Effect of Ultraprofound Hypothermia on the ex vivo Contractile Response of Cerebral Arteries: Relevance to Cerebrovascular Dysfunction during Cardiopulmonary Bypass • 238

Applied hypothermia is a proven adjunctive technique for brain protection during surgical procedures that require circulatory and/or cardiac arrest. Nevertheless, cerebrovascular dysfunction during, or following hypothermic cardiopulmonary bypass is thought to contribute to injury sustained by the central nervous system. We are investigating an experimental approach to use ultraprofound hypothermia and total blood replacement with Hypothermosol™ (HTS), a hypothermic blood substitute, to effect greater neuroprotection during extended periods of cardiac arrest. This study focuses upon the effect of ultraprofound hypothermia and blood substitution (UHBS) on isolated middle cerebral arteries (MCA) using tissue bath techniques. After 1 hr at 37°C in normal Kreb's buffer solution (KBS), MCA rings (n=8) were subjected to a simulation of UHBS, as previously applied and reported in vivo, as follows: Bath temperature was decreased (0.5°C/min) from 37°C to 7°C×3hrs then rewarmed. KBS was replaced with HTS-purge (HTS-P) solution and HTS-maintenance (HTS-M) solution as illustrated (Figure). Control MCA rings (n=8) remained in normal KBS. Control MCA rings exhibited a marked contractile response to hypothermia, peaking at 12°C, followed by partial relaxation below 11°C. There was a slow phase contraction over the three hrs at 7°C. Rewarming resulted in initial contraction (peak at 18°C) followed by rapid relaxation. UHBS with HTS completely abolished the MCA contractile response to cooling. Induction of ultraprofound hypothermia has a direct impact on cerebrovascular function which depends on the rate, magnitude, duration, and direction of the temperature change. Amelioration of cerebrovascular reactivity and improved perfusion during cooling/rewarming phases may be a basis for previously reported beneficial aspects of UHBS strategies.

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(AHERF Neurosciences grant #G9603-004)

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Wagerle, L., Taylor, M., Dahdah, N. et al. Effect of Ultraprofound Hypothermia on the ex vivo Contractile Response of Cerebral Arteries: Relevance to Cerebrovascular Dysfunction during Cardiopulmonary Bypass • 238. Pediatr Res 43, 43 (1998). https://doi.org/10.1203/00006450-199804001-00259

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