The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function.

No abstract

Phosphodiesterase-5 (PDE5) is highly expressed in the pulmonary vasculature, but its expression in the myocardium is controversial. Cyclic guanosine monophosphate (cGMP) activates protein kinase G (PKG), which has been hypothesized to blunt cardiac hypertrophy and negative remodeling in heart failure. Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) failed to show a beneficial effect. These results highlight the controversy regarding the role and expression of PDE5 in the healthy and failing heart. This study used one- and two-dimensional electrophoresis and Western blotting to examine PDE5 expression in mouse (before and after trans-aortic constriction), dog (control and HFpEF) as well as human (healthy and failing) heart. We were unable to detect PDE5 in any cardiac tissue lysate, whereas PDE5 was present in the murine and bovine lung samples used as positive controls. These results indicate that if PDE5 is expressed in cardiac tissue, it is present in very low quantities, as PDE5 was not detected in either humans or any model of heart failure examined. Therefore in cardiac muscle, it is unlikely that PDE5 is involved the regulation of cGMP-PKG signaling, and hence PDE5 does not represent a suitable drug target for the treatment of cardiac hypertrophy. These results highlight the importance of rigorous investigation prior to clinical trial design.

Objectives: To investigate the intracochlear position of the latest Cochlear Nucleus 532 electrode array compared with the straight Nucleus 522 and the precurved 512 arrays and determine the effect of the electrode–modiolus distance on electrically evoked compound action potential, C-levels, electrically evoked stapedius reflex thresholds (ESRTs), and impedances. Methods: Postoperative high-resolution cone beam computational tomography images of 30 patients with Cochlear Nucleus 532, 522, and 512 implants were evaluated using the Comet (Cochlea Measurement Tool) program to determine the distance between the 22 individual electrode contacts and the medial wall. ESRTs were documented intraoperatively and electrophysiological as well as psychophysical parameters were measured at multiple time points including the first fitting after the initial activation. Results: The electrode–modiolus distance in perimodiolar arrays is uniformly small across the array, whereas in a straight electrode carrier it varies significantly along the length of the array. Electrically evoked compound action potential thresholds and C-levels are larger with increased distance to the modiolus. Impedances and stapedius reflex thresholds do not differ significantly between the arrays. Our results show that the electrode position has a significant effect on both electrophysiological and psychophysical parameters, while impedances and ESRTs are not impacted. Conclusion: Novel tools can be used in the evaluation of high resolution cone beam computational tomography images to determine individual electrode–modiolus distances after cochlear implantation. The results of this study suggest that the correlations between electrode–modiolus distance and electrophysiological and psychophysical parameters are not sufficiently strong to adjust CI-fitting based on imaging data.

No abstract

Tinnitus, vertigo and dizziness are symptoms commonly reported among Long and Post COVID patients, however the severity of these symptoms has not been assessed in large trials. Therefore, in this study a large cohort of Long COVID patients was surveyed about the presence and severity of tinnitus and vertigo or dizziness symptoms. The online survey was completed by a German cohort of 1,082 adult Long COVID patients after a mean period of 43.2 weeks ± 23.4 weeks after infection. Eighty percent were not fully vaccinated (at least two vaccinations) at the time of their first COVID symptoms and 9.8% were hospitalized in the course of their acute SARS-CoV-2 infection. At the time of the survey, 60% of patients reported the presence of vertigo or dizziness with a mean severity of 4.6 ± 2.7 on a scale of 1 (least severe) to 10 (most severe) and 30% complained of tinnitus with a mean severity of 4.8 ± 3.0. Approximately one fifth of the participants with tinnitus and vertigo or dizziness, rated their symptoms to be severe. The data shown in this study confirms that tinnitus and vertigo or dizziness are common symptoms in Long COVID patients and demonstrates, that a compelling number of patients rate their symptoms as severe. The self-reported severity highlights the need for Long COVID clinics to address these symptoms effectively. We suggest a multidisciplinary diagnostic and therapeutic approach to prevent further morbidity and socioeconomic burden for Long COVID patients suffering from severe vertigo, dizziness or tinnitus.