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Ann Thorac Surg 1996;62:393-400
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Fetal Cardiac Bypass Using an In-Line Axial Flow Pump to Minimize Extracorporeal Surface and Avoid Priming Volume

Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, California

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Progressive metabolic acidosis, hypoxia, and hypercarbia develop rapidly after fetal cardiac bypass mainly as a result of an increase in placental vascular resistance and a decrease in placental blood flow. A number of factors including fetal stress, priming substances, and extracorporeal surfaces have been identified as possible stimuli causing this placental dysfunction. The purpose of this study was to examine the effects of avoiding priming volume and minimizing extracorporeal surface area on placental hemodynamics and function.

Methods. Fetal sheep (n = 16) at 118 to 122 days of gestation were subjected to cardiac bypass for 30 minutes using either an in-line axial-flow pump (Hemopump group: n = 8, no prime) or a roller pump with a venous reservoir (control group: n = 8, priming volume = 150 mL). After bypass, the fetuses were observed for 90 minutes. Placental blood flow and combined ventricular output were continuously measured with ultrasonic flow probes, and fetal blood gases were measured at specific intervals.

Results. Three fetuses in the control group died during the study, whereas all 8 fetuses in the Hemopump group remained in stable condition throughout the study period. During and after bypass, placental blood flow was significantly higher (p < 0.0001) and placental vascular resistance was significantly lower (p < 0.0001) in the Hemopump group than in the control group. Arterial pH and partial pressure of arterial oxygen declined significantly less (p < 0.0001), and partial pressure of arterial carbon dioxide increased significantly less (p = 0.0002) in the Hemopump group than in the control group.

Conclusions. Reducing the extracorporeal surface area and avoiding external priming substances preserves placental hemodynamics after fetal cardiac bypass. An in-line axial-flow pump is useful in miniaturizing the bypass circuits for potential use in fetal cardiac surgery.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
There are a number of congenital heart lesions for which in utero intervention is predicted to result in better outcomes than are seen with current methods of neonatal or infant repair [1]. For many fetal cardiac surgical interventions, some form of fetal extracorporeal circulation (fetal cardiac bypass) will be required. Previous work [2–9] has demonstrated the feasibility of fetal cardiac bypass and identified the physiologic barriers to successful fetal cardiac bypass. This work has also characterized and identified the possible mechanisms of the placental dysfunction that occurs after fetal bypass. Stimuli likely responsible for placental dysfunction are extracorporeal surfaces, priming substances, flow characteristics, and fetal stress. Extracorporeal surfaces are nonphysiologic and activate a number of humoral pathways and formed elements of blood [10–14]. Large volumes of priming substances cause fetal hemodilution, and adult blood in the prime is not ideal because of the differences in the oxygen affinity of adult and fetal hemoglobin.

Therefore, a novel fetal bypass circuit was designed to minimize the extracorporeal surface and avoid external priming substances. The purpose of the present study, in which the new circuit is compared with the conventional neonatal type of circuit, is to examine the effects on placental function of minimizing the surface area of the extracorporeal circuitry and avoiding priming substances.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Extracorporeal Circuits
HEMOPUMP CIRCUIT.
The circuit is depicted in Figure 1. The novel component of this circuit is an in-line axial-flow pump (Hemopump, modified model HP24 sternotomy pump; Johnson & Johnson Interventional Systems, Rancho Cordova, CA). The Hemopump is a miniature axial-flow pump, the working details of which have been described previously [15, 16]. A commercially available Hemopump (model HP24) was modified by removing the silicone inlet cannula so that the Hemopump could be housed in a short piece of -inch (0.625-cm) polyvinyl tubing. One end of this tubing is fitted into the proximal end of a 16F venous cannula (DLP-Medtronic, Grand Rapids, MI), and the other end is connected to the stem of a -inch (0.625-cm) Y connector. The drive cable for rotating the axial pump is brought out through a watertight silicone plug inserted into one limb of the Y connector. The drive cable is then passed through an electromagnetic stator that is connected to the console. Another short piece of -inch polyvinyl tubing with an in-line flow probe (Transonic Systems, Inc, Ithaca, NY) is connected to the other limb of the Y connector. A 12F arterial cannula (Elektrocatheter Corp, Rahway, NJ) connected to this -inch tubing completes the circuit.

View larger version (32K): [in this window] [in a new window]   Fig 1. . Hemopump circuit. The Hemopump is housed as shown, and the internal rotating axial pump is depicted in the inset. (Ao = aorta; IVC = inferior vena cava; PA = main pulmonary artery; RA = right atrium; SVC = superior vena cava.)

CONVENTIONAL CIRCUIT.
This circuit, shown in Figure 2, consists of a polyvinyl tubing venous line inch (0.625 cm) in diameter, a collapsible infant venous reservoir (Terumo Medical, Somerset, NJ), a roller pump (Sarns, Ann Arbor, MI), and a polyvinyl tubing arterial line inch in diameter with an in-line flow probe. The arterial and venous cannulas are the same as those in the Hemopump circuit. The circuit is primed with 150 mL of a fluid mixture consisting of equal volumes of fresh adult sheep venous blood and crystalloid solution (Normosol-R, pH 7.4; Abbott Laboratories, North Chicago, IL).

View larger version (20K): [in this window] [in a new window]   Fig 2. . Conventional roller-pump circuit used in control group fetuses. Abbreviations are the same as in Figure 1.

The ewes were fasted for 24 hours before the study and were premedicated with ketamine hydrochloride (10 mg/kg intramuscularly) and buprenorphine hydrochloride (0.01 mg/kg intramuscularly). The ewe was then placed in the supine position on the operating table. The trachea was intubated, and the ewe was ventilated with an inspired oxgyen fraction of 40% using a Bennett MA2 ventilator (Puritan-Bennett, Carlsbad, CA) on volume-cycled mode. Arterial access and venous access were obtained by cannulating the anterior tarsal artery and vein and advancing the two catheters into the descending aorta and the inferior vena cava, respectively. Maternal anesthesia was maintained with an intravenous ketamine infusion of 3 to 5 mg•kg^-1•h^-1. A maternal central venous line was placed by cannulating the jugular vein. Maternal heart rate, arterial pressure, and central venous pressure were monitored, and lactated Ringer's solution was administered at a rate of 4 mL•kg^-1•h^-1. Maternal blood gases were monitored every 30 minutes to ensure adequate ventilation. A midline laparotomy was performed, the uterus was exposed, and the number and the orientation of the fetus or fetuses were determined by gentle palpation. If twin fetuses were present, the fetus that would give the better exposure was studied.

A small hysterotomy was made over the fetal left flank, and ketamine (10 mg/kg intramuscularly) and succinylcholine chloride (2 mg/kg intramuscularly) were administered and repeated every hour or as needed. Five minutes later, an oblique 4-cm incision centered just above the posterior-superior iliac spine was made over the fetal left flank. With sharp extraperitoneal dissection, the descending aorta was exposed and followed to the trifurcation into right and left iliac arteries and common umbilical artery. The common umbilical artery was dissected, and the posterior lumbar branch or branches were divided. A No. 6 S series ultrasonic perivascular flow probe was placed around the common umbilical artery for continuous monitoring of placental blood flow. A 20-gauge arterial catheter was placed into the descending aorta 2.54 cm (1 inch) proximal to the common umbilical artery and secured. The arterial line and the flow probe were exteriorized, and the fetal incision and hysterotomy were closed.

A second hysterotomy was made over the fetal chest, after which the fetal forelimbs were extracted from the uterus and the fetus was gently supinated to expose the sternum. Fetal electrocardiographic leads were placed to monitor the heart rate. A jugular venous line was placed to monitor the fetal central venous pressure and administer intravenous fluids. A temperature probe was placed into the fetal peritoneal cavity, and the uterus was wrapped in a thermal heating blanket (40°C) and connected to a thermal regulating device (Hemotherm; Cincinnati Subzero, Cincinnati, OH). In addition, warm saline solution was intermittently poured over the fetus and the uterus. With these techniques, fetal temperature was generally maintained higher than 37°C and was always greater than 36°C.

Midline fetal sternotomy and pericardiotomy were performed, and the heart was exposed. The main pulmonary artery and the ascending aorta were dissected, and perivascular flow probes (No. 8 S probe on the main pulmonary artery and No. 6 S probe on the aorta) were placed around them for continuous monitoring of the combined ventricular output (CVO). Pursestring sutures were placed on the main pulmonary artery for arterial cannulation and on the superior vena cava adjacent to its junction with the right atrium for venous cannulation.

Experimental Protocol
FETAL CARDIAC BYPASS.
The fetus was anticoagulated with 300 U/kg of heparin sodium given into the superior vena cava. The right atrium was cannulated through the superior vena cava with a 16F angled-tip venous cannula, and the bypass circuit was filled with fetal blood and deaired. A 12F arterial cannula was placed into the main pulmonary artery, filled with fetal blood, and deaired. In the Hemopump group, the arterial and venous components of the circuit were connected, and bypass was initiated. In the control group, the venous cannula was connected to the venous line, the arterial cannula was connected to the arterial line, and bypass was initiated. During bypass, the main pulmonary artery flow probe was removed, and the main pulmonary artery flows were equal to pump flows. Backflow from the main pulmonary artery into the ventricle and vice versa (from the ventricle into the main pulmonary artery) was prevented by cross-clamping the pulmonary artery proximal to the cannulation site, just above the pulmonary valve.

Pump flows were maintained at the maximum achievable flow in any given animal (generally about 250 to 300 mL•kg^-1•min^-1); this was done on the basis of previous studies in our laboratory [1] and others [17] showing that high flows are required in fetal cardiac bypass when the placenta is used as the oxygenator. Pump flows were continuously monitored with the in-line flow probe. Bypass was continued for 30 minutes. After the discontinuation of bypass, the fetus was monitored for 90 minutes, at which time the study was terminated.

After completion of the study, the ewes and fetuses were killed by an overdose of intravenously administered sodium pentobarbital. The dead fetuses were delivered, and a postmortem examination was performed to confirm the position of all vascular catheters. The amniotic fluid was dried, and the fetuses were weighed.

All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH publication 85-23, revised 1985). The experimental protocol was approved by the Committee for Animal Care at the University of California, San Francisco.

MEASUREMENTS.
All baseline hemodynamic measurements (maternal and fetal heart rates, maternal and fetal central venous pressures, maternal and fetal arterial pressures) were continuously recorded during the entire study. Maternal blood gases were measured every 30 minutes to ensure adequate ventilation. Fetal blood gases were measured after instrumentation, just prior to bypass, every 10 minutes during bypass, and every 15 minutes after bypass. At each of these points, the hemodynamic data were also recorded. Fetal hemoglobin concentration was measured before, during, and after bypass.

DATA ACQUISITION.
Fetal and maternal systemic arterial pressures and fetal and maternal central venous pressures were measured using Statham P23Db pressure transducers (Statham Instruments, Hato Rey, PR). Mean pressures were obtained by electric integration. Heart rate was measured by a cardiotachometer triggered from the phasic systemic arterial pressure pulse wave. All flows were measured on an ultrasonic flowmeter (Transonic Systems Inc). All hemodynamic variables were continuously recorded on a Gould multichannel electrostatic recorder (model TA11; Gould Inc, Cleveland, OH). Fetal and maternal arterial blood gases and pH were measured on a Corning 158 pH/blood gas analyzer (Corning Medical and Scientific, Medfield, MA), and all fetal oximetric variables were corrected for fetal temperature. Hemoglobin concentration was measured by a hemoxometer (model OSM 2; Radiometer, Copenhagen, Denmark).

DATA ANALYSIS.
Placental, systemic, and total vascular resistances were calculated using standard formulas relating resistance to pressure and flow (Ohm's law). Combined ventricular output was calculated as the sum of the ascending aortic and main pulmonary artery flows. Systemic blood flow was estimated as the difference between CVO and placental blood flow. Descriptive statistics were calculated using Microsoft Excel version 5.0 (Microsoft Corporation, Redmond, WA); analytic statistics were calculated with SPSS for Windows version 6.01 (SPSS Inc, Chicago, IL). Linear regression analysis was used to examine the significance of time trends within groups and changes over time between groups.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Hemodynamic and blood gas data before, during, and after bypass are presented in Table 1. All fetuses in the Hemopump group were hemodynamically stable throughout the study period. In the control group, however, 3 fetuses became progressively bradycardic and hypoxic after bypass, went into ventricular fibrillation, and died. One fetus died 40 minutes into bypass, and data were included on this fetus up through 30 minutes after bypass. Two other fetuses died after 75 and 80 minutes of bypass, and data on these fetuses were included through 60 minutes after bypass. To determine whether the removal (death) of these animals at the later time points unduly influenced the statistical analysis, separate linear regression analyses were conducted with 60 minutes after bypass and 90 minutes after bypass as end points. Results did not differ significantly between the two end points.

Systemic arterial blood pressure did not differ significantly between groups before bypass (Hemopump group, 55.8 ± 10.3 mm Hg; control group, 58.5 ± 4.8 mm Hg) or after bypass (Hemopump group, 52.9 ± 5.3 mm Hg; control group, 52.8 ± 6.9 mm Hg), but there was a significant difference during bypass (after 10 minutes of bypass: Hemopump group, 52.9 ± 15.7 mm Hg; control group, 68.3 ± 8.8 mm Hg). Central venous pressure did not differ significantly before bypass (Hemopump group, 6.9 ± 1.3 mm Hg; control group, 6.9 ± 1.5 mm Hg) or after bypass (Hemopump group, 7.6 ± 1.1 mm Hg; control group, 8.0 ± 1.8 mm Hg). During bypass, central venous pressure measurements could not be taken accurately because of interference by the venous bypass cannula.

Combined Ventricular Output
There was no significant difference in CVO between the Hemopump and control groups prior to (250 ± 64 mL•min^-1•kg^-1 and 273 ± 21 mL•min^-1•kg^-1, respectively) and up to 60 minutes after bypass. At 90 minutes after bypass, however, CVO in the control group (185 ± 47 mL•min^-1•kg^-1) dropped to a level that was significantly lower by t test than that in the Hemopump group (260 ± 55 mL • min^-1 • kg^-1; p = 0.02). Figure 3 demonstrates the changes in CVO over time for both groups; there was a gradual decline after cessation of bypass. Though the magnitude of changes over time were small, time trends were significant by linear regression for both the Hemopump (p = 0.0003) and control groups (p < 0.0001). The difference between trends over time between the groups was not significant (p = 0.48).

View larger version (26K): [in this window] [in a new window]   Fig 3. . Fetal combined ventricular output (CVO) immediately prior to, during, and after cardiac bypass in fetal sheep using Hemopump or control conventional roller pump. Pump On indicates the time fetal cardiac bypass was initiated and baseline CVO values were recorded; Pump Off indicates the time of cessation of fetal cardiac bypass. The p value indicates significance level for the difference in CVO over time between the Hemopump circuit and the control circuit as determined by linear regression analysis. (Format of the figures is same for figures 3 to 8.)

View larger version (27K): [in this window] [in a new window]   Fig 4. . Placental blood flow (PBF). The p value indicates significance level for the difference in PBF over time between the Hemopump circuit and the control circuit as determined by linear regression analysis.

Total Vascular Resistance
There was no significant difference in total vascular resistance between the Hemopump group (0.23 ± 0.06 mm Hg•mL^-1•min^-1•kg^-1) and the control group (0.22 ± 0.03 mm Hg•mL^-1•min^-1•kg^-1) before bypass. In both groups, total vascular resistance decreased during bypass, increased immediately after bypass, and plateaued. The trends over time for both the Hemopump group (p = 0.03) and the control group (p = 0.0005) were significant by linear regression analysis, as was the difference in the time trends between the two groups (p = 0.004).

Placental Vascular Resistance
There was no difference in placental vascular resistance between the Hemopump and control groups prior to the institution of bypass. Placental vascular resistance was significantly higher during and after bypass in the control group than in the Hemopump group. As shown in Figure 5, the difference in trends between the groups was dramatic and highly significant (p < 0.0001). Over time, the trend toward increasing placental vascular resistance was significant in both groups (Hemopump group, p < 0.0001; control group, p < 0.0001).

View larger version (25K): [in this window] [in a new window]   Fig 5. . Placental vascular resistance (PVR). The p value indicates significance level for the difference in PVR over time between the Hemopump circuit and the control circuit as determined by linear regression analysis.

Arterial pH
Prior to bypass, arterial pH was nearly identical in the two groups. On the institution of bypass, pH started to fall in both groups. As shown in Figure 6, the difference in pH between the groups was highly significant (p < 0.0001), with mean pH reaching its lowest point in both groups at 90 minutes after bypass. The decrease in pH over time was significant in both groups (p < 0.0001).

View larger version (25K): [in this window] [in a new window]   Fig 6. . Fetal arterial pH. The p value indicates significance level for the difference in arterial pH over time between the Hemopump circuit and the control circuit as determined by linear regression analysis.

View larger version (24K): [in this window] [in a new window]   Fig 7. . Fetal partial pressure of arterial carbon dioxide (PCO2). The p value indicates significance level for the difference in arterial PCO2 over time between the Hemopump circuit and the control circuit as determined by linear regression analysis.

View larger version (25K): [in this window] [in a new window]   Fig 8. . Fetal partial pressure of arterial oxygen (PO2). The p value indicates significance level for the difference in arterial PO2 over time between the Hemopump circuit and the control circuit as determined by linear regression analysis.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

As the previous studies were done using bypass circuits of the standard neonatal type, they required large amounts of priming volume, which necessarily involved the addition of adult blood to the prime [2–4, 9]. These circuits have two disadvantages: (1) larger extracorporeal surface area predisposes to relatively greater damage to cellular elements and activation of humoral pathways, possibly resulting in placental dysfunction; and (2) the adult hemoglobin included in the priming solution is, in theory, less useful for gas exchange in the fetus and may, in addition, contribute to the activation of humoral pathways.

We hypothesized that by decreasing the extracorporeal surface and avoiding external priming substances, we could better preserve placental and fetal hemodynamics during and after fetal bypass. To test this hypothesis, a novel fetal bypass circuit was developed and compared, in the present study, with a conventional roller-pump circuit. The variables of comparison were fetal and placental hemodynamics and fetal arterial blood gases.

Before bypass, there were no significant differences in fetal hemodynamics, placental hemodynamics, and fetal arterial blood pH, partial pressure of arterial carbon dioxide, and PaO₂ between the two groups. During and after bypass, however, placental hemodynamics and fetal arterial blood gases were significantly better in the Hemopump group than in the control group. There was no significant difference (by linear regression) in CVO between the two groups, which suggests that the differences in placental hemodynamics were not secondary to a difference in CVO. In the Hemopump group, placental vascular resistance gradually increased with the institution of bypass and continued to rise, reaching a 50% increase over prebypass resistance at the end of the study period. The rise in placental vascular resistance was significantly more dramatic in the control group, reaching a level nearly 300% higher than the baseline value by the end of the study period (see Fig 5). Similarly, placental blood flow decreased significantly more in the control group than in the Hemopump group (see Fig 4).

Fetal arterial blood gases also reflected the changes in placental blood flow in both groups. In addition, priming the control group circuit with adult sheep blood might also have been partly responsible for lower fetal PaO₂ because of differences in the oxygen affinity of fetal and adult hemoglobin. The control fetuses became more acidotic, more hypercapnic, and more hypoxic than fetuses in the Hemopump group (see Table 1, Figs 6–8).

It is evident from this study and previous studies that fetal bypass causes placental dysfunction regardless of the method of bypass. However, the present study clearly shows that with modifications in the extracorporeal circuit and avoidance of priming substances, placental function is preserved to a significant extent. In the present study, indomethacin was not used, fetal anesthesia techniques were identical in both groups, and the fetuses were grouped randomly. Thus, the differences in placental function and fetal blood gases are most likely due to differences in the extracorporeal circuit and priming substances.

Although the bypass circuit described here appears promising, the most important criticisms of this circuit are that it is overly simplistic and there are no means to protect against air embolism. These are valid concerns, and improvements to address them are necessary; clinical usage would likely require the incorporation of bubble traps or circuit breakers tied to air bubble detectors, and this circuit can easily be modified for dual venous cannulation. Nevertheless, it is clear from the results of this study that fetal cardiac bypass will require modifications in extracorporeal techniques to optimize placental hemodynamics and fetal outcome.

In summary, reducing the extracorporeal surface area and avoiding external priming substances improves placental hemodynamics during and after fetal cardiac bypass. An in-line axial-flow pump is useful in miniaturizing the bypass circuit for potential use in fetal cardiac surgery.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This work was made possible by grant 2 RO1 HL-43357-01 from the National Institutes of Health.

We acknowledge the technical help provided by Roger Chang and the technical help and support of Walid K. Abol Hosn and Mike Wright of Johnson & Johnson Interventional Systems, Rancho Cordova, CA.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presented at the Poster Session of the Thirty-first Annual Meeting of The Society of Thoracic Surgeons, Palm Springs, CA, Jan 30-Feb 1, 1995.

Address reprint requests to Dr Reddy, Division of Cardiothoracic Surgery, University of California, San Francisco, 505 Parnassus Ave, M593, San Francisco, CA 94143-0118.

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Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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