The effect of ischemia and reperfusion on microvascular function: a human in vivo comparative study with conduit arteries

Although microvascular dysfunction is of critical importance in the pathophysiology of myocardial ischemic syndromes, no study has investigated whether there are differences in the sensitivity to ischemia and reperfusion injury between microvessels and conduit arteries. Ten healthy young nonsmoking male volunteers (age range 24-45) were enrolled. Parameters measured included radial (conduit) artery (endothelium-dependent) flow-mediated dilation, microvascular cutaneous reactive hyperemia (using laser Doppler) and acetylcholine-induced microvascular vasodilation (laser Doppler iontophoresis). Data were acquired before and after ischemic injury (15 minutes of ischemia of the brachial artery followed by 15 minutes reperfusion) and analyzed in a randomized, blinded fashion. Conduit artery FMD was significantly blunted after ischemia (before: 7.5 +/- 1.1%; after: 2.9 +/- 1.0%, P < 0.05). Conversely, ischemia had no effect on microvascular reactive hyperemia (P = ns) and acetylcholine-induced vasodilation (P = ns). Using a human in vivo model, we demonstrate that microvessels are more resistant to ischemic injury as compared to conduit arteries.     

Familial HDL deficiency due to ABCA1 gene mutations with or without other genetic lipoprotein disorders

Mutations in ABCA1 have been shown to be the cause of Tangier disease (TD) and some forms of familial hypoalphalipoproteinemia (HA), two genetic disorders characterized by low plasma HDL levels. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of which are previously unreported. Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1. Two subjects found to be compound heterozygotes for ABCA1 mutations did not have overt clinical manifestations of TD. Three subjects, all with premature coronary artery disease (pCAD), had a combination of genetic defects. Besides being heterozygotes for ABCA1 mutations, two of them were also carriers of the R3500Q substitution in apolipoprotein B and the third was a carrier of N291S substitution in lipoprotein lipase. By extending family studies we identified 17 heterozygotes for ABCA1 mutations. Plasma HDL-C and Apo A-I values in these subjects were 38.3 and 36.9% lower than in unaffected family members and similar to the values found in heterozygotes for Apo A-I gene mutations which prevent Apo A-I synthesis. This survey underlines the allelic heterogeneity of ABCA1 mutations and suggests that: (i) TD subjects, if asymptomatic, may be overlooked and (ii) there may be a selection bias in genotyping towards carriers of ABCA1 mutations who have pCAD possibly related to a combination of genetic and environmental cardiovascular risk factors.     

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.     

Pain perception and laser evoked potentials during menstrual cycle in migraine

The association between estrogens “withdrawal” and attacks of migraine without aura is well-known. The aim of the study was to examine the features of laser evoked potentials (LEPs), including habituation, in women suffering from migraine without aura versus healthy controls, during the pre-menstrual and late luteal phases. Nine migraine without aura and 10 non-migraine healthy women, were evaluated during the pre-menstrual phase and late luteal phase. The LEPs were recorded during the inter-critical phase. The right supraorbital zone and the dorsum of the right hand were stimulated. Three consecutive series of 20 laser stimuli were obtained for each stimulation site. Laser pain perception was rated by a 0–100 VAS after each stimulation series. Migraine patients exhibited increased LEPs amplitude and reduced habituation compared to normal subjects. Laser-pain perception was increased during the pre-menstrual phase in both patients and controls. Migraine patients and controls showed increased P2 and N2–P2 amplitude in the pre-menstrual phase, on both stimulation sites. During the pre-menstrual phase the N2–P2 habituation appeared to be reduced in both migraine and healthy women. The estrogen withdrawal occurring during the menstrual cycle may favor reduced habituation of nociceptive cortex, which may facilitate pain symptoms and migraine in predisposed women.     

Thrombosis,fracture, and percutaneous removal of a patent foramen ovale closure device 1 month after successful deployment

Several different devices have been developed for the percutaneous closure of interatrial defects and patent foramen ovale. Although the implantation of these devices is both safe and effective, a number of complications, both in the early and the late follow‐up, may occur. We describe a case of device fracture manifested early (1 month after implantation) with the formation of massive thrombosis on the right atrial disc. The patient was treated with anticoagulants and the device was percutaneously retrieved. Our images allowed early noninvasive therapy and emphasize the need for echocardiographic follow‐up early after implantation. © 2010 Wiley‐Liss, Inc.     

A novel mutation of the apolipoprotein A-I gene in a family with familial combined hyperlipidemia

We report a large family in which four members showed a plasma lipid profile consistent with the clinical diagnosis of familial combined hyperlipidemia (FCHL). One of these patients was found to have markedly reduced HDL cholesterol (HDL-C) (0.72 mmol/l) and Apo A-I (72 mg/dl) levels, a condition suggestive of the presence of a mutation in one of the HDL-related genes. The analysis of APOA1 gene revealed that this patient was heterozygous for a cytosine insertion in exon 3 (c.49–50 ins C), resulting in a frame-shift and premature stop codon at position 26 of pro-Apo A-I (Q17PFsX10). This novel mutation, which prevents the synthesis of Apo A-I, was also found in four family members, including three siblings and the daughter of the proband. Carriers of Apo A-I mutation had significantly lower HDL-C and Apo A-I than non-carriers family members (0.77 ± 0.15 mmol/l vs. 1.15 ± 0.20 mmol/l, P < 0.005; 71.4 ± 9.1 mg/dl vs. 134.0 ± 14.7 mg/dl, P < 0.005, respectively). Two of the APOA1 mutation carriers, who were also heavy smokers, had fibrous plaques in the carotid arteries causing mild stenosis (20%). The intimal-media thickness in the two other adult carriers was within the normal range. The other non-carriers family members with FCHL had either overt vascular disease or carotid atherosclerosis at ultrasound examination. This observation suggests that the low HDL-C/low Apo A-I phenotype may result from a genetic defect directly affecting HDL metabolism, even in the context of a dyslipidemia which, like FCHL, is associated with low plasma HDL-C.     

Very late thrombosis in a bare metal stent: an under-recognized problem

Recent publications have emphasized the concept that restenosis of a bare metal stent is not as clinically benign as previously believed. A case of very late (seven years) thrombosis after implantation of a bare metal stent is described. While doubts on the long-term safety of drug-eluting stents are debated, registry data and clinical reports suggest that the long-term safety of coronary bare metal stent implantation should also be reconsidered.     

Habituation of single CO2 laser–evoked responses during interictal phase of migraine

A reduced habituation of averaged laser–evoked potential (LEP) amplitudes was previously found in migraine patients. The aim of the present study was to assess the habituation of single LEP responses and pain sensation during the interictal phase in migraine patients. Fourteen migraine patients were compared with ten control subjects. The pain stimulus was laser pulses, generated by CO₂ laser, delivered to right supraorbital zone. Patients were evaluated during attack–free conditions. The LEP habituation was studied by measuring the changes of LEP amplitudes across and within three consecutive repetitions of 21 non–averaged trials. In migraine patients the N2–P2 wave amplitudes did not show a tendency toward habituation across and, above all, within the three repetitions. Anomalous behaviour of nociceptive cortex during the interictal phase of migraine may predispose patients to headache occurrence and persistence.     

VATS biopsy for undetermined interstitial lung disease under non-general anesthesia: comparison between uniportal approach under intercostal block vs. three-ports in epidural anesthesia

Objective

Video-assisted thoracoscopic (VATS) biopsy is the gold standard to achieve diagnosis in undetermined interstitial lung disease (ILD). VATS lung biopsy can be performed under thoracic epidural anesthesia (TEA), or more recently under simple intercostal block. Comparative merits of the two procedures were analyzed.

Methods

From January 2002 onwards, a total of 40 consecutive patients with undetermined ILD underwent VATS biopsy under non-general anesthesia. In the first 20 patients, the procedures were performed under TEA and in the last 20 with intercostal block through a unique access. Intraoperative and postoperative variables were retrospectively matched.

Results

Two patients, one from each group, required shift to general anesthesia. There was no 30-day postoperative mortality and two cases of major morbidity, one for each group. Global operative time was shorter for operations performed under intercostal block (P=0.041). End-operation parameters significantly diverged between groups with better values in intercostal block group: one-second forced expiratory flow (P=0.026), forced vital capacity (P=0.017), oxygenation (P=0.038), PaCO₂ (P=0.041) and central venous pressure (P=0.045). Intraoperative pain coverage was similar. Significant differences with better values in intercostal block group were also experienced in 24-hour postoperative quality of recovery-40 questionnaire (P=0.038), hospital stay (P=0.033) and economic expenses (P=0.038). Histology was concordant with radiologic diagnosis in 82.5% (33/40) of patients. Therapy was adjusted or modified in 21 patients (52.5%).

Conclusions

Uniportal VATS biopsies under intercostal block can provide better intraoperative and postoperative outcomes compared to TEA. They allow the indications for VATS biopsy in patients with undetermined ILD to be extended.     

Axillary artery access for interventional procedures.

PURPOSE: To evaluate axillary artery access for the interventional treatment of carotid or splanchnic arteries that have angulated takeoff or complex anatomy when larger catheters (up to 9 F) are needed. TECHNIQUE: The axillary artery approach was used to treat the left internal carotid artery (ICA) in 3 patients (2 angulated takeoffs and 1 bovine arch) and a celiac axis aneurysm. An 8-F, 45-cm-long introducer sheath was inserted for the carotid procedures, whereas a 9-F, 90-cm sheath was chosen for the celiac aneurysm. Cerebral protection and stenting were successfully performed in all carotid patients; an 8x40-mm stent-graft was implanted to exclude the celiac artery aneurysm. An 8-F vascular closure device was used in the axillary arteries; hemostasis was immediate, and no hematoma or other complications were recorded in follow-up. CONCLUSIONS: This preliminary experience revisits the axillary approach as an alternative access route for interventional procedures. In association with a vascular closure device, this approach should be considered as a useful and safe option for those interventional procedures in which larger sheaths or catheters are required to cope with difficult arterial anatomies.