Paulus, Walter J.

Shah, Ajay M.

Vanderheyden, Marc

Wellens, Francis

Elsevier - Publisher Connector 

Reduced myocardial contractile effects of nitric oxide after heart transplantation: Implications for diastolic dysfunction of the cardiac allograft 

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I40A ABSTRACTS-Oral JACC February 1996 
8:45 
~ Increased Diastolic Chamber Stiffness Occurrln9 
During Supply, Demand, and Zero-Flow lechemlo Is 
Determined by Common Subcatfula~ Mechanisms 
Niraj Varma, Franz R, El0edi, Cad S. Apstein, Boston Univers#y, Boston, MA 
We compared mechanisms of thcreased iastolic hamber stiffness (tDCS) 
ocourdng in isolated Isovolumic (balloon.in-LV) blood perfused rabbit hearts 
dudng prolonged 1ow-fl0w ('supply", SI), demand (DI), and zero-flow is- 
chemia. We created I) SI by reducing coronary blood flow by 85% it) Ol 
by reducing coronary blood flow by 70% and superimposing tachycardia (7 
Hz), and ill) global zero-flow ischemia by stopping coronary blood flow. A 
5 rain int~cotonary infusion of butane-dione*monoxime (DAM, 5--10 raM), 
an agent which diminishes Ca++ activated tension, was imposed when Is- 
chemic dtastolio dysfunction had ocourrod in SI and DL In SI when DCS had 
increased, as asseSsed by an increase in isovolumic LVEDP of 5 mmHg (21 
-4- 4 mln ischemla), BDM reduced LV developed pressure (DevP) from 25 
-I* 1 to 15 4- 2 mmHg (n ~ 8, p < 0.001) but did not simultaneously reduce 
LVEDR Similarly In DI whan LVEDP had increased 7-.8 mmHg (n = 8, 14 4- 
2 rain tashycardia + ischemia) BDM reduced DevP from 35 to 25 mmHg (p 
< 0.01) but did not reduce LVEDP. We then ai~plied a quick stratch-rolease 
(Q~R) of 25% of intravenfficuler balloon volume to hearts during ischemic 
diastolio dysfunction. After zero-flow ischemia (18 :E 4 rain) when LVEDP had 
increased 10 mmHg from a baseline of ~.7 mmHg (ia "classic" rigor) QSR 
instantly lysed increased diastolio tension (LVEOP pre-vs post-QSR 2? 4- 1 
vs 1"/+ 1 mmHg, p < 0.00t, n = 6), a response known to be characteristic 
of rigor. QSR similarly lysed increased diastolic tension in both St (n = 6) 
and DI (n = 6) hearts when ?DOS had occurred such that isovolumic LVEDP 
returned precisely to pre*contraotore values. Hence TDCS ocoumng during 
both SI and DI was insensitive to BDM but was lysed by QSR similarly to 
contracturo sustained after zero-flow Ischemia. These results imply that the 
subcellular =sis for 1'DOS was common to these ischemfc states, and was 
a rigor, and not a Ca++ driven tension. 
9:00 
~ N o  Effect of  Angiotensln on Ischemic Diastolic II 
Dysfunction in Hypertrophied and Infarcted Rat 
Hearts 
Joseph R. Ubonati, Cad S. Apstein, $oeun Ngoy, Henry W. Sessleberg, 
Brian Herdck, Franz R. Eberli, Boston Univarsity, Boston, MA 
Prassure-ovedoad left vantioular hypertrophy (LVH) is associated with in. 
creased diastolic dysfunction dudng ischemia, whereas compansatory hyper- 
trophy following myocardial infarction is not. We tested if angioteosin f tANG 
II) would exacerbate ischemia-inducod iastolic dysfunction in these two 
models. Pressure-overload LVH (Pressure-LVH) was induced in uninephrec- 
tomized, daoxycorticostorona-sait treated rats, and infarction by ligation of 
the left anterior descending artery (Pest-MI), Mean infarct size was 27 ~: 3%. 
Isolated, isovofumio, red-cell perfused rat hearts were exposed to 60 rain of 
low-few isshemle (15% of baseline flow) followed by 30 rain of repeduslon. 
ANG II (10--7 M) infusion was steded at baseline end continued throughout 
Ischemia and reperfuston. ANG II exeded a vasooonstdctivo affect at base- 
line but did not affect LV end-diestolic pressure (LVEOP). During Ischemia, 
diastolic dysfunction was axaggereted In untreated pressure.LVH (n = 5) vs 
sham (n = 5) (ALVEDP 46 :~ 2 vs 25 4- 3 mmHg; p < 0,05), ANG It treatment 
did not furlher increasa LVEOP In Preasure-LVH (n = 7), but LVEDP tended 
t0 Increase In sham {n = 5)/.~LVEDP 43 d: 6 vs 40 :E 5 mmHg; ns}. In 
untreated post-MI hearts (n = 8), LVEDP increased to the same extent as 
sham (n - 7) (24 4- 5 vs 35 4- 5 mmHg; ns). Again, ANG II treatment did not 
increase LVEDP In post-MI (n = 7) or sham {n ,= 7) (&LVEDP 31 :E 4 and 35 
:E 5 mmHg; ns). Dudng reperfuslon, LVEDP remained increased in untreated 
Pressure-LVH but not post-ML ANG II did not adversely affect recovery In 
pressure LVH or post-MI, but slightly Increased LVEDP in sham. Summanj: 
Diastolic dysfunction dudng tschemla and reperfuslon tS exaggerated with 
pressure-overload hypertrophy, but not with Infarction. Extrinsic ANG II does 
not increase Ischaml¢ dlastcito dysfunction in these a~fmal models. Con- 
C/osicn: ANG II has a minimal role In modulating acute Ischemtc diastolic 
dysfuncfOn in these particular forms of LVH. 
9:15 
u m o ~  In Cardla~ Rcta.on mKI FIIHng 
S~ Nags, M~tU~ Sfu~r, Bamare eud~a,~, Andreas ~¢ste~, Stefan 
S. P.~',~, Petar aoe~mr, Otto M. He=. Ca~Vo~gy. Un/vms~ Ho~ta~ 
ar, d ETt.t. Zur~/~, Sw¢,~t  
~ =~nd ~ mo~on of tha he=1 was es~zs=ed with MR 
Methods: Twelve championship rowers (R), 10 I~tienls with aortic stonosis 
(AS) and 11 controls (C) unden~est myocardial taggin~ on a Philips ACS II 
(1.5 T) system with high temporal (35 ms) and epatial (1.4 x 1.4 ram) 
resolution. The left ventricle was labelled with a rectangular grid in 3 short- 
axis pianos (bas~, equator, apex) and cardlao rotation was calculated from 
the motion of the gdo crossing points: 
~'~12 ] ,, . ,~S ',-,-- = ¢ontlrOls (n=l 1) 
I:= ,,| ..P*_]ES ~,~ ---:AS(n:lO) 
"dO " _ o~=7-~' - - "  
Time I.sJ 
Systolic rotation is nomlal in rowers but enhanced in aortio stanasis. 
However, diastolic untwisting is significantly prolonged in aortic stsnosis but 
nut in rowers. 
Conclusions: Severe pressure ovedoad hypertrophy is associated with 
enhanced systolic rotation and prolonged un~tstiP, gwhich ovedaps diastolic 
filling. Thus, alterations in c~rdiac rotation ~.','e predominantly found during 
¢liastole In pathologic hypertrophy and mw explain the occurrence of diastolic 
dysfunction in thes~ patients. 
9:30 
~ Reducad Myocardial Contracti le Effects of  Nitric 
Oxide After Heart Tmnspiantatfun: Implications for  
Diastol ic Dysfunction of  the Cardiac AIIograft 
Waiter J. Paulus, Mare Vandorheyden, Francis Wellens, Ajay M. Shah 1. 
Cardiovascular Center, Aalst, Belgium; 1 Unive/sity of Wales College of 
Medicine, Cardiff. U.K. 
Diasto!ic left ven~cuiar(LV) dysfunction of the cardiac allograft(CA) ~duces 
exercise tolerance and results from decreased LV diastolic distensibility. In 
control subjects(C), a btcoronary(BIC) infusion tint) of the Nitric Oxide(NO)- 
donor sodium nitreprusside(SNP), induces myocardial coutTectile ffects con- 
sisting of a fall of LV peak systol~c(PS) pressure(P) and a rise of LV End- 
Dlestolic(ED) distensibility(Dis) (= lower LvEnP at larger LVEOVolume(V)). 
1"hose ffects result from a direct myocardial action of NO, unrelated to sys- 
temic vasodilation, as they are not reproduced by anght atrial Inf of SNP. In 
the present study, the myocardial contractile ffects of NO were compa~:l 
in C(n = 7) and in transplant recipients(Tx) (n = 14)o free of rejection or 
graft vasculopathy, by obtaining microfp LV pressures and LV angiograms 
at baseline and at the end of a 5 rain BIC lnf of SNP (4/~g/min), In Tx, BIC 
SNP caused a smaller ALVPSP(mmHg) (Tx: -7  -~ 6; C: -16 4- 7; p < 0.05) 
and a smaller rise in LVEDD is because of smaller ALVEDP(mmHg) (Tx: -3  
:E 3; C: -6  :t: 2 p = 0.07) at comparable ALVEDV(ml) (Tx: 7 4- 7; C: 10.4- 
13). In Tx, ALVPSP at tha end of BIC SNP was inversely related to baseline 
LVEDP (ALVPSP = 0.7 LVEDP -19; r = 0,68; p ,= 0.008) and to baseline time 
constant(T) of LVPdecay (ALVPSP = 1.1T - 46; r = 0.79; p :  0.02). Baseline 
diastolic LV dysfunction of the CA therefore predicts reduced myocardial 
contractile response to exogenous NO. A similar defcienoJ in myocardial 
response tO endothelial NO could contribute to LV diastolic dysfunction of the 
CA, Immune-reialed reaotive oxidants in the CA, which bind to and inactivate 
NO, could explain the deficient myocardial contractile respunsa to NO after 
Tx. 
9:45 
Inertial Nature of Pulmonary Vein F low~ Invasive 
and Doppler Correlation in Humans 
Grsgory M. Scotia, N~il L, Gresnbeq~, Patrtok M. McCarthy, Pialar 
M. V~mdervoort, James D. Thomas. Cleveland Clinic Foundation, 
Cleveland, Ohio 
Previous studies have shown a relation between pulmonary vein (PV) flow 
velocities and LA pressure. We hypothesized that inertial forces contdbute 
S,~lniflcant~ to the convective component obtained from such velocity data. 
hi 3 patients unde~ooing routine caMiac smgery, we measured LA and PV 
pressure & PV/LA gradient, while recording pulsed wave Doppler from the 
PV orifice. All cycles wera steedardlzed to a cycte length of 1000 ms #jld 
intewals frem the Gwase to PV z ~  S-wave, O wave aod A waves 
and gt~r conesponding peaks of LA/PV ~pzzdi~t tacoS, AccO, .~coA) were 
measured. Inerfarce (M) was calculated at the onset of S~am via 
M = (~.P -~pv2)ldVlrXt. 
Resutts: fCnre c~r~ac yms wem anCyzed wiU~ mean cym kmr~ of 77 3 
4- s3 ms. The PV/LA g~zG~nt rotated ~ ~'~ S-wave (AceS) flow prececled p. 
by251 ± e3 me m~d had ~ ~ el t 2 ~- 0.28 mml.~ AceD preceded 
the I)~rdve by 170 ~ 61 ms and had ~t ant~ el 1.04 + 0.44 ntnlH~ 


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Reduced myocardial contractile effects of nitric oxide after heart transplantation: Implications for diastolic dysfunction of the cardiac allograft

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