HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas A. Orszulak Richard C. Daly Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Plöchl, W. Articles by Daly, R. C. Search for Related Content PubMed PubMed Citation Articles by Plöchl, W. Articles by Daly, R. C.

Ann Thorac Surg 1998;66:118-123
© 1998 The Society of Thoracic Surgeons

---

Original articles: cardiovascular

Critical cerebral perfusion pressure during tepid heart operations in dogs

^a Department of Anesthesiology, Mayo Foundation and Mayo Clinic, Rochester, Minnesota, USA
^b Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Mayo Foundation and Mayo Clinic, Rochester, Minnesota, USA

Accepted for publication February 23, 1998.

Address reprint requests to Dr Cook, Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905
e-mail: (cook.david{at}mayo.edu)

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Background. The management of blood pressure during cardiopulmonary bypass varies widely. This may be particularly relevant with the trend to warmer bypass temperatures and an older patient population. Therefore, we examined the minimal perfusion pressure that maintains cerebral oxygen delivery during cardiopulmonary bypass at 33°C.

Methods. Ten dogs were placed on bypass and body temperature was reduced to 33°C (-stat pH management). At six randomly ordered mean arterial blood pressures (35, 40, 45, 50, 60, and 70 mm Hg), cerebral blood flow, oxygen delivery, and metabolic rate were determined.

Results. Cerebral oxygen delivery was stable if the mean arterial pressure was greater than or equal to 60 mm Hg. If mean arterial pressure was less than or equal to 50 mm Hg, cerebral oxygen delivery decreased, and at less than 45 mm Hg cerebral ischemia was seen.

Conclusions. In a dog without vascular disease, the brain becomes perfusion pressure-dependent at a mean arterial pressure of approximately 50 mm Hg. There is no leftward shift of the cerebral autoregulatory curve during bypass at 33°C. Greater support of mean arterial pressure during "tepid" cardiopulmonary bypass is indicated in the current adult surgical population that is older and has vascular comorbidity.

	Introduction

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Patients undergoing cardiac operations have a significant incidence of neurologic morbidity. As many as 6% to 9% may experience stroke or encephalopathy, whereas 50% may demonstrate neurocognitive abnormalities postoperatively [1–3]. The etiology of this dysfunction is multifactorial but presumably includes hypoperfusion as well as cerebral embolization [4–7].

Under nonbypass conditions, autoregulation maintains cerebral blood flow (CBF) over a wide range of perfusion pressures; the lowest mean arterial pressure (MAP) at which CBF is stable is approximately 60 mm Hg [8]. During hypothermic cardiopulmonary bypass (CPB) autoregulation remains active if -stat pH management is used [9, 10]. However, it has been reported that cerebral perfusion is independent of MAPs as low as 20 to 35 mm Hg during hypothermia [11–13]. These findings were interpreted to mean that during hypothermic CPB the cerebral autoregulatory curve is shifted leftward [12, 14]. However, the results indicating this leftward shift must be viewed with caution. Those studies pooled single measurements of MAP and CBF from multiple patients because in a clinical population it is difficult to do multiple CBF measurements and because it is unacceptable to push the cerebral circulation to perfusion pressures at which cerebral oxygen delivery is compromised. However, pooled clinical data are unlike repeated measurements done at varying pressures in an experimental model. During CPB, CBF is a function of temperature, arterial carbon dioxide tension, hematocrit, and MAP. Because there is a large variability among patients in these physiologic determinants, autoregulation curves cannot reliably be drawn from pooled data because large amounts of data scatter may obscure meaningful relationships.

In contrast to those clinical studies, laboratory reports have not indicated a significant leftward shift of the autoregulatory curve during hypothermic CPB but have demonstrated a small positive slope to the pressure–CBF relationship under both normothermic and hypothermic conditions [15]. Newman and colleagues [16] described a similar relationship in patients when two CBF–MAP data pairs were determined during CPB. With the shift toward higher CPB temperatures during the last few years and the increasing age of the cardiac surgical population, maintenance of an adequate cerebral perfusion pressure is of critical importance. However, it is not clear what the minimal blood pressure is that supports cerebral oxygen delivery (CDO₂) during "tepid" CPB.

In this context, it is important to recognize the unique features of CPB. During CPB, patients undergo both temperature change and hemodilution, so changes in CBF alone may not capture important differences in cerebral oxygen delivery. As such, during CPB it is maintenance of CDO₂ that is of critical importance. Although the brain may tolerate small reductions in CDO₂ and maintain its metabolic rate, this capacity is limited, and it is probably prudent in today’s surgical population to maintain a perfusion pressure at which CDO₂ is stable. Managing perfusion so that the brain is not required to increase oxygen extraction may provide an acceptable margin of safety. This study is an initial attempt to better characterize the minimal blood pressure that maintains cerebral oxygenation during CPB under differing degrees of CPB hypothermia.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Experimental protocol
After review and approval by the Institutional Animal Care and Use Committee, 10 unmedicated fasting adult mongrel dogs weighing 18 to 28 kg (mean, 21 ± 3 kg) were studied. The dogs were placed in a Plexiglas box and anesthesia was induced with halothane (3% to 4% inspired). Peripheral intravenous access was then secured, muscle relaxation was obtained with pancuronium 0.1 mg · kg^-1, and the trachea was intubated. Ventilation was controlled to maintain arterial carbon dioxide tension at 35 to 40 mm Hg and an arterial oxygen tension at 150 to 250 mm Hg. Anesthesia was maintained with fentanyl and midazolam (bolus, 250 µg · kg^-1 fentanyl and 350 µg · kg^-1 midazolam, followed by infusion, fentanyl 3.0 µg · kg^-1 · min^-1 and midazolam 9.6 µg · kg^-1 · min^-1). Muscle relaxation was maintained by continuous infusion of pancuronium (0.8 µg · kg^-1 · min^-1).

Cannulas were surgically inserted into a femoral artery for MAP measurements and blood sampling. After anticoagulation with heparin (400 units · kg^-1 intravenously), the sagittal sinus was exposed, isolated, and cannulated as described previously [17, 18] for direct measurements of CBF from the anterior, superior, and lateral portions of both hemispheres. Flow was recorded continuously with a flow-through electromagnetic flow probe (EP300 API, Carolina Medical Electronics, Inc., King, NC), calibrated as necessary against a graduated cylinder. Body temperature was measured with an esophageal thermistor and brain temperature with a parietal epidural thermistor. Intracranial pressure was transduced using a fiberoptic epidural sensor (LADD Industries, Burlington, VT). The cranium was then closed with Surgicel (Johnson & Johnson, Inc, Arlington, TX) and adhesive.

For CPB, a left-side thoracotomy was performed. The bypass machine was primed with approximately 750 mL of 6% dextran 70. Venous drainage to the extracorporeal circuit was by a 36F cannula placed in the right atrium through the right atrial appendage. The blood was circulated by a centrifugal pump through a combined heat exchanger–oxygenator (Bentley Spiral Gold, Irvine, CA) and returned through a cannula (4.5-mm ID) into the root of the aorta.

After completion of the surgical preparation and before the establishment of CPB, measurements were obtained. After the onset of CPB animals were allowed to stabilize (brain temperature, 38°C) and a second set of measurements were done. Thereafter the animals were cooled to a brain temperature of 33°C. After stable CPB conditions were achieved the minimal blood pressure supporting cerebral oxygenation was evaluated. At six randomly varied MAPs (35, 40, 45, 50, 60, and 70 mm Hg) cerebral physiologic measurements were obtained. Each level of MAP was maintained for 15 minutes or until CBF was stable, whichever was longer. Cerebral blood flow was recorded and arterial and cerebral venous blood samples were obtained. Arterial blood was drawn from the femoral line and cerebral venous blood was drawn from the sagittal sinus cannula. Mean arterial blood pressure was varied by altering pump flow rate. Changing pump flow rate independent of MAP does not affect CBF [18, 19]. No vasoconstrictors or vasodilators were used.

Oxygen content and CDO₂ and consumption were calculated by means of standard formulas.

Arterial or venous oxygen content:

where Hgb = hemoglobin concentration: SxO₂ = oxygen saturation; PxO₂ = partial pressure of oxygen; x = arterial (a), cerebral venous (v).

Cerebral oxygen delivery (CDO₂):

Cerebral metabolic rate for oxygen (CMRO₂):

Oxygen extraction ratio (OER):

Arterial hemoglobin concentration and blood gas data were continuously monitored by in-line detectors (CDI 100 and CDI 400; Cardiovascular Devices, Inc, Tustin, CA). At each MAP step, hemoglobin and arterial oxygen tension were measured directly by blood gas analyzer and co-oximeter (IL 1306 pH/blood gas analyzer and IL 482 co-oximeter; Instrumentation Laboratory, Lexington, MA). Blood oxygen content was calculated from oxyhemoglobin concentrations and oxygen tensions measured on electrodes maintained at 37°C. Coefficients for dog hemoglobin were used.

Statistical analysis
Comparisons of cerebral and systemic physiologic variables among the six different levels of MAP were assessed using repeated measures analysis of variance. An MAP of 60 mm Hg served as the control value. Differences among the six periods were determined using the Student-Newman-Keuls test when necessary. Regression curves for CBF, CMRO₂, and CDO₂ were generated from individual values for each variable at MAPs from 35 to 50 mm Hg and for MAPs from 60 to 70 mm Hg. The figures present these curves, as well as mean values and standard deviations for each variable.

	Results

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
During stable CPB at 38°C, mean CBF and CMRO₂ were 45 ± 6 and 3.2 ± 0.8 mL · 100 g^-1 · min^-1, respectively. Reduction of brain temperature to 33°C at an equivalent MAP, arterial carbon dioxide tension, and hematocrit reduced CBF to 73% and CMRO₂ to 72% of the values measured at 38°C.

Systemic physiologic data during the six pressure-regulated CPB periods are shown in Table 1. The three most potent determinants of CBF, temperature, arterial carbon dioxide tension, and hematocrit, were kept within narrow ranges throughout each of the six experimental steps. Hemoglobin was maintained between 7.5 and 8 g · dL^-1, arterial carbon dioxide tension at 36 mm Hg, and brain temperature at 32° to 33°C throughout the study (Tables 1, 2).

Below MAP of 60 mm Hg, CBF and CDO₂ became pressure-dependent such that any reduction in perfusion pressure was paralleled by a decrease in CBF and CDO₂ (Figs 1, 2). Cerebral metabolic rate for oxygen was maintained during MAP reduction by a higher oxygen extraction ratio until MAP of 45 mm Hg was reached. Reduction in MAP to 40 mm Hg resulted in cerebral ischemia as indicated by the reduction in CMRO₂ (Fig 2). At MAP of 40 mm Hg, mean CMRO₂ was 1.9 ± 0.5 versus 2.3 ± 0.3 mL · 100 g^-1 · min^-1 at 60 mm Hg (p < 0.05).

View larger version (11K): [in this window] [in a new window]   Fig 1. Cerebral blood flow (CBF) (mL · 100 g-1 · min-1) versus mean arterial blood pressure (MAP). Values are mean ± standard deviation. Regression curves for CBF were generated from individual CBF values for MAPs from 35 to 50 mm Hg and for MAPs from 60 to 70 mm Hg. The curve consists of a pressure-independent flat portion for MAPs greater than or equal to 60 mm Hg and a pressure-dependent steep portion for MAPs less than or equal to 50 mm Hg. (*p < 0.05 versus MAP of 60 mm Hg by repeated-measures analysis of variance followed by Student-Newman-Keuls test.)

View larger version (14K): [in this window] [in a new window]   Fig 2. Cerebral oxygen delivery (CDO2) and cerebral metabolic rate for oxygen (CMRO2) versus mean arterial pressure (MAP). Values (mL · 100 g-1 · min-1) are mean ± standard deviation. Regression curves for CDO2 and CMRO2 were generated from individual values for each variable at MAPs from 35 to 50 mm Hg and for MAPs from 60 to 70 mm Hg. The reduction in MAP to 50 mm Hg revealed in a significant decrease in CDO2 whereas CMRO2 was maintained by an increase in cerebral oxygen extraction ratio until MAP of 45 mm Hg. (*p < 0.05 versus MAP of 60 mm Hg by repeated measures analysis of variance followed by Student-Newman-Keuls test.)

	Comment

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Autoregulation maintains CBF over a range of perfusion pressures; this is independent of cardiac output. Under non-CPB conditions cerebral perfusion is stable between perfusion pressures of approximately 60 and 150 mm Hg [8]. During CPB the data have been less clear. Because the determinants of cerebral perfusion are the same under bypass and nonbypass conditions, one would anticipate that MAP during CPB would determine cerebral perfusion in the same way as under nonbypass conditions. However, clinical studies in the 1980s deemphasized the role of MAP in determining cerebral perfusion and argued that CBF is maintained with -stat pH management to MAPs as low as 20 to 35 mm Hg under hypothermic conditions. Murkin and associates [12] reported that autoregulation was intact between perfusion pressures of approximately 25 and 80 mm Hg at 26°C, and Govier and colleagues [11] indicated that cerebral perfusion was unchanged with hypothermic CPB between MAPs of approximately 35 and 110 mm Hg. Also, Brusino and coworkers [13] did not show a dependence of CBF on perfusion pressures as low as 20 mm Hg in patients undergoing CPB at 21° to 28°C. This body of results was interpreted to mean that the cerebral autoregulatory curve was shifted leftward during hypothermia [12, 14] and is in part responsible for the tendency in clinical practice to allow lower MAPs as temperature is reduced during CPB.

Clinical studies of this type are limited by the number of CBF measurements that can be made using conventional techniques and by the inability to assess the lower limits of autoregulation in a clinical population. As such, in these reports autoregulatory curves were constructed by pooling individual CBF values from multiple patients. This is an important methodologic limitation because there is large between-patient variability in CBF and its determinants during CPB. The appropriate design for assessment of autoregulatory capacity is to obtain multiple CBF measurements at differing MAPs within a single subject.

These limitations are overcome in animal models, in which multiple cerebral physiologic measurements can be made at differing MAPs with extremely tight physiologic control (Table 1) and the lower limits of autoregulation can be rigorously tested. In contrast to the clinical studies, laboratory reports have not indicated a leftward shift of the autoregulatory curve during hypothermic CPB [15, 20]. Mutch and associates [15] showed a positive slope in autoregulatory curves at both normothermia and hypothermia (28°C) during CPB between 50 and 90 mm Hg in dogs. Sadahiro and colleagues [20] reported that during normothermic as well as hypothermic (25°C) CPB, CBF remained essentially unchanged so long as cerebral perfusion pressure remained higher than 50 mm Hg.

We found that during CPB with mild hypothermia (33°C) CBF and CDO₂ become pressure-dependent between MAPs of 60 and 50 mm Hg. The relationship between CBF, CDO₂, and MAP consists of two parts: a pressure-independent portion and a pressure-dependent portion. Autoregulation of CBF is preserved at MAPs of 60 mm Hg and higher. At MAPs less than or equal to 50 mm Hg CBF and, more importantly, CDO₂, are pressure-dependent. However, frank cerebral ischemia is not demonstrated during CPB at 50 mm Hg because the reduction in CDO₂ is compensated by an increased cerebral oxygen extraction. Although in our study the reduction in CMRO₂ was first statistically significant at MAP of 40 mm Hg, it is important to note that MAP of 45 mm Hg may not be physiologically adequate for brain metabolism, because at this pressure CMRO₂ was already reduced by 13% relative to control.

Although the appropriate changes in CMRO₂ with temperature reduction are established, it is not clear what is a "normal" CBF as brain temperature is reduced. Fundamentally, CDO₂ must be sufficient to support metabolic demand. Therefore, the definition of a normal or adequate MAP during CPB is best defined in terms of maintenance of CDO₂ (which captures both changes in CBF and hematocrit). The critical CDO₂ is defined as that at which CMRO₂ becomes delivery-dependent. Although the brain has a limited capacity to maintain CMRO₂ by increasing oxygen extraction when oxygen delivery is decreased, the maintenance of stable CDO₂ should probably be our physiologic goal. With this, some safety margin for the brain will exist. In this context, it is important to note that in a healthy dog, CDO₂ is significantly reduced at MAP of 50 mm Hg. Because age, hypertension, diabetes, and vascular disease alter ischemic tolerance and autoregulatory capacity [21–23], the minimum perfusion pressure supporting cerebral oxygenation in our clinical population should probably be at least 60 mm Hg.

There is an impression that hemodilution increases tolerance for hypotension because hemodilution increases organ blood flow. Although this flow increase helps maintain oxygen delivery, hemodilution does not increase the tolerance to hypotension. During CPB with MAP of 50 mm Hg, organ blood flow might be equal to or higher than in the pre-CPB period; however, if arterial oxygen content (because of reduced hematocrit) is 40% lower than it was before bypass the organ may still be ischemic. Pressure-dependency remains after hemodilution; the focus on flow alone, or on flow-metabolism ratios is misleading [24]. After hemodilution, normal autoregulatory curves can be constructed for brain; the absolute levels of flow are shifted upward but the curve seems to break at about the same pressures. This was well demonstrated by Henriksen [9].

Our study may be criticized for a number of reasons. First, it can be argued that previous studies indicated that bypass perfusion pressure is not a determinant of neurologic outcome [25, 26], thus the physiologic changes we document are not clinically relevant. Although it is true that physiologic measurements do not translate directly into clinical outcomes, there are good reasons to readdress the importance of perfusion pressure during CPB. First, our surgical population is changing. It is older and has significantly more hypertension, diabetes, and vascular disease than when many prior outcomes studies were done [27, 28]. These comorbidities directly impair the brain tolerance of reduced perfusion pressure [21–23]. Additionally, outcome studies have typically been descriptive or retrospective and did not randomly assign patients to a higher or lower perfusion pressure during CPB. When this was done recently by Gold and colleagues [29], greater support of perfusion pressure during CPB improved neurologic outcome. Finally, a large body of data suggests that the majority of, if not all, patients experience cerebral embolic events during CPB [6, 7]. In this context, regional cerebral perfusion is dependent on MAP [30, 31]. Thus, for a variety of reasons, a strong argument can be made for more than rigid control of MAP during CPB.

Some lesser criticisms might also be leveled. To do this study we used pump flow changes to alter MAP during CPB. Clinically, MAP is controlled by altering pump flow and using anesthetics and nitrosovasodilators. However, nitrosovasodilators and anesthetics are very active in the cerebral circulation, and their use to manipulate blood pressure would clearly confound our results. Conversely there is a body of literature that indicates that pump flow itself does not alter CBF if a minimum perfusion pressure is maintained [18, 20, 32, 33]. Similarly, high pump flows do not support cerebral perfusion in the context of hypotension [19]. Therefore, pump flow is primarily relevant inasmuch as it generates a perfusion pressure.

When pump flow (or cardiac output) is low, a greater proportion of blood is shunted from viscera and muscle to brain such that cerebral perfusion is maintained [18, 32]. This is the same physiology as is active under nonbypass conditions. Therefore, although the flows used to achieve hypotension in our study compromised systemic perfusion, the experimental evidence does not support the claim that critical cerebral perfusion was the result of low pump flow per se rather than low pressure.

Second, it might be questioned whether our preparation remains stable after exposing our animals to periods of hypotension that compromised cerebral oxygenation. To respond, first, all animals in the study showed an appropriate physiologic recovery of CBF, CDO₂, and CMRO₂ after low perfusion pressure conditions. Second, intracranial pressure remained stable throughout the experiments, and third, the MAP sequence was randomized so any experimental effect would be carried through every experimental period. With these observations and precautions, we believe the data we provide is rigorous.

Another potential criticism is that we assessed the dependency of cerebral oxygenation on MAP and not cerebral perfusion pressure, which may be technically more correct. However, Table 2 shows that with the low intracranial pressures we documented, cerebral perfusion pressure is virtually identical to MAP. In addition, our study was designed to try to reflect what is monitored during clinical practice. In the operating room, intracranial pressure is not measured, so what is of practical importance in a study of this type is identifying critical MAP during bypass.

Finally, we cannot provide a single value for the minimal blood pressure supporting cerebral oxygenation during tepid CPB, or what the ideal perfusion pressure is. Our data indicate that 60 mm Hg is adequate in our model but that 50 mm Hg is too low. In the clinical population there is probably greater variability and generally a higher perfusion pressure requirement than in our dogs. Brief periods of hypotension can also be tolerated, but some patients probably require MAPs significantly greater than 60 mm Hg during CPB. Our goal in this study was not to dictate but to provide a physiologic foundation for MAP management as CPB practice shifts toward temperatures approximating 33°C.

In summary, this study shows that during CPB at 33°C, CDO₂ is compromised at MAP of 50 mm Hg in a canine model. Because the current adult surgical population is older and suffers from coexisting vascular diseases, our study strongly argues for rigorous blood pressure support during CPB. We believe an MAP of 60 mm Hg is indicated as a starting point when the hemoglobin is 7.5 to 8 g · dL^-1.

	Acknowledgments

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
Walter Plöchl, MD, is supported by grant 201357-MED from the Austrian Science Foundation, Vienna, Austria. This work is supported by the American Heart Association—Minnesota Affiliate and the Mayo Foundation.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Roach G.W., Kanchuger M., Mangano C.M., et al. Adverse cerebral outcomes after coronary bypass surgery. N Engl J Med 1996;335:1857-1863.[Abstract/Free Full Text]
2. Tuman K.J., McCarthy R.J., Najafi H., Ivankovich A.D. Differential effects of advanced age on neurologic and cardiac risks of coronary artery operations. J Thorac Cardiovasc Surg 1992;104:1510-1517.[Abstract]
3. Shaw P.J., Bates D., Cartlidge N.E., et al. Neurologic and neuropsychological morbidity following major surgery: comparison of coronary artery bypass and peripheral vascular surgery. Stroke 1987;18:700-707.[Abstract/Free Full Text]
4. Stockard J.J., Bickford R.G., Schauble J.F. Pressure-dependent cerebral ischemia during cardiopulmonary bypass. Neurology 1973;23:521-529.[Free Full Text]
5. Blossom G.B., Fietsam R., Jr, Bassett J.S., Glover J.L., Bendick P.J. Characteristics of cerebrovascular accidents after coronary artery bypass grafting. Am Surg 1992;58:584-589.[Medline]
6. Pugsley W., Klinger L., Paschalis C., Treasure T., Harrison M., Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994;25:1393-1399.[Abstract]
7. Blauth C.I., Arnold J.V., Schulenberg W.E., McCartney A.C., Taylor K.M., Loop F.D. Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988;95:668-676.[Abstract]
8. Paulson O.B., Strandgaard S., Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990;2:161-192.[Medline]
9. Henriksen L. Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO₂, O₂, and blood pressure. J Cereb Blood Flow Metab 1986;6:366-378.[Medline]
10. Hindman B.J., Dexter F., Cutkomp J., Smith T., Tinker J.H. Hypothermic acid-base management does not affect cerebral metabolic rate for oxygen at 27 degrees C. A study during cardiopulmonary bypass in rabbits. Anesthesiology 1993;79:580-587.[Medline]
11. Govier A.V., Reves J.G., McKay R.D., et al. Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg 1984;38:592-600.[Abstract]
12. Murkin J.M., Farrar J.K., Tweed W.A., McKenzie F.N., Guiraudon G. Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO₂. Anesth Analg 1987;66:825-832.[Abstract/Free Full Text]
13. Brusino F.G., Reves J.G., Smith L.R., Prough D.S., Stump D.A., McIntyre R.W. The effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass. J Thorac Cardiovasc Surg 1989;97:541-547.[Abstract]
14. Davis R.F., Dobbs J.L., Casson H. Conduct and monitoring of cardiopulmonary bypass. In: Gravlee G.P., Davis R.F., Utley J.R., eds. Cardiopulmonary bypass: principles and practice. Baltimore: Williams & Wilkins, 1993:578-602.
15. Mutch W.A.C., Sutton I.R., Teskey J.M., Cheang M.S., Thomson I.R. Cerebral pressure-flow relationship during cardiopulmonary bypass in the dog at normothermia and moderate hypothermia. J Cereb Blood Flow Metab 1994;14:510-518.[Medline]
16. Newman M.F., Croughwell N.D., White W.D., et al. Effect of perfusion pressure on cerebral blood flow during normothermic cardiopulmonary bypass. Circulation 1996;94(Suppl 2):353-357.[Abstract/Free Full Text]
17. Michenfelder J.D., Milde J.H. The relationship among canine brain temperature, metabolism, and function during hypothermia. Anesthesiology 1991;75:130-136.[Medline]
18. Cook D.J., Orszulak T.A., Daly R.C. The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow in dogs. J Cardiothorac Vasc Anesth 1997;11:420-427.[Medline]
19. Schwartz A.E., Sandhu A.A., Kaplon R.J., et al. Cerebral blood flow is determined by arterial pressure and not cardiopulmonary bypass flow rate. Ann Thorac Surg 1995;60:165-169.[Abstract/Free Full Text]
20. Sadahiro M., Haneda K., Mohri H. Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion. J Thorac Cardiovasc Surg 1994;108:446-454.[Abstract/Free Full Text]
21. Baumbach G.L., Heistad D.D. Cerebral circulation in chronic arterial hypertension. Hypertension 1988;12:89-95.[Abstract/Free Full Text]
22. Coyle P., Heistad D.D. Blood flow through cerebral collateral vessels in hypertensive and normotensive rats. Hypertension 1986;8(Suppl 2):67-71.
23. Croughwell N., Lyth M., Quill T.J., et al. Diabetic patients have abnormal cerebral autoregulation during cardiopulmonary bypass. Circulation 1990;82(Suppl 4):407-412.[Abstract/Free Full Text]
24. Cook D.J. The CBF-CMRO₂ ratio is a misleading concept during cardiopulmonary bypass (CPB) in adults. Anesth Analg 1995;80:SCA69.
25. Slogoff S., Reul G.J., Keats A.S., et al. Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 1990;50:911-918.[Abstract]
26. Gardner T.J., Horneffer P.J., Manolio T.A., et al. Stroke following coronary artery bypass grafting: a ten-year study. Ann Thorac Surg 1985;40:574-581.[Abstract]
27. Weintraub W.S., Wenger N.K., Jones E.L., Craver J.M., Guyton R.A. Changing clinical characteristics of coronary surgery patients. Differences between men and women. Circulation 1993;88:79-86.
28. Hammermeister K.E., Burchfiel C., Johnson R., Grover F.L. Identification of patients at greatest risk for developing major complications at cardiac surgery. Circulation 1990;82(Suppl 4):380-389.
29. Gold J.P., Charlson M.E., Williams-Russo P., et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 1996;110:1302-1311.
30. Dirnagl U., Pulsinelli W. Autoregulation of cerebral blood flow in experimental focal brain ischemia. J Cereb Blood Flow Metab 1990;10:327-336.[Medline]
31. Muhonen M.G., Sawin P.D., Loftus C.M., Heistad D.D. Pressure-flow relations in canine collateral-dependent cerebrum. Stroke 1992;23:988-994.[Abstract/Free Full Text]
32. Fox L.S., Blackstone E.H., Kirklin J.W., et al. Relationship of brain blood flow and oxygen consumption to perfusion flow rate during profoundly hypothermic cardiopulmonary bypass. An experimental study. J Thorac Cardiovasc Surg 1984;87:658-664.[Abstract]
33. Tanaka J., Shiki K., Asou T., Yasui H., Tokunaga K. Cerebral autoregulation during deep hypothermic nonpulsatile cardiopulmonary bypass with selective cerebral perfusion in dogs. J Thorac Cardiovasc Surg 1988;95:124-132.[Abstract]

This article has been cited by other articles:

				S. Maier, W. R. Hasibeder, C. Hengl, W. Pajk, B. Schwarz, J. Margreiter, H. Ulmer, J. Engl, and H. Knotzer Effects of phenylephrine on the sublingual microcirculation during cardiopulmonary bypass Br. J. Anaesth., April 1, 2009; 102(4): 485 - 491. [Abstract] [Full Text] [PDF]

				J. C. Halstead, M. Meier, M. Wurm, N. Zhang, D. Spielvogel, D. Weisz, C. Bodian, and R. B. Griepp Optimizing selective cerebral perfusion: Deleterious effects of high perfusion pressures. J. Thorac. Cardiovasc. Surg., April 1, 2008; 135(4): 784 - 791. [Abstract] [Full Text] [PDF]

				M. Brueck, W. Kramer, P. Vogt, N. Steinert, P. Roth, G. Gorlach, M. Schonburg, and M. C. Heidt Antiplatelet therapy early after bioprosthetic aortic valve replacement is unnecessary in patients without thromboembolic risk factors Eur. J. Cardiothorac. Surg., July 1, 2007; 32(1): 108 - 112. [Abstract] [Full Text] [PDF]

				M. Dworschak, M. Czerny, M. Grimm, G. Grubhofer, and W. Plochl The impact of asymptomatic carotid artery disease on the intraoperative course of coronary artery bypass surgery Perfusion, January 1, 2003; 18(1): 15 - 18. [Abstract] [PDF]

				D. J. Cook Optimal Conditions for Cardiopulmonary Bypass Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2001; 5(4): 265 - 272. [Abstract] [PDF]

				W. Plochl, D. J. Cook, T. A. Orszulak, and R. C. Daly Intracranial Pressure and Venous Cannulation for Cardiopulmonary Bypass Anesth. Analg., February 1, 1999; 88(2): 329 - 329. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thomas A. Orszulak Richard C. Daly Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Plöchl, W. Articles by Daly, R. C. Search for Related Content PubMed PubMed Citation Articles by Plöchl, W. Articles by Daly, R. C.