Anker, S.D.

Coats, A.J.S.

Pllaum, C.-D.

Poole-Wilson, P.A.

Strasburger, C.J.

Volterrani, M.

Elsevier - Publisher Connector 

204A AI{,";TRACI"S -. Oral JACC Fchnmry I~)ql'l 
with antibodies to PKC-/I1 and -/+2 was slight in NF myocyte, but intense in 
the myocytes of fallod LV, In situ hybridization revealed Increased expression 
ot PKC-ttl and/~2 mRNA in cardtomyocytos ot failed human heart tlssuo, 
Total PKC activity wee incroasod in membrane trectlonn from failed hoarts 
11219 ~ 188 v~, 609 ~ 171 pmol/mln/mg protein; tsllod va, NF; P • 0,05). 
LY333531, I~ aolectlve Inhibitor of PKC.tt, significantly decroaned PKC ~ctlvlty 
from failed he~rls by 24%, 
Concl~tslon~: PKC.II1 end .112 are elevated In tmled human heart, and 
inhibition of PKC.II may represent a novel therapeutic approach to henri 
tnlluro, 
2:30 
~ rowth Hormone Raals tanoo In Chrenl¢ Heart 
Failure 
SID, Ankor, M, Voltnrranl, C.D Ptlnt~m, P,A, PooIo-WII~on, 
C,J, Stmsburger, A,J,S, Co~ts, Cardiac Medicine, NHLI London, UK; Dept 
Of CnMiotolgy, Git,~f~¢l;lO, It~ly 
Acquired growth hormlDnlD (GH) rem~tanco occurs In t~evsro illness and 
cachaxta, and mrty explain ll~e different responses to OH in mlDent st~!d. 
~ns el p~,lient~l with chronic hlDrlrt niluro (CHF), 
In 72 CHF p~tianf~ (~ge 61 t ly ,  po~k VO: 16,5 ~ 0,7 ml/kglmtn) 
and ~0 healthy contml~ ([Con] ~ t 2y, p ,. 007) the L3H - IGF.I axis 
was Sh, ldtod tn ml~lilDn to IGF binding protein 3 (IGFBP-3) and GH.binding 
protein (GH.BP) (cenlrul~ vs CHF dilferenct~s = NS), The CHF patients were 
sub-dovidod ~CCordmg to cacholDti~ (tel, • 7,5% wolgbt loss over ~ 6 months) 
or non.c~ch0ctic (no) ~fate, The iooIGF.I/GH ratio (O AM) w~s c~lculatod 
~ Index oi GH sensitivity, and was round to correlate well with mean OH 
overnight levet.'~ 111 CHF patients', blood samples for 8 hm, eve~ 20 ram, r = 
-0,60, p m 0.05), and mlDan overnight IoglGF-ItGH ratio (r ,. 072, p m 0,01 ). 
Cor~ n¢CHF OCt'iF nCCHF ~,~. cCHF ~,..s cCHF ~,,'s 
o + ~6 n ~ ~1 n = 21 Co~ tPf Con (pf ncCHF ttrt 
tet,~l GH tngtml) t~ID3 1~t03 ~3113 N~ . 0 01DOt . 0 I0001 
intact GH (ng!m!t 05101 04!['11 t6tOS NS (~ IDnz~r ID 0017 
tGF.t (n&~'T~t) 1511~ 15SIS 12410 N~ 0169 000 
log IGF,I/GH ~ 7~ID~ 20~ID 1 17~0~ NS ID I60162 00001 
IOFBP-3 (+,g;ml) 36+ID I 37+01 31~0~ N,~ ID I012 e012 
GH.BP (pmolflt 8.~2 ~B3 950~ S4 6107 t6,t NS 006 O IDI047 
mo~n :t SEM; NS = p 0 20 Sample tmw ID AM 
Correlations: log IGF-I/GH vs %ideal weight (Con: r = 0,.23, p = NS: CHE 
r = 0.54, p - 0.00Or), and t..s GH-BP (Con: r = 079; CHF: r = 0,61, both p - 
0.0001:nc:r=0,50, p- 0,01; c: r = 0.68, p 0001). 
Cnchectic patients w~th CHF show the b~ochom~cal Ioaturos et acquired 
GH resistance possibly duo to a down regutabon of Gtt roceptom The 
presence at GH resistance may ~nlluonce the response to GH therapy and 
should be assessed peer te tro~Hment 
2 :45  
~ T h e  Growth Hormone Secretagogue Hexarelln 
Improves Cardlsc Function In Rats After 
Experimental Myocardlal Infarct ion 
A, Tivosten, E. Botlano, V. Kujacic, K. Caidahl, X.Y. Sun, T. Hedner, 
A Hjatmarson, B-A Bengtsson, J Isgnnrd, Re.~eamh Center of 
Endocnnology and Metabolism, Sahlgrenska University Hospital, Stt~ttlen 
Background; Accumulating evidence indicate that growth hormone (GH) can 
enhance cardiac performance both tn rats after experimental myocardial 
infarction (MI) and in patients with congestive heart failure. Hexarelin is 
one of several synthetic compunds with capacity to stimulate GH secretion 
in animals and humans. The aim of the ?r:sent study was to investigate 
if administration ef Hexarelin could improve cardiac function in rats after 
oxpenmontal MI. 
Methods: Male rats were treated for two weeks with either Hexarolin in 
a dose of 5 or 50 ~9 • kg ~, recombinant human GH (rhGH) in a dose 
of 1 mg , k9 ~ or saline injected s.c twice daily four weeks after ligation 
of the left coronary artery Intact rats were used as controls. Transthoracic 
echocardiography was performed before and alter the treatment period. 
Results: Stroke volume (SV) was increased 49% 10% by rhGH, 53% ~: 
16% by Hexarelin 10 t,g kg ~ . day ~. and 55% = 2~% by Hexarolin 100 ~g 
kg ~ day ~, (p .  0,05 vs baselinc). Ca,disc output (CUt was increased 
62% ± 21% by rhGH, 48% ± 19°,o by Hexarettn 10 I~g kg ~ • day ~ and 
51% :~ 13% by Hoxaretin 100 ,,g. kg t • day ~, There were no effects on 
SV and CO in the saline treated groups. 
Conclusion: HexarlDlin improves cardiac pedormance to a similar extent 
as exogenously administered rhGH in rats after experimental myocardial 
infarction. This may have clinical =mptications if beneficial effects can also be 
obtained in patients with congestive heart failure. 
3:00 
~']  Renal and Effects of Growth Hemodynamlc 
Hormone Treatment In Experimental Heart Failure 
R. Witlonbrock, I, Paget, M. Schauermann, K,-J, Osforziol. R. Dielz 
Franz.Voll~.KIInik, Berlin, Germany 
Chronic growth hormone (GH) treatment is a now approsch for the Ihorapy 
of heart failure. We nn~lyzod whether c~trdlac and mnst function could I~ 
improved by chronic applie~tion of GH in experimental heart fmlura, Manifest 
henri tmluro was induced by .~ largo ~ortocavctl shunt in male Wist~r rats 
which wore tra~ted with recombinant human GH (2 mgtd~y s,¢,) for 30 
dtWs, We ~nyi~tod ron~t oxcmton/lungfish by g~ing rrmtabolio genes ~ed 
measured cardiac pressures ~nd contractility, 
Rats frosted with GH developed ,1 significant higher body weight a!msdy 
attar 0 d~ys of treatment, Allot 30 d~ya, the GH treated rats weighed 333 
t g vs, 305 .t: 0 g in plneobo trar~ted shgflt~ rats (p • 0,01), The tatative 
heart weight increased in situated rats from 319 t ? to 583 ~ 40 mg!100 
g, compared 1o sham operated controls, but was net in l lue~ by GH 
tm~lma_nl C,rdiac onddinslolic pressures were o!evuted in ~hunted trats 
compared to sham.operated controls, but worn not medilied by GH Slm=!a~, 
catdialD contractility (dPldt) wa~ Iowor in shunted rats (4820 :~ 210 vs, 5400 
t 433 mmHgisoc, p - 0,05) and was 001 improved by OH therapy Water 
intake w~s net different bolweon GH. and placebo treated shunted an*mats 
Wdte~ aed sodium excretion, however, was enhancer'1 by GH: natnurosis 
Increased Item 154 , 0.06 to 2,01 ~ 0.10 mmol;d (p - 005) and diurests 
from 17,4 t P,01023,1 t 3.0mild(p- 0,05). 
Our results suggest thai chronic treatment with growth hormone m=ght not 
improve cardiac 16nction in this mode! of heart lailure but seems to have a 
beneficial effect on water and sodium homeostasis, 
3:15 
L~51~ 17/3.Estred,ol Protects  Against ,he Oevelopment ot 
Pressure Overload Cardiac Hypertrophy in Rats 
L.-R Gas, B -Q Zhu. Y.-P Sun, RE. Sievets. TM. Chou. R Lee, 
K. Chatteqoe. K. Sudhff. Universffy of Cal#ornra...~m Francisco. CA, USA 
Cardmc hypertrophy shows gender-based differences with markedly h~gher 
mortality in men The irdlueece el estrogens on cardiac hypertrophy is poorly 
understood. Thcs study examined the protective effect o! 17p-estradtol rE2) 
against the development o1 cardiac hypertmpby induced by abdominal aortic 
banding for 6 weeks. One hundred 8-wk old male (M) and evanectomlzed 
tamale iF) Spraguo Dawley rats were randomized to sham-operated iS). 
banding + placebo (P) and banding + E2 rE2, 10 mg slow release pellets 
implanted 48 h before surgery) groups. We measured carotid and left ventnc- 
ular systolic (CSP, LVSP, mmHgl and diastolic pressure (COP. LVDP). ratio ot 
left venbicular woight to body weight (LVWIBW. m~}'g). LV : dp/dt (mmH&'s) 
and LV wall thmkness (LVW.T. mmL and cardmc myosin boaW chain (MHC) 
mRNAs by Nodhem blo1 analysis. 
Group LVW~BW CSP LVSP LV + dp/dt LVW+T 
P(Mt 28±01 177.'11 127~7 4573 ~ 169 440e2 
E2 tM) 23 t ID t' 117 ~ 4" 95 t 4" 3372 : 201" 36 : 01" 
P tFt 30 ~: O r r55 t 3 99 ~ S 4406 : 232 6 t t 02 
E2 iF) 2 5 t so" 118 ~ 3" 79 t 3" 3624 t 148" 3 7 : 0 1" 
Moan ~ SEM. ' p - O I05 oompamd with group P 
E2 significantly attenuated hypertension and reduced felt ventricular mus- 
cle mass in both male and ovenectomized female rats. Further. E2 but not P 
decreased expression of/~-MHC mRNA. 114.3% in male: 152% in female: 
both P .: 0.05) but increased .-MHC mRNA (9.8% in male: 11 3% in female: 
both P • 0.05). 
Conclusions: 17/~-Est,adiol prevents the development of hypertension 
and cardiac hypertrophy in rats with experimental hypertension. 


Growth hormone resistance in chronic heart failure 

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Growth hormone resistance in chronic heart failure

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