Measurement Of Coronary Blood Flow Research Articles

Transesophageal echocardiographic measurement of coronary sinus blood flow to estimate the adequacy of revascularization in patients undergoing coronary artery bypass graft: a prospective observational study

Transesophageal echocardiographic measurement of coronary sinus blood flow to estimate the adequacy of revascularization in patients undergoing coronary artery bypass graft: a prospective observational study

Role of potassium as a coronary metabolic vasodilator

K+ release from the myocardium is associated with decreased coronary vascular resistance. Accumulation of extracellular K+ has been linked to mechanisms of vasodilation in the coronary circulation including activation of the electrogenic Na+-K+ pump in smooth muscle (Murray and Sparks, Circ. Res. 1977) and endothelial-mediated hyperpolarization via Kir2.1 channels (Zhao et al., PNAS 2020). Our objective was to examine K+ as a coronary metabolic vasodilator in vivo. Further, we addressed two potential shortcomings of previous studies: the short duration of the bolus K+ stimulus employed and the seemingly high concentrations required to produce vasodilation. We hypothesized that continuous, steady-state intracoronary infusions of K+ would produce sustained coronary vasodilation in a concentration-dependent manner. Our methods involved instrumenting anesthetized, open-chest Yorkshire swine (male and female, 60 kg) for measurements of coronary blood flow, as well as arterial and coronary venous blood sampling. The left anterior descending coronary artery was cannulated and perfused under the control of a pressure servo, allowing us to determine flow and infuse K+. Our results show small, but statistically significant (* represents p < 0.05), effects of K+ on coronary hemodynamics. The coronary venous K+ concentration was 4.0 ± 0.1 mM at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary venous K+ to 4.9 ± 0.2*, 6.4 ± 0.2*, and 7.9 ± 0.2* mM. Higher K+ concentrations caused fatal arrhythmias. Coronary blood flow was 0.73 ± 0.14 ml/min/g at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary blood flow to 0.78 ± 0.14*, 0.82 ± 0.15*, and 0.86 ± 0.16* ml/min/g. These small coronary blood flow changes were sustained during continuous K+ infusion. We conclude that K+ is a coronary vasodilator, as has been demonstrated previously. Importantly, however, we emphasize that the effects of K+ are extremely modest and the concentrations required to produce physiologically significant vasodilation are life-threatening. With the assumption that the venous K+ concentration is in equilibrium with that surrounding the smooth muscle and cardiac muscle of the working heart, we urge caution in interpreting isolated artery studies that routinely use 15-20 mM K+ to elicit hyperpolarization and vasodilation. Our data do not support the idea that K+ plays a major role in regulating coronary vascular resistance. This work was supported by National Institutes of Health grant R01 HL158723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

Research on individualized distribution approach of coronary resting blood flow for noninvasive calculation of fractional flow reserve

Background and ObjectivesThe distribution of coronary resting blood flow is critical for accurately calculating the computed tomography (CT) angiography-derived fractional flow reserve (FFRCT). However, the diagnostic accuracy of FFRCT calculated by the fixed exponents between two risk factors and coronary resting blood flow, including myocardial mass and diameter of the coronary artery branch, was insufficient compared with invasive fractional flow reserve (FFR). In this study, we proposed the individualized distribution of coronary resting blood flow based on coronary ultrasound blood flow measurement, to improve the diagnostic accuracy of FFRCT calculation. MethodsFive risk factors and an unknown coefficient K were integrated to calculate the individualized distribution of coronary resting blood flow. The K value was fit using the least square method based on coronary ultrasound blood flow measurement results of 30 volunteers. We developed a novel approach for calculating the individualized distribution of coronary resting blood flow and applied it to calculate FFRCT (FFRCTI). Then, we tested the performance of the individualized distribution approach by comparing it with the approach proposed by Taylor based on coronary ultrasound blood flow measurement results of 13 volunteers. Finally, we tested the diagnostic accuracy of FFRCT calculated by two approaches in invasive FFR of 121 vessels with coronary stenosis. ResultsWe identified five risk factors and 6.83×10−5 for K value, including cardiac output, mean arterial pressure, myocardial mass, coronary artery volume, and diameter of the coronary artery branch, to calculate the individualized distribution of coronary resting blood flow. The mean square error of the individualized distribution approach (0.0088) was significantly less than that of the approach proposed by Taylor (0.0799). The diagnostic accuracy of FFRCTI calculated by the individualized distribution approach (91.74%) was higher than that of the approach proposed by Taylor (FFRCTT) (82.64%). ConclusionsThe individualized distribution approach of coronary resting blood flow can significantly improve the diagnostic accuracy of FFRCT calculation compared with invasive FFR, and support its wide clinical application for diagnosing myocardial ischemia caused by coronary stenosis.

Comparison of quantitative flow ratio with instantaneous wave-free ratio and resting full-cycle ratio during daily routine in the catheterization laboratory.

Quantitative flow ratio (QFR) is a novel, software-based method to evaluate the physiology of coronary lesions. The aim of this study was to compare QFR with the established invasive measurements of coronary blood flow using instantaneous wave-free ratio (iFR) or resting full-cycle ratio (RFR) in daily cathlab routine. 102 patients with stable coronary artery disease and a coronary stenosis of 40%-90% were simultaneously assessed with QFR and iFR or RFR. QFR-computation was performed by two certified experts using the appropriate software (QAngio XA 3D 3.2). QFR showed a significant correlation (r = 0.75, p < 0.001) to iFR and RFR. The area under the receiver curve for all measurements was 0.93 (95% confidence interval, 0.87-0.98) for QFR compared to iFR or RFR. QFR based assessment required less time with a median of 501 s (IQR 421-659 s) compared to iFR or RFR which required a median of 734 s to obtain the result (IQR 512-967 s; p < 0.001). The median use of contrast medium was similar with 21 mL (IQR 16-30 mL) for the QFR-based and 22 mL (IQR 15-35 mL) for the iFR- or RFR-based diagnostic. QFR diagnostic required less radiation. The median dose area product for QFR was 307cGycm2 (IQR 151-429 cGycm2 ) compared to 599 cGycm2 (IQR 345-1082 cGycm2 ) for iFR or RFR, p < 0.001. QFR measurements of coronary artery blood flow correlate with iFR or RFR measurements and are associated with shorter procedure times and reduced radiation dose.

Characterization and implications of intracoronary hemodynamic assessment during coronary spasm provocation testing.

Current diagnostic criteria for coronary spasm are based on patient's symptoms, ECG shifts and epicardial vasoconstriction during acetylcholine (ACh) spasm testing. To assess the feasibility and diagnostic value of coronary blood flow (CBF) and resistance (CR) assessment as objective parameters during ACh testing. Eighty-nine patients who underwent intracoronary reactivity testing including ACh testing with synchronous Doppler wire-based measurements of CBF and CR were included. Coronary microvascular and epicardial spasm, respectively, were diagnosed based on COVADIS criteria. Patients were 63 ± 13years old, predominantly female (69%) and had preserved LV ejection fraction (64 ± 8%). Overall, assessment of CBF and CR during ACh testing revealed a decrease in CBF of 0.62 (0.17-1.53)-fold and an increase of CR of 1.45 [0.67-4.02]-fold in spasm patients compared to 2.08 (1.73-4.76) for CBF and 0.45 (0.44-0.63) for CR in patients without coronary spasm (both p < 0.01). Receiver operating characteristic revealed a high diagnostic ability of CBF and CR (AUC 0.86, p < 0.001, respectively) in identifying patients with coronary spasm. However, in 21% of patients with epicardial spasm and 42% of patients with microvascular spasm a paradoxical response was observed. This study demonstrates feasibility and potential diagnostic value of intracoronary physiology assessments during ACh testing. We observed opposite responses of CBF and CR to ACh in patients with positive vs. negative spasm test. While a decrease in CBF and an increase in CR during ACh seem pathognomonic for spasm, some patients with coronary spasm demonstrate paradoxical ACh response demanding further scientific investigations.

Quantifying the Cardiovascular Physiology of REBOA and Partial REBOA: How REBOA Facilitates Resuscitation but Also Strains the Left Ventricle

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used as an endovascular approach to aortic occlusion. This can provide complete or partial aortic occlusion and is thereby known to augment afterload relative to the extent of occlusion. Despite the increasing use of this tool, little cardiovascular physiology has been quantified across clinically relevant REBOA transitions: placement of occlusive REBOA, then transition to partially occlusive REBOA, and lastly, REBOA removal. The goal of this study is to use pressure-volume loop analysis and direct left coronary artery blood flow measurements to capture these transitions in a swine model of hemorrhagic shock to elucidate the underlying physiologic mechanism of clinical REBOA use. Swine underwent complex surgical and vascular access instrumentation to capture real-time left ventricular pressure-volume loops and directly measure left coronary flow (Figure 1). Animals were hemorrhaged to 45 mmHg with subsequent placement of fully occlusive REBOA, followed by transition to partial REBOA while these data were captured. A full methodological protocol has been published: https://doi.org/10.21203/rs.3.pex-1646/v1. Five male swine underwent this protocol (mean weight, 53.6 ± 3.6 kg). Hemorrhagic shock was induced and maintained with reduction of stroke work (baseline: 3.1 L × mmHg vs shock: 1.2 L × mmHg; P < .01) and average end systolic pressure (109.8 vs 59.6 mmHg; P = .02). REBOA augmented the end systolic pressure volume relationship. Stroke work evolved with placement of occlusive REBOA (1.2 vs 4.3 mmHgL; P < .01). End systolic elastance was augmented from baseline by shock and REBOA placement (1.01 vs 0.39 vs 4.50 mL/mmHg; P < .01) and remained elevated with transition to partial REBOA (3.22 mL/mmHg) (Figure 2). Percent time in antegrade coronary blood flow decreased during shock (94% to 71.8%; P < .01) and was rescued with REBOA, but REBOA also increased peak coronary flow compared with shock (271 vs 93 mL/min; P < .01) and total coronary flow, even beyond baseline (peak: 2136 vs baseline: 424 mL/min; P < .01). No REBOA state augmented the end diastolic pressure volume relationship. REBOA maintains the end diastolic pressure volume relationship, but increases afterload, thereby augmenting the end systolic pressure volume relationship and left ventricle contractility with partial REBOA. REBOA alters coronary artery blood flow by reversing shock-induced retrograde coronary flow, and increasing peak coronary artery flow, therefore increasing total flow. The afterload modulation from REBOA underlies its resuscitative capability but may drive the mechanism of cardiovascular injury. Partial REBOA with resuscitation balances the afterload improvement against undue left ventricle strain.Fig 2End systolic elastance (Ees; the slope of the end systolic pressure volume relationship) evolution across study periods. *P = .003; **P = .048; ***P = .01; ****P = .015.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Underlying Cardiovascular Mechanisms of Resuscitation and Injury of REBOA and Partial REBOA.

Introduction: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is used for aortic control in hemorrhagic shock despite little quantification of its mechanism of resuscitation or cardiac injury. The goal of this study was to use pressure-volume (PV) loop analysis and direct coronary blood flow measurements to describe the physiologic changes associated with the clinical use of REBOA. Methods: Swine underwent surgical and vascular access to measure left ventricular PV loops and left coronary flow in hemorrhagic shock and subsequent placement of occlusive REBOA, partial REBOA, and no REBOA. PV loop characteristics and coronary flow are compared graphically with PV loops and coronary waveforms, and quantitatively with measures of the end systolic and end pressure volume relationship, and coronary flow parameters, with accounting for multiple comparisons. Results: Hemorrhagic shock was induced in five male swine (mean 53.6 ± 3.6 kg) as demonstrated by reduction of stroke work (baseline: 3.1 vs. shock: 1.2 L*mmHg, p < 0.01) and end systolic pressure (ESP; 109.8 vs. 59.6 mmHg, p < 0.01). ESP increased with full REBOA (178.4 mmHg; p < 0.01), but only moderately with partial REBOA (103.0 mmHg, p < 0.01 compared to shock). End systolic elastance was augmented from baseline to shock (1.01 vs. 0.39 ml/mmHg, p < 0.01) as well as shock compared to REBOA (4.50 ml/mmHg, p < 0.01) and partial REBOA (3.22 ml/mmHg, p = 0.01). Percent time in antegrade coronary flow decreased in shock (94%–71.8%, p < 0.01) but was rescued with REBOA. Peak flow increased with REBOA (271 vs. shock: 93 ml/min, p < 0.01) as did total flow (peak: 2136, baseline: 424 ml/min, p < 0.01). REBOA did not augment the end diastolic pressure volume relationship. Conclusion: REBOA increases afterload to facilitate resuscitation, but the penalty is supraphysiologic coronary flows and imposed increase in LV contractility to maintain cardiac output. Partial REBOA balances the increased afterload with improved aortic system compliance to prevent injury.

Relationship Between Plasma Total Homocysteine Levels and Mean Corrected TIMI Frame Count in Patients with Acute Myocardial Infarction.

ObjectiveTo explore the relationship between the plasma total homocysteine (tHcy) levels and slow coronary flow (SCF) measured by mean corrected TIMI frame count (CTFC) in patients with acute myocardial infarction (AMI).MethodsNinety-one patients with primary myocardial infarction were enrolled in this study. The quantitative measurement of coronary blood flow was performed using the mean CTFC method. Plasma tHcy levels were determined using enzymatic assay from venous blood samples. Multivariable linear regression models indicated were used to estimate the effect size (β) of plasma tHcy levels on mean CTFC levels.ResultsCompared with patients with the mean CTFC ≤23.61 frames per second (FPS) group, there were increased plasma tHcy levels in patients of the second, third and highest mean CTFC quartiles (P < 0.001). Linear regression models indicated that plasma tHcy levels were positively associated with mean CTFC levels (adjusted-β per SD increase: 1.96, 95% CI 1.20 to 2.73, P < 0.001). Compared to the tHcy ≤12.30 μmol/L group, the third and highest tHcy-quartile groups had higher mean CTFC levels (adjusted-β: 2.52, 95% CI 0.39 to 4.65, P = 0.023; adjusted-β: 5.07, 95% CI 2.98 to 7.16, P < 0.001, respectively; P for trend <0.001). Moreover, this positive relationship was modified by diabetes mellitus (P-value for interaction was 0.046).ConclusionWe found a positive relationship between plasma tHcy levels and mean CTFC levels in patients with AMI. Moreover, diabetes mellitus played an interactive role in this positive association between the plasma tHcy levels and mean CTFC levels.

Thermodilution-derived volumetric resting coronary blood flow measurement in humans.

Quantification of microvascular function requires the measurement of flow and resistance at rest and during hyperaemia. Continuous intracoronary thermodilution accurately measures coronary flow during hyperaemia. The aim of this study was to investigate whether continuous coronary thermodilution using lower infusion rates also enables volumetric coronary blood flow measurements (in mL/min) at rest. In 59 patients (88 arteries), the ratio of distal to proximal coronary pressure (Pd/Pa), as well as absolute blood flow (in mL/min) by continuous thermodilution, was recorded using a pressure/temperature guidewire. Saline was infused at rates of 10 and 20 mL/min. In 27 arteries, Doppler average peak velocity (APV) was measured simultaneously. Pd/Pa, APV, thermodilution-derived coronary flow reserve (CFRthermo) and coronary flow velocity reserve (CFVR) were assessed. In 10 arteries, simultaneous recordings were obtained at saline infusion rates of 6, 8, 10 and 20 mL/min. Compared to baseline, saline infusion at 10 mL/min did not change Pd/Pa (0.95±0.05 versus 0.94±0.05, p=0.49) or APV (22±8 versus 23±8 cm/s, p=0.60); conversely, an infusion rate of 20 mL/min induced a decrease in Pd/Pa and an increase in APV. Stable thermodilution tracings were obtained during saline infusion at 8 and 10 mL/min, but not at 6 mL/min. Mean values of CFRthermo and CFVR were similar (2.78±0.91 versus 2.76±1.06, p=0.935) and their individual values correlated closely (r=0.89, 95% CI: 0.78-0.95, p<0.001). In addition to hyperaemic flow, continuous thermodilution can quantify absolute resting coronary blood flow; therefore, it can be used to calculate coronary flow reserve and microvascular resistance reserve.

Measurement of coronary sinus blood flow using transesophageal echocardiography to estimate the adequacy of revascularization in patients undergoing off-pump coronary artery bypass grafting

Introduction Revascularization of coronary artery increases the blood flow in the coronary sinus (CS) too. The study aimed to measure the CS blood flow using transesophageal echocardiography (TEE) to estimate the adequacy of revascularization in patients undergoing off-pump coronary artery bypass grafting. Patients and methods After ethical committee approval, 100 patients scheduled for elective coronary artery bypass grafting were included in this study. After induction of balanced anesthesia according to institutional protocol, a 5-Hz multiplane phased-array TEE probe was inserted into patients’ esophagus, and the following parameters were calculated at pre-revascularization and post-revascularization periods: velocity time integral of CS, coronary sinus diameter, coronary sinus cross-section area, and coronary sinus blood flow (CSBF) per beat and per minute. Results Our study showed a statistically significant increase in velocity time integral in the post-revascularization period as compared with the pre-revascularization period (P Conclusion TEE is a superior modality to evaluate CSBF before and after coronary artery bypass revascularization to determine the adequacy of surgical revascularization in real time during off-pump coronary artery bypass revascularization.

Thermodilution-Based Invasive Assessment of Absolute Coronary Blood Flow and Microvascular Resistance: Quantification of Microvascular (Dys)Function?

During the last two decades, there has been a sharp increase in both interest and knowledge about the coronary microcirculation. Since these small vessels are not visible by the human eye, physiologic measurements should be used to characterize their function. The invasive methods presently used (coronary flow reserve (CFR) and index of microvascular resistance (IMR)) are operator-dependent and mandate the use of adenosine to induce hyperemia. In recent years, a new thermodilution-based method for measurement of absolute coronary blood flow and microvascular resistance has been proposed and initial procedural problems have been overcome. Presently, the technique is easy to perform using the Rayflow infusion catheter and the Coroventis software. The method is accurate, reproducible, and completely operator-independent. This method has been validated noninvasively against the current golden standard for flow assessment: Positron Emission Tomography-Computed Tomography (PET-CT). In addition, absolute flow and resistance measurements have proved to be safe, both periprocedurally and at long-term follow-up. With an increasing number of studies being performed, this method has great potential for better understanding and quantification of microvascular disease.

Coronary Blood Flow Measurement in Conventional Coronary Angiograms by a New Method Based on Contrast Density Detection. A Physiological Insight.

ResumoFundamento O grau de fluxo TIMI e a contagem quadro a quadro TIMI corrigida (CTFC) são métodos amplamente utilizados para avaliar o fluxo sanguíneo coronariano angiográfico. A medição do fluxo sanguíneo coronariano (FSC) na coronariografia (CAG) padrão despertou grande interesse recentemente, tentando combinar o conceito de CTFC com novos métodos para pós-angioplastia e avaliação da síndrome cardíaca X. Além disso, o fluxo coronariano lento é considerado um critério importante para a angina microvascular.Objetivo Explorar uma nova abordagem de medição angiográfica quantitativa do FSC com base na detecção densitométrica de contraste na CAG offline, usando um software acessível para obter uma avaliação mais precisa e confiável do FSC.Métodos Trinta pacientes foram estudados e divididos em 2 grupos: fluxo sanguíneo coronariano normal (FN) e fluxo sanguíneo coronariano lento (FL), de acordo com a definição da CTFC. O MD foi aplicado à amostra do estudo para diferenciar entre FN e FL. A estatística não paramétrica foi usada para avaliar diferenças entre os grupos com p<0,05.Resultados O valor de referência normal do MD obtido para o fluxo sanguíneo coronariano foi de 9 [5–10] quadros. Os grupos FN vs. FL foi comparado e expresso como mediana [intervalo interquartil], para a artéria descendente anterior esquerda: 10 [7–11] vs. 21 [8–33]; p=0,016; artéria circunflexa: 9 [4–13] vs. 14 [11–30]; p=0,012 e artéria coronária direita: 5 [3–11] vs. 13 [8–26]; p=0,009.Conclusão O MD mostrou a viabilidade de medir o fluxo sanguíneo coronariano com precisão, consistência e reprodutibilidade em um angiograma coronariano padrão, mostrando a capacidade adicional de diferenciar FN de FL em pacientes com dor precordial e artérias coronárias normais. (Arq Bras Cardiol. 2020; 115(3):503-512)

Heart Rate-Induced Myocardial Ca2+ Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction.

BackgroundIncreases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca2+ overload caused by increased myocardial Na+ levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension.Methods and ResultsIn 22 fully sedated and instrumented patients (12 controls and 10 patients with HFpEF) in sinus rhythm with a preserved ejection fraction (≥50%) we assessed left‐sided filling pressures and volumes in sinus rhythm and with atrial pacing (95 beats per minute and 125 beats per minute) before atrial fibrillation ablation. Coronary sinus blood samples and flow measurements were also obtained. Seven women and 15 men were studied (aged 59±10 years, ejection fraction 61%±4%). Patients with HFpEF had a history of hypertension, dyspnea on exertion, concentric LV remodeling and a dilated left atrium, whereas controls did not. Pacing at 125 beats per minute lowered the mean LV end‐diastolic pressure in both groups (controls −4.3±4.1 mm Hg versus patients with HFpEF −8.5±6.0 mm Hg, P=0.08). Pacing also reduced LV end‐diastolic volumes. The volume loss was about twice as much in the HFpEF group (controls −15%±14% versus patients with HFpEF −32%±11%, P=0.009). Coronary venous [Ca2+] increased after pacing at 125 beats per minute in patients with HFpEF but not in controls. [Na+] did not change.ConclusionsHigher resting heart rates are associated with lower filling pressures in patients with and without HFpEF. Incomplete relaxation and LV filling at high heart rates lead to a reduction in LV volumes that is more pronounced in patients with HFpEF and may be associated with myocardial Ca2+ retention.

Intracoronary Saline-Induced Hyperemia During Coronary Thermodilution Measurements of Absolute Coronary Blood Flow: An Animal Mechanistic Study.

BackgroundAbsolute hyperemic coronary blood flow and microvascular resistances can be measured by continuous thermodilution with a dedicated infusion catheter. We aimed to determine the mechanisms of this hyperemic response in animal.Methods and ResultsTwenty open chest pigs were instrumented with flow probes on coronary arteries. The following possible mechanisms of saline‐induced hyperemia were explored compared with maximal hyperemia achieve with adenosine by testing: (1) various infusion rates; (2) various infusion content and temperature; (3) NO production inhibition with L‐arginine methyl ester and endothelial denudation; (4) effects of vibrations generated by rotational atherectomy and of infusion through one end‐hole versus side‐holes. Saline infusion rates of 5, 10 and 15 mL/min did not reach maximal hyperemia as compared with adenosine. Percentage of coronary blood flow expressed in percent of the coronary blood flow after adenosine were 48±17% at baseline, 57±18% at 5 mL/min, 65±17% at 10 mL/min, 82±26% at 15 mL/min and 107±18% at 20 mL/min. Maximal hyperemia was observed during infusion of both saline at body temperature and glucose 5%, after endothelial denudation, l‐arginine methyl ester administration, and after stent implantation. The activation of a Rota burr in the first millimeters of the epicardial artery also induced maximal hyperemia. Maximal hyperemia was achieved by infusion through lateral side‐holes but not through an end‐hole catheter.ConclusionsInfusion of saline at 20 mL/min through a catheter with side holes in the first millimeters of the epicardial artery induces maximal hyperemia. The data indicate that this vasodilation is related neither to the composition/temperature of the indicator nor is it endothelial mediated. It is suggested that it could be elicited by epicardial wall vibrations.

Absolute microvascular resistance by continuous thermodilution predicts microvascular dysfunction after ST-elevation myocardial infarction

AimsContinuous thermodilution using intracoronary saline infusion is a novel technique able to provide accurate measurements of absolute coronary blood flow and microvascular resistance (Rmicro). The aim of this study was to assess the ability of Rmicro, measured by continuous thermodilution, to predict microvascular dysfunction in patients with ST-elevation myocardial infarction. Methods and resultsIn this prospective observational study, continuous thermodilution was used to measure Rmicro in the culprit coronary artery of 32 patients with STEMI (mean age ± SD, 66 ± 10 years; 78% male) immediately post-primary percutaneous coronary intervention (PCI). Concomitant measurements of the index of microvascular resistance (IMR) and coronary flow reserve (CFR) were obtained by bolus thermodilution. Microvascular dysfunction was defined as an IMR > 40 or a CFR < 2. Rmicro was higher in patients with microvascular dysfunction based on the predefined thresholds; for IMR: 863 (IQR, 521–1079) vs 474 (IQR, 337–616) Wood units, p = .004 and for CFR: 633 (IQR, 455–1039) vs 474 (IQR, 271–579) Wood units, p = .02. Receiver-operator characteristic analysis demonstrated that Rmicro was predictive of microvascular dysfunction; area under curve (AUC) 0.800 (95% CI: 0.637–0.963, p = .005) for IMR-defined microvascular dysfunction and AUC 0.758 (95% CI: 0.593–0.924, p = .02) for CFR-defined microvascular dysfunction. An Rmicro threshold of greater than 552 Wood units was optimal for predicting microvascular dysfunction defined by IMR > 40. ConclusionsRmicro is able to identify STEMI patients in whom IMR and CFR measurements suggest significant microvascular dysfunction at the end of primary PCI.

Investigation of Elastic Properties of Aorta in Patients with Coronary Slow Flow

Objective: Coronary slow flow (CSF) phenomenon is characterized by delayed opacification of coronary vessels in a normal coronary angiogram. Although clinical and pathological features have been previously described, the underlying pathophysiology has not been fully understood yet. Aortic elastic properties have a predictive value in detecting early stages of atherosclerosis. In this study, we aimed to the evaluate the elastic properties of ascending aorta in patients with CSF. Materials and Methods: This single-center study enrolled 50 angiographically identified patients with CSF (23 female, mean age: 51.6 ± 9.7 years), along with 50 controls (19 female, mean age: 53.5 ± 8.7 years) with normal coronary flow. The quantitative measurement of coronary blood flow was performed using the thrombolysis in myocardial infarction frame count method. Aortic elastic parameters including aortic strain, aortic distensibility, aortic stiffness index and aortic compliance were calculated using M-mode echocardiography derived aortic diameters using accepted formulae. Results: There was no significant difference in terms of clinical, demographic, echocardiographic and laboratory parameters between the patients with CSF and the controls. The hemodynamic parameters including aortic pulse pressure, aortic mean pressure, aortic fractional pulse pressure and aortic pulsatility index were similar between patients with CSF and controls. Systolic and diastolic aortic diameters and pulsatile aortic diameter change were similar between the groups. There was also no significant difference in terms of aortic strain, aortic distensibility, aortic stiffness index and aortic compliance between the groups. Conclusion: The results demonstrated that there was no significant difference in terms of hemodynamic parameters and elastic properties of ascending aorta between CSF patients and control group with a similar risk profile and demographic characteristics. Further large scale studies are required to determine the relationship between CSF and elastic properties of aorta.

Evaluation of homocystein and asymmetric dimethyl arginine levels in patients with coronary slow flow phenomenon

BackgroundPrevious studies have demonstrated that homocysteine and asymmetric dimethyl arginine (ADMA) levels were strongly associated with cardiovascular diseases including coronary artery disease. The aim of this study was to investigate the role of plasma homocysteine and ADMA levels in the pathogenesis of coronary slow flow (CSF) phenomenon.MethodsTwenty-three patients with CSF and 25 controls with normal coronary flow were included in this study. The quantitative measurement of coronary blood flow was performed using the thrombolysis in myocardial infarction frame count method. Plasma homocysteine and ADMA levels were determined using enzymatic assays from venous blood samples.ResultsThe patients with CSF had significantly higher plasma homocysteine levels than controls (16.2 ± 7.6 vs. 12.2 ± 2.2 μM/L; p = 0.023). The uric acid levels were significantly higher in CSF group than controls (5.4 ± 1.1 vs. 4.6 ± 0.9 mg/dl; p = 0.011). Plasma ADMA levels were also higher in the CSF group; however, this was not statistically significant (0.6 ± 0.1 vs. 0.5 ± 0.2 μM/L; p = 0.475).ConclusionsIncreased homocysteine and uric acid levels may play an important role in the pathogenesis of CSF. Further large scale studies are required to determine the relationship between ADMA levels and CSF.

Absolute coronary blood flow and microvascular resistance: Correlation with instrumen tedcoronary artery blood flow ring measurements and coronary histology analysis in swine

Measurement of absolute coronary blood flow (ABF) and microvascular resistance, assessed by coronary thermodilution using a dedicated infusion catheter (RayFlow, HexaCath, Paris, France) is available in clinical practice. We sought to compare ABF and resistances values obtained at different infusion rates, to coronary artery blood flow ring measurements and histological analysis of the infused vessel in animals. Domestic swine were instrumented with coronary artery blood flow (CBF) rings on the left anterior descending (LAD) and circumflex (LCx) coronary arteries. We performed ABF using saline infusion at flow rates of 5, 10, 15 and 20 mL/min. After measurement, histological analysis of the infused vessel was performed, at the level of the infusion and at least 60 mm distal to the infusion area (control). In 13 swines, we compared 72 pairs of measurements in the LAD and the LCx. The correlation between ABF and CBF at flow rates of 5 and 10 mL/min and 15 and 20 mL/min were respectively R = 0.67 (0.45–0.82) ( n = 40 pairs) and R = 0.84 (0.69–0.92) ( n = 32 pairs). The correlation between resistances assessed with ABF and CBF at flow rates of 5 and 10 mL/min and 15 and 20 mL/min were respectively R = 0.63 (0.34–0.80) ( n = 40 pairs) and R = 0.76 (0.56–0.88) ( n = 32 pairs). Histological analysis was performed in 14 coronary arteries (28 samples), and showed no coronary dissections after ABF measurement. Some endothelial injury was observed in both infusion and control samples: 62 ± 39% and 53 ± 38% ( P = 0.53), respectively. Endothelial injury in the control sample parts might be due to trauma caused by the pressure wire ( Fig. 1 ). ABF and microvascular resistance correlate well with CBF in animals at flow rates ≥ 15 mL/min. Measurement using coronary thermodilution with Rayflow infusion catheter is accurate in vivo and, in clinical practice, at flow rates of 15 to 20 mL/min, induce maximal hyperemia and may be as safe as FFR measurement.

GLP-1 Is a Coronary Artery Vasodilator in Humans.

BackgroundThe mechanism underlying the beneficial cardiovascular effects of the incretin GLP‐1 (glucagon‐like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP‐1.Methods and ResultsTen stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post–percutaneous coronary intervention coronary blood flow measurement using a pressure‐flow wire before and after peripheral GLP‐1 administration. Coronary sinus and artery bloods were sampled for GLP‐1 levels. A further 11 control patients received saline rather than GLP‐1 in the coronary blood flow protocol. GLP‐1 receptor (GLP‐1R) expression was assessed by immunohistochemistry using a specific GLP‐1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP‐1 on absolute forearm blood flow or forearm blood flow ratio after GLP‐1, systemic hemodynamics were not affected, and no binding of GLP‐1R monoclonal antibody was detected in vascular tissue. GLP‐1 reduced resting coronary transit time (mean [SD], 0.87 [0.39] versus 0.63 [0.27] seconds; P=0.02) and basal microcirculatory resistance (mean [SD], 76.3 [37.9] versus 55.4 [30.4] mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean [SD], 0.48 [0.24] versus 0.83 [0.41] seconds; P<0.001) and basal microcirculatory resistance (mean [SD], 45.9 [34.7] versus 66.7 [37.2] mm Hg/s; P=0.02). GLP‐1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP‐1 extraction was observed.Conclusions GLP‐1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP‐1R immunohistochemistry suggests that GLP‐1 coronary vasodilatation is indirectly mediated by ventricular‐coronary cross talk.