raise the interesting hypothesis that increased vascular smooth muscle reactivity in subjects of African ancestry may be related to greater activity of the enzyme creatine kinase in vascular muscle cells.Our study was not designed to elucidate the biochemical mechanisms of ethnic differences in vascular reactivity, but it is nevertheless interesting to consider our findings with the creatine kinase hypothesis in mind.If increased creatine kinase activity in blacks, resulting in increased ATP-buffering capacity for muscle contractility, contributes importantly to the enhanced α 1 -adrenergic receptor (α 1 -AR)-mediated vasoconstriction compared with whites, this ethnic difference would be also expected to occur in α 2 -ARmediated vasoconstriction, in view of shared common downstream vasoconstrictor pathways.However, we previously reported that α 2 -AR-mediated venoconstriction in response to the α 2 -AR-selective agonist dexmedetomidine did not differ between white and black subjects. 2,3Additionally, we and others found little correlation between an individual's α 1 -AR-and α 2 -AR-mediated vasoconstriction in either blacks or whites. 4,5We interpret these findings as suggesting that ethnic differences in α 1 -AR-mediated venoconstriction are more likely to be related to differences in pathways linked specifically to α 1 -AR signaling rather than to downstream vasoconstrictor mechanisms shared by α 1 -AR and α 2 -AR activation.Further studies will be necessary to elucidate factors contributing to ethnic differences in α 1 -AR-mediated vasoconstriction.
Retroaortic course of left innominate vein is a rare venous anomaly which is usually associated with CHD. Isolated retroaortic innominate vein is exceedingly rare with only a handful of reported cases. We report an otherwise healthy newborn with isolated retroaortic innominate vein and right aortic arch, a combination which has previously not been reported.
Background The presynaptic norepinephrine transporter (NET) mediates synaptic clearance and recycling of norepinephrine. NET-deficient transgenic mice have elevated blood pressure (BP), heart rate, and catecholamine concentrations. However, the in-vivo effects of common NET variants on cardiovascular regulation at rest and during exercise are unknown. Methods We studied cardiovascular responses and plasma catecholamine concentrations at rest and during bicycle exercise at increasing workloads (25, 50, and 75 W) in 145 healthy participants. We used multiple linear regressions to analyze the effect of common, purportedly functional polymorphisms in NET (rs2242446 and rs28386840) on cardiovascular measures. Results 44 and 58.9% of participants carried at least one variant allele for NET T-182C and A-3081T, respectively. Systolic BP during exercise and systolic BP-area under the curve were higher in carriers of variant NET alleles (P=0.003 and 0.009 for T-182C and A-3081T, respectively) and NET haplotype -182C/-3081T compared with -182T/-3081A (all P<0.01). Diastolic BP during exercise was also higher at lower, but not at higher exercise stages in carriers of NET -182C (P<0.01) and -3081T variants (P<0.05). NET genotypes were not associated with catecholamine concentrations or heart rate. Conclusion Common genetic NET variants (-182C and -3081T) are associated with greater BP response to exercise in humans.
Key Teaching Points•Loperamide abuse can present with severe cardiotoxicity. Profound electrocardiogram (ECG) abnormalities (sinus bradycardia, wide QRS, prolonged PR, markedly prolonged QTc, Brugada-like ECG pattern), malignant ventricular arrhythmias, and ventricular dysfunction have all been reported.•There is wide interindividual variability in toxic dose, ECG and clinical abnormalities, and duration of loperamide toxicity.•The determinants of this variability have not been identified.•QTc prolongation can persist for weeks to months after the last reported intake in loperamide abusers. The duration for which these patients need to be monitored is unclear but it should at least be for a few weeks.•Loperamide is not detected on routine blood and urine toxicity screens. A special assay, which is not readily available, is required for detection of loperamide in the serum. •Loperamide abuse can present with severe cardiotoxicity. Profound electrocardiogram (ECG) abnormalities (sinus bradycardia, wide QRS, prolonged PR, markedly prolonged QTc, Brugada-like ECG pattern), malignant ventricular arrhythmias, and ventricular dysfunction have all been reported.•There is wide interindividual variability in toxic dose, ECG and clinical abnormalities, and duration of loperamide toxicity.•The determinants of this variability have not been identified.•QTc prolongation can persist for weeks to months after the last reported intake in loperamide abusers. The duration for which these patients need to be monitored is unclear but it should at least be for a few weeks.•Loperamide is not detected on routine blood and urine toxicity screens. A special assay, which is not readily available, is required for detection of loperamide in the serum.
Reports thus far suggest a mild course for acute COVID-19 infection in children; however, its effects in vulnerable paediatric populations, including children with haemodynamically significant congenital heart disease, have rarely been reported. We therefore report on a 4-month-old Hispanic male with a moderate sized conoventricular ventricular septal defect and pulmonary overcirculation who presented with COVID-19-associated pneumonia.
We report the case of a 16-year-old boy who had myopericarditis following the first dose of a selective androgen receptor modulator called Testolone ("RAD-140"). These drugs are widely abused by physically active young adults; however, the drugs' side effects, which can be life-threatening, are not well characterized.
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