Z. Melik

Cognitive and autonomic dysfunction in presymptomatic and early Huntington's disease.

Huntington’s disease is characterized by disorders of movement, cognition and behavior. Individuals with Huntington’s disease display aberrant changes in the autonomic nervous system that are detected even before the onset of other symptoms. Subtle cognitive dysfunction may start before other clinical manifestations. The aim of the present study was to investigate the autonomic nervous system response to mental arithmetic and the relationship between the autonomic and cognitive/motor function in presymptomatic and early Huntington’s disease. We examined 15 presymptomatic Huntington’s disease gene carriers (PHD), 15 early Huntington’s disease patients (EHD) and 30 healthy controls. PHD and EHD groups were determined according to Unified Huntington’s Disease Rating Scale (UHDRS) motor score. ECG, heart rate, systolic and diastolic blood pressure, and cutaneous laser Doppler flux were measured during rest and during a simple mental arithmetic test. UHDRS cognitive test battery was applied to determine cognitive dysfunction. During mental arithmetic, the heart rate of PHD/EHD increased significantly less than that of controls. Decreased microvascular response to mental arithmetic was found in EHD. Significant correlations for the PHD/EHD group were found between laser Doppler flux response and Symbol Digit Modalities Test score, and between laser Doppler flux response and UHDRS motor score. It seems that central autonomic dysregulation of cardiovascular system in Huntington’s disease goes along with the degeneration of other central neuronal systems. This finding is relevant as it could enable simple and noninvasive testing of disease progression.

Functional impairment of precerebral arteries in Huntington disease

BACKGROUND Cardiovascular pathology of Huntington disease (HD) appears to be complex; while microvascular dysfunction seems to appear early, deaths from cardiomyopathy and stroke might occur in the late phase of HD. METHODS Our study evaluated global risk factors for coronary heart disease (CHD), structure and function of precerebral arteries in 41 HD subjects and 41 matched controls. HD subjects were divided into groups by the United Huntington disease rating scale (presymptomatic-PHD, early-EHD, midstage-MHD and late-LHD). CHD risk factors assessment and Doppler examination of precerebral arteries were performed, including measurements of the carotid artery intima-media thickness (IMT), and parameters indicating local carotid artery distensibility (stiffness index β, pulse wave velocity, pressure strain elasticity module and carotid artery compliance). RESULTS In the HD and controls we identified a comparable number of non-obstructive plaques (<50% lumen narrowing). No obstructive plaques (>50% lumen narrowing) were found. There was significantly increased IMT in MHD. In PHD and EHD the parameters of arterial stiffness were significantly higher and the carotid artery compliance was significantly lower. CONCLUSIONS Our results reveal functional vascular pathology in PHD, EHD, and MHD. Precerebral arteries dysfunction in HD therefore appears to be mostly functional and in agreement with recently described autonomic nervous system changes in HD.

Effect of transcutaneous application of gaseous carbon dioxide on cutaneous microcirculation

BACKGROUND The inefficient healing of chronic wounds is a result of poor blood perfusion at the wound and surrounding tissues. Artificially applied carbon dioxide (CO2) has the potential to improve the perfusion and oxygenation of tissues, hence is useful for the healing of chronic wounds. OBJECTIVE The aim of the present study was to determine the effect of a transcutaneous application of physiological vasodilator gaseous CO2 on cutaneous blood flow. METHODS Laser Doppler (LD) flux in cutaneous microcirculation, skin temperature, electrocardiogram and arterial blood pressure were measured simultaneously in a group of 33 healthy men, aged 21-28 years, during rest and a 35-minute CO2 therapy. One lower limb of each subject represented the studied extremity, being exposed to gaseous CO2. The contralateral limb was the control, being exposed to air. Each limb was sealed in a plastic bag. RESULTS During CO2 therapy the LD flux in the studied extremity increased from 5.8 PU ± 3.9 PU to 30.3 PU ± 16.7 PU (mean ± standard deviation; paired t-test, p <  0.001), while that in the control extremity did not change significantly. CONCLUSIONS Our results confirm a local vasodilatory effect of applied CO2 therapy. This finding indicates its potential clinical use.

Evidence of cardiac electrical remodeling in patients with Huntington disease

Although Huntingtons disease (HD) is a disease of the central nervous system, HD mortality surveys indicate heart disease as a major cause of death. Cardiac dysfunction in HD might be a primary consequence of peripherally expressed mutant huntingtin or secondary to either a general decline in health or the onset of neurological dysfunction. The aim of the study was to clarify the heart muscle involvement.

L-arginine as dietary supplement for improving microvascular function

BACKGROUND Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. OBJECTIVE The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. METHODS We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. RESULTS After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p < 0.05), while in the other groups it remained the same. There were no differences in the endothelium-independent vasodilation after ingestion of L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. CONCLUSION Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.