Prevention of blockage of partially obstructed coronary arteries with prostacyclin correlates with inhibition of platelet aggregation

Aiken, James W.; Gorman, Robert R.; Shebuski, Ronald J.

doi:10.1016/0090-6980(79)90001-7

Cited by 134 publications

(37 citation statements)

References 9 publications

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“…In addition, fresh thrombi in the coronary arteries were also found in some cases of exercise-related sudden death. 25 [35][36][37] A left thoracotomy was performed through the fifth intercostal space, and the fifth rib was removed. The heart was exposed and suspended in a pericardial cradle.…”

Section: Interaction Between Plasma Potassium Andmentioning

confidence: 99%

Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.

Lin

Young

1994

Circulation

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BACKGROUND Both plasma potassium ([K]) and epinephrine concentrations have been known to increase during exercise and decrease rapidly shortly after exercise; in addition, it is also known that exercise can promote coronary thrombosis in human and animal subjects. Many studies have shown that epinephrine has a stimulatory effect on coronary thrombosis; however, little information is available concerning the effect of raising plasma [K] on coronary thrombosis. The present study was designed to investigate the effect of raising plasma [K] and its interaction with epinephrine infusion on coronary thrombosis. METHODS AND RESULTS A canine model of coronary thrombosis was used, and the frequency of cyclic blood flow reductions (CFRs) resulting from thrombus formation in the circumflex artery was analyzed in the study. By acutely raising plasma [K] to approximately 6.0 mEq/L, the frequency of CFRs was reduced from 8.0 +/- 0.6 to 3.7 +/- 1.0 in 40 minutes (P < .01). Epinephrine infusion (0.5 microgram.kg-1 x min-1) stimulated the frequency of CFRs from 7.1 +/- 0.5 to 11.5 +/- 0.7 in 40 minutes (P < .01). However, if plasma [K] was raised to approximately 6.0 mEq/L while the epinephrine infusion was continued, the frequency fell from 11.5 +/- 0.7 to 7.7 +/- 1.1 in 40 minutes (P < .01). CONCLUSIONS The present study demonstrated that acutely raising plasma [K] inhibited coronary thrombosis in dogs and also blocked the potentiating effect of epinephrine on coronary thrombosis. These findings may suggest that raising plasma [K] exerts a protective effect against coronary thrombosis and that a rapid decrease in plasma [K], such as that occurring shortly after exercise, facilitates coronary artery thrombosis when the artery has a preexisting pathological condition.

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Section: Interaction Between Plasma Potassium Andmentioning

confidence: 99%

Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.

Lin

Young

1994

Circulation

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“…Aiken et al 22 showed in the canine coronary occlusion model that a shift of 2 uM to the right in the ADP dose-response curve is needed to slow the rate of coronary occlusion. During our 24-hour infusions at 4.0 ng/kg/min, there was a consistent 4-7-,gM shift to the right in the platelet ADP dose-response curve.…”

Section: Platelet Aggregationmentioning

confidence: 99%

Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels.

Data¹,

Molony²,

Meinzinger³

et al. 1981

Circulation

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SUMMARY Clinical tolerance, inhibition of platelet aggregation and intracellular platelet adenosine 3': 5'-cyclic monophosphate (cyclic AMP) levels were evaluated in normal volunteers given i.v. infusions of prostacyclin sodium at rates up to 15 ng/kg/min. Short-term infusions (30 and 60 minutes) were tolerated at rates up to 10.0 ng/kg/min; higher rates produced headaches, anxiety, nausea and vomiting. Six-hour and 24-hour infusions were tolerated at rates up to only 4.0 ng/kg/min. Twenty-four-hour infusions at 4 ng/kg/min produced a consistent 4-7-1.M shift to the right in the platelet ADP dose-response curve; this platelet inhibitory activity did not diminish during the infusion. Prostacyclin sodium infusion elevated intracellular cyclic AMP levels, the increases corresponding to the onset of measurable inhibition of ADP-induced aggregation, although the magnitude of the increase did not necessarily reflect the degree of inhibition. Increased template bleeding times were seen with a greater than 10-gM shift in the ADP dose-response curve. We conclude that although prostacyclin sodium has a narrow safety margin, the drug does produce platelet inhibition at infusion rates generally tolerated by healthy volunteers.

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“…Aiken, Gorman & Shebuski (1979) have shown that prostacyclin, applied epicardially to the dog's heart, can prevent or reverse platelet aggregation at sites of obstruction in the major coronary arteries. The endothelial vascular surface of the coronary circulation may not always be a sufficient source of prostacyclin to protect against thrombosis, particularly when the output of this substance is diminished by atherosclerotic vascular disease (Dembinska-Kiec, Gryglewska, Zmuda & Gryglewski, 1977;Sinzinger, Feigel, Silberbauer, 1979).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Prostacyclin Release From the Epicardium of Anaesthetized Dogs

Dusting

Nolan

1981

British J Pharmacology

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1 The generation of prostanoids in the hearts of anaesthetized dogs was studied by irrigating in situ the epicardial surface with Krebs solution. Prostanoids were measured by direct bioassay on smooth muscles and by radioimmunoassay of 6-oxo-prostaglandin Fl,. (6-oxo-PGF1,) and prostaglandin E2 (PGE2) in the epicardial irrigation fluid. 2 The epicardial irrigation fluid contained a prostacyclin-like substance, as indicated by the bioassay tissues, and immunoreactive 6-oxo-PGF1c; PGE2-like materials were also detected. By both methods the output of the prostacyclin-like substance, which decreased with time of epicardial irrigation, was increased by manipulating the heart and by adding arachidonic acid (3 pg/ml), and decreased by adding indomethacin (1 pg/ml) to the irrigating fluid.3 Bioassayed prostacyclin and immunoreactive 6-oxo-PGFi, in the epicardial irrigation fluid increased by about 3-5 ng/ml during and after infusion of isoprenaline (0.1 g kg-1 min-). The substance was not released by isoprenaline when indomethacin was added to the irrigating fluid, or when propranolol (0.5 mg/kg) was given intravenously. 4 Aortic constriction, bilateral carotid artery occlusion and intravenous angiotensin infusion all increased output of the prostacyclin-like substance into the epicardial irrigation fluid. The output was abolished by treating the heart with indomethacin (10 mg/kg intravenously or 1 jig/ml epicardially). 5 The prostacyclin-like substance was also released by all of the above stimuli after the parietal pericardium had been removed and replaced by a plastic sheet. 6 It is concluded that prostacyclin is continually released from tissues close to the epicardial surface and from the pericardium, and that prostacyclin generation increases when cardiac workload increases. Prostacyclin of epicardial or pericardial origin might therefore contribute to metabolic regulation of coronary blood flow.

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Prevention of blockage of partially obstructed coronary arteries with prostacyclin correlates with inhibition of platelet aggregation

Cited by 134 publications

References 9 publications

Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.

Interaction between plasma potassium and epinephrine in coronary thrombosis in dogs.

Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3':5'-cyclic monophosphate levels.

Stimulation of Prostacyclin Release From the Epicardium of Anaesthetized Dogs

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