Abdul Razakjr Omar

New Set of Intravascular Ultrasound-Derived Anatomic Criteria for Defining Functionally Significant Stenoses in Small Coronary Arteries (Results from Intravascular Ultrasound Diagnostic Evaluation of Atherosclerosis in Singapore (IDEAS) Study)

We sought to determine the intravascular ultrasound-derived anatomic criteria for functionally significant lesions in small coronary arteries with a reference segment diameter <3 mm. A fractional flow reserve (FFR) of <0.75, as determined by pressure wire using high-dose (100 to 150 microg) intracoronary adenosine, was used as the reference standard for functional significance. For the 94 patients/lesions involved in the present study, the average reference vessel diameter was 2.72 mm. The FFR was <0.75 in 38 patients (40.4%) and > or =0.75 in 56 patients (59.6%). Logistic regression analysis identified the minimal lumen area, plaque burden, and lesion length as the 3 most important determinants of the FFR. Using classification and regression tree analysis, the best cutoff values for these determinants to discriminate a FFR of <0.75 versus > or =0.75 were a minimal lumen area of < or =2.0 mm(2) (sensitivity 82.35%, specificity 80.77%), plaque burden of > or =80% (sensitivity 87.9%, specificity 78.9%), and lesion length of > or =20 mm (sensitivity 63.6%, specificity 78.9%). A significant increase was found in the area under the receiver operating characteristic curve of the combined parameters (minimal lumen area plus plaque burden plus lesion length) compared to the plaque burden (p = 0.014) and other individual parameters (p <0.001). In conclusion, we found that intravascular ultrasound-derived anatomic criteria are able to predict the functional significance of intermediate lesions in small coronary arteries. A minimal lumen area of < or =2.0 mm(2), plaque burden of > or =80%, and lesion length of > or =20 mm predicted a FFR of <0.75 with good sensitivity and specificity.

Reducing ischaemia/reperfusion injury through δ-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling

AIMS The purpose of this study was to determine whether intrinsic cardiac adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting synergistic adrenopeptidergic cardioprotection. METHODS AND RESULTS In situ hybridization coupled with immunostaining demonstrated that ICA cells exclusively expressed CGRP mRNA and co-expressed CGRP and delta-opioid receptor in human and rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP release from ICA cells in human and rat hearts. The delta-opioid agonist [D-Pen(25)]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with DPDPE reduced infarct size (IS) by 51 +/- 16% (P < 0.01). Co-infusion of beta(2)-adrenergic receptor (beta(2)-AR) and CGRP receptor (CGRP-R) antagonists increased IS by 62 +/- 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS reduction. Pre-treatment of ICA cell-myocyte co-culture with the beta(2)-AR/CGRP-R antagonists increased myocyte death rate by 24 +/- 4% (P < 0.01) and abolished DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O(2)). In the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection. Supplementing ICA cell-depleted myocyte culture with beta(2)-AR/CGRP-R agonists reduced hypoxia/re-O(2)-induced myocyte death by 24 +/- 5% (P < 0.01), simulating endogenous neurohormonal effects of ICA cells. Western blot analysis showed that DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was abolished in the presence of beta(2)-AR/CGRP-R blockade. Terminal dUTP nick-end labelling staining analysis of the LV infarct zone demonstrated that DPDPE reduced myocyte apoptosis by 58 +/- 19% (P < 0.05), an effect that was eliminated in the presence of beta(2)-AR/CGRP-R blockade. Finally, echocardiography showed that DPDPE increased LV contractility in a manner dependent on beta-AR/CGRP-R stimulation. CONCLUSION ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.