Experimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion

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1 xperimental study of cerebral autoregulation during cardiopulmonary bypass with or without pulsatile perfusion Twenty-four adult mongrel dogs were divided into four equal groups according to the following method of cardiopulmonary bypass: normothermic continuous (so-called nonpulsatile)' perfusion, normothermic pulsatile perfusion, hypothermic continuous perfusion, and hypothermic pulsatile perfusion. Cerebral blood flow was deterniined by measuring the volume of sagittal sinus venous blood outflow with a transit-time ultrasonic flowmeter. Cardiopulmonary bypass was initiated at a flow rate of 8 mi/kg per minute. Cerebral temperature was maintained at 37 C in the normothermic groups and at 25 C in the hypothermic groups. Arterial ph and carbon dioxide were maintained within the physiologic range by alpha-stat acid-base regulation. Mean cerebral perfusion pressure and blood flow were not affected during 9 minutes of the bypass. The respective values were 67.1 mm Hg and 37.1 mi/i gm brain per minute with normothermic continuous perfusion, 72.8 mm Hg and 39. mi/i gm per minute with nonpulsatile perfusion, 98. mm Hg and 23. mi/ gm per minute with hypothermic continuous perfusion, and 86.8 mm Hg and 22.3 mi/1 gm per minute with hypothermic pulsatile perfusion. Pump flow rates were altered from 1 to 12 mi/kg per minute in a stepwise fashion to obtain graded changes of perfusion pressure. Cerebral blood flow, however, was not changed significantly by cerebral perfusion pressure so long as perfusion pressure was greater than 5 mm Hg. Conversely, cerebral blood flow changed proportionally with cerebral perfusion pressure at a pressure less than 5 mm Hg. The correlation between cerebral blood flow and perfusion pressure was described as two separate lines determined by linear regression. The slope of the regression line relating cerebral blood flow to perfusion pressure was.16 ±.8 for a cerebral perfusion pressure above 5 mm Hg and.68 ±.11 below 5 mm Hg in the normothermic continuous perfusion group;.14 ±.9 and.32 ±.9 with normothermic pulsatile perfusion;.1 ±.4 and.62 ±.18 with hypothermic continuous perfusion;.9 ±.8 and.39 ±.4 in the hypothermic pulsatile perfusion group. The slope above 5 mm Hg was significantly smaller and closer to zero in all groups than it was at a perfusion pressure below 5 mm Hg (p <.5). The slope and cerebral blood flow for a perfusion pressure above 5 mm Hg between pulsatile and continuous perfusion groups was not significantly different, whereas the value of the slope and cerebral blood flow in pulsatile groups when cerebral perfusion pressure was less than 5 mm Hg was significantly (p <.5) smaller and higher, respectively. These data suggest that cerebral autoregulation is intact at a cerebral perfusion pressure greater than 5 mm Hg during either normothermic or hypothermic cardiopulmonary bypass. In addition, compared to continuous (nonpulsatile) perfusion, pulsatile bypass generated a higher cerebral blood flow at a cerebral perfusion pressure less than 5 mm Hg. (J THORAC CARDIOVASC SURG 1994;18:446-54) Mitsuaki Sadahiro, MD, Kiyoshi Haneda, MD, and Hitoshi Mohri, MD, Sendai, Japan From the Department of Thoracic and, Tohoku University School of Medicine, Sendai, Japan. Presented in part at the Thirty-ninth Congress of the uropean Society for, Budapest, Hungary, Sept. 9-12, 199. Received for publication July 3,1993. Accepted for publication Feb. 22,1994. Address for reprints: Mitsuaki Sadahiro, MD, Department of Thoracic and, Tohoku University School of Medicine, 1-1 Seiryocho, Aobaku, Sendai, 98, Japan. Copyright 'Cl 1994 by Mosby-Year Book, Inc /94 $ /1/

2 The Journal of Thoracic and Volume 18, Number 3 Sadahiro, Haneda, Mohri 447 The relationship between systemic pressure and the autoregulation of cerebral blood flow (CBF) appears to be dependent on metabolism and is determined locally by metabolic demand. CBF under physiologic condition is maintained by autoregulation over a wide range of arterial pressures (6 to 15 mm Hg).1,2 Autoregulation is important during cardiopulmonary bypass (CPB) because maintenance of an adequate perfusion pressure may protect the brain from injuries caused by cerebral ischemia or hyperperfusion. Several recent studies reported pressure-flow autoregulation and the cerebrovascular response to arterial carbon dioxide tension during moderately hypothermic CPB (26 to 28 C) and alpha-stat blood gas management (arterial carbon dioxide tension 38 to 42 mm Hg, analyzed at 37 C).3-6 However, the effect of nonpulsatile CPB on the autoregulatory mechanism and its relationship to cerebral circulation has not been fully elucidated. Some investigators suggest that pulsatility is necessary for the maintenance of vasomotor tone to preserve autoregulation. 7,8 Pulsatile assist devices are used occasionally during cardiac operations, and several advantages of pulsatile compared with nonpulsatile perfusion during CPB have been reported The absence of a consensus as to the specific merits of the various perfusion modalities that are currently available led us to investigate the extent to which autoregulation of CBF occurs during normothermic as well as moderately hypothermic CPB and to determine the effect of pulsatile perfusion on the relationship between CBF and cerebral perfusion pressure (CPP) during CPB. Materials and methods xperimental design. Twenty-four adult mongrel dogs with an average body weight of 16.6 ± 3.8 kg were used. They were divided into the following groups: NC group, normothermic CPB with continuous (nonpulsatile) perfusion (n = 6, brain temperature 37 C); NP group, normothermic CPB with pulsatile perfusion (n = 6, brain temperature 37 C); HC group, hypothermic CPB with continuous (nonpulsatile) perfusion (n = 6, brain temperature 25 C); and HP group, hypothermic CPB with pulsatile perfusion (n = 6, brain temperature 25 C). Anesthesia was induced with intravenous thiopental sodium (25 mg/kg) and intramuscular atropine sulfate (.2 mg/kg). After endotracheal intubation, the animals' lungs were ventilated with a volume-constant respirator (model 48-6, Shinano, Tokyo, Japan) adjusted to a tidal volume of 2 ml/kg at a rate of 25 breaths/min. Anesthesia was maintained with.5% halothane in 1% oxygen. Transfemoral polyethylene catheters advanced to the level of the aortic arch were placed for hemodynamic monitoring and arterial sampling. CPB was maintained at a flow rate of 8 mljkg per minute for 9 minutes in all groups before flow rate was altered for subsequent studies. Brain temperature was kept at 37 C in the normothermic groups (NC, NP). Core cooling to 25 C averaged 3 minutes in the hypothermic groups (HC, HP). A pul- satile assist device was used in the pulsatile perfusion groups (NP, HP) to generate a pulse pressure throughout CPB. Graded changes in perfusion pressure were obtained by increasing pump flow rate from 8 to 1 to 12 ml/kg per minute and then decreasing it in a stepwise fashion from 8 to 6,4,2, and 1 ml/kg per minute. After the preparation had stabilized at each flow rate, mean perfusion pressure and CBF were recorded to document the correlation between CPP and CBF. In addition, arterial and sagittal sinus blood were withdrawn for determination of oxygen content and calculation of cerebral oxygen consumption. Measurement of CBF. CBF was determined by measuring the volume of sagittal sinus venous outflow with a transit-time ultrasonic flowmeter (Transonic system T21, Transonic System Inc., Ithaca, N.Y.). The sagittal sinus was exposed about 1 cm anterior to the occipital process by a round midline craniotomy with a diameter of 3 cm. After heparin (3 mg/kg) was administered, an 8F polyethylene tube (outer diameter 2.75 mm) was inserted into the sagittal sinus and the tip of the tube was advanced anterior to the level of the coronal suture. Venous blood flow from the sagittal sinus passed into superior vena cava through the outflow tube, which was inserted from the azygos vein. The ultrasonic transit-time flow probe was placed in the circuit between the sagittal sinus and the superior vena cava. The distal tip of the outflow tube, which drained into the superior vena cava, was placed in a reservoir to maintain a constant sagittal sinus outflow pressure whenever pump flow rate was changed. The reservoir was initially primed with saline solution, and the fluid level was set at the level of the right atrium by returning the collected venous flow to the perfusion circuit via a roller pump. Sagittal sinus outflow pressure was continuously monitored distal to the flow probe and maintained at less than 4mmHg. Thermistors were placed in the esophagus and brain. The brain thermistor was positioned 5 mm deep in the outer cerebral cortex of the mid-central parietal lobe through a burr hole in the skull. Intracranial pressure was measured by an epidural pressure-monitoring balloon catheter that was introduced into the epidural space through the same burr hole that was used for the brain thermistor (Fig. 1). Great care was paid to avoid excessive surgical trauma to the head to avoid losing physiologic control of cerebral vessels during dissection and instrumentation of the preparation. CPB. The heart was approached from a right lateral thoracotomy and CPB was initiated at a flow rate of 8 ml/min per kilogram. The ascending aorta was cannulated (Sarns 5.2 mm cannula, Sarns Inc./3M Health Care, Ann Arbor, Mich.) and venous return was accomplished with bicaval cannulas (2F, 24F) inserted via the right atrium. The ascending aorta was crossclamped and the left atrium was vented to the extracorporeal circuit. The perfusion system consisted of a conventional roller pump, cardiotomy reservoir, and membrane oxygenator with an internal heat exchanger (HPO-25, Mera, Tokyo, Japan). The reservoir was primed with homologous heparinized blood and lactated Ringer's solution, dextran, sodium bicarbonate, and mannitol. The oxygenator was ventilated with 1% oxygen at a ventilation/perfusion ratio of 1: 1 and.5% halothane was added. Carbon dioxide was not added during CPB (nontemperaturecorrected arterial carbon dioxide tension of about 4 mm Hg). Arterial blood ph was maintained at approximately 7.4 with sodium bicarbonate. Arterial carbon dioxide tension was

3 448 Sadahiro, Haneda, Mohri The Journal of Thoracic and September 1994 Superior sagittal sinus Sampling of sagittal venous blood Drainage to SVC Fig. 1. Method for measurement of CBF and epidural pressure. SVC, Superior vena cava. kept between 35 and 45 mm Hg (analyzed at 37 C) by adjusting flow rate of the gas mixture. Additional drugs were not used to control perfusion pressure. Hematocrit value during CPB was kept between 2% to 25%. An assist device (Datascope PAD system 42, Datascope Corp., Montvale, N.J.) was used to generate pulsatile flow throughout the period of CPB in the pulsatile groups (NP, HP). Pulse frequency was set at 8 per minute to maintain a pulse pressure between 25 and 3 mm Hg at a flow rate of 8 ml/kg per minute. The brain was weighed at completion of the experiment. Data analysis. CBF was measured and converted to milliliters per 1 gm of brain per minute according to the method of Michenfelder, Messik, and Theye. J3 CPP was taken as the difference between perfusion pressure and intracranial pressure. Cerebral vascular resistance was calculated as the ratio between CBF and CPP. Blood samples were drawn from the arterial and venous lines of the extracorporeal circuit and from the sagittal sinus drainage tube. The samples were analyzed at 37 C for ph, oxygen tension, and carbon dioxide tension with an IL gas analyzer (model 813, Instrumentation Laboratory, Inc., Lexington, Mass.). Oxygen content and cerebral oxygen consumption were calculated by the following formulas: CO2 (vol%) = (1.34 Hb. %2sat.)/I +.3. P2 Cerebral oxygen consumption (mi/ioo gm/min) = (Cao2 - Cso2)/1. CBF (mi/ioo gm/min) where Caz is oxygen content; Hb is hemoglobin; Cao2 is arterial oxygen content, and Cso2 is sagittal sinus blood oxygen content. The relationship between CBF and CPP was analyzed by least-squares linear regression. The slope of the regression line was used to determine the autoregulatory response and to compare the correlation of CBF to CPP between experimental groups. Statistics. All values are expressed as a mean ± 1 standard deviation. Differences in CBF at different flow rates were calculated by analysis of variance for repeated measures and the Scheffe test. Systemic variables, cerebral values, and the slope of regression coefficients were compared between normothermic and hypothermic conditions or between pulsatile and nonpulsatile conditions by means of analysis of variance. A p value ofless than.5 was considered to be statistically significant. This study was approved as a class B experiment by the Committee of Animal xperimentation, Tohoku University School of Medicine, in reference to "The Classification of Biomedical xperiments Based on thical Concerns for Non-human Species," Laboratory Animal Science, Special Issue, 1987:14-6. Results The average weight of the brain and brain/body weight ratio was 81 ± 11 gm and.55% ±.9%, respectively. Table I shows CBF, cerebral vascular resistance, cere-

4 The Journal of Thoracic and Volume 18, Number 3 Sadahiro, Haneda, Mohri 449 c '" ~ U. m C as Q) : NC NP --- HC ---- HP +-~~~~~~~--~~~~--~'-~-4 o Perfusion Flow Rate (ml/kg/min) Fig. 2. The relationship between mean CBF and perfusion flow rate during CPB. CBFwas not significantly changed until perfusion flow rate was less than 4 ml/kg per minute in normothermic and hypothermic groups with or without pulsatile perfusion. *Statistically significant between perfusion flow rates of 4 to 12 ml/kg per minute (p <.5). NC, Normothermic continuous perfusion; NP, normothermic pulsatile perfusion; HC, hypothermic continuous perfusion; HP, hypothermic pulsatile perfusion. bral oxygen consumption, and systemic variables in all groups while perfusion flow was kept at a constant rate of 8 ml/kg per minute. The changes in mean CBF, cerebral vascular resistance, and cerebral oxygen consumption in the hypothermic groups (HC, HP) were significantly different (p <.5) from those in the normothermic groups (NC, NP) as brain temperature decreased. CBF, cerebral vascular resistance, and cerebral oxygen consumption in the HC group were 62%,228%, and 61%, respectively, of those in the N C group. CBF, cerebral vascular resistance, and cerebral oxygen consumption in the HP group were 57%, 24%, and 54%, respectively, of values in the NP group. Mean CPP in the HC group was significantly (p <.5) higher than it was in the NC and NP groups. However, no significant differences were detected in cerebral values between the continuous perfusion (NC, HC) and pulsatile perfusion groups (NP, HP). Relationship between CBF and perfusion flow rate. CBF did not change significantly over pump flow rates ranging from 4 to 12 ml/kg per minute, but CBF decreased significantly when flow rate was less than 2 ml/kg per minute during both normothermic and hypothermic CPB with or without pulsatile perfusion (Fig. 2). Relationship of CPP to perfusion flow rate. Perfusion pressure changed as a function of flow rate. The relationship between CPP and perfusion flow rate was represented by the best fit curve described by the log of Y = logx (r =.86) in the NC group; Y = log)( (r =.76) in the NP group; Y = logx (r =.75) in the HC group; Y = logx (r =.76) in the HP group (where Y is CPP and X is perfusion flow rates). Mean CPP ranged from 16.8 ± 5.8 t83.2 ± 5.2mmHgin the NC group, 17.2 ± 4.8 to 85. ± 17.6 mm Hg in the NP group,42.1 ± 15. to ± 25.8 mm Hg in the HC group, and 36.1 ± 7.8 to 96.1 ± 19.5 mm Hg in the HP group; flow rate varied from 1 to 12 mljkg per minute (Fig. 3). Relationship between CBF and CPP. Fig. 4 shows a continuous recording of the mean perfusion pressure and CBF of a typical case. Immediately after pump flow rate was decreased, perfusion pressure dropped and a decrease in CBF followed. CBF, however, gradually returned to the previous level within 1 minute. When CBF stabilized it remained essentially unchanged so long as perfusion pressure remained higher than 5 mm Hg. Conversely, at a perfusion pressure below 5 mm Hg, CBF did not recover to its prior level and decreased proportionally with a further reduction in perfusion pressure. The relationship between CBF and CPP revealed that changes in CBF were minimal until perfusion pressure decreased to 5 mm Hg, after which CBF decreased proportionally with the reduction in CPP in both the normothermic and hypothermic groups with or without pulsatile perfusion (Fig. 5). Therefore, CPP-CBF plots were divided into two parts, a horizontal portion (above 5 mm Hg of CPP) and a

5 45 Sadahiro, Haneda, Mohri The Journal of Thoracic and September 1994 Table I. Cerebral values and systemic variables at perfusion flow rates of 8 mljkg per minute during normothermic and hypothermic CPB with or without pulsatile perfusion Normothermia HYfXJthermia Continuous INC) Pulsatile INP) Continuous (HC) Pulsatile (HP) Cerebral values CBF (ml/1 gm/min) 37.1 ± ± ± 5.7* 22.3 ± 3.6* CPP (mm Hg) 67.1 ± ± ± 19* 86.6 ± 16 CVR (mm Hg/mi/IOO gm/min) 1.87 ± ± ± 1.' 3.95 ±.8* VOz (ml/1 gm/min) 3.1 ± ± ±.2* 1.9 ±.3* rcp (mm Hg) 9.7 ± ± ± ± 4.6 Systemic variables Paoz (mm Hg) 286 ± ± ± ± 77 Paco2 (mm Hg) 41.2 ± ± ± ± 5.5 ph 7.33 ± ± ± ±.9 Hematocrit (%) 2.6 ± ± ± ± 5.2 Pulse pressure (mm Hg) <5 24 ± 5.8 <5 28 ± 6.6 Brain temperature ( C) 36.2 ± ± l.l 25.4 ± ±.8 CBF, Cerebral blood flow; CPP, cerebral perfusion pressure; CVR, cerebral vascular resistance; VOl, cerebral oxygen consumption; ICP, intracranial pressure. 'Significant difference compared with values during normothermic CPB (HC versus NC and NP, HP versus NC and NP), p <.5. Table II. Relationship of CBF to CPP (CPP greater than 5 mm Hg) Slope (ml/1 gm/min/mm Hg) r CBF (ml/ioo gm/min)* CVR (mm Hg/ml/1 gm/min)* Continuous (NC).16 ± ± ±.4 Normothermia Pulsatile (NP).14 ± ± ±.5 Continuous (HC).1 ± ± ±.9 HYfXJthermia Pulsatile (HP).9 ± ± ±.8 CBF, Cerebral blood flow. CPP, cerebral perfusion pressure. CVR. cerebral vascular resistance. r = mean coefficient of CBF-CPP relationship derived by linear regression. Averaged CBF and CVR at a CPP between 7 and 8 mm Hg. Table III. Relationship of CBF to CPP (CPP less than 5 mm Hg) Slope (mljloo gm/min/mm Hg) r CBF (mi/ioo gm/min)* CVR (mm Hg/ml/IOO gm/min)* Continuous (NC).68 ±.11 t ± ±.3 Normothermia Pulsatile (NP).32 ±.9t:j: ± 2.9* 1.32 ±.2* Continuous (HC).62 ± O.l8t ± ±.9 H.VfXJthermia Pulsatile (HP).39 ±.4t:j: ± 3.7* 2.24 ±.7* CBF, Cerebral blood flow; CPP. cerebral perfusion pressure; CVR, cerebral vascular resistance. r = mean coefficient of the relationship between CBF and CPP. 'Averaged CBF and CVR at a CPP between 3 and 4 mm Hg. tthe slope of the CBF-CPP relationship at a CPP less than 5 mm Hg is significantly higher (p <.5) than the slope of CPP greater than 5 mm Hg (shown in Table II) when compared in each group. :j:significant difference from continuous groups (NC vs NP, HC vs HP), P <.5. steeper pressure-dependent portion (below 5 mm Hg of CPP). The slopes of the regression equation relating CBF to CPP with normothermic continuous perfusion were.16 ±.8 fora CPPabove 5mm Hg and.68 ±.11 for a CPP below 5 mm Hg;.14 ±.9 and.32 ±.9 with normothermic pulsatile perfusion;.1 ±.4 and.62 ±.18 with hypothermic continuous perfusion;.9 ±.8 and.39 ±.4 with hypothermic pulsatile perfusion, respectively (Fig. 6). Value of the slopes for a CPP above 5 mm Hg was

6 The Journal of Thoracic and Volume 18, Number 3 Sadahiro. Haneda. Mohri 451 close to zero and significantly smaller than a slope derived from a perfusion pressure less than 5 mm Hg in all groups, suggesting the presence of an intact autoregulatory vascular response. Neither slope of the regression coefficient nor CBF and cerebral vascular resistance at a CPP between 7 and 8 mrn Hg was significantly different between continuous and pulsatile perfusion groups during normothermic and hypothermic CPB (NC versus NP; HC versus HP) (Table II). The slope of the regression line in the steeper pressuredependent po~iion (below 5 mm Hg of CPP) in pulsatile perfusion groups (NP, HP) was significantly smaller than the slope in continuous perfusion groups (NC, HC). Furthermore, CBF and cerebral vascular resistance in pulsatile perfusion groups, which were averaged at a perfusion pressure between 3 and 4 mrn Hg, were significantly higher and lower, respectively, than in the continuous perfusion groups with either normothermic or hypothermic perfusion (NC versus NP; HC versus HP, p <.5) (Table III). Discussion The measurement of sagittal sinus venous outflow allows the continuous monitoring of hemodynamic changes in the brain and is extremely useful for the detection of cerebral autoregulatory response. However, this method cannot completely distinguish between intracranial and extracranial venous communications. 3, 14 Michenfelder, Messik, and Theye l3 assumed that areas of the brain that are drained by the sagittal sinus varied little between individual preparations and averaged 43% of the total brain weight if a sagittal sinus cannulation drainage technique was used to assess flow. CBF and cerebral oxygen consumption of this study during normothermic CPB at a perfusion flow rate of 8 mljkg per minute were within the ranges reported by other investigators. 3 6 In addition, both CBF and cerebral oxygen consumption decreased proportionally during hypothermic (25 C) CPB, suggesting the presence of a flow-metabolic coupling in the brain, This is consistent with results reported by Michenfelder and Theye l5 that cerebral oxygen consumption decreased by an average of approximately 55% at a temperature of 1 C. Autoregulation of CBF refers to alternations in cerebral vascular resistance that occur so that CBF does not change whether CPP increases or decreases. It is generally considered that vasomotor tone is responsible for CBF autoregulation and is based in part on adenosine release,16 as well as myogenic reflexes. l? The presence of autoregulatory response during CPB has been of interest because of nonphysiologic conditions imposed by CBF 12 ~ 1 :z: g (.J C ca 4 CI) :e Perfusion Flow Rate (ml/kg/min) Fig. 3. Relationship between CPP and perfusion flow rate during CPR N C, Normothermic continuous perfusion; NP, normothermic pulsatile perfusion; He, hypothermic continuous perfusion; HP, hypothermic pulsatile perfusion. such as nonpulsatile flow, hypothermia, and hemodilution.?,8 Several studies indicate that cerebral pressureflow autoregulation is preserved under most bypass conditions except for those in which ph-stat blood gas management,18 deep hypothermia «22 C), and circulatory arrest l9 are used. CBF in our study did not change significantly between flow rates of 4 and 12 mlj kg per minute. The autoregulatory mechanism appeared to be intact until perfusion pressure decreased to about 5 mm Hg under normothermic and moderately hypothermic conditions regardless of continuous or pulsatile perfusion. The presence of an autoregulatory response was based on the following: (1) continuous measurement of CBF and CPP demonstrated a rapid recovery of CBF to its prior level within 3 to 6 seconds after an initial change in CBF. This occurred concomitantly with an alternation of CPP, which suggests a myogenic response; (2) CBF was not significantly changed when CPP was greater than 5 mm Hg; (3) CBF-CPP plots were divided into two parts and were analyzed by means of individual fitting lines by least squares linear regression. The slope of the representative line for a CPP above 5 mm Hg was significantly different from the slope of the steeper line for a CPP below 5 mmhg. Halothane is a potent vasodilator that increases CBF in normal and in ischemic brain tissue. However, Morita and associates 2 demonstrated that autoregulation was intact during.5% halothane anesthesia, an observation that is also consistent with our results. We applied alpha-stat acid-base regulation during

7 452 Sadahiro, Haneda, Mohri The Journal of Thoracic and September 1994 Pump Flow (ml/kg/min) Perfusion Pressure (mmhg) 1 5 J : I : : 8-:-6 -:-- 4 -:-2 -: r I,,,.:.:.:.:,"'~, ',, ' o ' ~' ~ CBF (ml/min) o Fig. 4. Continuous monitoring of perfusion pressure and CBF during perfusion flow rates from 8 to 1 ml/kg per minute. Arrows indicate the point at which the relationship between CBF and perfusion pressure was evaluated. Black arrows show the presence of an autoregulatory response with CBF returning to its prior level after an initial drop. White arrows show the loss of a vascular response. 5 c: 4 '" - 3 U. m 2 1 o+-~ ~~~ o cpp (mmhg) Fig. 5. Typical plot of CBF and CPP with normothermic nonpulsatile perfusion. CBF-CPP plots are divided into two parts and are represented by different linear regression lines. hypothermic CPB. Two different strategies, alpha-stat (nontemperature-corrected arterial carbon dioxide tension of about 4 mm Hg) and ph-stat management (temperature-corrected arterial carbon dioxide tension at about 4 mm Hg at the actual temperature) have been used. 21 ph-stat management may increase CBF because arterial carbon dioxide tension is higher than it is when alpha-stat management is used. However, this is associa ted with vasodila ta tion, which may compromise cerebral autoregulation. Johnsson,6 Murkin,18 and their associates.. 5 Steeper Autoregulation - pressure-. responu dependent preserved C portion portion ' 4 til,~ Q Q!:: 3. U. m 2 /,,~ //>/~ ", " 1,, """,,, "," "",", 5 1 CPP (mmhg) Fig. 6. Relationship between CBF and CPP. CBF-CPP plots are divided into two parts, an autoregulation portion and a pressure-dependent portion, and are represented by linear regression lines. Autoregulation of CBF was observed at a CPP greater than 5 mm Hg. The slope of the regression line in the pressure-dependent portion was significantly steeper than it was in the autoregulated portion during normothermic and hypothermic CPB with or without pulsatile perfusion (NC, NP, HC, HP). have reported that alpha-stat blood gas management prevents cerebral hyperemia and preserves a physiologic coupling of CBF and cerebral metabolic rate of oxygen and an intact autoregulatory mechanism. These findings are consistent with results from the present study. The benefits of pulsatile flow are widely known and are

8 The Journal of Thoracic and Volume 18, Number 3 Sadahiro, Haneda, Mohri 453 prominent in the CPB literature. Pulsatile perfusion better preserved renal function,22 maintained outer cortical flow,23 and prevented ischemic changes 24 in kidneys. Pulsatile perfusion improved subendocardial coronary flow and myocardial metabolism in the fibrillating heart during CPB. 25 Also, Dernevik, Arvidson, and William-Olsson lo reported that CBF to the gray matter of the brain during normothermic CPB was significantly higher with pulsatile perfusion. Pulsatile perfusion in this study of the CBF-CPP relationship in the presence of an autoregulatory response was not significantly different from nonpulsatile perfusion when CPP was greater than 5 mm Hg. Conversely, when CPP was out of the autoregulatory range «5 mm Hg), pulsatile flow resulted in a significant improvement in the correlation between CPP and CBF. Pulsatile perfusion under normothermic or moderate hypothermic conditions resulted in a consistently higher CBF at any CPP and was also associated with a smaller decrease in CBF as CPP decreased. These results confirm the advantageous effects of pulsatile perfusion at an extremely low flow rate as reported by Watanabe and associates 9 and appears to support the efficacy of pulsatile perfusion as a modality for achieving a significantly higher recovery ratio after profound hypothermic circulatory arrest ll or acute local ischemia. 12 Pulsatile flow has been said to preserve the microcirculation,26,27 improve tissue metabolism and blood flow,26 and inhibit sludging and edema formation. 27 The mechanism by which pulsatile perfusion improves the microcirculation is not clear. Shepard, Simpson, and Sharp28 determined that the energy needed to deliver pulsatile flow is 2.3 times that needed to produce non pulsatile flow at the same mean perfusion pressure. It is believed that this extrahydraulic energy of each systolic thrust is distributed into the microcirculation and this helps to maintain peripheral perfusion by keeping capillary beds patent and simultaneously encourage lymphatic flow. 29 This study indicates that pulsatile perfusion was more effective at a lower perfusion pressure, below the lower limit of autoregulation, in which the cerebral vasculature was maximally dilated and a myogenic response was lost. We speculate that pulsatile energy is more hemodynamically efficient in a situation in which the cerebral vasculatures is dilated and myotonic vascular response is absent and in which the forward thrust of the mean perfusion pressure is not high enough to adequately maintain the peripheral circulation. Conclusion 1. Results from this study suggest that cerebral autoregulation is intact at a CPP greater than 5 mm Hg during either normothermic or hypothermic CPB. 2. Pulsatile perfusion resulted in a higher CBF at a CPP less than 5 mm Hg. RFRNCS 1. Fog M. Cerebral circulation: the reaction of the pial arteries to a fall in blood pressure. Arch Neurol Psychiatry 1937;37: Rapela C, Green HD. Autoregulation of canine cerebral blood flow. Circ Res 1964;15(Suppl):I 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: Henriksen L, Hjelms, Lindeburgh T. Brain hyperperfusion during cardiac operations: cerebral blood flow measured in man by intra-arterial injection of xenon 133- evidence suggestive of intraoperative microembolism. J Thorac Cardiovasc Surg 1983;86: Govier A V, Reves JG, McKay RD, et al. Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg 1984; 38: Johnsson P, Messeter K, Ryding, Kugelberg J, Stashl. 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