Restoration of coronary flow in myocardial infarction by intravenous chimeric 7E3 antibody without exogenous plasminogen activators. Observations in animals and humans.
BACKGROUND
Coronary thrombus is composed of platelets and fibrin, and during thrombolytic treatment, reflow may be slowed by platelet deposition. It may be possible to initiate coronary reflow without exogenous plasminogen activators by blocking platelet aggregation while fibrin generation is impeded with heparin.


RESULTS
In 14 dogs, left anterior descending coronary artery thrombosis was produced by endothelial trauma and thrombin instillation in the presence of stenosis distally. Reflow was monitored by flow probe during treatment with (1) heparin, (2) heparin and aspirin, and (3) heparin, aspirin, and intravenous 7E3. Eighty percent of dogs treated with the third combination showed stable reflow (> or = 25% of prestenotic flow) in 50 +/- 9 minutes. In addition, 13 patients were studied during intravenous administration of c7E3 10 minutes before primary angioplasty for acute myocardial infarction and Thrombolysis In Myocardial Infarction (TIMI) grade 0 or 1 flow. Pretreatment included heparin and oral aspirin. Flow increased during a 10-minute period by at least one TIMI grade in 11 (85%) of 13 and reached TIMI grade 2 or 3 in 7 (54%) of 13 patients. Average TIMI grade flow increased from 0.31 +/- 0.5 to 1.54 +/- 0.8 (P < .001). Thrombus length 10 minutes after c7E3 was 5.1 +/- 3.5 mm. All but 1 patient then underwent angioplasty. There were no complications.


CONCLUSIONS
Coronary reflow can be initiated by intravenous 7E3 administration in the presence of heparin and aspirin. In human patients, this flow can be observed in 10 minutes without exogenous thrombolytic agents.
Gold
H K
HK
Department of Medicine, Massachusetts General Hospital, Boston 02114, USA. gold(@olorin.mgh.harvard.edu
Garabedian
H D
HD
Dinsmore
R E
RE
Guerrero
L J
LJ
Cigarroa
J E
JE
Palacios
I F
IF
Leinbach
R C
RC
D000077284:Abciximab; D000328:Adult; D000368:Aged; D000800:Angioplasty, Balloon; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011292:Premedication; D015912:Thrombolytic Therapy
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D001241:Aspirin; D000077284:Abciximab