PHARMACOLOGICAL CHARACTERIZATION OF CORONARY SMALL ARTERIES FROM PIGSWITH CHRONIC ISCHEMIC MYOCARDIAL REMODELING

1. The effect of chronic ischaemic myocardial remodelling on small cor onary 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 circumfl ex artery causing scattered myocardial fibrosis, After an observation period of 130 days, heart dimensions and ejection fraction were determ ined with magnetic resonance imaging, Small arteries were isolated fro m the left ventricle and mounted as ring preparations in a myograph, C ontrol arteries were taken from matched non-embolized pigs, 3. Compare d with control pigs, end-systolic and -diastolic volumes increased and left ventricular mass nearly doubled in embolized pigs, This indicate s substantial myocardial hypertrophy, as the fraction area of fibrosis was only 12%.4. Coronary small arteries preconstricted with 30 mmol/l KCl showed a normal contractile response to acetylcholine and 5-hydro xytryptamine. 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-h ydroxytryptamine in the presence of ketanserin was similar. After inhi bition of nitric oxide synthase with N-G-nitro-L-arginine the sensitiv ity to acetylcholine increased to a similar extent in arteries from em bolized pigs and controls. N-G-Nitro-L-arginine abolished the relaxing effects of bradykinin and of 5-hydroxytryptamine in the presence of k etanserin. 5. We conclude that both the contractile function of the sm ooth muscle cells and the endothelial production or action of nitric o xide is preserved or slightly enhanced in coronary small arteries from pigs with chronic myocardial remodelling.