Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts

Objective: Postinfarction hypertrophied hearts have been shown to display a lower capillary density and reduced mechanical efficiency amplified by tachycardia. We investigated whether pharmacological reduction of postinfarction tachycardia would induce capillary growth by treating myocardial infarcted (MI) rats with aspirin, methylprednisolone, moxonidine or captopril, during the first 3 weeks after infarction. Methods and Results: Effects on in vivo heart rate were measured in conscious unrestrained rats, while in vitro heart rate effects were evaluated in isolated perfused hearts. Compared to sham-rats, MI-rats manifested a significant in vivo as well as in vitro tachycardia (increase 9% and 20% vs. sham, respectively). Whereas aspirin, methylprednisolone and moxonidine significantly reduced postinfarction in vivo tachycardia, captopril rather increased in vivo heart rate. In vitro tachycardia of MI-hearts was reduced to sham-values with aspirin and methylprednisolone (P<0.05), but not with moxonidine and captopril. Capillary density defined as the number of Lectin stained capillaries per tissue area, which significantly decreased in MI-hearts (decrease 42% vs. sham), was restored by all treatments (P<0.05). Concentric left ventricular hypertrophy after MI, defined as increased cross-sectional area of transversally cut Gomori stained myocytes, was indicated by almost double myocyte size (P<0.05), while capillary to myocyte ratio remained unchanged. Methylprednisolone, moxonidine and captopril, but not aspirin, prevented hypertrophy (P<0.05). However, treatment with aspirin and methylprednisolone, but not moxonidine and captopril, increased capillary to myocyte ratio (P<0.05) up to twice the values of non-treated MI hearts, indicating newly formed capillaries. Conclusions: The above findings confirm that post-MI pharmacological treatment can increase capillary density in the remodeled left ventricle. Whereas prevention of left ventricular hypertrophy normalizes capillary density without actually affecting capillary number, increased capillary to myocyte ratio (at preserved hypertrophic response) indicates actual capillary growth.

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