Tanja Mijacika

Hypercapnia is essential to reduce the cerebral oxidative metabolism during extreme apnea in humans

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 prior hyperventilation (HV), yielding severe hypoxemia only, and (c) with prior 100% oxygen breathing (HX), yielding the greatest level of hypercapnia, but in the absence of hypoxemia. The CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Secondary measures included net-cerebral glucose/lactate exchange and nonoxidative metabolism. Reductions in CMRO2 were largest in the HX condition (−44 ± 15%, p < 0.05), with the most severe hypercapnia (PaCO2 = 58 ± 5 mmHg) but maintained oxygen saturation. The CMRO2 was reduced by 24 ± 27% in NM (p = 0.05), but unchanged in the HV apnea where hypercapnia was absent. A net-cerebral lactate release was observed at the end of apnea in the HV and NM condition, but not in the HX apnea (main effect p < 0.05). These novel data support hypercapnia/pH as a key mechanism mediating reductions in CMRO2 during apnea, and show that severe hypoxemia stimulates lactate release from the brain.

Organ perfusion during voluntary pulmonary hyperinflation; a magnetic resonance imaging study.

Pulmonary hyperinflation is used by competitive breath-hold divers and is accomplished by glossopharyngeal insufflation (GPI), which is 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 perfusion were evaluated by magnetic resonance imaging in 10 elite breath-hold divers at rest and during moderate GPI. Cardiac chamber volumes, stroke volume, and thus CO were determined from cardiac short-axis cine images. Organ volumes were assessed from gradient echo sequences, and organ perfusion was evaluated from first-pass images after gadolinium injection. During GPI, lung volume increased by 5.2 ± 1.5 liters (mean ± SD; P < 0.001), while spleen and liver volume decreased by 46 ± 39 and 210 ± 160 ml, respectively (P < 0.05), and inferior caval vein diameter by 4 ± 3 mm (P < 0.05). Heart rate tended to increase (67 ± 10 to 86 ± 20 beats/min; P = 0.052) as right and left ventricular volumes were reduced (P < 0.05). Stroke volume (107 ± 21 to 53 ± 15 ml) and CO (7.2 ± 1.6 to 4.2 ± 0.8 l/min) decreased as assessed after 1 min of GPI (P < 0.01). Left ventricular myocardial perfusion maximum upslope and its perfusion index decreased by 1.52 ± 0.15 s(-1) (P < 0.001) and 0.02 ± 0.01 s(-1) (P < 0.05), respectively, without transmural differences. Pulmonary tissue, spleen, kidney, and pectoral-muscle perfusion also decreased (P < 0.05), and yet liver perfusion was maintained. Thus, during pulmonary hyperinflation by GPI, CO and organ perfusion, including the myocardium, as well as perfusion of skeletal muscles, are reduced, and yet perfusion of the liver is maintained. Liver perfusion seems to be prioritized when CO decreases during GPI.

Disturbed blood flow worsens endothelial dysfunction in moderate-severe chronic obstructive pulmonary disease

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-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P < 0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated circulating markers of endothelial cell apoptosis (CD31+/CD41b− microparticles) in COPD patients, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41b− microparticles, and improved FMD after accounting for the shear stress stimulus. We have demonstrated that acutely disturbed blood flow with increased retrograde shear stress further deteriorates the already impaired endothelial function with attendant endothelial apoptosis in patients with moderate-severe COPD.

Ventilation inhibits sympathetic action potential recruitment even during severe chemoreflex stress

The current study demonstrates that the sympathetic neural recruitment patterns observed during chemoreflex activation induced by rebreathing or apnea are restrained and/or inhibited by the act of ventilation per se, despite similar, or even greater, levels of severe chemoreflex stress. Therefore, ventilation modulates not only the timing of sympathetic bursts but also the within-burst axonal recruitment normally observed during progressive chemoreflex stress.

Forced vital capacity and not central chemoreflex predicts maximal hyperoxic breath-hold duration in elite apneists

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 hyperoxic (100% oxygen) pre-breathing, and a central chemoreflex test via a hyperoxic re-breathing technique (hyperoxic-hypercapnic ventilatory response: HCVR); expressed as the increase in ventilation (pneumotachometry) per increase in arterial CO2 tension (PaCO2; radial artery). FVC was assessed using standard spirometry. Maximal apnea duration ranged from 807 to 1262s (mean=1034s). Average HCVR was 2.0±1.2Lmin-1mmHg-1 PaCO2. The hyperoxic apnea duration was related to the FVC (r2=0.45, p<0.05), but not the HCVR (r2<0.01, p>0.05). These findings were interpreted to suggest that during a hyperoxic apnea, a larger initial lung volume prolongs the time before reaching intolerable discomfort associated with pending lung squeeze, while CO2 sensitivity has little impact.

Sports-related lung injury during breath-hold diving.

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 pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise. In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions. Acutely, repetitive breath-hold diving may result in increased transpulmonary capillary pressure, leading to noncardiogenic oedema and/or alveolar haemorrhage. Furthermore, during a breath-hold dive, the chest and lungs are compressed by the increasing pressure of water. Rapid changes in lung air volume during descent or ascent can result in a lung injury known as pulmonary barotrauma. Factors that may influence individual susceptibility to breath-hold diving-induced lung injury range from underlying pulmonary or cardiac dysfunction to genetic predisposition. According to the available data, breath-holding does not result in chronic lung injury. However, studies of large populations of breath-hold divers are necessary to firmly exclude long-term lung damage. Breath-hold diving may result in acute respiratory symptoms, but does not lead to chronic lung dysfunction http://ow.ly/D03r302uMOD

Oxygen therapy improves cerebral oxygen delivery and neurovascular function in hypoxaemic chronic obstructive pulmonary disease patients

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 obstructive pulmonary disease patients. This improvement in cerebral oxygen delivery and neurovascular function might provide a physiological link between oxygen therapy and a reduced risk of cerebrovascular disease (e.g. stroke, mild cognitive impairment and dementia) in chronic obstructive pulmonary disease.

Wavelet decomposition analysis is a clinically relevant strategy to evaluate cerebrovascular buffering of blood pressure after spinal cord injury

The capacity of the cerebrovasculature to buffer changes in blood pressure (BP) is crucial to prevent stroke, the incidence of which is three- to fourfold 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 cerebrovascular buffering of BP, such as transfer function, have been used in SCI research. This approach does not account for inherent nonlinearity and nonstationarity components of cerebrovascular regulation, often depends on perturbations of BP to increase the statistical power, and does not account for the influence of arterial CO2 tension. Here, we used a nonlinear and nonstationary analysis approach termed wavelet decomposition analysis (WDA), which recently identified novel sympathetic influences on cerebrovascular buffering of BP occurring in the ultra-low-frequency range (ULF; 0.02-0.03Hz). WDA does not require BP perturbations and can account for influences of CO2 tension. Supine resting beat-by-beat BP (Finometer), middle cerebral artery blood velocity (transcranial Doppler), and end-tidal CO2 tension were recorded in cervical SCI ( n = 14) and uninjured ( n = 16) individuals. WDA revealed that cerebral blood flow more closely follows changes in BP in the ULF range ( P = 0.0021, Cohens d = 0.89), which may be interpreted as an impairment in cerebrovascular buffering of BP. This persisted after accounting for CO2. Transfer function metrics were not different in the ULF range, but phase was reduced at 0.07-0.2 Hz ( P = 0.03, Cohens d = 0.31). Sympathetically mediated cerebrovascular buffering of BP is impaired after SCI, and WDA is a powerful strategy for evaluating cerebrovascular buffering in clinical populations.

Alarming blood pressure changes during routine bladder emptying in a woman with cervical spinal cord injury

IntroductionMany 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 recognition and management is associated with increased incidence of cardiovascular events and disease. As it is commonly triggered by bladder distension, AD continues to be a major concern for individuals living with SCI, both on a daily basis and in the long-term.Case presentationA 58-year-old woman with C3 AIS B SCI presented with low resting blood pressure (BP) at 100/64 mmHg. She reported frequent episodes of AD that were most commonly attributed to urinary bladder filling. During our testing session, her systolic BP rose to 130 mmHg, at which point her care aide stepped in to utilize the Credé maneuver, which was part of her daily routine for bladder emptying. Application of suprapubic pressure further elevated her systolic BP to 230 mmHg. Throughout the episode of AD, the participant experienced a pounding headache and erythema above the LOI.DiscussionClinical guidelines for bladder management after SCI recommend avoiding the Credé maneuver due to potential complications such as hernia or bruising. This current case report demonstrates the additional risk of inducing AD and dangerously high BP elevation.

Effect of pulmonary hyperinflation on central blood volume: An MRI study

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 breath-hold divers at rest and during apnea with GPI. Pulmonary blood volume was determined from pulmonary blood flow and transit times for gadolinium during first-pass perfusion after intravenous injection. During GPI, the lung volume increased by 0.8±0.6L (11±7%) above the total lung capacity. All cardiac chambers decreased in volume and despite a heart rate increase of 24±29 bpm (39±50%), pulmonary blood flow decreased by 2783±1820mL (43±20%). The pulmonary transit time remained unchanged at 7.5±2.2s and pulmonary blood volume decreased by 354±176mL (47±15%). In total, central blood volume decreased by 532±248mL (46±14%). Voluntary pulmonary hyperinflation leads to ∼50% decrease in pulmonary and central blood volume.