Dennis Madden

Bubbles, microparticles, and neutrophil activation: changes with exercise level and breathing gas during open-water SCUBA diving

The study goal was to evaluate responses in humans following decompression from open-water SCUBA diving with the hypothesis that exertion underwater and use of a breathing mixture containing more oxygen and less nitrogen (enriched air nitrox) would alter annexin V-positive microparticle (MP) production and size changes and neutrophil activation, as well as their relationships to intravascular bubble formation. Twenty-four divers followed a uniform dive profile to 18 m of sea water breathing air or 22.5 m breathing 32% oxygen/68% nitrogen for 47 min, either swimming with moderately heavy exertion underwater or remaining stationary at depth. Blood was obtained pre- and at 15 and 120 min postdive. Intravascular bubbles were quantified by transthoracic echocardiography postdive at 20-min intervals for 2 h. There were no significant differences in maximum bubble scores among the dives. MP number increased 2.7-fold, on average, within 15 min after each dive; only the air-exertion dive resulted in a significant further increase to 5-fold over baseline at 2 h postdive. Neutrophil activation occurred after all dives. For the enriched air nitrox stationary at depth dive, but not for other conditions, the numbers of postdive annexin V-positive particles above 1 μm in diameter were correlated with intravascular bubble scores (correlation coefficients ∼0.9, P < 0.05). We conclude that postdecompression relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation appear to exist, but more study is required to improve confidence in the associations.

Regulation of brain blood flow and oxygen delivery in elite breath-hold divers

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 effects of apnea and IBM from the concurrent changes on ABG, end-tidal forcing (‘clamp’) was then used to replicate an identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23  to 37 mm Hg (30±7 mm Hg). Elevation in mean arterial pressure was greater during apnea than during clamp reaching +54±24% versus 34±26%, respectively; however, CBF increased similarly between apnea and clamp (93.6±28% and 83.4±38%, respectively). This latter observation indicates that during the overall apnea period IBM per se do not augment CBF and that the brain remains sufficiently protected against hypertension. Termination of apnea was not determined by reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial oxygen content, oxygen delivery was maintained by commensurately increased CBF.

Exercise before SCUBA diving ameliorates decompression- induced neutrophil activation

INTRODUCTION The goals of this study were to investigate the difference in responses between a scuba dive preceded by aerobic exercise (EX) and a nonexercise control dive (CON) and to further evaluate the potential relation between venous gas emboli (VGE) and microparticles (MP). We hypothesized that exercise would alter the quantity and subtype of annexin V-positive MP and VGE. METHODS Nineteen divers performed two dives to 18 m seawater for 41 min separated by at least 3 d, one of which was preceded by 60 min of treadmill interval exercise. Blood was obtained before exercise, before diving, and 15 min, 2 h, 4 h, and 24 h after surfacing. Intravascular bubbles were quantified by transthoracic echocardiography at 15, 40, 80, and 120 min. RESULTS The median VGE remained unchanged between the two dives; however, there was a significant increase in VGE in the exercise dive at 40 and 80 min at rest. MP were significantly elevated by approximately 2 times at all time points after CON compared with those after EX. Markers of neutrophil and platelet activation were elevated by both dives, and these elevations were attenuated in the EX dive. CONCLUSIONS We conclude that some of the differences observed between the EX and CON related to MP and platelet and neutrophil activation provide additional insight into the potential protective benefits of exercise; however, further study is needed to understand the mechanism and true potential of these benefits.

Exercise after SCUBA diving increases the incidence of arterial gas embolism

Arterialization of gas bubbles after decompression from scuba diving has traditionally been associated with pulmonary barotraumas or cardiac defects, such as the patent foramen ovale. Recent studies have demonstrated the right-to-left passage of bubbles through intrapulmonary arterial-venous anastamoses (IPAVA) that allow blood to bypass the pulmonary microcirculation. These passages open up during exercise, and the aim of this study is to see if exercise in a postdiving period increases the incidence of arterialization. After completing a dive to 18 m for 47 min, patent foramen ovale-negative subjects were monitored via transthoracic echocardiography, within 10 min after surfacing, for bubble score at rest. Subjects then completed an incremental cycle ergometry test to exhaustion under continuous transthoracic echocardiography observation. Exercise was suspended if arterialization was observed and resumed when the arterialization cleared. If arterialization was observed a second time, exercise was terminated, and oxygen was administered. Out of 23 subjects, 3 arterialized at rest, 12 arterialized with exercise, and 8 did not arterialize at all even during maximal exercise. The time for arterialization to clear with oxygen was significantly shorter than without. Exercise after diving increased the incidence of arterialization from 13% at rest to 52%. This study shows that individuals are capable of arterializing through IPAVA, and that the intensity at which these open varies by individual. Basic activities associated with SCUBA diving, such as surface swimming or walking with heavy equipment, may be enough to allow the passage of venous gas emboli through IPAVA.

Effect of Maximal Apnoea Easy-Going and Struggle Phases on Subarachnoid Width and Pial Artery Pulsation in Elite Breath-Hold Divers

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 assessment of sas-TQ and cc-TQ became possible due to recently developed method based on infrared radiation, called near-infrared transillumination/backscattering sounding (NIR-T/BSS). Methods The experimental group consisted of seven breath-hold divers (six men). During testing, each participant performed a single maximal end-inspiratory breath hold. Apnoea consisted of the easy-going and struggle phases (characterised by involuntary breathing movements (IBMs)). Heart rate (HR) was determined using a standard ECG. BP was assessed using the photoplethysmography method. SaO2 was monitored continuously with pulse oximetry. A pneumatic chest belt was used to register thoracic and abdominal movements. Cerebral blood flow velocity (CBFV) was estimated by a 2-MHz transcranial Doppler ultrasonic probe. sas-TQ and cc-TQ were measured using NIR-T/BSS. Wavelet transform analysis was performed to assess cardiac contribution to BP, CBFV and cc-TQ oscillations. Results Mean BP and CBFV increased compared to baseline at the end of the easy phase and were further augmented by IBMs. cc-TQ increased compared to baseline at the end of the easy phase and remained stable during the IBMs. HR did not change significantly throughout the apnoea, although a trend toward a decrease during the easy phase and recovery during the IBMs was visible. Amplitudes of BP, CBFV and cc-TQ were augmented. sas-TQ and SaO2 decreased at the easy phase of apnoea and further decreased during the IBMs. Conclusions Apnoea increases intracranial pressure and pial artery pulsation. Pial artery pulsation seems to be stabilised by the IBMs. Cardiac contribution to BP, CBFV and cc-TQ oscillations does not change throughout the apnoea.

Intrapulmonary Shunt and SCUBA Diving: Another Risk Factor?

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), it has been demonstrated that, even in large quantities, their presence does not always result in injury. Normally, VGE are trapped in the site of gas exchange in the lungs and eliminated via diffusion. When VGE crossover takes place in arterial circulation, they have the potential to cause more harm as they are redistributed to the brain, spinal column, and other sensitive tissues. The patent foramen ovale (PFO) was once thought to be the only risk factor for an increase in arterialization; however, IPAVAs represent another pathway for this crossover to occur. The opening of IPAVAs is associated with exercise and hypoxic gas mixtures, both of which divers may encounter. The goal of this review is to describe how IPAVAs may impact diving physiology, specifically during decompression, and what this means for the individual diver as well as the future of commercial and recreational diving. Future research must continue on the relationship between IPAVAs and the environmental and physiological circumstances that lead to their opening and closing, as well as how they may contribute to diving injuries such as DCS.

Very Few Exercise-Induced Arterialized Gas Bubbles Reach the Cerebral Vasculature.

INTRODUCTION Arterialization of venous gas emboli (VGE) formed after surfacing from SCUBA diving can become arterial gas emboli (AGE) through intrapulmonary arterial-venous anastomoses that open with exercise. METHODS We recruited twenty patent foramen ovale-negative SCUBA divers and conducted a field and a laboratory study with the aim of investigating the appearance of AGE in intracranial vessels. At the field, they performed a single dive to a depth of 18-m sea water with a 47-min bottom time and a direct ascent to the surface. Transthoracic echocardiography was used to score VGE and AGE, and transcranial Doppler was used to visualize middle and posterior cerebral arteries with automated objective bubble detection. Observations were conducted for 45-min after dive at rest and at the laboratory after agitated saline injection at rest and throughout an incremental cycle supine exercise test until exhaustion and for 10 min of recovery. RESULTS After resurfacing, all divers presented endogenous VGE and arterialization was present in three divers. Saline contrast injection led to AGE in nine of 19 subjects at rest. AGE that reached the cerebral arteries after dive were recorded in two divers at 60 W, three at 90 W, five at 120 W, six at 150 W, and four at 180 W and in three, four, five, nine, and nine, respectively, after saline contrast injection in the laboratory. All divers had AGE grades of 1 or 2, and only single AGE reached the cerebral vasculature. CONCLUSIONS These data suggest that few emboli of venous origin reach the brain through exercise-induced intrapulmonary arterial-venous anastomoses but cerebral embolization is not high risk in the studied population.

Peripheral chemoreflex inhibition with low-dose dopamine; new insight into mechanisms of extreme apnea

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 intravenous 2 μg·kg(-1)·min(-1) dopamine or volume-matched saline (placebo). The chemoreflex and hemodynamic response to dopamine was also assessed during hypoxia [arterial O2 tension, (PaO2 ) ∼35 mmHg] and mild hypercapnia [arterial CO2 tension (PaCO2 ) ∼46 mmHg] that mimicked the latter parts of apnea. Outcome measures included apnea duration, arterial blood gases (radial), heart rate (HR, ECG), mean arterial pressure (MAP, intra-arterial), middle (MCAv) and posterior (PCAv) cerebral artery blood velocity (transcranial ultrasound), internal carotid (ICA) and vertebral (VA) artery blood flow (ultrasound), and the chemoreflex responses. Although dopamine depressed the ventilatory response by 27 ± 41% (vs. placebo; P = 0.01), the maximal apnea duration was increased by only 5 ± 8% (P = 0.02). The PaCO2 and PaO2 at apnea breakpoint were similar (P > 0.05). When compared with placebo, dopamine increased HR and decreased MAP during both apnea and chemoreflex test (P all <0.05). At rest, dopamine compared with placebo dilated the ICA (3.0 ± 4.1%, P = 0.05) and VA (6.6 ± 5.0%, P < 0.01). During apnea and chemoreflex test, conductance of the cerebral vessels (ICA, VA, MCAv, PCAv) was increased with dopamine; however, flow (ICA and VA) was similar. At least in elite apnea divers, the small increase in apnea time and similar PaO2 at breakpoint (∼31 mmHg) suggest the apnea breakpoint is more related to PaO2 , rather than peripheral chemoreflex drive to breathe.

Ascorbic acid supplementation diminishes microparticle elevations and neutrophil activation following SCUBA diving

Predicated on evidence that diving-related microparticle generation is an oxidative stress response, this study investigated the role that 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 male subjects ingested placebo and 2-3 wk later ascorbic acid (2 g) daily for 6 days prior to performing either a 47-min dive to 18 m of sea water while breathing air (∼222 kPa N2/59 kPa O2) or breathing a mixture of 60% O2/balance N2 from a tight-fitting face mask at atmospheric pressure for 47 min (∼40 kPa N2/59 kPa O2). Within 30 min after the 18-m dive in the placebo group, neutrophil activation, and platelet-neutrophil interactions occurred, and the total number of microparticles, as well as subgroups bearing CD66b, CD41, CD31, CD142 proteins or nitrotyrosine, increased approximately twofold. No significant elevations occurred among divers after ingesting ascorbic acid, nor were elevations identified in either group after breathing 60% O2. Ascorbic acid had no significant effect on post-dive intravascular bubble production quantified by transthoracic echocardiography. We conclude that high-pressure nitrogen plays a key role in neutrophil and microparticle-associated changes with diving and that responses can be abrogated by dietary ascorbic acid supplementation.

The effects of nitroglycerin, norepinephrine and aminophylline on intrapulmonary arteriovenous anastomoses in healthy humans at rest

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 (3μgkg(-1)min(-1) and 6μgkg(-1)min(-1)) and NE (0.1μgkg(-1)min(-1) and 0.25μgkg(-1)min(-1)) as well as 30min following the administration of AMP at rate of 6mgkg(-1). Echocardiography was used to assign bubble scores (0-5) based on the number and spatial distribution of bubbles in the left ventricle. Doppler ultrasound was used to estimate pulmonary artery systolic pressure. Using a Finometer the following hemodynamic parameters were assessed: heart rate, stroke volume, cardiac output, total peripheral resistance as well as systolic, diastolic and mean arterial pressure. The most important finding from the current study was that nitroglycerin, norepinephrine and aminophylline in the applied doses were not found to promote IPAVA opening in healthy humans at rest.