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Ann Thorac Surg 1997;63:1243-1250
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Regional Blood Flow During Pulsatile Cardiopulmonary Bypass and After Circulatory Arrest in an Infant Model

Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina; Biomedical Engineering Program, University of Texas, Austin, Texas; and Division of Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, Texas

	Abstract

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Background. Pulsatile perfusion systems have been proposed as a means of improving end-organ perfusion during and after cardiopulmonary bypass. Few attempts have been made to study this issue in an infant model.

Methods. Neonatal piglets were subjected to nonpulsatile (n = 6) or pulsatile (n = 7) cardiopulmonary bypass and 60 minutes of circulatory arrest. Cerebral, renal, and myocardial blood flow measurements were obtained at baseline, on bypass before and after circulatory arrest, and after bypass.

Results. Cerebral blood flow did not differ between groups at any time and was diminished equally in both groups after circulatory arrest. Renal blood flow was diminished in both groups during bypass but was significantly better in the pulsatile group than in the nonpulsatile group prior to, but not after, circulatory arrest. Myocardial blood flow was maintained at or above baseline in the pulsatile group throughout the study, but in the nonpulsatile group, it was significantly lower than baseline during CPB prior to circulatory arrest and lower compared with baseline and with the pulsatile group 60 minutes after CPB.

Conclusions. Pulsatile bypass does not improve recovery of cerebral blood flow after circulatory arrest, may improve renal perfusion during bypass but does not improve its recovery after ischemia, and may have beneficial effects on myocardial blood flow during bypass and after ischemia compared with nonpulsatile bypass in this infant model.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
See also page 1250.

Although controversy remains as to whether substantial advantages exist for using pulsatile rather than nonpulsatile flow for cardiopulmonary bypass (CPB), nonpulsatile flow continues to be the standard of care. Previous studies comparing pulsatile with nonpulsatile CPB flow have suggested some [1–4] or no [5–8] benefit. However, very few groups have investigated the use of pulsatile perfusion in an infant model. For infants with congenital heart disease, nonpulsatile CPB is typically used, sometimes in combination with deep hypothermic circulatory arrest (DHCA). These techniques have repeatedly been shown to be associated with postoperative organ-system dysfunction, particularly alterations in cerebral blood flow (CBF) and metabolism, and occasionally with long-term neuropsychiatric disorders [9–12]. Various strategies for cerebral protection during circulatory arrest have been studied, but to date, no techniques employed before or after the period of arrest have proved effective in improving CBF after DHCA. We questioned whether CBF could be improved after CPB and DHCA by using a system that produces physiologic pulsatile blood flow in an infant model.

In addition to the brain, other organ systems have been shown to be adversely affected by standard nonpulsatile CPB. For example, renal perfusion has been shown to be compromised during CPB [13, 14], but relatively little has been done to evaluate the effect of DHCA on renal perfusion. Older studies have suggested that pulsatile perfusion is better for the kidneys than nonpulsatile perfusion, but only one [3] of them examined the effects of ischemia and recovery from ischemia with different types of perfusion systems, and few compared renal blood flow (RBF) during CPB to measurements obtained before and after CPB. None of these studies used an infant model. A review of the literature also reveals that very little information is available about the effect of CPB on myocardial blood flow (MBF), but one report [15] suggests that pulsatile perfusion may be beneficial in preventing myocardial damage from ischemia.

This study was undertaken to evaluate the effects of pulsatile versus nonpulsatile CPB on blood flow to different organ systems before and after DHCA in an infant model. We sought to determine whether or not pulsatile CPB could reduce the perfusion abnormalities seen in organs such as the kidneys during standard nonpulsatile CPB, and whether pulsatile bypass could improve end-organ perfusion-specifically to the brain, kidneys, and heart-after a period of ischemia.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Animal Preparation
Neonatal (1 to 2 weeks old) piglets weighing 2.2 to 3.1 kg were used for all experiments. The protocol was approved by the Animal Care and Use Committee, Duke University Medical Center, and animals were treated according to the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Animals were premedicated with intramuscular ketamine hydrochloride (20 mg/kg) and acepromazine maleate (1 mg/kg) and intravenous methylprednisolone (40 mg/kg). After endotracheal intubation and establishment of an intravenous line, intravenous boluses of fentanyl (100 µg/kg) and pancuronium bromide (0.3 mg/kg) were given, and mechanical ventilation was begun with an infant pressure-cycled ventilator (Sechrist Industries, Anaheim, CA) with initial settings including a peak inspiratory pressure of 20 cm H₂O, positive end-expiratory pressure of 1 cm H₂O, respiratory rate of 12, and an inspired oxygen fraction of 0.60. These settings were adjusted to maintain an arterial oxygen tension of 200 to 250 mm Hg and an arterial carbon dioxide tension of 35 to 45 mm Hg. Anesthesia was maintained with a fentanyl infusion (100 µg•kg^-1•h^-1).

An 18-gauge catheter was inserted in the right femoral artery for pressure and blood gas monitoring and reference arterial blood sampling. A micromanometer (Millar Instruments, Inc, Houston, TX) was inserted in the left femoral artery and advanced to the mid-abdominal aorta for acquisition of arterial pressure waveform data. A median sternotomy was then performed. An 8-mm flow probe (Transonic Systems, Ithaca, NY) was placed around the main pulmonary artery for cardiac output measurement. A left atrial catheter was inserted for microsphere injection. A small portion of the scalp was excised to expose the midline sagittal suture. A burr hole was made for insertion of a second micromanometer into the sagittal sinus for intracranial pressure monitoring.

	Regional Blood Flow Measurement

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Regional blood flow was measured using the radiolabeled-microsphere method. Fifteen-µm microspheres suspended in 10% dextran and 0.01% Tween labeled with one of five different radioisotopes (Du Pont, NEN Life Science Products, Boston, MA) were used. After sonication in a warm water bath and vigorous mixing of the suspension using a vortex mixer for 1 minute, 1 million to 2 million microspheres were injected at each of five different times. Pilot studies showed that this number of microspheres does not affect blood flow measurements over time.

An arterial blood gas sample was first obtained, and all CBF determinations were made with the arterial carbon dioxide tension between 35 and 45 mm Hg. Starting 10 seconds prior to microsphere injection, a reference blood sample was withdrawn from the femoral artery at a rate of 3 mL/min for a total of 3 minutes using a calibrated withdrawal pump (Harvard Apparatus, South Natick, MA). Microspheres were injected into the left atrial catheter before and after CPB and into the aortic cannula during CPB. At the completion of each study, the animal was sacrificed, and the brain, heart, and left kidney were removed. Specimens were weighed, digested in 2 mol/L KOH, and counted with the reference blood samples in a gamma counter (Packard Instrument Company, Meriden, CT). The results were used to calculate blood flows based on the reference sample method. Comparison of flow to the right and left cerebral hemispheres was done to assess the adequacy of microsphere mixing.

	Cardiopulmonary Bypass

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
The CPB circuit included a Capiox 308 hollow-fiber oxygenator/heat exchanger (Terumo Corporation, Tokyo, Japan), and either a standard roller pump (Stöckert-Shiley, Irvine, CA) for the nonpulsatile studies or the University of Texas neonate/infant pulsatile pump for the pulsatile studies. The pulsatile pump employed a compression plate design with passive intake and outlet valves. A hard-shell reservoir was used to load the pumping conduit, and the pump was placed proximal to the oxygenator in the circuit. The pump rate was held constant at 120 beats per minute, and the stroke volume was adjusted to maintain a constant flow of 100 mL•kg^-1•min^-1. The pump prime consisted of lactated Ringer's solution and fresh whole donor-pig blood to achieve a hematocrit of 22% to 24%. The gas mixture was adjusted and sodium bicarbonate was added to obtain a normal blood gas.

After baseline data collection, pursestring sutures were placed in the aortic root and right atrial appendage. After systemic heparinization (500 U/kg), an 8F (nonpulsatile studies) or a 10F (pulsatile studies) cannula was inserted into the aortic root, an 18F to 20F single-stage cannula was inserted into the right atrium, and CPB was established at a flow rate of 100 mL•kg^-1•min^-1. During core cooling and rewarming, alpha-stat blood gas management was employed, and the pump flow was held constant at 100 mL•kg^-1•min^-1. During DHCA, the heart was protected with topical iced saline slush. Throughout CPB, blood pressure was allowed to vary without intervention. At no point in the study were vasoactive or inotropic agents used.

	Experimental Design and Data Collection

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Piglets were subjected to either nonpulsatile (n = 6) or pulsatile (n = 7) CPB. After the completion of instrumentation, the following baseline data were collected (stage I): blood pressure, cardiac output, temperature, heart rate, sagittal sinus pressure, and an arterial blood gas measurement. Cardiac output was indexed by dividing by the animal's preoperative body weight. A CBF determination was made, and arterial pressure waveform data were recorded for 10 seconds, digitized, and stored as a computer file for later analysis. After institution of CPB and stabilization at normothermia as described, data were again collected (stage II). Animals were cooled over 20 minutes to a nasopharyngeal temperature of 18°C after which they were exsanguinated to the cardiotomy reservoir, and DHCA was commenced. After 60 minutes of DHCA, CPB was reestablished at a flow rate of 100 mL•kg^-1•min^-1, and animals were rewarmed for 45 minutes to normothermia. Data were again collected (stage III), and the animals were weaned from CPB. Data were collected at 30 minutes (stage IV) and 60 minutes (stage V) after CPB. After the final data collection, the animals were sacrificed for specimen removal as described.

	Waveform Analysis

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
At each relevant experimental stage, 10 seconds of data from the flow probe and aortic micromanometer were digitized at 200 Hz and stored as separate computer files. Waveform analysis was performed using a VAX computer (Digital Equipment Corporation, Maynard, MA) and Cardiac Data Analysis Software developed at Duke University Medical Center. Ejection was defined as the period between the start of the rise in aortic pressure and the dicrotic notch. Values for ejection time and pulse pressure at each stage were determined by averaging these values for the first seven cardiac cycles in each file.

	Statistical Analysis

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Two-way repeated-measures analysis of variance was used to compare the pulsatile and nonpulsatile groups over the five stages of the study. Where significant differences were determined, contrast analysis was performed using the Student's t test. Significance was presumed when the value of p was less than 0.05. All results are expressed as the mean ± the standard error of the mean.

	Results

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Evaluation of Microsphere Mixing
There were no differences in blood flow to the right and left cerebral hemispheres at any experimental stage in any of the studies. This indicates adequate mixing of microspheres within the arterial tree with both left atrial and aortic cannula injections.

	Experimental Conditions

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
The nonpulsatile group was slightly larger, on average, than the pulsatile group (2.97 ± 0.19 kg versus 2.61 ± 0.30 kg; p = 0.03). There were no differences between groups in hematocrit, arterial oxygen tension, arterial carbon dioxide tension, or nasopharyngeal temperature at baseline or at any of the experimental stages. Table 1 summarizes select data from the two experimental groups.

	Hemodynamic Data

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

View larger version (45K): [in this window] [in a new window]   Fig 1. . Representative aortic pressure, systemic flow, and aortic first derivative of developed pressure (dP/dt) waveforms for stage I (baseline), stage II (CPB pre DHCA), and stage III (CPB post DHCA) from the animal representing the median value for each variable. (CPB = cardiopulmonary bypass; DHCA = deep hypothermic circulatory arrest.)

STAGES II AND III (NORMOTHERMIC CPB BEFORE AND AFTER DHCA).
There were significant differences in systolic blood pressure (89 ± 9 mm Hg versus 50 ± 2 mm Hg; p = 0.003), mean arterial pressure (70 ± 9 mm Hg versus 46 ± 2 mm Hg; p = 0.03), and pulse pressure (35 ± 3 mm Hg versus 10 ± 1 mm Hg; p < 0.0001) between the pulsatile and nonpulsatile groups, respectively, at stage II and significant differences in systolic blood pressure (73 ± 4 mm Hg versus 42 ± 3 mm Hg; p < 0.0001), mean arterial pressure (51 ± 5 mm Hg versus 38 ± 2 mm Hg; p = 0.04), and pulse pressure (37 ± 4 mm Hg versus 10 ± 1 mm Hg; p < 0.0001) between the pulsatile and nonpulsatile groups, respectively, at stage III. There were no differences in diastolic blood pressure or intracranial pressure between the two groups during CPB before or after DHCA.

Within the pulsatile group, pulse pressure during pulsatile CPB did not differ from baseline and, as just noted, was significantly higher than the pulse pressure during nonpulsatile CPB. In contrast, ejection time was significantly longer, maximum dP/dt was significantly less, and stroke volume was significantly larger during pulsatile CPB compared with baseline. These data are summarized in Table 2.

	Cerebral Blood Flow

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
There was no significant difference in CBF between the pulsatile and nonpulsatile groups over time by analysis of variance (p = 0.85). Cerebral blood flow was diminished by 12.2 mL•min^-1•100 g^-1 from baseline (20.0%) in the pulsatile group (p = 0.02) and by 12.8 mL•min^-1•100 g^-1 (19.5%) in the nonpulsatile group (p = 0.07) after the start of CPB. There was, however, no difference between the two groups at this point (48.7 ± 2.8 mL•min^-1•100 g^-1 versus 52.6 ± 2.5 mL•min^-1•100 g^-1; p = 0.33). At each of the stages after DHCA (III, IV, and V), CBF was significantly lower than baseline for each group, but there were no significant differences between groups at any of these stages. Results for CBF are summarized in Figure 2.

View larger version (14K): [in this window] [in a new window]   Fig 2. . Cerebral blood flow at each stage for both groups. ( = p = 0.02 versus baseline in pulsatile group and p = 0.07 versus baseline in nonpulsatile group; * = p < 0.05 compared with baseline within each group for both groups.)

	Renal Blood Flow

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

View larger version (15K): [in this window] [in a new window]   Fig 3. . Renal blood flow at each stage for both groups. ( = p < 0.01 versus pulsatile group; * = p < 0.05 compared with baseline within each group for both groups.)

	Myocardial Blood Flow

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

View larger version (16K): [in this window] [in a new window]   Fig 4. . Left ventricular myocardial blood flow at each stage for both groups. ( = p < 0.05 versus pulsatile group; * = p < 0.05 compared with baseline within group.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

Probably the most important variable, however, is the type of pulsatile pump used. Prior studies have reported results for pulsatile systems ranging from simply modified roller pumps to sophisticated pumps specifically designed to produce a pressure waveform that is indistinguishable from the native arterial pressure waveform. Although some proponents of pulsatile flow claim that this explains the discrepancies in results, some studies that have employed systems producing near physiologic waveforms have shown no difference in the experimental value of interest [7], whereas other systems using pumps that produce a pulse pressure but not a physiologic waveform have shown positive results [1].

Another criticism of some of these studies is that although they compared pulsatile with nonpulsatile flow and found no difference in some measured variable, there was no assessment of whether one system or both systems were producing normal flows. Hindman and associates [8] performed experiments similar to those in the present study in which they compared CBF during pulsatile and nonpulsatile CPB in rabbits at normothermia. The authors found no differences between the two groups but did not include an assessment of prebypass CBF; thus, both systems may have been adequately supporting the cerebral circulation.

In any case, it seems logical that if pulsatile flow is deemed important or even necessary to support the organism's native physiologic state, then extracorporeal support systems that produce pulsatile flow should seek to imitate the native pressure and flow characteristics as closely as possible. Although it can be argued exactly what kind of waveform analysis need be used to evaluate this, several simple criteria have been employed to assess the quality of pulsatile flow produced by artificial pumps. These criteria include pulse pressure, stroke volume, maximal dP/dt, and ejection time [16]. According to these criteria, the pump used in these studies was able to produce physiologic pulsatile flow during in vitro testing [17]. However, in the current in vivo study, the pump was able to produce blood pressures, including pulse pressure, similar to physiologic values, but it failed to adequately reproduce physiologic dP/dt, ejection time, or stroke volume. These factors could have influenced the results obtained. This remains to be tested if a better pump design is developed.

It is apparent that part of the difficulty in producing physiologic pulsatile flow in this study has to do with the use of an infant model. The pump used produces a pulsatile waveform using stroke volumes similar to normal physiologic stroke volumes. This results in a normal-appearing pressure waveform in vitro, despite pumping through an oxygenator, which tends to dampen the waveform. However, it appears to be difficult to pump this stroke volume over a normal ejection period through the type and size of cannula necessary for neonatal or infant CPB. In this study, a 10F cannula was used and resulted in significant damping of the pressure waveform, which, in turn, led to reduced dP/dts and longer ejection times. When employed in an adult model, a larger pump with the same design used in combination with a large arterial cannula was able to produce an arterial pressure waveform with physiologic morphology [18]. Of note is that this study used a gravity-flow oxygenator proximal to the pump with the result that damping of the pulsatile waveform by the oxygenator was not an issue. Whether a pump can be developed that will reproduce physiologic pulsatile flow in an infant using clinically applicable techniques remains to be seen.

Another factor worth discussion is the choice of the CPB protocol in this and similar experiments. In designing this study, it was decided to maintain a constant flow during CPB and to allow the blood pressure to vary. Many other studies have varied the flow to maintain a constant pressure. In this study, there were fairly substantial differences in the systemic vascular resistance during CPB depending on whether pulsatile or nonpulsatile flow was used. If the pressure had been held constant by adjusting the flow rate, then increases in systemic vascular resistance would have been compensated by decreasing flow and thereby necessarily limiting the amount of flow an organ could receive. In our study in which flow remained constant, blood flow to individual organs depended not only on the overall vascular resistance but on the vascular resistance of the organs themselves. Because identical flow rates were used for both groups and the protocol was the same except for the type of pump used, the differences in blood flow to the organs should have been a direct effect of how the perfusion technique used affected the vascular resistance of the overall system and the vascular resistance of the specific organ.

Our laboratory has been interested in the derangement in CBF and cerebral metabolism seen after CPB and DHCA. If part of the mechanism causing reduced CBF, and hence the impaired metabolism after exposure to DHCA, were due to increased cerebral vascular resistance and one could find a way to overcome this resistance, CBF might be improved. It has been suggested that the beneficial effects of pulsatile perfusion are at the level of the microcirculation. The extra energy required to produce pulsatile flow may be distributed into the microcirculation where it acts to maintain capillary bed patency and may result in higher shear stresses leading to increased endogenous vasodilator release from the endothelium. Both of these effects would tend to decrease vascular resistance [19].

The results of this study suggest one of two conclusions regarding the nature of the deficit in CBF seen after circulatory arrest. The first is that it is not a result of a reversible increase in cerebral vascular resistance. This is supported by the fact that CBF remains depressed even after weaning from bypass and resumption of the native pulsatile circulation. This, however, does not usually occur until after a period of nonpulsatile perfusion. As intervention using the pulsatile pump for reperfusion occurs immediately after circulatory arrest, it could be speculated that the increase in resistance might be more easy to overcome on the basis of the preceding arguments if, in fact, a pulsatile waveform is important in this process. Because this was not observed in this study, one might conclude that the increased resistance is not reversible, at least by mechanical means. The second possibility is that our pulsatile pump was unable to overcome the degree of resistance produced in this model. Although this may be due to the failure of our pump to produce true physiologic pulsatile flow, it seems likely that were pulsatile flow beneficial to the cerebral circulation after circulatory arrest, one would have at least observed a trend in this direction in our study.

The effects observed on RBF are interesting for several reasons. The initiation of normothermic CPB is accompanied by a dramatic decrease in RBF. This impairment in flow is improved somewhat by the pulsatile pump, a finding that might be explained either by the fact that mean arterial pressure was better maintained in the pulsatile group or by the pulsatile nature of the flow itself. However, during CPB, RBF was far lower than baseline, thus making it apparent that renal autoregulation is not present during CPB. This is especially obvious when one compares RBF with CBF, which is relatively well maintained once bypass is initiated regardless of the type of flow. It is also interesting that RBF remains impaired after circulatory arrest, and equally so in both groups, but that after weaning from bypass and resumption of the native pulsatile circulation, it recovers to levels higher than those observed during CPB but still lower than baseline. This suggests that if the pump used in the study had been able to produce more physiologic pulsatile flow, RBF during pulsatile CPB might have been further improved.

Myocardial blood flow was better maintained by pulsatile CPB than by nonpulsatile CPB prior to ischemia. Interestingly, MBF was also relatively better maintained in both groups compared with RBF during CPB. This suggests that the renal circulation is more sensitive to the changes encountered with CPB, especially the nonpulsatile type. Recovery of myocardial flow also seemed better at all three time points after DHCA in the pulsatile group, a finding implying a benefit to pulsatile flow in myocardial recovery from ischemia. Of note is that specific measures were taken to protect the heart during ischemia to make it possible to wean from bypass. This may have made recovery from ischemia more feasible and therefore differences in recovery more easy to demonstrate. In the organ systems that were not specifically protected, ie, the brain and the kidneys, the ischemic injury may have been so severe that recovery was difficult to achieve regardless of the technique used, and therefore differences in recovery between technique would have been difficult to show.

In summary, pulsatile CPB seems to have had some beneficial effects on blood flow to different organs systems compared with nonpulsatile CPB in this study. These effects may have been limited by the fact that true physiologic pulsatile flow was not achieved by the pulsatile pump used and that the ischemic injury produced in the brain and the kidneys was severe enough to prevent demonstration of recovery by any technique. More closely stimulating the heart rate and stroke volume in a given animal model should lead to the production of better or more physiologic pulsatile flow. Whether these changes would result in less organ dysfunction after ischemia is speculative and should be the subject of future studies. Although physiologic pulsatile flow may be difficult to achieve in an infant because of the small cannulas necessary for CPB, this study suggests that further investigation of infant pulsatile flow systems is warranted.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
This study was supported in part by funds from The Duke Children's Miracle Network Telethon.

We thank Ronnie Johnson for technical assistance during these experiments.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 
Presented at the Forty-third Annual Meeting of the Southern Thoracic Surgical Association, Cancun, Mexico, Nov 7–9, 1996.

Address reprint requests to Dr Ungerleider, Department of Surgery, Duke University Medical Center, Box 3178, Durham, NC 27710 (e-mail: unger002{at}mc.duke.edu).

	References

Top Footnotes Abstract Introduction Material and Methods Regional Blood Flow Measurement Cardiopulmonary Bypass Experimental Design and Data... Waveform Analysis Statistical Analysis Results Experimental Conditions Hemodynamic Data Cerebral Blood Flow Renal Blood Flow Myocardial Blood Flow Comment Acknowledgments References

 

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