Chronic Heart Failure Model with Sequential Ligation of the Homonymous Artery and Its Diagonal Branch in the Sheep

Abstract

We report a reliable chronic heart failure model in sheep using sequential ligation of the homonymous artery and its diagonal branch. After a left anterior thoracotomy in Corridale sheep, the homonymous artery was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after 1 hour, the diagonal vessel was ligated at a point at the same level. Hemodynamic measurements were done preligation, 30 minutes after the homonymous artery ligation, and 1 hour after diagonal branch ligation. The electrocardiograms were obtained as needed, and cardiac function was also evaluated with ultrasonography. After a predetermined interval (2 months for five animals and 3 months for two animals), the animals were reevaluated in the same way as before, and were killed for postmortem examination of their hearts. All seven animals survived the experimental procedures. Statistically significant decreases in systemic arterial blood pressure and cardiac output and increases in pulmonary artery capillary wedge pressure were observed 1 hour after sequential ligation of the homonymous artery and its diagonal branch. Untrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals. The data from animals at 2 months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure. Left ventricular enddiastolic dimension and left ventricular end-systolic dimension on ultrasonographic studies were also increased. Electrocardiography showed severe ST elevation immediately after the ligation and pathologic Q waves were found at 2 months after ligation. The thin walled infarcted areas with chamber enlargement were clearly seen in the hearts removed at 2 and 3 months after ligation. In conclusion, we could achieve a reliable ovine model of chronic heart failure using a simple concept of sequential ligation of the homonymous and diagonal arteries. This animal model was comparable to the clinical situation.

Induction of heart failure: haemodynamic comparison of three different canine models

“…For ischaemic cardiomyopathy, coronary artery ligation (Millner et al 1993, Kim et al 2001) and coronary microembolization (Kashem et al 2001 are used. In our previous investigation we used an ameroid constrictor, placed on a branch of the left circumflex artery (Bolotin et al 2002a).…”

Development of an Ovine Model of Myocardial Infarction

“…Two other pilot experiments in which anti‐arrhythmic prophylaxis was not given failed to survive because of intractable VF. Hence, we recommend prophylactic use of anti‐arrhythmic medications such as intravenous lidocaine (2 mg/kg as preligation bolus dose and 1 mg/kg 15 min afterwards) as it is also emphasized in previous studies 3,4,7,12 …”

“…Coronary artery occlusion and hence inducing MI in large animal models is a practical method for examining novel therapeutic protocols in cardiovascular research. However, these animals, such as sheep, lack good coronary collateral circulation, which may lead to a remarkable incidence of fatal arrhythmias as a result of myocardial ischaemia during such procedures 6,7 …”

“…Despite the drawbacks in the use of large animal models for cardiovascular research, the most important being their need for substantial housing resources and care, they have recently become an issue of interest. The interest stems from their anatomical and physiological similarity to humans 1–7 . Coronary artery ligation to induce MI in these models is now considered a widely used and attractive method for experimental research because of its clinical relevance 7–12 .…”

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

“…This can be explained on the one hand by ME into the ramus interventricularis paraconalis (44), which is a sheep‐specific anatomical variant (a left anterior descending coronary artery branch, which supplies the RV), which could lead to direct hypoxic defects of the RV. On the other hand, higher AMPK levels in the RV could be the result of an increased pressure in the pulmonary circulation based on induced LV heart failure (34,45). Comparisons of the investigated groups (ShamOP and CME) showed an increase of AMPK phosphorylation without reaching statistical significance between the groups (Fig.…”