Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension

In patients with drug-resistant hypertension, chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction. We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation, and we analyzed the correlation with blood pressure changes. Twenty-one patients with drug-resistant hypertension were prospectively included in a substudy of the Device Based Therapy in Hypertension Trial. Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG. Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation (stimulator on). Chronic baroreceptor stimulation decreased office blood pressure from 185+/-31/109+/-24 mm Hg to 154+/-23/95+/-16 mm Hg (P<0.0001/P=0.002). Mean heart rate decreased from 81+/-11 to 76+/-10 beats per minute(-1) (P=0.001). Heart rate variability frequency-domain parameters assessed using fast Fourier transformation (FFT; ratio of low frequency:high frequency: 2.78 versus 2.24 for off versus on; P<0.001) were significantly changed during stimulation of the carotid baroreceptor, and heart rate turbulence onset was significantly decreased (turbulence onset: -0.002 versus -0.015 for off versus on; P=0.004). In conclusion, chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension; these changes correlate with blood pressure reduction. Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies.

Comparison of the effects of the alpha-2 agonists detomidine, romifidine and xylazine on nociceptive withdrawal reflex and temporal summation in horses

OBJECTIVE: To evaluate and compare the antinociceptive effects of the three alpha-2 agonists, detomidine, romifidine and xylazine at doses considered equipotent for sedation, using the nociceptive withdrawal reflex (NWR) and temporal summation model in standing horses. STUDY DESIGN: Prospective, blinded, randomized cross-over study. ANIMALS: Ten healthy adult horses weighing 527-645 kg and aged 11-21 years old. METHODS: Electrical stimulation was applied to the digital nerves to evoke NWR and temporal summation in the left thoracic limb and pelvic limb of each horse. Electromyographic reflex activity was recorded from the common digital extensor and the cranial tibial muscles. After baseline measurements a single bolus dose of detomidine, 0.02 mg kg(-1), romifidine 0.08 mg kg(-1), or xylazine, 1 mg kg(-1), was administered intravenously (IV). Determinations of NWR and temporal summation thresholds were repeated at 10, 20, 30, 40, 60, 70, 90, 100, 120 and 130 minutes after test-drug administration alternating the thoracic limb and the pelvic limb. Depth of sedation was assessed before measurements at each time point. Behavioural reaction was observed and recorded following each stimulation. RESULTS: The administration of detomidine, romifidine and xylazine significantly increased the current intensities necessary to evoke NWR and temporal summation in thoracic limbs and pelvic limbs of all horses compared with baseline. Xylazine increased NWR thresholds over baseline values for 60 minutes, while detomidine and romifidine increased NWR thresholds over baseline for 100 and 120 minutes, respectively. Temporal summation thresholds were significantly increased for 40, 70 and 130 minutes after xylazine, detomidine and romifidine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine, romifidine and xylazine, administered IV at doses considered equipotent for sedation, significantly increased NWR and temporal summation thresholds, used as a measure of antinociceptive activity. The extent of maximal increase of NWR and temporal summation thresholds was comparable, while the duration of action was drug-specific.

The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs

Objective To examine the influence of a low dose dexmedetomidine infusion on the nociceptive withdrawal reflex and temporal summation in dogs during isoflurane anaesthesia. Study design Prospective experimental blinded cross-over study. Animals Eight healthy mixed breed dogs, body weight Mean +/- SD 26.5 +/- 8.4 kg and age 25 +/- 16 months. Methods Anaesthesia was induced with propofol and maintained with isoflurane (Fe'ISO 1.3%) delivered in oxygen and air. After stabilization, baseline recordings (time 0) were obtained, then a dexmedetomidine bolus (1 mug kg(-1) IV) followed by a continuous rate infusion (1 mug kg(-1) hour(-1) ) or saline placebo were administered. At times 10, 30 and 60 minutes after the initial bolus, electrical stimulations of increasing intensity were applied over the lateral plantar digital nerve, and administered both as single and as repeated stimuli. The resulting reflex responses were recorded using electromyography. Data were analysed using a multivariable linear regression model and a Kruskal Wallis test for single stimulation data, and repeated measures anova and paired t-test for repeated stimulation data. Results The AUC for the stimulus-response curves after single stimulation were similar for both treatments at time 0. At times 10, 30 and 60 the AUCs for the stimulus-response curves were significantly lower with dexmedetomidine treatment than with placebo. Temporal summation was evident in both treatments at times 0, 10, 30 and 60 starting from a stimulation intensity of 10 mA. The magnitude of temporal summation was smaller in dexmedetomidine than in placebo treated dogs at time 10, 30 and 60, but not at time 0. Conclusions During isoflurane anaesthesia, low dose dexmedetomidine suppresses the nociceptive reflex responses after single and repeated electrical stimulation. Clinical relevance This experimental study confirms previous reports on its peri-operative efficacy under clinical conditions, and further indicates that dexmedetomidine might reduce the risk of post-operative chronic pain development.

Quantitative assessment of the nociceptive withdrawal reflex in healthy, non-medicated experimental sheep

This study aimed to characterize the nociceptive withdrawal reflex (NWR) and to define the nociceptive threshold in 25 healthy, non-medicated experimental sheep in standing posture. Electrical stimulation of the dorsal lateral digital nerves of the right thoracic and the pelvic limb was performed and surface-electromyography (EMG) from the deltoid (all animals) and the femoral biceps (18 animals) or the peroneus tertius muscles (7 animals) was recorded. The behavioural reaction following each stimulation was scored on a scale from 0 (no reaction) to 5 (strong whole body reaction). A train-of-five 1 ms constant-current pulse was used and current intensity was stepwise increased until NWR threshold intensity was reached. The NWR threshold intensity (It) was defined as the minimal stimulus intensity able to evoke a reflex with a minimal Root-Mean-Square amplitude (RMSA) of 20 μV, a minimal duration of 10 ms and a minimal reaction score of 1 (slight muscle contraction of the stimulated limb) within the time window of 20 to 130 ms post-stimulation. Based on this value, further stimulations were performed below (0.9It) and above threshold (1.5It and 2It). The stimulus-response curve was described. Data are reported as medians and interquartile ranges. At the deltoid muscle It was 4.4 mA (2.9–5.7) with an RMSA of 62 μV (30–102). At the biceps femoris muscle It was 7.0 mA (4.0–10.0) with an RMSA of 43 μV (34–50) and at the peroneus tertius muscle It was 3.4 mA (3.1–4.4) with an RMSA of 38 μV (32–46). Above threshold, RMSA was significantly increased at all muscles. Below threshold, RMSA was only significantly smaller than at It for the peroneus tertius muscle but not for the other muscles.

Accuracy of the withdrawal reflex for localization of the site of cervical disk herniation in dogs: 35 cases (2004-2007)

OBJECTIVE To evaluate the accuracy of neurologic examination versus magnetic resonance imaging (MRI) in localization of cervical disk herniation and evaluate the usefulness of withdrawal reflex testing in dogs. DESIGN Retrospective case series. ANIMALS 35 client-owned dogs with a single-level cervical disk herniation as determined via MRI. PROCEDURES 1 of 2 board-certified neurologists performed a complete neurologic examination in each dog. Clinical signs of a cervical lesion included evidence of neck pain and tetraparesis. The withdrawal reflex was used for neuroanatomic localization (C1-C5 or C6-T2). Agreement between results of neurologic and MRI examinations was determined. RESULTS Agreement between neurologic and MRI diagnoses was 65.8%. In 11 dogs in which the lesion was clinically localized to the C6-T2 segment on the basis of a decreased withdrawal reflex in the forelimbs, MRI revealed an isolated C1-C5 disk lesion. In 1 dog, in which the lesion was suspected to be at the C1-C5 level, MRI revealed a C6-T2 lesion. Cranial cervical lesions were significantly associated with an incorrect neurologic diagnosis regarding site of the lesion. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the withdrawal reflex in dogs with cervical disk herniation is not reliable for determining the affected site and that a decreased withdrawal reflex does not always indicate a lesion from C6 to T2.

Antinociceptive effect of buprenorphine and evaluation of the nociceptive withdrawal reflex in foals.

OBJECTIVE To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. STUDY DESIGN Prospective, experimental cross-over trial. ANIMALS Nine Norwegian Fjord research foals. METHODS Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. RESULTS We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine. CONCLUSION AND CLINICAL RELEVANCE These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.

Electrical carotid baroreceptor stimulation

The Barostim neo ™ system is a novel implantable device that activates the carotid baroreflex. It decreases the sympathetic activity and inhibits the renin system, which results in reduced blood pressure and heart rate. In patients with resistant hypertension, electrically activation of the baroreflex leads to an average decrease in systolic blood pressure of 38, 36, 40 and 53 mmHg at 1, 2, 3 and 4 years, respectively. Additionally, cardiac remodelling with reduced left ventricular mass and posterior wall thickness has been observed in long-term studies. In a limited number of patients with heart failure, baroreflex activation therapy leads to a decrease in muscle sympathetic nerve activity and to improved quality of life and functional capacities. The implantation procedure is safe and associated with risks comparable with those of other active implantable devices. Barostim neo is currently available in several European countries.

Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.

The aim of this study was to determine the reliability of the conditioned pain modulation (CPM) paradigm assessed by an objective electrophysiological method, the nociceptive withdrawal reflex (NWR), and psychophysical measures, using hypothetical sample sizes for future studies as analytical goals. Thirty-four healthy volunteers participated in two identical experimental sessions, separated by 1 to 3 weeks. In each session, the cold pressor test (CPT) was used to induce CPM, and the NWR thresholds, electrical pain detection thresholds and pain intensity ratings after suprathreshold electrical stimulation were assessed before and during CPT. CPM was consistently detected by all methods, and the electrophysiological measures did not introduce additional variation to the assessment. In particular, 99% of the trials resulted in higher NWR thresholds during CPT, with an average increase of 3.4 mA (p<0.001). Similarly, 96% of the trials resulted in higher electrical pain detection thresholds during CPT, with an average increase of 2.2 mA (p<0.001). Pain intensity ratings after suprathreshold electrical stimulation were reduced during CPT in 84% of the trials, displaying an average decrease of 1.5 points in a numeric rating scale (p<0.001). Under these experimental conditions, CPM reliability was acceptable for all assessment methods in terms of sample sizes for potential experiments. The presented results are encouraging with regards to the use of the CPM as an assessment tool in experimental and clinical pain. Trial registration: Clinical Trials.gov NCT01636440.

Detecting dementia in patients with normal neuropsychological screening by Short Smell Test and Palmo-Mental Reflex Test: an observational study

BACKGROUND General practitioners (GPs) are in best position to suspect dementia. Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) are widely used. Additional neurological tests may increase the accuracy of diagnosis. We aimed to evaluate diagnostic ability to detect dementia with a Short Smell Test (SST) and Palmo-Mental Reflex (PMR) in patients whose MMSE and CDT are normal, but who show signs of cognitive dysfunction. METHODS This was a 3.5-year cross-sectional observational study in the Memory Clinic of the University Department of Geriatrics in Bern, Switzerland. Participating patients with normal MMSE (>26 points) and CDT (>5 points) were referred by GPs because they suspected dementia. All were examined according to a standardized protocol. Diagnosis of dementia was based on DSM-IV TR criteria. We used SST and PMR to determine if they accurately detected dementia. RESULTS In our cohort, 154 patients suspected of dementia had normal MMSE and CDT test results. Of these, 17 (11 %) were demented. If SST or PMR were abnormal, sensitivity was 71 % (95 % CI 44-90 %), and specificity 64 % (95 % CI 55-72 %) for detecting dementia. If both tests were abnormal, sensitivity was 24 % (95 % CI 7-50 %), but specificity increased to 93 % (95 % CI 88-97 %). CONCLUSION Patients suspected of dementia, but with normal MMSE and CDT results, may benefit if SST and PMR are added as diagnostic tools. If both SST and PMR are abnormal, this is a red flag to investigate these patients further, even though their negative neuropsychological screening results.

Raum – Perspektive – Medium 2: Wahrnehmung im Blick. reflex: Tübinger Kunstgeschichte zum Bildwissen

Im zweiten Workshop zum Thema „Raum – Perspektive – Medium“, der im Februar 2009 am Kunsthistorischen Institut der Universität Tübingen stattfand, kristallisierten sich zwei zentrale Thesen heraus, die im nun folgenden Band aus interdisziplinärer Perspektive beleuchtet werden: Erstens die Frage nach dem Anteil des Betrachters am Bildprozess und zweitens eine damit einhergehende Bewertung des Medienbegriffs. In reflex 2 sind nun die Texte versammelt, die aus dem Workshop „Raum – Perspektive – Medium 2“ hervorgegangen sind.