Restored capillary density in spared myocardium of infarcted rats improves ischemic tolerance.
Myocardial infarction (MI)-induced hypertrophy is associated with a decreased capillary density, which may negatively affect ischemic tolerance of the spared myocardium. The current study investigated the effects of moxonidine, a centrally acting sympatholytic, on left ventricular (LV) hypertrophy and capillary density in relation to sensitivity to ischemia in infarcted hearts. Infarcted rats were randomized to receive 3 or 6 mg/kg/d of moxonidine from 1 to 21 days after MI. LV hypertrophy after MI was indicated by increased ventricular to body weight ratio and was significantly inhibited by moxonidine. Histologic analysis revealed that MI-induced concentric hypertrophy of the spared myocardium, as indicated by almost double cross-sectional area of Gomori-stained myocytes, was completely prevented by 6 mg/kg/d of moxonidine. This effect was accompanied by a a restored number of lectin-stained capillaries per tissue area. However, capillary-to-myocyte ratio was similar in all groups. LV dysfunction after MI, measured in isolated perfused hearts, was confirmed by decreased LV systolic pressure and +dP/dtmax and was not affected by moxonidine. Low-flow ischemia, induced by lowering perfusion pressure from 85 to 15 mm Hg for 30 min, resulted in a further reduction of cardiac perfusion compared with sham rats, which was normalized with 6 mg/kg/d of moxonidine. Ischemic sensitivity in MI hearts, as reflected by increased maximal coronary flow during reperfusion, was reduced with moxonidine. This was further supported by substantially lower purines and lactate concentrations in the coronary effluent during ischemia. These results indicate that moxonidine-induced prevention of hypertrophy may preserve capillary density without affecting capillary number, thereby improving ischemic tolerance of the spared myocardium.
Van Kerckhoven
Roeland
R
Deparment of Pharacology, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands. vankerckhoven@farma.fgg.eur.nl
Saxena
Pramod R
PR
Schoemaker
Regien G
RG
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects
D007093:Imidazoles; C043482:moxonidine