Subendomyocardial exhaustion of blood flow reserve and increased fibrosis in conscious dogs with heart failure.
The effects of near-maximal coronary vasodilation were examined in conscious dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by either aortic banding alone or aortic banding plus a peripheral arteriovenous shunt. The findings were compared with results in littermates with compensated LV hypertrophy and with a third group of normal dogs. At rest, there was a marked difference in the intramyocardial distribution of coronary flow, measured with radiolabeled microspheres. The endocardial/epicardial (endo/epi) flow ratio in the LV failure dogs was 0.96 +/- 0.08 as compared with control dogs (1.28 +/- 0.06, p less than 0.05) or dogs with compensated LV hypertrophy (1.23 +/- 0.08, p less than 0.05). During near-maximal coronary vasodilation with adenosine, all groups showed similar increases in subepimyocardial (epi) flow. While significant increases in subendomyocardial (endo) flow during adenosine infusion were seen in the control group (0.88 +/- 0.10 to 3.53 +/- 0.24 ml/min/g) and in dogs with compensated LV hypertrophy (1.12 +/- 0.14 to 3.60 +/- 0.16 ml/min/g), there was no change in endo flow in the LV failure dogs (1.55 +/- 0.20 to 1.71 +/- 0.47 ml/min/g) and a further significant reduction in the endo/epi flow ratio was observed (0.30 +/- 0.06, p less than 0.01). These hemodynamic changes were associated with chronic multifocal interstitial or discrete areas of fibrosis observed preferentially in endo layers. Thus, endo flow reserve is nearly exhausted in dogs with decompensated pressure overload LV hypertrophy, which may induced periodic episodes of endo ischemia resulting in myocyte necrosis and fibrosis, which in turn results in exacerbation of LV failure.
Hittinger
L
L
Department of Medicine, Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts.
Shannon
R P
RP
Bishop
S P
SP
Gelpi
R J
RJ
Vatner
S F
SF
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology*; D003243:Consciousness; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004699:Endocardium / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D009206:Myocardium / Q000473:pathology*
D000241:Adenosine