The Mechanism of Action of Carbon Dioxide in the Regulation of Cerebral Blood Flow

The Mechanism of Action of Carbon Dioxide in the Regulation of Cerebral Blood Flow

103 The Mechanism of Action of Carbon Dioxide in the Regulation of Cerebral Blood Flow M. N. SHALIT*, S. SHIMOJYO, 0. M. R E I N M U T H , W. S. LOCK...

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The Mechanism of Action of Carbon Dioxide in the Regulation of Cerebral Blood Flow M. N. SHALIT*, S. SHIMOJYO, 0. M. R E I N M U T H , W. S. LOCKHART, Jr.**, A N D P. SCHEINBERG Department of Neurology, University of Miami School of Medicine, Miami, Florida (U.S.A.)

The response of cerebral circulation to changes in arterial C02 tension is well known and has been confirmed in numerous experiments and clinical observations. Nonetheless, the mechanism of action of this gas is not completely understood although certain theories are presently generally accepted. The dilatation of the cerebral vessels following an increase of arterial C02 tension has been said to be the result of the direct action of the gas on the smooth muscle of the cerebral arterial wall. Reviewing previous pertinent work it was somewhat surprising to discover that no direct demonstration of the effect of COZon the cerebral arteries had been described. The only investigation quoted in various reviews dealing with this subject is the work of Cow (1911) who observed that isolated segments of carotid artery dilate when COz is added to the Ringer’s solution in which they are immersed. We believe that this experiment is inadequate evidence to support the conclusions so widely drawn. Our principle objection is the fact that Cow used the carotid artery which, in our opinion, is not a proper representative of the end arterial branches of the cerebral vessels. Moreover, Cow did not specify if he used the intra- or extra-cranial portion of the carotid artery. This distinction is important since Cow sharply distinguished between the “carotid artery” and “cerebral artery” in describing the opposite effect of epinephrine on these vessels. Apparently, Cow did not intend at all to demonstrate the effect of C02 on cerebral vessels themselves, although his observations have been so interpreted many times since as one of the main evidences for the direct effect of C02 on the cerebral vascular smooth muscle. Regarding the importance of this point, we have designed an alternate method of testing in vivo the effect of changes of the intra-luminal C02 tension on the blood flow through distal branches of the cerebral vessels. In nine dogs we cannulated one of the main branches of the middle cerebral‘artery and perfused it with arterial blood of various COZtensions, keeping the perfusion pressure at a constant level. It was found that an increase of the perfusion blood C02 tension from low levels of about 25 mm Hg to high levels of about 70 mm Hg decreased the perfusion rate 2040%.

* Research fellow Department of Neurosurgery, Hadassah University Hospital, Jerusalem, Israel. * * Department of Neurosurgery, University of Miami School of Medicine, Miami, Florida (U.S.A.). References p . 106

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When the C02 tension of the perfused blood was reduced back to the low level the perfusion rate usually returned to its former level. An increase of the perfusion blood COz tension never resulted in an increase of the perfusion rate. On the other hand, an increase of systemic arterial PCO,was followed by a significant increase of the perfusion rate, although the P ~ o in , the perfused vessels did not change. This phenomenon was observed also in cases where the perfusion pressure was reduced to levels below systemic arterial pressure, indicating that the increase of perfusion rate was a consequence of decreased resistance in the perfused vessels rather than escape of blood through the dilated collaterals into the surrounding vessels (Figs. 1 and 2). The possibility of a neural regulatory mechanism for the cerebral circulation has been widely assumed to be negligible or non-existent because of failure of autonomic denervation or stimulation to affect cerebral blood flow significantly. Moreover, according to a review by Wolff (1936), the cerebral vasodilating effect of COZpersists after decerebration, spinal transection and section of various cranial nerves.

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Fig.1 . Perfusion experiment by cannulating branches of the middle cerebral artery.

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Fig. 4. Effectivenessof brain lesions on the response of CBF to systemic arterial Pcoa alterations.

On the other hand, the existence of a rich supply of nerves which accompanies the major arteries of the brain, the pial vessels, and those vessels that dip back into the cortex should not be ignored. The absence of clear demonstration of their function is not an adequate reason to assume them functionless. Furthermore, in spite of the obvious importance of the observations of Wolff, it is disappointing to discover that Wolff refers to them all as “unpublished observations”. In order to obtain further information concerning this important problem we studied in 18 dogs the response of the cerebral blood flow (measured by the nitrous oxide method) to altered arterial Pcoa, following lesions at various levels of the brain stem. It was found that following a lesion in the mid brain, the pons, and the upper part of the medulla the response of the cerebral circulation to COZdiminished significantly or disappeared. By the use of Cooper’s cryosurgical system, reversible lesions in areas in the mid brain could be achieved there by producing concomitant variations in the response of the cerebral circulation to changes in the arterial COZ tensions (Figs. 3 and 4). It is suggested, therefore, that the response of the cerebral circulation to changes in arterial COZtension is not due to a direct effect of this gas on the smooth muscle in the cerebral arterial walls, but depends upon a neural reflex mechanism which can be interrupted or impaired by lesions in certain levels of the brain stem.

REFERENCES Cow,D. (1911); Some reactions of survivingarteries.J. Physiol., 42,125. WOLFF,H. G., (1936); The cerebral circulation.Plrysiol. Rev., 16,545.