Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat.
The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin. In the clinical setting of ischemia/reperfusion however, the cyclooxygenase inhibitor aspirin is widely used to prevent platelet aggregation. The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat. Fifteen dogs received either 1 mg/(kg.day) (group I, n = 7) or 10 mg/(kg.day) (group II, n = 8) aspirin orally for 1 week. Both dosages of aspirin inhibited ADP-induced platelet aggregation. The dogs were then anesthetized thoracotomized and subjected to 15 min LCx-occlusion and 4 h reperfusion. Before LCx-occlusion, groups I and II received ramiprilat (20 micrograms/kg, i.v.). Systemic hemodynamics, posterior myocardial blood flow (PMBF, colored microspheres) and wall thickening (PWT, sonomicrometry) of these groups were measured and data compared to placebo-controls (group III, n = 11) and dogs receiving only ramiprilat before LCx-occlusion (group IV, n = 11). Four dogs received 10 mg/(kg.day) aspirin without ramiprilat (group V). Mean aortic pressure was kept constant by an intra-aortic balloon, and heart rate did not change. PMBF was not different between the five groups. Under control conditions and during myocardial ischemia PWT was also not different. At 4 h reperfusion PWT was still depressed in group III (-5 +/- 20% of control) and group V (-23 +/- 6%) whereas PWT recovered to the same extent in groups I (46 +/- 23%), II (50 +/- 15%) and IV (58 +/- 18%) (all P < 0.05 v groups III and V). The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is not prevented by aspirin in dosages which are nevertheless sufficient to inhibit platelet aggregation.
Rose
J
J
Department of Pathophysiology, University of Essen Medical School, Germany.
Ehring
T
T
Sakka
S G
SG
Skyschally
A
A
Heusch
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D017682:Myocardial Stunning / Q000139:chemically induced* / Q000517:prevention & control; D010974:Platelet Aggregation / Q000187:drug effects; D011180:Postmortem Changes; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D012039:Regional Blood Flow
D000806:Angiotensin-Converting Enzyme Inhibitors; D016861:Cyclooxygenase Inhibitors; C052549:ramiprilat; D017257:Ramipril; D001241:Aspirin