Mitochondrial abnormalities in myocardium of dogs with chronic heart failure

Abstract

The number, size and structural integrity of mitochondria (MIT) were evaluated in the myocardium of 12 dogs with chronic heart failure (CHF) produced by sequential intracoronary microembolizations (EMB). Tissue specimens for transmission electron microscopy were obtained from the left ventricular (LV) free wall, septum and right ventricular free wall 3 to 4 months after the last EMB. Comparisons were made with samples obtained from identical sites in 9 control dogs. In dogs with CHF, LV ejection fraction decreased from 61 +/- 1% at baseline (prior to EMB) to 22 +/- 2% 3 to 4 months after the last EMB (P < 0.01) while plasma norepinephrine (PNE) concentration increased from 364 +/- 12 pg/ml to 837 +/- 150 pg/ml (P < 0.01). The number of MIT in an area of 100 square sarcomeres was greater in CHF dogs compared to controls (92 +/- 5 vs 64 +/- 2) (P < 0.001); whereas the average size of MIT was smaller (0.53 +/- 0.03 vs. 0.78 +/- 0.04 microm2) (P < 0.001). Injury ranging in severity from matrix depletion to myelinization and membrane disruption was present in 27 +/- 4% of MIT of CHF dogs compared to only 3 +/- 1% of MIT of controls (P < 0.001). MIT abnormalities were present to the same extent in all three regions of the heart. The severity of MIT injury, assessed on the basis of an injury index, was significantly higher in CHF dogs with PNE > or = 600 pg/ml (0.64 +/- 0.07) compared to CHF dogs with PNE < 600 pg/ml (0.32 +/- 0.08) (P < 0.01). Among CHF dogs, the MIT injury index was linearly related to PNE concentration (r = 0.57, P < 0.05), LV ejection fraction (r = 0.57, P < 0.05) and LV end-diastolic pressure (r = 0.57, P < 0.05). These data indicate that profound MIT abnormalities are present in the myocardium of dogs with CHF and are related to PNE concentration and to the severity of LV dysfunction.