Characterization of atherosclerotic plaques in blood vessels with low oxygenated blood and blood pressure (Pulmonary trunk): role of growth differentiation factor-15 (GDF-15).

BACKGROUND: Growth differentiation factor (GDF)-15 is linked to inflammation, cancer, and atherosclerosis. GDF-15 is expressed in most tissues but is extremely induced under pathological conditions. Elevated serum levels are suggested as a risk factor and a marker for cardiovascular diseases. However, the cellular sources and the effects of GDF-15 on the cardiovascular system have not been completely elucidated including progression, and morphology of atherosclerotic plaques. Thus, this work aimed to characterize the influence of GDF-15 deficiency on the morphology of atherosclerotic plaques in blood vessels with low-oxygen blood and low blood pressure as the pulmonary trunk (PT), in hypercholesterolemic ApoE-/- mice. METHODS: GDF-15-/- ApoE-/- mice were generated by crossbreeding of ApoE-/-- and GDF-15-/- mice. After feeding a cholesterol-enriched diet (CED) for 20 weeks, samples of the brachiocephalic trunk (BT) and PT were dissected and lumen stenosis (LS) was measured. Furthermore, changes in the cellularity of the PT, amounts of apoptosis-, autophagy-, inflammation- and proliferation-relevant proteins were immunohisto-morphometrically analyzed. Additionally, we examined an atherosclerotic plaque in a human post mortem sample of the pulmonary artery. RESULTS: After CED the body weight of GDF-15-/-ApoE-/- was 22.9% higher than ApoE-/-. Double knockout mice showed also an 35.3% increase of plasma triglyceride levels, whereas plasma cholesterol was similar in both genotypes. LS in the BT and PT of GDF-15-/-ApoE-/- mice was significantly reduced by 19.0% and by 6.7% compared to ApoE-/-. Comparing LS in PT and BT of the same genotype revealed a significant 38.8% (ApoE-/-) or 26.4% (GDF-15-/-ApoE-/-) lower LS in the PT. Immunohistomorphometry of atherosclerotic lesions in PT of GDF-15-/-ApoE-/- revealed significantly increased levels (39.8% and 7.3%) of CD68 + macrophages (MΦ) and α-actin + smooth muscle cells than in ApoE-/-. The density of TUNEL + , apoptotic cells was significantly (32.9%) higher in plaques of PT of GDF-15-/-ApoE-/- than in ApoE-/-. Analysis of atherosclerotic lesion of a human pulmonary artery showed sm-α-actin, CD68+, TUNEL+, Ki67+, and APG5L/ATG+ cells as observed in PT. COX-2+ and IL-6+ immunoreactivities were predominantly located in endothelial cells and subendothelial space. In BT and PT of GDF15-/-ApoE-/- mice the necrotic area was 10% and 6.5% lower than in ApoE-/-. In BT and PT of GDF15-/-ApoE-/- we found 40% and 57% less unstable plaques than ApoE-/- mice. CONCLUSIONS: Atherosclerotic lesions occur in both, BT and PT, however, the size is smaller in PT, possibly due to the effect of the low-oxygen blood and/or lower blood pressure. GDF-15 is involved in atherosclerotic processes in BT and PT, although different mechanisms (e.g. apoptosis) in these two vessels seem to exist.

Leukotriene-B4 concentrations in breathing condensate before and after simulated deep dives.

During diving the respiratory tract is exposed to occupational hazards (increased oxygen partial pressure, pulmonary vessel engorgement during submersion, inert gas micro embolism during decompression). Leukotriene-B4 [LTB4] concentrations in the exhaled breath mirrors the inflammatory activity of the airways if the respiratory tract has been exposed to occupational hazards. In this study LTB4-concentrations in the exhaled breath and spirometry data obtained before and after simulated dives helped to elucidate any contributions by hyperbaric exposure to impaired lung function and to separate effects of ambient pressure from those of submersion and increased oxygen partial pressure. Thirty two healthy subjects carried out dives in a hyperbaric chamber using a cross over design to 600 kPa ambient pressure with and without submersion and a dry exposure to pure oxygen at 120 kPa ambient pressure (durations: 43 min). Pre-dive and four hours after surfacing the exhaled breath was collected non-invasively. Condensate was measured by a standard enzyme immuno-assay for LTB4 in parallel with lung function values (FVC, FEV1, MEF 25-75). Pre-exposure baseline values of LTB4-concentrations and lung function values were in the normal range. Post-exposure values did not differ significantly from the baseline values. The data gave no evidence of any inflammatory activity in the subjects' airways after hyperbaric exposure.

Incidence of abnormal cerebral findings in the MRI of clinically healthy divers: role of a patent foramen ovale.

BACKGROUND: To investigate incidence and number of abnormal cerebral hyperintensities (ACFs) in Magnet Resonance Imaging (MRI) and its relation to a patent foramen ovale (PFO) in divers with no history of decompression illness. METHODS: Cohort study on 50 divers (21-5500 dives). MAIN OUTCOME MEASURES: Incidence and number of ACFs visualized by cranial MRI and presence and size of a PFO as documented by echocardiography and transcranial Doppler ultrasound (TCD) with echocontrast. RESULTS: A total of 137 ACFs was found in the 50 subjects, with a significant correlation between the number of dives and number of ACFs (r = 0.28; p < 0.05); but after correction for age, the remaining correlation (r = 0.15) did not reach significance. In 18 divers, a PFO was present by either the application of echocardiography or TCD; in 12 divers, the PFO was of high hemodynamic relevance. Ten of 18 divers with a PFO had at least one ACF, while in the remaining 32 divers, only 14 had at least one ACF (56% versus 44%, p = NS). Seven of 14 divers (50%) with 4 ACFs had a PFO, compared to 11 of 36 (31%) with less than 4 ACFs (p = NS). CONCLUSION: In this cohort of healthy divers, in contrast to an earlier report, no significant association was found between PFO presence and incidence or number of ACFs.

Effects of ambient cold and depth on lung function in humans after a single scuba dive.

This study evaluated the subacute respiratory effects of diving, to try to separate the effects of ambient temperature from those of depth. In the first experiment 10 healthy men made a compressed-air dive to 50 m that exposed them to cold. They were compared with 10 matched control subjects who underwent the same dive profile but were exposed to a comfortable temperature. In the second experiment 16 healthy subjects made randomized cold dives to both 50 m and 10 m. Pulmonary function tests were made before, after 1 h, and 24 h after the dives. In the first experiment there was an increase in residual volume (P < 0.05) and a decrease in forced expiratory volume at 1 s (FEV1), in forced vital capacity (FVC) and in mid-expiratory flow at 75% of FVC (MEF75) 1 h after the cold dives (P < 0.05). In the second experiment significant increases in specific airways resistance (sR(AW)) (P < 0.05) and decreases in FEV1 (P<0.01), in MEF75 (P<0.05), and in mid-expiratory flow at 25% of FVC (P<0.05), were obtained after the 50 m-dives, whereas SR(AW) increased after the 10 m-dives (P<0.05). The respiratory pattern observed 1 h after cold dives to 50 m indicated airway narrowing. The changes after cold dives to 10 m, however, were of minor magnitude. Both cold and depth seemed to contribute to the adverse effects of a single compressed-air dive on pulmonary function.

Respiratory effects of a single dive to 50 meters in sport divers with asymptomatic respiratory atopy.

Increasing popularity of sports diving makes it likely that subjects with allergic respiratory diseases will be involved in diving with self contained underwater breathing apparatus (scuba). The present study evaluated the effects of a single scuba-dive on pulmonary function in subjects with respiratory atopy. Specific airways conductance (sGaw), residual volume (RV), forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), mid expiratory flow at 50% of FVC (MEF50), and transfer factor for carbon monoxide (TLCO) were measured in 9 sport divers with a history of hay fever and 9 matched healthy sport divers (control) before, 3 hours and 24 hours after a wet hyperbaric chamber dive to a depth of 50 m. Airway hyperresponsiveness (AHR) was assessed by methacholine challenge 4 weeks after the dive. Atopic subjects and controls did not differ with respect to anthropometric data, diving experience, and predive lung function. A 3% reduction in FVC was found 24h after the dive (p < 0.05) in both groups, whereas sGaw decreased by 15% 24 h after the dive (p < 0.05) in the subjects with respiratory atopy only. Postdive changes in RV, FEV1, MEF50, and TLCO did not reach level of statistical significance. AHR was obtained in 8/9 subjects with respiratory atopy. We conclude that subjects with atopic sensitization and asymptomatic AHR may be more susceptible to effects of diving on pulmonary function.

[Simultaneous transthoracic echocardiography and transcranial doppler ultrasonography with ultrasound contrast agents for the detection of a patent foramen ovale in diving medicine]. / Simultane transthorakale Echokardiographie und transkranielle Dopplersonographie mit Ultraschallkontrastmittel zum Nachweis eines persistenten Foramen ovale in der Tauchmedizin.

OBJECTIVE: Presentation of a non-invasive method for the identification of a patent foramen ovale (PFO) in screening of diving-candidates or for the investigation of diving accidents. METHOD: Simultaneous transthoracic echocardiography and transcranial Doppler sonography of the middle cerebral artery using ultrasound contrast media. RESULTS: In an unselected collective of amateur and professional divers a PFO was identified according to statistical prediction. CONCLUSION: This method can be used in diving medicine for PFO detection as an alternative procedure to transesophageal echocardiography.

Arteriovenous bubbles following cold water sport dives: relation to right-to-left shunting.

Neurologic injury subsequent to decompression from diving may be due to paradoxical arterialization of venous gas emboli. Of 40 divers who performed 53 open water dives after being tested for a patent foramen ovale (PFO), arterial gas emboli were detected in 7 of 13 dives, which resulted in venous bubbles. In five of these seven dives, there was evidence of a PFO by contrast transcranial Doppler sonography, indicating an increased risk of arterializing venous bubbles in divers with a PFO.

Computed chest tomography in an animal model for decompression sickness: radiologic, physiologic, and pathologic findings.

This study was conducted to investigate the early pulmonary effects of acute decompression in an animal model for human decompression sickness by CT and light microscopy. Ten test pigs were exposed to severe decompression stress in a chamber dive. Three pigs were kept at ambient pressure to serve as controls. Decompression stress was monitored by measurement of pulmonary artery pressure and arterial and venous Doppler recording of bubbles of inert gas. Chest CT was performed pre- and postdive and in addition the inflated lungs were examined after resection. Each lung was investigated by light microscopy. Hemodynamic data and bubble recordings reflected severe decompression stress in the ten test pigs. Computed tomography revealed large quantities of ectopic gas, predominantly intravascular, in three of ten pigs. These findings corresponded to maximum bubble counts in the Doppler study. The remaining test pigs showed lower bubble grades and no ectopic gas by CT. Sporadic interstitial edema was demonstrated in all animals--both test and control pigs--by CT of resected lungs and on histologic examination. A severe compression-decompression schedule can liberate large volumes of inert gas which are detectable by CT. Despite this severe decompression stress, which led to venous microembolism, CT and light microscopy did not demonstrate changes in lung structure related to the experimental dive. Increased extravascular lung water found in all animals may be due to infusion therapy.