Svein Erik Gaustad

High incidence of venous and arterial gas emboli at rest after trimix diving without protocol violations

SCUBA diving is associated with generation of gas emboli due to gas release from the supersaturated tissues during decompression. Gas emboli arise mostly on the venous side of circulation, and they are usually eliminated as they pass through the lung vessels. Arterialization of venous gas emboli (VGE) is seldom reported, and it is potentially related to neurological damage and development of decompression sickness. The goal of the present study was to evaluate the generation of VGE in a group of divers using a mixture of compressed oxygen, helium, and nitrogen (trimix) and to probe for their potential appearance in arterial circulation. Seven experienced male divers performed three dives in consecutive days according to trimix diving and decompression protocols generated by V-planner, a software program based on the Varying Permeability Model. The occurrence of VGE was monitored ultrasonographically for up to 90 min after surfacing, and the images were graded on a scale from 0 to 5. The performed diving activities resulted in a substantial amount of VGE detected in the right cardiac chambers and their frequent passage to the arterial side, in 9 of 21 total dives (42%) and in 5 of 7 divers (71%). Concomitant measurement of mean pulmonary artery pressure revealed a nearly twofold augmentation, from 13.6 ± 2.8, 19.2 ± 9.2, and 14.7 ± 3.3 mmHg assessed before the first, second, and the third dive, respectively, to 26.1 ± 5.4, 27.5 ± 7.3, and 27.4 ± 5.9 mmHg detected after surfacing. No acute decompression-related disorders were identified. The observed high gas bubble loads and repeated microemboli in systemic circulation raise questions about the possibility of long-term adverse effects and warrant further investigation.

Venous gas embolism as a predictive tool for improving CNS decompression safety

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached.

Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model ☆

BACKGROUND Animal studies show reduced inotropic effects of cardiac β-adrenoceptor agonists like epinephrine (Epi) during hypothermia and rewarming, while drugs targeting other pharmacological mechanisms have positive effects. This study therefore aimed to determine β-adrenoceptor sensitivity in isolated cardiomyocytes and investigate hemodynamic effects of Epi and its ability to stimulate cardiac β-adrenoceptors at different temperatures in vivo. METHODS Isolated rat myocardial cells were incubated with the radioactive β-adrenoceptor ligand [(3)H]-CGP12177 and propranolol, used as a displacer. Cells were subjected to normothermia (37 °C) or hypothermia (15 °C). After incubation, radioactivity was measured to estimate β-adrenoceptor affinity for propranolol (IC50), as a measure of β-adrenoceptor sensitivity. In separate in vivo experiments, Epi (1.25 μg/min) was administered the last 5min of experiments in normothermic (37 °C, 5h), hypothermic (4h at 15 °C) and rewarmed rats (4h at 15 °C, and subsequently rewarmed to 37 °C). Hemodynamic parameters were monitored during infusion. Hearts were thereafter freeze-clamped and tissue cAMP was measured. RESULTS In vitro measurements of IC50 for propranolol showed a hypothermia-induced increase in β-adrenoceptor sensitivity at 15 °C. Corresponding in vivo experiments at 15 °C showed decreased cardiac output and stroke volume, whereas total peripheral resistance (TPR) increased during Epi infusion, simultaneous with a 4-fold cAMP increase. CONCLUSIONS This experiment shows a hypothermia-induced in vivo and in vitro increase of cardiac β-adrenoceptor sensitivity, and simultaneous lack of inotropic effects of Epi in the presence of increased TPR. Our findings therefore indicate that hypothermia-induced reduction in inotropic effects of Epi is due to substantial elevation of TPR, rather than β-adrenoceptor dysfunction.

Ultrasonic evidence of acute interstitial lung edema after SCUBA diving is resolved within 2-3h.

Recently, an increase in extravascular lung water (EVLW) accumulation with diminished left ventricular contractility within 60 min after SCUBA diving was reported. We have observed previously that diving was associated with reduced diffusing lung capacity for carbon monoxide (DLCO) and arterial oxygen pressure for up to 60-80 min postdive. Here we investigated whether increased EVLW persists 2-3h after successive deep dives in a group of seven male divers. The echocardiographic indices of pulmonary water accumulation (ultrasound lung comets (ULC)) and left ventricular function, respiratory functional measurements and arterial oxygen saturation (SaO(2)) were assessed 2-3h post diving, while venous gas bubbles (VGB) and the blood levels of NT-proBNP and proANP were analyzed 40 min after surfacing. Spirometry values, flow-volume, DLCO, SaO(2) and ULC were unchanged after each dive, except for significant increase in ULC after the second dive. Left ventricular function was reduced, while NT-proBNP and proANP levels were significantly elevated after majority of dives, suggesting a cardiac strain.

A valid and reproducible protocol for testing maximal oxygen uptake in rabbits

Background Physiological studies of long-term cardiovascular adaptation to exercise require adequate testing procedures to quantify the outcome. Such test procedures are well established in rats and mice. However, the use of these species may have limitations, and to study several physiological parameters mimicking ‘the human adaptation’ larger animal models may be preferable. Here, we established a valid and reproducible exercise test protocol for measuring maximal oxygen uptake (VO2max) in rabbits. Methods and results The VO2max protocol was studied in six adult female New Zealand White rabbits running on a treadmill at inclinations ranging from 0 to 20°.VO2max was reached at all inclinations indicating that the rabbits reach exhaustion independent of inclination. Average VO2max for test and retest were 35.1 ± 4.2 and 35.8 ± 4.0 ml/kg per min, respectively. Oxygen uptake and heart rate increased linearly with increased running speed. Average running speed at VO2max was 0.51 ± 0.09 m/s, and there was an increase oxygen pulse up to the intensity corresponding to VO2max, where it leveled off and declined. Conclusion This study shows that rabbit is a suitable species for studying responses to training and could be of great importance for showing novel cellular cardiac adaptations to training.

Cardiorespiratory Reference Data in Older Adults: The Generation 100 Study.

Purpose Cardiorespiratory fitness (CRF) is regarded a clinical vital sign, and accurate reference values for all age groups are essential. Little data exist on CRF and cardiorespiratory function in older adults. The aim of this study was to provide normative values for CRF and cardiorespiratory function in older adults, including people with history of cardiovascular diseases (CVD). Methods In total, 1537 (769 women) participants age 70 to 77 yr underwent clinical examinations and cardiopulmonary exercise tests. Peak oxygen uptake (V˙O2peak), ventilation (V˙Epeak), expiration of carbon dioxide (VV˙CO2peak), breathing frequency (BFpeak), tidal volume (VTpeak), oxygen pulse (O2 pulsepeak), ventilatory efficiency (EqV˙O2peak and EqV˙CO2peak), and 1-min HR recovery were assessed. Results Men compared with women had higher V˙O2peak (31.3 ± 6.7 vs 26.2 ± 5.0 mL·min−1·kg−1), BFpeak (41.8 ± 8.0 vs 39.7 ± 7.1 breaths per minute), VTpeak (2.3 ± 0.5 vs 1.6 ± 0.3), O2 pulsepeak (16.4 ± 3.2 vs 11.3 ± 2.0), V˙CO2peak (2.9 ± 0.2 and 1.9 ± 0.1 L·min−1), V˙Epeak (96.2 ± 21.7 vs 61.1 ± 21.6 L·min−1), EqV˙O2peak (38.0 ± 6.9 vs 35.1 ± 5.6), and EqV˙CO2peak (33.5 ± 5.7 vs 31.9 ± 4.5). Women and men with CVD had lower V˙O2peak (14% and 19%), peak HR (5% and 6%), V˙Epeak (8% and 10%), VTpeak (7% and 4%), and lower EqV˙CO2peak (4% and 6%) compared with their healthy counterparts, respectively. Compared with healthy women and men, 1-min HR recovery was 12% and 16% lower for women and men with CVD. Conclusions This study represents the largest reference material on directly measured CRF and cardiorespiratory function in older men and women, with and without CVD. This novel information will help researchers and clinicians to interpret data form cardiopulmonary testing in older adults.

Acute exhaustive aerobic exercise training impair cardiomyocyte function and calcium handling in Sprague-Dawley rats

Introduction Recent data from long-distance endurance participants suggest that cardiac function is impaired after completion. Existing data further indicate that right ventricular function is more affected than left ventricular function. The cellular mechanisms underpinning cardiac deterioration are limited and therefore the aim of this study was to examine cardiomyocyte and molecular responses of the right and left ventricle to an acute bout of exhaustive endurance exercise. Materials and methods Male Sprague-Dawley rats were assigned to sedentary controls or acute exhaustive endurance exercise consisting of a 120 minutes long forced treadmill run. The contractile function and Ca2+ handling properties in isolated cardiomyocytes, protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban including two of its phosphorylated states (serine 16 and threonine 17), and the mitochondrial respiration in permeabilized cardiac muscle fibers were analyzed. Results The exercise group showed a significant reduction in cardiomyocyte fractional shortening (right ventricle 1 Hz and 3 Hz p<0.001; left ventricle 1 Hz p<0.05), intracellular Ca2+ amplitude (right ventricle 1 and 3 Hz p<0.001; left ventricle 1 Hz p<0.01 and 3 Hz p<0.05) and rate of diastolic Ca2+ decay (right ventricle 1 Hz p<0.001 and 3 Hz p<0.01; left ventricle 1 and 3 Hz p<0.01). Cardiomyocyte relaxation during diastole was only significantly prolonged at 3 Hz in the right ventricle (p<0.05) compared to sedentary controls. We found an increase in phosphorylation of phospholamban at serine 16 and threonine 17 in the left (p<0.05), but not the right, ventricle from exhaustively exercised animals. The protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban was not changed. Furthermore, we found a reduction in maximal oxidative phosphorylation and electron transport system capacities of mitochondrial respiration in the right (p<0.01 and p<0.05, respectively), but not the left ventricle from rats subjected to acute exhaustive treadmill exercise. Conclusion Acute exhaustive treadmill exercise is associated with impairment of cardiomyocyte Ca2+ handling and mitochondrial respiration that causes depression in both contraction and diastolic relaxation of cardiomyocytes.

Erratum to: Venous gas embolism as a predictive tool for improving CNS decompression safety

Erratum to: Eur J Appl PhysiolDOI 10.1007/s00421-011-1998-9An incorrect citation was included in the originalpublication:Vince RV, Chrismas B, Midgley AW, McNaughton LR,Madden LA (2009) Hypoxia mediated release of endo-thelial microparticles and increased association ofS100A12 with circulating neutrophils. Oxid Med CellLongev 2:2–6The correct reference should be:Vince RV, McNaughton LR, Taylor L, Midgley AW,Laden G, Madden LA (2009) Release of VCAM-1 asso-ciated endothelial microparticles following simulatedSCUBA dives. Eur J Appl Physiol 105:507–513

Immersion before dry simulated dive reduces cardiomyocyte function and increases mortality after decompression.

Diving and decompression performed under immersed conditions have been shown to reduce cardiac function. The mechanisms for these changes are not known. The effect of immersion before a simulated hyperbaric dive on cardiomyocyte function was studied. Twenty-three rats were assigned to four groups: control, 1 h thermoneutral immersion, dry dive, and 1 h thermoneutral immersion before a dive (preimmersion dive). Rats exposed to a dive were compressed to 700 kPa, maintained for 45 min breathing air, and decompressed linearly to the surface at a rate of 50 kPa/min. Postdive, the animals were anesthetized and the right ventricle insonated for bubble detection using ultrasound. Isolation of cardiomyocytes from the left ventricle was performed and studied using an inverted fluorescence microscope with video-based sarcomere spacing. Compared with a dry dive, preimmersion dive significantly increased bubble production and decreased the survival time (bubble grade 1 vs. 5, and survival time 60 vs. 17 min, respectively). Preimmersion dive lead to 18% decreased cardiomyocyte shortening, 20% slower diastolic relengthening, and 22% higher calcium amplitudes compared with controls. The protein levels of the sarco-endoplasmic reticulum calcium ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and phospholamban phosphorylation in the left ventricular tissue were significantly reduced after both dry and preimmersion dive compared with control and immersed animals. The data suggest that immersion before a dive results in impaired cardiomyocyte and Ca2+ handling and may be a cellular explanation to reduced cardiac function observed in humans after a dive.