Vitamin E treatment in insulin-deficient diabetic rats reduces cardiac arrhythmias and mortality during severe hypoglycemia.

In people with type 1 diabetes, hypoglycemia can induce cardiac arrhythmias. In rodent experiments, severe hypoglycemia can induce fatal cardiac arrhythmias, especially so in diabetic models. Increased oxidative stress associated with insulin-deficient diabetes was hypothesized to increase susceptibility to severe hypoglycemia-induced fatal cardiac arrhythmias. To test this hypothesis, Sprague-Dawley rats were made insulin deficient with streptozotocin and randomized into two groups: 1) control (n = 22) or 2) vitamin E treated (four doses of α-tocopherol, 400 mg/kg, n = 20). Following 1 week of treatment, rats were either tested for cardiac oxidative stress or underwent a hyperinsulinemic-severe hypoglycemic (10-15 mg/dL) clamp with electrocardiogram recording. As compared with controls, vitamin E-treated rats had threefold less cardiac oxidative stress, sixfold less mortality due to severe hypoglycemia, and sevenfold less incidence of heart block. In summary, vitamin E treatment and the associated reduction of cardiac oxidative stress in diabetic rats reduced severe hypoglycemia-induced fatal cardiac arrhythmias. These results indicate that in the setting of diabetes, pharmacological treatments that reduce oxidative stress may be an effective strategy to reduce the risk of severe hypoglycemia-induced fatal cardiac arrhythmias.NEW & NOTEWORTHY For people with type 1 diabetes, severe hypoglycemia can be fatal. We show in our animal model that insulin-deficient diabetic rats have fatal cardiac arrhythmias during severe hypoglycemia that are associated with increased cardiac oxidative stress. Importantly, treatment with vitamin E, to reduce oxidative stress, decreased fatal cardiac arrhythmias during severe hypoglycemia.

Geographic Proximity of Medical Students to PM&R Residency Programs is Associated with Increased Match Rates into PM&R.

ABSTRACT: Despite the growing popularity of Physical Medicine & Rehabilitation (PM&R) as a specialty among medical students, meaningful experiences and mentorship can be challenging to obtain and may significantly vary depending on opportunities available to interact with physiatrists. This study explores the association between the geographic proximity of PM&R residency programs to medical schools and the match rate of medical students into PM&R from 2019 to 2021. Data on US medical schools, graduates, and PM&R residency programs were collected from publicly available sources, and a sample of 1,193 PM&R residents from US medical schools was analyzed using a one-sample proportion test. The proportion of PM&R residents originating from medical schools with PM&R residency programs in the same metropolitan area was significantly greater than the corresponding proportion of expected residents based on medical school graduates, even when controlling for medical school affiliations with PM&R residency programs. These findings suggest that exposure and opportunities provided by PM&R residency programs may influence nearby medical students and that expanding residency programs into geographic regions without existing PM&R programs may foster interest and promote growth in the field of physiatry.

Severe Hypoglycemia-Induced Fatal Cardiac Arrhythmias Are Mediated by the Parasympathetic Nervous System in Rats.

The contribution of the sympathetic nervous system (SNS) versus the parasympathetic nervous system (PSNS) in mediating fatal cardiac arrhythmias during insulin-induced severe hypoglycemia is not well understood. Therefore, experimental protocols were performed in nondiabetic Sprague-Dawley rats to test the SNS with 1) adrenal demedullation and 2) chemical sympathectomy, and to test the PSNS with 3) surgical vagotomy, 4) nicotinic receptor (mecamylamine) and muscarinic receptor (AQ-RA 741) blockade, and 5) ex vivo heart perfusions with normal or low glucose, acetylcholine (ACh), and/or mecamylamine. In protocols 1-4, 3-h hyperinsulinemic (0.2 units/kg/min) and hypoglycemic (10-15 mg/dL) clamps were performed. Adrenal demedullation and chemical sympathectomy had no effect on mortality or arrhythmias during severe hypoglycemia compared with controls. Vagotomy led to a 6.9-fold decrease in mortality; reduced first- and second-degree heart block 4.6- and 4-fold, respectively; and prevented third-degree heart block compared with controls. Pharmacological blockade of nicotinic receptors, but not muscarinic receptors, prevented heart block and mortality versus controls. Ex vivo heart perfusions demonstrated that neither low glucose nor ACh alone caused arrhythmias, but their combination induced heart block that could be abrogated by nicotinic receptor blockade. Taken together, ACh activation of nicotinic receptors via the vagus nerve is the primary mediator of severe hypoglycemia-induced fatal cardiac arrhythmias.