Partial Resistance to Thyroid Hormone-Induced Tachycardia and Cardiac Hypertrophy in Mice Lacking Thyroid Hormone Receptor ß.

Background: Thyroid hormones regulate cardiac functions mainly through direct actions in the heart and by binding to the thyroid hormone receptor (TR) isoforms α1 and ß. While the role of the most abundantly expressed isoform, TRα1, is widely studied and well characterized, the role of TRß in regulating heart functions is still poorly understood, primarily due to the accompanying elevation of circulating thyroid hormone in TRß knockout mice (TRß-KO). However, their hyperthyroidism is ameliorated at thermoneutrality, which allows studying the role of TRß without this confounding factor. Methods: Here, we noninvasively monitored heart rate in TRß-KO mice over several days using radiotelemetry at different housing temperatures (22°C and 30°C) and upon 3,3',5-triiodothyronine (T3) administration in comparison to wild-type animals. Results: TRß-KO mice displayed normal average heart rate at both 22°C and 30°C with only minor changes in heart rate frequency distribution, which was confirmed by independent electrocardiogram recordings in freely-moving conscious mice. Parasympathetic nerve activity was, however, impaired in TRß-KO mice at 22°C, and only partly rescued at 30°C. As expected, oral treatment with pharmacological doses of T3 at 30°C led to tachycardia in wild-types, accompanied by broader heart rate frequency distribution and increased heart weight. The TRß-KO mice, in contrast, showed blunted tachycardia, as well as resistance to changes in heart rate frequency distribution and heart weight. At the molecular level, these observations were paralleled by a blunted cardiac mRNA induction of several important genes, including the pacemaker channels Hcn2 and Hcn4, as well as Kcna7. Conclusions: The phenotyping of TRß-KO mice conducted at thermoneutrality allows novel insights on the role of TRß in cardiac functions in the absence of the usual confounding hyperthyroidism. Even though TRß is expressed at lower levels than TRα1 in the heart, our findings demonstrate an important role for this isoform in the cardiac response to thyroid hormones.

A Comparison of Miller Straight Blade and Macintosh Blade Laryngoscopes for Intubation in Morbidly Obese Patients.

The primary objective of this study was to demonstrate whether the Miller blade laryngoscope could provide better visualization of the vocal cords in morbidly obese patients than the Macintosh blade laryngoscope. The secondary objective was to identify the patient-measured factors associated with better visualization of the vocal cords when using the Miller vs. Macintosh blade, as well as whether the application of external pressure might improve the visibility of the glottis during intubation. A prospective, observational study encompassing 110 patients with a BMI > 40 undergoing elective bariatric surgery and intubation procedure was performed. The evaluation of the vocal cords was performed according to the Cormack-Lehane scale and POGO scale in the same patient during intubation, performed with a Miller and a Macintosh blade laryngoscope, in a random matter. The following parameters were assessed: body weight, height, BMI, neck circumference, thyromental distance, sternomental distance, mouth opening, and Mallampati scale and their impact on visualization of the vocal cords using the Miller blade without the application of external pressure. The Miller blade provides an improved view of the glottis compared to the Macintosh blade measured with both the Cormac-Lehane scale (45 (40.91%) without external pressure application on the larynx, and 18 (16.36%) with external pressure application on the larynx) and the POGO scale (45 (40.91%) without external pressure application on the larynx, and 19 (17.27%) with external pressure application on the larynx). The application of laryngeal pressure improved the view of the glottis. Among the measured features, a significant improvement in the visibility of the glottis could be found in patients with a BMI over 44.244 kg/m2 and a neck circumference over 46 cm. To conclude, the usage of the Miller blade improves the visibility of the glottis compared to the Macintosh blade in morbidly obese patients. The recommendation to use the Miller blade in this group of patients requires further investigation, taking into account the effectiveness of the intubation. Trial Registration: NCT05494463.