Cardiac output, oxygen consumption and renal blood flow in essential hypertension

Transcription

1 Clinial Siene (1984) 67, Cardia output, oxygen onsumption and renal blood flow in essential ypertension G M LONDON?, M SAFAR*, J L BOUTHIR? AND R M GITLMANt *Diagnosis Center and t Hypertension Resear Center, Broussais Hospital, Paris (Reeived 29 Deember 198; aepted 2 Februaty 1984) Summary 1 Cardia output, oxygen onsumption, total blood volume and mean irulatory transit time were investigated at rest in men wit sustained essential ypertension in omparison wit normal subjets of te same age and sex 2 In normal subjets and in patients wit ypertension, oxygen onsumption was positively orrelated to ardia output In ypertensives, te slope of te urve was signifiantly sallower wit an inrease in arteriovenous oxygen differene Oxygen onsumption in bot populations was negatively orrelated wit mean irulatory transit time but not wit total blood volume 4 In normal subjets, mean irulatory transit time and arteriovenous oxygen differene were positively orrelated Te orrelation was not signifiant in ypertensive patients 5 Te study suggests important abnormalities in te transport and ost of energy in erytroytes of patients wit sustained essential ypertension Key words: borderline ypertension, ardia output, essential ypertension, oxygen onsumption, renal filtration fration Introdution Cardia output is normal in men wit sustained essential ypertension In several papers (see reviews [l, 2]), it as been sown tat te normal value of ardia output results from several adaptative meanisms involving: (i) a lesser ontribution of neurogeni fators, (ii) an Correspondene: Professor Safar, Centre de Diagnosti, Hopital Broussais, 96 rue Didot, 7514 Paris inreased ontribution of volume fators [] and finally (iii) a derease in venous ompliane [4, 51 Te fat tat tese adaptative meanisms in ypertensives were different from tose of normal subjets {2] suggested tat te relationsip between ardia output and oxygen onsumption ould not be te same in normal subjets and in men wit sustained essential ypertension Te urve relating ardia output to oxygen onsumption as been extensively studied in ypertensive subjets, mainly during exerise [6-91 At rest, an inrease in te arteriovenous oxygen differene as been observed [6, 71 In most ases, te latter finding as been attributed to some degree of ongestive eart failure [6, 71 However, reent studies, mainly based on eograpi findings, did not favour tis interpretation, sine most of te patients wit moderate unompliated ypertension ave only ardia ypertropy wit no ongestive eart failure [lo, 111 Consequently, te inreased arteriovenous oxygen differene ould also be related to periperal as well as to ardia Fators For tis reason, we ave studied ardia output, oxygen onsumption and renal blood flow at rest in patients wit sustained essential ypertension and ompared te results wit tose of normal subjets of te same age and sex Materials and metods Patients Sixty-four male subjets were inluded in te study: 29 normal ontrol subjets and 5 sustained ypertensive patients Te two groups were of similar age (Table 1) All patients were untreated or ad disontinued teir terapy at least 4 weeks before te study Tey were

2 ~ 14 G M London et al TABL 1 Clinial arateristis Values given are means It SM *P < 5 Control Sustained Age (years) 5 k22 9 f 16 Weigt (kg) 721 f t 29* Heigt (m) 17 t t 166 Body surfae area (ml) 185 t * 27* ospitalized for 6 days and plaed on a sodium diet of 1 mmol/day Te subjets were onsidered as normal wen te reason for teir admission was not ardiovasular disease and wen te linial and extensive laboratory investigations were stritly normal Te patients were onsidered to ave sustained ypertension wen teir diastoli pressure was onstantly above 1 mmhg during te untreated ambulatory period Te 64 subjets were submitted to extensive investigations, inluding blood and urinary eletrolyte and ateolamine determinations, endogenous reatinine learane, and timed intravenous pyelograpy All te patients were listed as aving essential ypertension None ad ardia or neurologial involvement In all ases, ongestive eart failure was absent and reatinine learane was above 8 ml/min Clinial arateristis are given in Table 1 Consent for investigations was obtained after a detailed desription of te proedure Te protool was approved by INSRM (Institut National de la Santd et de la Reere MBdiale) Haemodynamis Haemodynami variables were determined on te tird day of ospitalization After overnigt fasting, te patients were brougt to te aemodynami laboratory witout aving reeived premediation A transutaneous ateter was inserted via an anteubital vein into te sublavian vein, for te injetion of indoyanine green dye An 18 gauge tin-walled needle was also inserted into a braial artery for te measurement of intra-arterial pressure and sampling of blood for indiator dilution urves Cardia output was measured at least twie wit te subjet in te supine position aording to te Stewart-Hamilton metod [, 41 Cardia index (CI) was expressed as ml min-' m-2 by orreting for body surfae area Total periperal resistane (dyn s-' m-') was alulated as MAP/CI x 8 were MAP is mean arterial pressure (mmhg) Before te aemodynami study, oxygen onsumption (Vo,) was measured after min rest using a onventional Douglas bag and a low resistane open iruit system [6, 71 Samples of expired air were analysed by te Solander (5 ml) metod Te volume of expiratory air was measured by a gasometer, alibrated frequently by a bell spirometer and te volume onverted to stp Arteriovenous oxygen differene was te ratio between oxygen onsumption (ml min-' m-') and ardia index (ml min-' m-') Total blood volume Before te ardia output measurements, total blood and plasma volumes were measured by te isotopi dilution metod, using radiodinated albumin, as previously desribed and disussed [12] After witdrawal of a ontrol sample, pci were injeted Ten minutes later, a single sample was taken for ounting and volume estimations In 27 of te 64 patients, several onseutive blood samples were taken and ativity was plotted against time Te volume was alulated from te extrapolated ativity at zero time Te volume was lower tan tat obtained from te single 1 min sample but te differene (5 f %) was not signifiant So, te determination wit te single 1 min sample was used as an estimation of intravasular volume in all patients Blood volume was expressed in ml/m2 [5] Aording to te dilution equations [ 11, mean irulatory transit time (s) was alulated as te ratio between total blood volume (ml/m2) and ardia index (ml s-l m-') Renal indies At te same time as blood volume was measured, renal blood and plasma flows were estimated wit '21-labelled ippuran learane (2 pci), by te single injetion metod [12] After a ontrol sample ad been taken, te injetion was made at zero time and five blood samples were olleted between minutes 1 and 2 Radioativity onentrations were plotted against time on semilogaritmi paper Calulations were made by using te one ompartment model, as previously desribed [12] Renal blood flow was alulated from renal plasma flow and paked ell volume Statistial study [ 141 Mean, standard error and orrelation oeffiients were alulated aording to standard statistial metods Regression analyses were arried out by

3 ~~ Oxygen onsumption in ypertension 15 using te least squares metod Differenes in means between two groups were assessed by using te Student's t-test A P value of less tan 5 was aepted as being statistially signifiant Results Mean values Table 1 sows tat age was similar in te two groups of subjets wile body weigt and body surfae area were sligtly inreased in ypertensives (P < 5) Table 2 indiates tat blood pressure and total periperal resistane were signifiantly inreased (P< 1) in ypertensives wile eart rate was witin te normal range Cardia index TABL 2 Haemodynami fators Values given are means f SM ***P <,1 Control Sustained Systoli arterial 127 r21 182i42*** pressure (mmhg) Diastoli arterial 724 f 1 18 f 17*** pressure (mmhg) Cardia index 75 f f 81 (ml min-' m-2) Heart rate (beats/min) Total periperal 74 f f5 72 f *66*** resistane (dyn s-' m-' m-') remained witin te normal range in ypertensives Table sows tat oxygen onsumption was similar in te two groups of subjets Arteriovenous oxygen differene was sligtly but insignifiantly inreased in sustained ypertensives Total blood volume was redued (P < 5) wile mean irulatory transit time remained witin te normal range Renal blood flow and te renal fration of ardia output were signifiantly redued (P < 1 ; P < 5) Correlations Table 4 sows te orrelation oeffiients of oxygen onsumption wit age and aemodynami and renal variables Oxygen onsumption was signifiantly orrelated wit age and ardia index in bot groups (Table 4) For te orrelation wit age, te normotensive and te ypertensive urves were not signifiantly different (Fig 1) For te orrelation wit ardia index, te slope of te ypertensive urve was signifiantly sallower (Fig 2), indiating tat, for te same ardia index level, oxygen onsumption was iger in ypertensive groups Oxygen onsumption was not signifiantly orrelated wit blood volume Te orrelation wit mean irulatory transit time was signifiant bot in te normotensive (r = - 48; P < 1) and te ypertensive groups (r = - 6; P < 5) (Fig ) TABL Oxygen onsumption, total blood volume, mean irulatory transit time and renal indies Values given are means 2 SM *P < 5; ** P < 1 Mean irulatory 474 f 14 transit time (s) Total blood volume 289 f 45 (ml/mz) Oxygen onsumption 181 f57 (ml m-l m-2) Oxygen arteriovenous 5 f 15 oxygen differene (ml/l) Paked ell volume (%) Renal blood flow (ml m-l min-*) Renal fration of ardia output (%) Control Sustained 45 i7 85 f f7 466 t i52* 1849 i i i7 75 i1** 28 fo9* TABL 4 Correlation oeffiients for te relationsip of oxygen onsumption wit age and aemodynami and renal Variables *P<OO5; **P<OO2; ***P<OOl; ****P< 1 Correlations of oxygen Control Sustained onsumption (mlmin-i m-l) wit: Age (years) Cardia index --66**** -44*** 5*** 4**** (mlmin-' m-*) Total periperal -64**** -2 resistane (dyn s-' m-5 m-') Mean irulatory transit -48*** -6** time (s) Total blood volume 17 1 (ml/mz 1 Arteriovenous oxygen 56**** 62**** differene (m1/1 ml) Renal fration of -51*** -6* ardia output (%)

4 16 G M London eta,! riyl I (a) Norrnotensive n I I(b) Hyperterive 25 * * I &e (yea=) Ape (years) FIG 1 Relationsip between oxygen onsumption and age in normotensive (a) and ypertensive subjets (b) Te normotensive and te ypefiansive urves were not signifiantly different (a) r = - 66; y = 1 7~ ; P < 1 (b) r = - 44; y = 1 8~ -I- 2411; P< 1 (------) Mean regression line of normotensive subjets n 5 a 45 la) Normotensive (b) Hypertensive,,, g 5 zl B J Oxygen onsumption (ml mir- m-z) Oxygen onsumption (ml min- m-z) FIG 2 Relationsip between oxygen onsumption and ardia index in normotensive (a) and ypertensive subjets (b) Te slope of te ypertensive urve (812 t 21) was signifiantly sallower tan tat of te normotensive urve (141 f 2) (P< 1) (a) r = 5; y = 141~ ; P< 1 (b) r = 54; y = 812x -I ; P< 1 (------) Mean regression line of normotensive subjets, In ontrols, mean irulatory transit time was uxygen onsumption was negatively orrelated - 1 _-1 I I I n rn,,, nr, :rl *-A-l --:-L--l ---:-*---- :- ---*-l- I _ positively orreiarea wirn age tr = u 5~;r < UUSJ Wllll LULal ~txl~ii~ld1 IGblbLallLC 111 CUIllIUIb (r and arteriovenous oxygen differene (r = 42; -64; P< 1) but not in ypertensives P < 5) Te latter orrelation existed even for a (r=-2) Bot in ontrols and in yperonstant age (partial orrelation) In ypertensives, tensives, arteriovenous oxygen differene and no signifiant orrelations were observed between oxygen onsumption were positively orrelated mean irulatory transit time and age or mean (Fig 5) However, for a given oxygen onsumpirulatory transit time and arteriovenous oxygen tion, arteriovenous differene was onstantly differene (Fig 4) iger in ypertensives

5 Oxygen onsumption in ypertension 17 (a) Normotensive b) Hypertensive 7- * : S 6 *8 ** * * a 4 * Oxygen onsumption (ml min-' m-') Oxygen onsumption (ml min-' m-l) FIG Relationsip between oxygen onsumption and mean irulatory transit time in normotensive (a) and ypertensive subjets (b) (a) r = - 48; y = 1 lx 4-671; P< 1 (b) r = - 62; y = 88~ 4-642; P< 5 (------) Mean regression line of normotensive subjets v lor a 2 4 m I) Age (years) Age (years) io 4 5 sb 7 Mean irulatory transit time (s) do!-jb 6 7 Mean irulatory transit time (s) FIG 4 Relationsip of mean irulatory transit time wit age in normotensive (a) and ypertensive subjets (b), and wit arteriovenous oxygen differene in normotensive () and ypertensive subjets (d) (a) r = 9; y = 24~ 4-87, P< 5; (b) r = 28; y = 21~ -I- 87; not signifiant; () r = 42; y = 44~ 4-292;P< 2; (d) r = ; y = 2~ -I- 79; not signifiant (------) Mean regression line of normotensive subjets

6 18 G M London et al Oxygen onsumption was negatively orrelated wit te renal fration of ardia output (Table 4) Te orrelation was less signifiant (r = - 6; P < 5) in ypertensives tan in ontrols (r = -OSl;P<OOl)(Fig 6) Disussion In te present study, ardia index and oxygen onsumption were found to be similar in normal subjets and in patients of te same age and sex wit sustained essential ypertension In bot groups, a strong positive orrelation was observed 9 between ardia index and oxygen onsumption measured at rest Sine a negative orrelation was observed between oxygen onsumption and te renal fration of ardia output, te positive orrelation between oxygen onsumption and ardia index onerned mainly te extrarenal part of ardia output Te slope of te urve relating ardia index to oxygen onsumption was signifiantly sallower Oxygen onsumption (ml min-' m-') in ypertensives For a given ardia index, oxygen FIG 5 Relationsip between oxygen onsumption onsumption was iger in patients tan in and arteriovenous oxygen differene in bot ontrols Finally, arteriovenous oxygen differene groups Te interepts of te two urves were was found to be sligtly elevated in patients wit signifiantly different (261 k 58 vs 227 It: 57; sustained essential ypertension Comparable P < 2) Normotensive (-- -): r = 56; y = results ave been observed by Sannerstedt [7] and ~; P<OOOl Hypertensive (u): Lund-Joansen [6] during exerise, bot in rossr=62;y= x;P<1 setional [6, 71 and in longitudinal [15] studies Tus, in ypertensive subjets, oxygen demand is satisfied in te presene of a normal ardia output by an inrease in oxygen extration (Fig 5) Cardia output is bot te ratio between oxygen onsumption and arteriovenous oxygen differene and te ratio between total blood volume and mean irulatory transit time [16] Sine oxygen onsumption was found to be related to mean irulatory transit time rater s 5 5 * a L g 2 - i- m G 15 (a) Normotensive 1 5 (6) Hvpertensive 5 - a a $ 25-2 g 2- - * m " - 15 p?, 2 ia 'Oi Oxygen onsumption (ml minp mp) Oxygen onsumption (ml min-' m-') FIG 6 Relationsip between oxygen onsumption and te renal fration of ardia output in normotensive (a) and ypertensive subjets (b)(a) r = 51 ; y = 6~ 4-4; P< 1 (b) r = 6;~ = 6~ + 2;P< 5 (------) Mean regression line of normotensive subjets

7 Oxygen onsumption in ypertension 19 tan in blood volume (Fig ), a relationsip was expeted to our between transit time and arteriovenous oxygen differene In normal subjets, an age-independent relationsip between tese two variables as been observed: te sorter te transit time of erytroytes, te lower te arteriovenous oxygen differene and, onsequently, te more redued te apaity of erytroytes to provide oxygen to tissues In te present study, su a pysiologial adaptive meanism between te transit time and te liberating apaity of erytroytes was not observed in patients wit sustained essential ypertension Mean irulatory transit time is well known as an index of te veloity of erytroytes witin te ardiovasular iruit [ 161: te sorter te transit time, te iger te veloity of erytroytes Indeed, te veloity of erytroytes as been sown to be modified in patients wit sustained essential ypertension In partiular, veloity is redued wen te setion of large arteries is inreased, as sown in te braial artery [17], and inreased in te resistane vessels wose alibre is narrowed Veloity is an important parameter sine te kineti energy of erytroytes depends on power two ofveloity [16] On te oter and, it must be stressed tat te inreased arteriovenous oxygen differene of ypertension reflets a redution in oxygen ontent of erytroytes in te venous side of te irulation [6, 71 and onsequently a modifiation in te oxygen transport aross te membrane of tese intravasular ells Indeed important abnormalities in ation transport aross te membranes of erytroytes ave been also reently reported in ypertensives [18] Tus, te results of te present study ould suggest tat te loss in te relationsip between transit time and arteriovenous oxygen differene in ypertensives reflets important anges in te transport and ost of energy in erytroytes of patients wit sustained essential ypertension Weter tese modifiations are ause or onsequene of ypertension is unknown Su a subjet as been poorly investigated in man and requires furter study Aknowledgments Tis study was supported by a grant from te Institut National de la Sant6 et de la Reere M6diale (INSRM), te Assoiation pour YUtilisation du Rein Artifiiel (AURA) and te Wl6gation G6n6rale de la Re6re Sientifique et Tenique (DGRST), Paris We tank Mrs Marie- Jose ggers and Mrs Dani6le Saque for teir exellent tenial assistane Referenes 1 Lund-Joansen, P (198) State of te art review: aemodynamis in essential ypertension Clinial Siene, 59, 4s-55s 2 Safar, M, Weiss, YA, London, GM, Simon, AC & Cau, NP (1981) Hemodynami anges in mild early ypertension In: Hypertension in te Young and te Old, pp d Onesti, G & Kim, K Grune and Stratton, New York Cau, NP, Safar, M, Weiss, YA, London, GM, Simon, AC & Milliez, PL (1978) Relationsip between ardia output, eart rate and blood volume in essential ypertension Clinial Siene, 54, Safar, M, London, GM, Levenson, JA, Simon, AC & Cau, NP (1979) Rapid dextran infusion in essential ypertension Hypertension, 1, Cau, NP, Coleman, TG, London, GM & Safar, M (1982) Meaning of te ardia output-blood volume relationsip in essential ypertension Amerian Journal of Pysiology, 24, Lund-Joansen, P (1967) Hemodynamis in early essential ypertension Ata Media Sandinavia, 18 (Suppl), Sannerstedt, R (1966) Hemodynami response to exerise in patients wit arterial ypertension Ata Medial Sandinavia, 18 (Suppl 458), Amery, A, Julius, S, Witlok, LS & Conway, J (1967) Influene of ypertension on te emodynami response to exerise Cirulation, 6, Julius, S, Amery, A, Witlok, LS & Conway, J (1967) Influenes of age on te ernodynami response to exerise Cirulation, 6, Sen, S, Tarazi, RC & Bumpus, FM (1977)Cardia ypertropy and antiypertensive terapy Cardiovasular Resear, 5, Safar, M, Lener, JP, Vinent, M, Plainfosse, MT & Simon, AC (1979) oardiograpi dimensions in borderline and sustained ypertension Amerian Journal of Gzrdiology, 44, Safar, M, London, GM, Weiss, YA & Milliez, PL (1977) Altered blood volume regulation in sustained essential ypertension: a ernodynami study Kidney International, 8, Yu, NP (1969) Pulmonary Blood Volume in Healt and Disease, pp Lea Febiger, Piladelpia 14Croxton, F & Cowden, DS (1941) Applied General Statistis, pp Prentie Hall, New York 15 Lund-Joansen, P (1979) Spontaneous anges in entral emodynamis in essential ypertension - a 1 years' follow up study In: Hypertension: Determinants, Compliations and Interventions, pp d Onesti, G & Klirnt, Cr Grune and Stratton, New York 16 O'Rourke, MF (1982) Arterial Funtion in Healt and Disease, p 141, p 156, p 159, p 178, p 19 Curill Livingstone, dinburg 17 Safar, M, Peronneau, J, Levenson, J & Simon, A (1981) Pulsed Doppler: diameter, veloity and flow of braial artery in sustained essential ypertension Cirukztion, 6 (2), Meyer, P, Garay, RP & DeMendoqa, M (198) Ion transport systems in ypertension In: Hypertension, Pysiopatology and Treatment, 2nd edn, pp MGraw-Hill, New York