Circulating endothelin in patients undergoing coronary artery bypass grafting

Matheis, G.; Haak, Thomas; Beyersdorf, Friedhelm; Baretti, Rufus; Polywka, C; Br, Winkelmann

doi:10.1016/s1010-7940(05)80161-7

Cited by 36 publications

(25 citation statements)

References 25 publications

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“…ET levels are elevated in a number of cardiovascular disorders including following myocardial infarction, heart failure and following cardioplegic arrest and cardiac surgery [7][8][9][10][11][12]. It has been suggested that elevated ET-1 levels following ischaemia may result in the so called ' low coronary reflow ' phenomenon [13].…”

Section: Introductionmentioning

confidence: 99%

Differential effects of endothelin-1 on isolated working rat hearts before and after ischaemia and reperfusion

et al. 2002

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Endothelin (ET) may have both detrimental (reduced coronary flow) and beneficial effects (positive inotrope, reduced arrhythmogenesis) following ischaemia. We examined the effects of ET on cardiac function during reperfusion following prolonged hypothermic cardioplegic arrest in a protocol mimicking cardiac transplantation. Isolated working rat hearts were perfused with Krebs buffer to which increasing concentrations of ET-1 or sarafotoxin S6c had been added. Identical experiments were performed after 4 h of cardioplegic arrest at 4 degrees C. Under pre-ischaemic conditions ET-1 caused a dose-dependent decrease in cardiac function compared with controls. In contrast, following ischaemia low doses of ET-1 (10(-10) M) caused a significant and beneficial increase in cardiac output (109.1% versus 81.3%), dP/dt i.e. the rate of change of pressure with time (94.7% versus 75.6%) and stroke volume (100.3% versus 77.5%) compared with controls (P<0.05). At higher doses of ET-1 there was a detrimental effect on cardiac output, dP/dt and stroke volume similar to that seen prior to ischaemia. Sarafotoxin S6c had no significant effect pre or post ischaemia on any of the parameters measured compared with controls (P=not significant). ET-1 at low concentrations during reperfusion can improve the recovery of cardiac function mediated via ET(A) receptors. ET may play an important physiological role in the recovery of cardiac function following prolonged ischaemia.

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Section: Introductionmentioning

confidence: 99%

Differential effects of endothelin-1 on isolated working rat hearts before and after ischaemia and reperfusion

et al. 2002

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“…It is documented that ET-1 might affect postoperative outcome negatively in patients undergoing cardiac surgery [8,9,18]. Previous studies have reported that during cardiac surgery, the use of CPB leads to elevated plasma levels of ET-1 [19,20], and that levels remain elevated for 24 h [8,18]. Zhu et al [21] demonstrated that plasma ET-1 peaked after cessation of CPB in patients undergoing valvular surgery and correlated positively with bypass time.…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 in the Human Myocardium and Circulating Plasma: Evaluation before, during and after Correction of Aortic Stenosis with Aortic Valve Replacement

Majak¹,

Bjørnstad²,

Braathen³

et al. 2012

Cardiology

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Objectives: Due to the pathological effects of endothelin-1 (ET-1) on cardiomyocytes and the extracellular matrix, ET-1 levels may impact on the prognosis of aortic stenosis (AS) patients operated with aortic valve replacement (AVR). We examined ET-1 levels in AS patients throughout the whole AVR process, thus exposing potential therapeutic windows of opportunity. Methods: Plasma ET-1 levels were measured before and 2 days, 6 and 12 months after AVR in 22 patients with AS. Myocardial ET-1 was measured in biopsies from 7 patients undergoing AVR. Peroperatively, plasma ET-1 was analyzed in the coronary sinus and radial artery before aortic cross-clamp and at 5 and 20 min of reperfusion, in a second group of 30 patients. Results: Circulating ET-1 levels were transiently increased 2.6-fold 2 days following AVR. Myocardial ET-1 protein was 2.1-fold higher in patients with AS compared to controls. Plasma levels of ET-1 correlated to echocardiographic markers of diastolic dysfunction postoperatively. There was no increase in plasma ET-1 during early reperfusion, but veno-arterial differences indicated potential cardiac ET-1 extraction. Conclusions: Plasma ET-1 increases 2 days following AVR and myocardial ET-1 protein levels are increased in patients with AS before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.

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“…ET levels are elevated in a number of cardiovascular disorders, including following myocardial infarction, heart failure and following cardioplegic arrest and cardiac surgery [4][5][6][7][8][9]. This may appear surprising in the absence of the up-regulation of preproET-1 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also demonstrated the role of ET-1 in basal coronary tone in rats [2] and humans [3]. ET levels are elevated in a number of cardiovascular disorders, including following myocardial infarction, heart failure and following cardioplegic arrest and cardiac surgery [4][5][6][7][8][9]. It has been suggested that elevated ET-1 levels following ischaemia may result in the so-called ' low coronary reflow ' phenomenon [10,11].…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest

et al. 2002

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Endothelin-1 (ET-1) is believed to play an important role in cardiac ischaemia/reperfusion injury. ET-1 is synthesized from preproET-1 by the action of ET-converting enzyme (ECE). It is unclear to what extent the ET system is activated following prolonged ischaemia. In this study we used a model mimicking the conditions of the donor heart during transplantation. Isolated rat hearts perfused with Krebs-Henseleit buffer were subjected to 30 min of normothermic perfusion, then 4 h of cardioplegic arrest at 4 degrees C with St Thomas' Hospital solution, followed by reperfusion for 2 h. Hearts were freeze-clamped at different time points during the protocol. Using quantitative reverse transcription-PCR, relative levels of ET-1 and ECE mRNA expression were measured and compared with a housekeeping gene (ribosomal protein L32). During reperfusion there was a consistent decrease in coronary flow to approx. 85-90% of pre-ischaemic flow. There was no significant alteration in preproET-1 mRNA expression during 2 h of reperfusion. However, ECE mRNA expression was increased by 77.5% at 1 h and by 74.6% at 2 h following ischaemia compared with pre-ischaemic values (P<0.05). Thus we conclude that ECE mRNA expression is increased following prolonged hypothermic cardioplegic arrest. Elevations in the expression of this enzyme may help to explain the role of the ET system in the pathogenesis of ischaemia/reperfusion injury following cardiac surgery and transplantation.

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Circulating endothelin in patients undergoing coronary artery bypass grafting

Cited by 36 publications

References 25 publications

Differential effects of endothelin-1 on isolated working rat hearts before and after ischaemia and reperfusion

Differential effects of endothelin-1 on isolated working rat hearts before and after ischaemia and reperfusion

Endothelin-1 in the Human Myocardium and Circulating Plasma: Evaluation before, during and after Correction of Aortic Stenosis with Aortic Valve Replacement

Up-regulation of endothelin-converting-enzyme mRNA expression following cardioplegic arrest

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