Comparison of myocardial infarction with sequential ligation of the left anterior descending artery and its diagonal branch in dogs and sheep.

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

Autologous cardiomyocyte transplantation in an ovine myocardial infarction model.

BACKGROUND: To evaluate the possibility of autologous cardiomyocyte transplantation, we transplanted cultured autologous cells into an infarct region developed by coronary artery ligation in an ovine model. MATERIALS AND METHODS: A chronic heart failure model with a considerable portion of myocardial infarction was created in sheep using sequential ligation of the homonymous artery and its diagonal branch. Autologous cardiomyocytes were cultured and isolated from the right ventricular infundibulum. After a predetermined interval (one animal for two months and the other for three months), the two animals were reanesthetized and a suspension of cultured autologous vetricular cells in 0.3 ml of culture medium (1.2 x 10(7) cells) was injected into the center of three out of the four sites in the infarcted area using a tuberculin syringe. The same amount of culture medium was injected with an identical procedure into the center of the remaining site, as control. The animals were kept alive for a further month, and then sacrificed for postmortem heart examinations. Light microscopic analysis and immunohistochemical study for myoglobin were done. RESULTS AND CONCLUSIONS: On postmortem gross examination, well-demarcated thin-walled anteroseptal infarcts with chamber enlargement were clearly seen in specimens from the two animals. Microscopic analysis showed homogenous fibrosis throughout the infarcted areas. In both animals, one of the three sites of cardiomycyte injection showed an islet of cardiomyocytes in the mid-myocardium, while none were observed in the control site of either animal. A layer of cardiomyocytes was observed in subendocardial regions, as it was in the control areas. In conclusion, cardiomyocyte transplantation into the infarct regions developed by coronary artery ligation in an ovine model was achieved with only limited success. An understanding of why only 33% of cardiomyocyte-injection sites demonstrated viable cardiomyocytes, in the form of tiny cell islets, remains to be elucidated.