Evaluation of heart rate variability measurement as perioperative pain control in castration model in pigs
Measurement of heart rate variability (HRV) is a non-invasive technique visualizing the functionality of the autonomic nervous system at the heart (von Borell 2007). HRV analysis is used besides various clinical applications of human and veterinary medicine in anesthesiology and pain research in pigs. For instance, the sympathovagal balance describing parameter LF/HF changes in pigs after tail biting (Zupan et al. 2012). Frequency-related parameters in pigs are equally affected by surgical manipulations during general anesthesia (Martin-Cancho et al. 2006).
HRV measurement in pigs has so far been conducted using invasive measurement methods in addition to non-invasive telemetric measurement methods in order to also perform measurements on non-restrained pigs. Telemetric measurements in pigs are achievable on the one hand by the means of telemetric ECG devices (Suzuki et al. 1998, Kuwahara et al. 1999, Kuwahara et al. 2004, Olmstead et al. 2005) or by telemetric chest strap systems primarily designed for humans (Marchant-Forde and Marchant-Forde 2004, Marchant-Forde et al. 2004, Düpjan et al. 2011, Zupan et al. 2012, Mahnhardt et al. 2014, Leliveld et al. 2016). The chest strap BioHarnessTM 3 utilized in this study (Zephyr Technology, Medtronic, Annapolis, USA; below called: BioHarness chest strap) has not yet been used on pigs before.
The aims of this study were to evaluate the BioHarness chest strap’s measurement accuracy with an established telemetric ECG device (Televet® 100, Engel Engineering GmbH, Heusenstamm, Germany; below called: Televet 100) and after assessing the suitability of the BioHarness chest strap, to determine whether HRV-analysis allows for a valid analgesia monitoring in the castration model. For this purpose, HRV parameters at the time of intraoperative pain reactions (based on a pain scoring) were compared with pre- and postoperative base values.
To evaluate the BioHarness chest strap in the pilot study, simultaneous measurements were carried out on five male rearing pigs (German Landrace/German Large White x Piétrain/Duroc; 28 – 58 kg) with the BioHarness chest strap and Televet 100.
For the HRV-analysis with the BioHarness chest strap in the main study, 30 male rearing pigs (genetics see above; 36 – 48 kg) were castrated for imminent fattening and slaughtering. One day before castration, the pigs in waking state were kept in temporary separate housing and recorded by BioHarness chest strap in their lying resting position. Castration at Regio Pubis was conducted under ketamine-azaperone general anesthesia customary in practice.
Each intraoperative step (measurements in parts of 3 minutes) was assessed with a pain scoring, where score 0 describes no defense reaction (surgical tolerance) and score 1 or higher the presence and intensity of defense reactions. 24 hours after surgery, HRV was recorded like one day before surgery and a clinical examination of pain symptoms was performed.
The evaluation of BioHarness chest strap resulted in a comparable measuring accuracy to the Televet 100 ECG-device. Results of the HRV analysis with the BioHarness chest strap related to intraoperative steps or manipulations compared to the base value before castration in main study were an increase of meanRR parameter and decrease of SDNN and RMSSD parameters. There was an increase of parameter LF (n.u.) and LF/HF that reflects sympathetic activity at the time of skin incision, incision of vaginal process and traction of spermatic cord. The mainly by vagal activity affected parameter HF (n.u.) decreased at the time of skin incision and incision of vaginal process. Pertaining to the pain scoring, there was a significant rise of LF (n.u.) when Score 1 to 3 occurred compared to surgical tolerance (Score 0). The parameters HF (n.u.) and LF/HF narrowly missed out the significance level (p < 0,05). Only two pigs had postoperative potentially pain-related symptoms (fever or wound irritation), so it is not possible to make a conclusive statement. In general, pigs tolerated the chest strap very well, species-specific habits of eating, resting and activity were not influenced by it.
In this study, it is recognizable that pain specific defense reactions correlate positively with LF, which is also described in the literature with intraoperative pain stimuli and other painful conditions in pigs (see above). Both somatic (skin incision) and visceral pain components (incision of vaginal process and traction of spermatic cord) influence LF (n.u.), HF (n.u.) and LF/HF parameters. For an effective and predictive management of analgesia, further studies should be conducted with a greater number of animals or number of data records establishing a threshold value for LF (n.u.) or possibly other parameters which allows for detecting pain due to decreasing anesthesia before the onset of defense reactions. Prospectively, the BioHarness chest strap could also be used to examine animal welfare impairments in other clinicals contexts or zootechnical interventions in pigs.
Aktualisiert: 2021-04-16
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Influence of testosterone on proteinuria and nephropathy in the rat models of chronic renal disease
Albuminuria associated with chronic renal disease is the most important poly-genetic characteristic for the origin of cardiovascular as well as renal diseases. Many studies have revealed that androgens such as testosterone are of paramount importance for the progression of chronic renal disorders. For example, there is an enhanced de-cline of renal functions in male compared to female patients leading to an accelerat-ed formation of proteinuria as well as albuminuria. Due to their genetically determined mode animal models such as MWF as well as Dahl/SS-rats can be employed to show the correlation between albuminuria and their hormonal balance. The aim of this work was to verify whether it is possible to influence albuminuria in combination with different accompanying phenotypic characteristics such as blood pressure by castration. By this procedure testosterone should have been eliminated nearly com-pletely. The studies were performed in MWF and Dahl/SS-rats using Wistar rats as control group. Further the inhibition of all testosterone receptors in combination with castration and hormone replacement therapy was investigated. In preliminary studies to this work, three different aspects were covered. Firstly, physiological values of tes-tosterone in every rat strain were evaluated. Secondly, it could be shown that castra-tion of MWF as well as Dahl/SS-rats has independent from its timing a protective ef-fect towards the origin of an albuminuria. Already one week after castration a signifi-cant decline of an albuminuria could be detected even in rats with a progressed renal disorder. Thirdly, it was evaluated whether physiological values of testosterone could be achieved by its substitution to be able to perform the hormone replacement thera-py. On the basis of the preliminary studies a group design could be elaborated and used within this work. As a double controlled study a hormone substitution after cas-tration in parallel with the inhibition of testosterone receptors by flutamide - a selec-tive antagonist against androgens receptor - was performed. A clear and significant decline of an albuminuria could be shown within the castrated groups in both rat populations - namely MWF and Dahl/SS. Castration was performed at 10 weeks of age. The treatment with flutamide revealed that this decline was solely due to effect of testosterone. An effect on blood pressure in all examined study groups did not show a significant change concluding that testosterone does not have a detectable effect on blood pressure. Nevertheless, a direct correlation of presence and absence of testosterone and renal clearance of albumin could be impressively demonstrated within this work. After castration, the degree of albuminuria decreased about 50%. This effect could further be dramatically increased by additional inhibition of testos-terone receptors. In addition, different other phenotypic characteristics were evaluat-ed. The determination of a biomarker for renal function called cystatin C did not re-veal a significant difference between the different study populations. The histological-ly determined parameters showed a regression of renal impairment in castrated as well as testosterone and flutamide medicated study groups. Renal impairment mark-ers Kim1 and Ngal were determined molecular genetically. Results here also showed that values significantly decreased after castration and subsequent medication with testosterone as well as flutamide. The values obtained were comparable to values of the control Wistar group. Interestingly, Kim1 also showed decreasing values after pure castration. The obtained results of the performed study provide significant evi-dence that albuminuria in MWF as well as Dahl/SS-rats could be decreased after nearly complete elimination of testosterone production and inhibition of testosterone receptors. In addition, histological markers as well as molecular markers such as Ngal and Kim1 support these findings by testifying a decline in renal impairment. The results of this set the stage for potential translations of these findings into individual and standardized therapeutic strategies for treatment or prevention of renal diseases in humans.
Aktualisiert: 2019-12-31
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