The effects of oxygen level and glucose concentration on the metabolism of porcine TMJ disc cells.

OBJECTIVE: To determine the combined effect of oxygen level and glucose concentration on cell viability, ATP production, and matrix synthesis of temporomandibular joint (TMJ) disc cells. DESIGN: TMJ disc cells were isolated from pigs aged 6-8 months and cultured in a monolayer. Cell cultures were preconditioned for 48 h with 0, 1.5, 5, or 25 mM glucose DMEM under 1%, 5%, 10%, or 21% O2 level, respectively. The cell viability was measured using the WST-1 assay. ATP production was determined using the Luciferin-Luciferase assay. Collagen and proteoglycan synthesis were determined by measuring the incorporation of [2, 3-(3)H] proline and [(35)S] sulfate into the cells, respectively. RESULTS: TMJ disc cell viability significantly decreased (P < 0.0001) without glucose. With glucose present, decreased oxygen levels significantly increased viability (P < 0.0001), while a decrease in glucose concentration significantly decreased viability (P < 0.0001). With glucose present, decreasing oxygen levels significantly reduced ATP production (P < 0.0001) and matrix synthesis (P < 0.0001). A decreased glucose concentration significantly decreased collagen synthesis (P < 0.0001). The interaction between glucose and oxygen was significant in regards to cell viability (P < 0.0001), ATP production (P = 0.00015), and collagen (P = 0.0002) and proteoglycan synthesis (P < 0.0001). CONCLUSIONS: Although both glucose and oxygen are important, glucose is the limiting nutrient for TMJ disc cell survival. At low oxygen levels, the production of ATP, collagen, and proteoglycan are severely inhibited. These results suggest that steeper nutrient gradients may exist in the TMJ disc and it may be vulnerable to pathological events that impede nutrient supply.

Viscoelastic shear properties of porcine temporomandibular joint disc.

OBJECTIVES: To investigate the intrinsic viscoelastic shear properties in porcine TMJ discs. MATERIALS AND METHODS: Twelve fresh porcine TMJ discs from young adult pigs (6-8 months) were used. Cylindrical samples (5 mm diameter) with uniform thickness (~1.2 mm) were prepared from five regions of the TMJ disc. Torsional shear tests were performed under 10% compressive strain. Dynamic shear was applied in two methods: 1) a frequency sweep test over the frequency range of 0.1-10 rad/s with a constant shear strain amplitude of 0.05 rad and 2) a strain sweep test over the range of 0.005-0.15 rad at a constant frequency of 10 rad/s. Transient stress relaxation tests were also performed to determine the equilibrium shear properties. RESULTS: As the frequency increased in the frequency sweep test, the dynamic shear complex modulus increased, with values ranging from 7 to 17 kPa. The phase angle, ranging from 11 to 15 degrees, displayed no pattern of regional variation as the frequency increased. The dynamic shear modulus decreased as the shear strain increased. The equilibrium shear modulus had values ranging from 2.6 to 4 kPa. The posterior region had significantly higher values for dynamic shear modulus than those in the anterior region, while no significant regional difference was found for equilibrium shear modulus. CONCLUSION: Our results suggest that the intrinsic region-dependent viscoelastic shear characteristics of TMJ disc may play a crucial role in determining the local strain of the TMJ disc under mechanical loading.

Regional cell density distribution and oxygen consumption rates in porcine TMJ discs: an explant study.

OBJECTIVE: To determine the regional cell density distribution and basal oxygen consumption rates (based on tissue volume and cell number) of temporomandibular joint (TMJ) discs and further examine the impact of oxygen tension on these rates. DESIGN: TMJ discs from pigs aged 6-8 months were divided into five regions: anterior, intermediate, posterior, lateral and medial. The cell density was determined using confocal laser scanning microscopy. The change in oxygen tension was recorded while TMJ disc explants were cultured in sealed metabolism chambers. The volume based oxygen consumption rate of explants was determined by theoretical curve-fitting of the recorded oxygen tension data with the Michaelis-Menten equation. The rate on a per-cell basis was calculated based on the cell density measurements and volume based rate measured in another group of discs. RESULTS: The overall cell density [mean, 95% confidence interval (CI)] was 51.3 (21.3-81.3) × 10(6) cells/mL wet tissue. Along the anteroposterior axis, the anterior band had 25.5% higher cell density than the intermediate zone (P<0.02) and 29.1% higher than the posterior band (P<0.008). Along the mediolateral axes, the medial region had 26.2% higher cell density than the intermediate zone (P<0.04) and 25.4% higher than the lateral region (P<0.045). The overall volume and cell based maximum oxygen consumption rates were 1.44 (0.44-2.44) µmol/mL wet tissue/h and 28.7 (12.2-45.2)nmol/10(6)cells/h, respectively. The central regions (intermediate, lateral, and medial) had significantly higher volume based (P<0.02) and cell based (P<0.005) oxygen consumption rates than the anterior and posterior bands. At high oxygen tension, the oxygen consumption rate remained constant, but dropped as oxygen tension fell below 5%. CONCLUSIONS: The TMJ disc had higher cell density and oxygen consumption rates than articular cartilage reported in the literature. These results suggest that a steeper oxygen gradient may exist in the TMJ disc and may be vulnerable to pathological events that impede nutrient supply.

Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.

Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting various oncogenic pathways. It has been demonstrated that miR-489 directly targets HER2 and inhibits the HER2 signaling pathway; however, its role in mammary gland development and HER2-induced tumor initiation hasn't been studied. To dissect the role of miR-489, we sorted different populations of mammary epithelial cells and determined that miR-489 was highly expressed in mammary stem cells. MMTV-miR-489 mice that overexpressed miR-489 in mammary epithelial cells were developed and these mice exhibited an inhibition of mammary gland development in early ages with a specific impact on highly proliferative cells. Double transgenic MMTV-Her2-miR489 mice were then generated to observe how miR-489 overexpression affects HER2-induced tumorigenesis. miR-489 overexpression delayed HER2-induced tumor initiation significantly. Moreover, miR-489 overexpression inhibited tumor growth and lung metastasis. miR-489 overexpression reduced mammary progenitor cell population significantly in preneoplastic mammary glands of MMTV-Her2 mice which showed a putative transformed population in HER2-induced tumorigenesis. The miR-489 overexpression reduced CD49fhiCD61hi populations in tumors that have stem-like properties, and miR-489 overexpression altered the HER2 signaling pathway in mammary tumors. Altogether, these data indicate that the inhibition of HER2-induced tumorigenesis by miR-489 overexpression was due to altering progenitor cell populations while decreasing tumor growth and metastasis via influencing tumor promoting genes DEK and SHP2.

Correction: Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.

In the published version of this paper the author A. Awgulewitsch's surname was incorrectly given as Awagulerwitsch instead of Awgulewitsch. This has now been corrected in the HTML version of the paper, the PDF was correct at the time of publication.

Effect of Sustained Joint Loading on TMJ Disc Nutrient Environment.

The temporomandibular joint (TMJ) disc nutrient environment profoundly affects cell energy metabolism, proliferation, and biosynthesis. Due to technical challenges of in vivo measurements, the human TMJ disc extracellular nutrient environment under load, which depends on metabolic rates, solute diffusion, and disc morphometry, remains unknown. Therefore, the study objective was to predict the TMJ disc nutrient environment under loading conditions using combined experimental and computational modeling approaches. Specifically, glucose consumption and lactate production rates of porcine TMJ discs were measured under varying tissue culture conditions (n = 40 discs), and mechanical strain-dependent glucose and lactate diffusivities were measured using a custom diffusion chamber (n = 6 discs). TMJ anatomy and loading area were obtained from magnetic resonance imaging of healthy human volunteers (n = 11, male, 30 ± 9 y). Using experimentally determined nutrient metabolic rates, solute diffusivities, TMJ anatomy, and loading areas, subject-specific finite element (FE) models were developed to predict the 3-dimensional nutrient profiles in unloaded and loaded TMJ discs (unloaded, 0% strain, 20% strain). From the FE models, glucose, lactate, and oxygen concentration ranges for unloaded healthy human TMJ discs were 0.6 to 4.0 mM, 0.9 to 5.0 mM, and 0% to 6%, respectively, with steep gradients in the anterior and posterior bands. Sustained mechanical loading significantly reduced nutrient levels (P < 0.001), with a critical zone in which cells may die representing approximately 13.5% of the total disc volume. In conclusion, this study experimentally determined TMJ disc metabolic rates, solute diffusivities, and disc morphometry, and through subject-specific FE modeling, revealed critical interactions between mechanical loading and nutrient supply and metabolism for the in vivo human TMJ disc. The results suggest that TMJ disc homeostasis may be vulnerable to pathological loading (e.g., clenching, bruxism), which impedes nutrient supply. Given difficulties associated with direct in vivo measurements, this study provides a new approach to systematically investigate homeostatic and degenerative mechanisms associated with the TMJ disc.

The same CCAAT box-binding factor binds to the promoter of two coordinately regulated major histocompatibility complex class II genes.

Using competition mobility shift, methylation interference, and proteolytic clipping DNA binding assays, we demonstrate that the protein binding the major histocompatibility complex A beta CCAAT box is indistinguishable from the protein previously named NF-Y, which binds the major histocompatibility complex E alpha CCAAT box. Although the two CCAAT boxes share the same 10-base core sequence, termed the Y box, their flanking sequences, known to be important for binding, are very different.

The Prx1 homeobox gene is critical for molar tooth morphogenesis.

The paired-related homeobox genes, Prx1 and Prx2, encode transcription factors critical for orofacial development. Prx1(-/-)/Prx2(-/-) neonates have mandibular hypoplasia and malformed mandibular incisors. Although the mandibular incisor phenotype has been briefly described (ten Berge et al., 1998, 2001; Lu et al., 1999), very little is known about the role of Prx proteins during tooth morphogenesis. Since the posterior mandibular region was relatively normal, we examined molar tooth development in Prx1(-/-)/Prx2(-/-) embryos to determine whether the tooth malformation is primary to the loss of Prx protein or secondary to defects in surrounding tissues. Three-dimensional (3D) morphological reconstructions demonstrated that Prx1(-/-)/Prx2(-/-) embryos had molar malformations, including cuspal changes and ectopic epithelial projections. Although we demonstrate that Prx1 protein is expressed only mesenchymally, 3D reconstructions showed important morphological defects in epithelial tissues at the cap and bell stages. Analysis of these data suggests that the Prx homeoproteins are critical for mesenchymal-epithelial signaling during tooth morphogenesis.

Coronary physiology revisited : practical insights from the cardiac catheterization laboratory.

Various coronary physiological measurements can be made in the cardiac catheterization laboratory using sensor-tipped guidewires; they include the measurement of poststenotic absolute coronary flow reserve, the relative coronary flow reserve, and the pressure-derived fractional flow reserve of the myocardium. Ambiguity regarding abnormal microcirculation has been reduced or eliminated with measurements of relative coronary flow reserve and fractional flow reserve. The role of microvascular flow impairment can be separately determined with coronary flow velocity reserve measurements. In addition to lesion assessment before and after intervention, emerging applications of coronary physiology include the determination of physiological responses to new pharmacological agents, such as glycoprotein IIb/IIIa blockers, in patients with acute myocardial infarction. Measurements of coronary physiology in the catheterization laboratory provide objective data that complement angiography for clinical decision-making.

Predictors of mortality and mortality from cardiac causes in the bypass angioplasty revascularization investigation (BARI) randomized trial and registry. For the BARI Investigators.

BACKGROUND: The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. METHODS AND RESULTS: In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P<0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P<0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P=0.019). CONCLUSIONS: A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

Fractional flow reserve compared with intravascular ultrasound guidance for optimizing stent deployment.

BACKGROUND: Determination of fractional flow reserve (FFR) has been proposed as a means to assess stent deployment. In this prospective, multicenter trial, we evaluate the use of FFR to optimize stenting by comparing it with standard intravascular ultrasound (IVUS) criteria. METHODS AND RESULTS: Eighty-four stable patients with isolated coronary lesions underwent coronary stent deployment starting at 10 atm and increased serially by 2 atm until the FFR was >/=0.94 or 16 atm was achieved. IVUS was then performed. FFR was measured with a coronary pressure wire with intracoronary adenosine to induce hyperemia. The diagnostic characteristics of an FFR <0.94 to predict suboptimal stent expansion by IVUS, defined in both absolute and relative terms, were calculated. Over a range of IVUS criteria, the highest sensitivity, specificity, and predictive accuracy of FFR were 80%, 30%, and 42%, respectively. Receiver operator characteristic analysis defined an optimal FFR cut point at >/=0.96; at this threshold, the sensitivity, specificity, and predictive accuracy of FFR were 75%, 58%, and 62%, respectively (P=0.03 for comparison of predictive accuracy, P=0.01 for concordance between FFR and IVUS). The negative predictive value was 88%. Significantly better diagnostic performance was achieved in a subgroup that received higher doses (>30 microgram) of intracoronary adenosine during pressure measurements, suggesting that FFR might be overestimated in the other group. CONCLUSIONS: A fractional flow reserve <0.96, measured after stent deployment, predicts a suboptimal result based on validated intravascular ultrasound criteria; however, an FFR >/=0.96 does not reliably predict an optimal stent result. Higher doses of intracoronary adenosine than previously used to measure FFR improve these results.

From research to clinical practice: current role of intracoronary physiologically based decision making in the cardiac catheterization laboratory.

Decisions regarding coronary interventions should be combined with objective evidence of myocardial ischemia. The most common physiologic approach utilizes hospital facilities outside the catheterization laboratory, requiring additional time and cost. With the introduction of sensor-tipped angioplasty guide wires, distal coronary flow velocity and pressure can be obtained in the cardiac catheterization laboratory, facilitating physiologically based decisions regarding the need for intervention. In the catheterization laboratory, physiologically significant stenoses can be characterized as having impaired post-stenotic coronary flow reserve < 2.0 and pressure-derived fractional flow reserve < 0.75, both variables related strongly to positive ischemic perfusion imaging or stress testing results. Deferring coronary interventions on the basis of normal translesional physiology is safe and is associated with a low rate (< 10%) of lesion progression over a 10-month follow-up period. Preliminary data indicate that excellent physiologic and anatomic end points after balloon angioplasty are associated with low (< 20%) restenosis rates at 6-month follow-up. Clinically relevant relations of in-laboratory physiology support the insight that physiologic, as much as or more than anatomic variables, ultimately determine the functional status of a patient. Current data suggest that an intracoronary physiologic approach complements coronary lumenology and appears to have important clinical and economic implications for patients undergoing invasive evaluation and treatment of coronary artery disease.

Diastolic function in patients undergoing coronary angioplasty: influence of degree of revascularization.

To assess the early effects of successful coronary angioplasty on Doppler-derived left ventricular filling patterns and the significance of the extent of revascularization on these variables, 31 patients undergoing coronary angioplasty were examined within 24 h before and after the revascularization procedure. After angioplasty, the peak early to late velocity ratio increased from 0.89 +/- 0.2 to 1.05 +/- 0.3 (p less than 0.0001) and the one-third filling fraction increased from 42 +/- 10% to 48 +/- 10% (p less than 0.0001). The percent atrial contribution to filling decreased from 45 +/- 7% to 41 +/- 8% (p less than 0.01), and the pressure half-time and the isovolumetric relaxation time shortened from 55 +/- 15 to 43 +/- 13 ms (p less than 0.001) and from 100 +/- 14 to 82 +/- 17 ms (p less than 0.0001), respectively. When comparing patients with complete (n = 23) and incomplete (n = 8) revascularization, the same changes in the Doppler variables were observed. However, the mean rate of acceleration of early filling increased significantly after angioplasty only in those patients with complete revascularization. These data indicate that the left ventricular diastolic filling pattern is modified significantly as early as 24 h after successful coronary angioplasty. Improvement in impaired relaxation appears to be the most likely explanation for these changes, although increased myocardial stiffness in patients with incomplete revascularization is an alternative hypothesis.

Intravenous adenosine: continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease.

To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Enhanced coronary blood flow velocity during intraaortic balloon counterpulsation in critically ill patients.

OBJECTIVES: The aim of this study was to assess coronary blood flow during intraaortic balloon counterpulsation by direct measurement. BACKGROUND: In a majority of human studies, increased coronary blood flow during intraaortic balloon counterpulsation measured by indirect techniques has not been consistently demonstrated. METHODS: Hemodynamic variables and coronary blood flow velocity (20-MHz Doppler-tipped catheter) data were measured in 19 patients requiring intraaortic balloon pumping for clinical indications (11 patients had acute myocardial infarction [9 with shock], 6 had unstable angina, 1 had acute mitral regurgitation and 1 was at high risk undergoing angioplasty). Hemodynamic data, mean and phasic diastolic flow velocity and velocity-time integrals (computed from digitized waveforms) were analyzed during periods of 1:1 balloon counterpulsation. RESULTS: Intraaortic balloon pumping decreased systolic pressure (6 +/- 10%, p < 0.001) and increased diastolic pressure (80 +/- 30% from baseline, p < 0.001) without changing RR interval. Peak phasic, mean coronary flow velocity and diastolic flow velocity integral were significantly increased (115 +/- 115%, 67 +/- 61%, 103 +/- 81%, respectively, all p < 0.001) during intraaortic balloon pumping. In addition, although a wide splay of data was evident due to operator set variations in balloon inflation and deflation timing, the greater increases in diastolic flow velocity integral (DFVi) occurred in patients with basal systolic pressure < or = 90 mm Hg (% delta DFVi = 102 - 0.1.[unaugmented systolic pressure], SEE = 21.7 mm Hg, r = 0.30, p < 0.001). CONCLUSIONS: Intraaortic balloon pumping unequivocally and significantly augments proximal coronary blood flow velocity, nearly doubling the coronary flow velocity integral in most patients. This mechanism may be a significant means of ischemia relief in hypotensive patients.

Coronary angioplasty: a therapeutic option for symptomatic patients with two and three vessel coronary disease.

Coronary angioplasty is a widely applied revascularization procedure for patients with multivessel coronary artery disease. However, follow-up in this patient subgroup is relatively limited. From 1983 to 1986, coronary angioplasty was performed in 349 and 121 patients with, respectively, two- and three-vessel coronary disease with a primary success rate of 83 and 88%. The in-hospital mortality rate was 2.8% (13 of 470 patients). Complete revascularization was achieved in 128 patients. Among the 397 patients with a successful outcome, 373 (94%) were followed up greater than or equal to 1 year; 79% were free of death, nonfatal myocardial infarction or the need for coronary bypass grafting, and 82% of patients had symptomatic improvement by at least one angina functional class. A second coronary angioplasty procedure was required in 13% of patients. After a mean follow-up period of 27 months, an increased incidence of coronary bypass grafting was noted in patients with incomplete versus complete revascularization (16 versus 7%, p less than 0.05). Among the 222 patients who had repeat cardiac catheterization performed an average of 7 months after angioplasty, 103 were symptomatic; 50% of the 222 patients had at least one vessel with greater than or equal to 50% restenosis and 14% of patients had multiple restenoses. In conclusion, coronary angioplasty can be performed with a high initial success rate and marked symptomatic improvement in patients with multivessel coronary disease. However, in this group's experience, the majority of patients selected for coronary angioplasty with multivessel coronary disease will have incomplete revascularization that can be predicted in the majority of patients before the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficiency and safety of optically modified fiber tips for laser angioplasty.

To evaluate the safety and efficiency of optically modified fiber tips, craters were created in human cadaver atherosclerotic arterial walls using sapphire contact probes and lensed fibers connected to a continuous wave neodymium yttrium aluminum garnet (Nd-YAG) laser. Laser energy was emitted at a constant level of 50 J. The sapphire contact probe catheter consisted of a round 2.2 mm diameter synthetic sapphire attached to an 8F catheter into which a 0.2 mm diameter optical fiber was inserted with the distal tip maintained at 3 mm from the sapphire. The lensed fiber catheter consisted of a 0.2 mm optical fiber at the end of which a 1 mm diameter lens was made. The fiber was inserted into a 5F low profile balloon catheter with the lens maintained 3 mm beyond the catheter tip. During laser emissions the catheter tips were maintained in a stationary position in contact with tissue targets immersed in blood at an angle of 90 degrees. The diameter of holes at the entry and exit of craters, the depth of craters and thermal injury to adjacent tissue (rim of carbonization and vacuolization) were measured with microscopy. The volume of tissue removed was derived from these values. Controlled effect index was determined as the ratio of diameter of holes and the extent of thermal injury. Efficiency was determined as the ratio of volume of tissue removed and the energy required to vaporize tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular diastolic function: comparison of pulsed Doppler echocardiographic and hemodynamic indexes in subjects with and without coronary artery disease.

To evaluate the influence of left ventricular chamber stiffness and relaxation on Doppler echocardiographic indexes of diastolic function, 35 patients (mean age 60 +/- 12 years) were examined; 24 had coronary artery disease and 11 (Group I) had no cardiovascular disease. Micromanometer left ventricular pressure was recorded simultaneously with Doppler echocardiograms of mitral valve inflow and M-mode echocardiograms of left ventricular diameter. The chamber stiffness constant (k) was derived from the pressure-diameter relation. Relaxation was assessed by the isovolumic relaxation time constant (tau) derived from the exponential left ventricular pressure decay. The patients with coronary artery disease were classified into two groups on the basis of complete (Group II; n = 10) and incomplete (Group III; n = 14) relaxation. In Group I (no coronary disease), significant correlations were demonstrated between the chamber stiffness constant and the peak early filling velocity (r = 0.73; p less than 0.02), peak early to atrial filling velocity ratio (r = 0.82; p less than 0.005), atrial time-velocity integral (r = -0.73; p less than 0.02), early to atrial time-velocity integral ratio (r = 0.70; p less than 0.05), percent atrial contribution to filling (r = -0.64; p less than 0.05) and one-half filling fraction (r = 0.73; p less than 0.02). In Group II (coronary disease with complete relaxation), the chamber stiffness constant correlated with peak early filling velocity (r = 0.68; p less than 0.05), early filling time-velocity integral (r = 0.65; p less than 0.05) and early to atrial time-velocity integral ratio (r = 0.74; p less than 0.02). No correlations between k and Doppler indexes were found in Group III (coronary disease with incomplete relaxation). However, Group III demonstrated significant correlations between tau and the peak early filling velocity (r = -0.71; p less than 0.005), percent atrial contribution to filling (r = 0.56; p less than 0.05) and mean acceleration rate of early filling (r = -0.79; p less than 0.002). Thus, in subjects with normal relaxation, increasing chamber stiffness was associated with an enhanced peak early filling velocity and volume and decreased filling during atrial systole. This finding differs strikingly from the proposed influence of chamber stiffness on diastolic filling postulated by several researchers.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of pharmacologic coronary hyperemia on echocardiographic left ventricular function in patients with single vessel coronary artery disease.

To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricular wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 +/- 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group. Although intracoronary mean flow velocity measured in the 14 group 1 patients and in 5 normal control subjects during papaverine treatment increased from 125% to 400% of basal flow velocity, papaverine induced new left ventricular wall motion abnormalities in only 5 of the 14 patients before coronary angioplasty. In three of five patients, left ventricular wall motion abnormalities persisted after successful coronary angioplasty. Four of the 14 patients demonstrated augmentation of left ventricular wall motion with papaverine. After intravenous dipyridamole, only 3 of the 13 group 2 patients developed new left ventricular regional asynergy. These data suggest that selective (papaverine) and, most likely, global (dipyridamole) augmentation of coronary flow alone does not reliably identify potential ischemic left ventricular regions affected by critical single vessel coronary artery disease.

Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements.

OBJECTIVES: The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND: The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS: Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS: In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS: These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.