Prevention of occlusive coronary artery thrombosis by prostacyclin infusion in the dog.

Romson, Joseph L.; Haack, David W.; Abrams, Gerald D.; Lucchesi, Benedict R.

doi:10.1161/01.cir.64.5.906

Cited by 39 publications

(21 citation statements)

References 25 publications

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“…Although potentiating effects are difficult to evaluate in a model where the response is of the all-or-none type, these authors were able to demonstrate an antithrombotic efficiency of a phosphodiesterase inhibitor with low doses of PGI2 in vivo. These combinations induced only moderate depressor effects compared to single PGI2 infusions with identical protective effects studied in the same model (Romson et al, 1981).…”

Section: ±4mentioning

confidence: 76%

In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725

Darius

Lefer

Leprán

et al. 1985

British J Pharmacology

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1 Prostacyclin (PGI2) inactivates platelets by stimulation of adenylate cyclase, and its effect can be potentiated in vitro by simultaneous inhibition of cyclic AMP phosphodiesterase. 2 The interaction of synthetic PGI2 and the potent phosphodiesterase inhibitor HL 725 was studied in a model of systemic platelet activation by intravenous injection of collagen. Platelet aggregate formation was evaluated by continuous on-line measurement of the circulating platelet count. 3 Collagen injection in rabbits receiving vehicle caused a 30 3% decrease in the circulating platelet count. Infusion of PGI2 (0.05, 0.1 and 0.75 fg kg-' min-) dose-dependently inhibited this decrease. HL 725 (0.5, 1 and 3 Ag kg-l min-i) caused a slight but significant effect. 4 Combinations of PGI2 and HL725, respectively, at 0.25 + 1.0 and 0.1 + 0.5 tig kg-' min-' inhibited platelet aggregate formation to a greater extent than when either substance was used alone and produced a comparable inhibition to PGI2 at 0.75 ytg kg-' min-. 5 Collagen induced an acute fall in the mean arterial blood pressure (MABP) which also was inhibited by PGI2, HL 725 and their combinations. 6 The infusion of a combination of PGI2 and HL 725 before collagen produced a decrease in the MABP which was greater than when either compound was used on its own. 7 Thus, PGI2 and the phosphodiesterase inhibitor HL725 interact in vivo to inhibit platelet aggregation and lower MABP.

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Section: ±4mentioning

confidence: 76%

In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725

Darius

Lefer

Leprán

et al. 1985

British J Pharmacology

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“…Prostacyclin (PGI2) has been shown to affect cardiac rhythm following coronary ischemia in a beneficial manner (6) and to prevent coronary thrombosis and arrhythmias (7). In the present study, we tested the ability of PGI2 to influence the incidence of ventricular fibrillation.…”

Section: Fiedler and Mardin Pgie On Sudden Cardiac Death 41mentioning

confidence: 99%

Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death

Fiedler

Mardin

1986

Basic Res Cardiol

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The antifibrillatory, antithrombotic and hemodynamic properties of intraventricular prostacyclin (PGI2) application were studied in conscious canine model of sudden cardiac death. In anesthetized dogs, a wire electrode was implanted into the left circumflex coronary artery (LCX) and acute myocardial ischemia was produced by 90 min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. An intracardiac pressure transducer measured ventricular pressure, heart rate, filling pressure and dP/dt. The ECG was obtained from subcutaneous chest needles. Six days later while in ambulatory state, a 180 microA DC current was applied for 4 h to the LCX intimal lining in Tris-HCl (n = 10) and PGI2-treated dogs (50 and 100 ng/kg/min, 11 and 12 dogs, respectively). Myocardial injury and coronary thrombosis induced by electrical stimulation produced ventricular fibrillation in all vehicle-treated dogs at 145 +/- 33 min (mean +/- S.D.). In PGI2-treated hearts only 2 animals fibrillated at 150 +/- 29 min and 180 +/- 52 min following 50 and 100 ng/kg/min of the prostanoid, respectively. Thus, 18/23 PGI2-treated dogs survived 4 h electrical stimulation of the artery. Within the LAD perfusion zone infarction was observed of equal volumes in vehicle and PGI2-treated animals. No ischemia occurred distal to the LCX coronary thrombosis. Ventricular pressure fell in all groups. Heart rate increased in the controls and those animals treated with 50 ng/kg/min PGI2 while 100 ng/kg/min PGI2 increased heart rate by 22 +/- 5% (p less than 0.05). Filling pressure increased in controls but fell in the PGI2-treated hearts. The results indicate that PGI2 can prevent ventricular fibrillation resulting from acute ischemia at a site distant to previous myocardial ischemia with superimposed intimal injury and coronary thrombosis. The PGI2 properties are due to prevention of coronary thrombosis and the occlusion of the artery. Antifibrillatory effects of the prostanoids are suggested.

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“…It would thus be of great interest to investigate if these substances could prevent thrombus formation in vivo. Consequently, in the present study the effect of NTG, ISDN and M was investigated in a recently developed model of coronary artery thrombosis in the anesthetized dog (24).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

Martorana¹,

Kettenbach²,

Göbel³

et al. 1984

Basic Res Cardiol

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Platelet activation and aggregation in the coronary circulation may be important in the pathogenesis of myocardial ischemia. Molsidomine (M), isosorbide dinitrate (ISDN) and nitroglycerin (NTG) have been found to inhibit platelet aggregation in vitro. In the present study, the activity of these compounds was investigated in a model of coronary artery thrombosis in vivo. Dogs were anesthetized, thoracotomized, and their heart was exposed. An electrode was inserted into the left circumflex coronary artery and set to rest on the intima. Electrical stimulation (9 V, 150 microA) lasted for 6 h. Compounds (each in 2 dose levels) were given as an i.v. infusion starting 30 min after the beginning of the stimulation and lasting for the duration of the experiment. All control (saline-treated) animals underwent thrombotic occlusion of the coronary artery as assessed by flow measurement. On the other hand, 2/8 dogs treated with the lower M dose and 4/8 dogs treated with the higher M dose did not have a coronary occlusion. Neither ISDN nor NTG, at both doses, prevented the coronary occlusion. In control animals thrombus wet weight was 74.43 +/- 11.25 mg. M reduced the thrombus weight in a dose-related manner, while ISDN (marginally) and NTG (significantly at the higher dose) increased this parameter. Following the coronary thrombosis, all control animals developed myocardial infarcts as assessed by the tetrazolium technique. Similarly all animals treated with ISDN and with NTG (at both doses) showed infarcts. However, 3/8 M-dogs did not have a myocardial infarction in the lower as well as in the higher dose groups. The hemodynamic changes induced by the 3 compounds were similar in magnitude. Thus M but not ISDN or NTG showed in this in-vivo study antithrombotic and consequently antiischemic activity.

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Prevention of occlusive coronary artery thrombosis by prostacyclin infusion in the dog.

Cited by 39 publications

References 25 publications

In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725

In vivo interaction of prostacyclin with an inhibitor of cyclic nucleotide phosphodiesterase, HL 725

Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death

Comparison of the effects of molsidomine, nitroglycerin and isosorbide dinitrate on experimentally induced coronary artery thrombosis in the dog

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