Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Abstract

SUMMARYDeep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min -1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. Received 25 March 2013; Accepted 4 September 2013Key words: hibernation, MyHC, echocardiogram, atrial contraction, cardiac function. Echocardiogram and myosin of hibernatorsThe myosin heavy-chain isoforms (MyHC) are crucial determinants of contractile performance in cardiac muscle t...

Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal

“…This switch to the ␣-myosin heavy chain MYH6 is likely important for maintaining contractile function during hibernation, with ␣-myosin heavy chains allowing for greater force contractility. This increase in MYH6 was previously observed (70), and we propose this to be important for continuous pumping of blood with higher viscosity due to decreased temperature. These dissimilarities between the fetal gene expression profile in pathological hypertrophy versus that seen in hibernation are likely important for maintaining cardiac function without progressing to cardiac dysfunction and heart failure.…”

Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics

“…Shifts in these cardiac isoforms of myosin are thought to be important for maintaining cardiac performance at low temperatures, at which time increased contractile force and stroke volume is required to counteract loss of contractile protein function and increased blood viscosity at low temperatures. Hypertrophy of the heart, and increased MYH6 have been reported[18][19] , however this is the first report of quantitative protein expression changes by MS/MS analysis. This data correlates with the shift in myosin isoforms occurring prior to the hibernation season observed in Nelson and Rourke19 , and likely reflects a major…”

“…Hypertrophy of the heart, and increased MYH6 have been reported[18][19] , however this is the first report of quantitative protein expression changes by MS/MS analysis. This data correlates with the shift in myosin isoforms occurring prior to the hibernation season observed in Nelson and Rourke19 , and likely reflects a major…”

Winter metabolic depression does not change arterial baroreflex control of heart rate in the tegu lizard (Salvator merianae)

“…Juvenile tegu lizards undergo cardiac hypertrophy in anticipation of winter hibernation (da Silveira et al, 2013), which could be a compensatory mechanism to maintain blood pressure at low f H by sustaining stroke volume; however, the maintenance of blood pressure during dormancy in tegu lizards does not exclude a possible contribution from increased peripheral vascular resistance. It is interesting to note that hibernating goldenmantled ground squirrels (Callospermophilus lateralis) undergo an ∼30% increase in the left ventricular chamber mass maintaining extremely low f H , while stroke volume is significantly increased (Nelson and Rourke, 2013). Heart hypertrophy has also been reported in the Andean lizard, Liolaemus nigroviridis, during hibernation (Naya et al, 2009).…”