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J Thorac Cardiovasc Surg 2001;121:817-818
© 2001 The American Association for Thoracic Surgery

Letters to the Editor

Alkalosis induced by alpha-stat management: Cause of neuronal injury after deep hypothermic perfusion

^aResearch Department, Kokura Memorial Hospital 1-1 Kifune-cho, Kokura-kitaku, Kitakyushu-shi 802-8555, Japan

^bAssistant Professor II, Department of Physiology, The University of Ryukyus School of Medicine, Okinawa, Japan

To the Editor:

Kurth and associates ¹ are to be congratulated for identifying the histopathologic mechanisms of brain damage after deep hypothermic circulatory arrest (DHCA).

Because short cardiopulmonary bypass (CPB) time induced no neurologic deficits or histologic damage, alpha-stat hypothermic perfusion was assumed to have no effects. However, in their study neurologic performance that correlated with brain injury worsened as the duration of pre-arrest CPB cooling increased. The severity of apoptosis, found in all animals subjected to DHCA, correlated with factors leading to hypoxia during rewarming. Thus, it appeared that some metabolic derangement had occurred before arrest and that the final reperfusion-rewarming blow led to cell death. One more indication was thereby added to the many clinical and experimental detrimental effects so far attributed to hypothermia, age, or rewarming, which likely are due to the alkalosis induced by alpha-stat management.

We believe the alkalosis-induced increase in hemoglobin oxygen affinity causes hypoxic (Bohr effect) metabolic derangement during induction of hypothermia. Added to the ischemic/hypoxic conditions during the period of arrest, this derangement helps to exacerbate the injury caused by postarrest alkalotic reperfusion-rewarming. The injury is further aggravated by the continuing Bohr effect in the early rewarming phase, resulting in cell death.

If hypoxic injury occurred in newborn infants, who supposedly have more resistance to hypoxia because of their higher taurine content in the brain, ^2,3 its occurrence in the aged (lower taurine content) with even shorter arrest times at lower temperatures is not surprising. ⁴

Nature has coped with hypothermia-hypoxia successfully over millions of years with eucapnic ventilation (equivalent to pH-stat strategies), as observed in ectothermic animals, hibernating and diving mammals. ⁵ Human beings should be no different; eucapnic ventilation would be particularly important in hypoxia-sensitive areas (hippocampus) of the more vulnerable aged brain.

Better postoperative neurologic outcome has been obtained with pH-stat than alpha-stat management for deep hypothermic perfusion in infants. ⁶ We ⁷ found that esophageal temperature differences as small as 0.5°C separated recovering (29.4°C ± 0.15°C) from non-recovering (29.9°C ± 0.13°C) rabbits (60 minutes of spinal cord ischemia) cooled by surface-induced hypothermia after normoxic eucapnic ventilation. Assuming the regression line between 38.3°C and 29.4°C would remain straight down to 15°C, 2 hours of complete protection at 19°C, not 90 minutes of incomplete protection as described by the authors, and 150 minutes not 29 minutes at 15°C ⁴ could be theoretically obtained.

It is essential to avoid the initial hypoxia to preserve metabolic integrity and fully realize the protective effects of hypothermia other than metabolic suppression (inhibition of excitatory amino acid release and hyperpolarization due to increase of Na⁺ efflux). It is also necessary to minimize the exacerbation of hypoxic/ischemic injury caused by Ca⁺⁺ influx, which alkalotic reperfusion promotes. Mild acidosis, that is, pH-stat management, should prevent the initial hypoxic N-methyl-D-aspartate activation and also decrease the unavoidable reperfusion insult by reducing Na⁺ and Ca⁺⁺ influx induced by N-methyl-D-aspartate. ⁸

If their alpha-stat CPB control group (hypothermic perfusion) had been tested for as long as the DHCA group and if groups of pH-stat CPB and pH-stat DHCA animals had been included, the long debated controversy of whether alpha-stat is better than pH-stat management, or vice versa, could have been ended.

12/8/112522doi:10.1067/mtc.2001.112522

References

1. Kurth CD, Priestley M, Golden J, McCann J, Raghupathi R. Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs. J Thorac Cardiovasc Surg 1999;118:1068-77.[Abstract/Free Full Text]
   
2. Wright CE, Tallan HH, Lin YY, Gaull GE. Taurine: biological update. Annu Rev Biochem 1986;55:427-53.[Medline]
   
3. Huxtable RJ. Taurine in the central nervous system and the mammalian actions of taurine. Prog Neurobiol 1989;22:471-533.
   
4. McCullough JN, Zhang N, Reich DL, Juvonen TS, Klein JJ, Spielvogel D, et al. Cerebral metabolic suppression during hypothermic circulatory arrest in humans. Ann Thorac Surg 1999;67:1895-9.[Abstract/Free Full Text]
   
5. Lutz PL, Nilsson GE. The brain without oxygen. Austin (TX): Landes Bioscience and Chapman & Hall; 1997. p. 1-205.
   
6. du Plessis AJ, Jonas RA, Wypij D, Hickey PR, Riviello J, Wessel DL, et al. Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants. J Thorac Cardiovasc Surg 1997;114:991-1001.[Abstract/Free Full Text]
   
7. Miyamoto, TA, Miyamoto KJ, Ohno N. Objective assessment of CNS function within 6 hours of spinal cord ischemia in rabbits. J Anesth 1998;12:189-94.
   
8. Giffard RG, Monyer H, Christine CW, Choi DW. Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Brain Res 1990;506:339-42.[Medline]
   

This article has been cited by other articles:

				C. Wong Alkalosis induced by alpha-stat management: Cause of neuronal injury after deep hypothermic circulatory arrest? J. Thorac. Cardiovasc. Surg., February 1, 2002; 123(2): 394 - 395. [Full Text]

				C. D. Kurth and M. Priestley Reply J. Thorac. Cardiovasc. Surg., February 1, 2002; 123(2): 395 - 396. [Full Text]

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