite marked increase in the products of dopamine oxidative metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Role of physical countermaneuvers in the management of orthostatic hypotension: efficacy and biofeedback augmentation.

OBJECTIVE: To evaluate the efficacy of various physical countermaneuvers in reducing orthostatic hypotension and its associated symptoms and to assess the efficacy of biofeedback training in enhancing the effectiveness of physical countermaneuvers. MATERIAL AND METHODS: In nine study subjects with neurogenic orthostatic hypotension, four training sessions on physical countermaneuvers were performed after tilt-up, three with visual feedback on the effect of physical countermaneuvers on blood pressure and other cardiovascular variables. Blood pressure change and orthostatic symptoms during tilt-up were determined, as were the changes in total peripheral resistance, stroke index, and heart rate. RESULTS: The five female and four male patients had a mean age of 53 years and a mean duration of symptoms of 4.2 years. On an orthostatic symptom scale of 0 to 10, these patients had a mean symptom score of 7.3. The increment in systolic blood pressure was better for some maneuvers (such as leg crossing and a combination) than others (such as neck flexion and abdominal contraction). Three patterns of responses to biofeedback were found. Simple maneuvers such as squatting did not improve with training; visual feedback was needed for maneuvers such as thigh contraction, and performance declined without biofeedback; the third pattern, seen in maneuvers such as leg crossing, showed continued improvement with training, even without biofeedback. A survey at 3 to 4 months after training revealed continued use of physical maneuvers (3.8 +/- 3.1 per day), increased standing time with each episode of presyncopal symptoms (8.3 +/- 5.8 minutes), and continued global symptomatic improvement. Total peripheral resistance, but not heart rate or stroke index, showed significant regression with blood pressure improvement. CONCLUSION: Physical countermaneuvers are efficacious in reducing orthostatic hypotension, can be augmented by use of biofeedback, and may significantly improve the functional outcome. The major mechanism of improvement is an increase in total peripheral resistance, presumably by reducing the vascular capacitance.

Adult↗
PubMed1995

Localization and possible interactions of catecholamine-and NADPH-diaphorase neurons in human medullary autonomic regions.

The human medulla contains catecholamine-and NADPH-diaphorase (NADPH-d) neurons in both the ventrolateral medulla (VLM) and nucleus of the solitary tract (NTS). There is abundant experimental evidence for the critical role of these areas in control of arterial pressure. We sought to determine the pattern of distribution and topographic relationship between tyrosine hydroxylase (TH)-immunoreactive and NADPH-d-reactive cell groups in normal human VLM and NTS, in view of their potential implications in human autonomic control and involvement in central autonomic disorders. Medullae from three patients with no neurologic disease were obtained at autopsy within 24 h of death. Individual sections, obtained from the rostral and caudal medulla, were stained for TH, NADPH-d or both. We found that: (1) TH-and NADPH-d positive neurons are topographically segregated in the VLM; (2) in the VLM, TH and NADPH-d neurons may coexist within a given area but both markers do not appear to coexist in single neuron; (3) NADPH-d-reactive fibers and processes overlap the distribution of TH neurons within the VLM; and (4) both TH-and NADPH-d-reactive processes appear to innervate intrinsic blood vessels in the VLM and NTS. Thus, there are important topographic relationships between catecholamine and NO-synthesizing neurons in human VLM and perhaps NTS, including innervation of intrinsic blood vessels. This may have important implications in regulation of autonomic reflexes, sympathetic excitatory drive and intrinsic control of cerebral blood flow in humans.

Aged↗
PubMed1995

Vasoreactivity to prostaglandins of rat peripheral nerve.

1. We evaluated the effect of the local superfusion of prostaglandins E1, I2 and F2 alpha (PGE1, PGI2 and PGF2 alpha, respectively) on rat sciatic nerve blood flow and microvascular resistance. 2. PGE1 increased nerve blood flow (NBF) in a dose-dependent fashion with an EC50 of 10(-6.7) M and an asymptote of 20.1 ml (100 g)-1 min-1. 3. PGI2 increased NBF in a linear dose-dependent fashion, with an EC50 of 10(-5.1) M. PGI2 appeared to be about 1.5 orders of magnitude less potent than PGE1. 4. PGF2 alpha also increased NBF in a dose-dependent fashion. The threshold dose appeared to be identical with PGI2 but may have a reduced capacity of response. The EC50 of 10(-5.8) M was slightly lower than that of PGI2.

Alprostadil↗
PubMed1995

Experimental ischemic neuropathy: salvage with hyperbaric oxygenation.

Hyperbaric oxygenation is effective in augmenting the delivery of oxygen to tissue, but also causes oxidative stress. As part of our focus on improving peripheral nerve salvage from ischemic fiber degeneration, we evaluated whether hyperbaric oxygenation rescues peripheral nerve, rendered ischemic by microembolization, from ischemic fiber degeneration. The supplying arteries of rat sciatic nerve were embolized with microspheres of 14 microns diameter at moderate (2 x 10(6)) and high (5.6 x 10(6)) doses. Rats were randomized to receive hyperbaric oxygenation treatment (2.5 atm 100% oxygen for 2 hours/day for 7 days beginning within 30 minutes of ischemia), or room air. End points for the embolized limb were (1) behavioral scores (0-11 in increasing levels of limb function), (2) nerve action potential of sciatic-tibial nerve, (3) nerve blood flow, and (4) histological grade as percentage of fibers undergoing ischemic fiber degeneration (0 = < 5%; 1 = 5-25%; 2 = 26-50%; 3 = 51-75%; 4 = > 76%). Nerve blood flow and nerve action potential were uniformly absent and more than 90% of fibers had degenerated in both control and treatment groups receiving high doses. Control and treatment groups receiving moderate doses were well matched by level of ischemia (8.5 +/- 0.3 [N = 18] vs 7.7 +/- 0.4 ml/100 gm/min [N = 18], p > 0.05) but were significantly different by behavior score (5.6 +/- 0.7 vs 9.2 +/- 0.5 [N = 19], p < 0.001), nerve action potential (1.4 +/- 1.0 vs 3.9 +/- 0.5 [N = 6], p < 0.05), and histology (2.4 +/- 0.4 [N = 5] vs 0.8 +/- 0.5 [N = 4], p < 0.05). On single teased fiber evaluation, the predominant abnormality was E (axonal degeneration). We conclude that hyperbaric oxygenation will effectively rescue fibers from ischemic fiber degeneration, providing the ischemia is not extreme.

Action Potentials↗
PubMed1995

No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease.

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.

Aged↗
PubMed1995

Oxidized cellulose causes focal neuropathy, possibly by a diffusible chemical mechanism.

We observed incidentally that rat sciatic nerve in contact with oxidized cellulose (OC), an absorbable hemostatic agent, underwent focal fiber degeneration, and we undertook studies to determine the mechanism of its production. Topically applied OC generated acute nerve damage within the adjacent nerve fascicle of rat sciatic nerve in a dose-dependent fashion (r = 0.99, P < 0.01, threshold amount: 9.9 mg). IN single teased fibers, the predominant type of myelinated fiber damage was axonal degeneration. The subperineurial blood flow of the rat sciatic nerve was serially measured by microelectrode hydrogen polarography, and the reduction at 90 min after application of OC was not greater than that of controls. A thin polyethylene membrane interposed between OC and the sciatic nerve almost completely prevented the nerve damage. These data suggest that the chief mechanism of nerve damage by OC was neither compression nor ischemia, but was a diffusible chemical mechanism. Care should be taken to avoid direct OC application around peripheral nerves.

Animals↗
PubMed1995

Effect of cilostazol on experimental diabetic neuropathy in the rat.

Two proposed mechanisms of diabetic neuropathy are microvascular ischaemia and a reduction in Na,K-ATPase activity. We evaluated the effect of cilostazol, a drug that is both a potent phosphodiesterase inhibitor that normalizes nerve Na,K-AT-Pase and a vasodilator, on nerve blood flow (NBF) to determine whether it would improve experimental diabetic neuropathy. We examined whether epineurally applied cilostazol acted as a vasodilator on the peripheral nerve of normal and diabetic rats, and whether feeding the rats a cilostazol-supplemented diet could improve diabetic neuropathy. Cilostazol increased nerve blood flow (NBF) in a dose-dependent fashion with an EC50 of 10(-5.74) mol/l. Cilostazol also normalized NBF in experimental diabetic neuropathy with a 10(-4) mol/l local application on the sciatic nerve. In diabetic neuropathy, a cilostazol-supplemented diet improved both NBF and nerve conduction in a dose- and time-dependent fashion. Potential mechanisms of action of cilostazol on the nerve include its effect on NBF, Na, K-ATPase, and restoration of the thromboxane:prostacyclin ratio. Cilostazol may have potential in the treatment of diabetic neuropathy.

Animals↗