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J Thorac Cardiovasc Surg 2002;124:1260-1261
© 2002 The American Association for Thoracic Surgery

Letters to the Editor

Alpha-stat strategy: Cause of ischemia in brains with old cerebral infarction despite selective cerebral hypothermic antegrade perfusion

Research Department, Kokura Memorial Hospital, Kitakyushu-City, Japan^a, Assistant Professor II Department of Physiology, The University of the Ryukyus School of Medicine, Okinawa, Japan^b

To the Editor:

Washiyama and associates ¹ are to be congratulated for experimentally verifying the anticipated susceptibility of brains with old infarction to become ischemic even during hypothermic selective continuous antegrade perfusion (SCP).

We do not doubt that SCP is better than no perfusion or retrograde perfusion, regardless of the pH management. However, despite SCP, ischemia developed in brains with old infarcts. Had the presented data been fully analyzed and interpreted without prejudice, the mechanisms of that ischemia would have been clear.

In our opinion, the alkalosis induced by alpha-stat hypothermic perfusion ² explains every fact that the authors could not satisfactorily explain:

1. Although the authors failed to recognize and statistically analyze the increasing brain lactate efflux even in the control group from sample 1 to sample 4 during SCP, such increase seems to us significant. In our opinion, alpha-stat-induced alkalosis inhibits the creatine kinase catalyzed phosphorylation reactions. ³ This causes failure to aerobically synthesize high-energyP bonds and switch to anaerobic metabolism with consequent adenosine triphosphate consumption and lactate production even in the control group without prior infarct, despite the continuous perfusion.
   
2. Further lactate efflux increase in the infarct group after rewarming. Failure to use glucose aerobically becomes overt after rewarming following alpha-stat hypothermic uninterrupted perfusion at 20°C for 60 minutes. ⁴
   

As pointed out by the authors, the penumbra area of an infarct is dependent on collateral flow. The vasoconstriction and decreased brain flow caused by alpha-stat strategies will certainly reduce such collateral flow, maximizing the metabolic effects of pH management. Sakamoto and associates ⁵ demonstrated brain anoxia development during early alpha-stat cooling before arrest. These effects are not limited to the period of cold perfusion but continue also during alpha-stat rewarming; thus, the lactate efflux at 32°C is maximal, even if circulatory arrest was not induced.

Obtaining the glutamate samples from the maxillary vein as often as the lactate samples would have answered whether the switch of aerobic to anaerobic metabolism and lactate efflux of the control group was enough to cause hypoxic excitotoxicity. ⁶

pH-stat strategies increase brain blood flow and clearly should have been advantageous for perfusion of brains with old infarcts ⁷; pH-stat hypothermic selective antegrade perfusion might prevent or minimize the metabolic effects of alpha-stat strategies even in brains with collateral flow-dependent penumbra areas.

References

1. Washiyama N, Kazui T, Takinami M, Yamashita K, Fujita S, Terada H, et al. Experimental study on the effect of antegrade cerebral perfusion on brains with old cerebral infarction. J Thorac Cardiovasc Surg. 2001;122:734-40.[Abstract/Free Full Text]
   
2. Miyamoto TA, Miyamoto KJ. Alpha-stat induced anaerobiosis: Cause of transient neurologic deficits and hepatic mitochondrial oxido-reduction impairment during hypothermic cardiopulmonary bypass [letter]. J Thorac Cardiovasc Surg. In press.
   
3. Lawson JWR, Veech RL. Effects of pH and free Mg²⁺ on the K_eq of the creatine kinase reaction and other phosphate hydrolyses and phosphate transfer reactions. J Biol Chem. 1979;254:6526-37.
   
4. Miyano H, Inagaki M, Hashimoto N, Shishido T, Kawada T, Miyake Y, et al. Regional cerebral blood flow during rewarming of cardiopulmonary bypass correlates with posthypothermic regional glucose use. J Thorac Cardiovasc Surg. 1998;116:503-10.[Abstract/Free Full Text]
   
5. Sakamoto T, Zurakowski D, Duebener LF, Hatsuoka S, Lidov HGW, Holmes G, et al. Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury in a survival piglet model with deep hypothermic circulatory arrest. Ann Thorac Surg. 2002;73:180-9.[Abstract/Free Full Text]
   
6. Tseng EE, Brock MV, Kwon CC, Annanata M, Lange MS, Troncoso JC, et al. Increased intracerebral excitatory aminoacids and nitric oxide after hypothermic circulatory arrest. Ann Thorac Surg. 1999;67:371-6.[Abstract/Free Full Text]
   
7. Cook DJ, Boston US, Orszulak TA, Slater JM. Carbon dioxide management and the cerebral response to hemodilution during hypothermic cardiopulmonary bypass in dogs. Ann Thorac Surg. 2001;72:1331-5.[Abstract/Free Full Text]
   

This article has been cited by other articles:

				K. Ohkura, T. Kazui, S. Yamamoto, K. Yamashita, H. Terada, N. Washiyama, T. Suzuki, K. Suzuki, M. Fujie, and K. Ohishi Comparison of pH management during antegrade selective cerebral perfusion in canine models with old cerebral infarction J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 378 - 385. [Abstract] [Full Text] [PDF]

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