Brief Reports

Endothelin-1 release from atherosclerotic plaque after percutaneous transluminal coronary angioplasty in stable angina pectoris and single-vessel coronary artery disease

Percutaneous coronary intervention (PCI) is known to induce atherosclerotic plaque rupture, which may affect resting distal microvascular perfusion either through distal microvascular spasm or through embolization. We evaluated the effect of PCI on resting microvascular flow.

We performed cardiovascular magnetic resonance imaging to assess left ventricular systolic function and microvascular perfusion in 15 patients with stable coronary artery disease before and within 24 hours after PCI and in 10 control subjects without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Microvascular perfusion was evaluated at rest after injecting a bolus of gadolinium–diethylenetriamine pentaacetic acid (0.1 mmol/kg) by calculating the time to 50% maximum myocardial enhancement (T_{50% max}), as well as the relative upslope, of the myocardial signal intensity curve. Regional perfusion and systolic thickening were evaluated using a 16-segment left ventricular model with the slice locations matched anatomically pre-PCI and post-PCI. The relative contrast delay in the region of myocardium subtended by the PCI artery was calculated by subtracting the T_{50% max} of a remote region from the PCI region.

In subjects with coronary artery disease, PCI resulted in a regional contrast delay (mean delay 0.6 ± 0.2 seconds post-PCI vs 0.0 ± 0.2 seconds pre-PCI, P < .05) and a reduction in the relative upslope (8.6 ± 0.5 post-PCI vs 10.1 ± 0.7 pre-PCI, P = .02), consistent with reduced microvascular perfusion. This was unaccompanied by any change in regional systolic thickening (54% ± 7% pre-PCI vs 53% ± 5% post-PCI, P = NS).

The data show PCI-induced impairment of resting microvascular perfusion in the area of myocardium subtended by the treated artery after PCI, a likely consequence of iatrogenic atherosclerotic plaque rupture.

Plasma levels of endothelin-1 (ET-1) increase after coronary angioplasty (PTCA) due to endothelial injury during the procedure. ET-1 has been found in human endocardial and myocardial cells. It is not known whether ET-1 increases after thermal injury induced by radiofrequency catheter ablation (RFA).

We determined plasma ET-1 levels at baseline, immediately after, and at 2 and 6 h post-procedure in 31 patients undergoing PTCA and 16 patients undergoing RFA. Patients subjected to diagnostic coronary angiography (n=15) or electrophysiology study (n=13) served as controls.

Compared to baseline, ET-1 levels increased significantly immediately post-PTCA (55.1±20.1 vs. 42.7±14.9 pg/ml, p<0.01) and at 2 h post-RFA (98.0±11.7 vs. 53.0±17.4 pg/ml, p<0.01) and returned to baseline measurements at 2 h post-PTCA and 6 h post-RFA. There was no change of ET-1 levels in the control groups. ET-1 kinetics curve was significantly higher post-RFA compared to post-PTCA (p<0.001). ET-1 immediately post-PTCA correlated with total pressure–time product applied for balloon inflation during the procedure (r=0.56, p<0.01). There was no correlation between ET-1 levels and the number of RFA applications. No patient developed ischemia post-PTCA. There were no complications or arrhythmia recurrences post-RFA.

Endocardial thermal injury incurred during RFA is another mechanism of endothelin increase apart from mechanical injury of the coronary endothelium during PTCA and represents further evidence for the existence of the peptide in human endocardial endothelial and myocardial cells. ET-1 increase is delayed and more pronounced post-RFA compared to post-PTCA. Despite that, it does not seem to have any clinical impact in the immediate post-RFA period.

Direct stenting may reduce trauma to the vessel wall, thereby having a positive impact on acute and long-term results. This study evaluated acute vessel trauma and acute and follow-up angiographic and intravascular ultrasound (IVUS) results after direct stenting in comparison to conventional stenting.

Two hundred forty-nine patients were randomly assigned to direct stenting (n = 124) or stenting after predilatation (n = 125) and were followed up by angiography at 6 ± 2 months. Intracoronary serum endothelin (ET-1) levels were determined distal to the lesion before and after coronary intervention to define vessel trauma, and IVUS was performed before and after intervention and at follow-up to determine induced changes in vessel morphology and intimal hyperplasia in a subgroup of 40 patients.

Feasibility of direct stenting was 91%, with 9% requiring crossover to predilatation. There were no differences between the 2 groups in immediate clinical, angiographic, and intravascular ultrasound results. Intracoronary ET-1 levels increased significantly after intervention, without differences between the 2 groups (increase in ET-1 level, 0.79 ± 1.06 vs 0.96 ± 1.22 fmol/L, P = .206). At 6-month follow-up, angiographic late loss (0.76 ± 0.86 vs 0.69 ± 1.09 mm, P = .788) and restenosis rate (21% vs 20%, P = 1.000) were similar for direct stenting versus conventional stenting, respectively. IVUS demonstrated comparable intimal hyperplasia areas for direct versus conventional stenting (2.0 ± 1.5 mm² vs 2.2 ± 1.6 mm², respectively, P = .243).

Direct stenting is highly feasible and results in similar vessel trauma and change in vessel morphology and acute lumen dimensions compared with stenting after predilatation. Similar acute angiographic and IVUS results persist at 6-month follow-up.

Early microvascular constriction following atherosclerotic plaque rupture may be mediated via serotonin and/or endothelin-1. Atherosclerotic lesions in the rabbit hindlimb underwent plaque rupture, resulting in a rapid reduction of distal flow (7.1±0.7 ml/min pre-rupture versus 3.6±0.6 ml/min post-rupture, P<0.001) and a rise in distal microvascular resistance (10.5±0.9 mm Hg min/ml pre-rupture versus 23.5±3.5 mm Hg min/ml post-rupture, P=0.01). Distal microvascular resistance remained elevated following endothelin-1 receptor antagonism and control vehicle, but normalised after serotonin receptor antagonism with ritanserin (10.5±0.9 mm Hg min/ml pre-rupture versus 22.2±6.0 mm Hg min/ml post-endothelin-1 receptor antagonism [P<0.05] versus 21.6±6.2 mm Hg min/ml post-control vehicle [P<0.05] versus 11.6±2.0 mm Hg min/ml post-ritanserin [P=NS]). Early antagonism of serotonin receptors protects against distal microvascular constriction following atherosclerotic plaque rupture.