Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables

Burns, T.A.; Dembek, Katarzyna; Kamr, Ahmed; Dooley, Steven; Dunbar, L.K.; Aarnes, Turi K.; Bednarski, Linda; O’Brien, Caitlin E.; Lakritz, Jeffrey; Byrum, Beverly; Wade, Angie; Farmer, Rosemary; Tan, Sherilyn; Toribio, Ramiro E.

doi:10.1111/jvim.15029

Cited by 12 publications

(11 citation statements)

References 20 publications

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“…In our six study horses, we have demonstrated that after regular cobalt dosing over 7 weeks, no change in haematocrit was observed. This finding was consistent with that of Knych et al and Burns et al, bringing into question the validity of the proposed ‘performance enhancing effect’ of cobalt salts, namely stimulation of erythropoiesis.…”

Section: Discussionsupporting

confidence: 90%

“…By applying a statistical process to calculate the predicted measurement rather than plotting raw data, a smoothed line is generated while maintaining the same error bars to provide a graphical representation of the measurements in an easy to interpret format (Figures ). The sample size used in this study was sufficient to demonstrate the cumulative nature of cobalt and compared favourably with sample numbers used in other studies in this area …”

Section: Discussionmentioning

confidence: 60%

“…This approach was supported by Mobasheri who stated that cobalt is ‘potentially lethal’. The levels used in this study are a small fraction of those used by Burns et al when they reported acute toxic signs (up to 2000 mg of cobalt chloride per horse). In our study, the maximum blood cobalt levels recorded were under 70 μg/L, a fraction of the human chronic toxic threshold of between 300 and 800 μg/L proposed by Finley et al…”

Section: Discussionmentioning

confidence: 94%

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Cobalt accumulation in horses following repeated administration of cobalt chloride

et al. 2019

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Objective To monitor cobalt concentrations in urine, red blood cells and plasma after chronic parenteral administration of cobalt chloride evaluate these results against the current International Federation of Horseracing Authorities thresholds for detecting cobalt misuse. Design Eight mares were randomly assigned to four treatment groups, with two mares in each group: Group 1 – control group, Group 2 – 25 milligrams cobalt intravenously as CoCl2 weekly, Group 3 – 50 milligrams cobalt intravenously as CoCl2 weekly, and Group 4 – 25 milligrams cobalt intravenously mid‐week and at the end of the week. Urine and blood samples were collected before each weekly administration so that trough levels were assessed. In the group receiving two doses per week, urine and blood were collected prior to the dose given at the end of each week. Samples were initially collected at time zero then weekly for 10 weeks. Three further collections of urine and blood were made at days 81, 106 and 127. Methods Urine creatinine measurements to assess horse hydration status were performed by the Jaffe reaction method. Cobalt determinations in plasma, blood and urine were by inductively coupled plasma—mass spectrometry. Haematocrit concentrations, used to calculate red cell cobalt levels, were performed using a microhematocrit centrifuge. Statistical analyses were conducted in Genstat (v17, VSNi). Results Marked cobalt accumulation was evident with increasing cobalt concentrations for all sample matrices in specimens collected immediately prior to cobalt administration. Correlation between the sample matrices improved when urine cobalt concentration was adjusted for creatinine level. Red cell cobalt levels remained elevated for at least 12 weeks after cessation of administration, consistent with the lifespan of the red cell. There was no significant change in haematocrit concentrations for the duration of the study. Conclusion The current urine cobalt threshold was only effective at detecting acute cobalt exposure while the plasma cobalt threshold was able to consistently identify chronic high‐level cobalt exposure and potential cobalt misuse. The threshold values legislated for urine cobalt do not correlate with those set for plasma. The acute nature of urinary cobalt excretion provides a relatively small window through which cobalt administration is detected. Plasma and red cell cobalt concentrations can provide a clearer picture of potential cobalt misuse.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 94%

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Cobalt accumulation in horses following repeated administration of cobalt chloride

et al. 2019

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“…Moreover, a recent study demonstrated direct adverse effects of cobalt injections on cardiovascular system in horses. In particular, it has been revealed that Co infusion resulted in tachycardia, hypertension, muscle tremors, as well as elevation of Adrenocorticotropic hormone, cortisol, and troponin I levels (Burns et al, 2017), that may subsequently result in cardiac arrest and death (Mobasheri and Proudman, 2015).…”

Section: The Use Of Cobalt In Equine Sports and Its Limitationsmentioning

confidence: 99%

Cobalt in athletes: hypoxia and doping - new crossroads

Skalny¹,

Zaitseva²,

Gluhcheva³

et al. 2019

J Appl Biomed

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Cobalt is an essential trace element that is known to mimic hypoxia and hypoxic training. Inorganic Co compounds are capable of Hypoxiainducible factor-1 (HIF-1) activation, resulting in up-regulation of gene expression including erythropoietin (Epo). Experimental studies have demonstrated that Co treatment may increase hypoxic tolerance of different tissues, improve muscle metabolism and exercise performance. Other mechanisms may also involve modulation of steroid hormone and iron metabolism. Based on these experimental studies, in 2017 inorganic cobalt compounds were added into the World Anti-Doping Agency (WADA) prohibited list as doping agents. However, the existing data on beneficial effects of cobalt on exercise performance in athletes are scarce. Similarly, only experimental studies demonstrated exercise-induced decrease in tissue Co levels, whereas human data are inconsistent. In addition, multiple studies have demonstrated that excessive Co intake may be toxic due to prooxidant, proinflammatory, and proapoptotic activity. Therefore, monitoring of Co deficiency and overload is required to prevent potential health hazards in athletes. At the same time, modulation of Co status should be performed through supplementation avoiding excessive doses of inorganic cobalt that are used for doping and are accompanied by adverse health effects of metal toxicity.

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“…A single IV dose of 49 mg of Co (Knych et al, 2015) achieved Co plasma concentrations in excess of 300 μg/l for only a few hours. Chronic dosing of about 1000 mg of Co (Burns et al, 2018) increased plasma Co concentrations above 300 μg/l for 50 days, and chronic dosing over 35 days with doses that failed to achieve the 300 ng/ml level (Wenzel et al, 2019) have also been performed. None of these studies demonstrated any effect on red blood cell parameters in the experimental horses, and none of these studies investigated effects of Co on exercise.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of cobalt as a performance enhancing drug (PED) in racehorses

McKeever

Malinowski

Fenger

et al. 2020

CEP

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Cobalt is a required trace element in animals, but administration in excess is considered dangerous and potentially performance enhancing in equine athletes. This study seeks to determine if cobalt may actually act as a performance enhancing drug (PED) by altering biochemical parameters related to red blood cell production as well as markers of aerobic and anaerobic exercise performance. In addition, for adequate regulation of naturally occurring substances, such as cobalt, its distribution among the population must be defined. In order to identify this distribution, plasma Cobalt was determined from 245 Standardbred horses with no cobalt supplementation from farms in New York and New Jersey, including horses at the Rutgers University Equine Science Center. Samples were analysed by Inductively Coupled Plasma Mass Spectrometry. Seven healthy, race fit Standardbreds (4 geldings, 3 mares, age: 5±3 years, ~500 kg) were used for the PED experiment. An incremental graded exercise test (GXT) to measure maximal aerobic capacity (V̇O2max) and markers of performance, measurement of plasma volume and blood volume as well as the measurement of lactate, erythropoietin (EPO), and various blood haematological factors were determined 7 days prior to cobalt administration. Each horse was administered a sterile solution of cobalt salts (50 mg of elemental Co as CoCl2 in 10 ml of saline, IV) at 9 AM on three consecutive days via the jugular vein. Blood samples were obtained from the contralateral jugular vein before and at 1, 2, 4 and 24 h after administration. Plasma and blood volume were measured one day after the last dose of cobalt, and a post administration GXT was performed the next day. Horses were observed for signs of adverse effects of the cobalt administration (agitation, sweating, increased respiration, etc.). Plasma cobalt concentration increased from a pre-administration mean of 1.6±0.6 to 369±28 μg/l following 3 doses of the cobalt solution (P<0.05). This Co concentration was unaccompanied by changes in aerobic or anaerobic performance, plasma EPO concentration, plasma volume, resting blood volume, total blood volume, or estimated red blood cell volume (P>0.05). There were no observed adverse effects.

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Effect of Intravenous Administration of Cobalt Chloride to Horses on Clinical and Hemodynamic Variables

Cited by 12 publications

References 20 publications

Cobalt accumulation in horses following repeated administration of cobalt chloride

Cobalt accumulation in horses following repeated administration of cobalt chloride

Cobalt in athletes: hypoxia and doping - new crossroads

Evaluation of cobalt as a performance enhancing drug (PED) in racehorses

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