Contractile Response of Isolated Newborn Lamb Coronary vessels Exposed to Profound Hypothermia and Anoxia: The Protective Role of Hypothermosol, a New Preservation Medium 97

Introduction: Ultraprofound hypothermia (4°-10°C) an essential method for myocardial preservation has been associated with postoperative coronary artery dysfunction. Hypothermosol (HTS) is an acellular solution designed for myocardial and tissue protection during ultraprofound hypothermia. This study evaluates the effect of hypothermia (7°C) in the presence of either Krebs physiological buffer or HTS on the preserved function of coronary vessels isolated from newborn lambs. Methods: A total of 48 (3.5× 1 mm) vessel rings were isolated from freshly harvested hearts(n=7) and treated in tissue baths. Three groups were studied: Krebs/3hr-hypothermia (n=15); HTS/3hr-hypothermia (n=15) where Krebs buffer was substituted with HTS during hypothermia; and time-control/normothermia(n=18) maintained for 3 hours in Krebs at 37°C. After hypothermia and gradual rewarming to 37°C, precontracted vessels (5.10^-6M indomethacin + 10^-7M U46619 a Thromboxane-A₂ mimetic) were subjected to anoxia (0% O₂, 5% CO₂ × 0.5hr) followed by 10^-4M L-arginine. Values are given as a percentage of precontraction tension for each group (mean±SEM). Results: Throughout hypothermia higher tension was observed in Krebs-treated vessels. During rewarming a peak contraction was prominent at 17°C in the Krebs/hypothermia but not in the HTS/hypothermia group. A biphasic response was observed during anoxia: initial vasoconstriction, followed by a relaxation (table). Anoxia relaxation was significantly reduced in Krebs/hypothermia group compared to the time-control and the HTS/hypothermia groups. L-arginine did not modify the response significantly in either group. Conclusion: These data indicate a protective role of HTS in the preservation of coronary vessel response to anoxia after prolonged ultraprofound hypothermia.

Table 1 Table legends: *: p<0.05 (krebs/hypothermia vs. time-control); ^$: p<0.05 (vs. early response); ^#: p<0.05 (Krebs/hypothermia vs. time-control and HTS/hypothermia)

(For HTS composition refer to: Taylor et.al., Circulation 1995;91:431-444.)