Objectives: The Rostral Ventromedial Medulla (RVMM) is a key area in the control of autonomic function and metabolism, promoting thermogenesis (1). In the present study, the effects on sleep and cardiovascular parameters of the induction of a torpor-like state by the pharmacological inhibition of RVMM were investigated in the rat. Methods: Male Sprague–Dawley rats (n = 18, 300–350 g) adapted to an ambient temperature (Ta) of 25C, were implanted, under general anaesthesia (diazepam, 5 mg/kg, i.m., ketamine, 100 mg/kg, i.p.), with electrodes for EEG and EMG recording, a thermistor for detecting hypothalamic temperature (Thy), a catheter for arterial blood pressure recording, and a microcannula within the RVMM. After a week of recovery, animals were kept for 3 days at Ta 15C and then they were microinjected within the RVMM (1 injection/h, for 6 h) with either the GABAA agonist muscimol [1 mM, 100 nl; Group 1 (n = 6) and Group 2 (n = 6)] or saline [0.9%, 100 nl, Group 3 (n = 6)]. In order to favour the return to normothermia, 1 h after the last injection Ta was raised to 28C for Groups 1 and 3 and, for Group 2, to 37C, which was kept for 1 h and then taken to 28C. Results: Muscimol induced a deep hypothermia (Thy: 22.8 ± 0.8C) which was accompanied by: (i) a reduction of EEG activity; (ii) a decrease in heart rate (HR), from 440 ± 13 to 201 ± 12 bpm; (iii) a substantial maintenance of mean arterial pressure (MAP) at normal levels. Group 2 recovered normothermia faster than Group 1. Recovery was characterized by: (i) a progressive normalization of HR; (ii) the occurrence of a peak in MAP compared to saline (Group 3, 92 ± 4 mmHg), that was larger (P < 0.01) in Group 2 (125 ± 4 mmHg) than in Group 1 (116 ± 2 mmHg); (iii) the building up, in Groups 1 and 2, of a large SWS rebound in NREM sleep and of a not significant rebound in REM sleep. Conclusion: The effects of RVMM inhibition on cardiovascular and sleep parameters resembled those observed in natural torpor (2, 3). The increase in MAP observed during the recovery may be favoured by an excess in sympathetic activity. The effects on sleep observed after the recovery of normothermia indicate that the hypothermic bout and/or the rewarming generated a homeostatic need for SWS, but not for REM sleep. References: 1) Morrison S, Nakamura K. Front Biosci (2011) 16: 74–104. 2) Swoap SJ, Gutilla MJ. Am J Physiol RICP (2009) 297:R769–774. 3) Deboer T, Tobler I. Sleep (2003) 26: 567–72.

Deep hypothermia-induced changes in sleep and cardiovascular function

AMICI, ROBERTO;CERRI, MATTEO;DEL VECCHIO, FLAVIA;LUPPI, MARCO;MARTELLI, DAVIDE;MASTROTTO, MARCO;PEREZ, EMANUELE;TUPONE, DOMENICO;ZAMBONI GRUPPIONI, GIOVANNI
2012

Abstract

Objectives: The Rostral Ventromedial Medulla (RVMM) is a key area in the control of autonomic function and metabolism, promoting thermogenesis (1). In the present study, the effects on sleep and cardiovascular parameters of the induction of a torpor-like state by the pharmacological inhibition of RVMM were investigated in the rat. Methods: Male Sprague–Dawley rats (n = 18, 300–350 g) adapted to an ambient temperature (Ta) of 25C, were implanted, under general anaesthesia (diazepam, 5 mg/kg, i.m., ketamine, 100 mg/kg, i.p.), with electrodes for EEG and EMG recording, a thermistor for detecting hypothalamic temperature (Thy), a catheter for arterial blood pressure recording, and a microcannula within the RVMM. After a week of recovery, animals were kept for 3 days at Ta 15C and then they were microinjected within the RVMM (1 injection/h, for 6 h) with either the GABAA agonist muscimol [1 mM, 100 nl; Group 1 (n = 6) and Group 2 (n = 6)] or saline [0.9%, 100 nl, Group 3 (n = 6)]. In order to favour the return to normothermia, 1 h after the last injection Ta was raised to 28C for Groups 1 and 3 and, for Group 2, to 37C, which was kept for 1 h and then taken to 28C. Results: Muscimol induced a deep hypothermia (Thy: 22.8 ± 0.8C) which was accompanied by: (i) a reduction of EEG activity; (ii) a decrease in heart rate (HR), from 440 ± 13 to 201 ± 12 bpm; (iii) a substantial maintenance of mean arterial pressure (MAP) at normal levels. Group 2 recovered normothermia faster than Group 1. Recovery was characterized by: (i) a progressive normalization of HR; (ii) the occurrence of a peak in MAP compared to saline (Group 3, 92 ± 4 mmHg), that was larger (P < 0.01) in Group 2 (125 ± 4 mmHg) than in Group 1 (116 ± 2 mmHg); (iii) the building up, in Groups 1 and 2, of a large SWS rebound in NREM sleep and of a not significant rebound in REM sleep. Conclusion: The effects of RVMM inhibition on cardiovascular and sleep parameters resembled those observed in natural torpor (2, 3). The increase in MAP observed during the recovery may be favoured by an excess in sympathetic activity. The effects on sleep observed after the recovery of normothermia indicate that the hypothermic bout and/or the rewarming generated a homeostatic need for SWS, but not for REM sleep. References: 1) Morrison S, Nakamura K. Front Biosci (2011) 16: 74–104. 2) Swoap SJ, Gutilla MJ. Am J Physiol RICP (2009) 297:R769–774. 3) Deboer T, Tobler I. Sleep (2003) 26: 567–72.
R. Amici; A. Al Jahamany; M. Cerri; F. Del Vecchio; M. Luppi; D. Martelli; M. Mastrotto; E. Perez; D. Tupone; G. Zamboni
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/396862
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