A proposed mechanism(s) of transitory ischemic injury to myocardium.
The main objective of this study was to produce primary acute ischemic injury to myocardium in a live animal. In vitro, guinea pig platelets were sensitive to perturbation and aggregation by a suspension of ultrafine fibrillary collagen material isolated from the aorta of an aged burro (Equus asinus). The platelets responded to the stimulatory action of this material down to 100 to 200 ng (dry weight) added to 0.45 ml of platelet-rich plasma, as determined by aggregometric technique. Aortic fibrillary collagen material injected IV into guinea pigs (350 to 1900 microgram protein/kg of weight) produced a transitory disappearance of virtually all circulating platelets within 5 minutes. In animals in which blood samples were taken 2.5 hours after injection, 50 to 75% of the average base-line platelets in the circulation of controls returned to the circulation. In other experiments, 3 anesthetized animals were injected by jugular vein with an amount of active fibrillary collagen material (300 microgram as protein/kg of animal weight) estimated to produce reversible platelet aggregation in vivo. Two control animals were injected with the same dose of the material that had been inactivated (15 minutes at 100 C) to abolish platelet aggregation. Treated and control animals were maintained under general anesthesia for 2.5 hours. Intraventricular pressures and electrocardiographs (ECG) were monitored continuously for the first 30 minutes. The injection of the active fibrillary collagen material caused a large ventricular pressure elevation (170/10, 180/10, and 150/10 mm of Hg) in approximately 40 s. Preinfusion ventricular pressures in the 3 animals were 65/0, 85/5, and 88/0 mm of Hg, respectively. Within 60 s, there was a reduction in the absolute platelet number in the peripheral circulation. The elevation of ventricular pressure persisted for approximately 5 minutes and was followed within 30 minutes by a set of ECG events suggestive of acute myocardial ischemic injury, which included premature ventricular contractions, transient S-T segment depression concurrent with ventricular hypertension, and S-T segment elevation with reversed tall upright T-waves in association with a decrease to the preinfusion ventricular base line. Other ECG changes included prolongation of the P-R segment, missed ventricular contractions, and arrhythmia. The ECG changes seemed to be subsequent to platelet microthrombus formation in the pulmonary arterial microcirculation. By 2.5 hours after the treatment, platelets "rebounded" into the circulation in 2 surviving guinea pigs, and left ventricular pressures and ECG profiles returned to the preinfusion base lines. Guinea pigs IV infused with similar amounts of inactivated (15 minutes at 100 C) fibrillary collagen material did not show changes.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D001794:Blood Pressure; D003094:Collagen / Q000494:pharmacology; D003238:Connective Tissue / Q000473:pathology / Q000648:ultrastructure; D003326:Coronary Circulation; D003327:Coronary Disease / Q000209:etiology / Q000473:pathology / Q000662:veterinary*; D004562:Electrocardiography; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000503:physiopathology; D007511:Ischemia / Q000662:veterinary; D008168:Lung / Q000098:blood supply / Q000648:ultrastructure; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000494:pharmacology; D013931:Thromboxanes / Q000494:pharmacology
D011453:Prostaglandins; D013931:Thromboxanes; D003094:Collagen