TY - JOUR
T1 - Effects of sildenafil on myocardial blood flow in humans with ischemic heart disease
AU - Tawakol, Ahmed
AU - Aziz, Kusai
AU - Migrino, Raymond
AU - Watkowska, Justyna
AU - Zusman, Randall
AU - Alpert, Nathaniel M.
AU - Fischman, Alan J.
AU - Gewirtz, Henry
PY - 2005/11
Y1 - 2005/11
N2 - Background: We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease. Methods: Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given ∼2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow < 1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow > 1.65 ml/min per g were averaged and combined into a normal zone for that patient. Results: At rest, rate pressure product (heart rate × systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76 ± 0.48 placebo versus 0.64 ± 0.20 sildenafil, both P = NS; mean ± SD). Both rate pressure product and myocardial blood flow increased (P < 0.01) with cold pressor stress (11 ± 3K and 1.14±0.59 placebo versus 1013 K and 1.21 ± 0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6 ± 0.7) exceeded that with adenosine and placebo (2.0 ± 1.3, P < 0.04, paired sign test). Conclusion: Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that α-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease.
AB - Background: We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease. Methods: Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given ∼2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow < 1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow > 1.65 ml/min per g were averaged and combined into a normal zone for that patient. Results: At rest, rate pressure product (heart rate × systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76 ± 0.48 placebo versus 0.64 ± 0.20 sildenafil, both P = NS; mean ± SD). Both rate pressure product and myocardial blood flow increased (P < 0.01) with cold pressor stress (11 ± 3K and 1.14±0.59 placebo versus 1013 K and 1.21 ± 0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6 ± 0.7) exceeded that with adenosine and placebo (2.0 ± 1.3, P < 0.04, paired sign test). Conclusion: Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that α-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease.
KW - Ischemic heart disease
KW - Myocardial blood flow
KW - Sildenafil
UR - http://www.scopus.com/inward/record.url?scp=27344442599&partnerID=8YFLogxK
U2 - 10.1097/00019501-200510000-00005
DO - 10.1097/00019501-200510000-00005
M3 - Article
C2 - 16205453
AN - SCOPUS:27344442599
SN - 0954-6928
VL - 16
SP - 443
EP - 449
JO - Coronary Artery Disease
JF - Coronary Artery Disease
IS - 7
ER -