Most of the evidence supporting the efficacy of digital hypothermia for prevention and treatment of acute laminitis has arisen from experimental studies where conditions were carefully controlled. In these experimental studies,1–6 horses were confined to stocks, and digital hypothermia was achieved by continuous ice water immersion of the distal limb (including the foot), which resulted in profound and consistent cooling of the feet. However, similar methods of ice water immersion are impractical in the clinical setting due to the weight and bulk of the water column that must be carried with the limb when a horse is free to ambulate in a stall. Cooling systems utilizing ice packs or ice sleeves are more practical and convenient for clinical use; however, there is conflicting evidence regarding their cooling efficacy. The ice pack system (ICEPACK) and ice sleeve system (SLEEVE) were apparently ineffective in some studies7,8 but had comparable cooling efficacy to ice water immersion in others.9,10 Inconsistency in both the location of temperature measurement (lamellar tissue [LAM], hoof wall [HW], or hoof surface [HS]) as well as variation in management of the ambulatory conditions of the horses (confined to stocks, crosstied, or free in stalls) complicates interpretation and direct comparability of the results from these existing studies. Although direct measurement of LAM temperature is ideal for the evaluation of cooling methods, it is impractical in ambulatory horses for extended periods. For this reason, HW temperature (surface or embedded) is often utilized; however, the relationship between HW and tissue temperature has not been established and is likely to differ depending on the cooling method.
We sought to evaluate the efficacy of different cooling methods under clinically relevant conditions. The specific aims of the current study were to (1) determine the relationship between HW temperature and LAM temperature for different cooling techniques and (2) evaluate the efficacy of different cooling techniques in ambulatory, stall-confined horses over extended periods by using HW temperature to estimate LAM temperature. We hypothesized that cooling using ice water immersion would be more effective for reducing LAM temperature compared to ice pack or sleeve methods.
Methods
This project was approved by the institution’s animal ethics committee.
Subject inclusion
Eight university-owned adult horses (3 Standardbreds, 3 Thoroughbreds, and 2 Warmbloods; 6 geldings and 2 mares; bodyweight, 472 to 622 kg) were used for the study. The horses were clinically healthy and sound at the walk when examined on a hard surface. The horses had no evidence of laminitis on standard lateral-medial radiographs obtained of the forefeet at the beginning of the study. An a priori sample size calculation (α, 0.05; power, 0.8) using LAM temperature data from a previous study8 indicated that a sample size of at least 4 horses would be sufficient to detect a 5 °C difference between cooling methods.
Experimental design
All experiments were performed in a climate-controlled barn (temperature set at 22 °C). In experiment 1, 5 horses had both forefeet instrumented with temperature probes in 3 separate locations: in the LAM, embedded in the HW, and attached to the HS. Four different cooling methods were then applied, and temperatures were continuously logged at each probe site over a 4-hour period, during which the horses were crosstied in stalls. Two cooling methods were tested at once by simultaneous application to the forelimbs. After a 1-hour washout period (and confirmation that the temperature at each probe site had returned to within 2 °C of the precooling temperature), the experiment was repeated using the remaining 2 methods.
In experiment 2, 6 horses had both forefeet instrumented with a temperature probe embedded in the HW only. Four different cooling methods were applied, and temperatures were continuously logged at each probe site over an 8-hour period, during which the horses were free in stalls. Two cooling methods were tested at once (simultaneous application to each of the forelimbs), with a 12-hour washout period before repeating the experiment with the remaining 2 methods. Control data (no cooling) for each limb were recorded for 15 minutes prior to the application of the first cooling method. For both experiments 1 and 2, the order of application and limb assignment (left or right) was determined by random number generator.
Temperature probe instrumentation
Eighteen-gauge, 152-cm-long tissue temperature probes (IT-18 Special Flexible Microprobe; Physitemp Instruments Inc) were used in all probe locations in both experiments. Lamellar tissue temperature was measured by insertion of probes using a placement method similar to that previously described for LAM microdialysis probes.11,12 Briefly, after resecting 10 X 10-mm holes in the keratinized tissue of the white line region, abaxial sesamoid perineural anesthesia, and aseptic preparation, the probes were introduced using an 18-gauge, 15-cm spinal needle with a preloosened grip-hub (DTN-18–15.0; Cook Inc) inserted via the white line, parallel with the dorsal HW. With the probe in place, the needle was removed and the temperature probe secured to the dorsal HW and skin of the pastern, metacarpal region, and antebrachium using adhesive tape. Standard lateral-medial radiographs were obtained of both forefeet to confirm the location of the probe tip in the region of the lamellae (Figure 1).
A representative photograph (A) and radiograph (B) of a foot instrumented with 3 thermocouple probes for simultaneous measurement of temperature in experiment 1. The 3 thermocouple probes are visible in the magnified radiograph (C) at the HS (HS; blue arrow), embedded in the hoof wall (HW; orange arrow), and within the middorsal lamellar tissue (red arrow).
Citation: American Journal of Veterinary Research 86, 3; 10.2460/ajvr.24.10.0291
For HW placement, the thickness of the radiodense portion of the dorsal HW was first measured radiographically at a point halfway between the coronary band and the ground surface. A 2-mm-diameter hole was drilled perpendicular to the dorsal HW at this site to a depth 75% of the radiographically measured HW thickness. The probe, covered with some heat sink paste (Cool Blue Heat Sink Paste; Uniweld Products Inc), was introduced into the hole and secured to the HW surface using adhesive tape.
For HS probe placement, the temperature probe was positioned on the mid-dorsal HW surface on the midline and secured in place using an adhesive tape patch, which was further secured to the dorsal HW with a screw at each corner and cyanoacrylate glue on each perimeter.
The temperature probe leads were secured to the limb at the pastern, midcannon region, and antebrachium using vinyl tape. Temperature was simultaneously logged at 1-minute intervals using data logging devices (RDXL6SD; Omega Engineering Inc) secured by a harness to the pectoral region. Ambient temperature was recorded using an additional probe that was positioned free in the air.
Cooling methods and application
Four different cooling methods were evaluated (Figure 2): (1) A commercially available ice pack system (ICEPACK) incorporating elastic material to hold gel ice packs in contact with the HW and distal limb from the fetlock distally (Pro Therapy Laminitis Boot by Ice Horse; MacKinnon Products); (2) A commercially available SLEEVE was secured to the pastern via a foam-lined cuff and held ice (but not water, which was free to leak out) in contact with the distal limb from the level of the upper metacarpus to the pastern, not including the hoof (Cordura Ice Boots; Jack’s Inc); (3) A commercially available ice water immersion boot with a relatively low volume (LV-IMMERSION) consisted of a boot with a sole and continuous sleeve extending from the midcannon level distally, which held ice and water against the limb and the hoof (Original Boot; CryoStride). The total volume of the boot was approximately 6 L; (4) A commercially available ice water immersion boot with a higher volume (HV-IMMERSION) consisted of a boot that extended from a level just distal the carpus, holding ice and water against the limb and hoof (Ice Spa Pro; Soft-Ride). The total volume of the boot was approximately 10 L. This boot was difficult to maintain in ambulatory horses during experiment 1; therefore, for experiment 2 a custom prototype HV-IMMERSION made of a lightweight material with a similar overall size and total volume (15 L) was used (Soft-Ride). The material was impervious only in the distal 22 cm (approx level of the midcannon distally), and therefore water was contained only within this distal portion, which had a volume of 8 L. A harness system held it in place during ambulation. For the initial filling of LV-IMMERSION and HV-IMMERSION devices, the boots were first filled with ice, and then water was added to cover the ice. Subsequently, ice (without additional water) was restocked (or ice packs changed) every hour for the first 2 hours, then every 2 hours afterwards in both experiments 1 and 2. Ice was produced by a commercial ice maker (CU3030SA-1; Scotsman Ice Systems), producing cubes with approximate dimensions of 2 cm X 2 cm X 1 cm.
Photographs of the cooling methods used in the experiment. A—An ice pack system (ICEPACK) holds gel ice packs in contact with the HW and distal limb. B—An ice sleeve system (SLEEVE) holds ice in contact with the distal limb with water free to leak out the cuff at the level of the pastern (not including the hoof). C—An ice water immersion boot with a relatively low volume (LV-IMMERSION) holding approximately 6 L of ice and water against the distal limb and the hoof. D—A higher volume boot (HV-IMMERSION) holding approximately 10 L of ice and water against the distal limb and hoof. E—A custom prototype HV-IMMERSION boot (used in experiment 2) was made of a lightweight material impervious to water only in the distal portion (holding approx 8 L) and incorporated a harness system to help hold it in place during ambulation.
Citation: American Journal of Veterinary Research 86, 3; 10.2460/ajvr.24.10.0291
Data analysis
All analyses were conducted using Stata/MP, version 15.1 (StataCorp LLC), with 2-sided tests of hypotheses and P < .05 as the criterion for statistical significance. Descriptive statistics are expressed as mean (95% CI) for normally distributed variables and median (IQR) for other continuous variables. The Shapiro-Wilk test was used to assess the normality of data.
A linear regression model was used to examine the relationship between temperature measured as the outcome at the different probe sites (HS, HW, and LAM) for each cooling method. From this, an equation for predicting lamellar temperature from HS and HW was developed for each cooling method. The strength of association was examined using Lin concordance calculated for HS versus LAM and HW versus LAM. The measured LAM temperature over the final hour in experiment 1 was compared between methods using a mixed-effects linear regression model, with the fixed effect of method and random effects set on the level of the individual animal. For experiment 2, LAM temperatures were predicted from HW temperature using the equations developed in experiment 1. The predicted LAM temperature was compared over time and between cooling methods using a mixed-effects linear regression model, with the fixed effect of cooling method (confounded by time) and random effects set on the level of the animal. Post hoc comparisons of the fixed portion of the linear predictions were performed to compare tissue temperature over the 8-hour experiment (excluding the first 120 minutes) between modalities and also to the control period data (15 minutes preapplication of the cooling device). In order to permit for possible departures from normality for some of the outcomes, robust estimation of the variance was used. Post hoc analysis was performed on the model-adjusted means. Model-adjusted means and effects were reported together with their 95% CI.
Results
The mean (± SD) ambient temperature was 22 ± 0.4 °C over the entire experimental period.
Experiment 1
Both HV-IMMERSION and LV-IMMERSION caused significant decreases in LAM temperature over time (P < .001), whereas the other modalities did not (Figure 3). The LAM temperature (marginal mean [95% CI]) for the fixed portion of the modeled data was 19.3 °C (16.7 to 21.0) for HV-IMMERSION, 30.5 °C (25.2 to 35.8) for LV-IMMERSION, 33.8 °C (33.0 to 34.6) for SLEEVE, and 32.8 °C (30.3 to 35.4) for ICEPACK. From the data acquired from this experiment, the regression equation, LAM = HW X coefficient + 7.09, was determined to predict LAM based on HW using a specific coefficient for each method (SLEEVE, 0.86; ICEPACK, 0.91; LV-IMMERSION, 0.97; HV-IMMERSION, 1.08). Using this equation, the predicted LAM tissue temperatures showed good concordance (ρc = 0.93 [0.93 to 0.94]; P < .001) and correlation (r = 0.93; P < .001) with actual measured LAM temperature. Prediction of LAM based on surface temperature had lower concordance (ρc = 0.82 [0.81 to 0.83]; P < .001) and correlation (r = 0.83; P < .001) with measured LAM temperature; therefore, LAM prediction based on HW was used for experiment 2.
Plots of mean (95% CI) temperature against time for 4 different methods of distal limb cooling applied to a single limb in 5 healthy horses standing crosstied in a stall. Temperature was measured simultaneously by 3 thermocouple probes placed on the HS, embedded in the HW, and embedded in the lamellae (LAM). AMB = Ambient temperature.
Citation: American Journal of Veterinary Research 86, 3; 10.2460/ajvr.24.10.0291
Experiment 2
The LV-IMMERSION and HV-IMMERSION methods were associated with rapid, sustained decreases in HW and estimated LAM temperatures (Figure 4). The temperatures decreased more rapidly with HV-IMMERSION and stabilized after approximately 2 hours, whereas LV-IMMERSION was associated with a slower decrease in HW and estimated LAM temperatures, stabilizing after approximately 6 hours. The HW and estimated LAM temperatures did not decrease in a similar way with SLEEVE and ICEPACK. The fixed portions of the modeled marginal mean (95% CI) for measured HW temperatures were: HV-IMERSION, 4.7 °C (2.5 to 7.0); LV-IMMERSION, 11.1 °C (8.0 to 14.1); ICEPACK, 25.3 °C (21.9 to 28.7); SLEEVE, 27.6 °C (23.1 to 32.2); and control, 29.7 °C (29.2 to 30.2). The estimated LAM temperatures were significantly lower for HV-IMMERSION (12.3 °C [10.0–14.6]) and LV-IMMERSION (17.8 °C [14.9 to 20.8]) compared to control (32.7 °C [32.2 to 33.2]; P < .001); however, ICEPACK (30.0 °C [26.9 to 33.1]; P < .08) and SLEEVE (30.9 °C [27.0 to 34.8]; P < .4) were not different from control (Table 1).
A comparison of the mean (95% CI) HW temperature (A) and predicted lamellar tissue temperature (B) between 4 different cooling devices fitted to healthy horses free to move in a stall environment over an 8-hour period. Rapid and sustained decreases in HW and predicted lamellar tissue temperatures were seen with ice and water immersion methods (LV-IMMERSION and HV-IMMERSION), which were associated with lower mean temperatures in the last 4 hours of the experiment compared to the ice sleeve and ice pack (P < .001).
Citation: American Journal of Veterinary Research 86, 3; 10.2460/ajvr.24.10.0291
Lamellar tissue temperatures (°C) estimated using temperatures recorded using thermocouples embedded deep in the hoof wall during an 8-hour cooling period using 4 different cooling methods compared to control (a 15-minute preapplication period).
| Method | Mean (95% CI) | Contrast vs control (95% CI) | P value vs control | Contrast vs HV-IMMERSION (95% CI) | P value vs HV-IMMERSION |
|---|---|---|---|---|---|
| Control | 32.7 | 20.4 | < .001 | ||
| 32.2 to 33.2 | 17.8 to 22.9 | ||||
| ICEPACK | 30 | −2.7 | .08 | 17.7 | < .001 |
| 26.9 to 33.1 | −5.6 to −0.3 | 13.0 to 22.3 | |||
| SLEEVE | 30.9 | −1.8 | .4 | 18.6 | < .001 |
| 27.0 to 34.8 | −5.6 to −2.0 | 14.8 to 22.4 | |||
| LV-IMMERSION | 17.8 | −14.9 | < .001 | 5.5 | .001 |
| 14.8 to 20.8 | −17.7 to −12.1 | 2.2 to 8.8 | |||
| HV-IMMERSION | 12.3 | −20.4 | < .001 | ||
| 10.0 to 14.6 | −22.9 to −17.8 | ||||
HV-IMMERSION = High-volume ice water immersion. ICEPACK = Ice pack system. LV-IMMERSION = Low-volume ice water immersion. SLEEVE = Ice sleeve system.
The 6 horses were free to ambulate in a stall.
Discussion
Immersion in ice and water was the most effective means of cooling the lamellae in this study. The high-volume immersion method was more effective than the lower-volume immersion method. These results were first confirmed in crosstied horses using direct LAM temperature measurement, then in horses free to ambulate in the stall. This study also demonstrates that LAM temperature can be accurately predicted using HW temperature measured using a probe embedded in the HW, close to the lamellae. This minimally invasive method facilitated accurate measurement of lamellar cooling efficacy in horses kept under conditions that would closely approximate a hospitalized clinical case. The horses were free to ambulate in a stall over an extended cooling period, and there was no requirement for sedatives or local analgesia for instrumentation or during the cooling period.
The results of the current study differ from some previous studies where the same or similar cooling methods were tested. A previous study9 examined the cooling efficacy of the SLEEVE device over a 3-hour period, with LAM temperature measured using a probe inserted into the proximal aspect of the dorsal lamellae via the coronary band. In that study, the SLEEVE device reduced LAM temperatures to a minimum of approximately 10 °C over the 3-hour study period. In the current study, the mean LAM temperature was approximately 34 °C after 4 hours of SLEEVE application in crosstied horses. Furthermore, in the ambulatory horses in the current study, the estimated LAM temperature was approximately 31 °C after 8 hours of SLEEVE application. The discrepant results could be due to some key differences in methods between these studies. Confinement to stocks in the previous study (vs crosstying or free ambulation) may have improved the cooling performance of the SLEEVE; however, it is unlikely that such a large difference would be due to this factor alone. It is possible that crushed ice, as used in the previous study, could allow for more rapid or effective cooling of the limb due to the smaller ice particle size and resultant larger area of skin contact compared to the ice cubes used in the current study. However, the ice cubes used in the current study were relatively small (approx half the size of standard drinking ice cubes), and crushed ice is not routinely used in clinical practice. Although identical temperature probes were used in both studies, insertion through the coronary band using a 16-gauge, 1.5-inch needle (as used in the previous study) positions the thermocouple in the proximal-most portion of the lamellae, and the body of the embedded probe must course across the dorsal aspect of the distal interphalangeal joint capsule. Despite radiographic confirmation of the thermocouple position within the lamellae at the beginning of the experiments in that study, withdrawal of the probe over time into a more superficial location over the course of the experiment is possible with flexion of the distal limb, even in horses confined to stocks. This is compounded by the Teflon coating on these particular temperature probes, which makes them difficult to secure to the limb with adhesives. In the current study, the LAM probes were introduced from distal to proximal via the white line in order to ensure the thermocouple was positioned in the mid-dorsal lamellae. Furthermore, the probe was mechanically secured as it doubled back on itself through the hoof defect in the white line, where it was held in place by a molded plug of silicone impression material, then secured to the HW using an adhesive tape patch that was also mechanically fastened to the HW. This method of placement ensured the thermocouple was secure in the mid-dorsal lamellae and less prone to displacement due to motion, especially since the embedded probe did not cross a joint. The differences in probe placement and fixation are likely to be the main source of the variation in temperature reported between these studies. In the only other published evaluation of the SLEEVE device,7 the mean HW surface temperature was 26 °C after 8 hours, which was consistent with the current study.
In a previous study10 evaluating a similar ICEPACK device in 6 horses crosstied in a stall, the median HW surface temperature was approximately 11 °C over an 8-hour application period. In the current study, HW surface temperature decreased to approximately 20 °C over the 4-hour application period in experiment 1; however, the LAM temperature in experiment 1 (and the estimated LAM temperature in experiment 2) remained > 30 °C, indicating that although this method cooled the HS, it did not effectively cool the deeper tissues, including the lamellae. Although HW surface temperature correlates with lamellar temperature under most circumstances, caution must be exercised when using it to interpret the LAM cooling efficacy of specific modalities. The results of the current study are consistent with a previous study8 in which temperature was also measured directly within the lamellae and the digital vein in response to the application of different distal limb cooling modalities. In that study, a similar gel ice pack boot caused only a 2 °C decrease in lamellar temperature; however, ice and water immersion, either to the level of the upper pastern (using a 5-L fluid bag) or the mid-to-upper cannon (using a wader-style vinyl boot) achieved rapid cooling to approximately 11 °C over a 2-hour treatment period.
Ice and water immersion of the distal limb appears to be the most effective way to overcome the barriers to effective heat transfer and cooling of the equine distal limb, which include the hair coat (acting as an insulator by trapping air) and the inflow of warm arterial blood. A water interface against the haired skin of the limb overcomes the conduction barrier of the coat and negates the difficulty in achieving consistent contact with the uneven surface of the equine distal limb. Immersion of the foot itself in the cooling boot prevents heat transfer from the environment through convection from ambient air and by conduction from the ground surface. The equine foot is also adapted to extreme cold: numerous arteriovenous anastomoses within the lamellae,13 common to tissues with thermoregulatory functions, can open and rapidly increase net perfusion of the foot to rapidly warm it, an intermittent phenomenon detectable during continuous immersion in recirculating cold water under controlled experimental conditions.14 Regardless, ice water immersion, as used in all published studies evaluating hypothermia for laminitis prevention and treatment, appears to provide consistent cooling of the distal limb. The greatest challenge when using ice and water immersion is adapting it to the freely ambulatory horse, and, indeed, this necessitated the creation of a prototype HV-IMMERSION device for experiment 2 in the current study.
The important therapeutic mechanisms of hypothermia and the ideal therapeutic temperature for laminitis prevention and therapy remain unclear. In both sepsis-related and hyperinsulinemia-associated laminitis, direct anti-inflammatory and hypometabolic effects of hypothermia within the LAM itself are thought to be the most important therapeutic mechanisms.5 Findings from experimental models suggest that although ischemia is likely to contribute to the development of supporting-limb laminitis,11 vasoconstriction and ischemia are not key components of the pathogenesis of acute sepsis-related or hyperinsulinemia-associated laminitis.6,15,16 Conversely, hypothermia-induced vasoconstriction may actually be a key therapeutic effect of foot cooling, reducing the delivery of blood-borne pathogens, pathogen-associated molecular patterns, or damage associated molecular patterns17 in sepsis-related laminitis or limiting the delivery of insulin to the lamellae during hyperinsulinemia.5 Vasoconstriction is thought to be the major mechanism (together with hypometabolism) by which hypothermia effectively prevents alopecia in human cancer patients undergoing chemotherapy.18–20 It should be noted that constriction of vasculature supplying the equine foot could be achieved using a device, such as the SLEEVE, even in the absence of profound cooling of the lamellae; however, more research on the effects of such regional cooling on perfusion of the foot would be required to investigate this. Until more specific information is published on ideal therapeutic temperatures, it is rational in the clinical situation to aim to reproduce the profound local LAM hypothermia that has proved effective in experimental studies. As the results of the current study confirm, ice and water immersion to a level of the mid-to-upper metacarpus ensures effective LAM hypothermia through local cooling of the foot as well as cooling of the arterial blood supply. Although the ice and water level relative to the limb was similar for LV-IMMERSION and HV-IMMERSION methods, the latter was more effective, likely due to the higher volume of water and ice around the limb and thus a greater capacity for heat transfer from the limb. Refinement of a method with sufficient volume to maximize tissue cooling yet still allow ambulation should be a priority.
Our study had some limitations. For logistical reasons, each cooling device was only applied to 1 forelimb of each horse in both experiments 1 and 2 while the other limb was simultaneously fitted with a different device. Although the order of application was randomized, and therefore the pairing of devices in the same horse was also random, the possibility exists that one device could have affected the efficacy of another, either through systemic cooling effects or unidentified effects on autonomic tone. In experiment 2, it would have been ideal to directly measure LAM temperature; however, to facilitate assessment under clinically relevant conditions, LAM was estimated based on HW temperature. This method appeared to be accurate based on the results of experiment 1, and the predicted LAM temperatures in experiment 2 were similar to those observed in experiment 1 for each cooling method. The impervious portion of the prototype HV-IMMERSION device used in experiment 2 had a higher volume compared with the HV-IMMERSION device used in experiment 1 (8 vs 6 L), and this would likely have improved the cooling performance; however, it is unlikely that this change would have meaningfully affected the estimate of LAM temperature, which was based on results from experiment 1. Another limitation is that only healthy horses were used for the study; therefore, the effect of acute laminitis (which causes persistent increases in hoof temperature) on the performance of the devices was not determined. Finally, the boots were only applied for an 8-hour period, whereas they would be applied for longer in a clinical setting. The data showed that LAM temperatures tended to plateau within 4 hours, and therefore the results should be representative of longer periods; however, it would be ideal to evaluate different cooling methods over longer periods under similar conditions to further test clinical applicability.
In conclusion, immersion in ice and water was most effective for cooling the lamellae under conditions similar to those that would be encountered in the clinic, with horses free to ambulate in a stall environment. Further refinement of techniques that allow for high-volume immersion of the distal limb without interfering with ambulation should be pursued.
Acknowledgments
The authors would like to acknowledge Dr. Elizabeth Nelson and Dr. Matthew Ford for their contributions to the experimental work.
Disclosures
Ice pack system boots were generously donated by MacKinnon Products, ice water immersion boots with a relatively low volume were generously supplied by CryoStride, and ice water immersion boots with a higher volume were generously supplied by Soft-Ride.
Funding
Funded by the Laminitis Research Fund, University of Pennsylvania.
References
- 1.↑
Dern K, Burns TA, Watts MR, van Eps AW, Belknap JK. Influence of digital hypothermia on lamellar events related to IL-6/gp130 signalling in equine sepsis-related laminitis. Equine Vet J. 2020;52(3):441–448. doi:10.1111/evj.13184
- 2.
Van Eps A, Pollitt C. Equine laminitis: cryotherapy reduces the severity of the acute lesion. Equine Vet J. 2004;36(3):255–260. doi:10.2746/0425164044877107
- 3.
van Eps AW, Leise BS, Watts M, Pollitt CC, Belknap JK. Digital hypothermia inhibits early lamellar inflammatory signalling in the oligofructose laminitis model. Equine Vet J. 2012;44(2):230–237. doi:10.1111/j.2042-3306.2011.00416.x
- 4.
van Eps AW, Pollitt CC, Underwood C, Medina-Torres CE, Goodwin WA, Belknap JK. Continuous digital hypothermia initiated after the onset of lameness prevents lamellar failure in the oligofructose laminitis model. Equine Vet J. 2014;46(5):625–630. doi:10.1111/evj.12180
- 5.↑
Stokes SM, Belknap JK, Engiles JB, et al. Continuous digital hypothermia prevents lamellar failure in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. Equine Vet J. 2019;51(5):658–664. doi:10.1111/evj.13072
- 6.↑
Stokes SM, Bertin FR, Stefanovski D, et al. The effect of continuous digital hypothermia on lamellar energy metabolism and perfusion during laminitis development in two experimental models. Equine Vet J. 2020;52(4):585–592. doi:10.1111/evj.13215
- 7.↑
van Eps AW, Orsini JA. A comparison of seven methods for continuous therapeutic cooling of the equine digit. Equine Vet J. 2016;48(1):120–124. doi:10.1111/evj.12384
- 8.↑
Reesink HL, Divers TJ, Bookbinder LC, et al. Measurement of digital laminar and venous temperatures as a means of comparing three methods of topically applied cold treatment for digits of horses. Am J Vet Res. 2012;73(6):860–866. doi:10.2460/ajvr.73.6.860
- 9.↑
Burke MJ, Tomlinson JE, Blikslager AT, Johnson AL, Dallap-Schaer BL. Evaluation of digital cryotherapy using a commercially available sleeve style ice boot in healthy horses and horses receiving i.v. endotoxin. Equine Vet J. 2018;50(6):848–853. doi:10.1111/evj.12842
- 10.↑
Morgan J, Stefanovski D, Lenfest M, Chatterjee S, Orsini J. Novel dry cryotherapy system for cooling the equine digit. Vet Rec Open. 2018;5(1):e000244.
- 11.↑
van Eps AW, Belknap JK, Schneider X, et al. Lamellar perfusion and energy metabolism in a preferential weight bearing model. Equine Vet J. 2021;53(4):834–844. doi:10.1111/evj.13356
- 12.↑
Medina-Torres CE, Pollitt CC, Underwood C, et al. Equine lamellar energy metabolism studied using tissue microdialysis. Vet J 2014;201(3):275–282. doi:10.1016/j.tvjl.2014.05.030
- 13.↑
Pollitt CC, Molyneux GS. A scanning electron microscopical study of the dermal microcirculation of the equine foot. Equine Vet J. 1990;22(2):79–87. doi:10.1111/j.2042-3306.1990.tb04215.x
- 14.↑
van Eps AW, Pollitt CC. Equine laminitis model: cryotherapy reduces the severity of lesions evaluated seven days after induction with oligofructose. Equine Vet J. 2009;41(8):741–746. doi:10.2746/042516409X434116
- 15.↑
Medina-Torres CE, Underwood C, Pollitt CC, et al. Microdialysis measurements of lamellar perfusion and energy metabolism during the development of laminitis in the oligofructose model. Equine Vet J. 2016;48(2):246–252. doi:10.1111/evj.12417
- 16.↑
Stokes SM, Bertin FR, Stefanovski D, et al. Lamellar energy metabolism and perfusion in the euglycaemic hyperinsulinaemic clamp model of equine laminitis. Equine Vet J. 2020;52(4):577–584. doi:10.1111/evj.13224
- 17.↑
Leise BS, Fugler LA. Laminitis updates: sepsis/systemic inflammatory response syndrome-associated laminitis. Vet Clin North Am Equine Pract. 2021;37(3):639–656. doi:10.1016/j.cveq.2021.08.003
- 18.↑
Hershman DL. Scalp cooling to prevent chemotherapy-induced alopecia: the time has come. JAMA. 2017;317(6):587–588. doi:10.1001/jama.2016.21039
- 19.
Nangia J, Wang T, Osborne C, et al. Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: the scalp randomized clinical trial. JAMA. 2017;317(6):596–605. doi:10.1001/jama.2016.20939
- 20.↑
Mokbel K, Kodresko A, Trembley J, Jouhara H. Therapeutic effect of superficial scalp hypothermia on chemotherapy-induced alopecia in breast cancer survivors. J Clin Med. 2024;13(18):5397. doi:10.3390/jcm13185397
