Does Dopram Work?

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Dopram Use in Puppies

The study presented was a randomized, double-blinded, placebo-controlled clinical trial assessing the efficacy and safety of doxapram in newborn puppies, following the Consolidated Standards of Reporting Trials (CONSORT statement). The primary aim was to determine if doxapram improved 7-day survival rates and time to reach a maximum APGAR score of ten, compared to saline, in puppies delivered by elective caesarean. The study also examined the influence of brachycephaly on these outcomes, given its association with higher whelping complications. 

Doxapram is a respiratory stimulant used in both human and veterinary medicine, with its mechanism believed to involve excitation of peripheral chemoreceptors and inhibition of TASK potassium channels, leading to increased ventilation. However, its safety and efficacy, particularly in neonatal animals, have been unclear, with studies showing mixed results regarding its impact on survival rates and health outcomes. 

The study's findings indicated insufficient evidence to support a survival advantage or health benefit for puppies treated with intralingual doxapram compared to those receiving saline. Furthermore, being brachycephalic did not significantly affect 7-day survival rates or the likelihood of reaching a maximum APGAR score of ten. Higher baseline APGAR scores were associated with lower puppy mortality, and factors such as the age and parity of the bitch, litter size, and puppy size influenced survival and health outcomes. 

Doxapram was administered intralingually to improve drug absorption reliability, considering the challenges of venous access in newborn puppies. This method was simple, with no adverse effects observed, and was chosen over sublingual or umbilical vein administration due to technical difficulties with the latter. 

Limitations of the study include the lack of a no-intervention group, which could have clarified the impact of the intralingual injection itself on outcomes. The study's design and blinding procedures could be adjusted in future research to include such a group. 

The study's results suggest that intralingual doxapram does not offer a significant benefit over saline for neonatal puppies' survival and health as measured by APGAR scores. The findings highlight the need for further research into the safest and most effective interventions for neonatal puppies, especially those that are apnoeic or in respiratory distress. 

Hyndman, T. H., Fretwell, S., Bowden, R. S., Coaicetto, F., Irons, P. C., Aleri, J. W., Kordzakhia, N., Page, S. W., Musk, G. C., Tuke, S. J., Mosing, M., & Metcalfe, S. S. (2023). The effect of doxapram on survival and APGAR score in newborn puppies delivered by elective caesarean: A randomized controlled trial. Journal of Veterinary Pharmacology and Therapeutics, 46, 353–364. https://doi.org/10.1111/jvp.13388 

Bottom line — No significant benefit noted.

Genetic Basis for Fractures in Horses?

The study focused on understanding the genetic basis of fracture risk in Thoroughbred racehorses, particularly looking at a specific region on equine chromosome 18 (ECA18) associated with such risks. It involved developing a cell model using skin fibroblasts from horses categorized into high and low fracture risk groups based on genome-wide polygenic risk scores. The choice of skin fibroblasts was due to their ease of culture and ability to differentiate into osteoblasts, making them suitable for bone gene studies. 

A significant part of the research was the gene expression analysis in these cells, particularly focusing on genes within the ECA18 region. Among these, COL3A1 and STAT1 were found to be differentially expressed between high- and low-risk groups, suggesting a potential link to fracture risk. Whole-genome sequencing was conducted to identify regulatory DNA variants, but no significant findings were made near the STAT1 gene, indicating other regulatory mechanisms might be involved. 

The study also found an SNP upstream of COL3A1 significantly associated with fracture risk, hinting at a role in gene regulation potentially influenced by transcription factors like SOX11 and KLF13. The modulation of COL3A1 expression by SOX11 was demonstrated, although the complete mechanism needs further exploration. 

Despite its insights, the study faced limitations such as small sample sizes and technical challenges, indicating a need for further research. The findings underscore the complexity of genetic factors in fracture risk and open avenues for novel risk mitigation strategies in the future. 

Palomino Lago E, Baird A, Blott SC, McPhail RE, Ross AC, Durward-Akhurst SA, Guest DJ. A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses. Animals. 2024; 14(1):116. https://doi.org/10.3390/ani14010116 

Bottom line — Polygenetic and complicated but an interesting approach to help decrease the incidence.

Salt and Cats.

 This study investigates the impact of a high-sodium diet on the health of aging cats, particularly focusing on renal and cardiovascular safety. The main findings from the study are: 

• Background and Rationale: Previous research suggested that high-salt diets in cats don't adversely affect blood pressure or renal function, even in those with kidney impairments. However, longer-term studies were needed, especially for aging cats, due to the known effects of age on blood pressure and renal function. 

• Study Design: The study was a long-term (5 years), prospective, randomized, blinded, and controlled trial focusing on the effects of a high-salt diet on healthy aged cats. The study aimed to examine the impacts on renal and cardiovascular health, with particular interest in chronic kidney disease and hypertension. 

• Dietary Details: The high-salt diet used had a sodium content of 3.26 g/Mcal ME. Cats were also fed diets containing moderate amounts of dietary phosphorus. 

• Key Findings: 

• Renal Function: The study found no significant effect of the high-salt diet on glomerular filtration rate (GFR), a key indicator of renal health. Some cats developed early chronic kidney disease (CKD) or azotemia, but these rates were consistent with other studies in aging cats. 

• Cardiovascular Health: Systolic blood pressure and indicators of cardiovascular disease, such as left ventricular mass and wall thicknesses, were not adversely affected by the high-salt diet. 

• Overall Health: The occurrence of diseases like CKD, lymphoma, diabetes, and hyperthyroidism in some study cats was consistent with general health issues in older cats. The study did not find a negative impact of the high-salt diet on overall health. 

• Limitations: One limitation was the small number of cats, especially in later stages of the study. This issue was addressed by analyzing rates of change in key variables. 

• Conclusions: The study concludes that a high-sodium diet (about three times higher than a standard diet) is safe regarding renal and cardiac function, blood pressure, and other health outcomes in healthy aging cats. The frequency of CKD was lower than in some population studies, and a diet with 1 g of dietary phosphorus per Mcal was deemed safe for chronic feeding in aged cats. 

Reynolds BS, Chetboul V, Elliott J, et al. Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study). J Vet Intern Med. 2024; 38(1): 285-299. doi:10.1111/jvim.16952 

Bottom line — Higher salt diet seems to be safe for cats.

Just putting things in perspective …