A Comparison of Four Potential Agents for Reducing Necrosis after Prolonged Coronary Occlusion

Weisse, Allen B.; Regan, Timothy J.

doi:10.1002/j.1552-4604.1978.tb01589.x

Cited by 7 publications

(1 citation statement)

References 33 publications

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“…Salvage of myocardium was attributed primarily to the increase in collateral blood flow to the ischemic region. Several other groups have also shown the effectiveness of dipyridamole in reducing myocardial ischemic injury (2,3,4). However, in our view the precise mechanism of action of the salutary effects of dipyridamole is not known.…”

Section: Introductionmentioning

confidence: 93%

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog

1985

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The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n = 9), 0.1 (group B, n = 10) or 0.5 (group C, n = 9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9 +/- 5.4% vs. 25.2 +/- 7.7% in group A (n = 9), 21.8 +/- 7.3% vs. 18.3 +/- 5.2% in group B (n = 9), and 22.3 +/- 7.7% vs. 16.2 +/- 4.8% in group C (n = 8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42 +/- 7 nmol/gww in group C and 40 +/- 5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395 +/- 6 nmol/gww in group C: p less than 0.01, 55 +/- 10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.

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Section: Introductionmentioning

confidence: 93%

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog

1985

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Effects of oxygen administration and alteration in arterial Pco2 on ischemic myocardial changes following experimental coronary artery ligation

Weisse¹,

Moore²,

Zweil³

et al. 1982

American Heart Journal

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Salvage of ischemic myocardium by dipyridamole in the conscious dog.

et al. 1981

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SUMMARY We investigated the effect of i.v. dipyridamole, a potent small-vessel coronary vasodilator, on myocardial infarct size in conscious dogs. Dipyridamole, ,ug/kg; 15 dogs) or saline (15 dogs) was infused for 6 hours beginning 10 minutes after acute permanent occlusion of the mid-circumflex coronary artery. After sacrifice, 48 hours after occlusion, stereoscopic postmortem angiography was used to define the mass DRUGS that dilate the coronary arteries are often categorized by their predominant site of action, the large epicardial conductance arteries or the small, precapillary (arteriolar) resistance vessels. Large-vessel dilators, such as nitrates or slow-channel calcium blockers, have been shown to reduce ischemic injury during coronary artery occlusion by increasing collateral flow,1-5 reducing myocardial oxygen demands6' 7 or both; small-vessel dilators have produced variable results. In some studies these agents have produced a deleterious effect by diverting flow away from ischemic myocardium toward nonischemic regions -a socalled coronary steal. This problem has been associated in the dog with the presence of occlusive lesions in more than one coronary artery.8 In other reports, hypotension resulting from the systemic effects of these small-vessel dilators has led to reduced coronary perfusion pressure and diminished collateral flow.This study was designed to determine whether dipyridamole, a prototype coronary arteriolar dilator, could augment collateral blood flow and reduce ultimate infarct size in conscious dogs with permanent coronary artery occlusion. By using a model with a single coronary artery occlusion and by using dipyridamole in small doses that produced minimal From Circulation 64, No. 5, 1981. decreases in blood pressure, we hypothesized that beneficial effects on myocardial salvage would be found. Methods InstrumentationThirty-eight dogs, 18-24 kg, were instrumented under pentobarbital general anesthesia. A left thoracotomy was performed and an occluder snare placed around the left circumflex coronary artery just past the first large marginal branch, 2-3 cm from the aorta. The snare consisted of a silk thread that was attached to a plastic tube at one end and looped around the coronary artery before exiting through the same plastic tube. Polyethylene catheters were placed in the right external jugular vein, right common carotid artery and left atrium. The distal ends of these catheters and the tube containing the snare thread were externalized at the back of the neck through a subcutaneous tunnel. Penicillin (1 million units) and Streptomycin (1 g) were given intramuscularly after surgery and the catheters were filled with heparinized saline.

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A Comparison of Four Potential Agents for Reducing Necrosis after Prolonged Coronary Occlusion

Cited by 7 publications

References 33 publications

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog

Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog

Effects of oxygen administration and alteration in arterial Pco2 on ischemic myocardial changes following experimental coronary artery ligation

Salvage of ischemic myocardium by dipyridamole in the conscious dog.

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