Pharmacological Characterization of Coronary Small Arteries from Pigs with Chronic Ischaemic Myocardial Remodelling

Abstract

1. The effect of chronic ischaemic myocardial remodelling on small coronary artery reactivity in vitro was studied in a newly developed pig model. 2. Pigs were subjected to selective intracoronary embolizations with microspheres in the left anterior descending artery and circumflex artery causing scattered myocardial fibrosis. After an observation period of 130 days, heart dimensions and ejection fraction were determined with magnetic resonance imaging. Small arteries were isolated from the left ventricle and mounted as ring preparations in a myograph. Control arteries were taken from matched non-embolized pigs. 3. Compared with control pigs, end-systolic and diastolic volumes increased and left ventricular mass nearly doubled in embolized pigs. This indicates substantial myocardial hypertrophy, as the fraction area of fibrosis was only 12%. 4. Coronary small arteries preconstricted with 30 mmol/l KCI showed a normal contractile response to acetylcholine and 5-hydroxytryptamine. Sensitivity of the relaxation to bradykinin was nearly 3-fold increased and also slightly enhanced to isoprenaline in arteries from embolized pigs compared with controls, whereas relaxation to 5-hydroxytryptamine in the presence of ketanserin was similar. After inhibition of nitric oxide synthase with NG-nitro-L-arginine the sensitivity to acetylcholine increased to a similar extent in arteries from embolized pigs and controls. NG-Nitro-L-arginine abolished the relaxing effects of bradykinin and of 5-hydroxytryptamine in the presence of ketanserin. 5. We conclude that both the contractile function of the smooth muscle cells and the endothelial production or action of nitric oxide is preserved or slightly enhanced in coronary small arteries from pigs with chronic myocardial remodelling.

Response to Letter Regarding Article “Large Animal Models of Heart Failure: A Critical Link in the Translation of Basic Science to Clinical Practice”

“…Huang et al 4 correlated apoptotic markers with left ventricular wall stress in a chronic ovine microembolization-induced heart failure model. A porcine model of microembolization-induced heart failure was used by Buus et al 5 to demonstrate the preservation of contractile function of the smooth muscle cells and endothelial production of nitric oxide in small coronary arteries. These studies exemplify the principle that although a multitude of large animal models of heart failure exist, it is crucial to select the model most appropriate to the clinical issue being investigated.…”