Mechanical abnormalities in the rat ischemic heart failure model which lie downstream to cAMP production.
OBJECTIVE
We previously showed diminished inotropic responses to isoproterenol in uninfarcted posterior papillary muscles of rats with anterior wall infarcts comprising > or = 30% of the left ventricle. We have also shown that this occurs in the absence of beta-receptor downregulation. Our objective was to show a mechanical defect in the rat infarct model which is secondary to cellular defects downstream to cAMP production.


METHODS
Sprague-Dawley rats were infarcted via coronary ligation. After 3 weeks, the uninfarcted papillary muscle was placed in a muscle bath and exposed to increasing concentrations of dibutyryl cAMP while contracting isometrically at 28 degrees C.


RESULTS
The large infarct group showed evidence of right ventricular hypertrophy which was manifested by an increased right ventricular mass. No differences were found in baseline measurements of developed tension (DT); rate of tension development (dT/dt); rate of relaxation (-dT/dt); time to peak tension (TPT); and relaxation time (t1/2R). When these muscles were stimulated with dibutyryl cAMP, the large infarct group had a reduced inotropic response as measured by +dT/dt and TPT. No consistent abnormalities were noted in relaxation. The findings are similar to those we noted previously with isoproterenol stimulation.


CONCLUSIONS
The impaired response to beta stimulation in uninfarcted myocardium from rats with large myocardial infarctions is due to cellular defects which lie downstream to cAMP production.
Stuver
T P
TP
Department of Medicine, University of Rochester Medical Center 14642.
Cove
C J
CJ
Hood
W B
WB
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003994:Bucladesine; D000242:Cyclic AMP