Distal Coronary Resistance Research Articles

Patient-specific fluid-structure simulations of anomalous aortic origin of right coronary arteries.

ObjectivesAnomalous aortic origin of the right coronary artery (AAORCA) may cause ischemia and sudden death. However, the specific anatomic indications for surgery are unclear, so dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid–structure interaction (FSI) modeling can simulate the pulsatile hemodynamics and tissue deformation. We sought to evaluate the feasibility of simulating the resting and dobutamine-stress iFR in AAORCA using patient-specific FSI models and to visualize the mechanism of ischemia within the intramural geometry and associated lumen narrowing.MethodsWe developed 6 patient-specific FSI models of AAORCA using SimVascular software. Three-dimensional geometries were segmented from coronary computed tomography angiography. Vascular outlets were coupled to lumped-parameter networks that included dynamic compression of the coronary microvasculature and were tuned to each patient's vitals and cardiac output.ResultsAll cases were interarterial, and 5 of 6 had an intramural course. Measured iFRs ranged from 0.95 to 0.98 at rest and 0.80 to 0.95 under dobutamine stress. After we tuned the distal coronary resistances to achieve a stress flow rate triple that at rest, the simulations adequately matched the measured iFRs (r = 0.85, root-mean-square error = 0.04). The intramural lumen remained narrowed with simulated stress and resulted in lower iFRs without needing external compression from the pulmonary root.ConclusionsPatient-specific FSI modeling of AAORCA is a promising, noninvasive method to assess the iFR reduction caused by intramural geometries and inform surgical intervention. However, the models’ sensitivity to distal coronary resistance suggests that quantitative stress-perfusion imaging may augment virtual and invasive iFR studies.

Patient-specific 3D-printed coronary models based on coronary computed tomography angiography volumes to investigate flow conditions in coronary artery disease

Background: 3D printed patient-specific coronary models have the ability to enable repeatable benchtop experiments under controlled blood flow conditions. This approach can be applied to CT-derived patient geometries to emulate coronary flow and related parameters such as Fractional Flow Reserve (FFR). Methods: This study uses 3D printing to compare such benchtop FFR results with a non-invasive CT-FFR research software algorithm and catheter based invasive FFR (I-FFR) measurements. Fifty-two patients with a clinical indication for I-FFR underwent a research Coronary CT Angiography (CCTA) prior to catheterization. CT images were used to measure CT-FFR and to generate patient-specific 3D printed models of the aortic root and three main coronary arteries. Each patient-specific model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for two coronary outflow rates (‘normal’, 250 ml min−1; and ‘hyperemic’, 500 ml min−1) by adjusting the model’s distal coronary resistance. Results: Pearson correlations and ROC AUC were calculated using invasive I-FFR as reference. The Pearson correlation factor of CT-FFR and B-FFR-500 was 0.75 and 0.71, respectively. Areas under the ROCs for CT-FFR and B-FFR-500 were 0.80 (95%CI: 0.70–0.87) and 0.81 (95%CI: 0.64–0.91) respectively. Conclusion: Benchtop flow simulations with 3D printed models provide the capability to measure pressure changes at any location in the model, for ultimately emulating the FFR at several simulated physiological blood flow conditions. Clinical Trial Registration: https://clinicaltrials.gov/show/NCT03149042

Nicardipine and adenosine “flush cocktail” to prevent no-reflow during rotational atherectomy

Rotational atherectomy (RA) has a unique mechanism of action-it utilizes plaque abrasion with microparticle embolization in order to achieve luminal enlargement. This microscopic atheroembolic debris can lead to platelet activation, with vasoconstriction and/or mechanical obstruction of distal coronary resistance vessels, leading to no-reflow and myocardial necrosis. We developed a prospective registry to evaluate the efficacy of the prophylactic administration of intracoronary nicardipine and adenosine within the RA "flush cocktail" as a method of preventing no-reflow and non-Q-wave myocardial infarction (MI) in patients treated with RA in their native coronary arteries. One hundred seventy-six consecutive patients (204 lesions; mean age, 66+/-12 years) were treated with a flush cocktail containing nicardipine (10 microg/ml), adenosine (5 microg/ml), nitroglycerin (10 microg/ml), and unfractionated heparin (1 IU/ml) during RA. The primary study end points were postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow score and non-Q-wave MI, as determined by creatine phosphokinase (CPK) and creatine phosphokinase-MB (CPK-MB) levels. Secondary end points included baseline and acute final minimum lumen diameters, and percent diameter stenosis. TIMI flow scores were analyzable in 155 of 176 patients (88%), and in 181 of 204 treated vessels/lesions (88.7%). As compared to baseline, the final TIMI score worsened in 4 patients (2%), was unchanged in 121 patients (78%), and improved in 30 patients (19%). One hundred fifty of 155 patients (96.7%), and 175 of 181 treated vessels (96.6%) had TIMI 3 flow at the completion of the procedure. Excluding those patients with elevated baseline CPK values of >190 IU/l (n=7), only 5 of 176 (2.8%) patients had CPK-MB values more than three times the upper limit of normal at 12-18 h postprocedure. There were no in-hospital Q-wave MIs or deaths. An intracoronary flush cocktail containing a combination of two potent arteriolar vasodilators, nicardipine and adenosine, appears to be a safe and effective regimen for minimizing no-reflow events and periprocedural myonecrosis during RA.

Platelet glycoprotein IIb/IIIa receptor blockade and coronary resistance in unstable angina

ObjectivesWe designed a study to explore the effect of glycoprotein (GP) IIb/IIIa blockade on the atherosclerotic plaque and distal coronary vasculature. BackgroundPlatelet GP IIb/IIIa blockers have been proven to be beneficial in acute ischemic syndromes. This effect has also been attributed to the prevention of microvascular obstruction, although the underlying mechanisms have not been fully defined. MethodsEighteen patients with unstable refractory angina pectoris underwent cardiac catheterization and angioplasty. Trans-stenotic and microvascular resistances to flow were measured at baseline, during hyperventilation, and after intracoronary adenosine. Measurements were repeated early after abciximab administration and after successful percutaneous transluminal coronary angioplasty. ResultsHyperventilation induced an ischemic attack in 12 of 18 patients and increased epicardial (12.8 ± 16.9 vs. 6.1 ± 6.1 mm Hg/ml per min, p < 0.05) and microvascular (9.9 ± 7.5 vs. 6.8 ± 5.8 mm Hg/ml per min, p < 0.05) coronary resistance. Abciximab had no significant effect on epicardial resistance, although it significantly reduced distal coronary resistance under all study conditions, including baseline (4.8 ± 4.8 mm Hg/ml per min, p < 0.01), hyperventilation (5.1 ± 5.4 mm Hg/ml per min, p < 0.01), and intracoronary adenosine (2.7 ± 3.0 vs. 4.3 ± 4.3 mm Hg/ml per min, p < 0.05). The hyperventilation test became negative in all patients after abciximab administration. ConclusionsThese observations confirm the immediate beneficial effects of platelet GP IIb/IIIa blockade with abciximab in acute ischemic syndromes and suggest that improvement of microvascular function may play a central role in the mechanism of action of this drug.

Prostaglandin E1 and Nitroglycerin Effects on Canine Epicardial Conductance and Distal Coronary Resistance Vessels

Prostaglandin E1 (PGE1) has been reported to be a coronary vasodilator and has been considered clinically in the treatment of coronary vasospasm, but its mechanism of action is not known. To evaluate the vasomotor effect of PGE1, epicardial coronary and distal resistance vessel responses were compared by PGE1 and nitroglycerin infusion into the left anterior descending (LAD) artery of the closed-chest dog. Coronary angiography and 133Xe washout flow measurements were used to quantitate proximal and distal vessel responses, respectively. To evaluate potential inhibitory actions, vessels were contracted by continuous LAD infusion of prostaglandin F2 alpha (PGF2 alpha) or serotonin before dose-response testing with PGE1 or nitroglycerin. PGE1 alone produced a 20% dilation of the LAD in vivo but only with the highest dose (2.0 micrograms/min). PGE1, however, did not reverse epicardial vessel constriction induced by PGF2 alpha or serotonin. LAD flows (resistance vessel response) were increased comparably by PGE1 alone and with PGF2 alpha added (100 and 93% above control flow, respectively) but to a lesser extent with serotonin added (57% above control). In contrast, nitroglycerin completely reversed epicardial artery constrictions induced by PGF2 alpha and serotonin. Our findings indicate that although PGE1 is a vasodilator in vivo, it does not demonstrate a major effect in dilating epicardial conductance coronary arteries and therefore may not be beneficial in antagonizing endogenous contractile factors in treatment of coronary vasospasm. PGE1 does increase coronary blood flow by dilating distal resistance vessels. The beneficial effects of PGE1 in humans with unstable angina therefore are probably not due to vasorelaxing effects on epicardial coronary conductance arteries.

Quinidine Attenuates Sympathetically Induced Poststenotic Myocardial Ischemia

Beside its antiarrhythmic properties, which in particular are used for the treatment of atrial fibrillation, quinidine is known to have alpha-adrenoceptor blocking properties. On the other hand, atrial fibrillation is reported to cause activation of the sympathetic nervous system which, in turn, reduces coronary blood flow when the coronary reserve is already compromised. Therefore, we tested the effect of quinidine (3 mg/kg i.v.) on the coronary vasculature during electrical stimulation of cardiac sympathetic nerves in the presence and absence of a stenosis on the left circumflex coronary artery. In 7 anesthetized dogs the end-diastolic distal coronary resistance during cardiac sympathetic nerve stimulation in the presence of a severe stenosis on the left circumflex coronary artery increased by 18% before, and decreased by 17% after administration of quinidine. We conclude that quinidine inhibits the vasoconstriction of poststenotic coronary arteries during cardiac sympathetic nerve stimulation and thus might prevent a poststenotic stress-induced myocardial ischemia.

Changes of collateral perfusion pressure and segmental coronary resistances during reactive hyperemia in anesthetized dogs.

Changes of collateral perfusion pressure (CPP) and segmental coronary resistances during reactive hyperemia were studied in nine chloralose-urethan-morphine anesthetized open-chest dogs. Coronary perfusion pressure was controlled by a cannula in the left main coronary artery and inflow measured by an electromagnetic flowmeter. The first or second diagonal branch of the left anterior descending coronary artery was cannulated and perfused from a carotid artery; inflow was abolished by embolization with latex microspheres (diameter: 25 +/- 5 mu) and peripheral coronary pressure was assumed to represent CPP. Segmental coronary resistances were defined as follows: Proximal coronary resistance (R1) was calculated from the difference between coronary perfusion pressure and CPP divided by coronary inflow. Distal coronary resistance (R2) was calculated from CPP divided by coronary inflow. Reactive hyperemia was produced by interruption of coronary inflow for 15 s and analysed at 30 s and 60 s of reperfusion when cardiac function had recovered. At baseline, R1 was 0.52 +/- 0.04 mm Hg X min X 100 g/ml (RU) and R2 0.63 +/- 0.07 RU. At 30 s, R1 was reduced by 19 +/- 3% (P less than 0.01) this was less (P less than 0.05) than R2 which was reduced by 32 +/- 3% (P less than 0.01). At 60 s R1 and R2 were reduced by 11 +/- 2% and 13 +/- 2%, respectively; this was not significantly different. Accordingly, CPP (baseline: 59 +/- 4 mm Hg) at 30 s was reduced by 7 +/- 2% (P less than 0.03), at 60 s the reduction was not significant. The data suggest that reactive hyperemia, as a model of metabolic coronary dilatation, may reduce CPP equivalent to a coronary steal phenomenon.

Effect of norepinephrine on coronary hemodynamics in coronary stenotic canine model

The effect of intracoronary injection of 1μ norepinephrine was assessed in 14 open-chest dogs anesthetized with alpha chloralose. Studies were performed before and after partial coronary artery constriction by a circumferential snare. Aortic pressure, coronary pressure distal to the stenosis, and coronary flow were monitored before and after injection of norepinephrine. Calculated values were stenotic resistance and distal coronary resistance. Before coronary constriction, norepinephrine resulted in an early minimal increase in coronary flow and decrease in distal coronary resistance with prompt return to control values. In contrast with high grade coronary constriction, at 15 seconds after norepinephrine coronary flow decreased (29.8 ± 3.4 to 22.9 ± 3.6 ml./minute) (p < 0.05), coronary pressure decreased (58.8 ± 1.3 to 28.8 ± 2.6 mm. Hg) (p < 0.05), and stenotic resistance increased (2.04 ± 0.26 to 4.25 ± 2.66 mm. Hg/ml. min. −1) (p < 0.05) without change in heart rate or aortic pressure. These changes persisted over a two minute period of observation following norepinephrine. In the stenotic model the decrease in coronary pressure and coronary flow and increase in stenotic resistance were blocked by pretreatment with propranolol but not by phenoxybenzamine. Administration of isoproterenol resulted in changes similar to those induced by norepinephrine in the stenotic model. Simulation of alteration of peripheral resistance in an in vitro model demonstrated that with a high initial stenotic resistance, a decrease in peripheral resistance resulted in an increase in stenotic resistance. We conclude that the decrease in coronary pressure following norepinephrine was mediated by beta 1 or beta 2 adrenergic stimulation. We further postulate that the decreased coronary flow and increased stenotic resistance were caused by a passive decrease in radius at the stenotic site.

Altered coronary flow responses to vasoactive drugs in the presence of coronary arterial stenosis in the dog

Recent in vitro observations of human coronary arteries have suggested that intraluminal pressure can be a determinant of the resistance to flow through the stenosis. This study examined whether similar pressure-dependent changes in stenotic resistance could be observed and analyzed in an open chest, anesthetized, animal model of coronary arterial stenosis. Without stenosis, intracoronary isoproterenol (1 μg) or nitroglycerin (10 μg) increased flow and decreased coronary resistance, whereas methoxamine (500 μg) or vasopressin (0.2 U) decreased flow and increased coronary resistance. After partial arterial constriction, administration of isoproterenol (1 μg) resulted in a decrease in coronary pressure from 61.2 ± 2.5 to 39.4 ± 2.7 mm Hg (p ≤ 0.05), a 23 percent derease in distal coronary resistance (p ≤ 0.05) and a 22 percent decrease in flow associated with an increase in stenotic resistance of 2.34 ± 0.97 (p ≤ 0.05). Similarly, nitroglycerin caused a decrease in coronary pressure from 55.7 ± 3.1 to 42.1 ± 3.6 mm Hg (p ≤ 0.05), a 29 percent increase in distal coronary resistance and only a 1 percent increase in flow associated with a 38 percent increase in stenotic resistance. Methoxamine caused an increase in coronary pressure from 62.8 ± 2.0 to 73.6 ± 3.4 mm Hg (p ≤ 0.05), an 18 percent increase in distal coronary resistance, an 8 percent decrease in flow and a 10 percent decrease in stenotic resistance. Vasopressin caused an increase in coronary pressure from 61.0 ± 1.5 to 99.2 ± 7.1 mm Hg (p ≤ 0.05), a 239 percent increase in distal coronary resistance but only a 45 percent decrease in flow associated with a decrease in stenotic resistance of 1.33 ± 0.91 (p ≤ 0.05). Passive changes in the stenotic area caused by coronary pressure changes are postulated as part of the mechanism for the observed changes in stenotic resistance. This hypothesis is strengthened by the changes in stenotic resistance and radiographic analysis obtained from an in vitro carotid arterial preparation. The pressure-dependency of stenotic resistance could be an additional factor in the treatment of patients with coronary artery disease.

Dynamic changes in the haemodynamic severity of coronary artery stenosis in a canine model.

Coronary artery stenosis diminishes and eventually abolishes the peak reactive hyperaemic response following momentary coronary occlusion. If stenosis is increased beyond this point, it is generally believed that resting coronary blood flow and reactive blood flow will continue to be identical. This assumption was investigated in 14 anaesthetised dogs. Aortic pressure, distal coronary pressure, and coronary flow were measured. Stenotic resistance was calculated as the pressure gradient across the stenosis divided by the coronary blood flow. Before coronary artery constriction, the usual large coronary blood flow increase and distal coronary resistance decrease were observed. With moderate stenosis, distal coronary resistance decreased and coronary blood flow increased, although attenuated. With severe stenosis, coronary blood flow remained unaltered, the distal coronary resistance decrease being nullified by the stenotic resistance increase. With further constriction, coronary blood flow actually decreased following momentary coronary occlusion. The coronary blood flow decrease was associated with a large stenotic resistance increase. We believe the most plausible explanation for the observed stenotic resistance increase was a passive collapse of the vessel due to the distal coronary pressure reduction. This hypothesis is strengthened by our demonstration of similar stenotic resistance increases in an in vitro, constant flow perfused carotid artery, induced by reducing the peripheral resistance. This study demonstrates that stenotic resistance is not fixed, but is dynamic. Conceivably, in the presence of severe coronary artery stenosis, vasodilatation could increase stenotic resistance and thereby reduce coronary blood flow.