The effect of autonomic manipulation on heart rate variability in dogs

Beat‐to‐beat variation of heart rate is reflective of autonomic balance and has been used to assess pain and stress in human beings. The purpose of this investigation was to pharmacologically manipulate the autonomic nervous system and to determine the effect of these manipulations on heart rate variability (HRV) in dogs. Four adult male hound dogs (27 ± 1 kg) were used in the investigation. Each dog was given five treatments: Parasympathetic blockade (glycopyrrolate; 0.01 mg kg^–1 IV and 0.01 mg kg^–1 IM), parasympathetic stimulation (phenylephrine; 0.005 mg kg^–1 IV + 0.05 mg kg^–1hour^–1), sympathetic blockade (propranolol; 0.11 mg kg^–1 IV), sympathetic stimulation propranolol; 0.01 μg kg^–1 minute^–1), and saline control. At least 48 hours were allowed between treatments. ECG recordings were obtained using an ambulatory ECG monitor. A 5‐minutes period of continuous recording obtained ~30 minutes after initiation of drug administration was used for data analysis. Changes in HRV were evaluated by time and frequency‐domain analysis. The standard deviation of normal R‐R intervals (SDNN), as well as the standard deviation of successive differences in RR intervals (SDSD) were assessed for each treatment. Low frequency (LFP; 0.05–0.15 Hz), high frequency (HFP; 0.15–0.35 Hz), and total (TP; 0.017–0.5 Hz) spectral power were also determined. The LFP:HFP ratio was also evaluated. A two‐way anova with a Tukey's test was used to detect differences (p < 0.05). Administration of glycopyrrolate or isoproterenol increased HR and decreased SDNN and SDSD below control levels. Phenylephrine or propranolol administration were without effect. LFP was diminished by glycopyrrolate and isoproterenol, but was unaffected by phenylephrine and propranolol. HFP, TP, and LFP:HFP were unaffected by treatment. Both branches of the autonomic nervous system influence SDNN and LFP. SDSD, in contrast, is altered primarily by parasympathetic activity. Thus, it appears that parasympathetic activity modulates HRV in the resting dog, as either withdrawal of parasympathetic influence or accentuated sympathetic activity led to significant changes in these measures of HRV. Conversely, augmentation of parasympathetic activity or withdrawal of sympathetic tone minimally affected HRV.     

The effect of anesthesia and surgery on heart rate variability in dogs

Heart rate variability (HRV) may be useful for objective assessment of stress and pain in animals. The objective of this study was to describe the effect of anesthesia and surgery on HRV in dogs. We hypothesized that surgery would decrease HRV to a greater degree and for a longer duration than anesthesia alone. Four healthy male dogs (29 ± 2 kg) were instrumented for ambulatory ECG monitoring. Continuous ECG data was obtained for 1 day prior to, and 6 days following anesthesia alone (ANES) or anesthesia plus unilateral stifle arthrotomy (ANSX). The anesthetic protocol included xylazine (0.5 mg kg^–1 IM), morphine (0.5 mg kg^–1 IM), atropine (0.04 mg kg^–1 IM), thiopental (10 mg kg^–1 IV) and isoflurane in oxygen. A single dose of morphine (0.5 mg kg^–1 IM) was administered at extubation. Time domain analysis of HRV was performed on 5 minutes epochs of artefact‐ and arrhythmia‐free ECG data obtained at 12 noon and 12 midnight on each of the seven experimental days. Mean RR interval, standard deviation of normal R‐R intervals (SDNN), and the standard deviation of successive differences in RR intervals (SDSD) were compared to baseline for ANES and ANSX. Pain scores obtained during the day were also evaluated. Significance was set at p < 0.01. There were no differences between groups for any baseline data. Mean RR interval did not differ from baseline on days 1–6 in ANES or ANSX. SDNN and SDSD values at noon were not different from baseline on days 1–6 in ANES or ANSX. At midnight on days 1 and 2, SDNN was significantly decreased from baseline in ANSX, and on day 1 a significant difference between groups existed. ANSX values of SDSD at midnight were significantly decreased from baseline and ANES on day 1. Pain scores for ANSX were significantly greater than baseline on days 1–3, and different from ANES on days 1–5. These results suggest that HRV is decreased following anesthesia plus surgery, and that changes in HRV may be associated with pain.     

Road to ruin: targeting proteins for degradation in the endoplasmic reticulum

Some nascent proteins that fold within the endoplasmic reticulum (ER) never reach their native state. Misfolded proteins are removed from the folding machinery, dislocated from the ER into the cytosol, and degraded in a series of pathways collectively referred to as ER-associated degradation (ERAD). Distinct ERAD pathways centered on different E3 ubiquitin ligases survey the range of potential substrates. We now know many of the components of the ERAD machinery and pathways used to detect substrates and target them for degradation. Much less is known about the features used to identify terminally misfolded conformations and the broader role of these pathways in regulating protein half-lives.     

Endogenous Progesterone Concentrations Affect Progesterone Release from Intravaginal Devices Used for Oestrous Synchronization in Cattle

Intravaginal progesterone‐releasing devices are largely used both as contraceptives in humans and as a component of oestrous synchronization protocols in cattle. To reduce costs in large‐scale timed artificial insemination, the reuse of these releasing devices is common. Passive hormone diffusion, however, depends on the concentration gradient, which could affect the amount of residual progesterone present in these devices after a first use. To evaluate the effect of the presence of a corpus luteum in the release of progesterone from intravaginal devices, three synchronization protocols were designed to simulate the effects of inserting the device in the early dioestrus, late dioestrus or anoestrus. Holstein‐Zebu cross‐bred heifers were randomly allocated into one of these three treatments, and a series of blood samples was taken to evaluate the plasma progesterone concentrations. After 8 days, the intravaginal devices were removed and underwent a previously validated alcoholic extraction technique to measure the residual progesterone. Non‐used devices were used as controls. As expected, the simultaneous presence of the intravaginal device and a corpus luteum resulted in increased plasma progesterone concentrations. Conversely, the amount of residual progesterone in the devices after use was inversely proportional to the plasma progesterone concentration. These results demonstrate that the release rate of progesterone from intravaginal devices is affected by the endogenous concentration of this hormone; consequently, the strategy for reuse should account for the category and expected luteal cyclic activity of the animals undergoing synchronization protocols.     

Transitions between blocked and zonal flows in a rotating annulus with topography

The mid-latitude atmosphere is dominated by westerly, nearly zonal flow. Occasionally, this flow is deflected poleward by blocking anticyclones that persist for 10 days or longer. Experiments in a rotating annulus used radial pumping to generate a zonal jet under the action of the Coriolis force. In the presence of two symmetric ridges at the bottom of the annulus, the resulting flows were nearly zonal at high forcing or blocked at low forcing. Intermittent switching between blocked and zonal patterns occurs because of the jet's interaction with the topography. These results shed further light on previous atmospheric observations and numerical simulations.