Regional blood flows and cardiac output distribution in rats during acute anemia or pol yc y thernia

U. ACKERMANN A N D A. T. VERESS Drpurrrncrzt og'Phj.siolo,qj., tinivrrsitj) ),(!f'7hr(~1110, Torc~tzto, b)nt., C'rrnuch MjPd / A 8

Received August 23, 1979

A<-KERMANW, U., and A. T. VFZKFSS. 1980. Regional blood flows and cardiac output distribution in rats during acute anemia or polycythemia. Can. J. Bhysiol. Pharmacol. 58, 41 1-41 5.

Radioactively labelled rnicmspheres (15 p in diameter) were used to measure cardiac output (CO) distribution and blood flews in qpleen, kidneys, and skeletal muscle before and after nosrnovc~lernic anemia or polycythemia in anesthetized rats. Hernatocrits were changed frorx-a 45 to 33% or from 45 to 59%1 by an exchange tranasfusion of homologous plasma or packed cells. Anemia was accompanied by a 39% increase i n C 0 while polycythemia showed a 25% decrease. Following hernodilution the spleen as well as skeletal nluscle received greater than normal fiactioils of C O and in each the flow increase was greater than expected from the fall in viscosity. The renal fraction of C'O was unchanged. Following hernoconcentration "greater-than- normal" fractions of CO were distributed towards spleen and kidney. In these tissues the changes in flow were significantly greater than the change in resistance due to viscosity. Skeletal muscle Wow changes appeared to have been due mostly to increased viscosity. These observations imply that during acute, isovolemic changes in hernatocrit, the flow changes of indi- vidual vascular beds cannot be explained by viscosity changes alone but the importance of nervous control or of local n-aetabolic factors remains to be investigated.

ACKERMANN, U., et A. T. V~RRSS. 1980. Regional blood Bliows and cardiac output distribution in rats during acute anemia or polycythernia. Can. J . PhysioB. Pharmacol. 58, 41 1-415.

On a utilise des microspheres radioactives 111arquies (15 pm de diamktre) pour rnesurer le debit cardiaque (CO) ainsi que les debits sanguins dans la rate, les reins et les ~nuscles squelettiques de rats anesthesies avant et apres une anemie norn-ao- val&nique ou une polycythinaie. Un Cchange par transfusion de plasma hornologue ou de cellules groupkes rnodifie l'hk~natocrite de 45 B 33% ou de 45 B 59%- L'animie est accornpagnke d'une augmentation de 39%) du ('6) alors que la polycythemie lnontre une diminution de 25%. A la suite de I'hkmodilution, la rate tout cornme le muscle squelettique resoit des fractions de CO qui sont supkrieures a la normale et dails les deux cas, l'augmentation du dkbit est plus grande que celle prevue a partir de Ia chute de la viscositk. La fraction renale de CbB est inchangee. A la suite de l'htimoconcentration, des fractions de CO superieures a la normale sont distribuees verb la rate et le rein. Les changements de debit dans ces tissus sont significativement plus grands que Ie changement de resistance du ii la viscositi. Les changernents de &bit dans le muscle squelettique selnblent ktre dGs principalenlent i une viscosite augmentke. Ces observations impliquent que. au cours de changements isovolkrniques a i p s de l'hkniatocrite, les changements du debit des lits vasculaires pris il~dividuellement, ne peuvent &re expliquks par des changements de viscosite seuleanent; il reste encore h examiner l'importance d'un contrijle nerveux ou de facteurs rnktaboliques locaux.

[Traduit par le journal]

lntroduction Changes in cardiac output and other indices of car-

diovascular function during anemia or polycythemia have been studied in several laboratories (Richardson and Guyton 1959; Weisse el tal. 1964; Escobar et crl. 1966; Murray ct a / . 1969; Neill et a!. 1969; Vatner et a / . 1972; Chamorro t7t ul . 1973). ]It is generally accepted that anernia is ascornpanled by increases in cardiac out- put, that polycythemia is accompanied by decreases in cardiac output, and that these changes are due ~nostly to changes in total peripheral resistance. Anernia is char- acterized by decreased peripheral resistance (Richard- son and Guyton 1959; Escobar ct ul. 1966; Murray et al. 1969) while increased peripheral resistance is a fea- ture of polycythemia (Richardson and Guyton 1959; Weisse et al . 1964). If these resistance changes were the result of altered blood viscosity alone. then proportion- ately equal resistance changes would occur in all vas- cular beds and there should be no change in the frac- tional distribution of cardiac output. On the other hand, if factors in addition to blood viscosity determined local

resistance in anemia or polycythemia then cardiac out- put distribution to various regions would differ between the two conditions. Although the study of Vatner et a / . (1972) suggested that in chronic anemia different vas- cular beds are affected to different degrees, no specific study of the phenomenon has been reported. Accord- ingly, we measured in acutely anemic or polycythernic, anesthetized rats the distribution of cardiac output to three vascular beds: to the kidneys because of the dem- onstrated effect of hematocrit on kidney function (Na- shat and Portal 1947; Brenner and Galla 197 i ) , to skel- etal muscle because of the important role of that vasculature 111 peripheral resistance adjustments (Mel- lander 1960). and to the spleen because of its possible role as an erythrocyte storage organ regulating total body hematocrit (Grayson and Mendel 1965; Gunther- 0th and Mullills 1943).

Methods The study was performed in 24 male Sprague-Dawley rats

(394 lb 8 g (mean + SEM)). Anesthesia was by Inactin,' 100

'Henley and Company, New York.

0008-42 1218010404 1 1 -05$0 1 100/0 1980 National Research Council of Canada/ConseiB national de recherches du Canada

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412 CAN. J. PHYSIOL. PHARMACBL. VQL. 58, 1980

~ragdkg body weight, i.p. Following a tracheostomy, polyeth- ykne catheters were inserted into the right comn-eon carotid ,artery (PE-50), the right external jugular vein (PE-90). the left fernoral artery (PE-50), the left fen~oral vein (PE-50). and the bladder (PE-90). The cannula in the carotid artery was ad- vanced until its tip lay just outside the aortic valve. Micro- spheres were injected though this cannula. The jugular venous catheter, advanced to the level of the right atrium, served the nzeasure~nent of central venous pressure as well as the infusion of rat plasma or packed erythrocytes during hematocrit alter- ations. Arterial blood pressure was recorded from the femoral arterial catheter and all blood samples were taken there.

After surgery 30 rnin was allowed for stabilization. There followed a 20-min control period during which pressures were accorded continuously and one 100-yL blood sanaple was taken for determination of hematocrit by the micromethod (centrifugatis~n for 5 man at 12 000 X g) and of plasma protein concentration by refractornetry . The Tirst injection of micro- spheres was givcn at the end of the control period. During the next 10 rnin the rats were rendered either anemic or polycy- thernlc by a sin~ultaneous infusion-withdrawal procedure in which plasma (or packed cells) frown a donor rat was ex- changed for an equal volume of the experinaental animal's cir- culating blood. This exchange maneuver was followed by two 20-min observation periods, a second microsphere injection being given at the end of the first period. The micrc)spheres were 15 2 5 ,urn in diameter, labelled with '"Ce or 8%r,%nd suspended in 4.5% bovine serum albumin solution. A cumu- lative total elf 75 000 - 100 000 spheres was injected.

Cardiac output and its distribution were measured by the reference sa~nple method (Malik et al . 19'76). Ten seconds before inicrosphere iiajection, blood withdrawal was started frorn the cannulated fen-eoral artery at I anL/min. A vibrated microsphere suspension was injected and flushed in during the next 6-10 s. Blood withdrawal was continued to the 1-min ~ n x k . At the end of the experinlent, the spleen, both kidneys, and mast of the thigh nluscles were removed and weighed. The tissues and the withdrawn blood were each digested over- night in identical voluanes of concentrated hydrochloric acid at 440°C. Total gamma activities were deterinined in a two- channel counter. It was not necessary to correct for Ce spill- aver into the Sr channel. However, spillover of Sr into the Ce channel was approximately 44% of Sr counts at the optimal counter settings and required co~rection by standard algebraic techniques. The absolute blood flow rate to any tissue was calculatecf from the formula, tissue blood flow = total tissue cpm x blood withdrawal rate/cprn in withdrawn blood. Sim- ilarly, cardiac output (CO) was calculated as C4P = total in- jected cprn X blood withdrawal ratelcp~n in withdrawn blood. It was not possible to calculate skeletal muscle blood flow as a fraction of cardiac output kecaaese only a portion of total body muscle Inass was counted.

Total peripheral resistance was calculated as the quotient of the difference between mean arterial and central venous pres- sures and the cardiac output. The relative viscosity of whole blood, TB, was calculated from the forralula given by Charna and Kurland (199%):

q, = 1/(1-0.07407 P1,)(l - 1.2 MTCT) where P., = plasma protein concentration in g r m s per 1m mL; HTCCCT = hematocrit.

The importance of variations in viscosity and driving pres- sure as a cause of Wow clnange was assessed on the basis of Poiseuille's la\w" by comparing the ratio of experimental:camtrd .- --

"M Canada Limited, London, Ontario. r r 4 LIP - x - where r = radius, I = length.

TR

-- values of bP/qB (where LC# = AWP - C V P ) with the ratio of experimental:control values of each of the measured re- gional flows. Equality of the two ratios was taken to mean that the change in flow from its co~ltrol value was the result p1-i- mxily of changes in blood viscosity and driving pressure. 'This inference is only suggestive because it is based on central rather than local measurements and because changes in vas- cular length and radius were not known.

Results The measured and calculated variables are summa-

hazed in Table I .

Clmoges during arsernic~ Hernodilution was accompanied by decreased total

peripheral resistance (TPR, Table I ) . Judged by com- parison of the two expea%rnental:contd ratios (paired t- test), the resistance change was greater than that in rel- ative viscosity I$ < 0.005). Cardiac output (C0) in- creased to 139 + 8% of control. ThM~as not enough to maintain arterial blood pressure BABP) at its controB level.

The three vascular beds that were tested did not share the augmented flow equally. Flows to the spleen (Sp B F ) and to skeletal muscle (Sk MBF) changed to 183 + 14% of control and 187 + L 0% of control, respectively. Both were significantly greater than the increase in C'0 @I < 0.05 andp 0.005, respectively). In addition, their ratios of experimental flow to control f ow were larger ('p <.. 0.005) than the ratio of experimental M / q B to control n$/q,. The kidneys showed a different picture. The increase in their flow (RBF, Table I ) was the same as the increase in cardiac output and it was not different from that expected from the changes in perfusion pres- sure, L I P , and in blood viscosity.

Changes during poLycythem6n Unlike anemia, polycythemia was acconnpaaaied hy

a fractional increase in total peripheral resistance ('b'PR) equal to the fractional increase in relalive viscosity. Car- diac output decreased, but due to the higher TPR there was no change in mean arterial blood pressure. As it did in anemia, splenic flow hcreased in polycythe~nia and its change was greater than that in miaaB @J <:: 0.005). Renal blood ilow, although not changed in absolute value, represented an increased fraction of cardiac out- put. Its expekmentd:control ratio was significantly greater than expected on the basis of viscosity and driv- ing pressure values @I 0.005). Muscle flow decreased by a fraction that was not significantly different from the fdl in cardiac output to 75 ? 5% of its control value. Furthernaore, the change in thigh muscle blood flow was not different from the change in the ratio AP/qB.

In summary, the results suggest that in acute anemia the spleen and skeletal muscle vasculature showed in- creases in flow over and above those expected from the central changes in blood viscosity and perfusion pres-

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ACERhfBaNTN AND VERESS

sure. In acute polycythemia, on the other hand, the spleen and kidneys appeared to show active vasodila- tation. The tissues showing flow changes equal to those anticipated from changes in driving pressure and vis- cosity were the kidneys in anemia and skeletal muscle in polycythemia.

Discussion 'Fhe validity of the microsphere method of determin-

ing cardiac output distribution in the rat has been dem- onstrated by a number of investigators (Mendell and Hallenberg 197 1 : Sasaki and Wagner 197 1 ; Malik et e l l .

1976; McBevitt and Nies 1976). In addition, Kaihara et ~ l . (19699) showed that all regional Wows, with the exception of coronary arterial flow, are ineasured with equal accuracy and reproducibility whether the spheres are injected directly into a left cardiac chamber or into the aortic arch. This is also suggested by the agreement between our control values for cardiac output and its distribution and those reported by investigators who used intracardiac injections in normal anesthetized rats (Mendell and Hollenberg 197 1 : Rakusan and Blahitka 1974; Sasaki and Wagner 8971; Malik et uk. 1976; McDevitt and Nies 8 976).

The significant events acconlpanying a decrease or increase in the number of circulating erythrocytes were changes in viscosity, in peripheral resistance, in cardiac output, and in cardiac output distribution (Table 1). Oxygen-carrying capacity and oxygen delivery must have keen changed as well but these were not assessed.

A characteristic feature of anenlia is a significantly reduced arterial oxygen concentration (Cha~norro et ad. 19'73); a characteristic feature of polycythemia is de- pressed oxygen delivery because of impaired tissue blood Wow (Replogle and Merrill 1970; Wolfe and Hor- vath 1946). The interaction of these and other factors is complex. It is known that there is a difference from tis- sue to tissue in the response to altered hematocrit (Rak- usan and Rajhathy 1972), to altered rates of oxygen de- livery (Chalmers e r a / . 1967), and to altered viscosity (Glick et a / . 1964). Our data suggest that in any one tissue apparently converse stimuli need not produce op- posite effects. In anemia the spleen and skeletal muscle vasculatbare dilated reIatively more than other vascular beds; in polycyt%lernia the spleen and kidneys appeared to show active vasodilatation; changes in central driving pressure and viscosity alone could have accounted for blood flow changes in the kidney duri~ag a~aemia and in skeletal muscle during polycythemia. A13 these effects must have been the result of interactions anlong rhes- logical factors, metabolic and ~aeurohorrnonal factors, but little is known about the nature of the inter- actions at the Bevel of individual tissues.

Splenic blood flow is thought to be directly related to the rate of erythropoiesis, showing an increase in

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4 8 4 CAN. J . PMYSHBE. PHARMACQl,. VOL,. 58, 1980

cklronic anernaia and a decrease in chronic polyc ytkemia when erythropoiesis is suppressed (McCuskey and Mei- raeke 19'77). We found increased flows during acute ane-sraia as well as acute polycytiaernia and the changes cot~1d not ke ascribed cornpletel y to variations ira driving pressure ancl viscosity. As these observations were rnade only 20 rnin after helnatc~crit alteration, it is unlikely that the erytlaroyoietic system was involved significantly. Ifr,wever, the increased flow in anemia could have been a tcpcal response tc~ intrasplenic hypoxia (Chalmess et c ~ k . 196'7: Vatipel el a l , 1976) while the increase during polycythernia may have been adrenergically mediated as a reflex response to impaired flow in some other re- gion (Brc~oksby and Donald 19'72).

Renal blood flow is said to be subservient to the more vital areas of the body during anemia and polycythernia. That view is based on the observation of decreased flow in chronic anemia (Bradley and Bradley 1947; Paterson 195 1; Whitaker 1956) and of increased flow in chronic polycytl~eania (Scott and Elliott 1950; de Wardener et id. 1951). Acute, isovolemic changes in hematocrit are associated with a different pattern. Absolute renal blood flow was i~acreased following a decrease in heanaatocrit and it was unchanged from control following an increase in hernatocrit. Identical observations have been reported by Share (1952), Migdal et ( a ! . (1975), and Spencer (195 1). In our experiments, changes in perfusion pres- sure and viscosity could explain the altered flow in me- mia but the polycythernic flow must have been caused by significant renal vasodilatation. Spencer (195 1) has argued that the latter is a manifestation of autoregula- tion. Our polycythemia data are consistent with this con- cept, but the increased Wow in anenaia gives no evidence of autoregulation. It is possible that its cause was a re- ciprocal relationship between renal blood WOW and ar- terial P,,, (Wesson 1969). Significantly reduced arterial oxygen concentration has been demonstrated in anemia (Chamorno et u1. 1973) and the failure of the renal vas- canlature to constrict might have keen due to local hy- poxia (Fish~nann e? ul . 195 1).

The behaviour of muscle blood flow was in agreement with the generally held view that flow in this tissue is inflarenced strongly and persistently by local metabolic factors and relatively weakly and transiently by vaervous factors. Polycythernia appeared to have no significant effect over and above that due to changes in pressure and viscosity. Hf the changes in splenic flow during this condition were c a s e d by central neurohormonal fac- tors, then the vasculature of the thigh muscles seemed to have escaped frorn them at the time of measurement. During anemia, however, the flow increased Inore than expected from the fall in blood viscosity. As a decreased muscle oxygen tension has been demonstrated by other investigators during anemia of comparable severity (Crawford et ak. 1959; Haddy 1966), it is possible that

local hypoxia led to vasodilatation that was superim- posed on the decreased rheojogical resistance.

In summary, our results suggest that during acute isovolemic anenaia or polycythemia, rheological factors alone can explain the changes in some regional blood flows under scsnne conditions. Most flow changes, how- ever, are not explained sinnply by them. They probably result from complex interactions of rheology, tissue metabolism, and reflex regulation. Confirmation of this impression would require measurements of local vis- cosity, local hydrostatic pressure, and local P,,, in ad- dition to the measurements of local flow.

Acknowledgments We wish to thank his. Susan Lamb and Mr. Chee

Chong for their technical assistance. This work was sup- ported by the Ontario Heart Foundation (grants OHF 1- 3 B and OHF 1-47) and by the Medical Research Council of Canada (grant MA 5589).

BRADL F Y , S . E., and G. P. BRAD[ E Y . 1947. Renal function during chronic anernla in naan. Bloc~d. 2. 192-202.

BREYKER, B. M., and J . H. GAL LA. 1971. Influense of post- gloaalemlar heaalatocrit and protein concentration on rat ne- phroan Waaid transfer. Am. S. Physiol. 220, 148- 8 61.

BROOKSBY, G. A., and D. E. DONALD. 1972. Release of blood from the splanchnic circulation in dogs. Circ. Res. 31, 105-118.

CIIALMCKS, J . P., P. I. KQKNFR. and S. W. WHITE. 1967. Local and reflex factors affecting the distributiotn of the peripheral blood flow daaring arterial hypoxia in the rabbit. J. Physiol. (London), 192, 537-548.

CIIAMORWO, G., 9. A. ROLIRLGLJFZ, B . DLINLVIO, and E. RA- PAPOR 1 . 1973. Effect of acute isovolenmic anemia on cardiac output and estimated hepatic flow in the conscious dog. car-c. Wes. 32, 530-535.

CHARM, S. E., and S. E. KURI AND. 1972. Blood rheoiogy. In Cardiovascular fluid dynamic&. Chap. 15. Ecditcd by D. H. Bergel. Academic Press Inc., London.

CKAWE<ORD, H%. G., PI. M. FAIR(.HHI.D, and A. c. G r r u r o ~ . 1959. Oxygen lack as possible cause of reactive hyperemia. Am. J . Physiol. 199, 613-616.

Dp ~ A R I I E N E R , H. E.. R . R . M C S W I N ~ Y , md B . E. MILL\. 1951. Rend haeanodynamlcs in primary polycythernia. Lancet, ki, 204-206.

Esco~dinr, E., N. L. JONES, E. RAPAPOIZT. and J. B;. MCIRRAY. 1966. Ventricular performance in acute norrnovolemic anemia and effects of beta blockade. Am. 9. Physiol. 211, 877- 884.

Flsfi~,\N. A . P . , M. H. MAXCVEI I < , C. D. CRCPWDE.,K, and D. MORAI F,S. 195 1. Kidney function in cor- pulrnoraulr*. Par- ticular considerations of changes in renal hernodynamics and sodium excretion during valiation in level of oxygen- ation. Circulation, 3, 703-721.

Gr I~ .K. G., W. H. PL A B J K H , and E. BRALTKWAI D. 1964. Role of the autonomic nervous system in the circulatory response to acutely induced anemia in unanesthetized dogs. J . Clin. Invest. 43, 21 12-2124.

GKAYSON, J . , and D. MENDEP. 1965. Physiology of the splanchnic circulation. Edward Arnold Publishers Ltd., London. pp. 138-140.

Can

. J. P

hysi

ol. P

harm

acol

. Dow

nloa

ded

from

ww

w.n

rcre

sear

chpr

ess.

com

by

SAV

AN

NA

HR

IVN

AT

LA

BB

F on

11/

12/1

4Fo

r pe

rson

al u

se o

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AND VERESS 4 15

GUNHH~ROTH, W. G., and G. L. Mrr1,r INS. 1963. Liver and spleen as vencbus reservoirs. Ann. J. Physiol. 204, 35-41.

MADI,Y, F. J. 1966. Role of chemicals in local regulation of vascular resistance. Circ Res. 18 (Suppl. I), 14- 20.

KAIHAKA, S . , P. D. HE'I~KULN, T. MI(;BTA, and H. N. WAC,- NER. 1968. Measurement of distribution of cardiac output. J . Aggl. Physiol. 25, 696-700.

Miam aK, A. B. , J. E. KAH A U , and T. h?l. SARA. 1976. Kef- erence sample method for cardiac output and regional blood flow determinations in the rat. 8 . Appl. Physiol. 40, 472-475.

Mt7Cerr~k,u, R. S.. and M. ti. Mt.fera.k~. 1977. Studies of the hemopoietic ~lnicroenviron~azent. V. Erythropoietin-induced release of vast~actjve substance(s) from erythropoietin-re- spon5ive stem cells. Proc. Soc. Exp. Biol. bled. 1156, 181 - 185,

Mc H)a:vi~a, D. G. , and A. S . NIES. 1976. Simultaneous Inca- surenaenb of cardiac output and its d~stribution with micro- spheres in the rat. Cardiovasc. Res. 10, 494 498.

Mra I ~h DCR, S. 1960. Comparative stradies on the adrenergic neurohorrnonal control of resistance and capacitance blood ve\sels in the cat. Acta Physiol. Scmnd. 50 (SuppI. 1761, 1-86.

Mbi%~>t..~ I , P. L.. and N. M. Hor I t.N.rama,. 1971. Cardiac output distribution in the rat: connpasison sf rubidium and microsphere methods. Arn. J . Physiol. 221, 141 7 1620.

M I C ~ D A ~ , S., E. A. As FXXUUFR, F. J . B K U N ~ , A. I,. W I L ~ Y , and N. G. 1 , ~ v r ~ s k u . 1975. Effect of hemodilution on the distribution of renal blood fladw. Circ. Res. 36, 7 1-75.

M C ~ R R A B , .I. F., E. E ~ C O B A R , andE. RAPAPOKI. 1969. Effects s f blood viscosity on hernodynamic responses in acute nor movolernic anemia. (arms. J . PhyGol. 216, 638-642.

Nasriaa, F. S., and M. W. P ~ R J A ~ . 1967. Thc effects of changes in kaematocnt on renal function. J . Physiol* (Lon- don), 193, 513-522.

NFII I , W. A. , J . M. $ X P . ~ I ) I U P . , and S. C. M ~ O K E . 1969. Acute and chronic cardiovascular acfjustrnents to induced aneralia in dogs. Am. J. Phy\iol. 217, 710 784.

PAT ~ K ~ o N , 1. C. S. 195 1 . Effects of chronic anemia on renal functlon in the dog. Am. J . Physiol. 1164, 682-685.

R ~ K ~ ~ s A Y . K., and 9. Br AIII'FKX. 1974. Cardkc output dis- tribution in rats measured by injection of radioactave

naicrospl~eres via cardiac puncture. Can. J . Physirrl. Phar- rnacol. 52, 230-235.

RAKUSAN, K . , and J . R A J H A T I I ~ . 1972. Distribution of car- diac output and organ blood content in anemic and poly- cythernic rats. Can. J. Physiol. Pharmacol. 50, 7663-7 10.

R~,~rx)cr .e , W. L., and E. W. MERRILL. 1970. Experimental polycythemia and hemodilution. Physiologic and rhe8~Bogic effects. J. Thorac. Gardiovasc. Surg. 60, 582- 588.

R~c.rr,\~r)so%, T. Q., and A. $1. GUYTON. 1959. Effects of polycythe~mia and anemia on cardiac output and ofher cir- culatory factors. ?am. J. Physiol. 197. 1 1 hi' 1 1711.

SASAKI, Y., and H. N. WAGNER. 197 1 . Measurement of the distribution of cardiac output in alnanesthetized rats. 3. Appl. Phyciol. 30, 879- 884.

S I ~ I I , H. W., and S. R. EBIIOI 1 . 1950. Renal hacmodyra- amics in congenital cyanotic head disease. Johns FIopt6jlns Hosp. Bull. 86, 58 7 1 .

SH A K F , E. 1952. Primary effects of acute oligcbc~thh.,sl4iiate (PIP

renal function. Am. 3. Physiol. 178, 159 163. SPENVER, M . P. I95 1. Renal hemodyna~~aics in experimental

polycythemia. Am, J . Physisl. 165, 399 406. VA K ~ E K , S. F., C. B. HI(;<;[N,B, and D. FRAP,RL rn. 1974%.

Regional circulatory adjustments to moderate and severe chronic anemia in conscious dogs at rest and during exer- cise. Circ. Res. 30, 731-740.

VALJPE'I-, P., H. WUPPER~, and H. H U T B E N . 1976. Experi- mental and theoretical investigations on intrasplea~ic mir:m- circulation in rats. Irl Microcirculation. Editc.0 by J . Gray- son and W. Zingg. PBenun~ Publishing Corporation, New York. pp, 354 - 355.

Wr~sse, A. B., F. M. CAI I O Y , H. KUIIIA, and H. H. H W H I . B 964. Hemodynamic effects of normovolerraic pol ycy- thelnia in dogs at rest and during exercise. Arn. J . Phyhiol. 207, 1361 1366.

W~.ssuh , L. G. 1969. Physiology of the human kidney. Grune & Stratton, New York. p. 30.

WHI r AKFR, W. 1956. Sorne effects of severe chronic anerrail: csn the circulatory system. Q. $ . Med. 25, 175- 183.

Wol P F , R. R. . and S. M. HORVATBB. 1976. Hemtrdynar-s~ic responxsto acute hematocrit and blood volurne alterations in rats. Eur. J. Appl. Pbysiol. 35, 159 - 166.

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