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Impairment of urate excretion is an important mechanism for hyperuricemia in patients with heart failure
60, Journal of Cardiac Failure Vol. 5 No. 3 Suppl. 2 1999
P-29
P-30
EFFECTS OF POSITIVE ENI)'EXP[RATO.RY PRESSURE (PEEP)"ON. THE RIGHT VENTR[OULAR D[ASTQL[C EUNCT[QN IN PATIENTS WITH LEET CARDIAC FAILURE
IMPAIRMENT O.F, URATE EXCRETION IS AN IMPORTANT MECHANISM FOR HYPERURICEMIA IN PATIENTS WITH HEART FAILURE
Hideyo K.uga.~, Hjros.i Harasawa!, TakaakJ. Nakamoto~ [sap "l-aguchi~ y0sfumi Hori.kawaI Noboru Kar~eko~, Hideaki Sakio2 Department: qf Cardiology arg,d:Pneumology~ ; [ntesive Care Unit 2, D.okk~(,oUniversity School.of Medicine
Shuichi Osaki, Tom Kinugawa, Akihil:o Endo, Masahiko Kato, Tatsuo Kato, Kazuhide Ogino, Osamu Igawa, Ichim Hisatome, and Chi0ki Shigcmasa. The 1st Dept. of Internal Medicine, Tottori University, Yonago 683-8504, Japan.
[Purpose],Th~re have been no reports on the effect of ppsitive endexpiratou/pressure (PEEP) on the right ventricular diastolic function in
B a c k g r o u n d Hypcrnricemia is often observed in patients with heart failure (HF), and increased uric acid production due to hypoxia has been considered as a possible mechanism. This study determ,i~aed~ impaired_urate excret~n contributes to the hyperuricemia in patients with HF. M e t h o d s Serum uric acid (Sua: mg/dl) and unnary urate excretion (Uua: tug,day) wore measured, and fractional uric acid excretion (Cua/Ccr: %) was calculated from renal clearance tests for uric acid (Cua: ml/min) and creatinine (Ccr) in 49 patients with HF (NYHA 1: 19, II: 21, III: 9) and 16 controls. R e s u l t s See Table (mean±SEM, *p<0.05 vs. Control, #p<0.05 "¢s NYHA I). Furosemide dose (F:. rag/day), in.creasedas HF worsened. Sua was significantly-increased in class II-II'I HF patients compared tO confrols. Patientswkh HF had decreases in Uua, Cua, and Cua/Cer. When all subjects were examined together-, S,ua was negatively eorretate4with Cua (r=-0.73, p.<0..0O01}, and with CualCcy-(r-.-O.6.Q, P,<0,.0001)... C o n c l u s i o n s Sua levels incre~tsed as, HF worsened, patien,~s with HF had "me,pairment of urate excre6on, but did not exhibit uric acid. overproductiom Close association betwee.n the degree of imp~j,red urate exc[etign and Sua level s u.ggests that decreased urate excretion is resoonsible for fivoeri_iricemia in oatients With-HF. .... F Sii'a . . . . UU~i " C u a Cua/Ccr
pat ~nts Wth eft;o,ardac fa u(e TherefOrethe ri_ghtvent~cul~r dia~ol.ic ft~ncti:90' waz observed b~(. DoppJer e~h0ca(di0grapby d.uring .P,EE.P. ~Subject~s.and~MeLhods~.Thesu.bjects, were 24 p.atients who were being cared"for at th e inteslve care unit and who required respirators. They were:l.0 without cardiopulmonary disease (7 men and 3 women ;. meaD age, 54 +/- 11 years , N group) and 14 with left. cardi.ac failum (7 men and 7 women; mean age, 66 +/- 7 years, CHF group). For the CHF group, E w0ve, A wave. their ratio (E/A) , E wave dace era:Lion ti,me (DcT)., isovolumic (elaxation time (IRT) were determined before PEEP and re!lowing; 3{J mjn.t~tes qf PEEP 5cmH2O , 10cr0H20 ,. IS.er0H20 . Simu taneous y hemo=dynamc. parameters were rT~asuredby,u,sinE'e~e SyYa0~=Gapzca.thpte(.[ResuJts~l ~0tb DgT an,d .IRTfor th e CHF group were shortened n compar so0 w th the N g~'oup(144 +]- 41, vs 204 +/46 ms, p = Q.005~; 59 +,/- li2, ys 88: +/,- t:9 ms, I? --=0.0Q~)3') 2,. For I~/A, before PEEP De I" IRT, right atrial; (RA) and'tota.pu mona~ vascular resistance (TPR) f,or the OfF group no corre at on was fout?.d,amour E/A, IRA, aod TP~:; but negati,v,eco(rela,t,i.o.nwas~f~und between DcT 0,n~dT,pR, {h = 0 81 p, = 0 QQO5)@nd:[RT and T~pB:(g = 0..7~ p.- 0.002),. 3,. . Comp0re~ w.i~h:the da~, be:fore PE.~_p, E/K ~as redut~ed, ;DcT W..as i sigr~ificantly (p - 0 04). sho.tt-e~ed:at pI~EP liSqr0..H20 ; aad; [IRT ~(as prolonged .~Co~elu.s.ion~Thes~tudysuggested th0t PEEP e;
NYHAII" 25_+5 7,.2_+0;5", ~26~36" 4.3_+0.5* 6.8-+0.7* NYHAtlt 40_+8# 7.6_+0.7*- 336-+27* 3.3-+0.5* 6.6-+1.4"
P.32
P-31 Oj~J¢
Control, . . . . 5.-5~:2-600,-+-34 ~ 7.5~0,6- ).0.7-+1.3 NYHAI' 13---3 6.5±0.4 369-+34* 4.1-+0.7" 6.1_+0.9"
NEpHRCPATHY
IN cHRoNIC
cONGESi"IVE
ROLE OF LEUKEMIA INHIBffOR¥ FACTOR (LIP-)IN DIABETIC CARDIOVASCULAR DISORDER
H E A R T FAILURE
Na0fumi Ikeda, Hjdetomo Nakamo~, Hirokazu Okada, Souichi Sugahara, Hiromichi Suzuki D.ep.artmqnt of Nephr0!ggy:, Saitar0a Medical Scho0!, Saitama, Japan The purpo.s.e of this stqdy, was to identify the factors thatcontribute to, the development of diabetic nephropathy in congestive heart failure. We studied: 40 patients comprom zed • with; dja~etic (DM)(20) or non:diabetic N,DM) nephropathy with c onges~,v,e heart fai!ure (CHF), During 24 r0on,t,_hs, every month b.19oc pressure apd~ lev.els, of serum, creatin!ne were cheoked in- both group. Every. 6 rn0nths ejection fraction (EF) was .rne~mtJr,ed Blood; pr~essure was wffH c0ntr,O led in both groups with ACE nh b tore and ca c u m antagon sts. Despite of well controlle d blood Pre~,~ure during: the studY. 2 patients in DM group and 1 patient in N=DM group were died with acute myocardial infarction and 1, patient in DM group and 1 patient in N-DM groplp were died witil acute cereb,al infarction. 6 patients in DM group, and 4 patients in N-DM group were introduced to hemodialysis therapy. Serial. changes in EF were~ simi!ar~ betwee.n two groups througbqut the study, The rate of progression of renal dysfunct!on was faster in DM group, thanJn N-DM group. From these results regardless of cardiac function diabetic, nephr0Pathy per se is an important factor for deterioration of renal function.
Toshiki Iwate(1), Seiji Ito(t), Shuji Mukee(1), 8huichi Aoki(1,), Takashi Kategiri(1)~Mitsuham Kawemura(2)~Kazumi Chlyeda(2), Nobum Konno(2) (1)Third Department of Internal Medicine, Showa University,Tokyo 142-8666, Japan
(2)Departmentof Cardiology, Yamacashi Red Cross Hospital Yamanash1401-0002, Japan [,Purpose] Various ~fiemmatery cytokines are thought to play, an important role in the pathogat~tic mechanisms of diabetic complication. We investigated changes of leukemia inhibitoryfactom (UP--), a family of IL-6, in diabofic nephmpathy patientswith hemodlalysis. [Metho(~] The subjects were 60 hemndialysispatients (liD) and 20 healthy volunteersas control. The HD patients were classified into two groups (DM-HD, 20 patients:with diabetic nephropathy; NDM-HD, 40 patients with n o ~ i c nephropathy). We defined Angina. padiods, myocardial infarction and cardiac failure as cardiac events and then evaluated the ratio of cardiac events in each group. The ACE (I/D) polymoqohismwas typed with PCR, an.dthe LIFwesmeasuredbytheELISArnothed: [Flasults] The cardiac event ratio was 45.5% in DM-HD and 17.1% in NDM-HD. The blood cpncentratinn of LIF was 0.36_+0.04 pg/ml inthe control group, In DMHD; a significant difference was observed between the prer and post-
hemedielysis levels of bluadLIF..(0.374-0.,06 vs. 0,45-+0.1!). In corCaast, there were no significant differences between the 10re-and post-levels in NDM-HD (0.38±0.06 vs. 0.39±0.09). In addition,the bloodconcentration of L!F tended to behigher at post~=mtx~alysis than at Ixe-hemodlalysls in subjects with ID and DD ~ of ACE IConclusion]HD patients due to diabetic nephropathy had higher cardiac events ratios than those due to non-diabetic diseases. LIF, which has a crosstalk with angiotenshin II and other componentsof the renin-angintensinsystem, is Ill(elyto play a role in these events as a diabetic cardiovascular disorder.
P-29
P-30
EFFECTS OF POSITIVE ENI)'EXP[RATO.RY PRESSURE (PEEP)"ON. THE RIGHT VENTR[OULAR D[ASTQL[C EUNCT[QN IN PATIENTS WITH LEET CARDIAC FAILURE
IMPAIRMENT O.F, URATE EXCRETION IS AN IMPORTANT MECHANISM FOR HYPERURICEMIA IN PATIENTS WITH HEART FAILURE
Hideyo K.uga.~, Hjros.i Harasawa!, TakaakJ. Nakamoto~ [sap "l-aguchi~ y0sfumi Hori.kawaI Noboru Kar~eko~, Hideaki Sakio2 Department: qf Cardiology arg,d:Pneumology~ ; [ntesive Care Unit 2, D.okk~(,oUniversity School.of Medicine
Shuichi Osaki, Tom Kinugawa, Akihil:o Endo, Masahiko Kato, Tatsuo Kato, Kazuhide Ogino, Osamu Igawa, Ichim Hisatome, and Chi0ki Shigcmasa. The 1st Dept. of Internal Medicine, Tottori University, Yonago 683-8504, Japan.
[Purpose],Th~re have been no reports on the effect of ppsitive endexpiratou/pressure (PEEP) on the right ventricular diastolic function in
B a c k g r o u n d Hypcrnricemia is often observed in patients with heart failure (HF), and increased uric acid production due to hypoxia has been considered as a possible mechanism. This study determ,i~aed~ impaired_urate excret~n contributes to the hyperuricemia in patients with HF. M e t h o d s Serum uric acid (Sua: mg/dl) and unnary urate excretion (Uua: tug,day) wore measured, and fractional uric acid excretion (Cua/Ccr: %) was calculated from renal clearance tests for uric acid (Cua: ml/min) and creatinine (Ccr) in 49 patients with HF (NYHA 1: 19, II: 21, III: 9) and 16 controls. R e s u l t s See Table (mean±SEM, *p<0.05 vs. Control, #p<0.05 "¢s NYHA I). Furosemide dose (F:. rag/day), in.creasedas HF worsened. Sua was significantly-increased in class II-II'I HF patients compared tO confrols. Patientswkh HF had decreases in Uua, Cua, and Cua/Cer. When all subjects were examined together-, S,ua was negatively eorretate4with Cua (r=-0.73, p.<0..0O01}, and with CualCcy-(r-.-O.6.Q, P,<0,.0001)... C o n c l u s i o n s Sua levels incre~tsed as, HF worsened, patien,~s with HF had "me,pairment of urate excre6on, but did not exhibit uric acid. overproductiom Close association betwee.n the degree of imp~j,red urate exc[etign and Sua level s u.ggests that decreased urate excretion is resoonsible for fivoeri_iricemia in oatients With-HF. .... F Sii'a . . . . UU~i " C u a Cua/Ccr
pat ~nts Wth eft;o,ardac fa u(e TherefOrethe ri_ghtvent~cul~r dia~ol.ic ft~ncti:90' waz observed b~(. DoppJer e~h0ca(di0grapby d.uring .P,EE.P. ~Subject~s.and~MeLhods~.Thesu.bjects, were 24 p.atients who were being cared"for at th e inteslve care unit and who required respirators. They were:l.0 without cardiopulmonary disease (7 men and 3 women ;. meaD age, 54 +/- 11 years , N group) and 14 with left. cardi.ac failum (7 men and 7 women; mean age, 66 +/- 7 years, CHF group). For the CHF group, E w0ve, A wave. their ratio (E/A) , E wave dace era:Lion ti,me (DcT)., isovolumic (elaxation time (IRT) were determined before PEEP and re!lowing; 3{J mjn.t~tes qf PEEP 5cmH2O , 10cr0H20 ,. IS.er0H20 . Simu taneous y hemo=dynamc. parameters were rT~asuredby,u,sinE'e~e SyYa0~=Gapzca.thpte(.[ResuJts~l ~0tb DgT an,d .IRTfor th e CHF group were shortened n compar so0 w th the N g~'oup(144 +]- 41, vs 204 +/46 ms, p = Q.005~; 59 +,/- li2, ys 88: +/,- t:9 ms, I? --=0.0Q~)3') 2,. For I~/A, before PEEP De I" IRT, right atrial; (RA) and'tota.pu mona~ vascular resistance (TPR) f,or the OfF group no corre at on was fout?.d,amour E/A, IRA, aod TP~:; but negati,v,eco(rela,t,i.o.nwas~f~und between DcT 0,n~dT,pR, {h = 0 81 p, = 0 QQO5)@nd:[RT and T~pB:(g = 0..7~ p.- 0.002),. 3,. . Comp0re~ w.i~h:the da~, be:fore PE.~_p, E/K ~as redut~ed, ;DcT W..as i sigr~ificantly (p - 0 04). sho.tt-e~ed:at pI~EP liSqr0..H20 ; aad; [IRT ~(as prolonged .~Co~elu.s.ion~Thes~tudysuggested th0t PEEP e;
NYHAII" 25_+5 7,.2_+0;5", ~26~36" 4.3_+0.5* 6.8-+0.7* NYHAtlt 40_+8# 7.6_+0.7*- 336-+27* 3.3-+0.5* 6.6-+1.4"
P.32
P-31 Oj~J¢
Control, . . . . 5.-5~:2-600,-+-34 ~ 7.5~0,6- ).0.7-+1.3 NYHAI' 13---3 6.5±0.4 369-+34* 4.1-+0.7" 6.1_+0.9"
NEpHRCPATHY
IN cHRoNIC
cONGESi"IVE
ROLE OF LEUKEMIA INHIBffOR¥ FACTOR (LIP-)IN DIABETIC CARDIOVASCULAR DISORDER
H E A R T FAILURE
Na0fumi Ikeda, Hjdetomo Nakamo~, Hirokazu Okada, Souichi Sugahara, Hiromichi Suzuki D.ep.artmqnt of Nephr0!ggy:, Saitar0a Medical Scho0!, Saitama, Japan The purpo.s.e of this stqdy, was to identify the factors thatcontribute to, the development of diabetic nephropathy in congestive heart failure. We studied: 40 patients comprom zed • with; dja~etic (DM)(20) or non:diabetic N,DM) nephropathy with c onges~,v,e heart fai!ure (CHF), During 24 r0on,t,_hs, every month b.19oc pressure apd~ lev.els, of serum, creatin!ne were cheoked in- both group. Every. 6 rn0nths ejection fraction (EF) was .rne~mtJr,ed Blood; pr~essure was wffH c0ntr,O led in both groups with ACE nh b tore and ca c u m antagon sts. Despite of well controlle d blood Pre~,~ure during: the studY. 2 patients in DM group and 1 patient in N=DM group were died with acute myocardial infarction and 1, patient in DM group and 1 patient in N-DM groplp were died witil acute cereb,al infarction. 6 patients in DM group, and 4 patients in N-DM group were introduced to hemodialysis therapy. Serial. changes in EF were~ simi!ar~ betwee.n two groups througbqut the study, The rate of progression of renal dysfunct!on was faster in DM group, thanJn N-DM group. From these results regardless of cardiac function diabetic, nephr0Pathy per se is an important factor for deterioration of renal function.
Toshiki Iwate(1), Seiji Ito(t), Shuji Mukee(1), 8huichi Aoki(1,), Takashi Kategiri(1)~Mitsuham Kawemura(2)~Kazumi Chlyeda(2), Nobum Konno(2) (1)Third Department of Internal Medicine, Showa University,Tokyo 142-8666, Japan
(2)Departmentof Cardiology, Yamacashi Red Cross Hospital Yamanash1401-0002, Japan [,Purpose] Various ~fiemmatery cytokines are thought to play, an important role in the pathogat~tic mechanisms of diabetic complication. We investigated changes of leukemia inhibitoryfactom (UP--), a family of IL-6, in diabofic nephmpathy patientswith hemodlalysis. [Metho(~] The subjects were 60 hemndialysispatients (liD) and 20 healthy volunteersas control. The HD patients were classified into two groups (DM-HD, 20 patients:with diabetic nephropathy; NDM-HD, 40 patients with n o ~ i c nephropathy). We defined Angina. padiods, myocardial infarction and cardiac failure as cardiac events and then evaluated the ratio of cardiac events in each group. The ACE (I/D) polymoqohismwas typed with PCR, an.dthe LIFwesmeasuredbytheELISArnothed: [Flasults] The cardiac event ratio was 45.5% in DM-HD and 17.1% in NDM-HD. The blood cpncentratinn of LIF was 0.36_+0.04 pg/ml inthe control group, In DMHD; a significant difference was observed between the prer and post-
hemedielysis levels of bluadLIF..(0.374-0.,06 vs. 0,45-+0.1!). In corCaast, there were no significant differences between the 10re-and post-levels in NDM-HD (0.38±0.06 vs. 0.39±0.09). In addition,the bloodconcentration of L!F tended to behigher at post~=mtx~alysis than at Ixe-hemodlalysls in subjects with ID and DD ~ of ACE IConclusion]HD patients due to diabetic nephropathy had higher cardiac events ratios than those due to non-diabetic diseases. LIF, which has a crosstalk with angiotenshin II and other componentsof the renin-angintensinsystem, is Ill(elyto play a role in these events as a diabetic cardiovascular disorder.