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Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors—mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current ‘state of the art’ on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research. [ABSTRACT FROM PUBLISHER]

This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90% are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical methods used to analyse the data. Despite this high variability, the current data sets can be summarized with the concept of endothelial priming. In this concept, fluid flows confer protection by an up-regulation of anti-atherogenic, anti-thrombotic, and anti-inflammatory gene signatures. Consequently, predilection sites of atherosclerosis, which are associated with low-shear stress, confer low protection for atherosclerosis and are, therefore, more sensitive to high cholesterol levels. Recent studies in intact non-atherosclerotic animals confirmed these in vitro studies, and suggest that a spatial component might be present. Despite the large variability, a few signalling pathways were consistently present in the majority of studies. These were the MAPK, the nuclear factor-κB, and the endothelial nitric oxide synthase-NO pathways. [ABSTRACT FROM AUTHOR]

Aims: Studies in animals and patients indicate that rapamycin affects vasodilatation differently in outer and inner curvatures of blood vessels. We evaluated in this study whether rapamycin affects endothelial nitric oxide synthase (eNOS) responsiveness to shear stress under normo- and hypercholesteraemic conditions to explain these findings. [ABSTRACT FROM PUBLISHER]

Aims Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation. [ABSTRACT FROM PUBLISHER]

Aims The purpose of this study was to investigate the relation between acute coronary flow reduction and arterial wall temperature.Methods and results Five pigs with normal coronary arteries were catheterized. Arterial wall temperature was studied with a thermographic system that uses a 4-thermistor sensor tip. Flow velocity was studied at the same time and place with the temperature measurements, using a Doppler wire. In order to modify the coronary flow, a balloon was gradually inflated proximally to the thermographic sensors. Temperature differences and flow velocities were simultaneously recorded.Flow velocities above an average peak velocity (APV) of 9cm/s were associated with unaffected temperature measurements. At flow velocities around 4cm/s, the wall temperature was increased (ΔT=0.015±0.005oC, P∼0.05), following the heart-rate. When flow velocity dropped further below this value, the local wall temperature was logarithmically increased to a maximum value observed at total vessel occlusion (ΔT=0.188±0.023oC, P<0.001).Conclusion The reduction of coronary flow has an effect on the arterial wall temperature. This effect however, appears only below a critical threshold of APV and in a logarithmic fashion. Above this threshold, temperature measurements should be unaffected from flow reductions and related to the regional temperature heterogeneity. [ABSTRACT FROM PUBLISHER]

Objective: We investigated whether an increased oxygen cost of contractility and/or a decreased myofibrillar efficiency contribute to oxygen wastage of stunned myocardium. Because Ca2+-sensitizers may increase myofibrillar Ca2+-sensitivity without increasing cross-bridge cycling, we also investigated whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility. Methods: Regional fiber stress and strain were calculated from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumption (MVO2) was measured before contractility (end-systolic elastance, Ees) and total myofibrillar work (stress–strain area, SSA) were determined from stress–strain relationships. Atrial pacing at three heart rates and two doses of dobutamine were used to vary SSA and Ees, respectively. After stunning (two times 10-min ischemia followed by 30-min reperfusion), measurements were repeated following infusion of saline (n=8) or EMD 60263 (1.5 mg·kg−1 i.v., n=10). Linear regression was performed using: MVO2=α·SSA+β·Ees+γ·HR−1 (α−1, myofibrillar efficiency; β, oxygen cost of contractility; and γ, basal metabolism/min). Results: Stunning decreased SSA by 57% and Ees by 64%, without affecting MVO2, while increasing α by 71% and β by 134%, without affecting γ. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation–contraction coupling. EMD 60263 restored both α and β. Conclusions: Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar efficiency and to a lesser extent by an increased oxygen cost of contractility. Considering that EMD 60263 reversed both causes of oxygen wastage, it is most likely that this drug increases myofibrillar Ca2+-sensitivity without increasing myofibrillar cross-bridge cycling. [ABSTRACT FROM PUBLISHER]

Objective: Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood–air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial function from air embolism by lowering the surface tension of air bubbles. Methods: The effect of using antifoam as a surface-tension-reducing agent on air bubble entrapment and cardiac function was investigated in 6 anesthetized pigs (27±1 kg) and analyzed using a two-compartment diffusion model. Air bubbles with a diameter of 150 μm were selectively injected into the left anterior descending coronary artery (LADCA) in a carrying fluid in the presence or absence of antifoam. Myocardial systolic segment shortening in the LADCA region (SS-LADCA) was measured by sonomicrometry. Presence of emboli was detected by measuring the amount of reverberation of ultrasound scattered by trapped air bubbles. Results: SS-LADCA transiently decreased after injections of air bubbles in both the absence and presence of antifoam. However, in the presence of antifoam the regional depression recovered to normal sooner, the average depth of the depression was reduced, and bubbles from the embolized area cleared faster. These observations can be explained by a model derived from Laplace's law. [ABSTRACT FROM PUBLISHER]

Objective: Oxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data. Methods: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary artery and 30 min reperfusion, segment shortening, the slope of end systolic pressure segment length relationship (Ees), external work (EW, derived from the area inside the left ventricular pressure segment length loop), the efficiency of energy conversion (EET, = × 100%, where PLA = total pressure-segment length area), mechanical efficiency (), and their dependency on left ventricular end systolic pressure (Pes) were determined before and after induction of stunning, and during subsequent inotropic stimulation with dobutamine (1 and 3 μg·kg−1·min−1 over 15 min). Results: The stunning protocol not only caused significant decreases in segment shortening, external work, energy conversion efficiency, and but also increased the afterload dependency of these variab Before stunning an increase in Pes from 100 to 160 mm Hg decreased segment shortening from 18(SEM 1)% to 14(2)% (P > 0.05) and increased external work from 206(18) to 254(32) mm Hg·mm (P < 0.05). After induction of stunning the same increase in Pes caused a decrease in segment shortening from 9.5(1.8)% to −4.6(2.1)% (P < 0.05) and in external work from 149(21) to −11(10) mm Hg·mm (P < 0.05). The afterload dependency of the PLA was not altered by stunning, but the afterload dependency of energy conversion efficiency increased, since efficiency decreased from 67(3)% to 59(5)% as Pes was increased from 100 to 160 mm Hg before stunning, but from 57(5) to −7(5)% after induction of stunning (P < 0.05). Furthermore, the same increase in Pes resulted in an 8% decrease of before stunning and 107% after inducti stunning. Infusion of dobutamine not only restored segment shortening, external work, energy conversion efficiency, and of the stunned myocardium, but also attenuated their afterload dependency to levels. Conclusions: Myocardial stunning increases the afterload dependency of segment shortening, external work, energy conversion efficiency, and mechanical efficiency, which can be attenuated by inotropic stimulation with dobutamine. However, the decrease in left ventricular end systolic pressure, which accompanies the induction of stunning, counteracts the decrease in these variables. These two mechanisms can explain most of the reported scatter in mechanical efficiency. [ABSTRACT FROM PUBLISHER]

Objective: In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVO2) and its major determinants were studied in 10 open chest anaesthetised pigs. Methods: According to the time varying elastance concept, MVO2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVO2) equals the product of EW/PLA (=efficiency of energy transfer or EET) and PLA/MVO2. Eimx is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure-segment length loop. Systemic haemodynamics, regional segment shortening, and MVO2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats·min−1 increase in heart rate by atrial pacing and additional infusion of 2 μg·kg−1·min−1 dobutamine. Results: Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVO2 from 4.16(0.27) × 102 to 2.84(0.25) × 12 μ·mol·bear−1g−1, and Emax from 47(9) to 23(3) mm Hg·mm−1 (all p < 0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p < 0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVo, which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVO2 [4.12(0.53) μmol·beat−1·g−1] and EET [0.57(0.04)] returned to baseline. Conclusions: In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVO2.Cardiovascular Research 1993;27:740-747 [ABSTRACT FROM PUBLISHER]

Study objective — The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning.Design — In group 1 (n=6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 (μg·kg−1·min−1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats·min−1). In group 2 (n=6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning.Experimental material — The experiments were done on 12 anaesthetised swine, weight 25-39 kg.Measurements and main results — In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p<0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg·min·ml−1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg·min·ml−1 respectively. Infusion of either vasodilator enchanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p<0.05) and −1(34)% during pacing (p<0.05).Conclusions — Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows. [ABSTRACT FROM PUBLISHER]