Acute Hemodynamic and Coronary Circulatory Effects of
Experimental Autoimmune Myocarditis
*Friedman BJ, Grinberg OY, Ratcliffe NR, Hickey WF, Swartz HM.
*Division of Cardiology, Dartmouth Medical School, Hanover, NH 03755 - USA
EPR Center for the Study of Viable Biological Systems, Dartmouth Medical
School,
Hanover, NH 03755 - USA
INTRODUCTION: Clinically cardiomyopathy is a major problem but the
mechanism for this
syndrome remains to be elucidated. One potential cause is inflammation
(myocarditis) which
progresses to cardiomyopathy because of damage due to focal spasm of the
coronary
microcirculation and damage upon reperfusion. We have been able to study
this mechanism
using an experimental autoimmune myocarditis (EAM), induced with
cardiomyosin peptide
specific T cells(1) in Lewis rats and electron paramagnetic resonance (EPR)
oximetry to follow
the effects of local oxygenation.
METHODS: Fifteen experimental animals (5 each at 1, 2 and 3 weeks
after T cell injection) and 8
controls were studied using the constant pressure variant of the isolated
heart. Oxygen sensitive
lithium phthalocyanine crystals were injected into the left ventricular
myocardium for EPR
oximetry.
RESULTS: Coronary resistance decreased while coronary flow increased
(p<.05) in EAM hearts
after the first week. Rate-pressure product, +dP/dt and -dP/dt decreased
while heart/body weight
ratio increased (p<.05) compared to controls at 1 week but not at 2 or 3
weeks. Mean local
myocardial pO2, which reflects local oxygen delivery and consumption, and
MVO2 were not
different for EAM hearts. Compared to controls, however, myocardial pO2 in
animals with
EAM varied more widely and was often beyond the usual range, suggesting the
occurrence of
localized hypoxic and hyperoxic areas.
CONCLUSIONS: After one week there is a significant decrease in
coronary resistance in animals
with EAM, which then require higher flow to maintain a similar perfusion
pressure. These
changes in coronary resistance and flow, along with the heterogeneity and
extremes of local
myocardial pO2 levels without a significant change in MVO2 may be explained
by postulating
development of low resistance, high flow hyperoxic areas which steal flow,
causing hypoxia and
damage to myocytes in other areas. These results are consistent with the
postulated mechanism
of acute local hypoxia being a mechanism for the development of
cardiomyopathy. The next step
will be to test the validity of the hypothesis by taking steps to modify the
local changes.
Presented at the 26th annual ISOTT conference August, 1998. Manuscript
published:
B.J. Friedman, O.Y. Grinberg, N.R. Ratcliffe, H.M. Swartz, and W.F. Hickey,
“Acute Hemodynamic and
Coronary Circulatory Effects of Experimental Autoimmune Myocarditis,” Heart
Vessels 13:58-62 (1998).