Effect of Phosphodiesterase Type 5 Inhibition on Microvascular Coronary Dysfunction in Women: A Women's Ischemia Syndrome Evaluation (WISE) Ancillary Study

Abstract

SUMMARY Background Microvascular coronary dysfunction (MCD) is associated with symptoms, signs of ischemia, and adverse outcomes in women without macrovascular obstructive coronary artery disease (M-CAD). Although, MCD can be quantified using coronary flow reserve (CFR), treatment is poorly defined. Hypothesis Phosphodiesterase type 5 (PDE-5) inhibition acutely improves MCD in these women. Methods The subjects were 23 symptomatic women (age 54±11 years) participating in an ancillary study of the Women’s Ischemia Syndrome Evaluation (WISE) with baseline CFR ≤3.0 (Doppler flow wire and intracoronary adenosine) and without M-CAD. CFR was re-measured 45 minutes after PDE-5 inhibition (100 mg oral sildenafil). The primary measure of interest was change in CFR adjusted for baseline variables. Results The relationship between log2 transformed CFR post–PDE-5 inhibition (adjusted) and baseline was different from the line of identity (slope: 0.55 vs. 1.0, P=0.008; intercept: 0.73 vs. 0.0, P=0.01), indicating that PDE-5 inhibition improves CFR and the lower the baseline CFR, the greater the response. Among women with baseline CFR ≤2.5 (N=11), CFR increased from 2.1±0.2 to 2.7±0.6 (P=0.006). For women with baseline CFR >2.5 (N=12), CFR did not change (3.1±0.3 to 3.0±0.6; P=0.70). Conclusions For women with symptoms and signs of ischemia and no M-CAD, PDE-5 inhibition is associated with acute improvement in CFR and the effect concentrates among those with CFR ≤2.5. If these acute effects are sustained, then PDE-5 inhibition would provide a rational strategy for management of MCD in symptomatic women without M-CAD. The longer-term effects warrant study in a randomized trial using a sustained acting PDE-5 inhibitor.

Coronary microvascular dysfunction: sex-specific risk, diagnosis, and therapy

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Everything you ever wanted to know about phosphodiesterase 5 inhibitors and the heart (but never dared ask): How do they work?

“…/K ? ATPase activity [77] Authors suggest early use of PDE5i after ischemia [26] Myocardial infarction :Blood flow into ischemic myocardial region [77] :Viability of cardiomyocytes(simulated ischemia) [67] ;Apoptosis (border zone) &: cardiac function [28] ;Infarct size, cardiac fibrosis and remodeling [25,28,66,78,79] :VEGF, bFGF, Angiopoietin 1 and vascular density &; resident myocyte apoptosis and vascular density [80] ;LV dysfunction 3 days after MI [29] ;Vascular density [28,29,81] :LV function &; MI fibrotic scar [79] Short-term : CFR in women after PDE5i (100 mg) [82] Short-term : exercise tolerance and ischemic threshold in men with CAD and ED [31] :Safety after ischemic stroke (25 mg sildenafil 9 2 weeks) [32] Doxorubicin-induced cardiotoxicity ;Apoptosis& oxidative stress &:mitochondrial membrane potential-myofibrillar integrity-LV function [26,60] Apoptosis and LV dysfunction prevention [60] Preserved LV function [60] Cardiomyopathy due to Duchenne muscular dystrophy :Cardiac contractile performance, metabolic status, sarcolemmal integrity [61] :Cardiac function and survival [26,61] No effect [8] Cardiac betaadrenergic stimuli…”

Are Macrophages in Tumors Good Targets for Novel Therapeutic Approaches?

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