Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease

Hærem, Jørgen W.

doi:10.1016/0021-9150(72)90070-6

Cited by 186 publications

(47 citation statements)

References 15 publications

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“…Both are vasoconstrictors and can either induce or potentiate platelet aggregation (Siess, 1989;De Clerck & Herman, 1983). Platelets have been shown to play a role in coronary vasospasm and sudden cardiac death has been linked to the occurrence of platelet aggregation in the coronary circulation (Haerem, 1972). Sudden cardiac death may be the result of severe arrhythmias occurring as a consequence of either myocardial ischaemia or subsequent abrupt reperfusion.…”

Section: Introductionmentioning

confidence: 99%

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists

Shaw

Coker

1996

British J Pharmacology

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3BX1 The effects of the 5-HT2 antagonist, ICI 170,809 and the thromboxane A2 antagonist, ICI 192,605, given alone and in combination (n = 12 per group), were examined in anaesthetized rats. Haemodynamics and arrhythmias induced by permanent coronary artery occlusion or by reperfusion after 5 min of ischaemia were monitored. 2 In a study on reperfusion-induced arrhythmias, the only significant effect of ICI 170,809 (1 mg kg', i.v.) was a reduction in the number of ventricular premature beats (VPBs). ICI 192,605 (1 mg kg-' min-1, iv.) did not alter reperfusion-induced arrhythmias. However, in combination, when compared with controls, these drugs caused significant reductions in the incidence of ventricular tachycardia (VT), 100% to 58%; ventricular fibrillation (VF), 92% to 33%; and the mortality due to sustained VF, 67% to 17%. There was also a significant reduction in the number of VPBs following reperfusion. 3 In a second study with lower doses of drugs, ICI 170,809 (0.3 mg kg-1) and ICI 192,605 (0.3 mg kg-' min-') had no significant effects on reperfusion-induced arrhythmias either alone or in combination. 4 A third study examined the effects of the higher doses of the drugs on ischaemia-induced arrhythmias. Neither drug alone, nor in combination, altered the incidence of ischaemia-induced VT, VF, the mortality, or the number of VPBs. 5 These results indicate that, in contrast to the administration of either drug alone, combined administration of a 5-HT2 antagonist and a thromboxane A2 antagonist caused marked suppression of reperfusion-induced but not ischaemia-induced arrhythmias.

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Section: Introductionmentioning

confidence: 99%

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists

Shaw

Coker

1996

British J Pharmacology

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“…contrast, elevated cyclic AMP in platelets would inhibit their aggregation (Packham & Mustard, 1980) and this may protect against ischaemia since inappropriate platelet aggregation has been implicated in the genesis of sudden cardiac death (Haerem, 1972).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effects of isobutylmethylxanthine and milrinone on ischaemia‐induced arrhythmias and platelet aggregation in anaesthetized rabbits

Holbrook

Coker

1989

British J Pharmacology

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IThe aim of this study was to compare the effects of the non-selective phosphodiesterase (PDE) inhibitor, isobutylmethylxanthine (IBMX) and the selective PDE III inhibitor, milrinone, in a rabbit model of acute myocardial ischaemia. 2 Coronary artery occlusion caused changes in the ST-segment of the ECG and ectopic activity in all control rabbits. Ventricular fibrillation occurred in 10 out of 14 (71%) of these animals. Pretreatment with IBMX 1004ugkg-1 plus 1O0gkg-1min-', starting 10min before coronary artery occlusion, reduced ischaemia-induced ST-segment changes and ventricular fibrillation occurred in only 10% of this group (n = 10). A similar dose of milrinone had no antiarrhythmic activity, whereas with a lower dose of milrinone, 30 Mgkg-I plus 3 Mgkg' min' (n = 10), only 30% of rabbits fibrillated and ST-segment changes were attenuated. 3 Acute administration of both IBMX and milrinone reduced arterial blood pressure. With the higher dose of milrinone a significant effect was still present after 10min of drug infusion. A greater hypotensive response to the higher dose of milrinone was observed in the rabbits which subsequently fibrillated during ischaemia. A marked tachycardia was also observed after administration of the higher dose of milrinone. 4 At the end of the experiment platelet aggregation was studied ex vivo. ADP-induced aggregation was reduced by pretreatment of the rabbits with milrinone but not IBMX. Both PDE inhibitors enhanced the ability of isoprenaline to inhibit ADP-induced platelet aggregation but milrinone was more effective, particularly at the higher dose. 5 The results demonstrate that IBMX was antiarrhythmic but that this activity was not directly related to inhibition of platelet aggregation. Adverse haemodynamic effects may explain the failure of milrinone to have similar activity during myocardial ischaemia.

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“…3 The latter has earlier been observed in subjects dying suddenly and suggests an important role of blood platelet emboli for the development of myocardial electrical instability and subsequent lethal arrhythmias. 4 Although the Northwick Park Heart Study demonstrated prospectively a strong association between high plasma levels of factor VII activity and plasma fibrinogen and coronary heart disease (CHD) morSee page 936 tality,5 we are not aware of prospective studies presenting evidence for a possible association between blood platelet count and in vitro platelet responsiveness with mortality due to cardiovascular causes. The present study was designed to test this possibility.…”

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confidence: 99%

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

et al. 1991

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BACKGROUND Experimental animal and clinical studies indicate that blood platelets have an important role in atherosclerosis and formation of thrombi. Prospective studies presenting evidence of an association between blood platelet count and cardiovascular mortality have not been performed. METHODS AND RESULTS From 1973 to 1975, blood platelets were counted, and their responsiveness to aggregating agents was studied in healthy middle-aged men. The aim was to assess the possible association between these variables and coronary heart disease. At 13.5 years of follow up, a significantly higher coronary heart disease mortality was observed among the 25% of subjects with the highest platelet counts. Platelet aggregation performed in a random subsample (150 of the 487 men), moreover, revealed that the 50% with the most rapid aggregation response after ADP stimulation had significantly increased coronary heart disease mortality compared with the others. These associations could not be explained by differences in age, lipids, blood pressure, or smoking habits. CONCLUSIONS The present study is the first to present conclusive, prospective evidence of an association between platelet concentration and aggregability and long-term incidence of fatal coronary heart disease in a population of apparently healthy middle-aged men.

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Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease

Cited by 186 publications

References 15 publications

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists

Comparison of the effects of isobutylmethylxanthine and milrinone on ischaemia‐induced arrhythmias and platelet aggregation in anaesthetized rabbits

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

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Platelet aggregates in intramyocardial vessels of patients dying suddenly and unexpectedly of coronary artery disease

Cited by 186 publications

References 15 publications

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT2 and thromboxane A2 antagonists

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT2 and thromboxane A2 antagonists

Comparison of the effects of isobutylmethylxanthine and milrinone on ischaemia‐induced arrhythmias and platelet aggregation in anaesthetized rabbits

Blood platelet count and function are related to total and cardiovascular death in apparently healthy men.

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Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists

Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT₂ and thromboxane A₂ antagonists