Hypertrophic cardiomyopathy--state of the art in 2007

Hypertrophic cardiomyopathy (HCM) is a primary disease of the sarcomere, with considerable genetic heterogeneity and variability in phenotypic expression, whose main complication is sudden cardiac death (SCD). Genetic aspects of HCM, its molecular pathophysiology and genotype-phenotype relationships are the subject of this review, which is aimed at better understanding of practical management in this patient population. As HCM is a genetic disease whose initial manifestation can be sudden death, it is essential to establish the diagnosis at an early stage, to proceed with risk stratification and implementation of SCD prevention strategies, and to promote genetic counseling of patients and screening of their families. Detection of pathological mutations through progressive sequencing of the genes most commonly involved is the most efficient way to diagnose HCM, even in the absence of clinical evidence of the disease. Identification of individuals at high risk of SCD is a major challenge in the management of this population, since SCD can be prevented by use of an implantable cardioverter-defibrillator. The selection of patients for prophylactic implantation of these devices, particularly those who have only one major risk factor, is currently the subject of controversy.     

Retinal oscillatory potentials recorded by dermal electrodes

Dermal electrodes allowed the recording of retinal oscillatory potentials with similar shape and timing as tracings obtained with convential corneal electrodes. Normative data is presented. We concluded that dermal electrodes were a reproducible and more comfortable method of testing.The results were presented in part at the XXIV I.S.C.E.V. Symposium, Palermo (Italy), May 10–15, 1986.     

Impact of carvedilol on the mitochondrial damage induced by hypoxanthine and xantine oxidase--what role in myocardial ischemia and reperfusion?

OBJECTIVES: The cardioprotective effects of carvedilol (CV) may be explained in part by interactions with heart mitochondria. The objective of this work was to study the protection afforded by CV against oxidative stress induced in isolated heart mitochondria by hypoxanthine and xanthine oxidase (HX/XO), a well-known source of reactive oxygen species (ROS) in the cardiovascular system. METHODS: Mitochondria were isolated from Wistar rat hearts (n = 8) and incubated with HX/XO in the presence and in the absence of calcium. Several methods were used to assess the protection afforded by CV: evaluation of mitochondrial volume changes (by measuring changes in the optical density of the mitochondrial suspension), calcium uptake and release (with a fluorescent probe, Calcium Green 5-N) and mitochondrial respiration (with a Clark-type oxygen electrode). RESULTS: CV decreased mitochondrial damage associated with ROS production by HX and XO, as verified by the reduction of mitochondrial swelling and increase in mitochondrial calcium uptake. In the presence of HX and XO, CV also ameliorated mitochondrial respiration in the active phosphorylation state and prevented decrease in the respiratory control ratio (p < 0.05) and in mitochondrial phosphorylative efficiency (p < 0.001). CONCLUSIONS: The data indicate that CV partly protected heart mitochondria from oxidative damage induced by HX and XO, which may be useful during myocardial ischemia and reperfusion. It is also suggested that mitochondria may be a priority target for the protective action of some compounds.     

Functional Imaging of the Trigeminal System: Applications to Migraine Pathophysiology

Background.—Based largely on data from animal models, migraine is hypothesized to involve changes in neural function in brain areas that mediate nociception—specifically, the trigeminal nerve, spinal trigeminal nucleus, and thalamus. These hypotheses about migraine pathophysiology can be tested directly in humans for the first time, with recent advances in functional neuroimaging techniques, which allow assessment of functional activity of specific brain areas. This article discusses the hypothesized role of the trigeminovascular pain system in migraine, reviews recent findings involving functional imaging of the human trigeminal system, and considers applications of functional imaging in the study of migraine pathophysiology. Functional neuroimaging is the only noninvasive approach for the objective measurement of changes in neural activity in humans. Functional magnetic resonance imaging has been applied to the measurement of neural activation of the trigeminal nociceptive system in healthy volunteers, and in patients with pain syndromes such as trigeminal pain. Conclusions.—The demonstrated utility of functional magnetic resonance imaging at elucidating, in a regionally specific manner, the functional and temporal changes in neural activity in the trigeminal nociceptive system, promises to make it a useful tool for the study of migraine pathophysiology and the evaluation of therapeutic interventions.     

Capsaicin-induced thermal hyperalgesia and sensitization in the human trigeminal nociceptive pathway: an fMRI study

The aim of this study was to differentiate the processing of nociceptive information, matched for pain intensity, from capsaicin-induced hyperalgesic vs. control skin at multiple levels in the trigeminal nociceptive pathway. Using an event-related fMRI approach, 12 male subjects underwent three functional scans beginning 1 h after topical application of capsaicin to a defined location on the maxillary skin, when pain from capsaicin application had completely subsided. Brush and two levels of painful heat (low-Thermal-1 and high-Thermal-2) were applied to the site of capsaicin application and to the mirror image region on the opposite side. Temperatures for each side were set to evoke perceptually matched pain (mean temperatures [capsaicin/control]: Thermal-1=38.4/42.8 degrees C; Thermal-2=44.9/47.8 degrees C). We found differences in activation patterns following stimuli to treated and untreated sides in sensory circuits across all stimulus conditions. Across the trigeminal nociceptive pathway, Thermal-2 stimulation of hyperalgesic skin evoked greater activation in trigeminal ganglion and nucleus, thalamus, and somatosensory cortex than the control side. Thus, trigeminal nociceptive regions showed increased activation in the context of perceptually equal pain levels. Beyond these regions, contrast analyses of capsaicin vs. control skin stimulation indicated significant changes in bilateral dorsolateral prefrontal cortex and amygdala. The involvement of these emotion-related regions suggests that they may be highly sensitive to context, such as prior experience (application of capsaicin) and the specific pain mechanism (hyperalgesic vs. normal skin).     

HDL3-related decreased serum paraoxonase (PON) activity in uremic patients: comparison with the PON1 allele polymorphism

BACKGROUND: Patients with chronic renal failure on maintenance haemodialysis (HD) are at high risk of atherothrombotic events; an enhanced oxidant stress might have a major role. The decrease of human paraoxonase (PON1), an anti-oxidant high-density lipoprotein (HDL)-linked enzyme, is a possible mechanism for developing cardiovascular disease. To ascertain the causes of low PON1 in such patients, we investigated the contribution of both PON1 gene polymorphism and individual pattern of HDL. METHODS: On 74 HD patients (47 M and 27 F) and on 92 healthy individuals (HS, 48 M and 44 F), we studied PON1 activity, PON1 genotype (55 and 192 PON1 allelic polymorphisms) and the lipid profile, including the HDL subfractions. RESULTS: We observed in HD patients the following significant differences: (1) decreased median PON1 activity (73.5 vs. 110 U/l); (2) decreased mean HDL concentration (1.05 +/- 0.18 vs. 1.55 +/- 0.41 mmol/l); (3) decreased mean HDL3 concentration (0.79 +/- 0.21 vs. 1.28 +/- 0.24 mmol/l). Total HDL retained about 70% of serum activity, almost completely carried (95%) by the HDL3. Finally, PON1 activity remained significantly low in HD vs. HS after matching for the allelic polymorphism. CONCLUSIONS: The reduction of the HDL3, not the genetic PON1 polymorphism, seems the most important determinant of PON1 activity reduction in HD.     

Activation of the motor cortex during phasic rapid eye movement sleep

When dreaming during rapid eye movement (REM) sleep, we can perform complex motor behaviors while remaining motionless. How the motor cortex behaves during this state remains unknown. Here, using intracerebral electrodes sampling the human motor cortex in pharmacoresistant epileptic patients, we report a pattern of electroencephalographic activation during REM sleep similar to that observed during the performance of a voluntary movement during wakefulness. This pattern is present during phasic REM sleep but not during tonic REM sleep, the latter resembling relaxed wakefulness. This finding may help clarify certain phenomenological aspects observed in REM sleep behavior disorder. Ann Neurol 2016;79:326–330     

Laryngeal mask airway in neonatal resuscitation: a survey of current practice and perceived role by anaesthesiologists and paediatricians

Objectives: To survey current practice and to compare the opinion of paediatricians and anaesthesiologists regarding laryngeal mask airway (LMA) in neonatal resuscitation. Design: A structured postal questionnaire on the use of the laryngeal mask airway in neonatal resuscitation was sent to the heads of department of the paediatric and anaesthesiology services. Setting: Forty-three hospitals in the Veneto Region, Italy. Results: During the year 2000, 1526 out of 33708 (4.5%) neonates in our region needed resuscitation. Of these cases, 101 (6.6%) were ventilated using the LMA. Laryngeal mask airway availability was significantly greater in the anaesthesiology department compared to the paediatric department (90% versus 50%; P=0.002). However, 52% of anaesthesiologists and 72% of paediatricians had never used the laryngeal mask airway in their practice. The laryngeal mask airway was considered as an essential device more frequently by the anaesthesiologists than by the paediatricians (27% versus 5%; P=0.015); both groups considered the laryngeal mask airway particularly useful in specific situations. Interestingly, while 16% of the paediatricians described the laryngeal mask airway as having no value, none of the anaesthesiologists did (P=0.002). Staff competence was considered low by 70% of anaesthesiology heads of department compared with 90% of their pediatric colleagues. In both specialties, use of the laryngeal mask airway was limited to medical staff. With regard to training, 35% of anaesthesiologists and 22.5% of paediatricians had attended a course on laryngeal mask airway use. Conclusions: Laryngeal mask airway availability and perceived value were higher amongst anaesthesiologists than their paediatric colleagues. However, educational level, competence and utilization rates of the LMA in neonatal resuscitation were low in both groups.     

Transitory Activation of AMPK at Reperfusion Protects the Ischaemic-Reperfused Rat Myocardium Against Infarction

Purpose  

AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size.