Rosenfeldt, F, Ou, R, Salamonsen, R, Marasco, S, Zimmet, A, Byrne, J, Cosic, F, Saxena, P & Esmore, D 2016. ‘A Novel Combination Technique of Cold Crystralloid Perfusion But Not Cold Storage Facilitates Transplantation of Canine Hearts Donated After Circulatory Death – Cold crystralloid perfusion for DCD heart preservation’, Journal of Heart and Lung Transplantation. Unpublished manuscript.
Associated Institutions: Alfred Hospital and Monash University
The Experiment
This experiment used 12 greyhound dogs in an attempt to investigate methods of preserving resuscitated hearts (perfusion devices) following ‘donation after circulatory death’ (DCD), and to assess recovery following subsequent heart transplantation.
The 12 greyhounds were randomly allocated to one of two groups; 8 into the perfusion group, and 4 into the cold static storage group.
Dogs were premedicated with acetylpromazine (used in animals as a means of chemical restraint), and then anaesthetised, intubated, and mechanically ventilated (to allow them to breathe).
The left femoral vein (in the thigh) was cannulated (tube insertion) for fluid infusion and the artery for haemodynamic monitoring respectively. A catheter was also inserted via the right internal jugular vein (in the neck) for measurement of cardiac output and monitoring of filling pressure.
A median sternotomy was performed on the dogs and a baseline epicardial echocadiogram (a sonogram of the heart) was obtained.
Researchers then deliberately ceased ventilation (the provision of air allowing the dogs to breath) for 30 minutes in order to kill the dogs via asphyxia (suffocation), thereby causing circulatory death (the irreversible loss of function of the heart and lungs).
The hearts of the dogs were then surgically removed and preserved for 4 hours by either the static cold storage method, or the controlled reperfusion (followed by continuous cold perfusion with an oxygenated crystalloid perfusate) method.
After the 4-hour period, heart transplantation was performed and the dogs’ recovery was assessed over the following 4 hours.
All of the greyhounds were then killed.
Results
The 8 greyhounds of the perfusion group managed to be weaned off bypass and ‘produced cardiac output’ four hours post bypass. 3 of the 4 dogs in the cold storage group were unable to be weaned off from cardiopulmonary bypass, while the fourth dog managed to be weaned off bypass but exhibited low level function.
As the study was not conducted using human-biology based research methods, these results are only representative of the success of cold crystalloid perfusion and heart transplantation in canines, and therefore the results of the study have no direct clinical applications.
Relevance to Humans
There are major anatomical, genetic, dietetic, environmental, toxic, and immune differences between animals – including dogs – and humans1, making them inappropriate for use in studying human heart function and human disease. Many studies and systematic reviews show that there is discordance between animal and human studies, and that animal ‘models’ fail to mimic clinical disease adequately.2,3
Given this, one must seriously question whether using canine hearts to test the viability of these perfusion methods and transplantation success has any relevance whatsoever to human heart transplantation.
The researchers themselves have previously conducted human studies4, so it is extremely difficult to comprehend why they would conduct studies utilising hearts of a completely different species, and why the project proposal was approved by the Animal Ethics Committee given the availability of more accurate human biology-based replacements, thereby subjecting greyhounds to this needless suffering and death.
Further Questions
The publication itself notes that the experiment only examined “the early stage of recovery so it is unknown how these results would have changed had animals been allowed to recover for hours or days“.
Why did the researchers not allow the greyhounds to live and recover beyond four hours, given that the desired outcome of heart transplantation in humans is survival beyond four hours?
In any case, the assertion that this experiment has any relevance for human health outcomes is highly questionable – not only is the reasoning behind measuring the success of transplantation based on only a four hour recovery period flawed, the heart transplantation was conducted using a completely different species, which has entirely different heart function to humans.
Following international media coverage, Monash University released the following:
Monash statement on media reports about greyhounds in research
What You Can Do
Click here to sign our petition demanding an end to the use of dogs in experiments.
References
1 Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I; on behalf of the Reviewing Animal Trials Systematically Group. 2004. ‘Where is the evidence that animal research benefits humans?’, BMJ, 328, 514-7.
2 Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, et al. 2007. ‘Comparison of treatment effects between animal experiments and clinical trials: systemic review’, BMJ, 334:197.
3 Van der Worp H, Howells DV, Sena ES, Porritt MJ, Rewell S, O”Collins V, et al. 2010. ‘Can animal models of disease reliably inform human studies?’, PLoS Med.
4 Rosenfeld F, Ou R, Woodard J, Esmore D, Marasco S 2014. ‘Twelve-hour reanimation of a human heart following donation after circulatory death. Heart, lung & circulation, 23(1): 88-90.
