Coronary vasomotion in response to sympathetic stimulation in humans: Importance of the functional integrity of the endothelium

AbstractThe coronary vasomotor response to the cold pressor test was studied with use of quantitative coronary angiography in 32 patients without evidence of coronary artery disease and 55 patients with such disease; in a subset of 22 patients (9 with normal coronary arteries and 13 with coronary artery disease), the effects of the cold pressor test were compared with the effects of the endothelium-dependent vasodilator acetylcholine with simultaneous intracoronary Doppler flow velocity measurements to assess the influence of endothelial dysfunction. The cold pressor test induced vasodilation of 8.9 ± 5.7% in all 77 analyzed vessel segments of the group with normal arteries (p < 0.01). In contrast, in patients with coronary artery disease, the 52 analyzed stenotic segments were constricted by −12.1 ± 9.5% (p < 0.01), the 57 analyzed vessel segments with luminal irregularities were constricted by −8.9 ± 5.2% (p < 0.01) and 40 (85%) of 47 angiographically normal segments also were constricted by −7.0 ± 4.9% (p < 0.05).Preserved vasodilating capability was demonstrated by intracoronary nitroglycerin in all analyzed segments. In nine patients with normal coronary arteries, the analyzed vessel segments were dilated in response to both the cold pressor test and intracoronary acetylcholine by 10.9 ± 5.4% and 13.4 ± 4.7%, respectively. In contrast, in all 13 patients with coronary artery disease, vasoconstriction of identical vessel segments by −9.1 ± 3.75% and −23 ± 10.4%, respectively, was observed after both the cold pressor test and intracoronary acetylcholine. Intracoronary propranolol did not significantly affect either the vasodilative response in 11 normal coronary arteries (11.3 ± 4.4% before and 8.6 ± 4.3% after beta-blockade) or the vasoconstrictor response in 8 atherosclerotic coronary arteries (−11.4 ± 4.6% before and −14.6 ± 5.3% after betablockade).The dilation of normal and the constriction of atherosclerotic coronary arteries with cold pressor testing exactly mirror the response to the endothelium-dependent dilator acetylcholine. Endothelial dysfunction in coronary atherosclerosis resulted in a loss of normal dilator function and permitted vasoconstrictor responses to sympathetic stimulation. Thus, coronary vasomotion of large epicardial arteries in response to sympathetic stimulation by the cold pressor test in humans is intimately related to the integrity of endothelial function

Towards Additive Manufacture of Functional, Spline-Based Morphometric Models of Healthy and Diseased Coronary Arteries:In Vitro Proof-of-Concept Using a Porcine Template

The aim of this study is to assess the additive manufacture of morphometric models of healthy and diseased coronary arteries. Using a dissected porcine coronary artery, a model was developed with the use of computer aided engineering, with splines used to design arteries in health and disease. The model was altered to demonstrate four cases of stenosis displaying varying severity, based on published morphometric data available. Both an Objet Eden 250 printer and a Solidscape 3Z Pro printer were used in this analysis. A wax printed model was set into a flexible thermoplastic and was valuable for experimental testing with helical flow patterns observed in healthy models, dominating the distal LAD (left anterior descending) and left circumflex arteries. Recirculation zones were detected in all models, but were visibly larger in the stenosed cases. Resin models provide useful analytical tools for understanding the spatial relationships of blood vessels, and could be applied to preoperative planning techniques, but were not suitable for physical testing. In conclusion, it is feasible to develop blood vessel models enabling experimental work; further, through additive manufacture of bio-compatible materials, there is the possibility of manufacturing customized replacement arteries

Regulation of Coronary Blood Flow

The heart is uniquely responsible for providing its own blood supply through the coronary circulation. Regulation of coronary blood flow is quite complex and, after over 100 years of dedicated research, is understood to be dictated through multiple mechanisms that include extravascular compressive forces (tissue pressure), coronary perfusion pressure, myogenic, local metabolic, endothelial as well as neural and hormonal influences. While each of these determinants can have profound influence over myocardial perfusion, largely through effects on end-effector ion channels, these mechanisms collectively modulate coronary vascular resistance and act to ensure that the myocardial requirements for oxygen and substrates are adequately provided by the coronary circulation. The purpose of this series of Comprehensive Physiology is to highlight current knowledge regarding the physiologic regulation of coronary blood flow, with emphasis on functional anatomy and the interplay between the physical and biological determinants of myocardial oxygen delivery. © 2017 American Physiological Society. Compr Physiol 7:321-382, 2017

O Índice de Resistência Microcirculação Para o Estudo Invasivo da Microcirculação Coronária. Descrição e Validação de um Modelo Animal

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status

Effects of local coronary blood flow dynamics on the predictions of a model of in-stent restenosis

Computational models are increasingly used to study cardiovascular disease. However, models of coronary vessel remodelling usually make some strong assumptions about the effects of a local narrowing on the flow through the narrowed vessel. Here, we test the effects of local flow dynamics on the predictions of an in-stent restenosis (ISR) model. A previously developed 2D model of ISR is coupled to a 1D model of coronary blood flow. Then, two different assumptions are tested. The first assumption is that the vasculature is always able to adapt, and the volumetric flow rate through the narrowed vessel is kept constant. The second, alternative, assumption is that the vasculature does not adapt at all, and the ratio of the pressure drop to the flow rate (hydrodynamic resistance) stays the same throughout the whole process for all vessels unaffected by the stenosis, and aortic or venous blood pressure does not change either. Then, the dynamics are compared for different locations in coronary tree for two different reendothelization scenarios. The assumptions of constant volumetric flow rate (absolute vascular adaptation) versus constant aortic pressure drop and no adaptation do not significantly affect the growth dynamics for most locations in the coronary tree, and the differences can only be observed at the locations where a strong alternative flow pathway is present. On the other hand, the difference between locations is significant, which is consistent with small vessel size being a risk factor for restenosis. These results suggest that the assumption of a constant flow is a good approximation for ISR models dealing with the typical progression of ISR in the most often stented locations such as the proximal parts of left anterior descending (LAD) and left circumflex (LCX) arteries

Refining Our Understanding of the Flow Through Coronary Artery Branches; Revisiting Murray's Law in Human Epicardial Coronary Arteries

Background: Quantification of coronary blood flow is used to evaluate coronary artery disease, but our understanding of flow through branched systems is poor. Murray’s law defines coronary morphometric scaling, the relationship between flow (Q) and vessel diameter (D) and is the basis for minimum lumen area targets when intervening on bifurcation lesions. Murray’s original law (Q α D(P)) dictates that the exponent (P) is 3.0, whilst constant blood velocity throughout the system would suggest an exponent of 2.0. In human coronary arteries, the value of Murray’s exponent remains unknown. Aim: To establish the exponent in Murray’s power law relationship that best reproduces coronary blood flows (Q) and microvascular resistances (Rmicro) in a bifurcating coronary tree. Methods and Results: We screened 48 cases, and were able to evaluate inlet Q and Rmicro in 27 branched coronary arteries, taken from 20 patients, using a novel computational fluid dynamics (CFD) model which reconstructs 3D coronary anatomy from angiography and uses pressure-wire measurements to compute Q and Rmicro distribution in the main- and side-branches. Outputs were validated against invasive measurements using a Rayflow™ catheter. A Murray’s power law exponent of 2.15 produced the strongest correlation and closest agreement with inlet Q (zero bias, r = 0.47, p = 0.006) and an exponent of 2.38 produced the strongest correlation and closest agreement with Rmicro (zero bias, r = 0.66, p = 0.0001). Conclusions: The optimal power law exponents for Q and Rmicro were not 3.0, as dictated by Murray’s Law, but 2.15 and 2.38 respectively. These data will be useful in assessing patient-specific coronary physiology and tailoring revascularisation decisions

Quantitative angiographic comparison of elastic recoil after coronary excimer laser-assisted balloon angioplasty and balloon angioplasty alone.

AbstractObjectives. Coronary lumen changes during and after excimer laser-assisted balloon angioplasty were measured by quantitative coronary angiography, and the results were compared with the effects of balloon angioplasty alone.Background. Reduction of atherosclerotic tissue mass by laser ablation in the treatment of coronary artery disease may be more effective in enlarging the lumen than balloon angioplasty alone.Methods. A series of 57 consecutive coronary lesions successfully treated by xenon chloride excimer laser-assisted balloon angioplasty were individually matched with 57 coronary artery lesions successfully treated by balloon angioplasty alone. The following variables were measured by quantitative coronary analysis: 1) ablation by laser, 2) stretch by balloon dilation, 3) elastic recoil, and 4) acute gain.Results. Matching by stenosis location, reference diameter and minimal lumen diameter resulted in two comparable groups of 57 lesions with identical baseline stenosis characteristics. Minimal lumen diameter before excimer laser-assisted balloon angioplasty and balloon angioplasty alone were (mean ± SD) 0.73 ± 0.44 and 0.74 ± 0.43 mm, respectively. Laser ablation significantly improved minimal lumen diameter by 0.56 ± 0.44 mm before adjunctive balloon dilation. In both treatment groups, similar-sized balloon catheters (2.59 ± 0.35 and 2.56 ± 0.40 mm, respectively) were used. After laser-assisted balloon angioplasty, elastic recoil was 0.84 ± 0.30 mm (32% of balloon size), which was identical to that after balloon angioplasty alone, namely, 0.82 ± 0.32 mm (32%). Consequently, both interventions resulted in similar acute gains of 1.02 ± 0.52 and 1.00 ± 0.56 mm, respectively. Minimal lumen diameter after intervention was equal in both groups: 1.75 ± 0.35 and 1.75 ± 0.34 mm, respectively. The statistical power of this study in which a 25% difference in elastic recoil (0.2 mm) between groups was considered clinically important was 95%.Conclusions. In matched groups of successfully treated coronary lesions, xenon chloride excimer laser ablation did not reduce immediate elastic recoil after adjunctive balloon dilation or improve the final angiographic outcome compared with balloon angioplasty alone using similar-sized balloon catheters