Advances in the non-invasive assessment of vascular dysfunction in metabolic syndrome and diabetes: Focus on endothelium, carotid mechanics and renal vessels.

AIM: The present paper is a selective review on the methodology and clinical significance of techniques to assess specifically endothelial function, carotid mechanics and renal vascular function, particularly in the light of vascular dysfunction in metabolic syndrome and type 2 diabetes. DATA SYNTHESIS: Endothelial dysfunction appears to be earlier detectable in the microcirculation of patients with altered glucose metabolism, while it attains significance in the macrocirculation at more advanced disease stages. Smooth muscle cell dysfunction is now increasingly recognized to play a role both in the development of endothelial dysfunction and abnormal arterial distensibility. Furthermore, impaired glucose metabolism affects carotid mechanics through medial calcification, structural changes in extracellular matrix due to advanced glycation and modification of the collagen/elastin material stiffness. The assessment of renal vascular function by dynamic ultrasound or magnetic resonance imaging has recently emerged as an appealing target for identifying subtle vascular alterations responsible for the development of diabetic nephropathy. CONCLUSIONS: Vascular dysfunction represents a major mechanism for the development of cardiovascular disease in patients with abnormal glucose metabolism. Hence, the currently available non-invasive techniques to assess early structural and vascular abnormalities merit recommendation in this population, although their predictive value and sensitivity to monitor treatment-induced changes have not yet been established and are still under investigation.

Minimally invasive intraoperative estimation of left-ventricular end-systolic elastance with phenylephrine as loading intervention.

BACKGROUND: Left-ventricular end-systolic elastance (Ees) is an index of cardiac contractility, but the invasive nature of its assessment has limited perioperative application. We explored the feasibility of a minimally invasive method of Ees estimation for perioperative assessment of cardiac function and evaluated the suitability of phenylephrine as a loading intervention. METHODS: In 17 surgical patients, Ees was determined as the slope of the end-systolic pressure-volume relation, which was obtained from non-invasive or invasive continuous arterial pressure measurements and left-ventricular volume determinations using transoesophageal echocardiography (TOE). Ees was determined using as loading interventions preload reduction by inferior vena cava compression (IVCC) and afterload increase by phenylephrine administration. RESULTS: Median invasive Ees determined with phenylephrine estimated 1.05 (0.59-1.21) mm Hg ml(-1) and with IVCC 0.58 (0.31-1.13) mm Hg ml(-1). Bland-Altman analysis to evaluate the level of agreement between minimally invasive and invasive Ees estimation revealed a bias of -0.03 (0.12) mm Hg ml(-1) with limits of agreement from -0.27 to 0.21 mm Hg ml(-1) and the percentage error was 33%. Agreement between Ees obtained with phenylephrine and IVCC revealed a bias of 0.15 (0.69) mm Hg ml(-1) with limits of agreement from -1.21 to 1.51 mm Hg ml(-1) and a percentage error of 149%. CONCLUSIONS: It is feasible to determine Ees combining continuous non-invasive arterial pressure measurements and left-ventricular volume determinations with TOE. However, administration of phenylephrine cannot substitute IVCC as a loading intervention, indicating that estimation of Ees in the intraoperative setting remains a challenge.

The effect of oxygenator mechanical characteristics on energy transfer during clinical cardiopulmonary bypass.

The hollow-fibre oxygenator is a key component of any extracorporeal circuit used to provide cardiopulmonary bypass (CPB) during open-heart surgery. Since the oxygenator is placed downstream of the pump, the energy losses over it have a direct impact on the quality of pulsatile pressure and flow waveforms. The objective of this study was to describe the effects of hydrodynamic characteristics of the oxygenator on energy transfer during pulsatile, normothermic CPB. Twenty-three adult patients scheduled for coronary bypass surgery were divided randomly into two groups, using either an oxygenator (Group 1) with a relatively high-resistance and low-compliance (2079 ± 148 dyn.s.cm(-5) and 0.00348 ± 0.00071 ml.mmHg(-1), respectively) or an oxygenator (Group 2) with a relatively low-resistance and high-compliance (884 ± 464 dyn.s.cm(-5) and 0.01325 ± 0.00161 ml.mmHg(-1), respectively). During perfusion, pre- and post-oxygenator pressures, radial artery pressure, and blood flow were recorded simultaneously. A 32% decline of mean pressure was observed in Group 1 and a 16% decline in Group 2 (p<0.0001). Another decrease by approximately 73% in mean pressure in the rest of the perfusion system was noted in both groups. The mean radial artery pressure did not differ between the groups (74 ± 6 mmHg in Group 1 and 73 ± 6 mmHg in Group 2, p=0.608). Although lower total energy transfer indices were noticed through the low-resistance oxygenator (Group 2), both oxygenators showed a decrease of the generated pump oscillatory energy of approximately 50%. Despite the differences in resistance and compliance of the hollow-fibre oxygenators used, both oxygenators cause a comparable loss of generated oscillatory energy. Exclusion of the oxygenator downstream of the pulsatile pump would improve energy transfer during CPB.

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre)diabetes: The Maastricht Study.

AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown. METHODS: Subjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO. RESULTS: Fasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h [fasting: 1.12 (95% CI: 0.97-1.29); post-OGTT: 1.19 (1.01-1.41)], eGFR<60mL/min/1.73 m2 [fasting: 1.58 (95% CI: 1.38-1.82), post-OGTT: 1.57 (1.34-1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01-2.53), post-OGTT: 1.38 (0.77-2.48)]. No associations with prior CVD were found. CONCLUSION: Fasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.

Reserve-driven flow control for extracorporeal life support: proof of principle.

Extracorporeal life support systems lack volume-buffering capacity. Therefore, any decrease in venous intravascular volume available for drainage may result in acutely reduced support flow. We recently developed a method to quantify drainable volume and now conceived a reserve-driven pump control strategy, which is different from existing pressure or flow servo control schemes. Here, we give an outline of the algorithm and present animal experimental data showing proof of principle. With an acute reduction in circulatory volume (10-15%), pump flow immediately dropped from 4.1 to 1.9 l/min. Our pump control algorithm was able to restore bypass flow to 3.2 l/min (about 80% of the original level) and, thereby, reduced the duration of the low-flow condition. This demonstrates that a reserve-driven pump control strategy, based on the continuous monitoring of drainable volume, may maintain extracorporeal circulatory support flow, despite serious changes in filling conditions.

Orthogonal B-Mode Evaluation of Common Carotid Artery Plaques Reveals the Absence of Outward Remodeling.

To properly assess morphologic and dynamic parameters of arteries and plaques, we propose the concept of orthogonal distance measurements, that is, measurements made perpendicular to the local lumen axis rather than along the ultrasound beam (vertical direction for a linear array). The aim of this study was to compare orthogonal and vertical artery and lumen diameters at the site of a plaque in the common carotid artery (CCA). Moreover, we investigated the interrelationship of orthogonal diameters and plaque size and the association of artery parameters with plaque echogenicity. In 29 patients, we acquired a longitudinal B-mode ultrasound recording of plaques at the posterior CCA wall. After semi-automatic segmentation of end-diastolic frames, diameters were extracted orthogonally along the lumen axis. To establish inter-observer variability of diameters obtained at the location of maximal plaque thickness, a second observer repeated the analysis (subset N = 21). Orthogonal adventitia-adventitia and lumen diameters could be determined with good precision (coefficient of variation: 1%-5%. However, the precision of the change in lumen diameter from diastole to systole (distension) at the site of the plaque was poor (21%-50%). The orthogonal lumen diameter was significantly smaller than the vertical lumen diameter (p <0.001). Surprisingly, the plaques did not cause outward remodeling, that is, a local increase in adventitia-adventitia distance at the site of the plaque. The intra- and inter-observer precision of diastolic-systolic plaque compression was poor and of the same order as the standard deviation of plaque compression. The orthogonal relative lumen distension was significantly lower for echogenic plaques, indicating a higher stiffness, than for echolucent plaques (p <0.01). In conclusion, we illustrated the feasibility of extracting orthogonal CCA and plaque dimensions, albeit that the proposed approach is inadequate to quantify plaque compression.

A Rare Case of Intermittent Claudication Associated with Impaired Arterial Vasodilation.

Exercise-related intermittent claudication is marked by reduced blood flow to extremities caused by either stenosis or impaired vascular function. Although intermittent claudication is common in the elderly, it rarely occurs in the young and middle-aged individuals. Here, we report a case of exercise-related claudication in a 41-year-old woman, in the absence of overt vascular pathology. Using a series of imaging and functional tests, we established that her complaints were due to impaired arterial vasodilation, possibly due to a defect in nitrous oxide-mediated dilation. The symptoms were reversible upon administration of a calcium antagonist, showing reversibility of the vascular impairment. Identification of reversible vascular "stiffness" merits consideration in young and otherwise healthy subjects with claudication of unknown origin.