Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The normally positive force- and Ca2+ -frequency responses (FFR and CaFR) are inverted in heart failure (HF); whether oxidative stress contributes to these abnormalities is unknown. We evaluated the impact of acute and prolonged oxidative stress on contraction and Ca2+ handling in adult rat cardiomyocytes. Acute (30 min) exposure to H2O2 (100 microM) induced a twofold increase (P<0.025) in intracellular oxyradicals together with contractile depression despite preservation of the Ca2+ transient and the FFR and CaFR to 3 Hz, indicating reduced myofilament Ca2+ responsiveness. In contrast, prolonged (24 h) exposure to the copper-zinc superoxide dismutase inhibitor diethyldithiocarbamic acid (DDC, 1 microM) similarly augmented oxyradicals but also increased cell size, and contraction and Ca2+ transient duration (P<0.025). DDC-treated myocytes displayed inverted FFRs and attenuated (though still positive) CaFRs as compared to control, indicating reduced myofilament Ca2+ responsiveness coupled with altered Ca2+ handling. Protein levels of the Na+ -Ca2+ exchanger (NCX), sarcoplasmic reticular (SR) Ca2+ ATPase (SERCA2), and serine-16 phosphorylated phospholamban (pSer16-PLB) were increased (P<0.025), whereas dihydropyridine receptor abundance was decreased. Total PLB and ryanodine receptor protein expression were unchanged. Caffeine-induced Ca2+ release showed increased NCX activity (P<0.025) without changes in total releasable SR Ca2+, suggesting compensatory changes in SERCA2 and pSer16-PLB to maintain SR Ca2+ load. The superoxide scavenger Tiron attenuated these effects. Thus, acute oxyradical exposure rapidly depresses myofibrillar Ca2+ responsiveness. Prolonged oxidative stress further induces alterations in Ca2+ handling that combined with extant reductions in myofibrillar responsiveness invert the FFR. With regard to Ca2+ handling, reduced transsarcolemmal Ca2+ flux rather than reduced SR Ca2+ uptake was the primary determinant of a negative FFR. Analogous changes may be operative in HF, a state characterized by both oxidative stress and Ca2+ dysregulation.
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PMID:Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. 1628 76

Myocardial fractional flow reserve (FFR(myo)) and coronary flow reserve (CFR), measured with guidewire, and quantitative angiography (QA) are widely used in combination to distinguish ischemic from non-ischemic coronary stenoses. Recent studies have shown that simultaneous measurements of FFR(myo) and CFR are recommended to dissociate conduit epicardial coronary stenoses from distal resistance microvascular disease. In this study, a more comprehensive diagnostic parameter, named as lesion flow coefficient, c, is proposed. The coefficient, c, which accounts for mean pressure drop, Delta p, mean coronary flow, Q, and percentage area stenosis, can be used to assess the hemodynamic severity of a coronary artery stenoses. Importantly, the contribution of viscous loss and loss due to momentum change for several lesion sizes can be distinguished using c. FFR(myo), CFR and c were calculated for pre-angioplasty, intermediate and post-angioplasty epicardial lesions, without microvascular disease. While hyperemic c decreased from 0.65 for pre-angioplasty to 0.48 for post-angioplasty lesion with guidewire of size 0.35 mm, FFR(myo) increased from 0.52 to 0.87, and CFR increased from 1.72 to 3.45, respectively. Thus, reduced loss produced by momentum change due to lower percentage area stenosis decreased c. For post-angioplasty lesion, c decreased from 0.55 to 0.48 with the insertion of guidewire. Hence, increased viscous loss due to the presence of guidewire decreased c compared with a lesion without guidewire. Further, c showed a linear relationship with FFR(myo), CFR and percentage area stenosis for pre-angioplasty, intermediate and post-angioplasty lesion. These baseline values of c were developed from fluid dynamics fundamentals for focal lesions, and provided a single hemodynamic endpoint to evaluate coronary stenosis severity.
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PMID:Characterizing momentum change and viscous loss of a hemodynamic endpoint in assessment of coronary lesions. 1653 Feb 4

The use of Positive end-expiratory pressure (PEEP) as a strategy of mechanical ventilation offers its advantages, such as improved oxygenation, without causing alveolar overstretching and barotrauma. We aim to investigate the effect of several levels of PEEP on barotrauma and, whether an optimal level of PEEP exists. Forty-eight New Zealand rabbits (2.5-3.5 kg) were divided into four groups with PEEP settings of 0, 4, 8 and 12 cmH2O, at increasing levels of inspiratory volume (IV). This was done in blood perfused rabbit lungs and in lungs perfused with a Buffer-Albumin Solution. We observed that lungs ventilated with PEEP 0 cmH2O suffered pulmonary rupture at high IV (300cc), with significant increases of Pap (Pulmonary artery pressure) and FFR (Fluid filtration rate). Lungs ventilated with PEEP 8 and 12 suffered pulmonary rupture at lower IV (200cc and 150cc vs. 300cc respectively) On the other hand, lungs ventilated with PEEP 4 cmH2O reached the highest IV (400cc), in addition, they showed the lowest elevations of Pap and FFR. The acellular lungs ventilated with PEEP 4, 8 and 12 showed pulmonary rupture at lower IV when compared with cellular ones (300cc vs. 400cc: 100cc vs. 200cc and 100cc vs. 150cc respectively). We concluded that an optimal PEEP exists, which protects against barotrauma, however, excess of PEEP could enhance its development. The blood could contain some mediators which attenuate the damage induced by barotrauma.
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PMID:[Effect of using several levels of positive end-expiratory pressure over barotrauma's induced lung injury in a model of isolated and perfused rabbit lungs]. 1656 44

To evaluate the hemodynamic impact of coronary stenoses, the fractional (FFR) or coronary flow velocity reserve (CFVR) usually is measured. The combined measurement of instantaneous flow velocity and pressure gradient (v-dp relation) is rarely used in humans. We derived from the v-dp relation a new index, dp(v50) (pressure gradient at flow velocity of 50 cm/s), and compared the diagnostic performance of dp(v50), CFVR, and FFR. Before coronary angiography was performed, patients underwent noninvasive stress testing. In all coronary vessels with an intermediate or severe stenosis, the flow velocity, aortic, and distal coronary pressure were measured simultaneously with a Doppler and pressure guidewire after induction of hyperemia. After regression analysis of all middiastolic flow velocity and pressure gradient data, the dp(v50) was calculated. With the use of the results of noninvasive stress testing, the dp(v50) cutoff value was established at 22.4 mmHg. In 77 patients, 124 coronary vessels with a mean 39% (SD 19) diameter stenosis were analyzed. In 43 stenoses, ischemia was detected. We found a sensitivity, specificity, and accuracy of 56%, 86%, and 76% for CFVR; 77%, 99%, and 91% for FFR; and 95%, 95%, and 95% for dp(v50). To establish that dp(v50) is not dependent on maximal hyperemia, dp(v50) was recalculated after omission of the highest quartile of flow velocity data, showing a difference of 3%. We found that dp(v50) provided the highest sensitivity and accuracy compared with FFR and CFVR in the assessment of coronary stenoses. In contrast to CFVR and FFR, assessment of dp(v50) is not dependent on maximal hyperemia.
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PMID:The diastolic flow velocity-pressure gradient relation and dpv50 to assess the hemodynamic significance of coronary stenoses. 1681 84

Hypertrophy and failure (H/F) in humans and large mammals are characterized by a change from a positive developed force-frequency relationship (+FFR) in normal myocardium to a flattened or negative developed force-frequency relationship (-FFR) in disease. Altered Ca(2+) homeostasis underlies this process, but the role of intracellular Na(+) concentration ([Na(+)](i)) in H/F and frequency-dependent contractility reserve is unclear. We hypothesized that altered [Na(+)](i) is central to the -FFR response in H/F feline myocytes. Aortic constriction caused left ventricular hypertrophy (LVH). We found that as pacing rate was increased, contraction magnitude was maintained in isolated control myocytes (CM) but decreased in LVH myocytes (LVH-M). Quiescent LVH-M had higher [Na(+)](i) than CM (LVH-M 13.3 +/- 0.3 vs. CM 8.9 +/- 0.2 mmol/l; P < 0.001) with 0.5-Hz pacing (LVH-M 14.9 +/- 0.5 vs. CM 10.8 +/- 0.4 mmol/l; P < 0.001) but were not different at 2.5 Hz (17.0 +/- 0.7 vs. control 16.0 +/- 0.7 mmol/l; not significant). [Na(+)](i) was altered by patch pipette dialysis to define the effect of [Na(+)](i) on contraction magnitude and action potential (AP) wave shape at slow and fast pacing rates. Using AP clamp, we showed that LVH-M require increased [Na(+)](i) and long diastolic intervals to maintain normal shortening. Finally, we determined the voltage dependence of contraction for Ca(2+) current (I(Ca))-triggered and Na(+)/Ca(2+) exchanger-mediated contractions and showed that there is a greater [Na(+)](i) dependence of contractility in LVH-M. These data show that increased [Na(+)](i) is essential for maintaining contractility at slow heart rates but contributes to small contractions at fast rates unless rate-dependent AP shortening is prevented, suggesting that altered [Na(+)](i) regulation is a critical contributor to abnormal contractility in disease.
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PMID:Intracellular sodium determines frequency-dependent alterations in contractility in hypertrophied feline ventricular myocytes. 1701 60

Insights into intracellular calcium regulation and contractile state can be accomplished by changing pacing rate. Steady-state increases in heart rate (HR) (force-frequency relationship, FFR), and introduction of extrasystoles (ES) (force-interval relationship, FIR) have been used to investigate this relationship. This study focused on the recirculation fraction (RF) and potentiation ratio (PR), obtained from the recovery of the FFR and FIR. These parameters may provide insight on intracellular Ca(2+) regulation. Left ventricular (LV) pressures and HR were assessed in anesthetized canines (n = 7). Intrinsic data were collected prior to and following HR increases to 150, 180, and 200 bpm, as well as following delivery of an ES at 280 ms. The RF was calculated as the slope of dP/dt(max(n + 1)) vs. dP/dt(max(n)), where n = beat number. The PR was calculated by normalizing dP/dt(max) from the first beat following the ES (or the last paced beat) to the steady-state dP/dt(max). The RF due to an ES was not significantly different than that from a HR of 200 bpm. The PR from an ES was not significantly different than from a HR of 150 bpm. The impact of an ES delivered at an interval of 280 ms produces a PR similar to that from a HR of 150 bpm; yet, it recovers similarly to the termination of pacing at 200 bpm, eliciting a similar RF value. The method of measuring RF by an ES versus an increased HR may provide a safer and more feasible approach to collecting diagnostic information.
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PMID:Novel means to monitor cardiac performance: the impact of the force-frequency and force-interval relationships on recirculation fraction and potentiation ratio. 1731 31

The swelling of Lalpha-phases from the block copolymer polyethylenoxide-b-polydimethylsiloxane-polyethylenoxide (EO)15-(PDMS)15-(EO)15 in water/glycerol mixtures is reported. At low and medium polymer concentrations (<60%), the block copolymer forms a turbid vesicular dispersion in water. With time, the small unilamellar vesicles (SUV) and the large multilamellar vesicles (MLV) separate into a two phase L1/Lalpha-system. The turbid dispersions of the Lalpha-phase below 60% of the compound become more and more transparent with increasing glycerol and at 60% of glycerol become completely clear. Replacement of water by the solvent glycerol thus lowers the turbidity of the dispersion and swells the interlamellar distance between the bilayers. A 20% aqueous L1/Lalpha-dispersion can thus be transformed into a single birefringent transparent Lalpha-phase. The swelling of the Lalpha-phase in water and the decrease of the turbidity of the dispersion by the addition of glycerol is explained by the matching of the refractive index of the solvent to the refractive index of the bilayers of the block copolymer. The matching of a refractive index lowers the Hamaker constant in the DLVO theory between the bilayers and therefore decreases the attraction between the bilayers what allows them to swell to a larger separation. The microstructures in the phases were determined by cryo- and FFR-TEM. The interlamellar distance between the bilayers was determined by SAXS measurements. The viscous properties of the Lalpha-phases were determined by oscillatory rheological measurements. In comparison to other Lalpha-phases from normal surfactants, the Lalpha-phases from the block copolymer (EO)15-(PDMS)15-(EO)15 have low shear moduli. This is probably due to the high flexibility of the poly dimethylsiloxane block in the bilayers what can be recognized on the non-spherical shapes of the SUV's.
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PMID:Swelling of Lalpha-phases by matching the refractive index of the water-glycerol mixed solvent and that of the bilayers in the block copolymer system of (EO)15-(PDMS)15-(EO)15. 1748 29

The aim of this study was the determination of the pressure-derived collateral fractional flow reserve (FFR(coll)) in patients with three vessel disease and chronic occlusion of the right coronary artery undergoing surgical complete revascularization with the off-pump technique. The angiograms of eight patients were preoperatively analysed to quantify collaterality. FFR(coll) was determined before any revascularization (FFR(coll) 0), and after revascularization of the left coronary arteries, (FFR(coll) 1). FFR(coll) 0 was compared to the Rentrop grade, to the left ventricular ejection fraction (LVEF), and to FFR(coll) 1. No correlation was demonstrated between preoperative Rentrop grade and FFR(coll) 0. There was a linear statistically significant correlation between FFR(coll) 0 and LVEF (P;ie0.001). No significant variation of the FFR(coll) index was observed after performing left coronary artery bypass grafts. Collaterality observed on the coronary angiogram cannot be used as an estimation of the functional collaterality, which can be better appreciated with the LVEF. The absence of variation of FFRcoll before and after left coronary artery revascularization suggests that grafting of the occluded right coronary artery remains justified.
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PMID:Collateral flow reserve and right coronary occlusion: evaluation during off-pump revascularization. 1767 Mar 48

Patients with diabetes mellitus (DM) have poor long-term outcome after percutaneous coronary intervention (PCI) partly because of microvascular disease and distal embolization. Microvascular obstruction can be assessed by measuring coronary flow reserve (CFR). The Prediction of CK-MB RElease During Successful Stenting Correlating with Indicators of Microvascular ObstruCTion (PREDICT) trial compared the CFR in patients with versus without DM during PCI. Patients undergoing elective PCI were prospectively enrolled according to diabetic (n = 36) and nondiabetic (n = 36) status. All patients received drug-eluting stent with abciximab and were followed for 30-day major adverse cardiac events. CFR and FFR (fractional flow reserve) before and after stenting were measured before and after intracoronary adenosine bolus. Procedural success, MB enzyme of creatine-kinase (CK-MB), troponin I, and high-sensitive C-reactive protein elevation, vascular complications, and major adverse cardiac events were not different. FFR before stenting was 0.77 +/- 0.03 in patients with DM versus 0.76 +/- 0.02 in patients without DM (p = 0.69). FFR after stenting was 0.97 +/- 0.03 and 0.99 +/- 0.01 (p = 0.26), respectively. CFR before stenting was 1.36 +/- 0.31 in patients with DM versus 1.49 +/- 0.25 in patients without DM (p = 0.064). However, CFR after stenting was significantly lower in patients with versus without DM (1.89 +/- 0.30 versus 2.44 +/- 0.67, p <0.001, respectively). CFR after stenting only moderately correlated with CK-MB and high-sensitive C-reactive protein after PCI but did not correlate with 30-day major adverse cardiac events. In conclusion, patients with DM have significantly lower CFR after stenting despite equivalent FFR and myonecrosis compared with patients without DM, indicating greater microvascular obstruction after PCI despite abciximab.
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PMID:Comparison of coronary flow reserve and fractional flow reserve in patients with versus without diabetes mellitus and having elective percutaneous coronary intervention and abciximab therapy (from the PREDICT Trial). 1832 43

Input/output functions of the simultaneously recorded acoustic distortion product otoacoustic emissions (DPOAE) and neural frequency following-response distortion products (FFR-DP) at 2f1-f2 were evaluated to determine if these two representations of cochlear nonlinearity exhibit similar response behavior, which would suggest shared cochlear generators. Responses were recorded from normal-hearing adults for a tone burst stimulus pair (F1: 500 Hz; F2: 612 Hz) at 40-70 dB nHL. DPOAE responses were recorded from the ear canal, and FFR responses were recorded differentially from scalp electrodes, representing a vertical configuration. The input/output function for FFR-DP revealed a compressive saturating nonlinearity, whereas the DPOAE input/output function exhibited a linear growth at higher intensities following a compressive behavior at moderate levels. Results appear to suggest that cochlear generators may be contributing differentially to the acoustic and the neural distortion products. Also, FFR-DP responses appeared more identifiable and less variable, particularly at lower stimulus levels, than the corresponding DPOAE. These findings may point to a potential benefit of applying FFR testing to complement DPOAE in evaluating cochlear function at low frequencies.
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PMID:Comparison of the acoustic and neural distortion product at 2f1-f2 in normal-hearing adults. 1857 81


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