IntroductionTh e use of experimental models in medical research typically adheres to the following chain of actions: (1) select a model organism, (2) induce disease in this model organism, (3) interpret the results, and (4) develop a treatment. Th e most frequently used model animals in research laboratories are rodents, especially mice and rats. However, these models have a number of shortcomings. Experimental mice and rats are inbred, hypertensive, glucose-intolerant, prone to cancer and kidney failure, and on a trajectory to premature death.1 Most oft en these animals are kept at room temperature, which is well below their thermoneutral zone (30-32°C for mice) that in combination with light and absence of hiding space cause constant physiological stress. 2 Focusing on a few animal species confi nes the providence to those particular organisms, 3 which could partly explain the decline in medical research breakthroughs that lead to major disease elimination. 4 In this paper, we use brown bears ( Ursus arctos ) and black bears ( Ursus americanus ) as experimental animal models as inspiration for understanding human medicine. Th e pursuit of learning from Nature´s solution is termed biomimicry-a discipline successfully exploited within engineering, architecture, and medicine.Brown and black bears remain physically inactive inside their winter dens for half a year without eating, defecating, and with no or intermittent urination. Under similar conditions, humans would develop cardiovascular disease, kidney failure, muscle loss (sarcopenia), osteoporosis, and other deleterious conditions; however, bears readily exit their dens when spring arrives and show no signs of organ damage. In this review, we systematically discuss a number of key areas in which bear physiology might lead us to discover new ways to understand and treat human disease.
MethodsWe executed the literature searches using medical subjects headings terms in the PubMed database and free text searches in Google Scholar. To frame the search systematically, we identifi ed P opulation, I ntervention, C omparative intervention, and O utcomes (PICO) in the examined articles. Th ese PICO components defi ned the inclusion for our bibliographic search strategy, identifying research articles of relevance. We included research papers involving markers for heart failure, atherosclerosis, kidney failure, sarcopenia, and osteoporosis, which also showed relevance to the eff ects of hibernation in bears with comparisons to active bears or other mammals (including humans). Table 1 summarizes our literature search results.
Results
Down-regulated heart rate with respiratory sinus arrhythmiaExtreme heart rate reductions with profound respiratory sinus arrhythmia have been documented in hibernating bears ( Figure 1 ).
5-9Respiratory sinus arrhythmia has dramatic manifestations, where the duration of the cardiac cycle rises up to three times longer than the cycle length in active state (cycle length variations of 20% would be normal in humans) and up to 13-to 14-second ep...