Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction.
BACKGROUND
Immune modulation by the Celacade system (Vasogen Inc, Canada) decreases mortality and hospitalization in human heart failure.


OBJECTIVE
To study the effects of Celacade in rats on acute cytokine expression after coronary artery ligation, cardiac dimensions following myocardial infarction (MI), and systolic and diastolic function of cardiac muscle in MI.


METHODS
Celacade treatment was administered 14 days before coronary artery ligation and monthly after the surgery. Cytokine expression in cardiac tissue was measured on days 1 and 7 by ELISA in sham rats and in rats with MI (with or without Celacade treatment). Echocardiograms were obtained serially for 16 weeks. Force and sarcomere length (SL) were measured by strain gauge and laser diffraction in isolated right ventricle trabeculas at 16 weeks. The inotropic effect of pacing on force was quantified as F5 Hz/0.5 Hz. Diastolic dysfunction was quantified as the root mean square of spontaneous SL fluctuations.


RESULTS
Celacade inhibited transforming growth factor beta-1 production in the infarct area on day 7 (191.6+/-22.6 pg/mg versus 275.4+/-30.1 pg/mg; P<0.05), but did not attenuate cardiac dilation in MI. Celacade restored positive inotropism of pacing in MI (F5 Hz/0.5 Hz in Celacade, 219.1+/-46.7%; MI, 148.1+/-27.1% [P<0.05 compared with 211.4+/-37.9% in sham]). Celacade reduced diastolic dysfunction in MI (root mean square of spontaneous SL fluctuations: 121+/-15% and 143+/-19% with Celacade versus 184+/-19% and 190+/-26% without Celacade at 26 degrees C and 36 degrees C, respectively) compared with sham (100%; P<0.05).


CONCLUSIONS
Celacade reduces the increase of transforming growth factor beta-1 expression during the acute stage of MI in rats, but does not prevent chronic cardiac dilation. Celacade restores the positive inotropic effect of increased pacing rate in trabeculas from rat right ventricles with large MIs and reduces diastolic dysfunction.
Zhang
Mei Luo
ML
Department of Cardiovascular Sciences, Libin Cardiovascular Institute of Alberta, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1.
Mei
Jie
J
Archer
Lori Anne
LA
Obayashi
Masakazu
M
Diao
Ni
N
Stuyvers
Bruno
B
ter Keurs
Henk E D J
HE
D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006358:Hot Temperature; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010126:Ozone; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014463:Ultrasonography; D014466:Ultraviolet Rays
D016207:Cytokines; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone