Ann Thorac Surg 1995;60:1704-1708
© 1995 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Retrograde Abdominal Visceral Perfusion: Is It Beneficial?
Parachuri V. Rao, FRCS(CTh),
Russell F. Stahl, MD,
Babs R. Soller, PhD,
Kevin G. Shortt, MD,
Charles Hsi, MD,
Kevin J. Cotter, CCP,
Janice M. BelleIsle, BS,
John M. Moran, MD
Division of Cardiac and Thoracic Surgery, University of Massachusetts Medical Center, Worcester, Massachusetts
Accepted for publication July 21, 1995.
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Abstract
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Background. It is proposed that retrograde abdominal perfusion be used in combination with retrograde cerebral perfusion to provide total body visceral protection during aortic reconstruction; however, its physiologic effects remain unknown.
Methods. We compared the effect of superior vena caval perfusion alone with that of combined superior and inferior vena caval perfusion on the liver and kidney in 6 mongrel dogs. Organ blood flow was measured using ultrasonic flow probes on the hepatic artery, the portal vein, and the renal artery. Regional tissue blood flow to the liver and the kidney was assessed using colored microspheres and pH probes. Anesthetized dogs were placed on total cardiopulmonary bypass. After cooling to 20°C, retrograde perfusion was begun with 30 minutes of superior vena caval perfusion followed by another 30 minutes of bicaval perfusion, or vice versa.
Results. Very little renal blood flow was measured with either method of retrograde perfusion. Although the liver received more blood flow in comparison to the kidney, there was no significant difference between superior vena caval perfusion alone and bicaval perfusion. The addition of inferior vena caval perfusion results in portal hypertension, hepatic congestion, ascites, and bowel edema.
Conclusions. In the canine model, bicaval perfusion does not provide superior protection to the liver and kidneys when compared with superior vena caval perfusion alone.
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Introduction
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Retrograde cerebral perfusion has quickly become established as a useful technique to extend the safe duration of circulatory arrest during reconstruction of the aortic arch [1–4]. Indeed, clinical acceptance of this technique has preceded detailed scientific evidence that retrograde perfusion provides nutritional blood flow to the brain, which is both safe and sufficient [5]. Recently, Matalanis and Buxton [6], as well as Yasuura and colleagues [7, 8] have reported the clinical use of bicaval hypothermic retrograde perfusion. These investigators propose that visceral organs, including the liver and kidneys, can be sustained by oxygenated blood delivered through the systemic venous system at above normal but ``safe'' venous pressures. Although it has been shown that deep hypothermia (16° to 20°C) alone is adequate to protect the abdominal viscera [9], it was proposed that bicaval retrograde perfusion could be conducted without deep hypothermia, thereby avoiding its associated problems [6]. The aim of our study is to compare the effect of simultaneous perfusion of the superior vena cava (SVC) and inferior vena cava (IVC) with that of SVC perfusion alone on the liver and kidneys in a canine model.
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Material and Methods
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All the animals were handled and 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).
Surgical Technique
Six mongrel dogs (mean weight, 25.8 kg; range, 21.5 to 28.0 kg) were premedicated using intramuscular acepromazine (1.0 mg/kg) and anesthetized with intravenous sodium pentathol (15 mg/kg). The animals were intubated and mechanically ventilated using 2% halothane. The surface electrocardiogram was monitored. Ventilation was stopped after cardiopulmonary bypass (CPB) was begun, at which time intravenous fentanyl (0.05 mg/kg) was used to maintain anesthesia. At the completion of the experiments, the animals were killed by discontinuing CPB, still under anesthesia.
Median sternotomy and midline laparotomy were performed. Microtransducer pressure monitoring catheters (Millar Instruments Inc, Houston, TX) were placed in the aorta, the IVC, the high SVC, and the portal vein. Transit-time, ultrasonic flow probes (Transonic, Ithaca, NY) were placed on the portal vein (12-mm probe), right renal artery (4-mm probe), and the common hepatic artery (2.0-mm probe) after ligation of its gastroduodenal branch. The heart was cannulated for CPB with a 24F cannula in the aortic arch and 28F cannulae in the SVC and IVC. Figure 1
depicts the experimental protocol. Each phase of the experiment is 30 minutes in duration. Measurements of pressure, flow, and pH were recorded before cannulation for bypass and at the end of each perfusion phase. Microspheres were injected at each time point with biopsy specimens collected before the beginning of retrograde perfusion and at the end of retrograde perfusion.
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Fig 1. . Experimental protocol. (CPB = cardiopulmonary bypass; SVC = superior vena caval perfusion only; SVC & IVC = superior and inferior vena caval perfusion.)
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After institution of CPB, flow rates were maintained at 100 mL • min-1 • kg-1 as the animal was cooled to 20°C. Acid-base balance was managed using 
-stat strategy. After 30 minutes of antegrade CPB the animal was exsanguinated into the venous reservoir and retrograde perfusion was begun. In 3 animals we started with SVC perfusion alone for 30 minutes followed by bicaval perfusion for another 30 minutes. In the other 3 animals the sequence of retroperfusion was reversed (bicaval perfusion followed by SVC perfusion alone). During both SVC perfusion and bicaval perfusion the flow rates were adjusted to keep the mean SVC pressure at 25 mm Hg. During SVC perfusion alone the IVC cannula was clamped. The flow during SVC perfusion alone averaged 163 mL/min (range, 50 to 275 mL/min) and this increased with the addition of IVC perfusion to an average of 365 mL/min (range, 200 to 600 mL/min). Reported values for systemic flow and pressure, as well as ultrasonic flow measurements, were averaged over 1 minute and were recorded near the end of each 30-minute interval. The pH values represent the average of 3 minutes at the end of each interval.
Measurement of Organ Tissue Blood Flow Using Colored Microspheres
Nonradioactive, 12-µm colored microspheres (IMT International, Los Angeles, CA) were diluted with 3 mL of saline (approximately 5 million spheres/injection) and thoroughly mixed using a vortex. The microspheres were injected directly into the left atrium for the baseline study. During CPB the injections were made into the inflow cannula at least 30 cm proximal to the tip in the aorta or venae cavae. Reference blood samples were obtained during each injection from the femoral artery during antegrade circulation, from the SVC during retrograde SVC perfusion, and from the IVC during bicaval retroperfusion. The samples were collected for 90 seconds using a Harvard Pump (Harvard Apparatus Inc, Dover, MA) at a rate of 10 mL/min. Biopsy samples were obtained from the liver and kidney (approximately 2 to 3 g of each tissue) at the end of antegrade perfusion and at the end of retrograde perfusion. The number of microspheres in the biopsy specimen is estimated using flow cytometry after digestion of the tissue. Regional tissue blood flow (RTBF) is derived using the formula RTBF = (CT x R)/(CR x WT), where CT is the total number of microspheres in the tissue sample, R is reference flow rate (mL/min), CR is the total number of microspheres in the reference blood sample, and WT is the weight of the tissue sample in grams. Results were expressed as milliliters per gram per minuteAu: OK?. Different colored microspheres were used for determination of tissue blood flow at various time intervals.
Hepatic and Renal pH Measurements
The pH probes (Microelectrode Inc, Londonderry, NH) were placed in the parenchyma of the left lobe of liver and into the cortex of the right kidney. The reference electrode was connected to subcutaneous tissue with a KCl-saturated agar bridge. Temperature probes (Vascular Technology Inc, Chelmsford, MA) were inserted close to the pH probes. The pH measurements were corrected for both response of the electrode to temperature [10] and also for the effects of temperature on the dissociation of water in tissue (Rosenthal factor, 0.0147 pH units per 1°C difference from 37°C) [11].
Autopsy
At the end of each experiment, the external maxillary, hepatic, portal, and renal veins, and the IVC were inspected for the presence of valves.
Statistical Analysis
Statistical comparison between the two retrograde perfusion methods (SVC perfusion alone to that of bicaval perfusion) was performed using a paired t test. The measurements were expressed as mean ± standard error of mean or with 95% confidence limits for key parameters. A p value of less than 0.05 is considered statistically significant.
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Results
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Pressures
The pressures recorded at the end of each 30-minute period are presented in Figure 2. The systemic arterial pressure was low during retrograde perfusion, but not zero. The IVC pressure and portal vein pressure were generally equal during all phases of perfusion. During SVC perfusion alone the IVC and portal vein pressures were approximately 50% of the SVC pressure.
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Fig 2. . Pressures recorded during each phase of the experiment (mean ± standard error of the mean). (IVC = inferior vena cava; SVC = superior vena cava.)
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Organ Blood Flow
Organ blood flow measured by ultrasonic flow probes is summarized in Figure 3. During retrograde perfusion, there was reduced flow in the hepatic artery, the portal vein, and the renal artery. Overall, there were no significant differences in the amount of flow between SVC perfusion alone compared with bicaval perfusion in the hepatic artery (-2.06 mL/min, 95% confidence limits -4.24 to +0.12 versus -5.49 mL/min, 95% confidence limits -16.26 to +5.25), portal vein (+18.05 mL/min, 95% confidence limits -79.71 to +115.81 versus -25.00 mL/min, 95% confidence limits -107.70 to 57.70), and renal artery (-0.80 mL/min, 95% confidence limits -4.19 to +2.60 versus -1.15 mL/min, 95% confidence limits -4.53 to +2.23). Flow toward the organ is represented by a plus sign and flow away from the organ is represented by a minus sign. In theory, the direction of flow as recorded by the flow probe is expected to reverse during retrograde perfusion and therefore, represent the volume of blood entering the concerned organ. In our study, although the direction of flow in the hepatic and renal arteries was reversed during retroperfusion, the direction of blood flow in the portal vein was variable; in some dogs it was toward the liver, but in other dogs it was away from the liver. The explanation for this unpredictable flow may lie in the nature of collateral pathways between portal and systemic veins and the resistance to drainage of blood from the portal venous system.
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Fig 3. . Liver and kidney blood flow recorded using transit-time, ultrasonic flow probes. Flow toward the organ is represented by the bar orientated above the x-axis whereas flow reversal is indicated by bar below the x-axis (mean ± standard error of the mean).(NS = not significant; SVC = superior vena caval perfusion only; SVC & IVC = superior and inferior vena caval perfusion.)
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What was consistently observed but not quantified, however, was the engorgement of the liver during bicaval perfusion. In all 6 animals the portal vein was tense and the liver bled freely at biopsy sites during bicaval perfusion. The generation of ascites and bowel edema was also more evident when the IVC pressure was increased. We did not have the same observations during retroperfusion through the SVC alone.
Regional Blood Flow by Colored Microspheres
Tissue blood flow as measured by microspheres is presented in Figure 4. During baseline and antegrade perfusion the tissue blood flow in the liver was low as assessed by 12-µm microspheres (0.08 ± 0.04 mL • g-1 • min-1 and 0.11 ± 0.04 mL • g-1 • min-1, respectively). During retrograde perfusion with both SVC perfusion alone (0.11 ± 0.07 mL • g-1 • min-1) and bicaval perfusion (0.16 ± 0.11 mL • g-1 • min-1), the liver received tissue blood flow comparable with the antegrade period; this despite the finding that total systemic blood flow during retrograde perfusion was reduced compared with antegrade CPB.
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Fig 4. . Liver and kidney tissue blood flow measured using colored microspheres (n = 5). The measured renal tissue blood flows during retrograde perfusion were extremely small (mean ± standard error of the mean). (Abbreviations are the same as in Fig 3 .)
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Renal tissue flow during baseline and antegrade perfusion (3.61 ± 1.03 mL • g-1 • min-1 and 1.71 ± 0.41 mL • g-1 • min-1, respectively) were comparable with reported normal values (2 to 6 mL • g-1 • min-1) [12]. In contrast to the liver, renal tissue flows were negligible during retrograde perfusion either through the SVC alone or with combined SVC and IVC perfusion (less than 0.01 mL • g-1 • min-1).
pH Measurements
The temperature corrected pH of the liver and kidney near the end of each phase is depicted in Figure 5. Compared with the pH at baseline and during antegrade CPB (7.04 ± 0.10 and 6.97 ± 0.07, respectively), the kidney is relatively acidotic during both SVC perfusion (6.63 pH units, 95% confidence limits 6.12 to 7.15) and combined SVC and IVC perfusion (6.69 pH units, 95% confidence limits 6.27 to 7.11). In contrast to the kidney, the liver pH does not fall as much during SVC perfusion alone (6.93 pH units, 95% confidence limits 6.47 to 7.39). Although there is a slight rise in liver pH toward the end of bicaval perfusion (7.04 pH units, 95% confidence limits 6.48 to 7.60), this did not reach statistical significance.
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Fig 5. . Liver and kidney interstitial pH (n = 5) (mean ± standard error of the mean). (Abbreviations are the same as in Fig 3.)
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Comment
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Our study of retrograde abdominal organ perfusion in a canine model demonstrates that (1) actual blood flow to the liver and kidney is surprisingly low during venous perfusion; (2) retrograde blood flow is insufficient to prevent the accumulation of hydrogen ions in the kidney, indicative of organ ischemia, despite profound hypothermia; (3) there is no significant difference in organ blood flow between SVC perfusion and bicaval perfusion; and (4) considerable hepatic congestion with ascites and bowel edema may occur during retrograde bicaval venous perfusion.
A potential criticism of our experiment is the selection of an appropriate animal model. The dog is not an ideal model for the study of cerebral retroperfusion, as pointed out by Usui and colleagues [13], due to the presence of valves in the neck veins. In our autopsy studies, there was the consistent finding of competent valves in the external maxillary vein (the principal venous drainage route for the head in dogs). The renal veins occasionally had valves at the junction with the IVC, but these were mostly rudimentary and incompetent. The IVC and the hepatic veins were devoid of valves, a pattern similar to humans [14]. It is conceivable that the competent valves in the neck may have forced more blood through collateral channels to the lower body during SVC perfusion. Maintaining the SVC pressure at 25 mm Hg mimics our clinical technique of retrograde cerebral perfusion. Thus, although the dog's brain may not receive the portion of SVC perfusion that a human might, comparisons regarding the abdominal viscera remain justified.
Another methodologic issue involves the use of microspheres to assess tissue perfusion. This technique has been shown to correlate well with tissue blood flow [15] , but, in our study the hepatic perfusion was quite low during baseline and antegrade CPB (approximately 0.1 mL • g-1 • min-1). Although not determined precisely, normal hepatic blood flow in dogs is thought to be about 1 mL • g-1 • min-1. A possible explanation for this apparent low flow during antegrade circulation is that the portal vein, contributing at least two-thirds of total hepatic blood flow, is devoid of microspheres because it arises from the capillaries of the gut. In addition the high portal vein flow during antegrade circulation may have washed out microspheres from the liver sinusoids.
Although our statistical analysis did not reveal any difference in organ blood flow and pH between SVC perfusion alone and bicaval perfusion, the reader should be aware that the small sample size gives us the power to detect only large differences. However, the data show that for both types of retrograde perfusion, blood flow is considerably reduced compared with baseline values and kidney pH is significantly lower than baseline values.
The use of pH probes has been studied extensively in the context of myocardial ischemia [16, 17]. A change in pH from baseline values correlates well with the adequacy of tissue perfusion. Except for rare experimental studies [18], its application in abdominal visceral circulation is unique. A pilot study in our laboratory revealed good correlation between ischemia and a fall in pH in both the liver and the kidney. Presently there exist no clinical data to correlate the level of ischemia and its consequences to the decrease in pH.
This study demonstrates reduced blood flow to the liver and especially the kidney, during retrograde perfusion. In contrast, Oohara and colleagues [19] showed slightly higher renal blood flow using both colored microspheres during normothermic IVC perfusion (0.06 mL • g-1 • min-1), and a hydrogen clearance method during hypothermia (0.08 ± 0.31 mL • g-1 • min-1). Although the systemic venous pressure in their study (30 mm Hg) was higher than in ours (25 mm Hg), these values are still 1/100th the normal blood flow, and therefore, are probably inadequate for effective nutritional flow. This corresponds to our pH data that demonstrate a fall in renal pH during retrograde perfusion despite deep hypothermia (20°C). It is likely that this situation would be worse with normothermia or moderate hypothermia, refuting the proposed use of retrograde perfusion to avoid deep hypothermia and attendant coagulation problems [8].
Unlike the kidney, the liver appears to have better blood flow and maintenance of pH during retrograde perfusion. Again, there was no significant difference between SVC perfusion alone and combined SVC and IVC perfusion on the liver. In addition, with the onset of retrograde bicaval perfusion, portal hypertension developed along with a corresponding increase in hepatic congestion and ascites. Although we have not quantified either the hepatic distention or volume of ascites, they appear to be significant problems with bicaval perfusion, not seen with SVC perfusion alone. The liver is positioned between the portal and systemic venous systems and therefore, is vulnerable to the high hydrostatic pressures generated in these vascular beds during retrograde perfusion. In addition, lymphatic drainage from the abdominal viscera through the thoracic duct may be impaired by high venous pressure during bicaval perfusion. Our animals demonstrated significant ``third space'' losses of fluid and little return of blood through the aorta during retrograde perfusion. In their study, Oohara and colleagues [19] noted that only one-third of the perfusate returned by way of the aortic cannula during retrograde perfusion.
In summary, our canine model shows that retrograde SVC perfusion alone appears to provide some blood flow to the liver and kidney, probably through venous collaterals. The addition of IVC perfusion to SVC perfusion did not show improved circulation to the kidneys and liver. Furthermore, it carries a risk of severe congestion and edema of the liver and intestines. Before adaptation of IVC perfusion to clinical practice, it would seem prudent to perform additional studies, using other animal models, to further assess the possible advantages and disadvantages of retrograde abdominal organ perfusion during circulatory arrest.
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Footnotes
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Address reprint requests to Dr Stahl, Division of Cardiac and Thoracic Surgery, University of Massachusetts Medical Center, 55 Lake Ave, Worcester, MA 01655-0304.
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References
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Abstract
Introduction
