Acute hemodynamic and coronary circulatory effects of experimental autoimmune myocarditis.
Myocarditis and progression to cardiomyopathy is associated with focal spasm and reperfusion of the coronary microcirculation. Experimental autoimmune myocarditis (EAM), induced with cardiomyosin peptide-specific T cells in Lewis rats, was hypothesized to cause acute hemodynamic and coronary vasculature changes. Fifteen experimental animals (5 each at 1, 2, and 3 weeks after T-cell injection) and eight controls were studied using the constant pressure variant of the isolated heart. Coronary resistant decreased while coronary flow increased (P < 0.05) in EAM hearts after the first week. Rate-pressure product, +dP/dt and -dP/dt, decreased while the heart/body weight ratio increased (P < 0.05) compared with 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. However, compared with controls EAM myocardial PO2 varied more widely and was often beyond the usual range, suggesting the occurrence of localized hypoxic and hyperoxic areas. In summary, after the first week there was a significant decrease in coronary resistance in the EAM animals, which required 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, thus causing hypoxia in other areas.
Friedman
B J
BJ
Division of Cardiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Grinberg
O Y
OY
Ratcliffe
N R
NR
Swartz
H M
HM
Hickey
W F
WF
D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology* / Q000503:physiopathology; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D009205:Myocarditis / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values