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6. Validated model of platelet slip at stenosis and device surfaces

Author

Naval Postgraduate School (U.S.), Physics, Denardo, Scott J., Denardo, Bruce C., Carpinone, Paul L., Dean, William T., New, David M., Estrada, Luis E., Green, Cynthia L., Yock, Paul G., Karunasiri, Gamani, Naval Postgraduate School (U.S.), Physics, Denardo, Scott J., Denardo, Bruce C., Carpinone, Paul L., Dean, William T., New, David M., Estrada, Luis E., Green, Cynthia L., Yock, Paul G., and Karunasiri, Gamani

Abstract

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres–modeling platelets–slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200–400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20–90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective)and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm−1]×mean velocity [cm×sec−1]). Moreover, the

Published
2020

10. An Intravascular Ultrasound Analysis in Women Experiencing Chest Pain in the Absence of Obstructive Coronary Artery Disease: A Substudy from the National Heart, Lung and Blood Institute–Sponsored Womenʼs Ischemia Syndrome Evaluation (WISE)

Author

KHUDDUS, MATHEEN A., PEPINE, CARL J., HANDBERG, EILEEN M., MERZ, NOEL C. BAIREY, SOPKO, GEORGE, BAVRY, ANTHONY A., DENARDO, SCOTT J., McGORRAY, SUSAN P., SMITH, KAREN M., SHARAF, BARRY L., NICHOLLS, STEVEN J., NISSEN, STEVEN E., and ANDERSON, DAVID R.

Published
2010
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12. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: An INVEST substudy

Author

Denardo, Scott J., Gong, Yan, Nichols, Wilmer W., Messerli, Franz H., Bavry, Anthony A., Cooper-DeHoff, Rhonda M., Handberg, Eileen M., Champion, Annette, and Pepine, Carl J.

Subjects
Coronary heart disease -- Research, Coronary heart disease -- Risk factors, Coronary heart disease -- Demographic aspects, Hypertension -- Complications and side effects, Hypertension -- Research, Health, Health care industry
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2010.02.014 Byline: Scott J. Denardo (a), Yan Gong (b), Wilmer W. Nichols (a), Franz H. Messerli (c), Anthony A. Bavry (a), Rhonda M. Cooper-DeHoff (a)(d), Eileen M. Handberg (a), Annette Champion (e), Carl J. Pepine (a) Keywords: Age; Blood pressure control; Coronary artery disease; Elderly; Epidemiology; Hypertension Abstract: Our understanding of the growing population of very old patients (aged [greater than or equal to]80 years) with coronary artery disease and hypertension is limited, particularly the relationship between blood pressure and adverse outcomes. Author Affiliation: (a) Division of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville (b) Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville (c) Division of Cardiology, St Luke's-Roosevelt Hospital Center and Columbia University College of Medicine and Physicians, New York, NY (d) Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville (e) Abbott Laboratory, Abbott Park, Ill Article Note: (footnote) Funding: Financial support for this research: None. Financial support for original INVEST: University of Florida (Gainesville, Fla); Abbott Laboratories (Abbott Park, Ill)., Conflict of Interest: Potential conflicts of interest: Dr. Denardo: None; Dr. Gong: None; Dr. Nichols: None; Dr. Messerli: Abbott Laboratories (ad hoc consultant; speaker); Dr. Cooper-DeHoff: Abbott Laboratories (grant); Dr. Handberg: Abbott Laboratories (grant); Ms. Champion: Abbott Laboratories (employee; stock/stock options); Dr. Pepine: Abbott Laboratories (grant; ad hoc consultant)., Authorship: All authors had access to the data and a role in writing the manuscript.

Published
2010

14. Analysis of pulsed wave Doppler ultrasound spectra obtained from a model intracoronary catheter

Author

Denardo, Scott J., Talbot, Lawrence, Hargrave, Victor K., Fitzgerald, Peter J., Selfridge, Alan R., and Yock, Paul G.

Subjects
Blood flow -- Research, Laser Doppler blood flowmetry -- Research, Arteries -- Physiological aspects, Biological sciences, Business, Computers, Health care industry
Abstract

Abnormal arterial blood flow patterns have been implicated in the evolution of various vascular disease processes. Intravascular ultrasound techniques using the pulsed wave Doppler catheter offer the opportunity to characterize these abnormal flow patterns. We have developed a mathematical model that predicts the first two moments of the Doppler spectrum obtained using a Doppler catheter based on the distribution of ultrasonic beam power and velocity profile of fluid flow with an arbitrary distribution of flow disturbances. A scaled-up, invitro experimental arterial system was used to confirm the validity of the model. Comparison of the predicted first two moments of the Doppler spectrum to the experimental values in this system demonstrated that the distribution of beam power significantly affects the magnitude of the first two moments. Additionally, both velocity gradient and velocity fluctuation broadening effects play prominent roles in determining the magnitude of the second moment. These phenomena must therefore be considered when evaluating invivo Doppler spectra used for the characterization of abnormal flow patterns.

Published
1994

15. Correction: Effects of verapamil SR and atenolol on 24-Hour blood pressure and heart rate in hypertension patients with coronary artery disease: An international verapamil SR-trandolapril ambulatory monitoring substudy

Author

Denardo, Scott J., Denardo, S, Gong, Y, Cooper-DeHoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-DeHoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, Lï¿1⁄2szlï¿1⁄2, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, Pepine, Carl J., Denardo, Scott J., Denardo, S, Gong, Y, Cooper-DeHoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-DeHoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, Lï¿1⁄2szlï¿1⁄2, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, and Pepine, Carl J.

Abstract

This corrects the article DOI: 10.1371/journal.pone.0122726

Published
2016

18. Validated model of platelet slip at stenosis and device surfaces.

Author

Denardo, Scott J., Denardo, Bruce C., Carpinone, Paul L., Dean, William T., New, David M., Estrada, Luis E., Green, Cynthia L., Yock, Paul G., and Karunasiri, Gamani

Subjects
*LASER Doppler velocimetry, *BLOOD platelets, *PARTICLE image velocimetry, *LOGISTIC regression analysis, *BLOOD platelet aggregation, *FLUID flow, *BONE lengthening (Orthopedics)
Abstract

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres–modeling platelets–slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200–400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20–90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective) and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm−1]×mean velocity [cm×sec−1]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses. [ABSTRACT FROM AUTHOR]

Published
2020
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19. Association of Aortic Stiffness and Wave Reflections with Coronary Flow Reserve in Women without Obstructive Coronary Artery Disease: An Ancillary Study from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)

Author

Nichols, Wilmer W., Denardo, Scott J., Davidson, Jonathan B., Huo, Tianyao, Merz, C. Noel Bairey, and Pepine, Carl J.

Subjects
Adult, Fractional Flow Reserve, Myocardial, Vascular Stiffness, Statistics as Topic, Myocardial Ischemia, Humans, Arterial Pressure, Female, Middle Aged, Pulse Wave Analysis, Article
Abstract

Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited.CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized.Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P.001), systolic pressure time index (r = -0.37, P.008), and rate pressure product (r = -0.29, P.04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P.008) and aortic systolic pressure (P.01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P.001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P.008), AIx (32 ± 6.6 vs 27 ± 6.6%, P.003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P.02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P.008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P.04).Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Published
2015

20. Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease

Author

Denardo, Scott J., Gong, Yan, Cooper-DeHoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, László, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, and Pepine, Carl J.

Subjects
Heart--Diseases--Patients, Public health, Atenolol, Verapamil, Pathology, Medicine, Drugs, Hypertension--Treatment
Abstract

Elevated night-time blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P

Published
2015
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21. Correction: Effects of verapamil SR and atenolol on 24-Hour blood pressure and heart rate in hypertension patients with coronary artery disease: An international verapamil SR-trandolapril ambulatory monitoring substudy

Author

Denardo, S, Gong, Y, Cooper-DeHoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-DeHoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, L�szl�, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, Pepine, Carl J., Denardo, S, Gong, Y, Cooper-DeHoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-DeHoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, L�szl�, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, and Pepine, Carl J.

Abstract

This corrects the article DOI: 10.1371/journal.pone.0122726

Published
2016

23. Correction: Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease: An International Verapamil SR-Trandolapril Ambulatory Monitoring Substudy

Author

Denardo, Scott J., primary, Gong, Yan, additional, Cooper-DeHoff, Rhonda M., additional, Farsang, Csaba, additional, Keltai, Matyas, additional, Szirmai, László, additional, Messerli, Franz H., additional, Bavry, Anthony A., additional, Handberg, Eileen M., additional, Mancia, Giuseppe, additional, and Pepine, Carl J., additional

Published
2016
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24. Effects of verapamil SR and atenolol on 24-hour blood pressure and heart rate in hypertension patients with coronary artery disease: An international verapamil SR-trandolapril ambulatory monitoring substudy

Author

Denardo, S, Gong, Y, Cooper-Dehoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-Dehoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, László, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, Pepine, Carl J., Denardo, S, Gong, Y, Cooper-Dehoff, R, Farsang, C, Keltai, M, Szirmai, L, Messerli, F, Bavry, A, Handberg, E, Mancia, G, Pepine, C, Denardo, Scott J., Gong, Yan, Cooper-Dehoff, Rhonda M., Farsang, Csaba, Keltai, Matyas, Szirmai, László, Messerli, Franz H., Bavry, Anthony A., Handberg, Eileen M., Mancia, Giuseppe, and Pepine, Carl J.

Abstract

Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged >50 years with hypertension and CAD randomized to either verapamil SR-oratenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26-8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events.

Published
2015

25. Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease: An International Verapamil SR-Trandolapril Ambulatory Monitoring Substudy

Author

Denardo, Scott J., primary, Gong, Yan, additional, Cooper-DeHoff, Rhonda M., additional, Farsang, Csaba, additional, Keltai, Matyas, additional, Szirmai, László, additional, Messerli, Franz H., additional, Bavry, Anthony A., additional, Handberg, Eileen M., additional, Mancia, Giuseppe, additional, and Pepine, Carl J., additional

Published
2015
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26. Is the adaptation of right ventricular refractoriness to an abrupt increase in heart rate impaired in chronic heart failure?

Author

Denardo, Scott J. and Stevenson, William G.

Subjects
Heart -- Contraction, Heart -- Abnormalities, Sudden death -- Causes of, Heart failure -- Causes of, Health
Abstract

This paper explores the underlying mechanisms that contribute to the high rate of irregularities of ventricular contraction and subsequent sudden death that occurs in patients with chronic heart failure. The investigators explore as a possible factor the inability of these hearts to respond to an abrupt increase in heart rate. Twenty-eight patients with chronic heart failure and 11 patients with normal hearts were compared with regard to various measures of electrical activity of the heart. A specific physiologic measure, the refractory period, was found to be different in the patients with chronic heart failure. The refractory period is the time following a contraction when the heart muscle cannot again contract. The authors conclude that the chronic heart failure is associated with an increased refractory period, but that the ability of the heart to adapt to a sudden increase in rate is unimpaired in patients with chronic heart failure and unlikely to contribute to the increased incidence of irregular rates of contraction in heart failure.

Published
1989

33. EFFECT OF PHOSPHODIESTERASE TYPE 5 (PDE-5) INHIBITION ON CORONARY MICROVASCULAR DYSFUNCTION IN WOMEN: AN ANCILLARY STUDY FROM THE NHLBI-SPONSORED WOMEN’S ISCHEMIA SYNDROME EVALUATION (WISE)

Author

Denardo, Scott J., primary, Wen, Sheron, additional, Handberg, Eileen M., additional, Bavry, Anthony A., additional, Anderson, R. David, additional, Smith, Karen M., additional, Bairey-Merz, C. Noel, additional, Sopko, George, additional, Cooper-DeHoff, Rhonda M., additional, and Pepine, Carl J., additional

Published
2010
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42. Accuracy of Doppler Catheter Measurements: Effect of Inhomogeneous Beam Power Distribution on Mean and Peak Velocity 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California, San Francisco.

Author

Denardo, Scott J, primary, Talbot, Lawrence, additional, Hargrave, Victor K, additional, Selfridge, Alan R, additional, Ports, Thomas A, additional, and Yock, Paul G, additional

Published
1997
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45. Coronary angioscopy before and after stent deployment

Author

Denardo, Scott J., primary, Schatz, Richard A., additional, Rocha-Singh, Krishna J., additional, Wong, S. Chiu, additional, Morris, Nancy A., additional, Strumpf, Robert K., additional, Heuser, Richard R., additional, and Teirstein, Paul, additional

Published
1993
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