The Need for Speed
Mice, Men, and Myocardial Kinetic Reserve
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The in-bred laboratory mouse (hereafter referred to as simply mouse) has in the past decades emerged as the go-to animal model in the arena of cardiovascular research. The reasons are straightforward: the relative ease of genetic manipulation coupled with short gestation times, the much cheaper cost of maintaining large numbers, and a large number of similarities to human genomics, proteomics, and many aspects of function. These advantages make the mouse a powerful tool for a wide array of cardiac research.
The resting heart rate in the conscious unrestrained mouse is ≈500 to 700 bpm,1–3 roughly 10× faster than in a resting human. In addition, the mouse modulates heart rate, and, thus, contraction/relaxation kinetics, rather minimally; even during strenuous exercise, it only increases from the resting rate by 50% at most,1 typically by only ≈10% to 20%,3,4 whereas in humans, the heart rate can increase by ≤300%, typically 100% to 200%. As a result, exercise-induced increases in cardiac output (heart rate combined with an increase in stroke volume) can be 5- to 10-fold in the human, but are only 1.3- to maximally 2-fold in the mouse. In this viewpoint, we will convey how the high murine heart rate limits myocardial kinetic reserve (ie, the ability for the cardiac muscle to increase contraction and relaxation speed) and focus on the ramifications for extrapolating the regulation of contractile kinetics to human health and disease. In addition, we will discuss the use of contracting human tissue as a potential powerful ally in our quest to further understand contractile and kinetic regulation in health and disease.
Heart Rate and Heart Rate Changes in the Mouse
Critical differences are evident in the contractile/relaxation kinetics of cardiac muscle. Despite the fact that all the proteins of the contraction process are the same or similar between human and mouse cardiac …