Large Animal Models of Chronic Heart Failure (CHF)

Schmitto, Jan D.; Mokashi, Suyog A.; Lee, Lawrence S.; Popov, Aron Frederik; Coskun, Kasim Oguz; Sossalla, Samuel; Sohns, Christian; Bolman, R. Morton; Cohn, Lawrence H.; Chen, Frederick Y.

doi:10.1016/j.jss.2009.11.737

Cited by 23 publications

(23 citation statements)

References 70 publications

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“…The experiments on male adult pigs have some limitations, for example, the high costs of maintenance and the aggressive behavior of animals. Our TIC model does not require open-chest surgery, associated with potential risk of intraoperative complications, as in coronary ligation model [32]. While coronary ligation and microembolization create an ischemic HF limited to a specific region of the heart [32], our model could be used to study generalized myocardial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Expression and Complex Formation of MMP9, MMP2, NGAL, and TIMP1 in Porcine Myocardium but Not in Skeletal Muscles in Male Pigs with Tachycardia-Induced Systolic Heart Failure

Kiczak

Tomaszek

Bania

et al. 2013

BioMed Research International

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Matrix metalloproteinases (MMPs) are involved in the remodeling of extracellular matrix in various tissues. Their functioning could be related to the formation of complexes, containing MMP9, MMP2, tissue inhibitor of metalloproteinases type 1 (TIMP1), and neutrophil gelatinase-associated lipocalin (NGAL). Such complexes have not been investigated in either myocardial or skeletal muscles. We examined 20 male pigs with heart failure (HF), and 5 sham-operated animals. There were no differences in the mRNA expression of MMP9, MMP2, TIMP1, and NGAL between diseased and healthy animals, in either left ventricle (LV) myocardium or skeletal muscles. In LV from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we demonstrated the presence of high molecular weight (HMW) complexes (130, 170, and 220 kDa) containing MMP9, TIMP1, and NGAL (also MMP2 in 220 kDa complex) without proteolytic activity, and a proteolytically active 115 kDa MMP9 form together with 72 and 68 kDa bands (proMMP2 and MMP2). Proteolytically active bands were also spontaneously released from HMW complexes. In skeletal muscles from both diseased and healthy animals, in nonreducing and nondenaturing conditions, we found no HMW complexes, and proteolytic activity was associated with the presence of 72 and 68 kDa bands (proMMP2 and MMP2).

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Section: Discussionmentioning

confidence: 99%

Expression and Complex Formation of MMP9, MMP2, NGAL, and TIMP1 in Porcine Myocardium but Not in Skeletal Muscles in Male Pigs with Tachycardia-Induced Systolic Heart Failure

Kiczak

Tomaszek

Bania

et al. 2013

BioMed Research International

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“…Experimental animal models of chronic ischemic heart failure were established in several large animals (2) using different approaches, for example, single coronary ligations (7) and coronary microembolizations (3–6). While coronary microembolization models are well established and useful (3–6), due to the fact that the chest remains closed, these animal models require great experience and technical equipment (left heart catheter, fluoroscopy, etc.).…”

Section: Discussionmentioning

confidence: 99%

“…The earliest studies to ligate coronary arteries with simple suture techniques to develop a large animal model of chronic ischemic cardiomyopathy were described by Harris et al. in the 1940s (2,13,14). The authors ligated the left anterior descending coronary artery in dogs.…”

Section: Introductionmentioning

confidence: 99%

A Novel, Innovative Ovine Model of Chronic Ischemic Cardiomyopathy Induced by Multiple Coronary Ligations

Schmitto¹,

Mokashi²,

Lee³

et al. 2010

Artificial Organs

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Heart failure is one of the fastest-growing epidemics worldwide in health care today. Although a wide variety of animal models exist to create chronic heart failure, there are few truly successful, reproducible models with ischemic dilation and mitral regurgitation. Six healthy sheep (36 ± 5 kg) underwent multiple, strategic coronary artery ligations on the left ventricle (LV). Six to eight ligations were performed transmurally on three of four segments of the LV: anterior, lateral, and posterior. Side branches of the left anterior descending and circumflex arteries were ligated to create multiple, patchy areas of myocardial infarction. Cardiac global and regional systolic function was assessed by echocardiography and cardiac magnetic resonance imaging (MRI). The extent, the characteristics, and the location of the myocardial infarction were qualitatively and quantitatively assessed by late gadolinium enhancement imaging. The overall mortality rate was 16.7% (1/6 animals). Animals who survived showed a significantly reduced ejection fraction (mean 60 ± 5% to 28 ± 7%; P < 0.05); additionally, two out of the remaining five (40%) animals developed mild to moderate mitral regurgitation quantified by cardiac MRI. Furthermore, each animal developed clinical signs of heart failure (tachycardia, dyspnea, and tachypnea) consistent with global, dilated cardiomyopathy noted on MRI. Creating and reproducing a model of global, ischemic cardiomyopathy with functional mitral regurgitation is an arduous task. We have developed a promising model of ischemic heart failure using multiple ligations, which mimics the sequelae of human cardiomyopathy. Our proposed model is highly effective, reproducible, and may be used for experimental research on heart failure (cardiac assist devices, heart transplant, etc.).

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“…Although several animal models for systolic heart failure have been developed [8,9], there are no large animal models of ischemia-driven diastolic heart failure. Most of diastolic heart failure models imply the induction of hypertension (through renal or aortic banding) in order to induce LV hypertrophy and therefore affect myocardial relaxation [10].…”

Section: Introductionmentioning

confidence: 99%