Acid-base homeostasis and myocardial and cerebral preservation during and after induced hypothermia

Two acid-base strategies, pH-stat and alpha-stat, are used in hypothennic cardiac pulmonary bypass (CPB) although wide spread practice has not clarified which is the better (Swan, 1984; Takao, 1991; Aoki et al, 1994). pH-stat exists among the hibernators, which tends to preserve normothennic pH and PC02 values as body temperature falls (Malan, 1982). Alpha-stat, a term used to describe the responses of ectotherms and heterotherms, which tends to maintain an optimal function in all organ systems at all temperatures with a lower PC02 and a higher pH, but no change in plasma HC03- or C02 stores (Reeves, 1972). Previous investigations have compared pH-stat and alpha-stat and postulated that a more alkaline pH would be even more effective in preserving myocardial and cerebral function during hypothermia (Buckberg, 1985; Becker et al, 1981). In this study the effects of pre-alkalinization and pre-acidification on cerebral and cardiovascular function during and after hypothermia were investigated in 37 fentanylanaesthetised New Zealand rabbits. Animals were divided into four groups: a normothennic (Norn, n=6) and 3 hypothermic groups a) hypothennic control (HCo, n=9); b) hypothermic acidosis (HAc, n=lO); c) hypothennic alkalosis (HAI, n=12). Alkalosis was induced by injection of carbicarb (0.33 M Na2C03 and 0.33 M NaHC03, 2 ml kg-I, Rhee et al, 1993) and acidosis by NH4Cl (2 M, 2.5 ml kg-I) before reducing body temperature (Tb). Animals were sedated with fentanyl (4.2 µg kg-I min-I) during surgical operation and 2.1 µg kg-I min-1 during monitoring and ventilated with 35% Oi in N1. The experiment was divided into 5 phases: 1. normothennic control; 2. cooling; 3. profound hypothennia (Tb = 25±1°C for one hour); 4. rewanning and 5. normothennic recovery. Blood samples were taken for P02, PC02 and pH analysis. Heart rate (HR), mean aortic pressure (MAP), central venous pressure (CVP), carotid arterial blood flow (CrdBF), electrocardiograph (ECG) and electroencephalogram (EEG) were monitored. Cerebral oxygen delivery (D02), oxygen consumption (\\! 0 2) and oxygen extraction (ER) were calculated from oxygen content (CtQi) and CrdBF. pH increased when Tb was reduced. All pHa and pHv values were higher in HAI than those in other groups (P<0.01). During the one hour of profound hypothermia (phase 3), pHa was constant within the three hypothermic groups ( HCo: 7.52 ± 0.07 to 7.52 ± 0.08; HAI: 7.69 ± 0.06 to 7.67 ± 0.06; HAc: 7.43 ± 0.05 to 7.40 ± 0.05). After rewarming, only pHa of HAI in hypothennic group was 7 .37±0.09 and not different from the value of Norn (7.38±0.04). The other two groups were significantly lower, with values of 7 .17±0.08 for HCo and 7 .06±0.06 for HAc (P < 0.05). ECG records from HAI often showed conduction disturbances during cooling and hypothermia but returned to normal after rewarming. Conduction disturbances and arrhythmias were most severe and frequent in HAc during rewarming, and persisted after the Tb had returned to normal. HR fell during cooling and hypothermia in all animals but recovered better in HAI after rewarming. Also in HAI, MAP was higher, and stayed at a relatively constant level during hypothennia and returned to normal after rewarming. CrdBF and D02 decreased when Tb was reduced and were slightly higher in HAI than in HAc. ER was lower in HAI than in HAc during rewarming (P<0.05). Suppression of EEG started earlier in HAc and HCo than in HAI during cooling and recovered faster in HAI than in the other two groups. The results showed 1) a normal pH was attained after rewanning in HAI; 2) Prealkalinization has beneficial effects on cerebral and myocardial performance; 3) the rabbit provides a suitable small animal model for induced hypothermia, and has been successfully tested for experiments over 6 or more hours duration. This work suggests that alkalinization before cooling could reduce or eliminate anaerobic metabolism and subsequent acidosis, and thus could be the optimal acidbase strategy during induced hypothermia and during rewarming.