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1.
Atorvastatin treatment improves myocardial and peripheral blood flow in familial hypercholesterolemia subjects without evidence of coronary atherosclerosis.
Lario, FC, Miname, MH, Tsutsui, JM, Santos, RD, Kowatsch, I, Sbano, JC, Ramires, JA, Kalil Filho, R, Mathias, W
Echocardiography (Mount Kisco, N.Y.). 2013;(1):64-71
Abstract
BACKGROUND Hypercholesterolemia induces early microcirculatory functional and structural alterations that are reversible by cholesterol reduction. Real time myocardial contrast echocardiography (RTMCE) and vascular ultrasound evaluate the effects of hyperlipidemia on peripheral and central blood flow reserve. This study investigated the effects of lipid-lowering therapy on coronary and peripheral artery circulation in patients with familial hypercholesterolemia (FH). METHODS RTMCE and vascular ultrasound were performed in 10 healthy volunteers (validation group) at baseline and after 12-week clinical observation, and in 16 age- and sex-matched FH patients without obstructive coronary artery disease (CAD) by computed tomography angiography at baseline and after 12-week atorvastatin treatment. Indexes of relative myocardial blood flow (MBF) were obtained at rest and during adenosine infusion. RESULTS In validation group, there was no significant difference between flow-mediated dilation (FMD) at baseline and after 12 weeks (0.15 ± 0.02 vs. 0.14 ± 0.03; P = 0.39). Similarly, no differences were observed in MBF reserve at baseline and after 12 weeks (3.31 ± 0.63 vs. 3.48 ± 0.89; P = 0.89). FMD was blunted in FH patients, at baseline, as compared with validation group (0.08 ± 0.04 vs. 0.15 ± 0.02; P < 0.001) and became similar to that group (0.13 ± 0.05 vs. 0.14 ± 0.03; P = 0.07) after treatment. MBF reserve was blunted at baseline in FH patients in comparison with the validation group (2.78 ± 0.71 vs. 3.31 ± 0.63; P = 0.003). After treatment, MBF reserve values were no longer different (3.43 ± 0.66 and 3.48 ± 0.89; P = 0.84, respectively, for FH and validation groups). CONCLUSION Patients with FH and no obstructive CAD have blunted MBF reserve and lower FMD values as compared with healthy volunteers. Both FMD and MBF reserve were normalized after atorvastatin treatment.
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2.
Assessment of the effect of external counterpulsation on myocardial adaptive arteriogenesis by invasive functional measurements--design of the arteriogenesis network trial 2.
Pagonas, N, Utz, W, Schulz-Menger, J, Busjahn, A, Monti, J, Thierfelder, L, Dietz, R, Klauss, V, Gross, M, Buschmann, IR, et al
International journal of cardiology. 2010;(3):432-7
Abstract
BACKGROUND Stimulation of collateral artery growth is a promising therapeutic option for patients with coronary artery disease. External counterpulsation is a non-invasive technique suggested to promote the growth of myocardial collateral arteries via increase of shear stress. The Art.Net.2 Trial tests invasively and functionally for the first time the hypothesis whether a treatment course with external counterpulsation (over 7 weeks) can induce the growth of myocardial collateral arteries. METHODS This study is designed as a prospective, controlled, proof-of-concept study. Inclusion criteria are (1) age 40 to 80 years, (2) stable coronary disease, (3) a residual significant stenosis of at least one epicardial artery and (4) a positive ischemic stress-test for the region of interest. As primary endpoint serves the pressure-derived collateral flow index (CFIp), the invasive gold-standard to assess myocardial collateral pathways. CFIp is determined by simultaneous measurement of mean aortic pressure (Pa, mm Hg), distal coronary occlusive (wedge) pressure (Pw, mm Hg) and central venous pressure (Pv, mm Hg). The index is calculated as CFIp=(Pw-Pv)/(Pa-Pv). The pressure derived fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) are assessed as secondary invasive endpoints to investigate the effect of ECP on the myocardial vasculature. The non-invasive secondary endpoints include symptoms (CCS and NYHA classification), treadmill-testing and analysis of shear-stress related soluble proteins. CONCLUSIONS The Art.Net.-2 Trial will report within the next months whether direct evidence can be brought that ECP promotes coronary collateral growth in patients with stable angina pectoris.
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3.
Efficacy of clopidrogel on reperfusion and high-sensitivity C-reactive protein in patients with acute myocardial infarction.
Akbulut, M, Kutlu, M, Ozbay, Y, Polat, V, Bilen, MN, Baydas, A, Altas, Y
Mediators of inflammation. 2009;:932515
Abstract
We investigated the effects of clopidogrel on reperfusion and inflammatory process in STEMI. A total of 175 STEMI patients with similar clinical characteristics were included to this study. One was the standard pharmacological reperfusion therapy group (group 1, n : 90), who received 300 mg aspirin, 70 U/kg bolus, and 12 U/kg/hr continuous infusion of unfractioned heparin and accelerated t-PA. Clopidogrel 450 mg loading and 75 mg/d thereafter was added to standard reperfusion therapy in the other group (group 2, n : 85). The ST-segment resolution, CK-MB, and high-sensitive CRP (hs-CRP) parameters were measured. Complete ST resolution was observed in 32 patients (36.8%) in group 1 and 53 patients (63.8%) in group 2 (P < .001). Also in the first 24 hours, the CK-MB levels of patients in group 1 were significantly higher than those of group 2 (P = .001). The hs-CRP values were greater in group 1 than group 2 at 48th hour (group 1: 9.4 +/- 0.1 mg/L, group 2: 3.7 +/- 1.4 mg/L; P = .000). We concluded that adding clopidogrel to standard treatment in STEMI patients provided early reperfusion and suppression of inflammatory response.
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4.
Effect of hyperoxia and vitamin C on coronary blood flow in patients with ischemic heart disease.
McNulty, PH, Robertson, BJ, Tulli, MA, Hess, J, Harach, LA, Scott, S, Sinoway, LI
Journal of applied physiology (Bethesda, Md. : 1985). 2007;(5):2040-5
Abstract
Pathological formation of reactive oxygen species within the coronary circulation has been hypothesized to mediate some clinical manifestations of ischemic heart disease (IHD) by interfering with physiological regulation of coronary tone. To determine the degree to which coronary tone responds to acute changes in ambient levels of oxidants and antioxidants in vivo in a clinical setting, we measured the effect of an acute oxidative stress (breathing 100% oxygen) on coronary capacitance artery diameter (quantitative angiography) and blood flow velocity through the coronary microcirculation (intracoronary Doppler ultrasonography) before and after treatment with the antioxidant vitamin C (3-g intravenous infusion) in 12 IHD patients undergoing a clinical coronary interventional procedure. Relative to room air breathing, 100% oxygen breathing promptly reduced coronary blood flow velocity by 20% and increased coronary resistance by 23%, without significantly changing the diameter of capacitance arteries. Vitamin C administration promptly restored coronary flow velocity and resistance to a slightly suprabasal level, and it prevented the reinduction of coronary constriction with rechallenge with 100% oxygen. This suggests that acute oxidative stress produces prompt and substantial changes in coronary resistance and blood flow in a clinical setting in patients with IHD, and it suggests that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation. This observation may have relevance for clinical practice.
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5.
Nicorandil administration shows cardioprotective effects in patients with poor TIMI and collateral flow as well as good flow after AMI.
Toyama, T, Seki, R, Hoshizaki, H, Kawaguchi, R, Isobe, N, Adachi, H, Oshima, S, Taniguchi, K, Kasama, S
Annals of nuclear medicine. 2006;(4):277-85
Abstract
BACKGROUND Nicorandil (NCR) has been reported to have cardioprotective effects in patients with AMI. And collateral flow and TIMI flow are also important determinants of final salvaged myocardium in patients with AMI. There is no evidence as to whether TIMI or collateral flow modifies the cardioprotective effects of NCR in patients with AMI. METHODS AND RESULTS We studied 68 initial AMI patients without restenosis which was defined as 50% diameter reduction of the intervention site in the chronic period. On initial CAG, 41 patients with poor flow (collateral: Rentrop 0 or 1 and TIMI 0 or 1) were NCR/Non-NCR = 20/21. Twenty-seven patients with good flow (collateral: Rentrop 2 or 3 or TIMI 2 or 3) were NCR/Non-NCR = 13/14. NCR was administered intravenously (4 mg) via intracoronary injection (2 mg) or continuously (4 mg/h). 99mTc-tetrofosmin (TF) and 123I-BMIPP SPECT were performed in the subacute and chronic (6 Mo) periods. In 20 SPECT segments, summed defect scores (TDS) and regional wall motion (WMS: -1=dyskinesis -4 = normal) of AMI segments using TF-QGS were estimated. In poor flow patients, the following values for NCR patients were higher (p < 0.05) than for Non-NCR patients in the improvement degree of TDS (BMIPP) (NCR: 6.5 +/- 3.9 vs. Non-NCR: 4.0 +/- 3.4), the improvement degree of TDS (TF) (NCR: 5.7 +/- 4.6 vs. Non-NCR: 2.2 +/- 4.6), and delta WMS (NCR: 1.4 +/- 1.1 vs. Non-NCR: 0.9 +/- 1.0). In good flow patients, the following values for NCR patients were better (p < 0.05) than for Non-NCR patients in TDS (BMIPP) (subacute) (NCR: 9.9 +/- 5.2 vs. Non-NCR: 16.5 +/- 10.4) and (chronic) (NCR: 5.1 +/- 5.2 vs. Non-NCR: 12.4 +/- 8.5), WMS (subacute) (NCR: 1.7 +/- 1.3 vs. Non-NCR: 1.0 +/- 1.0), and WMS (chronic) (NCR: 3.0 +/- 1.5 vs. Non-NCR: 2.1 +/- 1.3). CONCLUSION We conclude that the cardioprotective effects of nicorandil administration are observable in both AMI patients with poor collateral and TIMI flow and good flow before reperfusion therapy.
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6.
An improved model for the measurement of myocardial perfusion in human beings using N-13 ammonia.
Hickey, KT, Sciacca, RR, Chou, RL, Rodriguez, O, Bokhari, S, Bergmann, SR
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2005;(3):311-7
Abstract
BACKGROUND Oxygen 15 water and nitrogen 13 ammonia are widely used for the quantitative measurement of myocardial perfusion with positron emission tomography. However, blood flow obtained with N-13 ammonia by use of the conventional 2-compartment model frequently underestimates flow by 30% to 50% compared with O-15 water. We hypothesized that this discrepancy is a result of the model configuration of N-13 ammonia and investigated changes to the mathematical model to determine whether more accurate measurements of perfusion could be obtained. METHODS AND RESULTS Twelve healthy volunteers were sequentially studied with O-15 water and N-13 ammonia at rest and during maximal coronary vasodilation with adenosine. Perfusion measurements obtained with the conventional and modified models were compared with values obtained with O-15 water. The conventional N-13 ammonia model underestimated flow by 37% +/- 16% at rest and by 20% +/- 24% with stress when compared with flows obtained with O-15 water. The modified model yielded flow values closer to the line of identity than the conventional model (y = 1.07x + 0.04 vs y = 0.69x + 0.08; respectively; P < .01). CONCLUSIONS Model changes made N-13 ammonia myocardial blood flow estimates more comparable to those obtained with O-15 and may allow for better comparison of flows obtained with these two tracers in the future. Further efforts are warranted to evaluate the accuracy of flow models in human subjects.
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7.
Myocardial perfusion and perfusion reserve in endurance-trained men.
Kalliokoski, KK, Nuutila, P, Laine, H, Luotolahti, M, Janatuinen, T, Raitakari, OT, Takala, TO, Knuuti, J
Medicine and science in sports and exercise. 2002;(6):948-53
Abstract
PURPOSE This study was undertaken to determine whether endurance training is associated with changes in myocardial perfusion in humans. METHODS Myocardial perfusion was measured in eleven trained and nine sedentary men at rest and during adenosine-stimulated hyperemia using positron emission tomography (PET). Left ventricular (LV) dimensions and mass were measured using echocardiography. Myocardial work per gram of tissue was calculated as (cardiac output. mean arterial blood pressure)/LV mass. RESULTS LV mass was significantly higher and myocardial work per gram of tissue lower in the trained than in the untrained subjects. Basal (0.78 +/- 0.10 and 0.76 +/- 0.15 mL. min-1. g-1, P = NS) and adenosine-stimulated perfusion (3.46 +/- 0.91 and 3.14 +/- 0.70 mL. min-1. g-1, P = NS) were similar between trained and untrained men, respectively. Consequently, myocardial perfusion reserve was similar in both groups (4.4 +/- 1.2 and 4.1 +/- 0.7, P = NS). In addition, coronary resistance at baseline (115 +/- 17 vs 119 +/- 22, mm Hg. mL. min-1. g-1, P = NS) and during adenosine infusion (28 +/- 8 vs 30 +/- 8, mm Hg. mL. min-1. g-1, P = NS) were similar in both groups. Resting myocardial work correlated with resting myocardial perfusion in both groups, but the relationship between perfusion and work was different between the groups so that perfusion for a given myocardial work was significantly higher in trained subjects (0.56 +/- 0.04 and 0.34 +/- 0.05 mL. (mm Hg. L)-1, P < 0.001). CONCLUSIONS These findings suggest that endurance trained subjects do not have different resting or adenosine-stimulated myocardial perfusion. However, the relationship between myocardial perfusion and work appears altered in the athletes.
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8.
Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction.
Werner, GS, Lang, K, Kuehnert, H, Figulla, HR
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. 2002;(4):444-51
Abstract
No-reflow is a frequent observation during direct PTCA for acute myocardial infarction (AMI) and associated with a poor clinical outcome. This study assesses the value of verapamil for reversal of no-reflow during PTCA for AMI. In a consecutive series of 212 direct or rescue PTCAs for AMI, a TIMI flow grade < 3 was observed in 23 patients (10.8%). Ten of these patients had received GP IIb/IIIa antagonists before PTCA. Seven patients with AMI and TIMI grade 3 flow served as controls. All lesions were treated by stents. In 18 patients with systolic blood pressure > 90 mm Hg, nitroglycerine (0.1 mg i.c.) was given. Verapamil (1 mg over 2 min) was given via an infusion catheter distal to the angioplasty site. Before and after nitroglycerine, after verapamil, and 15 min later coronary flow was assessed by the TIMI frame count method (TFC). Nitroglycerine had no effect on TFC. Verapamil reduced TFC from 56 +/- 9 frames to 24 +/- 4 (P < 0.001). In controls, TFC did not change significantly. The TIMI flow grade was restored to TIMI flow grade 3 in 65%. In two of seven right coronary and one of three circumflex arteries, intermittent AV block II occurred during verapamil injection, which disappeared after atropine. No-reflow after PTCA for AMI can be reversed by intracoronary verapamil. This supports the hypothesis that no-reflow is caused by acute microvascular dysfunction probably because of a disorder in calcium homeostasis or microvascular spasm.