Detection of early necrosis in a canine model of low flow myocardial ischemia using 125I-antimyosin (Fab')2.
Low flow myocardial ischemia in the distribution of the left anterior descending coronary artery was established in 32 anesthetized dogs. The early development of irreversible myocardial injury was identified using 125I-antimyosin (Fab')2--a specific immunological marker of myocardial necrosis.  The simultaneous injection of 131I-nonspecific (Fab')2 controlled for variables unrelated to specific antimyosin activity.  It was also possible to calculate the relative uptake of 125I-antimyosin (Fab')2 in the ischemic area.  In order to prevent recirculation of the (Fab')2, and to limit the time of exposure to the myocardium, the fragments were injected directly into the coronary circulation during diversion of the coronary sinus effluent.  The antibody fragments were given either two, three or five hours after the onset of low flow in different groups of dogs and the animals were sacrificed 60 minutes later.  Selective accumulation of 125I-antimyosin (Fab')2 in the ischemic area occurred between two and three hours after the onset of low flow ischemia indicating that necrosis was already established at this time.  Macroautoradiographs of cross sections of the left ventricle and autoradiographs of microscopic sections of the ischemic myocardium independently confirmed selective accumulation of 125I-antimyosin (Fab')2 and hence necrosis, at three hours after the onset of low flow.  In this study the use of 125I-antimyosin (Fab')2, in contrast to the use of histology, as a marker of necrosis avoided error due to sampling and also permitted the detection of cell death early during the ischemic process.  The demonstration, within a narrow time frame, of early necrosis in this low flow preparation provides a potential model with which to evaluate agents for myocardial preservation in obstructive coronary disease.
Timmis
A D
AD
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Lopez
J A
JA
Fallon
J T
JT
Khaw
B A
BA
Haber
E
E
Powell
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001345:Autoradiography; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D008297:Male; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000000981:diagnostic imaging; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009218:Myosins / Q000276:immunology* / Q000502:physiology; D009336:Necrosis; D011859:Radiography; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D009218:Myosins