Hemodynamic Changes in a Model of Chronic Heart Failure Induced by Multiple Sequential Coronary Microembolization in Sheep

Abstract

Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 +/- 2 kg), chronic heart failure was induced under fluoroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 microm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan-Ganz catheter (mean pulmonary arterial pressure [PAP mean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 +/- 4 bpm [base] to 93 +/- 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 +/- 5 [base] to 38 +/- 7 [3 mo][P < 0.05]), and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.

Large Animal Models of Chronic Heart Failure (CHF)

“…An important feature of Schmitto et al's model is the lack of recovery of LV-function after coronary embolizations are completed [25]. Partial recovery of LV-function after acute coronary occlusion has been described in dogs [21] and may be accounted for, in part, by the presence of a substantial collateral circulation, which is virtually absent in sheep.…”

The Role of Phospho‐Adenosine Monophosphate‐Activated Protein Kinase and Vascular Endothelial Growth Factor in a Model of Chronic Heart Failure

“…Various approaches were examined by different groups in order to establish a reproducible large animal model in the past with variable success (9,10,27–33). Therefore, our group used a novel approach to establish a stable and reproducible animal model of CHF in sheep induced by multiple sequential CMEs (11,12,34). In this study, we investigated the expression of bimolecular levels of AMPK and VEGF in the CHF model in sheep.…”

Adjustment and Characterization of an Original Model of Chronic Ischemic Heart Failure in Pig

“…This will take part in improving essential knowledge with regard to heart failure, to imagine new therapeutic concepts, whether medical or surgical. In the literature, there are numerous models of heart failure, whether the result of genetic modification [6], of a permanent ligature of the coronary arteries with, or without, reperfusion (models of infarction and not of ischemia) [7–9], of electrical stimulation at a rapid rate [10], of modifications of load [11], or of toxic origin [12, 13]. On the other hand, some models have been developed to induce myocardial ischemia without heart failure [14].…”