Development of porcine model of chronic tachycardia-induced cardiomyopathy.
BACKGROUND
There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy.


METHODS
Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR.


RESULTS
In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls.


CONCLUSIONS
In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level.
Paslawska
Urszula
U
Regional Specialist Hospital in Wroclaw, Research and Development Centre, Wroclaw, Poland.
Gajek
Jacek
J
Kiczak
Liliana
L
Noszczyk-Nowak
Agnieszka
A
Skrzypczak
Piotr
P
Bania
Jacek
J
Tomaszek
Alicja
A
Zacharski
Maciej
M
Sambor
Izabela
I
Dziegiel
Piotr
P
Zysko
Dorota
D
Banasiak
Waldemar
W
Jankowska
Ewa A
EA
Ponikowski
Piotr
P
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000097:blood; D002304:Cardiac Pacing, Artificial / Q000379:methods; D009202:Cardiomyopathies / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005080:Exercise Test / Q000379:methods; D005260:Female; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000097:blood; D011897:Random Allocation; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis / Q000097:blood; D013552:Swine; D013610:Tachycardia / Q000150:complications* / Q000201:enzymology / Q000378:metabolism*
D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases