Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Impact of Sublingual Nitroglycerin on the Assessment of Computed Tomography-derived Fractional Flow Reserve: An Intraindividual Comparison Study.

OBJECTIVE: The aim of this study was to investigate the impact of nitroglycerin (NTG) on the assessment of computed tomography-derived fractional flow reserve (CT-FFR). MATERIALS AND METHODS: Seventy-seven patients with suspected coronary artery disease were recruited, and they underwent computed tomography angiography (CCTA) before and after NTG administration. The CT-FFRs were compared at 2 CCTAs. The difference was compared using the Wilcoxon signed rank test. Patients were divided into normal and stenosis groups according to CCTA results. Vessels in the stenosis group were further divided into different groups based on coronary artery calcium score (CACS) and stenosis degree. The poststenotic CT-FFR differences before and after NTG (DCT-FFR) were calculated to evaluate the impact of stenosis degree and CACS. Terminal CT-FFRs derived from CCTAs before and after NTG in total and vessel-specific levels were compared in the normal group. RESULTS: Of 47 patients in the stenosis group, poststenotic CT-FFR was significantly increased after NTG at per-vessel level. By taking CT-FFR of 0.75 or lower as the threshold, 5 and 4 patients showed abnormal CT-FFR before and after NTG, respectively. No significant differences were noted among the various stenosis degree and CACS groups regarding DCT-FFR. Of 30 patients in the normal group, terminal CT-FFR was significantly increased after NTG in total level and vessel-specific level of left anterior descending and right coronary artery, but not in the left circumflex. CONCLUSIONS: Both post lesion and distal vessel CT-FFR significantly improved after the administration of GTN with the degree of change not affected by stenosis severity or CACS.

Assessment of tissue perfusion and vascular function in mice by scanning laser Doppler perfusion imaging.

Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular diseases. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.

Impact of sublingual nitroglycerin dosage on FFRCT assessment and coronary luminal volume-to-myocardial mass ratio.

OBJECTIVES: Fractional flow reserve computed tomography (FFRCT) depends upon nitroglycerin (NTG) inducing maximal hyperemia. However, the impact of NTG dosages on FFRCT analysis including coronary volume-to-mass ratio (V/M) is unknown. METHODS: Eighty patients with repeat coronary CT angiograms (CCTAs) with different sublingual spray NTG doses (0.4 mg and 0.8 mg) were retrospectively analyzed with 45 patients excluded. Patient and scan demographics, post-stenosis and nadir FFRCT values, coronary volume, and coronary volume-to-mass ratio (V/M) were compared at initial CCTA (0.4 mg NTG) and follow-up CCTA (0.8 mg NTG). Differences were compared by Wilcoxon signed-rank test. RESULTS: Thirty-five patients were included (time between CCTAs, 3.9 ± 1.6 years). Segment involvement score was 2.4 ± 3.3 and 2.8 ± 3.4 at initial and repeat CCTA (0.4 and 0.8 mg NTG), respectively (p = 0.004). There was similar image quality (4.1 ± 0.7 vs 4.1 ± 0.8; p = 0.51). Nadir FFRCT values did not differ in the left (0.4 mg, 0.80 ± 0.08 vs 0.8 mg, 0.80 ± 0.03; p = 0.66), right (0.4 mg, 0.90 ± 0.04 vs 0.8 mg, 0.90 ± 0.06; p = 0.25), or circumflex coronaries (0.4 mg, 0.87 ± 0.06 vs 0.8 mg, 0.88 ± 0.06; p = 0.34). Post-stenosis FFRCT values did not differ (p = 0.65). Coronary volume increased with 0.8 mg of NTG (2639 ± 753 mm3 vs 2844.8 ± 827 mm3; p = 0.009) but V/M ratio did not (p = 0.20). CONCLUSIONS: Use of 0.8 mg versus 0.4 mg of NTG in routine clinical CCTAs significantly increased coronary volume determined from FFRCT analysis but did not alter FFRCT or V/M. Further evaluation of repeat CCTAs in a more contemporaneous fashion using varied nitrate doses and disease severity is needed. KEY POINTS: • Fractional flow reserve from computed tomography (FFRCT) is a noninvasive method for evaluating the coronary arteries and relies on nitroglycerin (NTG) to induce coronary vasodilation, but the impact of different NTG dosages is unknown. • Retrospective analysis evaluated use of different NTG doses on FFRCT. • Increased NTG dose increased coronary luminal volume on FFRCTanalysis, but did not change FFRCTvalues.

Assessment of endothelium-independent vasodilation: from methodology to clinical perspectives.

: Vascular response to exogenously administered nitroglycerine, an index of endothelium-independent vasodilation, has been used as a control test for the assessment of endothelium-dependent vasodilation (endothelial function) in humans. However, evidence has been accumulating that not only endothelium-dependent vasodilation but also endothelium-independent vasodilation per se is impaired in individuals with cardiovascular risk factors and cardiovascular disease. Impaired endothelium-independent vasodilation is associated with structural vascular alterations and alterations in vascular smooth muscle cells. Several methods, including assessment of vascular responses to vasoactive agents using angiography in a coronary artery and vascular responses to vasoactive agents using venous occlusion plethysmography and ultrasonography in a peripheral artery, are used to assess endothelium-independent vasodilation in humans. Measurement of endothelium-independent vasodilation is also useful for assessment of atherosclerosis and may be a predictor of future cardiovascular events. In this review, we focus on assessment of endothelium-independent vasodilation from methodology aspects to clinical perspectives.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.

Nitroglycerine-induced vasodilation for assessment of vascular function: a comparison with flow-mediated vasodilation.

OBJECTIVE: Nitroglycerine-induced vasodilation has been used as a control test for flow-mediated vasodilation (FMD) to differentiate endothelium-dependent from endothelium-independent response when evaluating endothelial function in humans. Recently, nitroglycerine-induced vasodilation has also been reported to be impaired in patients with atherosclerosis. The purpose of this study was to determine the relationships between nitroglycerine-induced vasodilation and cardiovascular risk factors. APPROACH AND RESULTS: We measured nitroglycerine-induced vasodilation and FMD in 436 subjects who underwent health examinations (mean age, 53 ± 19 years; age range, 19-86 years), including patients with cardiovascular diseases. There was a significant relationship between nitroglycerine-induced vasodilation and FMD (r=0.42; P<0.001). Univariate regression analysis revealed that nitroglycerine-induced vasodilation correlated with age (r=-0.34; P<0.001), systolic blood pressure (r=-0.32; P<0.001), diastolic blood pressure (r=-0.24; P<0.001), heart rate (r=-0.21; P<0.001), glucose (r=-0.23; P<0.001), and smoking pack-year (r=-0.12; P=0.01), as well as Framingham risk score (r=-0.30; P<0.001). Nitroglycerine-induced vasodilation was significantly smaller in patients with cardiovascular disease than in both subjects with and without cardiovascular risk factors (10.5 ± 5.6% versus 13.7 ± 5.4% and 15.3 ± 4.3%; P<0.001, respectively), whereas there was no significant difference in nitroglycerine-induced vasodilation between subjects with and without cardiovascular risk factors. Multivariate analysis revealed that male sex, body mass index, hypertension, diabetes mellitus, baseline brachial artery diameter, and FMD were independent predictors of nitroglycerine-induced vasodilation. CONCLUSIONS: These findings suggest that nitroglycerine-induced vasodilation may be a marker of the grade of atherosclerosis. FMD should be interpreted as an index of vascular function reflecting both endothelium-dependent vasodilation and endothelium-independent vasodilation in subjects with impaired nitroglycerine-induced vasodilation.

The CAM-LDPI method: a novel platform for the assessment of drug absorption.

OBJECTIVES: This study aimed to explore the use of the chicken chorioallantoic membrane (CAM) with laser doppler perfusion imaging (LDPI) as a platform to assess absorption of vasoactive drugs. METHODS: The optimal age of the CAM to be employed in the test and the indicator of vasoactivity were first established. Test substances that included common solvents and vasoactive drugs were tested on the CAM surface to determine their irritancy and blood perfusion effects. KEY FINDINGS: Insignificant changes in blood perfusion were observed with deionized water, 0.9% w/v soldium chloride and 5% w/v glucose monohydrate, as well as theophylline and glucagon. Complex changes in blood perfusion were detected with ethanol, N-methyl-2-pyrrolidone, glycerin and propranolol. Both caffeine and glyceryl trinitrate resulted in a drop in blood perfusion. CONCLUSIONS: It was concluded that the LDPI offers a rapid and non-invasive method to measure blood perfusion in the CAM. The latter provides a potentially useful platform in formulation studies to evaluate the effects of additives on drug absorption using caffeine or glyceryl trinitrate as model drugs.

Assessment of aortic stiffness by local and regional methods.

The stiffness of large arteries has an important role in cardiovascular hemodynamics. Aortic stiffness (AoStiff) can be assessed non-invasively with regional and local methods. In this paper, we compared these two techniques for evaluating AoStiff. Our subjects comprised of 118 consecutive patients (85 men, mean age: 49 ± 14 years). We evaluated regional AoStiff with carotid-femoral pulse wave velocity (PWV) measured with a tonometric technique and by bioelectrical impedance (BI) wave velocity (IWV). The local AoStiff was calculated from BI signals recorded at the chest. We used glyceryl trinitrate (GTN) to test the effect of peripheral vasodilatation on both methods in a subgroup of 52 patients (37 men, mean age: 52 ± 11 years). We found a significant correlation between IWV and PWV measurements (r = 0.88, P < 0.0001) as well as between AoStiff and PWV measurements (r = 0.75, P < 0.0001). GTN administration decreased mean arterial blood pressure by 4% (95% confidence interval: 2-8%, P = 0.002) without significant changes in AoStiff and regional IWV. Local AoStiff is correlated with regional measurements and is not influenced by changes in arterial pressure because of systemic peripheral vasodilatation.

Investigation of endothelial function by pulse contour analysis: a protocol for drug administration and timing of pulse contour assessment.

AIMS: Pulse contour analysis (PCA) obtained by finger photoplethysmography produces a digital volume pulse (DVP) including an inflection point in its down-slope. The reflection index (RI: ratio of the inflection point height over the maximal DVP) is responsive to vasodilatation. We aimed to optimize the drug dose and time interval for assessing endothelial function using PCA in healthy volunteers and patients with severe coronary artery disease. METHODS: Time and dose to RI response relationships were constructed in 16 volunteers and nine patients to inhaled salbutamol (100-400 microg) or sublingual nitroglycerin (NTG; 25-400 microg). RESULTS: For the volunteers, the time to maximum RI response to inhaled salbutamol and sublingual NTG was 10.73 +/- 0.41 and 3.66 +/- 0.21 min, respectively. A plateau in the RI response to salbutamol occurred between 5 and 15 min after inhalation and results were averaged over this period. A dose-dependent response was observed to inhaled salbutamol and sublingual NTG (P= 0.05 and P < 0.001 by repeated-measures anova, respectively) in healthy volunteers. By contrast, in patients with severe coronary artery disease inhaled salbutamol (100-400 microg) did not cause a significant change in RI. CONCLUSIONS: In healthy volunteers the RI response to inhaled salbutamol (100-200 microg) averaged over 5-15 min after administration may be used to investigate endothelial function by PCA. The response to sublingual NTG (50 microg) should be determined at 4 min. This technique may not be suitable for the assessment of endothelial function in subjects with extensive coronary artery disease owing to the small responses observed and potential confounding effect of vasoactive medication.

Ultrasound assessment of popliteal vein compliance during a short deflation protocol.

The purpose of the present study was to determine whether ultrasound is a useful tool to measure the venous characteristics of the lower extremity during a standard venous collecting cuff deflation protocol. To accomplish this, lower extremity pressure-cross-sectional area (CSA) and pressure-volume relationships were measured in eight (25 +/- 1 yr) supine subjects. Popliteal vein CSA was assessed by using high-resolution ultrasound, while calf volume changes were simultaneously assessed by using venous occlusion plethysmography (VOP). Pressure-CSA and pressure-volume relationships were assessed at baseline, during the cold pressor (CP) test, and following sublingual nitroglycerin (NTG) administration. Relationships were modeled with a quadratic regression equation, and beta(1) and beta(2) were used as indexes of venous compliance. Popliteal vein regression parameters beta(1) (8.485 +/- 2.616 vs. 7.638 +/- 2.664, baseline vs. CP; 8.485 +/- 2.616 vs. 7.734 +/- 3.076, baseline vs. NTG; both P > 0.05) and beta(2) (-0.0841 +/- 0.0241 vs. -0.0793 +/- 0.0242, baseline vs. CP; -0.0841 +/- 0.0241 vs. -0.0771 +/- 0.0280, baseline vs. NTG; both P > 0.05) were not affected by CP or NTG. Similarly, calf regression parameters beta(1) and beta(2), obtained with VOP, were not altered during either trial. Intraclass correlations for venous compliance assessed with ultrasound and VOP were 0.92 and 0.97, respectively, indicating acceptable reproducibility. These data suggest that ultrasound is a functional and reproducible tool to assess the venous characteristics of the lower extremity, in addition to VOP. Additionally, popliteal vein and calf compliance were not affected by the CP test or NTG.

Non-invasive assessment of endothelial function: which technique?

OBJECTIVES: The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND: Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS: Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS: Reproducibility of FMD was high in adults and children (coefficient of variation [CV] = 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV = 11.5, children CV = 17.1) and PCA particularly in children (adults CV = 18.2, children CV = 36.3). Flow-mediated dilation (p < 0.001) and PWA with salbutamol (p = 0.03) responses fell after typhoid vaccination, and PCA (p = 0.7) was unchanged. CONCLUSIONS: Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flow-mediated dilation remains the most reproducible method.

Non-invasive assessment of coronary arterial tone using trans-thoracic Doppler echocardiography.

BACKGROUND: As coronary flow velocity (CFV) is inversely related to the luminal size that exists for the myocardial bed, the elevated arterial tone can be assessed as the higher flow velocity in the epicardial artery. We examined the usefulness of transthoracic Doppler echocardiography (TTDE) for the assessment of coronary arterial tone. METHODS AND RESULTS: A total of 32 patients underwent TTDE and angiography. The luminal diameter (LD) in the left anterior descending artery (LAD) was measured by using quantitative coronary angiography before and after nitroglycerin (NTG) administration. The ratio of post NTG LD to the control (LD(NTG/Pre)) was assessed as a standard parameter of coronary arterial tone. We also measured CFV and CFV reserve (CFVR) at the LAD by TTDE. We evaluated the change of CFV (CFV(NTG/Pre)) and CFVR (CFVR(NTG/Pre)) following NTG administration. The LD increased from 1.98+/-0.46 to 2.51+/-0.34 mm (p<0.001), while the CFV decreased from 23.9+/-10.0 to 16.3+/-5.6 cm/s (p<0.03), and the CFVR increased from 2.39+/-0.65 to 3.56+/-1.12 (p<0.001). There were significant correlations between CFV(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.532), and between the CFVR(NTG/Pre) and LD(NTG/Pre) (p<0.0001, R2 = 0.715). CONCLUSION: TTDE can assess the coronary arterial tone by measuring the responses of CFV and CFVR to NTG administration.

Pharmacological assessment of composite arterial conduits using angiography early in the postoperative period.

OBJECTIVES: Muscular arteries are vulnerable to vasospasm unlike elastic arteries. Having developed experimental models of composite arterial grafts, we assessed and compared the responses of the grafts with different pharmacological agents using angiography early in the postoperative period. SUBJECTS AND METHODS: We harvested the internal thoracic artery (ITA) and brachial-median artery (BMA) from 10 sheep. BMA was used as an alternative to the radial artery. Each vessel was assessed histologically and morphologically. Then, a serial composite graft was constructed so that BMA was interposed. On postoperative day one or two, angiography was performed on the composite graft to measure the diameter of each vessel in response to phenylephrine (alpha-adrenergic receptor agonist), nitroglycerin+phenylephrine, and milrinone+phenylephrine. RESULTS: The BMA had a wide media layer which consisted of abundant smooth muscle cells. The combined intima and media were thicker in BMA than in ITA (p<0.01). After injection of phenylephrine, the BMA diameter decreased (2.5+/-0.4 mm to 1.9+/-0.3 mm, p<0.01), while the ITA diameter remained unchanged (3.7+/-0.2 mm to 3.6+/-0.2 mm). Continuous infusion of nitroglycerin or milrinone prevented phenylephrine-induced vasoconstriction of the BMA (p<0.05). CONCLUSIONS: These results suggest that muscular arteries have a more pronounced vasoconstrictive response to alpha-adrenergic receptor agonists than the elastic arteries. To avoid potential decrease in graft flow of muscular artery, it is advisable to use a vasodilator nitroglycerin or milrinone early in the postoperative period.

Validation of 4 French catheters for quantitative coronary analysis: in vivo variability assessment using 6 French guiding catheters as reference scaling devices.

UNLABELLED: Although numerous studies have established the utility of 4 F catheters for routine coronary angiography, its adequacy for automatic quantitative coronary analysis has not been previously assessed. METHODS: In 32 consecutive patients, coronary angiography was performed sequentially with 4 F diagnostic catheters and 6 F guiding catheters after intracoronary nitroglycerin. A total of 43 lesions were evaluated for quantitative analysis using both types of catheter as scaling devices. Possible differences in the reference diameter, minimal luminal diameter and percent diameter stenosis were evaluated. All measurements were performed offline by the same operator and intraobserver variability estimation was performed by repeating the evaluation in 12 lesions randomly selected after 1 month. RESULTS: The mean reference diameter was 2.98+/-0.48 mm, mean minimal luminal diameter was 1.00+/-0.52 mm and percent diameter stenosis was 67.1+/-15.3%. Accuracy (mean difference of values) was 0.009 mm for reference diameter, 0.005 mm for minimal luminal diameter and 0.25% for percent diameter stenosis. Precision (mean standard deviation of the differences) was 0.17 mm for reference diameter, 0.19 mm for minimal luminal diameter and 5.93% for percent stenosis. Linear correlation for these three variables was 0.94, 0.93 and 0.93, respectively. Intraobserver variability analysis showed similar values for accuracy, precision and linear correlation. CONCLUSIONS: Angiography with 4 F catheters allows adequate quantification of luminal diameters as compared to most accepted clinical standards. These results may have implications for the selection of diagnostic catheters for routine follow-up assessment of percutaneous coronary interventions.

Assessment of vasoreactivity using videodensitometry coronary angiography.

BACKGROUND: Previous studies demonstrated that the dysfunction of vasomotor tone (VT) is closely linked to the development of atherosclerosis and it is considered important in the very early stages of atherogenesis. Currently, the evaluation of VT relies on lumen changes in response to vasoactive stimuli using quantitative coronary angiography (QCA) based on geometric edge detection (ED). However, using ED for measuring lumen diameters is inherently associated with large uncertainties. Videodensitometry (VD) methods have important advantages over ED for QCA. The objective of this study was to investigate the reliability of VD and ED techniques in determining the effect of nitroglycerin (NTG) on cross-sectional area (CSA) and volume changes in a swine animal model for evaluating coronary vasoreactivity. METHODS AND RESULTS: Coronary angiography was performed on four anesthetized swine. CSA and volume were measured in the left anterior descending (LAD) coronary artery using VD before and after intracoronary injection of 0.3 mg of NTG. CSA was also calculated using standard QCA based on ED. The average CSA changes in the proximal, middle and distal branches measured using VD were 23.83% (+/-10.76%), 30.78% (+/-18.39%), and 27.34% (+/-36.53%), respectively. Similarly, the average CSA changes in the proximal, middle, and distal branches measured using ED were 15.02% (+/-36.38%), 22.02% (+/-26.12), and 38.00% (+/-48.31%), respectively. The average lumen volume change measured using VD was 29.79% (+/-14.79%). In order to evaluate the relative reliability of the techniques. the significance of deviation (SOD) was calculated, which is the ratio of the change after NTG and the measurement error. The average SOD for CSA for all the branches based on VD and ED were 1.86 and 0.69, respectively. The SOD for volume measurement was 2.78. CONCLUSIONS: Lumen changes measured by VD showed substantial improvement in reliability when compared to the ED. Moreover, VD can be used to measure substantially smaller changes in lumen dimension in response to vasoactive stimuli than the standard QCA based on ED. Finally, VD allows the measurement of arterial volume, which is not possible with ED.

Echocardiographic assessment of coronary blood flow velocity during controlled hypotensive anesthesia with nitroglycerin.

OBJECTIVE: To determine the effect of nitroglycerin on coronary blood flow velocity during controlled hypotensive anesthesia in humans. DESIGN: Internally controlled prospective study. SETTING: Single university hospital. PARTICIPANTS: Twenty American Society of Anesthesiologists class I and II patients undergoing general anesthesia for surgical resection of a malignancy. INTERVENTIONS: General anesthesia was induced with thiopental, fentanyl, and succinylcholine and maintained with isoflurane and vecuronium. Transesophageal echocardiography was used to evaluate left ventricular wall motion and blood flow velocity in the left anterior descending coronary artery. Intravenous nitroglycerin was used to reduce systolic arterial pressure to 60 to 70 mmHg. Intravenous albumin 5% was administered to maintain pulmonary capillary wedge pressure >5 mmHg. MEASUREMENTS AND MAIN RESULTS: The left anterior descending coronary artery was visualized clearly in 16 of 20 patients. At a mean nitroglycerin dose of 16+/-14 microg/kg/min, peak diastolic left anterior descending flow velocity increased significantly from 32.5+/-10.3 cm/sec to 44.7+/-14.6 cm/sec (p = 0.0103). None of the patients developed any ST-segment changes. CONCLUSIONS: During nitroglycerin-induced hypotensive anesthesia, coronary blood flow as assessed by peak diastolic left anterior descending flow velocity is preserved or increased in most patients. Increases in left anterior descending flow velocity are predictably achieved only at nitroglycerin doses >5 microg/kg/min. Intraoperative transesophageal echocardiography is useful in monitoring coronary flow velocity responses to controlled hypotensive anesthesia.

Assessment of the drug interaction between alteplase and nitroglycerin: an in vitro study.

Alteplase is the most commonly administered thrombolytic agent in the United States. However, concurrent therapy with nitroglycerin reduces plasma alteplase concentrations and its clinical efficacy. We sought to determine if this interaction is concentration and pH dependent. Seventy plasma samples were prepared and divided into three groups: alteplase 500 IU/ml alone (group 1), alteplase 500 IU/ml plus nitroglycerin 5 ng/ml (group 2), and alteplase 500 IU/ml plus nitroglycerin 200 ng/ml (group 3). The samples were analyzed at time zero and 3 hours (incubated at 37 degrees C). Group 1 had significantly higher plasma alteplase concentrations than group 3 (p<0.001). When alteplase and nitroglycerin are combined, the degradation of alteplase in plasma is enhanced.

Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse.

The digital volume pulse can be recorded simply and noninvasively by photoplethysmography. The objective of the present study was to determine whether a generalized transfer function can be used to relate the digital volume pulse to the peripheral pressure pulse and, hence, to determine whether both volume and pressure pulse waveforms are influenced by the same mechanism. The digital volume pulse was recorded by photoplethysmography in 60 subjects (10 women, aged 24 to 80 years), including 20 subjects with previously diagnosed hypertension. Simultaneous recordings of the peripheral radial pulse and digital artery pulse were obtained by applanation tonometry and a servocontrolled pressure cuff (Finapres), respectively. In 20 normotensive subjects, measurements were obtained after the administration of nitroglycerin (NTG, 500 microgram sublingually). Transfer functions obtained by Fourier analysis of the waveforms were similar in normotensive and hypertensive subjects. In normotensive subjects, transfer functions were similar before and after NTG. By use of a single generalized transfer function for all subjects, the radial and digital artery pressure waveforms could be predicted from the volume pulse with an average root mean square error of 4.4+/-2.0 and 4.3+/-1.9 mm Hg (mean+/-SD) for radial and digital artery waveforms, respectively, similar to the error between the 2 pressure waveforms (4.4+/-1.4 mm Hg). The peripheral pressure pulse is related to the digital volume pulse by a transfer function, which is not influenced by effects of hypertension or NTG. Effects of NTG on the volume pulse and pressure pulse are likely to be determined by a similar mechanism.

Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function.

OBJECTIVES: This study assessed the clinical utility of mitral annulus velocity in the evaluation of left ventricular diastolic function. BACKGROUND: Mitral inflow velocity recorded by Doppler echocardiography has been widely used to evaluate left ventricular diastolic function but is affected by other factors. The mitral annulus velocity profile during diastole may provide additional information about left ventricular diastolic function. METHODS: Mitral annulus velocity during diastole was measured by Doppler tissue imaging (DTI) 1) in 59 normal volunteers (group 1); 2) in 20 patients with a relaxation abnormality as assessed by Doppler mitral inflow variables (group 2) at baseline and after saline loading; 3) in 11 patients (group 3) with normal diastolic function before and after intravenous nitroglycerin infusion; and 4) in 38 consecutive patients (group 4) undergoing cardiac catheterization in whom mitral inflow velocity and tau as well as mitral annulus velocity were measured simultaneously. RESULTS: In group 1, mean +/- SD peak early and late diastolic mitral annulus velocity was 10.0 +/- 1.3 and 9.5 +/- 1.5 cm/s, respectively. In group 2, mitral inflow velocity profile changed toward the pseudonormalization pattern with saline loading (deceleration time 311 +/- 84 ms before to 216 +/- 40 ms after intervention, p < 0.001), whereas peak early diastolic mitral annulus velocity did not change significantly (5.3 +/- 1.2 cm/s to 5.7 +/- 1.4 cm/s, p = NS). In group 3, despite a significant change in mitral inflow velocity profile after nitroglycerin, peak early diastolic mitral annulus velocity did not change significantly (9.5 +/- 2.2 cm/s to 9.2 +/- 1.7 cm/s, p = NS). In group 4, peak early diastolic mitral annulus velocity (r = -0.56, p < 0.01) and the early/late ratio (r = -0.46, p < 0.01) correlated with tau. When the combination of normal mitral inflow variables with prolonged tau (> or = 50 ms) was classified as pseudonormalization, peak early diastolic mitral annulus velocity < 8.5 cm/s and the early/late ratio < 1 could identify the pseudonormalization with a sensitivity of 88% and specificity of 67%. CONCLUSIONS: Mitral annulus velocity determined by DTI is a relatively preload-independent variable in evaluating diastolic function.