Zeljko Dujic's research while affiliated with University of Split and other places
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Publications (180)
Cervical spinal cord injury (SCI) leads to autonomic cardiovascular dysfunction that underlies the 3-4 fold elevated risk of cardiovascular disease in this population. Reduced common carotid artery (CCA) dilatory responsiveness during the cold-pressor test (CPT) is associated with greater cardiovascular disease risk and progression. The cardiovascu...
Accumulating data suggests that catestatin, an eclectic neuroendocrine peptide, is involved in the pathophysiology of primary hypertension (PH). Nevertheless, clinical studies concerning its role in PH are still scarce. Therefore, in the present study, we aimed to explore an association between serum catestatin levels, ambulatory blood pressure (BP...
New findings:
What is new and noteworthy? What is the central question of this study? Does the hyperbaric, hypercapnic, acidotic, hypoxic stress of apnoea diving lead to greater pulmonary vasoreactivity and increased right-heart work in apnoea divers? What is the main finding and its importance? Compared to sex- and age-matched controls, Divers ha...
Accumulating data from both human and animal studies suggest that cannabidiol (CBD) may be associated with improved cardiovascular function, markedly with regard to reduction in blood pressure and improved endothelial function. However, there is a lack of randomized studies to support these notions, especially in at-risk populations. The principal...
Physical activity is a powerful modifiable risk factor for disease and mortality. Physical activity levels in people with spinal cord injury (SCI) have not been quantified relative to uninjured individuals in a large population-based sample. We aimed to quantify and compare physical activity in people with and without SCI, and to examine the associ...
Objectives
During apnea diving, a patent foramen ovale (PFO) may function as a pressure relief valve under conditions of high pulmonary pressure, preserving left-ventricular output. However, PFO prevalence in apneic divers has not been previously reported. We aimed to determine the prevalence of PFO in apneic divers compared to non-diver controls....
Voluntary asphyxia imposed by static apnea challenges blood-brain barrier (BBB) integrity in humans through transient extremes of hypertension, hypoxemia and hypercapnia. In the present study, ten ultra-elite breath-hold divers performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxi...
Individuals with cervical spinal cord injury (SCI) are at an increased risk for cardiovascular disease. Exercise is well-established for preventing cardiovascular disease; however, there are limited straightforward and safe exercise approaches for increasing the activity of the cardiorespiratory system after cervical SCI. The objective of this stud...
Physiological field research on breath-hold divers (freedivers) is challenging as divers are exposed to hy- perbaric environments hostile to classical physiological measurement methods. Two main challenges are; I) The need of developing methods allowing measurements of physiological variables underwater at depth, II) To accompany the studied freedi...
Breath-hold diving involves highly integrative physiology and extreme responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure. With astonishing depth records exceeding 100 m, and up to 214 m on a single breath, the human capacity for deep breath-hold diving continues to refute expectations. The physiological ch...
In this case study, we evaluate the unique physiological profiles of two world-champion breath-hold divers. At close-to current world record depths, the extreme physiological responses to both exercise and asphyxia during progressive elevations in hydrostatic pressure are profound. As such, these professional athletes must be highly capable of mana...
New findings:
What is the central question of this study? How does deep breath-hold diving impact cardiopulmonary function, both acutely and over the subsequent 2.5 hours post-dive? What is the main finding and its importance? Breath-hold diving to depths below residual volume are associated with acute impairments in pulmonary gas exchange, that t...
New findings:
What is the central question of this study? To characterize cerebral blood flow (CBF) regulation following a single SCUBA dive to a depth of 18 m sea water with a 47-minute bottom time. What is the main finding and its importance? Acute alterations in CBF regulation at rest, including; extra-cranial vasodilation, reductions in shear...
People with spinal cord injury (SCI) have 3-4 fold greater risk of cardiovascular disease compared with those without SCI. Although circulating extracellular microvesicles are key effectors of vascular health and disease, how their functional phenotype might be altered with SCI is unknown. The aim of this study was to determine the effects of micro...
Objective:
To determine the population-level odds of individuals with spinal cord injury (SCI) experiencing fatigue and sleep apnea, to elucidate relationships with level and severity of injury, and to examine associations with abnormal cerebrovascular responsiveness.
Methods:
We used population-level data, meta-analyses, and primary physiologic...
Introduction
Therapeutic effects of cannabidiol (CBD) in specialized populations continue to emerge. Despite supra-physiological dosing being shown to be tolerable in various pathologies, optimization of CBD absorption has obvious benefits for general health and recreational usage. Our objectives were to: (1) to investigate a joint pharmacokinetic-...
The pathogenesis of predominantly neurological decompression sickness (DCS) is multifactorial. In SCUBA diving, besides gas bubbles, DCS has been linked to microparticle release, impaired endothelial function, and platelet activation. This study focused on vascular damage and its potential role in the genesis of DCS in breath-hold diving. Eleven br...
Study design:
Experimental study.
Objectives:
Compromised cerebrovascular function likely contributes to elevated neurological risk in spinal cord injury (SCI). Passive heating offers many cardiovascular and neurological health benefits; therefore, we aimed to determine the effects of an acute bout of heating on cerebrovascular function in chron...
Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represent the property of dynamic...
Intimate communication between neural and vascular structures is required to match neuronal metabolism to blood flow, a process termed neurovascular coupling. The number of laboratories assessing neurovascular coupling in humans is increasing due to clinical interest in disease states, and basic science interest in a non-anesthetized, non-craniotom...
Cardiovascular diseases (CVD) are highly prevalent in spinal cord injury (SCI), and peripheral vascular dysfunction might be a contributing factor. Recent evidence demonstrates that exposure to heat stress can improve vascular function and reduce the risk of CVD in uninjured populations. We therefore aimed to examine the extent of vascular dysfunct...
The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) likely plays an important role in the prevention of stroke, which is three- to fourfold more common after spinal cord injury (SCI). Although the directional relationship between BP and cerebral blood flow (CBF) has traditionally been thought to travel solely from BP to...
The underwater environment challenges human physiology in a unique way. Prolonged exposure to extreme conditions of immersion and increased ambient pressure can lead to injury and even death. Breath-hold and diving with self-contained underwater breathing apparatus (SCUBA diving) pose acute stress predominantly on the cardiovascular and pulmonary s...
We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single SCUBA dive to 18 msw for 47 mins. Twelve of the divers participated in a follow-up study involving breathing 60% oxygen at ambient pressure for 47 mins. Prior to bot...
New findings:
What is the central question of this study? How does oxygen therapy influence cerebral blood flow, cerebral oxygen delivery and neurovascular function in chronic obstructive pulmonary disease patients? What is the main finding and its importance? Oxygen therapy improves cerebral oxygen delivery and neurovascular function in chronic o...
The capacity of cerebrovasculature to buffer changes in blood pressure (BP) is crucial to prevent stroke, the incidence of which is 3-4 fold elevated after spinal cord injury (SCI). Disruption of descending sympathetic pathways within the spinal cord due to cervical SCI may result in impaired cerebrovascular buffering. Only linear analyses of cereb...
New findings:
What is the topic of this review? This review provides an up-to-date assessment of the physiology involved with extreme static dry-land breath holding in trained apneists. What advances does it highlight? We specifically highlight the recent findings involved with the cardiovascular, cerebrovascular, and metabolic function during a m...
Molecular oxygen (O2) is a vital element in human survival and plays a major role in a diverse range of biological and physiological processes. Although normobaric hyperoxia can increase arterial oxygen content (CaO2), it also causes vasoconstriction and hence reduces O2delivery in various vascular beds including the heart, skeletal muscle, and bra...
The presence of circulating gas bubbles and their influence on pulmonary and right heart hemodynamics was reported after uncomplicated self-contained underwater breathing apparatus (SCUBA) dive(s). Improvements in cardiac imaging have recently focused great attention on the right ventricle (RV). The aim of our study was to evaluate possible effects...
The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate...
Introduction:
Many individuals with high-level spinal cord injury (SCI) experience secondary conditions such as autonomic dysreflexia (AD), which is a potentially life-threatening condition comprising transient episodes of hypertension up to 300 mmHg. AD may be accompanied by symptoms and signs such as headache, flushing, and sweating. Delay in AD...
Static apnea provides a unique model that combines transient hypertension, hypercapnia, and severe hypoxemia. With apnea durations exceeding 5 min, the purpose of the present study was to determine how that affects cerebral free-radical formation and the corresponding implications for brain structure and function. Measurements were obtained before...
A strong relationship exists between acute coronary syndrome (ACS) and platelets (PLTs) volume. Mean platelet volume (MPV) is a parameter of PLT functions and a marker for increased PLT activation. The aim of this study was to determine early changes in number of total PLT and MPV in different manifestation of ACS and to find out predictive value o...
This study investigated the influence of ventilation on sympathetic action potential (AP) discharge patterns during varying levels of high chemoreflex stress. In seven trained breath-hold divers (33±12 yrs), we measured muscle sympathetic nerve activity (MSNA) at baseline, during preparatory rebreathing (RBR), and during i) functional residual capa...
We investigated the role of lung volume-induced changes in cardiac output (Q̇) on cerebrovascular regulation during prolonged apnoea. Fifteen elite apnoea divers (1F; 185 ± 7 cm, 82 ± 12 kg, 29 ± 7 years) attended the laboratory on two separate occasions and completed maximal breath-holds at total lung capacity (TLC) and functional residual capacit...
Pulmonary hyperinflation attained by glossopharyngeal insufflation (GPI) challenges the circulation by compressing the heart and pulmonary vasculature. Our aim was to determine the amount of blood translocated from the central blood volume during GPI. Cardiac output and cardiac chamber volumes were assessed by magnetic resonance imaging in twelve b...
Purpose:
Trained breath-hold divers hyperinflate their lungs by glossopharyngeal insufflation (GPI) to prolong submersion time and withstand lung collapse at depths. Pulmonary hyperinflation leads to profound hemodynamic changes.
Methods:
Thirteen divers performed preparatory breath-holds followed by apnea with GPI. Filling of extrathoracic vein...
Alteration of breathing pattern ranging from an increase of respiratory rate to overt hyperventilation during and after SCUBA diving is frequently reported and is associated with intrathoracic fluid overload. This study was undertaken to assess breathing efficiency after diving and the association with damage of alveolar cells. Ventilation efficien...
The determining mechanisms of a maximal hyperoxic apnea duration in elite apneists have remained unexplored. We tested the hypothesis that maximal hyperoxic apnea duration in elite apneists is related to forced vital capacity (FVC) but not the central chemoreflex (for CO2). Eleven elite apneists performed a maximal dry static-apnea with prior hyper...
The cerebral metabolic rate of oxygen (CMRO2) is reduced during apnea that yields profound hypoxia and hypercapnia. In this study, to dissociate the impact of hypoxia and hypercapnia on the reduction in CMRO2, 11 breath-hold competitors completed three apneas under: (a) normal conditions (NM), yielding severe hypercapnia and hypoxemia, (b) with pri...
Bailey, Damian M., Christopher K. Willie, Ryan L. Hoiland, Anthony R. Bain, David B. MacLeod, Maria A. Santoro, Daniel K. DeMasi, Andrea Andrijanic, Tanja Mijacika, Otto F. Barak, Zeljko Dujic, and Philip N. Ainslie. Surviving without oxygen: how low can the human brain go? High Alt Med Biol 00:000-000, 2016.-Hypoxic cerebral vasodilation is a high...
The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic...
Freedivers hold their breath while diving, causing blood oxygen levels to decrease (hypoxia) while carbon dioxide increases (hypercapnia). Whereas blood gas changes are presumably involved in the progression of respiratory diseases, less is known about their effect on healthy individuals. Here we have used gene expression profiling to analyze elite...
Introduction:
The pulmonary capillaries prevent stroke by filtering venous emboli from the circulation. Intrapulmonary arteriovenous anastomoses are large diameter (≥ 50μm) vascular connections in the lung that may compromise the integrity of the pulmonary capillary filter and have been recently linked to cryptogenic stroke and transient ischemic...
Key points:
The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radia...
We hypothesized that the cardioselective β1-adrenoreceptor antagonist esmolol would improve maximal apnea duration in elite breath hold divers. In elite national level divers (n=9), maximal apneas were performed in a randomized and counterbalanced order while receiving either i.v. esmolol (150μg ⋅ kg(-1) ⋅ min(-1)) or volume matched saline (placebo...
The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxemia at rest in chronic heart failure (CHF) subjects have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) could potentially contribute to arterial hypoxemia an...
The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compa...
Risk in SCUBA diving is often associated with the presence of gas bubbles in the venous circulation formed during decompression. Although it has been demonstrated time-after-time that, while venous gas emboli (VGE) often accompany decompression sickness (DCS), they are also frequently observed in high quantities in asymptomatic divers following eve...
Pulmonary hyperinflation is used by competitive breath-hold divers and is accomplished by glossopharyngeal insufflation (GPI) known to compress the heart and pulmonary vessels, increasing sympathetic activity and lowering cardiac output (CO) without known consequence for organ perfusion. Myocardial, pulmonary, skeletal muscle, kidney and liver perf...
The purpose of the study was to provide insight in diaphragmatic involuntary breathing movements (IBM) during struggle phase of apnea at total lung capacity (TLC) and functional residual capacity (FRC) using magnetic resonance imaging along with measurements of hemodynamics and arterial oxygenation. The study was performed in eight elite breath-hol...
Introduction. Conversion of images from DICOM format to other image formats affects measuring distances in images. Materials and methods. Distances in DICOM or JPEG images were measured with different zoom using 1.5T MRI scanning of human diaphragm during spontaneous breathing and during low and high lung volumes. Results. Correlation between dista...
Introduction. Conversion of images from DICOM format to other image formats affects measuring distances in images. Materials and methods. Distances in DICOM or JPEG images were measured with different zoom using 1.5T MRI scanning of human diaphragm during spontaneous breathing and during low and high lung volumes. Results. Correlation between dista...
The purpose of this study was to determine the impact of peripheral chemoreflex inhibition with low-dose dopamine on maximal apnea time, and the related hemodynamic and cerebrovascular responses in elite apnea divers. In a randomized order, participants performed a maximal apnea while receiving either I.V. 2µg･kg(-1)･min(-1) dopamine or volume matc...
Purpose:
The aim of the study was to assess changes in subarachnoid space width (sas-TQ), the marker of intracranial pressure (ICP), pial artery pulsation (cc-TQ) and cardiac contribution to blood pressure (BP), cerebral blood flow velocity (CBFV) and cc-TQ oscillations throughout the maximal breath hold in elite apnoea divers. Non-invasive assess...
Decompression sickness (DCS) is a systemic disorder assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles, vesicular structures with diameters of 0.1 to 1.0 µm, have been implicated but data in human divers has been lacking. We hypothesized that the number of blood-borne annexin V-positive micropar...
Predicated on evidence that diving-related microparticle generation is an oxidative stress response, this study investigated the role oxygen plays in augmenting production of annexin V-positive microparticles associated with open-water SCUBA diving and whether elevations can be abrogated by ascorbic acid. Following a cross-over study design, 14 mal...
Exercise training reduces pathological remodeling and improves cardiac function in ischemic heart failure, however, causal mechanisms underlying the cardiac benefits of exercise are poorly understood. Since opening of ATP-sensitive K (KATP) channels protects the heart during myocardial stress, we hypothesized that such a mechanism is responsible fo...
Laboratory and field investigations have demonstrated that intrapulmonary arteriovenous anastomoses (IPAVA) may provide an additional means for venous gas emboli (VGE) to cross over to the arterial circulation due to their larger diameter compared to pulmonary microcirculation. Once thought to be the primary cause of decompression sickness (DCS), i...
Arterialization of venous gas emboli (VGE) formed after surfacing from SCUBA diving can become arterial gas emboli (AGE) through intrapulmonary arterial-venous anastomoses (IPAVAs) that open with exercise.
METHODS:
We recruited twenty PFO negative SCUBA divers and conducted a field and a laboratory study with the aims to investigate the appearance...
The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and cardiorespiratory metrics were measured during maximum dry apneas in elite breath-hold divers (n=17). To isolate the eff...
AimSCUBA diving frequently involves repetitive exposures. The goal of this study was to see how exercise impacts microparticles (MPs), endothelial function and venous gas emboli (VGE) throughout multiple dives.Methods
Sixteen divers in two groups (G1 and G2) each completed six dives, three preceded by exercise (EX) and three as controls (CON). Bloo...
Background:
Venous gas emboli (VGE) have traditionally served as a marker for decompression stress after SCUBA diving and a reduction in bubble loads is a target for precondition procedures. However, VGE can be observed in large quantities with no negative clinical consequences. The effect of exercise before diving on VGE has been evaluated with m...
Background and Purpose: Leukocyte cell surface adhesion molecule CD11b, decorated with CD15s, plays a critical role in the regulation of P 2 integrin function during neutrophile endothelial transmigration. Hyperbaric oxygenation reduces neutrophil-endothelial cell adhesion, which is mediated by Mac-1 (CD11b/CD18) beta(2)-integrin. Materials and Met...
We have investigated the effects of the intravenous infusion of nitroglycerin (NTG), norepinephrine (NE) and aminophylline (AMP) on the opening and recruitment of intrapulmonary arteriovenous anastomoses (IPAVA) in healthy humans at rest. In ten volunteers saline contrast echocardiography was performed during administration of two doses of the NTG...
A single air dive causes transient endothelial dysfunction. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute synergistically to endothelial repair. In this study (1) the acute effects of diving on EPC numbers and CAC migration and (2) the influence of the gas mixture (air/nitrox-36) was investigated. Ten divers...
The goals of this study were to investigate the difference in responses between a SCUBA dive preceded by aerobic exercise (EX) and a non-exercise control dive (CON), and further evaluate the potential relationship between venous gas emboli (VGE) and microparticles (MP). We hypothesized that exercise would alter the quantity and subtype of annexin V...
Self-contained underwater breathing apparatus (SCUBA) diving is regularly associated with numerous asymptomatic changes in cardiovascular function. Freshwater SCUBA diving presents unique challenges compared with open sea diving related to differences in water density and the potential for dive locations at altitude. The aim of this study was to ev...
To examine whether dynamic cerebral autoregulation is acutely impaired during maximal voluntary apnoea in trained divers.
Mean arterial pressure (MAP), cerebral blood flow-velocity (CBFV) and end-tidal partial pressures of O2 and CO2 (PETO2 and PETCO2) were measured in eleven trained, male apnoea divers (28±2 yr; 182±2 cm, 76±7 kg) during maximal "...
In the present study we investigated the influence of end-expiratory breathing cessation on firing activity of muscle sympathetic fibers in 6 stable chronic heart failure (CHF) patients and in 6 healthy age and gender matched controls. Integrated multi-unit bursts, as well as action potentials (APs), were identified from multi-unit muscle sympathet...
