Lipid rescue reverses the bupivacaine-induced block of the fast Na+ current (INa) in cardiomyocytes of the rat left ventricle.

BACKGROUND: Cardiovascular resuscitation upon intoxication with lipophilic ion channel-blocking agents has proven most difficult. Recently, favorable results have been reported when lipid rescue therapy is performed, i.e., the infusion of a triglyceride-rich lipid emulsion during resuscitation. However, the mechanism of action is poorly understood. METHODS: The authors investigate the effects of a clinically used lipid emulsion (Lipovenös® MCT 20%; Fresenius Kabi AG, Bad Homburg, Germany) on the block of the fast Na current (INa) induced by the lipophilic local anesthetic bupivacaine in adult rat left ventricular myocytes by using the whole cell patch clamp technique. RESULTS: Bupivacaine at 10 µm decreased INa by 54% (-19.3 ± 1.9 pApF vs. -42.3 ± 4.3 pApF; n = 17; P < 0.001; VPip = -40 mV, 1 Hz). Addition of 10% lipid emulsion in the presence of bupivacaine produced a 37% increase in INa (-26.4 ± 2.8 pApF; n = 17; P < 0.001 vs. bupivacaine alone). To test whether these results could be explained by a reduction in the free bupivacaine concentration by the lipid (lipid-sink effect), the authors removed the lipid phase from the bupivacaine-lipid mixture by ultracentrifugation. Also, the resulting water phase led to an increase in INa (+19%; n = 17; P < 0.001 vs. bupivacaine), demonstrating that part of the bupivacaine had been removed during ultracentrifugation. The substantially less lipophilic mepivacaine (40 µm) reduced INa by 27% (n = 24; P < 0.001). The mepivacaine-lipid mixture caused a significant increase in INa (+17%; n = 24; P < 0.001). For mepivacaine, only a small lipid-sink effect could be demonstrated (+8%; n = 23; P < 0.01), reflecting its poor lipid solubility. CONCLUSION: The authors demonstrate lipid rescue on the single-cell level and provide evidence for a lipid-sink mechanism.

Findings From EuroTrak Surveys From 2009 to 2015: Hearing Loss Prevalence, Hearing Aid Adoption, and Benefits of Hearing Aid Use.

PURPOSE: The purpose of this study was to analyze data from the EuroTrak surveys performed from 2009 to 2015 in Germany, France, and the United Kingdom to identify factors that could account for the growth in hearing aid sales over that period. METHOD: Data of 132,028 people-approximately 15,000 for each of the 3 countries at 3-year intervals-were collected using a questionnaire. The sample in each country was weighted using the respective country age-gender populations to get balanced results. Furthermore, 11,867 persons with self-reported hearing impairment filled in a comprehensive questionnaire on hearing status and related matters; 4,631 were hearing aid owners. Data were pooled over the 3 countries for each of the years 2009, 2012, and 2015 and analyzed for developments over the 6-year period. In certain cases, data were pooled across countries and years. The analysis focused on hearing loss prevalence, hearing aid adoption rates, satisfaction with hearing aids, and benefits of hearing aid use. RESULTS: Hearing loss prevalence was stable over the period around 10%-slightly higher for men than for women. Hearing aid adoption overall increased from 33% to 37%, and bilateral use increased from 55% to 69%. Intervals between hearing aid renewals decreased. These factors contribute to increased hearing aid sales. Bilateral users are more satisfied with the hearing aid product features (76%) and performance (72%) and use their hearing aids 9.1 hr per day, compared with unilateral users where the corresponding numbers are 71%, 67%, and 7.8 hr, respectively. Satisfaction with hearing aid product features and performance in general is slightly increasing; hearing aid users are 14.5% less exhausted at the end of the day compared with nonusers with similar hearing loss and exhibit less depressive and forgetfulness symptoms. CONCLUSIONS: The prevalence of self-reported hearing loss is 10.6% and stable, and hearing aid adoption has increased, particularly of bilateral fittings that are more satisfactory and exhibit higher daily use patterns. Higher uptake of hearing aids contributes to growing hearing aid sales.

Specific role for the extracellular signal-regulated kinase pathway in angiotensin II- but not phenylephrine-induced cardiac hypertrophy in vitro.

The study addressed the question of why in adult ventricular rat cardiomyocytes ERK activation is required for the hypertrophic stimulation caused by angiotensin II but not in the case of alpha-adrenoceptor stimulation. We therefore compared in the same culture system the intracellular signaling steps that are involved in inducing the hypertrophic growth evoked by stimulating either of these two receptors. alpha-Adrenoceptor stimulation strongly increased protein synthesis ([14C]phenylalanine incorporation) up to 53% in a PKC- and p70s6k-dependent, but ERK-independent way. In contrast, angiotensin II increased protein synthesis less efficiently (by 23%), in a PKC-, p70s6k-, but ERK-dependent way. The kinetics of activation for ERK were different for the two hypertrophic stimuli: alpha-adrenoceptor stimulation caused a rapid and transient activation, but angiotensin II caused a rapid and sustained activation. In contrast to alpha-adrenoceptor stimulation, angiotensin II activated calcium-independent PKC isoforms but not calcium-dependent PKC isoforms. In conclusion, ERK activation by angiotensin II is sustained and leads to an increase in protein synthesis on adult ventricular cardiomyocytes, but ERK activation by alpha-adrenoceptor stimulation is transient and not involved in hypertrophic growth responsiveness. The ERK-dependent pathway seems to be less efficient than ERK-independent pathways. The difference in the hypertrophic responsiveness of cardiomyocytes exposed to either of the two stimuli may be explained by the activation of different PKC isoform types.