PubMed Health⌕ Search

Biomedical subjects

Cees A Visser

Publications and source records attributed to Cees A Visser.

53 records · Page 3Linked to original sources
PubMed2002

Assessment of coronary artery bypass graft disease using cardiovascular magnetic resonance determination of flow reserve.

OBJECTIVES: The purpose of this study was to assess the value of cardiovascular magnetic resonance (CMR)-determined graft flow and flow reserve in differentiating significant from non-significant vein graft disease. BACKGROUND: In patients after coronary artery bypass grafting (CABG), non-invasive testing may be helpful in the detection of recurrent graft disease. METHODS: Randomly selected patients (n = 21) scheduled for X-ray angiography because of recurrent chest complaints after CABG were included for evaluation of vein grafts (n = 40) by CMR. Three-dimensional contrast-enhanced CMR angiography was performed and followed by flow measurements at rest and during hyperemia in patent grafts only. Flow reserve was calculated when resting flow exceeded 20 ml/min. Analysis was based on four categories defined by X-ray angiography: occluded grafts (n = 3), grafts with stenosis >50% (n = 19), grafts with stenosis <50% with diseased graft run-off (n = 8), and grafts with stenosis <50% and normal run-off (n = 10). RESULTS: The CMR angiography demonstrated occlusion of three grafts. In nine of the 37 patent grafts, basal blood flow was <20 ml/min, all demonstrating significant stenosis at X-ray angiography. In grafts with resting flow >20 ml/min (n = 28), flow reserve significantly differed between grafts without stenosis and grafts with significant stenosis or with diseased run-off (2.5 +/- 0.7 vs. 1.8 +/- 0.9, p = 0.04). An algorithm combining basal volume flow <20 ml/min and graft flow reserve <2 had a sensitivity and specificity of 78% and 80% respectively for detecting grafts with significant stenosis or diseased run-off. CONCLUSIONS: This feasibility study showed that quantification of flow and flow reserve by CMR may serve as a non-invasive adjunct to differentiate between vein grafts without stenosis and grafts with significant stenosis or diseased run-off.

Adult↗
PubMed2002

Endomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart.

OBJECTIVE: In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure-volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study relates diastolic LV stiffness and LV systolic performance to intensity of endomyocardial NO synthase (NOS) gene expression in dilated cardiomyopathy and in athlete's heart. METHODS: Microtip LV pressures, conductance-catheter or angiographic LV volumes, echocardiographic LV wall thicknesses and snap-frozen LV endomyocardial biopsies were obtained in 33 patients with dilated cardiomyopathy and in three professional cyclists referred for sustained ventricular tachycardia. Intensity of LV endomyocardial inducible NOS (NOS2) and constitutive NOS (NOS3) gene expression was determined using quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Dilated cardiomyopathy patients with higher diastolic LV stiffness-modulus and lower LV stroke work had lower NOS2 and NOS3 gene expression at any given level of LV end-diastolic wall stress. The intensity of NOS2 and NOS3 gene expression observed in athlete's heart was similar to dilated cardiomyopathy with low LV diastolic stiffness-modulus and preserved LV stroke work. CONCLUSIONS: High LV endomyocardial NOS gene expression is observed in athlete's heart and in dilated cardiomyopathy with low diastolic LV stiffness and preserved LV stroke work. Favourable effects on the hemodynamic phenotype of high LV endomyocardial NOS gene expression could result from a NO-mediated decrease in diastolic LV stiffness and a concomitant rise in LV preload reserve.

Adult↗
PubMed2002

The diastolic flow-pressure gradient relation in coronary stenoses in humans.

OBJECTIVES: We assessed the feasibility and reproducibility of the instantaneous diastolic coronary flow velocity-pressure gradient relation to characterize different degrees of coronary stenoses. BACKGROUND: Assessment of the hemodynamic significance of coronary stenoses can be difficult. Using sensor-tipped guidewires, various physiologic indexes can be determined in the catheterization laboratory. Each of the current methods, however, has limitations. METHODS: After positioning a Doppler flow wire and a pressure wire distal of a coronary stenosis, the flow velocity signals and the proximal and distal pressure were sampled simultaneously, at baseline and after intracoronary administration of adenosine. The instantaneous diastolic flow velocity and pressure gradient of single cardiac cycles at baseline, at maximal and intermediate hyperemia were plotted. Data were fitted with a regression line using the equation: Delta P = 0 +kv+Sv(2). Measurements were performed in 11 normal coronary arteries, 20 intermediate stenoses and in 7 severe stenoses before and after percutaneous transluminal coronary angioplasty plus stenting. RESULTS: We found significant differences between normal coronary arteries, intermediate and severe stenoses. Percutaneous transluminal coronary angioplasty nearly normalized the highly abnormal flow-pressure gradient relation in the severe stenoses. A high degree of reproducibility was observed. In 3% of the measurements, analysis was not possible due to the occurrence of pressure drift or bad flow velocity signals. CONCLUSIONS: It is feasible to assess the diastolic flow velocity-pressure gradient relation over a wide range of stenoses. It characterizes the hemodynamics of epicardial coronary stenoses and allows discrimination between normal coronary arteries, intermediate and severe stenoses.

Aged↗
PubMed2002

Repeated assessment of coronary flow velocity pattern in patients with first acute myocardial infarction.

OBJECTIVES: The aim of this study was to evaluate the coronary blood flow velocity pattern immediately and 24 h after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) in relation to myocardial reperfusion and follow-up left ventricular (LV) function. BACKGROUND: Analysis of coronary blood flow velocity pattern after AMI may provide information about microvascular damage and the occurrence of a reperfusion injury. METHODS: Measurement of coronary blood flow velocity pattern was performed immediately after PTCA and after 24 h in 25 patients with first AMI using a Doppler guidewire. Measurements were related to reperfusion determined by intravenous myocardial contrast echocardiography (MCE) performed before PTCA and at 24 h and to LV function at four weeks. RESULTS: Using MCE, 13 patients showed reperfusion and 12 patients showed nonreperfusion. Compared with patients with reperfusion, patients with MCE nonreperfusion had a lower systolic peak flow velocity immediately after PTCA (10.0 +/- 0.3 cm/s vs. 19.3 +/- 0.8 cm/s, respectively) and after 24 h (12.3 +/- 0.4 cm/s vs. 21.3 +/- 0.1 cm/s, respectively, p = 0.0022), more frequent early systolic retrograde flow (6/12 vs. 0/13, p = 0.0052 immediately after PTCA and 24 h later) and a shorter diastolic deceleration time immediately after PTCA (483 +/- 6 ms vs. 737 +/- 0 ms, respectively) and after 24 h (551 +/- 9 ms vs. 823 +/- 2 ms, respectively, p = 0.0091). Similarly, patients with impaired LV function at four weeks had altered coronary flow pattern compared with patients with preserved function. The coronary flow velocity pattern showed a tendency for improvement after 24 h in the reperfusion and the nonreperfusion groups. CONCLUSIONS: The coronary flow velocity pattern immediately and 24 h after PTCA for AMI relates to myocardial perfusion determined by MCE and LV function at four weeks. The flow velocity pattern shows slight improvement during the first 24 h after revascularization, indicating the absence of a major reperfusion injury.

Aged↗
PubMed2002

Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping.

Sampling of arterialised venous blood (AVB) is often used as an alternative to sampling of arterial blood when determining the myocardial metabolic rate of glucose (MRGlu). This method, however, has not yet been validated for measurement of plasma fluorine-18 fluorodeoxyglucose (FDG) activity during a euglycaemic-hyperinsulinaemic clamp (EHC). In this study, dynamic FDG scans were performed with arterial blood sampling during EHC. Samples of arterial and AVB or venous blood were simultaneously withdrawn at five time points for measurement of FDG activity and plasma glucose in 36 patients. Both venous to arterial and AVB to arterial ratios were calculated for FDG activity and plasma glucose. Mean ratios between AVB and arterial FDG activity were then used to create calculated arterialised venous input functions from corresponding arterial input functions. The mean effect of arterialisation on the calculation of K(i) was assessed. In nine additional patients, K(i) obtained with continuous sampling of AVB was compared with K(i) obtained with a corresponding (quality-controlled) image-derived input function from the ascending aorta. Using AVB, measurements of FDG activity were much more reliable than with venous blood sampling. As compared with arterial sampling, however, FDG activity was underestimated early after injection, while it was overestimated after 20 min. In both analyses, AVB resulted in approximately 10%+/-10% overestimation of K(i). Because of a 5%+/-5% underestimation of plasma glucose concentration with AVB, the net effect on the final calculation of MRGlu was small (on average 5% overestimation). It is concluded that the use of AVB has a small average effect on the determination of MRGlu. This method does, however, contribute to variability in the results. This variability cannot be explained by different degrees of arterialisation.

Arm↗
PubMed2002

Feasibility, safety and image quality of cardiac FDG studies during hyperinsulinaemic-euglycaemic clamping.

Fluorine-18 fluorodeoxyglucose (FDG) imaging for the assessment of myocardial viability has become an integral part of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy. To ensure good image quality, in particular in patients with diabetes mellitus, hyperinsulinaemic-euglycaemic clamping has been proposed. In this study we evaluated the safety and the image quality of cardiac FDG imaging during clamping in a large group of patients, including a subgroup with diabetes mellitus. The incidence of viability (on both a segment and a patient basis) was also determined for patients with and without diabetes mellitus. The safety and image quality of cardiac FDG studies during clamping were evaluated in 131 patients, including 19 with diabetes mellitus. Image quality was assessed visually and quantitatively using heart-to-lung (H/L), heart-to-liver (H/Li) and myocardium-to-background (M/B) ratios. Blood samples were drawn at baseline and at the time of FDG injection to determine levels of glucose, free fatty acids and insulin. The metabolic circumstances were optimal for FDG imaging: high insulin levels, low free fatty acid levels and glucose levels in the normal range (levels of substrates were comparable between patients with and patients without diabetes mellitus). No serious side-effects occurred in any patient. Image quality (assessed visually) was good in all patients. The quantitative parameters of image quality (H/L, H/Li and M/B) were comparable between patients with and patients without diabetes mellitus. The incidence of viability was high: 38% of patients without and 58% of patients with diabetes mellitus had substantial viability despite contractile dysfunction. It is concluded that cardiac FDG imaging during clamping is safe and provides excellent image quality, including in patients with diabetes mellitus. The incidence of viability is high, in particular in patients with diabetes mellitus.

Aged↗
PubMed2002

Secretory type II phospholipase A(2) binds to ischemic myocardium during myocardial infarction in humans.

OBJECTIVE: An increase of circulating secretory Phospholipase A(2) (sPLA(2)) is a risk factor for coronary artery disease. We hypothesized that this reflects participation of sPLA(2) in local inflammatory reactions ensuing in ischemic myocardium. Therefore, we studied the course of circulating sPLA(2), in patients with acute myocardial infarction (AMI) or unstable angina pectoris (UAP), and investigated the presence of sPLA(2) in infarcted myocardial tissue. METHODS: Plasma samples of 107 patients with AMI or UAP, collected on admission and at varying intervals thereafter, were tested for the presence of sPLA(2) and C-reactive protein (CRP). Cumulative release values of these parameters were calculated, which allowed for comparison of the results rearranged in time according to the onset of symptoms. By immunohistochemistry we studied the presence of sPLA(2) and CRP in myocardial tissue of 30 patients who died subsequent to AMI. RESULTS: Levels of sPLA(2) became elevated during the disease course in 66 of the 87 patients with AMI, and were higher than those of the patients with UAP of whom 8 of the 20 had elevated levels. By immunohistochemistry sPLA(2) was found to be localized in the infarcted myocardium, particularly in its borderzone, from 12 h after the onset of AMI. Positive staining for sPLA(2) was more extensive than that for CRP. CONCLUSIONS: The localization pattern of sPLA(2) in infarcted myocardium as well as its plasma course, in relation to those of CRP, are in line with a supposed pro-inflammatory role during AMI for sPLA(2) as a generator of lysophospholipids serving as ligands for CRP.

Angina, Unstable↗
PubMed2002

The effect of rate responsive pacing in patients with angina pectoris on the extent of ischemia on 201-thallium exercise scintigraphy.

In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium (201 Tl) exercise scintigraphy in this mode of pacing in patients with CAD and angina. Eighteen consecutive patients with chronic atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more than 6 months participated in the study. In VVI and VVIR modes a symptom-limited exercise 201 Tl scintigram was performed in a single blind randomized crossover fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets, blood pressure, and analysis of the scintigrams were assessed during each pacing mode. Fifteen men and three women were included (age 65.9 +/- 4.9 years, LVEF 0.44 +/- 0.07). Four were in Class III angina pectoris, and 14 in class II. The mean exercise duration increased 28% in the VVIR group without an increase in anginal attacks per week or the use of NTG tablets. On scintigrams, no differences were seen between the two groups. One patient was withdrawn from the study because of an increase in angina pectoris (AP) attacks during VVIR pacing. Rate responsive pacing is safe and effective in patients with CAD without an increase in subjective and objective signs of ischemia.

Aged↗
PubMed2002

Importance of transducer displacement and tilting on three-dimensional echocardiographic volume assessment using apical or off-axis rotational acquisition: an in vitro study.

OBJECTIVE: The goal of this study was to assess effects of translation (horizontal displacement) and angulation (transducer tilting) on 3-dimensional (3D) echocardiographic volumes of both balloons and human left ventricles after autopsy. METHODS: Six water-filled (non-) aneurysmatic balloons of 150, 250, and 350 mL and 3 hearts of different sizes and shapes were suspended upright in a water bath. Angulation and/or translation was performed respectively by tilting the transducer with a mechanical arm in a vertical plane relative to the balloon tip or true apex of the hearts and by shifting the water bath in the same vertical plane. For balloon and left ventricular (LV) volume assessment, a 3D conical data set was obtained by TomTec rotational acquisition in combination with a HP Sonos 5500 ultrasound machine. RESULTS: For the 6 balloons, translation from 1 to 4 cm yielded volumes of up to 74% of the optimal volume (100%); angulation of 10 degrees or 20 degrees, volumes of up to 80% and 34%. Translation with 10-degree angulation yielded volumes up to 64%; for 20-degree angulation and translation, there was no volume loss. Results were similar for the left ventricles. CONCLUSIONS: Even minor angulation or translation of the transducer yields substantial underestimation of the true volume. Off-axis para-apical views, however, defined as angulation of 20 degrees and greater than 0.5 cm translation in this in vitro model, obviate volume underestimation. Such views in patients, if obtainable, may be an attractive alternative for conventional apical 3D acquisition, especially in dilated and aneurysmatic hearts.

Artificial Intelligence↗
PubMed2002

Intravenous myocardial contrast echocardiography predicts left ventricular remodeling in patients with acute myocardial infarction.

BACKGROUND: This study evaluated the ability of intravenous myocardial contrast echocardiography (MCE) performed in the setting of acute myocardial infarction for prediction of left ventricular (LV) remodeling. METHODS: Intravenous MCE was performed immediately before, 1 hour, and 24 hours after primary percutaneous transluminal coronary angioplasty (PTCA) in 35 patients with a first myocardial infarction. The MCE was used to define the relative perfusion defect size (in %; relMCD). Two-dimensional echocardiography was performed directly after angioplasty and after 4 weeks to determine LV end-diastolic volumes (LVEDV). The increase in LVEDV at 4 weeks defined a remodeling (> 15% increase) and a nonremodeling group (< or = 15% increase). RESULTS: Patients with remodeling had larger relMCD before (22.0 +/- 16.1 vs 8.0 +/- 11.9, P =.015), 1 hour (20.0 +/- 13.0 vs 4.9 +/- 11.6, P =.001), and 24 hours after PTCA (22.9 +/- 14.1 vs 1.2 +/- 2.8, P <.001). There was a significant correlation between relMCD 24 hours after PTCA and the increase in LVEDV at 4 weeks (r = 0.648; P <.001). Receiver operating characteristic (ROC) curve analysis revealed a relMCD at 24 hours of 5.1% or more to predict remodeling with a sensitivity of 94% and a specificity of 87% (area under ROC curve = 0.917; SE = 0.054). Multivariate analysis demonstrated relMCD at 24 hours to be the only predictor of remodeling (odds ratio = 173.4; P =.022). CONCLUSION: The size of the persistent MCE perfusion defect after revascularization for acute myocardial infarction has a high predictive value for LV remodeling during a 4-week follow-up period.

Aged↗
PubMed2002

Magnetic resonance imaging versus Doppler guide wire in the assessment of coronary flow reserve in patients with coronary artery disease.

BACKGROUND: Coronary flow velocity reserve (CFVR), defined as the ratio of maximal hyperaemic to baseline flow velocity, has been validated as a marker of physiological significance of a coronary lesion. Clinically, this parameter is measured invasively during X-ray angiography using the Doppler guide wire. With magnetic resonance (MR) imaging it is possible to quantify CFVR non-invasively. DESIGN: The purpose of the study was to compare CFVR, acquired with MR imaging and the Doppler guide wire in patients with coronary artery disease. METHODS: Twenty-two patients suffering from one- or two-vessel coronary artery disease as derived from diagnostic X-ray coronary angiography were included. Coronary flow velocity reserve was measured at baseline and during maximal hyperaemia, obtained by intravenous administration of adenosine using MR phase contrast velocity quantification. Within 2 weeks CFVR was measured invasively with a Doppler guide wire. RESULTS: In 26 coronary arteries CFVR was acquired with both techniques. Mean CFVR in the stenosed and healthy reference arteries was 1.5 +/- 0.7 and 2.7 +/- 1.0 (P < 0.01) respectively for MR measurements and 1.9 +/- 0.7 and 3.1 +/- 0.6 (P < 0.01) respectively for Doppler measurements. Bland-Altman analysis revealed a non-significant mean difference between the two techniques of 0.4 +/- 1.2. CONCLUSION: In a selected group of stable patients with coronary artery disease MR flow velocity quantification provides non-invasive data equivalent to the invasive Doppler guide wire data. Variability in both the MR and Doppler ultrasound measurement resulted in a significant scatter of data without systematic difference.

Blood Flow Velocity↗
PubMed2002

Intercellular adhesion molecule-1 in the heart.

Intercellular adhesion molecule-1 (ICAM-1) belongs to the superfamily of immunoglobulin-like adhesion molecules. Up-regulation of ICAM-1 occurs in many different pathophysiological processes. Also, cardiomyocytes can express ICAM-1-for example, in acute myocardial infarction. Moreover, inhibition of ICAM-1 expression in the heart dramatically reduces infarct size. Hence, inhibitors of ICAM-1 may provide a novel therapeutic option for acute myocardial infarction.

Animals↗
PubMedDate not supplied

Impact of scar on water-perfusable tissue index in chronic ischemic heart disease: Evaluation with PET and contrast-enhanced MRI.

BACKGROUND: The water-perfusable tissue index (PTI) is assumed to differentiate viable myocardium from scar tissue, but histological comparisons in humans are lacking. The present study compares PTI with delayed contrast-enhanced magnetic resonance imaging (DCE-MRI), a validated marker of fibrotic tissue, in patients with ischemic left ventricular (LV) dysfunction. In addition, the optimal PTI threshold for detection of myocardial viability was defined when DCE-MRI was taken as a reference. MATERIALS: Twenty patients with ischemic LV dysfunction were studied with positron emission tomography, using oxygen-15-labeled water and carbon monoxide as tracers, and DCE-MRI. RESULTS: Of the 200 analyzed segments, 112 demonstrated DCE and were subsequently divided in three subgroups according to the severity of enhancement. PTI was 1.04 +/- 0.21 in control segments and gradually decreased with increasing extent of DCE to 0.77 +/- 0.31 for segments with transmural enhancement (p < 0.001). However, PTI progressively underestimated infarct size with increasing quantities of scar tissue (r = 0.61, p < 0.01). A PTI cutoff value of 0.89 yielded the best diagnostic accuracy for detection of myocardial viability with sensitivity and specificity values of 75 and 77%, respectively. CONCLUSIONS: PTI is inversely related to the extent of scar tissue estimated by DCE-MRI in patients with chronic ischemic heart disease and LV dysfunction. However, with increasing quantities of scar tissue, PTI overestimates the extent of residual viable tissue. A PTI threshold of 0.89 yields the best diagnostic accuracy for viability detection.

Aged↗
PubMedDate not supplied

Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging.

BACKGROUND: Positron emission tomography (PET) with inhaled oxygen 15-labeled carbon monoxide (CO) is used as a marker of myocardial blood pool. Only a limited number of studies with small numbers of patients have reported on the assessment of left ventricular (LV) volumes by use of O-15-labeled CO. The aim of this study was to compare LV volumes and function as measured by routinely acquired blood pool images by use of gated O-15-labeled CO PET with the reference technique, cardiovascular magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty-four subjects with a varying degree of LV function were studied. LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were determined by both MRI and gated PET by use of O-15-labeled CO. Volumes were comparable with respect to LVEDV (196 +/- 83 and 192 +/- 91 mL, respectively; P = not significant). LVESV, however, was slightly overestimated by PET (119 +/- 85 and 136 +/- 94 mL, respectively; P < .05), resulting in a significant underestimation of LVEF (44% +/- 19% and 35% +/- 18%, respectively; P < .05). Observed correlations for LVEDV, LVESV, and LVEF were 0.90, 0.96, and 0.86, respectively (all P < .01). CONCLUSIONS: Gated O-15-labeled CO PET measurements of LVEDV, LVESV, and LVEF show good correlation with MRI over a wide range of LV volumes during routinely acquired blood pool images. LVEF, however, may be underestimated compared with MRI.

Adult↗
PubMedDate not supplied

Safety and feasibility of cardiac FDG SPECT following oral administration of Acipimox, a nicotinic acid derivative: Comparison of image quality with hyperinsulinemic euglycemic clamping in nondiabetic patients.

BACKGROUND: Image quality of cardiac fluorine-18-deoxyglucose (FDG) studies is highly dependent on the metabolic conditions during the study; hyperinsulinemic euglycemic clamping ensures adequate image quality. However, the approach is time-consuming. Data in a small number of patients suggest that oral administration of a nicotinic acid derivative (Acipimox, 250 mg; Byk, The Netherlands) results in good image quality. METHODS AND RESULTS: The safety and image quality of cardiac FDG single photon emission computed tomography studies after Acipimox administration were evaluated (21 patients, group 2); the results were compared with studies performed during hyperinsulinemic euglycemic clamping (69 patients, group 1). Image quality was assessed visually and quantitatively with use of heart-to-lung, heart-to-liver, and myocardium-to-background ratios. Blood samples were drawn at baseline and at the time of FDG injection to determine levels of glucose, free fatty acids, and insulin. Baseline characteristics of group 1 and 2 patients were comparable. No side effects occurred in group 1. Four patients in group 2 (19%) had paroxysmal flushing. Image quality, assessed visually, was good in 100% of group 1 patients and in 86% of group 2 patients. Images were uninterpretable in only 1 patient in group 2 (5%). All quantitative parameters of image quality (heart-to-lung, heart-to-liver, and myocardium-to-background ratios) were comparable between group 1 and 2 patients. Baseline plasma levels of all substrates were comparable between groups. At the time of FDG injection, plasma levels of glucose and free fatty acids were comparable between groups; insulin was higher in group 1 patients. CONCLUSIONS: Cardiac FDG single photon emission computed tomography after Acipimox is a simple and safe approach that renders comparable image quality to that obtained during hyperinsulinemic euglycemic clamping.

Administration, Oral↗