Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy.
Left ventricular hypertrophy following volume overload is regarded as an example of cardiac remodeling without increased fibrosis accumulation. However, infarction is associated with increased fibrosis within the noninfarcted, hypertrophied myocardium, particularly in the subendocardial regions. It is conceivable to suppose that, as also occurs postinfarction, low coronary driving pressure may also interfere with accumulation of myocardial fibrosis following aortocaval fistula.


OBJECTIVE
To investigate the role of acute hemodynamic changes in subsequent deposition of cardiac fibrosis in response to aortocaval fistula.


METHODS
Aortocaval fistula were created in 4 groups of Wistar rats that were followed over 4 and 8 weeks: aortocaval fistula 4 and aortocaval fistula 8 (10 rats each) and their respective controls (sham-operated controls - Sh), Sh4 and Sh8 (8 rats each). Hemodynamic measurements were performed 1 week after surgery. Hypertrophy and fibrosis were quantified by myocyte diameter and collagen volume fraction at the end of follow up.


RESULTS
Compared with Sh4 and Sh8, pulse pressure, left ventricular end-diastolic pressure, and +dP/dt were higher in aortocaval fistula 4 and aortocaval fistula 8, but -dP/dt was similar. Coronary driving pressure (mm Hg), used as an estimate of perfusion pressure, was lower in aortocaval fistula 8 (52.6 +/- 4.1) than in Sh8 (100.8 +/- 1.3), but comparable between aortocaval fistula 4 (50.0 +/- 8.9) and Sh4 (84.8 +/- 2.3). Myocyte diameter was greater in aortocaval fistula 8, whereas interstitial and subendocardial fibrosis were greater in aortocaval fistula 4 and aortocaval fistula 8. Coronary driving pressure correlated inversely and independently with subendocardial fibrosis (r(2) = .86, P <.001), whereas left ventricular systolic pressure (r(2) = 0.73, P = .004) and end-diastolic pressure (r(2) = 0.55, P = 012) correlated positively and independently with interstitial fibrosis.


CONCLUSIONS
Coronary driving pressure falls and ventricular pressures increase early after aortocaval fistula and are associated with subsequent myocardial fibrosis deposition.
Guido
Maria Carolina
MC
Laboratory of Medical Investigation 51, Hospital das Clínicas, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil. macguido@terra.com.br
Koike
Márcia Kiyomi
MK
Frimm
Clovis de Carvalho
Cde C
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003326:Coronary Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D004719:Endomyocardial Fibrosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D051381:Rats; D017208:Rats, Wistar