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17.6 Endogenous nitric oxide synthase inhibitors modulate the effect of pravastatin on coronary artery reactivity
Journal of Nuclear Cardiology V o l u m e 8, N u m b e r 1
Abstracts S a t u r d a y , M a y 5, 2 0 0 1
S 113
17.5
17.6
Comparison of myocardial contrast echocardiography and 199m]Tctetrofosmin SPECT to evaluate myocardial pcrfusion. LJ Klein, GT Sieswerda, E Aiazian, O Kamp, CA Visser, FC Visser. Dept. of Cardiology University Hospital VU Amsterdam Netherlands.
Endogenous nitric oxide synthase inhibitors modulate the effect of pravastatin on coronary artery reactivity.
A significant correlation between semi-quantitative evaluation of myocardial perfusion by intravenous myocardial contrast echocardiography (ivMCE) and perfusion scintigraphy (SPECT) has been reported. This two-center study compared quantitative segmental perfusion mapping by ivMCE and SPECT in the subacute phase of acute myocardial infarction (AMI). Sixteen patients (M:F 13:3; mean age 66 yrs) underwent ivMCE using 1:1 intermittent harmonic imaging 24 hours after first AMI treated with PTCA and stent implantation. Contrast echocardiograms from the three standard apical views were obtained atter iv. bolus injections of Sonazoid (Nycomed, Oslo, Norway). Baseline-corrected peak myocardial videointensity (bcPMVI) was determined automatically in 16 segments using a dedicated system (Axle Int., The Hague, The Netherlands). Resting [99m]Tc-tetrofosmin SPECT was performed within 1 day afler ivMCE. SPECT images were reoriented matching the echo views, and divided into the same echo segments. Mean count rate values were obtained in these segments. After normalization of segmental bcPMVI and SPECT count values per patient, linear regression analysis was performed. No clinical events occurred between both studies. After exclusion due to ivMCE or SPECT artifacts or attenuation, 210/256 (83%) segments remained. Normalized SPECT and bcPMVI correlated linearly: bcPMVI - 1.237 x SPECT - 35; r = 0.74, p <0.0001. See figure. This clinical study shows that videointensity increase as observed in quantitative myocardial contrast echocardiography is clearly correlated with SPECT tracer uptake in patients in the subacute phase of AMI. This further substantiates the use of ivMCE as a valid tool for the evaluation of myocardial perfusion.
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Comparison of SPECT and MCE
J Knuuti, T Lehtirrdiki 1, T Janatuinen, J Laakso 2, R Vesalalinen, R Laaksonen 3. Turku PET Centre Turku University Central Hospital Turku, ILaboratory of Atherosclerosis Genetics Tampere University Hospital Tampere, 2Dept. of Clinical Pharmacology University of Helsinki, 3Dept. Medicine and Clinical Chemistry University of Tampere, Finland. The aim of the study was to investigate whether endogenous nitric oxide (NO) synthesis inhibitors modulate the effect of pravastatin on myocardial flow reserve. In this double-blinded study 51 men (age 35±4 years) with mild to moderate hypercholesterolemia were randomly assigned to receive pravastatin 40 mg/day or placebo for six months. Myocardial blood flow was measured at rest and during adenosine-induced hypcremla using positron emission tomography (PET) and oxygen-15-1abcled water before and at the end of the treatment. Plasma levels of endogenous NO synthase inhibitors asymmetric dimethylated arginine (ADMA) and monomethyl arginine (NMMA) were assessed with high performance liquid chromatography. Results: At baseline serum ADMA and NMMA concentrations were similar in both treatment groups and remained unchanged during pravastatin treatment. They did not correlate with serum total cholesterol, low density lipoprotein cholesterol concentrations or myocardial flow parameters. However, baseline ADMA correlated significantly with hyperemic flow change during statin intervention (r=-0.50, p=0.002) and adenosine flow after statin treatment (r=0.43, p=0.049), while similar correlations were not seen atter placebo treatment. Furthermore, high baseline ADMA (over median value) concentration predicted lowering of adenosine-induced blood flow after statin intervention (baseline to follow-up change -22 %) and low baseline ADMA value (< median) improvement of adenosine flow (change +24 %, p=0.034). Conclusions: This study shows that an endogenous NO synthase inhibitors modulate the effect of pravastatin on coronary reactivity and high levels of inhibitors might delay and depress endothelial effects of statins.
Abstracts S a t u r d a y , M a y 5, 2 0 0 1
S 113
17.5
17.6
Comparison of myocardial contrast echocardiography and 199m]Tctetrofosmin SPECT to evaluate myocardial pcrfusion. LJ Klein, GT Sieswerda, E Aiazian, O Kamp, CA Visser, FC Visser. Dept. of Cardiology University Hospital VU Amsterdam Netherlands.
Endogenous nitric oxide synthase inhibitors modulate the effect of pravastatin on coronary artery reactivity.
A significant correlation between semi-quantitative evaluation of myocardial perfusion by intravenous myocardial contrast echocardiography (ivMCE) and perfusion scintigraphy (SPECT) has been reported. This two-center study compared quantitative segmental perfusion mapping by ivMCE and SPECT in the subacute phase of acute myocardial infarction (AMI). Sixteen patients (M:F 13:3; mean age 66 yrs) underwent ivMCE using 1:1 intermittent harmonic imaging 24 hours after first AMI treated with PTCA and stent implantation. Contrast echocardiograms from the three standard apical views were obtained atter iv. bolus injections of Sonazoid (Nycomed, Oslo, Norway). Baseline-corrected peak myocardial videointensity (bcPMVI) was determined automatically in 16 segments using a dedicated system (Axle Int., The Hague, The Netherlands). Resting [99m]Tc-tetrofosmin SPECT was performed within 1 day afler ivMCE. SPECT images were reoriented matching the echo views, and divided into the same echo segments. Mean count rate values were obtained in these segments. After normalization of segmental bcPMVI and SPECT count values per patient, linear regression analysis was performed. No clinical events occurred between both studies. After exclusion due to ivMCE or SPECT artifacts or attenuation, 210/256 (83%) segments remained. Normalized SPECT and bcPMVI correlated linearly: bcPMVI - 1.237 x SPECT - 35; r = 0.74, p <0.0001. See figure. This clinical study shows that videointensity increase as observed in quantitative myocardial contrast echocardiography is clearly correlated with SPECT tracer uptake in patients in the subacute phase of AMI. This further substantiates the use of ivMCE as a valid tool for the evaluation of myocardial perfusion.
~
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•
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a%~J,. :. ~,-'" ="
26"
u,.~_.
0
I -°6
- •
I EO
Norm~.llZed 5PE~T
~t I 76
I 100
O~)UlltS
Comparison of SPECT and MCE
J Knuuti, T Lehtirrdiki 1, T Janatuinen, J Laakso 2, R Vesalalinen, R Laaksonen 3. Turku PET Centre Turku University Central Hospital Turku, ILaboratory of Atherosclerosis Genetics Tampere University Hospital Tampere, 2Dept. of Clinical Pharmacology University of Helsinki, 3Dept. Medicine and Clinical Chemistry University of Tampere, Finland. The aim of the study was to investigate whether endogenous nitric oxide (NO) synthesis inhibitors modulate the effect of pravastatin on myocardial flow reserve. In this double-blinded study 51 men (age 35±4 years) with mild to moderate hypercholesterolemia were randomly assigned to receive pravastatin 40 mg/day or placebo for six months. Myocardial blood flow was measured at rest and during adenosine-induced hypcremla using positron emission tomography (PET) and oxygen-15-1abcled water before and at the end of the treatment. Plasma levels of endogenous NO synthase inhibitors asymmetric dimethylated arginine (ADMA) and monomethyl arginine (NMMA) were assessed with high performance liquid chromatography. Results: At baseline serum ADMA and NMMA concentrations were similar in both treatment groups and remained unchanged during pravastatin treatment. They did not correlate with serum total cholesterol, low density lipoprotein cholesterol concentrations or myocardial flow parameters. However, baseline ADMA correlated significantly with hyperemic flow change during statin intervention (r=-0.50, p=0.002) and adenosine flow after statin treatment (r=0.43, p=0.049), while similar correlations were not seen atter placebo treatment. Furthermore, high baseline ADMA (over median value) concentration predicted lowering of adenosine-induced blood flow after statin intervention (baseline to follow-up change -22 %) and low baseline ADMA value (< median) improvement of adenosine flow (change +24 %, p=0.034). Conclusions: This study shows that an endogenous NO synthase inhibitors modulate the effect of pravastatin on coronary reactivity and high levels of inhibitors might delay and depress endothelial effects of statins.