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Ghassan S Kassab

Publications and source records attributed to Ghassan S Kassab.

At least 19 recordsLinked to original sources
PubMed2007

Vasoactivity of blood vessels using a novel isovolumic myograph.

The vasoactivity of blood vessel is impaired by cardiovascular disease. The ex-vivo measurements of vasoactivity (wire and pressure myographs) have some inherent difficulties in the characterization of pharmacodynamics and biomechanics. Here, we introduce a novel isovolumic myograph which allows simultaneous measurement of both dynamic pressure and dimensional changes during vasoconstriction or vasodilation. The principle of the isovolumic myograph is based on the utility of a hydraulically closed system with low compliance such that contraction against an incompressible fluid increases the pressure with the closed system while dilation decreases it. We demonstrate the sensitivity and utility of the new technique by the response of elastic (carotid), muscular (femoral) arteries, and femoral veins. The results show characteristic dynamic pressure response for each vessel type. Furthermore, our results show a Hill-type equation for the tension-velocity relation for smooth muscles as well as characteristic curves for each contraction. These novel findings for blood vessels will advance our knowledge of endothelium and vascular smooth muscle mechanics and pharmacodynamics.

Animals↗
PubMed2007

Capillary perfusion and wall shear stress are restored in the coronary circulation of hypertrophic right ventricle.

It has been shown that right ventricle (RV) hypertrophy involves significant compensatory vascular growth and remodeling. The objective of the present study was to determine the functional implications of the vascular growth and remodeling through a full flow analysis of arterial tree down to first capillary segments. A computer reconstruction of RV branches including the proximal right coronary artery to the posterior descending artery was established based on measured morphometric data in arrested, vasodilated porcine heart. The flows were computed throughout the reconstructed trees based on conservation of mass and momentum and appropriate pressure boundary conditions. It was found that the flow rate was significantly increased in large epicardial coronary arteries in hypertrophic as compared with control hearts but normalized in the intramyocardial coronary arteries and smaller vessels in RV hypertrophy primarily because of the significant increase in number of arterioles. Furthermore, the wall shear stress was restored to nearly homeostatic levels throughout most of the vasculature after 5 weeks of RV hypertrophy. The compensatory remodeling in RV hypertrophy functionally restores the perfusion at the arteriolar and capillary level and wall shear stress in most of larger vessels. This is the first full analysis of coronary arterial tree, with millions of vessels, in cardiac hypertrophy that reveals the compensatory adaptation of structure to function.

Animals↗
PubMed2007

A hybrid one-dimensional/Womersley model of pulsatile blood flow in the entire coronary arterial tree.

Using a frequency-domain Womersley-type model, we previously simulated pulsatile blood flow throughout the coronary arterial tree. Although this model represents a good approximation for the smaller vessels, it does not take into account the nonlinear convective energy losses in larger vessels. Here, using Womersley's theory, we present a hybrid model that considers the nonlinear effects for the larger epicardial arteries while simulating the distal vessels (down to the 1st capillary segments) with the use of Womersley's Theory. The main trunk and primary branches were discretized and modeled with one-dimensional Navier-Stokes equations, while the smaller-diameter vessels were treated as Womersley-type vessels. Energy losses associated with vessel bifurcations were incorporated in the present analysis. The formulation enables prediction of impedance and pressure and pulsatile flow distribution throughout the entire coronary arterial tree down to the first capillary segments in the arrested, vasodilated state. We found that the nonlinear convective term is negligible and the loss of energy at a bifurcation is small in the larger epicardial vessels of an arrested heart. Furthermore, we found that the flow waves along the trunk or at the primary branches tend to scale (normalized with respect to their mean values) to a single curve, except for a small phase angle difference. Finally, the model predictions for the inlet pressure and flow waves are in excellent agreement with previously published experimental results. This hybrid one-dimensional/Womersley model is an efficient approach that captures the essence of the hemodynamics of a complex large-scale vascular network. The present model has numerous applications to understanding the dynamics of coronary circulation.

Animals↗
PubMed2006

Biomechanics of the cardiovascular system: the aorta as an illustratory example.

Biomechanics relates the function of a physiological system to its structure. The objective of biomechanics is to deduce the function of a system from its geometry, material properties and boundary conditions based on the balance laws of mechanics (e.g. conservation of mass, momentum and energy). In the present review, we shall outline the general approach of biomechanics. As this is an enormously broad field, we shall consider a detailed biomechanical analysis of the aorta as an illustration. Specifically, we will consider the geometry and material properties of the aorta in conjunction with appropriate boundary conditions to formulate and solve several well-posed boundary value problems. Among other issues, we shall consider the effect of longitudinal pre-stretch and surrounding tissue on the mechanical status of the vessel wall. The solutions of the boundary value problems predict the presence of mechanical homeostasis in the vessel wall. The implications of mechanical homeostasis on growth, remodelling and postnatal development of the aorta are considered.

Animals↗
PubMed2006

Vascular metabolic dissipation in Murray's law.

The metabolic dissipation in Murray's minimum energy hypothesis includes only the blood metabolism. The metabolic dissipation of the vascular tree, however, should also include the metabolism of passive and active components of the vessel wall. In this study, we extend the metabolic dissipation to include blood metabolism, as well as passive and active components of the vessel wall. The analysis is extended to the entire vascular arterial tree rather than a single vessel as in Murray's formulation. The calculations are based on experimentally measured morphological data of coronary artery network and the longitudinal distribution of blood pressure along the tree. Whereas the model includes multiple dissipation sources, the total metabolic consumption of a complex vascular tree is found to remain approximately proportional to the cumulative arterial volume of the unit. This implies that the previously described scaling relations for the various morphological features (volume, length, diameter, and flow) remain unchanged under the generalized condition of metabolic requirements of blood and blood vessel wall.

Animals↗
PubMed2006

A bilinear stress-strain relationship for arteries.

A comprehensive understanding of the mechanical properties of blood vessels is essential for vascular physiology, pathophysiology and tissue engineering. A well-known approach to study the elasticity of blood vessels is to postulate a strain energy function such as the exponential or polynomial forms. It is typically difficult to fit experimental data to derive material parameters for blood vessels, however, due to the highly nonlinear nature of the stress-strain relation. In this work, we generalize the strain definition to absorb the elastic nonlinearity and then propose a two-dimensional bilinear stress-strain relation between second Piola-Kirchhoff stress and the new strain measure. The model is found to represent the Fung's exponential model very well. The novel linearized constitutive relation simplifies the determination of material constants by reducing the nonlinearity and provides a clearer physical interpretation of the model parameters. The limitations of the constitutive model and its implications for vascular mechanics are discussed.

Animals↗
PubMed2006

Proper orientation of the graft artery is important to ensure physiological flow direction.

Arterial grafts such as right internal mammary artery (RIMA), radial artery (RA) or epigastric artery are being used with increasing frequency as free grafts or as composite grafts with left internal mammary artery (LIMA). Currently, there is no consideration of the orientation of the free artery graft to mimic the in vivo state. Hence, some grafts may be oriented such that the direction of blood flow exerted on the endothelium is reversed relative to the in vivo condition. Previous studies have shown that transient flow reversal lead to atherogenesis. A recent study demonstrated that nitric oxide is significantly reduced during reverse flow and the reduction is mediated through an increase in superoxide production. In light of these data, we suggest that the flow direction is important and recommend the assurance of proper orientation of the free arterial graft. Furthermore, we propose a new surgical procedure to modify the composite LIMA-RA or LIMA-RIMA configuration as a horseshoe or K composite graft to ensure proper orientation of the flow direction relative to the endothelium.

Animals↗
PubMed2006

Pulsatile blood flow in the entire coronary arterial tree: theory and experiment.

The pulsatility of coronary circulation can be accurately simulated on the basis of the measured branching pattern, vascular geometry, and material properties of the coronary vasculature. A Womersley-type mathematical model is developed to analyze pulsatile blood flow in diastole in the absence of vessel tone in the entire coronary arterial tree on the basis of previously measured morphometric data. The model incorporates a constitutive equation of pressure and cross-section area relation based on our previous experimental data. The formulation enables the prediction of the impedance, the pressure distribution, and the pulsatile flow distribution throughout the entire coronary arterial tree. The model is validated by experimental measurements in six diastolic arrested, vasodilated porcine hearts. The agreement between theory and experiment is excellent. Furthermore, the present pulse wave results at low frequency agree very well with previously published steady-state model. Finally, the phase angle of flow is seen to decrease along the trunk of the major coronary artery and primary branches toward the capillary vessels. This study represents the first, most extensive validated analysis of Womersley-type pulse wave transmission in the entire coronary arterial tree down to the first segment of capillaries. The present model will serve to quantitatively test various hypotheses in the coronary circulation under pulsatile flow conditions.

Animals↗
PubMed2006

A novel strategy for increasing wall thickness of coronary venules prior to retroperfusion.

The sudden exposure of veins to arterial pressures during coronary venous retroperfusion may cause rupture of small venules. Our rationale is to first occlude the coronary vein, which will cause an increase in pressure intermediate to arterial and venous values, and hence lead to remodeling and increased wall thickness of the veins prior to retroperfusion. To accomplish this objective, five pigs were subjected to left anterior descending (LAD) vein ligation while six pigs served as sham. Myocardial tissue samples were obtained from the area adjacent to the LAD vein at four transmural locations of the left ventricular free wall: epicardial surface, subepicardium, midmyocardium, and endocardium. Arterioles and venules from the experimental and sham control groups were photographed, and the following measurements were made: inner and outer circumferences, inner and outer areas, major and minor diameters, and intima-media thickness. Each vessel was categorized in four different orders according to lumen diameter. Our results show that intima-media thickness was larger in the experimental group in all four regions of the heart and in all four orders of the vessels, although venules from the epicardial region showed the largest increase in thickness. The intima-media thickness-to-radius ratio was also larger in the experimental group and decreased from epicardial to endocardial region of the heart and from order 1 to order 4 of the vessels. The present study provides a rationale for the development of coronary retroperfusion strategy that avoids vessel rupture and hemorrhage in the postcapillary venules.

Animals↗
PubMed2006

AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress.

OBJECTIVE: The regulation of AMP-activated protein kinase (AMPK) is implicated in vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS). In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner). METHODS AND RESULTS: By using flow channels with cultured ECs, AMPK Thr172 phosphorylation was increased with changes of flow rate or pulsatility. The activity of LKB1, the upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were concomitant with AMPK activation responding to changes in flow rate or pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore, aortic AMPK activity and level of eNOS phosphorylation were significantly elevated in the aortas of High-Runner mice. CONCLUSIONS: Our results suggest that shear stress activates AMPK in ECs, which contributes to elevated eNOS activity and subsequent NO production. Hence, AMPK, in addition to serving as an energy sensor, also plays an important role in regulating vascular tone.

AMP-Activated Protein Kinases↗
PubMed2006

Three-dimensional mechanical properties of porcine coronary arteries: a validated two-layer model.

The normal coronary artery consists of two mechanically distinct layers: intima-media and adventitia. The objective of this study is to establish a two-layer three-dimensional (3-D) stress-strain relation of porcine coronary arteries. Experimental measurements were made by a series of biaxial tests (inflation and axial extension) of intact coronary arteries and, subsequently, their corresponding intima-media or adventitia layer. The Fung-type exponential strain energy function was used to describe the 3-D strain-stress relation for each layer and the intact wall. A genetic algorithm was used to determine the material constants in the Fung-type constitutive equation by curve fitting the experimental data. Because one layer must be sacrificed before the other layer can be tested, the material property of the missing layer was computed from the material constants of the intact vessel and the tested layer. A total of 20 porcine hearts were used: one group of 10 hearts for the left anterior descending artery and another group of 10 hearts for the right coronary artery. Each group was further divided into two subgroups of five specimens tested for the intact wall and the intima-media layer and for the intact wall and the adventitia layer. Our results show statistically significant differences in the material properties of the two layers. The mathematical model was validated by experimental stress-strain data for individual layers. The validated 3-D constitutive model will serve as a foundation for formulation of layer-specific boundary value problems in coronary physiology and cardiology.

Algorithms↗
PubMed2006

Analysis of blood flow in an out-of-plane CABG model.

Coronary artery bypass graft (CABG) is a routine surgical treatment for ischemic and infarcted myocardium. A large number of CABG fail postoperatively because of intimal hyperplasia within months or years. The cause of this failure is thought to be partly related to the flow patterns and shear stresses acting on the endothelial cells. An accurate representation of the flow field and associated wall shear stress (WSS) requires a detailed three-dimensional (3D) model of the CABG. The purpose of this study is to present a detailed analysis of blood flow in a 3D aorto/left CABG, bypassing the occluded left anterior descending coronary (LAD) artery. The analysis takes into account the influence of the out-of-plane geometry of the graft. The finite volume technique was employed to model the 3D blood flow pattern to determine the velocity and WSS distributions. This study presents the flow field distributions of the velocity and WSS at four instances of the cardiac cycle, two in systole and two in diastole. Our results reveal that the CABG geometry has a significant effect on the velocity distribution. The axial velocity profiles at different instances of the cardiac cycle exhibit strong skewing; significant secondary flow and vortex structures are seen in the in-plane velocity patterns. The maximum WSS on the bed of the occluded LAD artery opposite to the graft junction is 14 Pa in middiastole, whereas there is a significantly lower and more uniform distribution of WSS on the bed of the anastomosis. The present results indicate that nonplanarity of the blood vessel along with the inflow conditions has a substantial effect on the fluid mechanics of CABG that contribute to the patency of graft.

Animals↗
PubMed2006

Myocardial protection in the failing heart: I. Effect of cardioplegia and the beating state under simulated left ventricular restoration.

OBJECTIVE: Heart failure was induced by cardiac pacing to evaluate myocardial flow distribution of the open ventricle during delivery of either cardioplegia or in the beating state during simulated left ventricular restoration. METHODS: Studies included 5 (pacing-induced) failing pig hearts and 6 control hearts. Pacing-induced cardiac failure reduced fractional shortening by approximately 22%, increased left ventricular end-diastolic diameter by 34%, caused pulmonary hypertension (mean blood pressure increased from 12 to 35 mm Hg), and led to significant ascites. Global and regional coronary blood flow were measured with microspheres during cardiopulmonary bypass at 80 mm Hg perfusion pressure in either vented (collapsed) or open (exposure by traction for left ventricular restoration) left ventricles during continuous perfusion under either beating-heart or cardioplegic conditions. RESULTS: In control hearts, venting and exposure ventriculotomy did not affect flow. In failing hearts decompressed by venting, coronary flow was lower during the beating and cardioplegic delivery than during control conditions at the same perfusion pressure of 80 mm Hg. Mean cardioplegic flow during ventricular decompression by venting exceeded beating flow by 97%. Conversely, traction to increase the ventricular radius during exposure ventriculotomy reduced endocardial cardioplegic coronary blood flow by 64% (from 0.97 to 0.59 mL/[min x g]), whereas the beating state raised endocardial flow by 95% (from 0.40 to 0.78 mL/[min x g]). Changing ventricular shape changed coronary vascular resistance in failing hearts during beating or cardioplegic delivery. CONCLUSIONS: Coronary blood flow alterations occurred only in failing hearts when geometry was changed from closed to open state. The beating method provided more endocardial flow than cardioplegic delivery during ventricular exposure for restoration. Vascular remodeling raised coronary vascular resistance in failing hearts, thereby requiring higher pressure for similar blood flows.

Animals↗
PubMed2006

Myocardial protection in the failing heart: II. Effect of pulsatile cardioplegic perfusion under simulated left ventricular restoration.

OBJECTIVE: The open ventricle was studied in pacing-induced experimental heart failure to determine the extent of coronary perfusion and distribution during either continuous or pulsatile cardioplegic perfusion compared with whole blood in the beating heart. METHODS: In 5 animals that underwent pacing-induced heart failure and in 6 control swine, regional coronary blood flows were measured on bypass in the open left ventricle (simulating exposure for left ventricle restoration) during (1) beating, (2) nonpulsatile cardioplegia, and (3) pulsatile cardioplegia modalities. Mean perfusion pressure was maintained at 80 mm Hg. RESULTS: Flow magnitude and distribution differed in control and failing hearts in the open left ventricle. In control hearts, transmural and endocardial cardioplegic flow of nonpulsatile and pulsatile flow (which were similar to each other) exceeded beating flow by 63% and 70%, respectively, in the open left ventricle condition. Transmural and subendocardial vascular resistance increased in failing hearts during cardioplegic delivery, resulting in lower subendocardial flow under nonpulsatile conditions for the same perfusion pressure. In failing hearts, subendocardial perfusion conditions did not change in the beating state (0.89 vs 0.78 mL/min/g in control and failing open beating states, respectively), but nonpulsatile cardioplegic flow was significantly reduced by 154%, and became lower than beating flow by 32.2% (0.78 vs 0.59 mL/min/g). Conversely, pulsatile cardioplegic delivery improved endocardial flow in the open failing hearts, as cardioplegic perfusion with pulsatility exceeded beating flow by 41%. In heart failure, pulsatility from either the beating heart, which causes extrinsic compression of coronary vessels, or intrinsic vessel distension during pulsatile cardioplegic perfusion preserved endocardial perfusion better than nonpulsatile cardioplegia at the same perfusion pressure. CONCLUSION: In the failing open ventricle (simulated geometry during ventricular restoration), subendocardial blood flow was maintained in the beating state, but decreased significantly from control values during nonpulsatile cardioplegic perfusion. Conversely, pulsatile cardioplegic delivery improved subendocardial perfusion of the open failing ventricle. These findings of improved subendocardial perfusion during pulsatile delivery (either during beating or cardioplegic perfusion) compared with nonpulsatile cardioplegic delivery may have important implications for myocardial protection in failing hearts.

Animals↗
PubMed2006

Biomechanical considerations in the design of graft: the homeostasis hypothesis.

Since its inception in the 1960s, coronary artery bypass graft (CABG) evolved as one of the most common, best documented, and most effective of all major surgical treatments for ischemic heart disease. Despite its widespread use, however, the outcome is not always completely satisfactory. The objective of this review is to highlight the physical determinants of biomechanical design of CABG so that future procedures would have prolonged patency and better outcome. Our central axiom postulates the existence of a mechanical homeostatic state of the blood vessel, i.e., the variation in vessel wall stresses and strains are relatively small under physiological conditions. Any perturbation of mechanical homeostasis leads to growth and remodeling. In this sense, stenosis and failure of a graft may be viewed as an adaptation process gone awry. We outline the principles of engineering design and discuss the biofluid and biosolid mechanics principles that may have the greatest bearing on mechanical homeostasis and the long-term outcome of CABG.

Animals↗
PubMed2005

Duration of no-load state affects opening angle of porcine coronary arteries.

The zero-stress state of a blood vessel has been extensively studied because it is the reference state for which all calculations of intramural stress and strain must be based. It has also been found to reflect nonuniformity in growth and remodeling in response to chemical or physical changes. The zero-stress state can be characterized by an opening angle, defined as the angle subtended by two radii connecting the midpoint of the inner wall. All prior studies documented the zero-stress state or opening angle with no regard to duration of the no-load state. Our hypotheses were that, given the viscoelastic properties of blood vessels, the zero-stress state may have "memory" of prior circumferential and axial loading, i.e., duration of the no-load state influences opening angle. To test these hypotheses, we considered ring pairs of porcine coronary arteries to examine the effect of duration in the no-load state after circumferential distension. Our results show a significant reduction in opening angle as duration of the no-load state increases, i.e., vessels that are reduced to the zero-stress state directly from the loaded state attain much larger opening angles at 30 min after the radial cut than rings that are in the no-load state for various durations. To examine the effect of axial loading, we found similar reductions in opening angle with duration in the no-load from the in situ state, albeit the effect was significantly smaller than that of circumferential loading. Hence, we found that the zero-stress state has memory of both circumferential and axial loading. These results are important for understanding viscoelastic properties of coronary arteries, interpretation of the enormous data on the opening angle and strain in the literature, and standardization of future measurements on the zero-stress state.

Animals↗
PubMed2005

Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide.

We have recently shown that estrogen causes vessel dilation through receptor-mediated stimulation of nitric oxide (NO) production. Here, we hypothesize that estrogen modulates the mechanical homeostasis in the blood vessel wall through NO production. The mechanical properties of female ovariectomized (ovx) mice, female mice lacking the gene for endothelial NO synthase (eNOS(-/-)), and control female and male mice were studied to test the hypothesis. The femoral and carotid arteries and aorta were cannulated in situ and mechanically distended. The stress, strain, elastic modulus, and wall thickness of vessels in ovx and eNOS(-/-) mice, as well as intact female and male mice, were determined. Western blot and immunohistochemistry were used to assess eNOS protein expression in the aorta. Moreover, NO by-products of the femoral and carotid artery were determined by measuring the levels of nitrite and nitrate. Our results show that ovariectomy and eNOS(-/-) significantly decrease the strain in all arteries. Furthermore, the eNOS protein was significantly reduced in ovx mice. Finally, the NO metabolites were significantly decreased both in ovx and eNOS(-/-) mice. We found statistically significant correlations between the structural (wall thickness), mechanical (stress, strain, and elastic modulus), and biochemical parameters (NO by-products). These novel results connect NO to the structural and mechanical properties of the vessel wall. Hence, the effect of endogenous estrogen on the arterial mechanical properties is mediated by the regulation of NO derived from eNOS.

Animals↗