Background The contribution of the lung or the plant gain ( PG ; ie, change in blood gases per unit change in ventilation) to Cheyne‐Stokes respiration ( CSR ) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated. Methods and Results Twenty patients with systolic heart failure (age, 72.4±6.4 years; left ventricular ejection fraction, 31.5±5.8%), 10 with relevant CSR (24‐hour apnea‐hypopnea index [ AHI ] ≥10 events/h) and 10 without ( AHI <10 events/h) at 24‐hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia ( ) and hypercapnia ( ) by rebreathing technique, lung‐to‐finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI , 0.91–0.99); the best‐fitting curve to express the PG was a hyperbola ( R 2 ≥0.98). Patients with CSR showed increased PG , (but not ), and lung‐to‐finger circulation time, compared with patients without CSR (all P <0.05). PG was the only predictor of the daytime AHI ( R =0.56, P =0.01) and together with the also predicted the nighttime AHI ( R =0.81, P =0.0003) and the 24‐hour AHI ( R =0.71, P =0.001). Lung‐to‐finger circulation time was the only predictor of CSR cycle length ( R =0.82, P =0.00006). Conclusions PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure.

Occurrence of liver gas embolism after rapid decompression was assessed in 31 female rats that were decompressed in 12 min after 42 min of compression at 7 ATA ( protocol A). Sixteen rats died after decompression ( group I). Of the surviving rats, seven were killed at 3 h ( group II), and eight at 24 h ( group III). In group I, bubbles were visible in the right heart, aortic arch, liver, and mesenteric veins and on the intestinal surface. Histology showed perilobular microcavities in sinusoids, interstitial spaces, and hepatocytes. In g roup II, liver gas was visible in two rats. Perilobular vacuolization and significant plasma aminotransferase increase were present. In g roup III, liver edema was evident at gross examination in all cases. Histology showed perilobular cell swelling, vacuolization, or hydropic degeneration. Compared with basal, enzymatic markers of liver damage increased significantly. An additional 14 rats were decompressed twice ( protocol B). Overall mortality was 93%. In addition to diffuse hydropic degeneration, centrilobular necrosis was frequently observed after the second decompression. Additionally, 10 rats were exposed to three decompression sessions ( protocol C) with doubled decompression time. Their mortality rate decreased to 20%, but enzymatic markers still increased in surviving rats compared with predecompression, and perilobular cell swelling and vacuolization were present in five rats. Study challenges were 1) liver is not part of the pathophysiology of decompression in the existing paradigm, and 2) although significant cellular necrosis was observed in few animals, zonal or diffuse hepatocellular damage associated with liver dysfunction was frequently demonstrated. Liver participation in human decompression sickness should be looked for and clinically evaluated.

In a previous study, we obtained histologic documentation of liver gas embolism in the rat model of rapid decompression. The aim of the study was to assess in the same model occurrence and time course of liver embolism using 2-D ultrasound imaging, and to explore by this means putative liver gas embolism in recreational scuba divers. Following 42 min compression at 7 ATA breathing air and 12 min decompression, eight surviving female rats were anesthetized and the liver imaged by ultrasound at 20 min intervals up to 120 min. A significant enhancement of echo signal was recorded from 60 to 120 min as compared to earlier post-decompression times. Enzymatic markers of liver damage (AST, ALT, and GGT) increased significantly at 24 h upon decompression. Twelve healthy experienced divers were studied basally and at 15-min intervals up to 60 min following a 30-min scuba dive at 30 msw depth. At 30 min upon surfacing echo images showed significant signal enhancement that progressed and reached plateau at 45 and 60 min. Total bilirubin at 24 h increased significantly (p = 0.02) with respect to basal values although within the reference range. In conclusion, 2-D ultrasound liver imaging allowed detection of gas embolism in the rat and defined the time course of gas accumulation. Its application to scuba divers revealed liver gas accumulation in all subjects in the absence of clear-cut evidence of liver damage or of any symptom. The clinical significance of our findings remains to be investigated.

Objective: Renal denervation (RDN) is increasingly used to reduce sympathetic outflow and improve blood pressure (BP) control in patients with resistant or difficult-to-treat arterial hypertension. However, the BP response to the procedure is variable, and factors influencing this variability remain largely unknown. Sympathetic outflow recorded before the procedure might predict the BP response to RDN, although results from different studies remain conflicting. These discrepancies might depend on the limited characterization of the sympathetic outflow before RDN, making its better definition an important goal to refine the patient selection. Design and method: We prospectively enrolled patients with difficult-to-treat arterial hypertension undergoing RDN. Patients underwent an extensive clinical evaluation, and the muscle sympathetic nerve activity (MSNA) in resting conditions and during respiratory maneuvers (controlled inspiratory apneas, evaluation of chemoreflex sensitivity to hypoxia and hypercapnia with the rebreathing technique) was recorded through microneurography. Sympathetic burst frequency, incidence, amplitude, duration and integral, as well as inter-burst interval, were calculated with a semi-automated in-house software. Results: Table 1 reports the clinical characteristics of the 10 patients that were enrolled and underwent MSNA recording before RDN. Only in 6 patients the MSNA signal was clearly interpretable and, of these, 5 subjects (Figure 1) completed the whole battery of the respiratory stimuli (2 patients couldn’t perform chemoreflex testing due to panic attack and loss of neural signal). Apnea increased the burst frequency and incidence in all patients, although the magnitude of the changes from the resting acquisition was variable. The MSNA responses to the other respiratory maneuvers were jeopardized. Burst duration remained stable, whereas an increased MSNA could be observed (subjects 1 and 3) in terms of risen burst integral and reduced inter-burst interval compared to baseline. The sympathetic response to inspiratory apneas seems mediated by chemoreflex responses in these patients. The other subjects did not show such variations. Conclusions: Respiratory maneuvers are feasible during MSNA acquisitions and unveil different patterns of sympathetic responses in patients with hypertension undergoing RDN. Such differences might be missed at rest but could represent novel predictors of the BP response to the procedure.

No abstract