Comparison of Nonpulsatile and Pulsatile Extracorporeal Circulation on Renal Cortical Blood Flow

Comparison of Nonpulsatile and Pulsatile Extracorporeal Circulation on Renal Cortical Blood Flow James D. Sink, M.D., W. Randolph Chitwood, Jr., M.D., Ronald C. Hill, M.D., and Andrew S. Wechsler, M.D. ABSTRACT Radioactive microsphereswere used to compare renal cortical blood flow with pulsatile and nonpulsatile extracorporeal perfusion in mongrel dogs. No difference was found in total renal cortical flow or in flow distributionusing pulsatile compared with nonpulsatile perfusion when mean perfusion pressure was held constant at a high (80 m m Hg) or low (50 mm Hg) level. Although the present investigation does not resolve the question of whether pulsatile perfusion has advantages over nonpulsatile perfusion in maintaining renal function, the data indicate that any differences between the two techniques must be explained by a mechanism other than increased total cortical blood flow or by redistribution of cortical flow.

monary bypass on total and transcortical blood flow distribution in the kidney was evaluated.

Material and Methods Adult mongrel dogs, weighing 21.2 f 0.7 kg, were anesthetized with intravenously administered sodium pentobarbital (30.0 mg per kilogram of body weight), intubated, and ventilated with a Harvard animal respirator (inspired oxygen fraction = 0.20). Following median sternotomy, the pericardium was opened and the heart was suspended in a pericardial sling. Fluid-filled polyvinyl chloride catheters (14 gauge) were inserted into the aortic arch through the right subclavian artery to monitor perfusion pressure and into the aorta through The physiological consequences of nonpulsatile the left subclavian artery for microsphere referblood flow have been a subject of consider- ence flow samples. able investigation. Nonpulsatile blood flow inA Shiley bubble oxygenator (Model S100) was creases systemic vascular resistance [7, 12, 20, primed with 2 to 3 liters of fresh heparinized 261 and decreases oxygen consumption and donor blood. The oxygenator blood hematocrit cellular metabolism [9, 12, 24, 281. Some inves- was maintained between 33 and 45 vol per 100 tigators have demonstrated an effect on blood ml (mean, 38.5 f 2.1) by adding whole blood or flow in the microcirculation [18, 211 and others, Normosol R (balanced salt solution) (pH, 7.4). a reduction in the safe duration of cardiopul- Each dog received systemic heparin (100 units monary bypass with nonpulsatile perfusion [12, per kilogram), and cardiopulmonary bypass 261. The data are not without controversy, how- was initiated with left carotid perfusion. Right ever, and nearly all of these conclusions have atrial cannulation provided venous drainage. been challenged by other investigators [l, 3, 8, To prevent ejection, the left ventricle was 16, 23, 271. vented through the apex. A model 1280 HewlettSpecifically, effects of pulsatile flow on renal Packard transducer, calibrated with a mercury function have been investigated, with con- manometer, was used to quantitate aortic prestradictory findings. In the present study, the sure throughout each study. effect of pulsatile perfusion during cardiopulDuring preparation for cardiopulmonary bypass, a midline abdominal incision was made, and the left renal artery was carefully From the Department of Surgery, Duke University Medical isolated. A 2.5 to 3.0 mm Howell ST electroCenter and the Durham Veterans Administration Medical Center, Durham, NC. magnetic flow probe was positioned on the Supported in part by Grant 5-R01-HL20226-02 from the renal artery and attached to a Statham M-400 National Institutes of Health, and the Medical Research electromagnetic flowmeter. Flow probes had Service of the Veterans Administration. been calibrated previously by allowing meaAccepted for publication May 4, 1979. sured amounts of physiological saline solution Address reprint requests to Dr. Sink, Box 3426, Duke University Medical Center, Durham, NC 27710. to flow through them over a known time pe57 0003-49751801010057-06$01.25@ 1979 by James D. Sink

58 The Annals of Thoracic Surgery Vol 29 No 1 January 1980

riod. Linearity was tested using different flow rates. Probe calibrations were found to have a standard deviation of f 4% and were linear, f 2%, for the range of flows encountered in the study. Data were recorded on an eight-channel direct writing recorder (Hewlett-Packard 7758A). In Group 1(6 male and 2 female dogs), a nonpulsatile perfusion pressure of 80 mm Hg was obtained using a standard roller pump. Flow was maintained between 75 and 125 ml per kilogram using an infrarenal aortic snare to help maintain a constant perfusion pressure. Following complete instrumentation, 10 minutes of stable perfusion was allowed prior to the first microsphere injection. Pulsatile perfusion was then initiated using an AVCO pulsatile bypass pump attached to a modified AVCO model 7 intraaortic balloon pump console, and mean perfusion pressure was carefully maintained at 80 mm Hg by adjusting the flow rate. Following 10 minutes of stable pulsatile perfusion, a second microsphere injection was made. The experiment was then terminated. In Group I1 (5 male and 3 female dogs), the same protocol was repeated at a perfusion pressure of 50 mm Hg. Pump flow rates at the perfusion pressure of 50 mm Hg were 40 to 70 ml per kilogram per minute. Bypass times ranged from 43 to 84 minutes (mean, 54.6 f 2.7 minutes). While on cardiopulmonary bypass, partial pressure of oxygen (Po2) averaged 158 f 23 mm Hg, and the pH was maintained between 7.38 and 7.45 (mean, 7.42 f 0.03) by administering sodium bicarbonate as needed.

Fig 1 . Following fixation in formalin, three coronal sections, 5 mm thick, were taken from each kidney. The capsule w a s removed from each section, and the medulla w a s separated from the cortex. Transcortical (TC)samples were taken, and the remainder of the cortex was divided into equal thirds. Tissues were weighed separately and quantitatively analyzed for gamma radioactivity.

microsphere injection technique was previously validated in this laboratory [14]. At the conclusion of the study, the left kidney was removed. Following five to seven days of fixation in 10% buffered formalin, three representative coronal sections, 5 mm thick, were taken from each kidney. The capsule was then gently removed from each section by blunt dissection. After separation of the medulla from the cortex by sharp dissection, transcortical samples were taken. The remainder of the cortex was divided into equal thirds (Fig 1). After they were weighed, the tissues were analyzed for gamma radioactivity using a M i c r o s p h e r e Blood Flow Determinations Beckman Biogamma Counter. An IBM 1130 digCarbonized microspheres,* 15 f 1 p in diame- ital computer was used to calculate regional ter, labeled with either cerium 141 or stron- renal blood flow. The Student t test for paired tium 85 were used to determine renal cortical data was used to determine statistical signifiblood flow. For each measurement, 3 X lo6 mi- cance ( p < 0.05). Data are reported as mean f crospheres suspended in l ml of 10% dextran standard error of the mean. solution were injected into the arterial perfusion cannula over thirty seconds with vigorous Results mixing. Simultaneously, arterial reference The average heart rate in the open chest in both samples were collected from the subclavian ar- groups of dogs prior to the institution of cartery catheter over 3 minutes with a calibrated diopulmonary bypass was 123 f 3 beats per Harvard peristaltic withdrawal pump. This minute, while aortic pressure was 112 f 7/78 f 4 mm Hg. A representative intraoperative recording of mean and pulsatile aortic pressure ‘3M Manufacturing Company, Minneapolis, MN.

59 Sink et al: Nonpulsatile and Pulsatile Extracorporeal Circulation

YMI-PULSATI LE PERFUSION

PULSATIU PERFUZN

35t

200 Ao PRESSURE (mmHg1

0

Ao

ME AN PRESSURE (mmHe1

zoor 100 0

-s

FLOW 091 (cclbeot)

I

20-

?

O[

9 Y

15-

MEAN FLOW

o Nonpulsatile

(cc/min)

0

Pulsatile

1 sec

Fig 2 . Representative intraoperative recording of aortic (Ao) pressure and renal artery flow from an animal in Group 1. Mean aortic pressure was 80 mm Hg with both pulsatile and nonpulsatile perfusion at 80 mm Hg perfusion pressure.

lot

0 2

(0UTER)I

CORTEX

3 (INNER)

LAYERS

Fig 4 . Transcortical renal blood flow (mllgmlmin) at 80 mm Hg perfusion pressure. There was no significant difference in blood flow to any layer with pulsatile as opposed to nonpulsatile perfusion. 200 Ao

MEAN PRESSURE

(mm Hol

100 0

FLOW (cc/beo~l

051

0

Fig 3. Representative intraoperative recording of aortic (Ao)pressure and renal artery flow from an animal in Group 11. Mean aortic pressure was 50 rnm Hg with both pulsatile and nonpulsatile perfusion.

and renal flow for each group is presented in Figures 2 and 3. In Group I, pulsatile pressure was 96 f 2/55.9 f 3 mm Hg (mean, 80 mm Hg) with a heart rate 0.8 beats per minute. In Group 11, the of 78 pulsatile pressure was 67.5 f 3134.8 f. 3 mm Hg (mean, 50 mm Hg) with a heart rate of 76 f 0.9. In Group I, renal artery flow was 72 f 10 ml per minute with nonpulsatile perfusion and 80 k 9 ml per minute with pulsatile perfusion. In Group 11, flows were 68.7 f 12.7 ml per minute and 76.1 f 15 ml per minute, respectively.

*

The transcortical distribution of renal blood flow in Group I is shown in Figure 4 and the Table. The ratio of flow of the outer two-thirds to inner one-third of renal cortex is shown in Figure 5. There is no significant difference in total flow or flow distribution with pulsatile as opposed to nonpulsatile perfusion with mean perfusion pressure held constant at 80 mm Hg. Figures 5 and 6 and the Table show transcortical flow distribution in Group 11. With perfusion pressure held constant at 50 mm Hg, there is no change in total flow or flow distribution with pulsatile as opposed to nonpulsatile perfusion.

Comment In 1889, Hamal [lo] suggested that kidney function is affected by the arterial pulse pressure. Studying the isolated kidney, he found that a reduction in pulse pressure resulted in a drop in urine output. Hamal’s conclusions were later confirmed by Hooker [ l l l and Gesell[6]. A direct correlation between pulse pressure and urine output was demonstrated by Judson and Rausch [131 in patients undergoing operation on the aorta. Senning and co-workers [25]

60 The Annals of Thoracic Surgery Vol 29 No 1 January 1980

Transcortical Renal Blood Flow with Pulsatile and Nonpulsatile Perfusion Layer PERPUSION PRESSURE

= 80

MM

Statistical Significance”

Pulsatile (mllminlgm)

2.71 f 0.56 2.79 f 0.63 2.94 f 0.74 2.73 f 0.60 1.97 f 0.10

p < 0.56 0.50 0.64 0.63 0.34

2.38 f 0.41 2.47 f 0.47 2.51 f 0.56 2.33 f 0.45 2.05 f 0.13

1.50 f 0.38 1.46 f 0.36 1.34 f 0.37 1.43 f 0.34 2.72 f 0.40

0.22 0.65 0.54 0.26 0.54

1.88 f 0.37 1.80 f 0.43 1.55 f 0.37 1.79 f 0.37 2.46 f 0.20

HG

Outer cortex Middle cortex Inner cortex Transcortex

on PERFUSION PRESSURE =

Nonpulsatile (mllmirdgm)

50 MM HG

Outer cortex Middle cortex Inner cortex Transcortex ON

aRepresents comparisons between nonpulsatile and pulsatile perfusion; statistical significance, p < 0.05. There is no significant difference in total flow or flow distribution with pulsatile compared with nonpulsatile perfusion at a perfusion pressure of 50 or 80 mm Hg. On = the ratio of flow of the outer two-thirds to the inner one-third of renal cortex.

3.5o Nonpulsatile

Pulsatile

3050mm Hg

T

- 2.5 E

\

E

1“ E 2.0

20

-

15

9

? Y

15 10

05

NOWPULSATILE

PULSAllLE

Fig 5. Flow ratios of the outer two-thirds to inner one-third of renal cortex (011) are represented for both pulsatile and nonpulsatile perfusion at perfusion pressures of 80 and 50 mm Hg. There was no significant difference in blood flow distribution with pulsatile compared with nonpulsatile perfusion.

O5

+ (0UTER)I

CORTEX

2

3 [INNER)

LAYERS

Fig 6 . Transcortical renal blood flow (mllgmlmin) at 50 mm Hg perfusion pressure. There was no significant difference in blood flow to any layer with pulsatile a$ opposed to nonpulsatile perfusion.

61 Sink et al: Nonpulsatile and Pulsatile Extracorporeal Circulation

showed that, in a canine model, nonpulsatile perfusion results in depressed renal function even at high flow rates. Several investigators have reported that a reduction in pulse pressure stimulates renin release 12, 151. Angiographic studies have demonstrated straightening and narrowing of both the main renal arteries and their interparenchymal branches with nonpulsatile perfusion [41. Many and co-workers El71 found that, in dogs, a reduction in pulse pressure to one kidney results in decreased urine output and sodium excretion in both kidneys. Jacobs and colleagues [12] demonstrated that during prolonged perfusion, renal function is better preserved with pulsatile perfusion than nonpulsatile perfusion. German and colleagues [51 demonstrated that nonpulsatile perfusion results in higher lactic acid levels and lower pH in renal vein samples than pulsatile perfusion during cardiopulmonary bypass. Despite the larger volume of evidence indicating that pulsatile flow is important in maintaining renal function, numerous investigators have found that as long as mean arterial pressure remains constant, pulsatile flow has no advantage over nonpulsatile flow in kidney function [8, 20, 23, 241. One important source of variance in the studies reported may be the conditions under which the perfusion techniques are tested. Our studies were performed at 37°C. Reducing perfusion temperature may interfere with autoregulation and make flow more pressure-dependent or may alter baseline vascular resistance, thereby enhancing the role of pulsatile perfusion. The discrepancy among various authors may also be related to the physical properties of the created pulse pressure and contour. It has been suggested that pulse tracings that demonstrate rapid upstroke and downstroke leave little time for diastolic runoff and approximate mean arterial flow despite the pulsatile appearance of the tracing 1191. In the present investigation, the AVCO pulsatile bypass pump was adjusted to produce the greatest pulsatile pressure achievable. Pulsatile pressure in Group I was 43.8 f 3.6 mm Hg and in Group 11, 32.8 k 3.5 mm Hg. While the pulse contour created by the AVCO system

was not identical to the pressure tracing in a normal vessel, the downstroke as seen in Figures 2 and 3 was sufficiently slow that good diastolic runoff would be expected. The present investigation was undertaken to evaluate renal cortical blood flow with pulsatile versus nonpulsatile perfusion using microspheres. No significant difference was found in total renal cortical flow or in flow distribution with pulsatile compared with nonpulsatile perfusion when mean perfusion pressure was held constant at a high (80 mm Hg) or low (50 mm Hg) level. This study does not resolve the question of whether one method of perfusion has advantages over the other in maintaining renal function. The data do indicate, however, that any differences between the two techniques must be explained by a mechanism other than increased total cortical blood flow or by redistribution of cortical flow.

Acknowledgments We thank the following persons: Ms. Ruby Griffin for secretarial assistance; Ms. Linda S. Sink for editorial comments; Mr. Gary L. Pellom and Mr. Edward L. Ristaino for technical assistance; and Mr. Donald G. Powell and Medical Media Productions (Durham Veterans Administration Medical Center) for creative illustrations.

References 1. Anabtawi IN, Womack CE, Ellison RG: Thoracic duct lymph flow during pulsatile and nonpulsatile extracorporeal circulation. Ann Thorac Surg 2:38, 1966 2. Corcoran AC, Page IH: Renal blood flow in experimental hypertension. Am J Physiol 135:361, 1942 3. Ead HW, Green JH, Neil E: A comparison of the effects of pulsatile and nonpulsatile blood flow through the carotid sinus on the reflexogenic activity of the sinus baroceptors in the cat. J Physiol (Lond) 118:509,1952 4. Finsterbusch W, Long DM, Sellers RD, et al: Renal arteriography during extracorporeal circulation in dogs, with preliminary report upon effects of low molecular weight dextran. J Thorac Cardiovasc Surg 41:252, 1961 5. German JC, Chalmers GS, Hirai J, et al: Comparison of non-pulsatile and pulsatile extracorporeal circulation on renal tissue perfusion. Chest 61:65, 1972

62 The Annals of Thoracic Surgery Vol 29 No 1 January 1980

6. Gesell RA: On relation of pulse pressure to renal function. Am J Physiol32:70, 1913 7. Giron F, Birtwell WC, Soroff HS, et al: Hemodynamic effects of pulsatile and nonpulsatile flow. Arch Surg 93:802, 1966 8. Goodyer AVN, Glenn WL: Relation of arterial pulse pressure to renal function. Am J Physiol 167:689, 1951 9. Halley MM, Reemtsma K, Creech 0 Jr: Cerebral blood flow, metabolism, and brain volume in extracorporeal circulation. J Thorac Surg 36:506, 1958 10. Hamel G: Die Bedeutung des Pulses fur den Blustrom. Z Biol 7:474, 1889 11. Hooker DR: Study of isolated kidney: influence of pulse pressure on renal function. Am J Physiol 279.1, 1910 12. Jacobs LA, Klopp EH, Seamone W, et al: Improved organ function during cardiac bypass with a roller pump modified to deliver pulsatile flow. J Thorac Cardiovasc Surg 58:703, 1969 13. Judson WE, Rausch NH: Effects of acute reduction of renal artery blood pressure on renal hemodynamics and excretion of electrolytes and water. J Lab Clin Med 50:923, 1957 14. Kleinman LH, Yarbrough JW, Symmonds JB, et al: Pressure-flow characteristics of the coronary collateral circulation during cardiopulmonary bypass: effects of hemodilution. J Thorac Cardiovasc Surg 75:17, 1978 15. Kohlstaedt KG, Page IH: Liberation of renin by perfusion of kidneys following reduction of pulse pressure. J Exp Med 72:201, 1940 16. Mandelbaum I, Berry J, Silbert M, et al: Regional blood flow during pulsatile and nonpulsatile perfusion. Arch Surg 91:771, 1965 17. Many M, Soroff HS, Birtwell WC, et al: The

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