The Correlation Between Wall Shear Stress and Plaque Composition in Advanced Human Carotid Atherosclerosis.

The role of wall shear stress (WSS) in atherosclerotic plaque development is evident, but the relation between WSS and plaque composition in advanced atherosclerosis, potentially resulting in plaque destabilization, is a topic of discussion. Using our previously developed image registration pipeline, we investigated the relation between two WSS metrics, time-averaged WSS (TAWSS) and the oscillatory shear index (OSI), and the local histologically determined plaque composition in a set of advanced human carotid plaques. Our dataset of 11 carotid endarterectomy samples yielded 87 histological cross-sections, which yielded 511 radial bins for analysis. Both TAWSS and OSI values were subdivided into patient-specific low, mid, and high tertiles. This cross-sectional study shows that necrotic core (NC) size and macrophage area are significantly larger in areas exposed to high TAWSS or low OSI. Local TAWSS and OSI tertile values were generally inversely related, as described in the literature, but other combinations were also found. Investigating the relation between plaque vulnerability features and different combinations of TAWSS and OSI tertile values revealed a significantly larger cap thickness in areas exposed to both low TAWSS and low OSI. In conclusion, our study confirmed previous findings, correlating high TAWSS to larger macrophage areas and necrotic core sizes. In addition, our study demonstrated new relations, correlating low OSI to larger macrophage areas, and a combination of low TAWSS and low OSI to larger cap thickness.

Assessment of Spinal Cord Ischemia With Near-Infrared Spectroscopy: Myth or Reality?

Non-invasive near-infrared spectroscopy is gaining popularity in the detection of spinal cord ischemia following aortic aneurysm repair. However, practical recommendations are lacking. This review focuses on the physiological and anatomical background, as well as on the clinical implementations of near-infrared spectroscopy as a tool for monitoring ischemia of the spinal cord. Clinical recommendations based on the currently available evidence are rendered.

An MRI-based method to register patient-specific wall shear stress data to histology.

Wall shear stress (WSS), the frictional force exerted on endothelial cells by blood flow, is hypothesised to influence atherosclerotic plaque growth and composition. We developed a methodology for image registration of MR and histology images of advanced human carotid plaques and corresponding WSS data, obtained by MRI and computational fluid dynamics. The image registration method requires four types of input images, in vivo MRI, ex vivo MRI, photographs of transversally sectioned plaque tissue and histology images. These images are transformed to a shared 3D image domain by applying a combination of rigid and non-rigid registration algorithms. Transformation matrices obtained from registration of these images are used to transform subject-specific WSS data to the shared 3D image domain as well. WSS values originating from the 3D WSS map are visualised in 2D on the corresponding lumen locations in the histological sections and divided into eight radial segments. In each radial segment, the correlation between WSS values and plaque composition based on histological parameters can be assessed. The registration method was successfully applied to two carotid endarterectomy specimens. The resulting matched contours from the imaging modalities had Hausdorff distances between 0.57 and 0.70 mm, which is in the order of magnitude of the in vivo MRI resolution. We simulated the effect of a mismatch in the rigid registration of imaging modalities on WSS results by relocating the WSS data with respect to the stack of histology images. A 0.6 mm relocation altered the mean WSS values projected on radial bins on average by 0.59 Pa, compared to the output of original registration. This mismatch of one image slice did not change the correlation between WSS and plaque thickness. In conclusion, we created a method to investigate correlations between WSS and plaque composition.

The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice.

The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in patients with previous heart failure. However, in patients without heart failure, no beneficial effect of Ivabradine was observed. Animal studies suggested a preventive effect of Ivabradine on atherosclerosis which was due to an increase in wall shear stress (WSS), the blood flow-induced frictional force exerted on the endothelium, triggering anti-inflammatory responses. However, data on the effect of Ivabradine on WSS is sparse. We aim to study the effect of Ivabradine on (i) the 3D WSS distribution over a growing plaque and (ii) plaque composition. We induced atherosclerosis in ApoE-/- mice by placing a tapered cast around the right common carotid artery (RCCA). Five weeks after cast placement, Ivabradine was administered via drinking water (15 mg/kg/day) for 2 weeks, after which the RCCA was excised for histology analyses. Before and after Ivabradine treatment, animals were imaged with Doppler Ultrasound to measure blood velocity. Vessel geometry was obtained using contrast-enhanced micro-CT. Time-averaged WSS during systole, diastole and peak WSS was subsequently computed. Ivabradine significantly decreased heart rate (459 ± 28 bpm vs. 567 ± 32 bpm, p < 0.001). Normalized peak flow significantly increased in the Ivabradine group (124.2% ± 40.5% vs. 87.3% ± 25.4%, p < 0.05), reflected by an increased normalized WSS level during systole (110.7% ± 18.4% vs. 75.4% ± 24.6%, p < 0.05). However, plaque size or composition including plaque area, relative necrotic core area and macrophage content were not altered in mice treated with Ivabradine compared to controls. We conclude that increased WSS in response to Ivabradine treatment did not affect plaque progression in a murine model.

Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice.

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE-/- mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition.

Phenotypic spectrum of Charcot-Marie-Tooth disease due to LITAF/SIMPLE mutations: a study of 18 patients.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) 1C due to mutations in LITAF/SIMPLE is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with PMP22 mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP). METHODS: Charcot-Marie-Tooth 1C patients were followed-up in referral centres for neuromuscular diseases or were identified by familial survey. All CMT1A and HNPP patients were recruited at the referral centre for neuromuscular diseases of Pitié-Salpêtrière Hospital. RESULTS: Two phenotypes were identified amongst 18 CMT1C patients: the classical CMT form ('CMT-like', 11 cases) and a predominantly sensory form ('sensory form', seven cases). The mean CMT neuropathy score was 4.45 in CMT1C patients. Motor nerve conduction velocities in the upper limbs were significantly more reduced in CMT1A than in CMT1C patients. On the other hand, the motor nerve conduction velocity of the median nerve was significantly lower in CMT1C compared to the HNPP group. Distal motor latency was significantly more prolonged in CMT1A patients compared to the CMT1C and HNPP groups, the latter two groups having similar distal motor latency values. Molecular analysis revealed five new LITAF/SIMPLE mutations (Ala111Thr, Gly112Ala, Trp116Arg, Pro135Leu, Arg160Cys). CONCLUSIONS: Our study delineates CMT1C as mostly a mild form of neuropathy, and gives clinical and electrophysiological clues differentiating CMT1C from CMT1A and HNPP. Delineating phenotypes in CMT subtypes is important to orient molecular diagnosis and to help to interpret complex molecular findings.

The effect of hydroxyethyl starch 6% 130/0.4 compared with gelatin on microvascular reactivity.

We compared the effects on microvascular reactivity of hydroxyethylstarch (Volulyte(®) ) and gelatin (Geloplasma(®) ) during acute haemodilution. The hypothesis was that Volulyte would provide better microvascular reactivity than Geloplasma. Forty patients undergoing elective cardiac surgery were randomly assigned to receive either Volulyte or Geloplasma as the exclusive priming solution of the cardiopulmonary bypass. To evaluate microvascular reactivity, postocclusive reactive hyperaemia was examined before and after cardiopulmonary bypass. Microvascular reactivity assessments included the rate of the occlusion and reperfusion slopes and reperfusion times. After cardiopulmonary bypass, increases in reperfusion time were significantly smaller in the Volulyte group (3 (-27 to 9 [-35 to 33]%) vs 29 (-17 to 76 [-34 to 137]%) in the Geloplasma group, p = 0.02 between groups). Rate of reperfusion increased in the Volulyte group (26 (-17 to 43 [-59 to 357])%), whereas it decreased in the Geloplasma group (-22 (-47 to 16 [-84 to 113])%), p = 0.02 between groups. The shorter reperfusion times and increased reperfusion rate suggest that Volulyte maintains better microvascular reactivity than Geloplasma.

Influence of variations in systemic blood flow and pressure on cerebral and systemic oxygen saturation in cardiopulmonary bypass patients.

BACKGROUND: Although both pressure and flow are considered important determinants of regional organ perfusion, the relative importance of each is less established. The aim of the present study was to evaluate the impact of variations in flow, pressure, or both on cerebral and whole-body oxygen saturation. METHODS: Thirty-four consenting patients undergoing elective cardiac surgery on cardiopulmonary bypass were included. Using a randomized cross-over design, four different haemodynamic states were simulated: (i) 20% flow decrease, (ii) 20% flow decrease with phenylephrine to restore baseline pressure, (iii) 20% pressure decrease with sodium nitroprusside (SNP) under baseline flow, and (iv) increased flow with baseline pressure. The effect of these changes was evaluated on cerebral (Sc(O2)) and systemic (Sv(O2)) oxygen saturation, and on systemic oxygen extraction ratio (OER). Data were assessed by within- and between-group comparisons. RESULTS: Decrease in flow was associated with a decrease in [from 63.5 (7.4) to 62.0 (8.5) %, P<0.001]. When arterial pressure was restored with phenylephrine during low flow, Sc(O2) further decreased from 61.0 (9.7) to 59.2 (10.2) %, P<0.001. Increase in flow was associated with an increase in Sc(O2) from 62.6 (7.7) to 63.6 (8.9) %, P=0.03, while decreases in pressure with the use of SNP did not affect Sc(O2). Sv(O2) was significantly lower (P<0.001) and OER was significantly higher (P<0.001) in the low flow arms. CONCLUSIONS: In the present elective cardiac surgery population, Sc(O2) and Sv(O2) were significantly lower with lower flow, regardless of systemic arterial pressure. Moreover, phenylephrine administration was associated with a reduced cerebral and systemic oxygen saturation.

Relation between mixed venous oxygen saturation and cerebral oxygen saturation measured by absolute and relative near-infrared spectroscopy during off-pump coronary artery bypass grafting.

BACKGROUND: We hypothesized that previously reported contradictory results regarding the equivalence of mixed venous (Smv(O(2))) and cerebral (rS(c)O(2)) oxygen saturation might be related to time delay issues and to measurement technology. In order to explore these two factors, we designed a prospective clinical study comparing with relative (INVOS(®)) and absolute (Foresight(®)) rS(c)O(2) measurements. METHODS: Forty-two consenting patients undergoing elective off-pump coronary artery bypass grafting were included. Two INVOS and two Foresight sensors continuously registered rS(c)O(2). Smv(O(2)) was measured continuously via a pulmonary artery catheter. Data were assessed by within- and between-group comparisons and correlation analysis. RESULTS: A similar time delay of 19 (4) and 18 (4) s was found for compared with rS(c)O(2) measurements by Foresight and INVOS, respectively, during haemodynamic changes. After adjusting for this time delay, the correlation between Smv(O(2)) and rS(c)O(2) increased from r=0.25 to 0.75 (P<0.001) for Foresight, and from r=0.28 to 0.73 (P<0.001) for INVOS. Comparison of Foresight and INVOS revealed significant differences in absolute rS(c)O(2) values (range 58-89% for Foresight and 28-95% for INVOS). Changes in rS(c)O(2) in response to acute haemodynamic alterations were significantly more pronounced with INVOS compared with Foresight (P<0.001). CONCLUSIONS: Considering the important time delay with Smv(O(2)), rS(c)O(2) seems to reflect more appropriately acute haemodynamic alterations. This might suggest its use as a valid alternative to invasive monitoring of tissue oxygen saturation. Relative and absolute rS(c)O(2) measurements demonstrated significant differences in measured rS(c)O(2) values and in the magnitude of rS(c)O(2) changes during haemodynamic alterations.

Near-infrared spectroscopy (NIRS) monitoring in contemporary anesthesia and critical care.

Near-infrared spectroscopy (NIRS) is a noninvasive technology that continuously monitors regional tissue oxygenation. Originally used for assessment of oxygen saturation of the brain, its use has now been expanded to evaluation of oxygenation of tissues other than the brain. There is also growing evidence for the larger applicability of NIRS as an estimate of systemic venous saturation in correspondence with the adequacy of the circulatory status. New and promising advances may further this technology to become part of our standard armamentarium, in order to optimize patient care in daily anesthesia practice. The present paper briefly reviews the basic principles of operation, the inherent limitations of the technology and the clinical data that have been acquired with NIRS monitoring in the broad field of acute clinical medicine.

Chromosome aneuploidy in the spermatozoa of two men with globozoospermia.

The objective of this study was to determine the aneuploidy level in spermatozoa in two men with globozoospermia. Sperm nuclei were analysed by fluorescence in-situ hybridization (FISH) in two infertile males with globozoospermia. Dual FISH for chromosomes 7 and 9, 13 and 21, and triple FISH for chromosomes X, Y, and 18 was performed. The main outcome measured was meiotic segregation differences between both globozoospermic men and controls. A statistically significant difference in disomies 13 and 21 was found between patients 1 and 2. The diploidy rate of spermatozoa of patient 1 (0.876%) was significantly increased compared with that of patient 2 (0.304%) and control men (0.293%). In conclusion there seems to be a slightly increased frequency of aneuploidy in round-headed spermatozoa. However, it is unlikely that these aneuploid spermatozoa would be used in assisted reproduction techniques.

Estimation of myocardial performance in CABG patients.

Myocardial performance index (MPI) permits a relative easy estimation of global left ventricular (LV) systolic and diastolic function. It was shown that MPI inversely correlated strongly with the maximum derivative of LV pressure with respect to time (+dP/dtmax). The current study evaluated the change of MPI during and immediately after coronary artery bypass surgery (CABG) surgery and analyzed the relationship between MPI and hydraulic energy (exemplified by preload adjusted maximal power-PAMP) during that same period. The study was conducted in 45 patients undergoing CABG. After induction of anaesthesia, 10 min after revascularization and 2 h postoperatively, haemodynamics were assessed. Preload was characterized by LV end-diastolic area indexed for BSA (LVEDAI); afterload was estimated by arterial elastance (Ea) and indexed systemic vascular resistance (SVRI). Global myocardial performance was indicated in terms of MPI and contractility was achieved by PAMP. Myocardial performance index increased postoperatively (0.44 +/- 0.13, 0.37 +/- 0.17 and 0.50 +/- 0.16, respectively; P < 0.001). Preload adjusted maximal power did not alter significantly (1.90 +/- 1.24, 2.02 +/- 1.34 and 2.12 +/- 1.00 W cm(-2)*10(4), respectively). Left ventricular enddiastolic area indexed did not change. Arterial elastance augmented to 0.76 +/- 0.39, 0.80 +/- 0.40 and 1.01 +/- 0.43 mmHg ml(-1), respectively; P < 0.001. Systemic vascular resistance did not change. A relationship was found between 1-MPI/LVEDAI2 and PAMP (R2 = 0.50). This study shows that in the setting of CABG surgery, MPI appears to be a good measure of global LV function.

Propofol versus remifentanil for monitored anaesthesia care during colonoscopy.

BACKGROUND AND OBJECTIVE: We conducted an open, prospective, randomized study to compare the efficacy, safety and recovery characteristics of remifentanil or propofol during monitored anaesthesia care in patients undergoing colonoscopy. METHODS: Forty patients were randomly assigned to receive either propofol (1 mg kg(-1) followed by 10 mg kg (-1) h(-1), n = 20) or remifentanil (0.5 microg kg(-1) followed by 0.2 microg kg(-1) min(-1), n = 20). The infusion rate was subsequently adapted to clinical needs. RESULTS: In the propofol group, arterial pressure and heart rate decreased significantly from the baseline. These variables remained unchanged in the remifentanil group, but hypoventilation occurred in 55% of patients. Early recovery was delayed in the propofol group (P < 0.002). Recovery of cognitive and psychomotor functions was faster in the remifentanil group. Fifteen minutes after anaesthesia, the Digit Symbol Substitution Test score was 28.6 +/- 12.8 versus 36.2 +/- 9.4 and the Trieger Dot Test score was 25.6 +/- 8.1 versus 18.7 +/- 4.1 in the propofol and remifentanil groups, respectively (both P < 0.05). Patient satisfaction, using a visual analogue scale, was higher in the propofol group (96 +/- 7 versus 77 +/- 21, P < 0.001). CONCLUSIONS: Remifentanil proved efficient in reducing pain during colonoscopy. Emergence times were shorter and the recovery of cognitive function was faster with remifentanil compared with propofol. Remifentanil provided a smoother haemodynamic profile than propofol; however, the frequent occurrence of remifentanil-induced hypoventilation requires the cautious administration of this agent.

Off-pump coronary surgery: surgical strategy for the high-risk patient.

OBJECTIVE: In a retrospective study, we compared two groups of consecutive patients operated by the same team during the year 2000 for coronary artery disease with the use of extracorporeal circulation (group 1, n=230) or on the beating heart using the Octopus II plus stabiliser (group 2, n=228). High-risk patients were identified by a EuroSCORE plus 6. EuroSCORE definitions and predicted risk models were utilized to compare the variables of the groups. METHODS: There were no significant differences between the preoperative variables of the groups in age, gender, left ventricular function, diabetes and peripheral vascular and renal disease as is indicated by the Euroscore (resp. 4.7/5.1 p=0.107). Calcification of the ascending aorta and chronic obstructive lung disease were statistically significant more prevalent in the beating heart group. No differences in preoperative variables in the high-risk patients group (Euroscore 8.5/8.1 p=0.356) except for calcification of the ascending aorta. RESULTS: All patients underwent a full revascularisation through a midline sternotomy. Significant more distal anastomoses were performed in group 1 (3.7 per patient (1-6)) with regard to group 2 (2.9 per patient (1-6)). Anesthesia, postoperative treatment and follow up were equal for both groups. A significant lower incidence of atrial fibrillation (p=0.010), shorter ICU stay (p=0.031) and renal insufficiency (p=0.033) was reported in group 2. In the low risk group, we could not diagnose any difference between the two groups, except for atrial fibrillation. The benefits of the beating heart surgery however were more pronounced in the high-risk patient as is indicated by a significant reduction of the ICU stay by 1 day (3.5d/2.5d (p=0.028)), better preservation of the renal function (p=0.017) and a significant reduction of the length of hospital stay by more than two days (p=0.040). A lower incidence of atrial fibrillation, however not significant. CONCLUSION: In our experience, beating heart surgery is a safe alternative for conventional coronary heart surgery. High-risk patients do benefit most from this technique. It became our first choice in the elderly patient and patients presenting with higher co-morbidities.

Remifentanil infusion for cardiac catheterization in children with congenital heart disease.

BACKGROUND: Cardiac catheterization of children with congenital heart disease is increasingly being performed under general anesthesia. Haemodynamic stability during anesthesia and fast and adequate recovery after the procedure is crucial in these patients. We performed a pilot study to evaluate hemodynamic stability when using remifentanil for anesthesia during cardiac catheterization. We also evaluated extubation times and recovery characteristics. METHODS: In a randomized, prospective, double-blind study 30 children (aged 1.5-20 months) received a continuous infusion of either 0.2 (group 0.2) or 0.3 microg/kg/min remifentanil (group 0.3) as part of a balanced anesthesia with 0.6 MAC sevoflurane. Heart rate, noninvasive arterial blood pressure, end tidal CO2 and pulse oxymetry were monitored throughout the procedure. Extubation times were noted, and recovery from anesthesia was evaluated using Aldrete scores. RESULTS: : Haemodynamic response to intubation was well blunted in both groups. No significant changes in hemodynamic variables were noted from induction of anesthesia until 10 min after intubation. From then on there was a decrease in HR and systolic arterial pressure, which remained significant throughout the procedure in both groups. Extubation times were similar in both groups: 7.3 min (2,1) in group 0.2 vs. 6.6 min (2,1) in group 0.3 (NS). The number of patients with an Aldrete score of nine or more was 14 (group 0.2) vs. 15 (group 0.3), 10 min after extubation (NS). CONCLUSION: Both dose regimens of remifentanil provided stable hemodynamic conditions during anesthesia for cardiac catheterization of children with congenital heart disease and allowed for rapid and adequate recovery.

[Dyggve-Melchior-Clausen syndrome: differential diagnosis of mucopolysaccharidosis type IV or Morquio disease]. / Le syndrome de Dyggve-Melchior-Clausen: diagnostic différentiel de la mucopolysaccharidose de type IV ou maladie de Morquio.

UNLABELLED: Dyggve-Melchior-Clausen syndrome (DMCS) is an autosomal recessive skeletal dysplasia. Clinical and radiological similarities with Morquio's syndrome can initially lead wrongly to this diagnosis. CASE REPORT: A nine-year-old boy had mental retardation and progressive postnatal dwarfism. Platyspondyly and dysplastic epiphyses and metaphyses resembled those of Morquio's disease; however, clinical and radiological data led to the diagnosis of DMCS. CONCLUSION: Clinical and paraclinical features allowing the differentiation of Morquio's syndrome and DMCS are discussed. Initial clinical presentation may be similar, but the intellectual prognosis is different.