Cold-impaired cardiac performance in rats is only partially overcome by cold acclimation

Abstract

SUMMARYThe consequences of acute hypothermia include impaired cardiovascular performance, ultimately leading to circulatory collapse. We examined the extent to which this results from intrinsic limitations to cardiac performance or physiological dysregulation/autonomic imbalance, and whether chronic cold exposure could ameliorate the impaired function. Wistar rats were held at a 12h:12h light:dark (L:D) photoperiod and room temperature (21°C; euthermic controls), or exposed to a simulated onset of winter in an environmental chamber by progressive acclimation to 1h:23h L:D and 4°C over 4 weeks. In vivo, acute cold exposure (core temperature, T b 25°C) resulted in hypotension (approximately -20%) due to low cardiac output (approximately -30%) accompanying a bradycardia (approximately -50%). Cold acclimation (CA) induced only partial compensation for this challenge, including increased coronary flow at T b 37°C (but not at T b 25°C), maintenance of ventricular capillarity and altered sympathovagal balance (increased low:high frequency in power spectral analysis, PSA), suggesting physiological responses alone were insufficient to maintain cardiovascular performance. However, PSA showed maintenance of cardiorespiratory coupling on acute cold exposure in both groups. Ex vivo cardiac performance revealed no change in intrinsic heart rate, but a mechanical impairment of cardiac function at low temperatures following CA. While CA involved an increased capacity for -oxidation, there was a paradoxical reduction in developed pressure as a result of adrenergic down-regulation. These data suggest that integrated plasticity is the key to cardiovascular accommodation of chronic exposure to a cold environment, but with the potential for improvement by intervention, for example with agents such as non-catecholamine inotropes. Supplementary material available online at

Is cold acclimation of benefit to hibernating rodents?

“…The increase in stroke volume observed for euthermic hamsters on acute cooling preserved cardiac output despite decreased f H , and demonstrates a Frank-Starling-mediated partial compensation in a manner similar to that found in non-hibernators (R. norvegicus) noted previously (Hauton et al, 2011). Preservation of total peripheral resistance also suggested that vascular tone and hence afterload were maintained.…”

“…One possible outcome of CA may also be the chronic β-adrenergic desensitisation of cardiac tissue, previously noted for CA rat hearts (Cheng and Hauton, 2008). Recent temporal changes noted in the transcriptome of the thirteen-lined ground squirrel suggested that hibernation triggers changes in Ca 2+ handling proteins within the cell to increase the amplitude of Ca 2+ release during torpor (Hauton et al, 2011). Interestingly, no changes were noted in the preceding period, which we suggest may correspond to 'cold acclimation' of the present study.…”

“…At T b =~37°C and 25°C some animals received radiolabelled microspheres ( 113 Sn,46 Sc; DuPont NEN, Mechelen, Belgium) delivered into the left ventricle via a right carotid arterial cannula to estimate myocardial blood flow. Reference flow was obtained by sampling from one brachial artery using a precision withdrawal pump (Hauton et al, 2011).…”

“…The trace was used to calculate f H (beatsmin −1 ) and R-R intervals (ms), as well as the relative duration of the cardiac cycle components (the latter sampled at 10kHz). Cardiovascular and respiratory measurements were collected as previously detailed (Hauton et al, 2011).…”

“…We have recently demonstrated that for non-hibernators (Rattus norvegicus), CA represents a partial compensation characterized by altered sympathovagal balance and poor left ventricle function (Hauton et al, 2011). Yet no such study has been undertaken in hibernators.…”