| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
* From the Departments of Anesthesiology,
Pediatrics, and
Neurological Surgery, Harborview Medical Center, University of Washington, Seattle, Washington, USA.
Address correspondence to: Dr. Lorri A. Lee, Department of Anesthesiology, Harborview Medical Center, Box 359724, 325 Ninth Avenue, Seattle, Washington 98104-2499, USA. Phone: 206-731-3059; Fax: 206-731-8009; E-mail: lorlee{at}u.washington.edu
 |
Abstract |
|---|
 TOP Abstract IntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Methods: Eight healthy awake subjects aged 28 to 50 yr were tested for CO2-reactivity in the ophthalmic artery using transcranial Doppler (TCD) insonation of blood flow velocity (Vop), while simultaneously recording the Vop of the middle cerebral artery (Vmca) as an internal control. Vop and Vmca recordings were made under hypocapnic, normocapnic and hypercapnic conditions.
Results: The CO2-reactivity slope of Vmca was 3.27% per mmHg PaCO2. From normocapnia to hypercapnia, Vop did not change significantly (mean ± SD, 18 ± 4 cm•sec–1 to 18 ± 6 cm•sec–1), (end-tidal CO2, etCO2, = 43 ± 5 mmHg to 53 ± 4 mmHg, respectively). In contrast, Vop increased significantly under hypocapnic conditions (etCO2 = 26 ± 4 mmHg) to 25 ± 5 cm•sec–1 (P < 0.05). The CO2-reactivity slope of Vop from normocapnia to hypocapnia was 2.57% per mmHg.
Conclusions: This study demonstrates that Vop increases with hypocapnia, but is unaffected by hypercapnia. The anastomoses of the ophthalmic artery with the external carotid artery, which displays a relatively fixed resistance, may account for these findings.
|
Introduction |
|---|
|
TOPAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Because of its proximity to the brain and the origin of its blood supply, it might be expected that blood flow to the eye would respond in a similar fashion to other intracranial vasculature in terms of autoregulation and carbon dioxide (CO2) vasoreactivity. Indeed retinal blood flow has been shown to increase with increasing CO2 tensions.3–6 However, perfusion to the eye as a whole appears to be more complex, as other investigations have revealed that ophthalmic artery blood flow velocity (Vop) does not increase with hypercapnia.4,5,7 Conversely, hypocapnia has been shown to cause a reduction in retinal artery blood flow,3,6 but the effects of hypocapnia on ophthalmic artery blood flow have not been studied.
Since the ophthalmic artery is the origin for the blood supply to the optic nerve, as well as the retina, the vasoreactivity of this vessel to CO2 may have important clinical implications. The purpose of this study is to determine the effects of hypocapnia and hypercapnia on the Vop in humans. Simultaneous measurement of flow velocity in the middle cerebral artery (Vmca) was undertaken to confirm the normal cerebral vascular response control.
|
Materials and methods |
|---|
|
TOPAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Experimental protocol
Subjects were placed in a semi-reclined position and the following variables were recorded: continuous non-invasive blood pressure, end-tidal CO2 (etCO2), Vop and Vmca. Vop and Vmca were measured simultaneously on the right side. With a nose clip in place, measurements were first made during normocapnia under stable conditions. The subjects then inhaled 5% CO2 in 40% oxygen for three minutes via a non-rebreathing valve. Following return to normocapnia with stable conditions for three minutes, subjects were instructed to voluntarily hyperventilate to maintain an etCO2 of approximately 25 mmHg for three minutes.
Blood flow velocity measurements
Vop and Vmca were measured simultaneously using a transcranial Doppler (TCD; DWL, Neuroscan, Sterling, VA, USA) with 2 MHz probes. Both vessels were identified using standard criteria. The MCA was insonated transtemporally with the TCD probe and measured at a depth between 45 to 50 mm. The probe was anchored using the Lam RackTM (DWL, Sterling, VA, USA) to maintain a constant angle of insonation.
The handheld probe for the ophthalmic artery was positioned over the closed eyelid angled posteriorly and slightly medially, as previously described.8 The depth was set at 50 mm with the power set at the lowest level consistent with satisfactory recordings. The probe for the ophthalmic artery cannot be anchored and was handheld during the study. To minimize error, all measurements were performed by only two individuals, and results were only accepted if optimal audio signals were obtained consistently. Because the ophthalmic artery runs directly outward horizontally from its origin, the error introduced by probe movement would be small.
etCO2 measurements
Calibration of the etCO2 monitor (Datex, Puritan Bennett Corp., Tewksberry, MA, USA) was performed at the start of each experiment. A plastic mouthpiece connected to a one-way valve was placed into the subject’s mouth. The one-way valve allowed separation of inflow gases from exhaled breath, without mixing and re-breathing. The etCO2 sampling line was on the outflow limb of the one-way valve. A clip was placed on the subject’s nose to prevent contamination from nasal breathing.
Blood pressure measurements
Continuous non-invasive blood pressure measurements (Colin Model 7000, Colin Medical Instruments Corp., San Antonio, TX, USA) were based on the radial arterial pulse. The continuous measurements of the arterial pulse displacement was calibrated against a conventional cuff placed on the ipsilateral arm. Automatic re-calibration occurred at 2.5-minute intervals throughout each study session.
CO2-reactivity calculations
Linear regression analysis was used to determine the relationship between etCO2 vs Vop, and etCO2 vs Vmca, and corrected to baseline velocity. Since Vop exhibited a non-linear relationship from hypocapnia to hypercapnia, CO2-reactivity was calculated for Vop as the percent change in blood flow velocity (V) per mmHg change in etCO2 from baseline to either hypercapnia or hypocapnia:
 |
Statistical analysis
etCO2 measurements were expressed as mean ± SD. Analysis of variance for repeated measures and Student’s two-tailed paired t test with Bonferonni’s correction for multiple comparisons were used to compare measurements obtained during normocapnia, hypocapnia and hypercapnia. A P value < 0.05 was considered statistically significant.
|
Results |
|---|
|
TOPAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
. MAP ± SD during hypocapnia, normocapnia and hypercapnia were 74 ± 14, 80 ± 11, and 79 ± 13 mmHg, respectively. There were no significant differences in MAP between groups (P = 0.74). Mean etCO2 ± SD during hypocapnia, normocapnia and hypercapnia were 26 ± 4, 43 ± 5, and 53 ± 4 mmHg, respectively. Vmca increased linearly with etCO2 (r = 0.97). The hypocapnic, normocapnic, and hypercapnic values for Vmca ± SD were 36 ± 9, 62 ± 18, and 92 ± 22 cm•sec–1, respectively. The CO2-reactivity slope for Vmca was 3.27% change in flow velocity per mmHg CO2. The Vop ± SD for the hypocapnic, normocapnic, and hypercapnic conditions were 25 ± 5, 18 ± 4, and 18 ± 6 cm•sec–1, respectively. Vop demonstrated a non-linear relationship with etCO2 (r = –0.75). The Vop during normocapnia were significantly different from those during hypocapnia (P < 0.05) with all subjects demonstrating a consistent increase in Vop with hypocapnia (mean increase = 42.6 ± 16.4%; Figure). The CO2-reactivity slope for Vop was 2.57% change in flow velocity per mmHg CO2 from normocapnia to hypocapnia. The Vop did not differ between normocapnia and hypercapnia (P = 0.31).
|
|
|
Discussion |
|---|
|
TOPAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
Although there has been a significant amount of research on retinal artery blood flow, little work has been done on ophthalmic artery blood flow which supplies the optic nerve. The blood vessels to the optic nerve are small and originate in a retrobulbar location, making them difficult to study. Retinal blood flow is more accessible to study and has been shown to increase with hypercapnia.3–6
Tsacopoulos and David showed that retinal artery blood flow in monkeys decreases with hypocapnia and increases with hypercapnia.6 Their study was confirmed in humans by Harris et al. who demonstrated decreased retinal artery blood flow velocity with hypocapnia3 and increased retinal blood flow velocity with hypercapnia.3–5 They also found that the blood flow velocity in the short posterior ciliary arteries, a branch of the ophthalmic artery, increased with hypercapnia.5 The results of these studies indicate that the retinal artery and the short posterior ciliary artery behave similarly to the intracranial blood vessels in response to CO2.
The ophthalmic artery may behave differently than the intracranial vessels in response to CO2 because of its many anatomic connections with branches of the external carotid artery, which displays a relatively fixed resistance with significantly less CO2-reactivity.11,12 Other extracranial vessels, such as the brachial artery, demonstrate no CO2-reactivity.13 The ophthalmic artery usually originates from the internal carotid artery, but occasionally originates from aberrant locations such as the middle meningeal artery.14,15 It maintains an anastomosis to the external carotid artery via the lacrimal artery and other extracranial vessels. Therefore, the central retinal artery and short posterior ciliary arteries, which supply only structures originating from neuroectoderm, may respond to CO2 like the intracranial vessels. On the other hand, the ophthalmic artery has anastomoses with the external carotid artery, which has little CO2-reactivity.12 Thus, a plausible explanation for the present findings is that hypocapnia causes increased Vop due to a diversion of blood flow ("inverse steal") away from the vasoconstricted intracranial vessels and toward the ophthalmic artery.
Although the effects of hypocapnia have not been previously studied, consistent with our present findings, other studies have demonstrated a lack of change in Vop with mild to moderate hypercapnia in the ophthalmic artery.4,5,7 If "inverse steal" occurs with hypocapnia resulting in increased flow in the ophthalmic artery, it is not clear why hypercapnia does not result in decreased flow in the ophthalmic artery. It is possible that the collateral blood supply from the external carotid is sufficient to prevent a decrease in flow. Adequacy of this collateral circulation is supported by the frequent observation of "retrograde" flow in the ophthalmic artery to maintain normal MCA flow in the presence of ipsilateral internal carotid occlusion.16
Since vasoconstriction of retinal and optic nerve head capillary blood vessels with hyperoxemia has been demonstrated previously,17 it is possible that the admixture of 40% oxygen (hyperoxemia) with the inhaled CO2 in this study caused some vasoconstriction of the ophthalmic artery and counteracted the vasodilatory effects of CO2. However, Roff and colleagues previously demonstrated a similar lack of change in Vop under normoxemic hypercapnic conditions.5 Therefore, it is unlikely that the addition of 40% oxygen in our study which was used to simulate intraoperative conditions, significantly altered the CO2 response.
An alternative explanation for the present findings is that the ophthalmic artery diameter changes in response to changing CO2 partial pressure, which would invalidate the use of TCD to determine blood flow through this vessel. TCD flow studies are based upon the assumption that the caliber of the vessel being insonated is relatively constant, so that changes in V reflect corresponding changes in blood flow. Agreement between studies utilizing direct blood flow measurements vs blood flow velocity measurements of the effects of CO2 on the retinal artery suggests that velocity measurements accurately reflect changes in blood flow.3–6
However, if the ophthalmic artery dilates in response to hypercapnia, then an unchanged Vop might actually represent an increase in blood flow. Conversely, if the ophthalmic artery is constricting in response to hypocapnia, then an increase in Vop may represent no change, or even a decrease, in blood flow. CO2 has been shown to have little influence on the MCA diameter, but its effect on the ophthalmic artery has never been studied.18,19
It is not feasible to measure the diameter of the ophthalmic artery with current technology. Using the brachial artery as a representative peripheral artery, and as a surrogate for the ophthalmic artery, we examined the influence of CO2 on its diameter and flow velocity using colour Doppler imaging. Preliminary data on five healthy volunteer subjects demonstrated no significant change in diameter or blood flow velocity with either hypocapnia (etCO2 25 mmHg, diameter 3.6 mm ± 0.04 SD, velocity 74.3 cm•sec–1 ± 21 SD) or hypercapnia (etCO2 53 mmHg, diameter 3.8 mm ± 0.05 SD, velocity 72 cm•sec–1 ± 22 SD) compared to baseline (etCO2 46 mmHg, diameter 4.0 mm ± 0.06 SD, 74.6 cm•sec–1 ± 19 SD, P > 0.05 for both diameter and velocity). Therefore, if the ophthalmic artery behaves in a similar fashion to the extracranial vessels because of its anastomoses with the external carotid artery, then the diameter should be unaffected by CO2, and TCD flow velocities should correlate with blood flow.
We have demonstrated in this study that hypocapnia increases flow velocity in the ophthalmic artery, whereas hypercapnia has no effect. Further research will need to be done to determine how blood flow in the short posterior ciliary arteries, which also supply the optic nerve, is affected by hypocapnia. Determination of the optimal conditions for maximizing perfusion to the eye and the optic nerve may help us to understand the pathophysiology of ischemic conditions of the optic nerve in the future. The present study suggests that mild hypocapnia may increase blood flow to the ophthalmic artery, but it is unclear whether or not this would result in increased blood flow to the optic nerve.
|
Footnotes |
|---|
Accepted for publication July 24, 2003. Revision accepted January 13, 2004.
|
References |
|---|
|
TOPAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
|---|
2 Hayreh SS. Anterior ischemic optic neuropathy. Clin Neurosci 1997; 4: 251–63.[Medline]
3 Harris A, Arend O, Wolf S, Cantor LB, Martin BJ. CO2 dependence of retinal arterial and capillary blood velocity. Acta Ophthalmol Scand 1995; 73: 421–4.[Medline]
4 Harris A, Sergott RC, Spaeth GL, Katz JL, Shoemaker JA, Martin BJ. Color Doppler analysis of ocular vessel blood velocity in normal-tension glaucoma. Am J Ophthalmol 1994; 118: 642–9.[Medline]
5 Roff EJ, Harris A, Chung HS, et al. Comprehensive assessment of retinal, choroidal and retrobulbar haemodynamics during blood gas perturbation. Graefe’s Arch Clin Exp Ophthalmol 1999; 237: 984–90.[Medline]
6 Tsacopoulos M, David NJ. The effect of arterial Pco2 on relative retinal blood flow in monkeys. Invest Ophthalmol 1973; 12: 335–47.
7 Schmetterer L, Findl O, Strenn K, et al. Role of NO in the O2 and CO2 responsiveness of cerebral and ocular circulation in humans. Am J Physiol 1997; 273: R2005–12.
8 Fujioka KA, Douville CM. Anatomy and freehand examination techniques. In: Newell DW, Aaslid R (Eds). Transcranial Doppler. New York: Raven Press, Ltd.; 1992: 9–31.
9 Markwalder TM, Grolimund P, Seiler RW, Roth F, Aaslid R. Dependency of blood flow velocity in the middle cerebral artery on end-tidal carbon dioxide partial pressure – a transcranial ultrasound Doppler study. J Cereb Blood Flow Metabol 1984; 4: 368–72.[Medline]
10 Eng C, Lam AM, Mayberg TS, Lee C, Mathisen T. The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans. Anesthesiology 1992; 77: 872–9.[Medline]
11 Truemper EJ, Fischer AQ. Cerebrovascular developmental anatomy and physiology in the neonate and child. In: Babikian VL, Wechsler LR (Eds). Transcranial Doppler Ultrasonography. St. Louis: Mosby; 1993: 245–81.
12 Breslau PJ, Knox R, Fell G, Greene FM, Thiele BL, Strandness DE Jr. Effect of carbon dioxide on flow patterns in normal extracranial arteries. J Surg Res 1982; 32: 97–103.[Medline]
13 Miyazaki M. Effect of some respiratory maneuvers on cerebral and peripheral circulation, with special reference to maximum breathing, voluntary hyperventilation and the valsalva maneuver. Jpn Circ J 1973; 37: 455–60.[Medline]
14 Liu Q, Rhoton AL Jr. Middle meningeal origin of the ophthalmic artery. Neurosurgery 2001; 49: 401–7.[Medline]
15 Hayreh SS, Dass R. The ophthalmic artery. I. Origin and intra-cranial and intra-canalicular course. Br J Ophthalmol 1962; 46: 65–98.
16 Kaneda H, Irino T, Arita N, Minami T, Taneda M, Shiraishi J. Relationship between ophthalmic artery blood flow and recanalization of occluded carotid artery. Ultrasonic Doppler study. Stroke 1978; 9: 360–3.
17 Langhans M, Michelson G, Groh MJ. Effect of breathing 100% oxygen on retinal and optic nerve head capillary blood flow in smokers and non-smokers. Br J Ophthalmol 1997; 81: 365–9.
18 Newell DW, Aaslid R, Lam A, Mayberg TS, Winn HR. Comparison of flow and velocity during dynamic autoregulation testing in humans. Stroke 1994; 25: 793–7.[Abstract]
19 Giller CA, Bowman G, Dyer H, Mootz L, Krippner W. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery 1993; 32: 737–42.[Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
