Mussadiq Shah

Urinary Bladder Detrusor Dysfunction Symptoms in Lyme Disease

Purpose Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. Methods A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. Results The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35%) and none of the controls (0%) had symptoms of detrusor dysfunction (P<0.01). Conclusions This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease.

A Discussion on the Regulation of Blood Flow and Pressure

This paper discusses two kinds of regulation essential to the circulatory system: namely the regulation of blood flow and that of (systemic) arterial blood pressure. It is pointed out that blood flow requirements sub-serve the nutritional needs of the tissues, adequately catered for by keeping blood flow sufficient for the individual oxygen needs. Individual tissue oxygen requirements vary between tissue types, while highly specific for a given individual tissue. Hence, blood flows are distributed between multiple tissues, each with a specific optimum relationship between the rate of oxygen delivery (DO2) and oxygen consumption (VO2). Previous work has illustrated that the individual tissue blood flows are adjusted proportionately, where there are variations in metabolic rate and where arterial oxygen content (CaO2) varies. While arterial blood pressure is essential for the provision of a sufficient pressure gradient to drive blood flow, it is applicable throughout the arterial system at any one time. Furthermore, It is regulated independently of the input resistance to individual tissues (local arterioles), since they are regulated locally, that being the means by which the highly specific adequate local requirement for DO2 is ensured. Since total blood flow is the summation of all the individually regulated tissue blood flows cardiac inflow (venous return) amounts to total tissue blood flow and as the heart puts out what it receives cardiac output is therefore determined at the tissues. Hence, regulation of arterial blood pressure is independent of the distributed independent regulation of individual tissues. It is proposed here that mechanical features of arterial blood pressure regulation will depend rather on the balance between blood volume and venous wall tension, determinants of venous pressure. The potential for this explanation is treated in some detail.

Pattern Of Dysautonomia In Patients With Functional Gastrointestinal Disorders

desaturations (p = 0.001) and 1 arousal (p N 0.05). No apneas were followed by desaturation and arousal. Hypopneas were the most frequent respiratory event and occurred primarily during sleep stage 1 and 2. In all FD-patients, we recorded 362 hypopneas with subsequent oxygen-desaturation that were followed by only 51 arousals. 12 hypopneas (p b 0.001) occurred in 3 controls (p= 0.085) and were followed by 3 arousals (p= 0.002).

Neuromuscular taping reduces blood pressure in systemic arterial hypertension

Systemic arterial hypertension, a well-known cause of morbidity, is associated with dysfunction of the autonomic nervous system. Neuromuscular taping (also known as kinesio taping, medical taping and Vendje neuromuscular) allows movement and muscle activity to treat pain, muscle disorders and lymphoedema, in which its mode of action may involve muscular stimulation leading to increased local blood circulation or stimulating dermatological, muscular and fascial structures with a form of passive massage. We hypothesised that neuromuscular taping may reduce blood pressure in systemic arterial hypertension. This hypothesis was tested by carrying out the first pilot study of its kind to determine whether the non-invasive technique of neuromuscular taping can reduce blood pressure in patients suffering from systemic arterial hypertension. Neuromuscular taping was symmetrically applied to the back, between C1 and T2, of seven hypertensive patients for 5-7 days. Cardiovascular autonomic parameters were assessed at baseline and at the end of the study. Taping was associated with falls in mean arterial blood pressure (p = .001), mean systolic blood pressure (p < .01), mean diastolic pressure (p < .01) and cardiac vagal tone at rest (p = .063). The beneficial effects on blood pressure appeared to last for at least five days post-neuromuscular taping. There is an indication, given the reduction in cardiac vagal tone at rest, that the mechanism of action of this intervention involves modulation of the brainstem parasympathetic system during cardiovascular control. Further studies are indicated to replicate the present findings, further investigate the effects of taping on autonomic functioning, and establish the optimum time-period and taping positioning.

Carbon dioxide therapy in hypocapnic respiratory failure

Oxygen therapy, usually administered by a facemask or nasal cannulae, is the current default treatment of respiratory failure. Since respiration entails intake of oxygen and release of carbon dioxide from tissues as waste product, the notion of administering carbon dioxide in respiratory failure appears counter-intuitive. However, carbon dioxide stimulates the chemosensitive area of the medulla, known as the central respiratory chemoreceptor, which activates the respiratory groups of neurones in the brainstem and stimulates inspiration thereby initiating oxygen intake during normal breathing. This vital initiation of normal breathing is via a reduction in the pH of the cerebrospinal fluid and the medullary interstitial fluid. We hypothesise that in cases of type I respiratory failure in which the PaCO2 is low, administration of carbon dioxide by inhalation would stimulate the respiratory groups of brainstem neurones and facilitate breathing, which would be of therapeutic value. Preliminary clinical evidence in favour of this hypothesis is presented and we recommend that a formal randomised study be carried out.

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Background Renal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α‐1‐adrenoceptor‐mediated autotransfusion during the Valsalva maneuver. Methods and Results In this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within‐group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double‐blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group. Conclusions Blood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.

[LB.03.06] ATTENUATION OF SPLANCHNIC AUTOTRANSFUSION FOLLOWING NON-INVASIVE ULTRASOUND RENAL DENERVATION: A NOVEL MARKER OF PROCEDURAL SUCCESS

Objective: In the Valsalva manoeuvre, autotransfusion in Phase IIi arises from sympathetically mediated capsular contraction of intra-abdominal organs including the kidneys. We hypothesised that following successful renal nerve ablation this response would be attenuated and could serve as a marker of procedural success. Design and method: 23 patients (mean age 59.4 ± 10.5 years; BMI 30.2; anti-hypertensive medication 4.2; 65% males and 35% females) with resistant HTN (On 3 or more anti-hypertensive drugs including a diuretic) were enrolled in the double-blind, sham controlled KONA Wave IV study. They were randomised either to bilateral RDN using therapeutic levels of ultrasound energy (n = 12, 75% male, mean age 57.2 ± 10.3 years) or the sham procedure using bilateral application of diagnostic levels of ultrasound energy (n = 11, 55% male, mean age 61.9 ± 10.6 years). Within group changes in autonomic parameters, office blood pressure (OBP) and ambulatory BP (ABP) were compared between baseline and 6 months in a double blind manner. Results: There was significant OBP reduction in both treatment (16.1 ± 27.3 mmHg, p < 0.05) and sham groups (27.9 ± 15.0 mmHg, p < 0.01). In the treatment group, heart rate (HR) was significantly reduced following RDN both at rest (4.3 ± 6.6 bpm, p < 0.05) and in response to postural changes. During phase IIi Valsalva, RDN resulted in substantial and significant reduction in MAP (21.8 ± 25.2 mmHg, p < 0.05) with no significant changes in the sham group. Figure. No caption available. Conclusions:BP reduction per se is not necessarily a marker of renal nerve ablation.Reduction in splanchnic auto-transfusion following RDN has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success.Sham therapy results in clinically meaningful BP reduction that has implications for future trial design.

Recovery from Cogwheel Rigidity and Akinesia and Improvement in Vibration Sense and Olfactory Perception following Removal of an Epoxy-Oleic Acid DNA Adduct

The epoxy fatty acid cis-12,13-epoxy-oleic acid, which acts as a DNA adduct, may be generated during long-term storage of many seed oils, including those used in cooking, with frying oils and fried foods being a major source in the modern human diet. Removal of this epoxy fatty acid from the locus of the N-formyl peptide receptors was associated with recovery from cogwheel rigidity and akinesia as well as with improvement in vibration sense and olfactory perception.

[PP.38.09] EFFECTS OF MILD DYNAMIC EXERCISE ON CIRCULATORY AND AUTONOMIC FUNCTION IN HEALTHY VOLUNTEERS

Objective: Valuable insights into BP regulation have arisen from the study of neurocirculatory responses to exercise. However most studies have focused exclusively on evaluation of responses to maximal/submaximal exercise with concomitant profound increase in muscle metabolic demand. We studied the effects of mild exercise in healthy volunteers to obviate the confounding effects of large metabolic changes. Design and method: 8 healthy volunteers undertook very mild dynamic exercise (< 3 METs) of 1 minute duration. Non-invasive arterial BP was monitored in all 8 subjects. In 5 subjects the arterial BP recording was used to derive haemodynamic variables (PulseCO®, LiDCO plc, London), including cardiac output (CO), mean arterial pressure (MAP), systemic vascular resistance (SVR) and heart rate. Autonomic nervous system investigation was undertaken in 7 subjects with high resolution monitoring of arterial pressure and electrocardiography to derive indices of sympathetic and parasympathetic tone (NeuroScope®, Medifit Instruments Ltd, London). Results: CO increased from an average resting value of 4.8 l min-1 to 6.2 l min-1 during exercise (a 30.4% increase, p = 0.003) and settled to 4.8 l min-1 afterwards. The reciprocal of SVR, conductance (100/SVR) was used to determine the role of the periphery on CO in positive terms (the other driver for the increase in CO being MAP change). The average increase in MAP and conductance was 4.4% (p = ns) and 23.8% (p = 0.01) respectively. Figure. No caption available. Cardiac sensitivity to baroreceptor function (CSB) fell from an average of 5.4 ± 1.2 SEM to 2.9 ± 1.2 SEM (p < 0.05) and cardiac vagal tone (CVT) fell from an average of 6.8 ± 1.3 SEM on a linear vagal scale to 4.1 ± 1.3 SEM, (p < 0.05). Following exercise rebound occurred with both to values above baseline. Conclusions: The main change driving the increase in CO was an increase in conductance rather than change in MAP. This is in contrast to dynamic cardiovascular exercise at higher workloads where MAP increases immediately and progressively with workload. Withdrawal of vagal tone at such mild exercise intensity is a new finding and is consistent with gradual heart rate increase as exercise intensity increases from the lowest levels.

[OP.8D.02] FIRST IN MAN TREATMENT OF SEVERE BP VARIABILITY WITH BAROREFLEX ACTIVATION THERAPY.

Objective: Profound BP variability (BPV) is a major cause of cardiovascular morbidity and poor quality of life as there are no optimal pharmacological strategies to help patients. We hypothesised that in a patient with baroreflex dysfunction and preserved efferent baroreflex pathway, carotid sinus stimulation may help control BP, BPV and heart rate variability (HRV). Design and method: A 52 year old man was referred with profound HR and BPV. Home SBPs were in a range of 60–250 mmHg and DBPs were 40–130 mmHg and heart rate (HR) of 60–200 bpm (confirmed with ABPM, see Figure) despite multiple medications including felodipine 30 mg daily, terazosin 16 mg daily, doxazosin 8 mg daily, bisoprolol 20 mg daily and butrans patch 17.5 mcg/hr. After extensive multi-disciplinary investigations the diagnosis was progressive central and peripheral dysautonomia consequent upon immune-mediated neuropathy secondary to undifferentiated connective tissue disease with Sjogrens syndrome. It was not possible to improve BP control with use of clonidine patches and he had frequent severe epistaxes due to hypertensive surges and blackouts due to hypotension and was therefore retired from work on medical grounds. Results: Autonomic function tests confirmed widespread dysautonomia with preserved but attenuated vasodepressor response to carotid sinus massage. Baroreflex activation therapy (BAT) was undertaken after numerous in-patient attempts to control BPV pharmacologically had failed. The Barostim Neo® device was implanted with a right carotid sinus electrode in March 2015 and subsequently device settings were reprogrammed on several occasions to optimise BP control. The patients BP profile improved considerably following BAT but significant hypotensive episodes continued and thus all antihypertensives were stopped with substantial improvement in HR and BP and halving of BPV and concomitant reduction in epistaxes and syncopal episodes. Figure. No caption available. Conclusions: Severe BPV is uncommon and challenging to manage when caused by baroreflex failure. Some antihypertensive drugs can increase BPV and elevate sympathetic tone which could further impair BP control in patients with this diagnosis. Use of BAT in this setting may be of benefit as long as the carotid sinus nerve and vasodepressor component of the baroreflex still function.