Potential markers of healing from near infrared spectroscopy imaging of venous leg ulcer. A randomized controlled clinical trial comparing conventional with hyperbaric oxygen treatment.

The aim of this study is to ascertain whether the simultaneous measurement of hemoglobin O2 saturation (StO2 ) and dimension of venous leg ulcers (VLU) by near infrared spectroscopy (NIRS) imaging can predict the healing course with protocols employing a conventional treatment alone or in combination with hyperbaric oxygen therapy (HBOT). NIRS 2D images of wound region were obtained in 81 patients with hard-to-heal VLU that had been assigned, in a randomized controlled clinical trial, to the following protocols: 30 HBOT sessions, adjunctive to the conventional therapy, either twice daily over 3 weeks (group A) or once daily over 6 weeks (group B), and conventional therapy without HBOT (group C). Seventy-three patients completed the study with a total of 511 NIRS images being analyzed. At the end of treatment, wound area was significantly smaller in all three groups. However, at the 3-week mark the wound area reduction tended to be less evident in group A than in the other groups. This trend continued up to the 6-week end-point when a significantly greater area reduction was found with group B (65.5%) and group C (56.8%) compared to group A (29.7%) (P < .01). Furthermore, a higher incidence of complete healing was noted with group B (20%) than with group A (4.5%) and group C (3.8%). When using a final wound reduction in excess of 40% to distinguish healing from nonhealing ulcers, it was found that only the former present NIRS StO2 values abating over the study period both at center and edge of lesions. In conclusion, NIRS analysis of StO2 and wound area can predict the healing course of VLU. Adjunctive HBOT significantly facilitates VLU healing compared to the conventional treatment alone. This positive action, however, becomes manifest only with a longer and less intensive treatment schedule.

A Pilot Study of Infrared Thermography Based Assessment of Local Skin Temperature Response in Overweight and Lean Women during Oral Glucose Tolerance Test.

Obesity is recognized as a major public health issue, as it is linked to the increased risk of severe pathological conditions. The aim of this pilot study is to evaluate the relations between adiposity (and biophysical characteristics) and temperature profiles under thermoneutral conditions in normal and overweight females, investigating the potential role of heat production/dissipation alteration in obesity. We used Infrared Thermography (IRT) to evaluate the thermogenic response to a metabolic stimulus performed with an oral glucose tolerance test (OGTT). Thermographic images of the right hand and of the central abdomen (regions of interests) were obtained basally and during the oral glucose tolerance test (3 h OGTT with the ingestion of 75 g of oral glucose) in normal and overweight females. Regional temperature vs BMI, % of body fat and abdominal skinfold were statistically compared between two groups. The study showed that mean abdominal temperature was significantly greater in lean than overweight participants (34.11 ± 0.70 °C compared with 32.92 ± 1.24 °C, p < 0.05). Mean hand temperature was significantly greater in overweight than lean subjects (31.87 ± 3.06 °C compared with 28.22 ± 3.11 °C, p < 0.05). We observed differences in temperature profiles during OGTT between lean and overweight subjects: The overweight individuals depict a flat response as compared to the physiological rise observed in lean individuals. This observed difference in thermal pattern suggests an energy rate imbalance towards nutrients storage of the overweight subjects.

Near-infrared spectroscopic imaging of the whole hand: A new tool to assess tissue perfusion and peripheral microcirculation in scleroderma.

OBJECTIVES: Systemic sclerosis (SSc) causes functional and structural microcirculatory dysfunction, affecting also distal extremities. Optical Near-InfraRed Spectroscopy (NIRS) of blood HbO2 saturation (stO2) is able to evaluate O2 delivery/consumption balance in the explored tissue. The NIRS-sensitive camera non-invasively detects stO2 values in superficial tissues, automatically generating 2D-imaging maps in real time. We aimed at testing whether NIRS hand imaging may evaluate peripheral microcirculatory dysfunction and its spatial heterogeneity in SSc patients compared to controls. METHODS: Forty SSc patients (aged 55.1 ±â€¯15.6 years) and twenty-one healthy controls (aged 54.3 ±â€¯14.5years, p = 0.89) were studied by palmar hand NIRS-2D imaging. A blood pressure cuff was applied to the forearm and 3 min ischemia was induced. Images were acquired at basal conditions and every 10 seconds during 3 minutes of ischemia and 5 minutes of reperfusion. Five regions of interest were positioned on each fingertip, from the second to the fifth finger and one on the thenar eminence. RESULTS: A significant difference was found between controls and SSc patients in basal stO2 (84.3 ±â€¯7.5 vs. 75.4 ±â€¯10.9%, p < 0.001), minimum stO2 (65.2 ±â€¯8.0 vs. 53.4 ±â€¯10.1%, p < 0.001) and time to maximum stO2 during hyperemia (63 ±â€¯38 vs. 85 ±â€¯49 s, p < 0.05). Among clinical characteristics, anti-Scl70 antibody positivity, digital ulcers history and smoke exposure affected NIRS parameters, as well as sildenafil and statins therapy. Conversely, no significant differences were found in NIRS-2D values between different nailfold-videocapillaroscopy patterns. CONCLUSION: NIRS-2D imaging is a simple, automated tool to non-invasively detect regional microcirculatory impairment in SSc, which seems to add significant functional information to the morphological picture of nailfold-videocapillaroscopy.

Long-term prognosis of unheralded myocardial infarction vs chronic angina; role of sex and coronary atherosclerosis burden.

BACKGROUND: Angina pectoris (AP) and unheralded myocardial infarction (MI) are considered random clinical equivalents of ischemic heart disease (IHD). Aim of the study was to evaluate the long-term progression of AP as opposed to unheralded MI as alternative first clinical presentations of IHD and the effect of sex on prognosis. METHODS: The study included 2272 consecutive patients, 1419 MI and 1353 AP, hospitalized from 1995 to 2007 at CNR Clinical Physiology Institute, Pisa, Italy and followed up to December 2013, who fulfilled the following criteria: unheralded MI or AP as first manifestation of IHD; age < = 70 years; known coronary anatomy; at least 10-year follow-up. Fatal and non fatal MI, all-cause, and cardiac deaths were the end-points. RESULTS: Males were predominant in MI (86%) as compared to AP (77%). Females were predominantly affected by AP (61%, MI 39%), and older than men (61 ± 7 vs 59 ± 8 years, p < 0.001). Coronary stenoses were prevalent in MI. During 115 ± 58 months follow-up, 628 deaths (23%) were observed, including 269 cardiac (43%), and 149 cancer deaths (24%). Long-term prognosis was significantly better in AP than MI group. The lowest prevalence of future MI was recorded in female AP (p < 0.001). CONCLUSIONS: MI as first clinical manifestation of IHD implies a more adverse prognosis than AP; future MI is a rare event in AP; sex influences the first presentation of IHD and its course with possible implications for preventive strategy.

Multimodal Imaging for the Detection of Brown Adipose Tissue Activation in Women: A Pilot Study Using NIRS and Infrared Thermography.

Purpose: A clear link between obesity and brown adipose tissue (BAT) dysfunction has been recently demonstrated. The purpose of this pilot study is to determine if near-infrared spectroscopy (NIRS) 2D imaging together with infrared thermography (IRT) is capable of identifying thermal and vascular response in the supraclavicular (SCV) areas after the ingestion of an oral glucose load as a thermogenic stimulation. Method: We studied two groups of women (obese versus lean) for discerning their different responses. NIRS and IRT images were acquired on the neck in the left SCV region during a 3 h oral glucose tolerance test (OGTT) and immediately after a cold stimulation. Results: We detected a significant thermal response of BAT in SCV fossa in both groups. Both during OGTT and after cold stimulation, skin temperature was persistently higher in lean versus obese. This response was not coupled with changes in oxygen saturation of subcutaneous tissue in that area. Discussion and Conclusion: The results show that NIRS/IRT may be a novel, noninvasive, radiation-free, easy to use, and low-cost method for monitoring, during the standard clinical practice, the diet and pharmacological intervention which aims to stimulate BAT as a potential therapeutic target against obesity and diabetes.

Percutaneous cardiac support during myocardial infarction drastically reduces mortality: perspectives from a swine model.

BACKGROUND/AIMS: Acute myocardial infarction (AMI) with cardiogenic shock (CS) remains the leading cause of in-hospital death in acute coronary syndromes. In the AMI-CS pig model we tested the efficacy of temporary percutaneous cardiorespiratory assist device (PCRA) in rescuing the failing heart and reducing early mortality. METHODS: In open-chest pigs we induced AMI by proximal left anterior descending coronary artery (LAD) ligation. Eight animals without PCRA (C group) were compared with 12 animals otherwise treated with PCRA (T group), starting approximately at 60 minutes post-occlusion and lasting 120-180 minutes. In 3 animals of the T group, regional myocardial oxygen content was also imaged by two-dimensional near infrared spectroscopy (2D-NIRS) with and without PCRA, before and after LAD reperfusion. RESULTS: All animals without PCRA died despite unrelenting resuscitation maneuvers (120 minutes average survival time). Conversely, animals treated with PCRA showed a reduction in life-threatening arrhythmia and maintenance of aortic pressure, allowing interruption of PCRA in all cases early in the experiments, with sound hemodynamics at the end of the observation period. During LAD occlusion, NIRS showed severe de-oxygenation of the LAD territory that improved with PCRA. After PCRA suspension and LAD reperfusion, the residual de-oxygenated area proved to be smaller than the initial risk area. CONCLUSIONS: In AMI, PCRA initiated during advanced CS drastically reduced early mortality from 100% to 0% in a 4-5 hour observation period. PCRA promoted oxygenation of the ischemic area during LAD occlusion. Results support the use of PCRA as first line of treatment in AMI-CS, improving myocardial rescue and short-term survival.

Differential proteome profile in ischemic heart disease: Prognostic value in chronic angina versus myocardial infarction. A proof of concept.

The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158m/z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD.

A comparative evaluation of two decompression procedures for technical diving using inflammatory responses: compartmental versus ratio deco.

INTRODUCTION: The aim of this study was to compare two decompression procedures commonly adopted by technical divers: the ZH-L16 algorithm modified by 30/85 gradient factors (compartmental decompression model, CDM) versus the 'ratio decompression strategy' (RDS). The comparison was based on an analysis of changes in diver circulating inflammatory profiles caused by decompression from a single dive. METHODS: Fifty-one technical divers performed a single trimix dive to 50 metres' sea water (msw) for 25 minutes followed by enriched air (EAN50) and oxygen decompression. Twenty-three divers decompressed according to a CDM schedule and 28 divers decompressed according to a RDS schedule. Peripheral blood for detection of inflammatory markers was collected before and 90 min after diving. Venous gas emboli were measured 30 min after diving using 2D echocardiography. Matched groups of 23 recreational divers (dive to 30 msw; 25 min) and 25 swimmers were also enrolled as control groups to assess the effects of decompression from a standard air dive or of exercise alone on the inflammatory profile. RESULTS: Echocardiography at the single 30 min observation post dive showed no significant differences between the two decompression procedures. Divers adopting the RDS showed a worsening of post-dive inflammatory profile compared to the CDM group, with significant increases in circulating chemokines CCL2 (P = 0.001) and CCL5 (P = 0.006) levels. There was no increase in chemokines following the CDM decompression. The air scuba group also showed a statistically significant increase in CCL2 (P < 0.001) and CCL5 (P = 0.003) levels post dive. No cases of decompression sickness occurred. CONCLUSION: The ratio deco strategy did not confer any benefit in terms of bubbles but showed the disadvantage of increased decompression-associated secretion of inflammatory chemokines involved in the development of vascular damage.

Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD), affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT), eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR) was measured at baseline and during infusions of acetylcholine (Ach) or sodium-nitroprusside (SNP) to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/-) showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels, consistent with a shift towards a vasoconstrictive pattern.

[Telemedicine and wireless devices in heart failure]. / Telemedicina e sistemi wireless nello scompenso cardiaco.

Telemedicine has the potential to constitute the central element of the future primary care and become an effective means of prevention and early warning of acute exacerbation of chronic diseases. Up to now, the application of telemedicine has found a variety of difficulties, regarding the types and methods of acquisition and transmission of biological signals, the acceptance and cooperation of the patient, etc. The latest technological developments involve the combined use of wireless technologies and smartphones, for the collection and the transmission of data, and specific softwares for their automatic analysis. This paper examines some of the critical aspects in the application of new technologies for heart failure remote management.

How stressful are 105 days of isolation? Sleep EEG patterns and tonic cortisol in healthy volunteers simulating manned flight to Mars.

Spaceflights "environment" negatively affects sleep and its functions. Among the different causes promoting sleep alterations, such as circadian rhythms disruption and microgravity, stress is of great interest also for earth-based sleep medicine. This study aims to evaluate the relationships between stress related to social/environmental confinement and sleep in six healthy volunteers involved in the simulation of human flight to Mars (MARS500). Volunteers were sealed in a spaceship simulator for 105 days and studied at 5 specific time-points of the simulation period. Sleep EEG, urinary cortisol (24 h preceding sleep EEG recording) and subjectively perceived stress levels were collected. Cognitive abilities and emotional state were evaluated before and after the simulation. Sleep EEG parameters in the time (latency, duration) and frequency (power and hemispheric lateralization) domains were evaluated. Neither cognitive and emotional functions alterations nor abnormal stress levels were found. Higher cortisol levels were associated to: (i) decrease of sleep duration, increase of arousals, and shortening of REM latency; (ii) reduction of delta power and enhancement of sigma and beta in NREM N3; and (iii) left lateralization of delta activity (NREM and REM) and right lateralization of beta activity (NREM). Stressful conditions, even with cortisol fluctuations in the normal range, alter sleep structure and sleep EEG spectral content, mirroring pathological conditions such as primary insomnia or insomnia associated to depression. Correlations between cortisol fluctuations and sleep changes suggest a covert risk for developing allostatic load, and thus the need to develop ad-hoc countermeasures for preventing sleep alterations in long lasting manned space missions.

The informative contribution of the "virtual medical visit" in a new heart failure telemedicine integrated system.

INTRODUCTION: Telemedicine systems consist of collection, transmission, and analysis of biometric data essentially based on instrumental measures. Our goal was to evaluate if information collected from patients has an incremental informative value in automatically rating the patient's health status. MATERIALS AND METHODS: We present preliminary results of a new telemedicine system (ASCOLTA) obtained by observation of 12 heart failure patients (New York Heart Association Class IIb-III). Instrumental data (electrocardiogram, oxygen saturation level, and respiration rate) were wirelessly collected daily together with clinical data (weight, heart rate, and blood pressure values) and patients' information obtained through a Web-based questionnaire, simulating a virtual medical visit. Health status was independently judged by two blinded cardiologists and by the patient's cardiologist on the basis of 348 daily clinical reports. Random forest classification analysis was applied to 240 complete clinical report variables in order to estimate the judged health status. RESULTS: The use of "patient's information" led to a better predictive ability in comparison with using only physiological parameters assessed by instruments. The complete set of variables (Patient+Instrumental) achieved 84% concordance, compared with 72% for the instrumental-only variables and 69% for the patient-only variables. The receiver operator characteristics curves graphically confirmed the described results. CONCLUSIONS: Patients have an active role in home monitoring, and their information appears relevant for a new telemedicine approach integrating subjective and objective vital signs. Combining patient information with instrumental parameters, it is possible to achieve a more correct automatic classification of health status of heart failure patients.

Stromal cell-derived factor-1-3'A polymorphism is associated with decreased risk of myocardial infarction and early endothelial disturbance.

AIM: Genome-wide association studies have identified single-nucleotide polymorphisms at the 10q11 locus as risk factors for myocardial infarction (MI). This locus lies upstream (∼80 kb) of the stromal cell-derived factor-1 (SDF1) gene that codify for a chemokine with protective atherogenetic effects and with a major role in the mobilization, homing, and differentiation of endothelial progenitor cells (EPCs). The purpose of this study was to investigate the possible association of SDF1-3'A polymorphism, that upregulates SDF1 protein expression, with MI and early endothelial dysfunction and atherosclerosis in young healthy subjects. METHODS: 200 patients (181 men age 57.3 ±â€Š7.7 years) and 230 healthy controls (96 men, age 52 ±â€Š11.9 years) were recruited to investigate the association between MI and SDF1-3'A polymorphism. The relationship between SDF1-3'A polymorphism and brachial artery flow-mediated dilation and the number of circulating EPCs was examined in 50 healthy young adults. RESULTS: A significant difference in SDF1-3'A genotype distribution was observed between patients and controls (P = 0.006). Patients carrying the A allele had a significantly reduced MI risk compared with subjects with GG genotype (odds ratio = 0.5, 95% CI = 0.3-0.9, P = 0.001). SDF1-3'A polymorphism presented a significant interaction with other cardiovascular risk factors (Pinteraction < 0. 0001). Controls carrying the A allele showed significantly higher flow-mediated dilation (13.9 ±â€Š4.9 vs 10.8 ±â€Š4.3, P = 0.03) and significantly higher values of EPCs (0.029 ±â€Š0.009 vs 0.022 ±â€Š0.008, P = 0.02) compared with GG homozygotes. CONCLUSION: SDF1-3'A polymorphism is associated with a decreased risk of MI and early endothelial dysfunction, strongly confirming the important atherogenic role of SDF1 gene at clinical level.

Up-regulation of heme oxygenase-1 after infarct initiation reduces mortality, infarct size and left ventricular remodeling: experimental evidence and proof of concept.

BACKGROUND: Up-regulation of HO-1 by genetic manipulation or pharmacological pre-treatment has been reported to provide benefits in several animal models of myocardial infarction (MI). However, its efficacy following MI initiation (as in clinical reality) remains to be tested. Therefore, this study investigated whether HO-1 over-expression, by cobalt protoporphyrin (CoPP) administered after LAD ligation, is still able to improve functional and structural changes in left ventricle (LV) in a rat model of 4-week MI. METHODS: A total of 144 adult male Wistar rats were subjected to either left anterior coronary artery ligation or sham-operation. The effect of CoPP treatment (5 mg/kg i.p. at the end of the surgical session and, then, once a week for 4 weeks) was evaluated on the basis of survival, electro- and echocardiography, plasma levels of B-type natriuretic peptide (BNP), endothelin-1 and prostaglandin E2, coronary microvascular reactivity, MI size, LV wall thickness and vascularity. Besides, the expression of HO-1 and connexin-43 in different LV territories was assessed by western blot analysis and immunohistochemistry, respectively. RESULTS: CoPP induced an increased expression of HO-1 protein with >16 h delay. CoPP treatment significantly reduced mortality, MI size, BNP concentration, ECG alterations, LV dysfunction, microvascular constriction, capillary rarefaction and restored connexin-43 expression as compared to untreated MI. These functional and structural changes were paralleled by increased HO-1 expression in all LV territories. HO activity inhibition by tin-mesoporphyrin abolished the differences between CoPP-treated and untreated MI animals. CONCLUSIONS: This is the first report demonstrating the putative role of pharmacological induction of HO-1 following coronary occlusion to benefit infarcted and remote territories, leading to better cardiac function in a 4-week MI outcome.

Genetic score based on high-risk genetic polymorphisms and early onset of ischemic heart disease in an Italian cohort of ischemic patients.

Several single-nucleotide polymorphisms (SNPs) have been recognized as associated with ischemic heart disease (IHD) although the optimal set of risk genotypes has not be identified. This study aimed to examine whether identified high-risk SNPs are associated with early onset of IHD. In the GENOCOR study, 44 high-risk SNPs were genotyped in 114 patients with early onset of IHD (46.2 ± 5.1 years) and 384 patients with late onset of IHD (60.7 ± 5.9 years). The associations between individual SNPs and early onset IHD were assessed. A multilocus genetic risk score (GRS) for each associated risk genetic markers was constructed by summing the number of risk alleles. The SNPs significantly associated with IHD were: -482C>T of Apolipoprotein C III gene (ApoC3, p=0.02); 1171 5A>6A of Matrix metalloproteinase 3 stromelisine I gene (p=0.01); G98T of Selectin E gene (p=0.05); C/G of 9p21.3 locus (p=0.01). Likelihood ratio test showed a strong interaction for increasing risk of early IHD between the presence of ApoC3 and 9p21.3 locus with hypertriglyceridemia (p=0.0008, 0.0011) as well as between 9p21.3 locus and smoking (p=0.0010) after correction for multiple testing. The OR for premature IHD for GRS unit was 1.3 (95% CI 1.1-1.6, p=0.001). Patients in the top tertile of GRS were estimated to have a 3.2-fold (95% CI 1.5-6.8; p=0.001) increased risk of early IHD compared with those in the bottom tertile. The results show that currently identified high-risk SNPs confer an additive biomarker for cardiovascular events. GRS may provide important incremental information on the genetic component of IHD.

Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation.

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 µm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 µm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 µm and < 100 µm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 µm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.

Brain responses to emotional stimuli during breath holding and hypoxia: an approach based on the independent component analysis.

Voluntary breath holding represents a physiological model of hypoxia. It consists of two phases of oxygen saturation dynamics: an initial slow decrease (normoxic phase) followed by a rapid drop (hypoxic phase) during which transitory neurological symptoms as well as slight impairment of integrated cerebral functions, such as emotional processing, can occur. This study investigated how breath holding affects emotional processing. To this aim we characterized the modulation of event-related potentials (ERPs) evoked by emotional-laden pictures as a function of breath holding time course. We recorded ERPs during free breathing and breath holding performed in air by elite apnea divers. We modeled brain responses during free breathing with four independent components distributed over different brain areas derived by an approach based on the independent component analysis (ICASSO). We described ERP changes during breath holding by estimating amplitude scaling and time shifting of the same components (component adaptation analysis). Component 1 included the main EEG features of emotional processing, had a posterior localization and did not change during breath holding; component 2, localized over temporo-frontal regions, was present only in unpleasant stimuli responses and decreased during breath holding, with no differences between breath holding phases; component 3, localized on the fronto-central midline regions, showed phase-independent breath holding decreases; component 4, quite widespread but with frontal prevalence, decreased in parallel with the hypoxic trend. The spatial localization of these components was compatible with a set of processing modules that affects the automatic and intentional controls of attention. The reduction of unpleasant-related ERP components suggests that the evaluation of aversive and/or possibly dangerous situations might be altered during breath holding.

Cardiac function and oxygen saturation during maximal breath-holding in air and during whole-body surface immersion.

INTRODUCTION: The magnitude of the oxygen-sparing effect induced by the diving response in humans is still under debate. We wished to compare cardiovascular changes during maximal breath-holding (BH) in air and during whole-body immersion at the surface in a group of BH divers. METHODS: Twenty-one divers performed a maximal static apnea in air or during whole-body immersion. Dopplerechocardiography, arterial blood pressure and haemoglobin saturation (SaO2) were obtained at the beginning of, and at 1/3, 2/3 and maximal BH time. RESULTS: BH time was on the average 3.6 ± 0.4 min, with no differences between the two conditions. SaO2 significantly decreased during BH in both conditions, but was significantly higher during immersion as compared to the dry (P = 0.04). In both conditions, BH induced a significant linear increase in right ventricular diameter (P < 0.001), left ventricular (LV) volumes (P < 0.001) and LV stroke volume (P < 0.001) but a significant linear decrease in LV ejection fraction (P = 0.033). In both conditions, Doppler diastolic parameters showed changes suggesting a constrictive/restrictive left ventricular filling pattern (i.e., an increase of early diastolic left ventricular filling velocity, P = 0.005, and a decrease in the deceleration time of early diastolic left ventricular filling. P < 0.001). CONCLUSION: BH induces progressive LV enlargement both in air and whole-body immersion, associated with reduced LV ejection fraction and progressive hindrance to diastolic filling. For a similar apnea duration, SaO2 decreased less during immersed BH, indicating an O2-sparing effect of diving, suggesting that interruption of apnea was not triggered by a threshold critical value of blood O2 desaturation.