Regulation of Animal Research in Science: How to Harm Both Science and Animal Protection

Influence of Medication-Induced Preconditioning or Remote Ischemic Preconditioning on the Intrinsic Vascular Extracellular RNA/Ribonuclease System in Cardioprotection

Animal experiments have been conducted for a very long time, and mankind has highly profited from such experiments that lead to understanding physiology and mechanisms of disease and their treatment. Such research is regulated by the German constitution (Grundgesetz für die Bundesrepublik Deutschland Ch. 5 Freedom of Research). There is also an opposition to animal experiments arguing that animals have the same rights as humans and that such experiments should be banned. Opponents as well as proponents argue with valid reasons, but the extreme positions sometimes pronounced cannot come to an agreement. Nevertheless, as a consensus, animal protection has been accepted by Western societies as an important aim, and animal protection laws have been implemented. They require everyone experimenting with animals to file an application providing a solid scientific reasoning. Rules for granting permission have been defined by law (e.g., German animal protection law TierSchG § 8) as well as set by the court (BVerwG, decision as of 20.01.2014 - 3 B 29.13 [ECLI:DE:BVerwG:2014:200114B3B29.13.0]).

The present investigation[1] by Tolkmitt et al addresses ischemia and reperfusion protection. Ischemia and reperfusion are conditions that cardiac surgeons induce on a daily basis. However, both result in cardiac damage, and the search for protection from such damage is still ongoing. Remote ischemic preconditioning has been found to be a potential option to reduce the I/R damage, but randomized clinical trials[2] [3] have failed to show any effect and ischemic preconditioning is controversially discussed.[4] One potential reason for failure to show an effect in this trial might have been the anesthetic medication used.[5] [6] The investigation by Tolkmitt et al aims to fill this gap and to advance our knowledge using an animal study in rats. While the study was well designed, the number of independent repeats (also known as n) was too low. The authors made it clear that they initially planned their investigation with sufficient numbers to test their hypothesis. However, their study was significantly limited due to the number of animals to be used, with the local authorities imposing a reduction of numbers. Here it becomes clearly visible that an excessive attempt to reduce the use of animals may lead to a decrease in scientific value of the investigation. With respect to the scientific value, this work should, in general, not be considered for publication. This aspect is further supported by the argument that acceptance might even reassure the local authorities, in their view, to reduce animal numbers independent of scientific reasoning. However, a decision to reject the study seems nevertheless difficult as it would directly penalize the scientists for working in a certain location under given circumstances.

The controversy whether or not to use animals in research will not be solved by the approach seen here. Opponents of animal research may argue that the experiments should not have been conducted at all. Proponents of animal research accepting them as necessary could as well argue that the study is of limited value due to the insufficient number of animals. The, therefore, preliminary data by Tolkmitt et al directly and profoundly ask for a repetition with at least twice the number of independent experiments to be conducted, leading to an overall increased number of animals compared with their initial proposal. Thus, the action of authorities seen here may be regarded as the induction of distress and harm to more animals than necessary, contradicting the role these authorities should normally fulfill. As a conclusion, this seems an impressive example of how both the intention to protect animals and the intention to conduct sound science may be harmed by one questionable regulation.

• References

• 1 Tolkmitt KJ, Simsekyilmaz S, Schipke J, Mühlfeld C, Preissner KT, Böning A. Influence of medication-induced preconditioning (MIPC) or remote ischemic preconditioning (RIPC) on the intrinsic vascular eRNA/RNase system in cardioprotection. Thorac Cardiovasc Surg 2018; ;66(Suppl 01): S1-S110
• 2 Meybohm P, Zacharowski K, Cremer J. , et al; RIP Heart-Study Investigator Group. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study. Eur Heart J 2012; 33 (12) 1423-1426
• 3 Hausenloy DJ, Candilio L, Evans R. , et al; ERICCA Trial Investigators. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 2015; 373 (15) 1408-1417
• 4 Zaugg M, Lucchinetti E. Remote ischemic preconditioning in cardiac surgery--ineffective and risky?. N Engl J Med 2015; 373 (15) 1470-1472
• 5 Landoni G, Baiardo Redaelli M, Votta CD. Remote ischemic preconditioning and cardiac surgery. N Engl J Med 2016; 374 (05) 489
• 6 Landoni G, Greco T, Biondi-Zoccai G. , et al. Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery. Br J Anaesth 2013; 111 (06) 886-896