Endothelin-1 exacerbates diastolic stunning in conscious dogs

Hayashida, Wataru; Donckier, Julian; Mechelen, Henri Van; Stoleru, L.; Pouleur, H.

doi:10.1152/ajpheart.1993.265.5.h1688

Cited by 7 publications

(3 citation statements)

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“…Since vasoconstriction can modulate myocardial ischemia, we evaluated plasma ET-1 levels during MS. While it has been established that coronary and systemic plasma concentrations of ET-1 increase following myocardial infarction, there is lack of evidence regarding the role of ET-1 endothelial release during MS. A significant role of ET-1 in the pathogenesis of diastolic MS was reported in conscious dogs (18). Our results are concordant with a previous clinical observation that while plasma ET-1 increases dramatically during reperfusion, it does not increase during myocardial ischemia per se (19).…”

Section: Endothelin-1supporting

confidence: 93%

Mild Myocardial Stunning Affects Platelet Aggregation and Certain Hemostatic Factors in Swine

Serebruany

Yurovsky

Gurbel

1999

Clin Appl Thromb Hemost

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Myocardial stunning is characterized by transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. Platelet activation and hemostatic abnormalities have been described in patients with unstable angina and acute myocardial infarction, however, their role in the pathogenesis of myocardial stunning is unknown. The purpose of this study was to determine if platelet aggregation and certain hemostatic factors change during myocardial stunning following brief coronary arterial occlusion. Nine Yorkshire swine underwent left anterior descending coronary artery occlusion for 8 minutes followed by 90 minutes of reperfusion. Blood samples were obtained at baseline, at 4 and 8 minutes of occlusion, and at 60 and 90 minutes of reperfusion. Platelet aggregability and concentrations of antithrombin III, protein C, protein S, fibronectin, endothelin 1, and the stable metabolites of thromboxane (TxB2) and prostacyclin (6-keto-PGF1a) were measured in systemic circulation. The occlusion phase was associated with a decline of endothelin 1 (-13.6%), and TxB2 (-19.6%), and elevation of antithrombin III (+40.2%) and protein C (+22.9%). Mild myocardial stunning was associated with a significant increase in platelet aggregation (+33.7%), endothelin-1 (+24.7%), 6-keto-PGF1a (+41.5%), TxB2 (+11.9%), and protein C (+42.3%) during the reperfusion phase. There were no changes in plasma fibronectin and total protein S. Thus, mild myocardial stunning following brief coronary artery occlusion is associated with substantial dynamic changes in platelet aggregability and certain hemostatic factors. These results may be relevant to understanding the mechanisms determining myocardial stunning and coronary arterial patency following reperfusion.

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Section: Endothelin-1supporting

confidence: 93%

Mild Myocardial Stunning Affects Platelet Aggregation and Certain Hemostatic Factors in Swine

Serebruany

Yurovsky

Gurbel

1999

Clin Appl Thromb Hemost

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“…In view of the ability of MIA to inhibit the effect of 0.4 nmol/L ET-1 on -dF/dt, one possible explanation for this effect may be Na+-H+ exchange activation by ET-1 using normally perfused rabbit hearts at an ET-1 concentration of 5 nmol/L, although, surprisingly, in that study neither a positive or negative inotropic effect of ET-1 was observed.5 Furthermore, it has very recently been reported that ET-1 infusion in conscious dogs exacerbates diastolic dysfunction after a 10-minute coronary artery occlusion and 60-minute reperfusion. 30 Thus, in that model ET-1 increased the degree of what the authors referred to as "diastolic stunning." Taken together, the evidence strongly suggests that diastolic dysfunction represents an important consequence of ET-1 administration, particularly at low doses or concentrations.…”

Section: Discussionmentioning

confidence: 89%

Role of Na(+)-H+ exchange in mediating effects of endothelin-1 on normal and ischemic/reperfused hearts.

Khandoudi

Karmazyn

1994

Circulation Research

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Endothelin (ET) has been shown to be elevated under conditions of cardiac pathology and to produce diverse cardiac effects, including coronary constriction and a positive inotropic influence. We characterized the concentration- and time-dependent effects of the most potent of the ET isoforms, ET-1 (0.4, 2, and 4 nmol/L), on myocardial contractility and coronary resistance and assessed its effects on the ischemic and reperfused heart. Because ET-1 has been shown to activate the Na(+)-H+ exchanger in cardiac myocytes, we determined the contribution of the antiport by examining the effects of ET-1 in the presence of the Na(+)-H+ exchange inhibitor methylisobutyl amiloride (MIA). At all three concentrations, ET-1 produced an initial positive inotropic effect that was reversed with continued perfusion, the degree of the reversal being dependent on ET-1 concentration. With 0.4 nmol/L, contractility returned to pre-ET-1 values, whereas after 75 minutes of perfusion with 4 nmol/L ET-1, contractility was depressed by 75%. At all concentrations, ET-1 produced a coronary-constricting effect, whereas an elevation in resting tension was observed only with 4 nmol/L ET-1. MIA significantly prevented the positive inotropic effect of ET-1 but had no effect on loss in function or elevation in resting tension produced by 4 nmol/L ET-1. Furthermore, MIA partially, but not significantly, attenuated the constricting effects of all ET-1 concentrations. In the ischemic heart, 0.4 nmol/L ET-1 appeared to delay the loss in contractility produced by cessation of flow, although the effect was not significant. Higher concentrations of ET-1 were without effect on ischemia-induced contractile depression, although their presence produced a marked elevation in resting tension during ischemia that was attenuated by MIA. Recovery in contractility was reduced by all concentrations of ET-1, although the effects of the lowest concentration were associated primarily with defective relaxation. The depressant effects of ET-1 either in normal or ischemic/reperfused hearts were irreversible. The inhibitory effects of ET-1 on contractile recovery were associated with diminished tissue glycogen and elevated lactate levels. High-energy phosphates after reperfusion were depressed in hearts treated with 4 nmol/L ET-1. The attenuation in contractile recovery and alterations in metabolite content were prevented by MIA. These results provide evidence that ET-1 produces complex effects on heart function that are likely mediated via different mechanisms and demonstrate its ability to aggravate ischemic and reperfusion injury through a mechanism possibly involving Na(+)-H+ exchange activation.

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“…Since vasoconstriction is an important fac tor in the modulation of myocardial ischemia, we evaluated plasma ET-1 levels during MS. Both coronary and systemic plasma concen trations of ET-1 increase following myocar dial infarction, there is lack of evidence re garding the role of ET-1 during systolic [23] and diastolic MS [24], Our results are condordant with a previous clinical observation that while plasma ET-1 increases during reperfu sion, it does not increase during myocardial ischemia per se [25], ET-1 has been shown to be released from the porcine heart during MS [26], which is also in agreement with the cur rent data.…”

Section: Discussionmentioning

confidence: 99%

Mac-1 Inhibitor Affects Certain Hemostatic Parameters during Myocardial Stunning in Swine

et al. 1996

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Myocardial stunning (MS) is a transient contractile dysfunction occurring subsequent to an episode of ischemia followed by reperfusion. NPC 15669 is a leumedin, which inhibits leukocyte adhesion to the endothelium by blocking Mac-1 upregulation. The effect of NPC 15669 supplementation on the hemostasis during MS is unknown. We linked the potential changes in the hemostasis with NPC 15669 therapy during mild MS. Twelve Yorkshire swine underwent coronary artery occlusion for 8 min followed by 90 min of reperfusion. NPC 15669 (10 mg/kg loading dose followed by constant infusion at 6 mg kg^–1 h^–1) was administered to 6 of the animals; another 6 swine received saline and served as the controls. Concentrations of antithrombin III (AT-III), protein C, total protein S, fibronectin, endothelin 1 (ET-1) and the stable metabolites of thromboxane (TxB₂) and prostacyclin (6-keto-PGF_1α) were measured in the systemic circulation. NPC 15669 therapy was associated with diminished ET-1 (37.4%) and 6-keto-PGF_1α (47.1%) levels and increased fibronectin (77.6%) concentrations during MS. There were no changes in the plasma concentrations of TxB₂ total protein S, protein C and AT-III in the NPC 15669 group when compared with controls. Mild MS is associated with substantial changes in the hemostatic profile. NPC 15669 administration in a swine model of MS affects certain hemostatic parameters. These data provide support for the involvement of cellular mechanisms in the pathogenesis of MS. The ability of leumedins to modulate hemostasis may have implications for their use in cardiovascular disease.

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Endothelin-1 exacerbates diastolic stunning in conscious dogs

Cited by 7 publications

References 0 publications

Mild Myocardial Stunning Affects Platelet Aggregation and Certain Hemostatic Factors in Swine

Mild Myocardial Stunning Affects Platelet Aggregation and Certain Hemostatic Factors in Swine

Role of Na(+)-H+ exchange in mediating effects of endothelin-1 on normal and ischemic/reperfused hearts.

Mac-1 Inhibitor Affects Certain Hemostatic Parameters during Myocardial Stunning in Swine

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