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Introduction: Elite breath-hold divers (BHD) possess several oxygen conserving adaptations to endure long dives similar to diving mammals. During dives, Bottlenose Dolphins may increase the alveolar ventilation (V A ) to perfusion (Q) ratio to increase alveolar oxygen delivery. We hypothesized that BHD possess similar adaptive mechanisms during apnea., Methods and Results: Pulmonary blood volume (PBV) was determined by echocardiography, 15 O-H 2 O PET/CT, and cardiac MRi, (n = 6) during and after maximum apneas. Pulmonary function was determined by body box spirometry and compared to matched controls. After 2 min of apnea, the PBV determined by echocardiography and 15 O-H 2 O-PET/CT decreased by 26% and 41%, respectively. After 4 min of apnea, the PBV assessed by echocardiography and cardiac MRi decreased by 48% and 67%, respectively (n = 6). Fractional saturation (F)O 2 Hb determined by arterial blood-gas-analyses collected after warm-up and a 5-minute pool-apnea (n = 9) decreased by 43%. Compared to matched controls (n = 8), spirometry revealed a higher total and alveolar-lung-capacity in BHD (n = 9), but a lower diffusion-constant., Conclusion: Our results contrast with previous studies, that demonstrated similar lung gas transfer in BHD and matched controls. We conclude that elite BHD 1) have a lower diffusion constant than matched controls, and 2) gradually decrease PBV during apnea and in turn increase V A /Q to increase alveolar oxygen delivery during maximum apnea. We suggest that BHD possess pulmonary adaptations similar to diving mammals to tolerate decreasing tissue oxygenation., New and Noteworthy: This manuscript addresses novel knowledge on tolerance to hypoxia during diving, which is shared by elite breath-hold divers and adult diving mammals: Our study indicates that elite breath-hold divers gradually decrease pulmonary blood volume and in turn increase VA/Q, to increase alveolar oxygen delivery during maximum apnea to tolerate decreasing oxygen levels similar to the Bottlenose Dolphin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kjeld, Isbrand, Arendrup, Højberg, Bejder, Krag, Vissing, Tolbod, Harms, Gormsen, Fuglø and Hansen.)

Introduction: Elite breath-hold divers (BHD) enduring apneas of more than 5 min are characterized by tolerance to arterial blood oxygen levels of 4.3 kPa and low oxygen-consumption in their hearts and skeletal muscles, similar to adult seals. Adult seals possess an adaptive higher hemoglobin-concentration and Bohr effect than pups, and when sedated, adult seals demonstrate a blood shift from the spleen towards the brain, lungs, and heart during apnea. We hypothesized these observations to be similar in human BHD. Therefore, we measured hemoglobin- and 2,3-biphosphoglycerate-concentrations in BHD ( n = 11) and matched controls ( n = 11) at rest, while myocardial mass, spleen and lower extremity volumes were assessed at rest and during apnea in BHD., Methods and Results: After 4 min of apnea, left ventricular myocardial mass (LVMM) determined by 15 O-H 2 O-PET/CT ( n = 6) and cardiac MRI ( n = 6), was unaltered compared to rest. During maximum apnea (∼6 min), lower extremity volume assessed by DXA-scan revealed a ∼268 mL decrease, and spleen volume, assessed by ultrasonography, decreased ∼102 mL. Compared to age, BMI and VO 2 max matched controls ( n = 11), BHD had similar spleen sizes and 2,3- biphosphoglycerate-concentrations, but higher total hemoglobin-concentrations., Conclusion: Our results indicate: 1) Apnea training in BHD may increase hemoglobin concentration as an oxygen conserving adaptation similar to adult diving mammals. 2) The blood shift during dry apnea in BHD is 162% more from the lower extremities than from the spleen. 3) In contrast to the previous theory of the blood shift demonstrated in sedated adult seals, blood shift is not towards the heart during dry apnea in humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kjeld, Krag, Brenøe, Møller, Arendrup, Højberg, Fuglø, Hancke, Tolbod, Gormsen, Vissing and Hansen.)

Introduction: The cardiac electrical conduction system is very sensitive to hypoglycemia and hypoxia, and the consequence may be brady-arrythmias. Weddell seals endure brady-arrythmias during their dives when desaturating to 3.2 kPa and elite breath-hold-divers (BHD), who share metabolic and cardiovascular adaptions including bradycardia with diving mammals, endure similar desaturation during maximum apnea. We hypothesized that hypoxia causes brady-arrythmias during maximum apnea in elite BHD. Hence, this study aimed to define the arterial blood glucose (Glu), peripheral saturation (SAT), heart rhythm (HR), and mean arterial blood pressure (MAP) of elite BHD during maximum apneas. Methods: HR was monitored with Direct-Current-Pads/ECG-lead-II and MAP and Glu from a radial arterial-catheter in nine BHD performing an immersed and head-down maximal static pool apnea after three warm-up apneas. SAT was monitored with a sensor on the neck of the subjects. On a separate day, a 12-lead-ECG-monitored maximum static apnea was repeated dry ( n = 6). Results: During pool apnea of maximum duration (385 ± 70 s), SAT decreased from 99.6 ± 0.5 to 58.5 ± 5.5% (∼PaO 2 4.8 ± 1.5 kPa, P < 0.001), while Glu increased from 5.8 ± 0.2 to 6.2 ± 0.2 mmol/l ( P = 0.009). MAP increased from 103 ± 4 to 155 ± 6 mm Hg ( P < 0.005). HR decreased to 46 ± 10 from 86 ± 14 beats/minute ( P < 0.001). HR and MAP were unchanged after 3-4 min of apnea. During dry apnea (378 ± 31 s), HR decreased from 55 ± 4 to 40 ± 3 beats/minute ( P = 0.031). Atrioventricular dissociation and junctional rhythm were observed both during pool and dry apneas. Conclusion: Our findings contrast with previous studies concluding that Glu decreases during apnea diving. We conclude during maximum apnea in elite BHD that (1) the diving reflex is maximized after 3-4 min, (2) increasing Glu may indicate lactate metabolism in accordance with our previous results, and (3) extreme hypoxia rather than hypoglycemia causes brady-arrythmias in elite BHD similar to diving mammals., Competing Interests: TKj was voluntary (unpaid) board member of the Danish National Diving Federation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kjeld, Isbrand, Linnet, Zerahn, Højberg, Hansen, Gormsen, Bejder, Krag, Vissing, Bøtker and Arendrup.)

Breath-hold divers (BHD) enduring apnea for more than 4 min are characterized by resistance to release of reactive oxygen species, reduced sensitivity to hypoxia, and low mitochondrial oxygen consumption in their skeletal muscles similar to northern elephant seals. The muscles and myocardium of harbor seals also exhibit metabolic adaptations including increased cardiac lactate-dehydrogenase-activity, exceeding their hypoxic limit. We hypothesized that the myocardium of BHD possesses similar adaptive mechanisms. During maximum apnea 15 O-H 2 O-PET/CT (n = 6) revealed no myocardial perfusion deficits but increased myocardial blood flow (MBF). Cardiac MRI determined blood oxygen level dependence oxygenation (n = 8) after 4 min of apnea was unaltered compared to rest, whereas cine-MRI demonstrated increased left ventricular wall thickness (LVWT). Arterial blood gases were collected after warm-up and maximum apnea in a pool. At the end of the maximum pool apnea (5 min), arterial saturation decreased to 52%, and lactate decreased 20%. Our findings contrast with previous MR studies of BHD, that reported elevated cardiac troponins and decreased myocardial perfusion after 4 min of apnea. In conclusion, we demonstrated for the first time with 15 O-H 2 O-PET/CT and MRI in elite BHD during maximum apnea, that MBF and LVWT increases while lactate decreases, indicating anaerobic/fat-based cardiac-metabolism similar to diving mammals.

Background: Acute kidney injury after cardiac surgery is common and associated with increased mortality. It is unknown whether an intended higher arterial pressure during cardiopulmonary bypass reduces the incidence of acute and chronic kidney injury., Methods: Patients were randomised either to a control group or a high pressure group (arterial pressure > 60 mmHg). The inclusion criteria were age > 70 years, combined cardiac surgery and serum creatinine < 200 μmol/L. Glomerular filtration rate using the Cr-EDTA clearance method was measured the day before surgery and 4 months postoperatively. The RIFLE criteria were used to define the presence of acute kidney injury. In addition, the ratio between urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and creatinine was measured., Results: Ninety patients were included. Mean age was 76 ± 4 years and 76% were male. Mean arterial pressure was 47 ± 5 mmHg in the control group and 61 ± 4 mmHg in the high pressure group (p < 0.0001). The change in glomerular filtration rate at follow-up was - 9 ± 12 ml/min in the control group and - 5 ± 16 ml/min in the high pressure group (p = 0.288, 95% CI - 13 to 4). According to the RIFLE criteria 38% in the control group and 46% in the high pressure group developed acute kidney injury (p = 0.447). The postoperative urinary NGAL/creatinine ratio was comparable between the groups., Conclusions: An intended increase in arterial pressure during cardiopulmonary bypass to > 60 mmHg did not decrease the incidence of acute or chronic kidney injury after cardiac surgery., Trial Registration: Clinicaltrials.gov, identifier: NCT01408420 . Registered 3rd of August 2011.

Background: The performance of elite breath hold divers (BHD) includes static breath hold for more than 11 minutes, swimming as far as 300 m, or going below 250 m in depth, all on a single breath of air. Diving mammals are adapted to sustain oxidative metabolism in hypoxic conditions through several metabolic adaptations, including improved capacity for oxygen transport and mitochondrial oxidative phosphorylation in skeletal muscle. It was hypothesized that similar adaptations characterized human BHD. Hence, the purpose of this study was to examine the capacity for oxidative metabolism in skeletal muscle of BHD compared to matched controls., Methods: Biopsies were obtained from the lateral vastus of the femoral muscle from 8 Danish BHD and 8 non-diving controls (Judo athletes) matched for morphometry and whole body VO2max. High resolution respirometry was used to determine mitochondrial respiratory capacity and leak respiration with simultaneous measurement of mitochondrial H2O2 emission. Maximal citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HAD) activity were measured in muscle tissue homogenates. Western Blotting was used to determine protein contents of respiratory complex I-V subunits and myoglobin in muscle tissue lysates., Results: Muscle biopsies of BHD revealed lower mitochondrial leak respiration and electron transfer system (ETS) capacity and higher H2O2 emission during leak respiration than controls, with no differences in enzyme activities (CS and HAD) or protein content of mitochondrial complex subunits myoglobin, myosin heavy chain isoforms, markers of glucose metabolism and antioxidant enzymes., Conclusion: We demonstrated for the first time in humans, that the skeletal muscles of BHD are characterized by lower mitochondrial oxygen consumption both during low leak and high (ETS) respiration than matched controls. This supports previous observations of diving mammals demonstrating a lower aerobic mitochondrial capacity of the skeletal muscles as an oxygen conserving adaptation during prolonged dives., Competing Interests: The authors have declared that no competing interests exist.

Closure of persistent foramen ovale (PFO) to avoid cryptogenic strokes is performed globally with enthusiasm but lacks prove of efficacy. We present a 79-year-old man who had had a PFO device introduced nine years previously because of cryptogenic strokes presenting as syncopes. The patient was referred from his general practitioner with two new syncopes. Transthoracic echocardiography revealed no cardiac causes of embolism. Transesophageal echocardiography (TEE) revealed a misplaced device like an umbrella in a storm, but no septum defects. Holter revealed seconds-long episodes of atrial fibrillation (AF). The patient was successfully treated with anticoagulation. A literature review showed that: (i) the efficacy of PFO closure devices has not been proven in any trial, but was demonstrated in a meta-analysis comparing three different devices; (ii) PFO devices are rarely controlled by TEE during or after insertion; (iii) residual shunts are detected in up to 45% of cases; (iv) there is an increased rate of post-arrhythmic complications; (v) the risk of AF in congenital heart disease increases with increasing age, with a 13% risk of transient ischemic attacks and stroke; and (vi) surgical treatment of PFO was found to have a 4.1% risk of complications including stroke. The question to be asked is whether device closure of PFO should be avoided, considering that PFO is a congenital heart defect with risks of AF and (cryptogenic) stroke? Heart surgery should be a treatment option for symptomatic PFO.

Unlabelled: Perioperative ischaemia and infarction after CABG are associated with increased morbidity and mortality., Objective: To study causes of perioperative ischaemia and infarction by acute re-angiography and to treat incomplete re-vascularization caused by graft failure or any other cause., Methods: Between 1990 and 1995, 2003 patients underwent an isolated CABG operation. Myocardial ischaemia was suspected if one or more of the following criteria were present: New changes in the ST-segment in the ECG; a CKMB value greater than 80 U/L; new Q-waves in the ECG; recurrent episodes of, or sustained ventricular tachyarrhythmia; ventricular fibrillation; haemodynamic deterioration and left ventricular failure. Acute coronary angiography was performed in stable patients, while haemodynamically severely compromised patients were rushed to the operating room., Results: A total of 71 (3.5%) patients of all CABGs with suspected graft failure were identified and included in the study. Patients were grouped according to whether they had an acute re-angiography (n = 59; group 1) or an immediate re-operation (n = 12; group 2) performed. In group 1, the acute re-angiography demonstrated graft failure/incomplete re-vascularization in 43 patients (73%). The angiographic findings were: Occluded vein graft(s) in 19 (32%); poor distal run-off to the grafted coronary artery in ten (17%); internal mammary artery stenosis in four (7%); internal mammary artery occlusion in three (5%); vein graft stenoses in three (5%); left mammary artery subclavian artery steal in two (3%); and the wrong coronary artery grafted in one (2%). Based on the angiography findings, 27 patients were re-operated and re-grafted. At the time of re-operation, 18 patients (67%) had evolving infarction documented by ECG or CKMB. Two patients (3%) experienced stroke in immediate relation to the re-angiography. The 30-day mortality was three (7%). In group 2, graft occlusions were found in 11 patients (92%). The 30-day mortality was six (50%)., Conclusion: An acute re-angiography demonstrated graft failure or incomplete re-vascularization in the majority of patients with myocardial ischaemia early after CABG. Re-operation for re-re-vascularization was performed with low risk. Few patients with circulatory collapse could be saved by an immediate re-operation without preceding angiography.