Elizabeth A. Martin

Endothelial function and vascular response to mental stress are impaired in patients with apical ballooning syndrome.

OBJECTIVES The aim of the current study was to test the hypothesis that vascular and endothelial functional responses to acute mental stress are abnormal in patients with apical ballooning syndrome (ABS). BACKGROUND Apical ballooning syndrome is a transient cardiomyopathy that occurs predominantly in post-menopausal women and may be triggered by acute mental stress. The mechanism for ABS is unknown. METHODS Reactive hyperemia as a parameter of endothelial function and vascular responses to acute mental stress were measured using peripheral arterial tonometry (PAT) at baseline and following 3 acute mental stress tests in female patients with ABS (n = 12, at least 6 months after being hospitalized or diagnosed with ABS), post-menopausal female controls (n = 12), and female patients with myocardial infarction (MI) (n = 4). Plasma catecholamine levels were measured at baseline and following the 3 mental stress tests. RESULTS Reactive hyperemia PAT scores following mental stress were significantly lower in patients with ABS compared with post-menopausal controls (p < 0.05). The PAT scores during mental stress were significantly lower in patients with ABS compared with patients with MI and post-menopausal controls (p < 0.05). There were no differences in PAT scores during acute mental stress in patients with MI versus post-menopausal controls. Furthermore, catecholamine levels were significantly increased in patients with ABS, compared with post-menopausal controls, following acute mental stress testing (p < 0.05). CONCLUSIONS There is increased vascular reactivity and decreased endothelial function in response to acute mental stress in patients with a prior episode of ABS. The findings implicate vasomotor dysfunction as a potential mechanism involved in the pathogenesis of this unique cardiomyopathy.

Exercise intensity-dependent contribution of β-adrenergic receptor-mediated vasodilatation in hypoxic humans

We previously reported that hypoxia‐mediated reductions in α‐adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that β‐adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29 ± 2 years) breathed hypoxic gas to titrate arterial O2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), α‐adrenoceptor inhibition (phentolamine), and combined α‐ and β‐adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end‐tidal CO2 were determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P < 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline (P < 0.05) were higher with hypoxia during all drug infusions. The change (Δ) in FBF during 10% hypoxic exercise was greater with phentolamine (Δ306 ± 43 ml min−1) vs. saline (Δ169 ± 30 ml min−1) or combined phentolamine/propranolol (Δ213 ± 25 ml min−1; P < 0.05 for both). During 20% hypoxic exercise, ΔFBF was greater with phentalomine (Δ466 ± 57 ml min−1; P < 0.05) vs. saline (Δ346 ± 40 ml min−1) but was similar to combined phentolamine/propranolol (Δ450 ± 43 ml min−1). Thus, in the absence of overlying vasoconstriction, the contribution of β‐adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

Adenosine transporter antagonism in humans augments vasodilator responsiveness to adenosine, but not exercise, in both adenosine responders and non‐responders

We previously demonstrated a bimodal distribution of forearm vasodilator responsiveness to adenosine (ADO) infusion in the brachial arteries of human subjects. We also demonstrated that ADO receptor antagonism blunted exercise hyperaemia during heavy rhythmic handgripping, but vasodilator responses to exogenous ADO were only blunted in ADO responders. In this study, we continued investigating the contribution of ADO to exercise hyperaemia and possible differences between responders and non‐responders. We hypothesized that ADO transporter antagonism would increase vasodilatation in response to exogenous ADO in responders only, but not effect exercise‐mediated vasodilation. To test this hypothesis, we compared forearm vascular conductance (FVC) during infusion of ADO to FVC during handgripping before and after infusion of dipyridamole (DIP) in 20 subjects. In ADO responders, change in FVC above baseline (ml min−1 (100 mmHg)−1) for low, medium and high doses of ADO, respectively, was 58 ± 8, 121 ± 22 and 184 ± 38, and after DIP was 192 ± 32, 238 ± 50 and 310 ± 79. For non‐responders, these values were 23 ± 2, 43 ± 5 and 66 ± 9, respectively, before DIP (P < 0.01 versus responders). Contrary to our hypothesis, these values were increased by DIP in non‐responders (P < 0.001) and therefore not different from responders (P > 0.20). We found that ADO transporter blockade had no effect on exercise hyperaemia in either subgroup. We conclude that there may be increased ADO transporter activity in non‐responders resulting in reduced ADO‐mediated vasodilatation. The failure of DIP to augment exercise hyperemia under these conditions suggests that ADO concentrations may not rise enough during rhythmic handgripping to have a major impact on these responses.

Changes in central venous pressure with vasoactive drug injections in humans.

We tested whether central venous pressure (CVP) changes during vasoactive drug injections used for baroreflex assessment in humans. We measured CVP during sequential intravenous boluses of nitroprusside (NTP) and phenylephrine (PHE; modified Oxford technique). NTP caused a decrease in CVP of 1.9±0.2 mmHg from baseline (P<0.01) and PHE caused an increase in CVP of 0.3±0.2mmHg above baseline. These changes in CVP may contribute to the observed integrated baroreflex responses.

Comparing EndoPAT and BIOPAC measurement of vascular responses to mental stress

There are currently no comparison measurements of stress‐induced changes in vascular function during acute mental stress tests to measurements made by BIOPAC MP150 systems technology, a standard polygraph device used to detect deception during polygraph examinations in military or law enforcement applications. Vascular responses to reactive hyperaemia and acute mental stress in 25 healthy subjects were measured by both peripheral arterial tonometry (EndoPAT) and a blood pressure cuff attached to a pressure transducer (BIOPAC) and compared. Reactive hyperaemia was performed at baseline and following three acute mental stress tests. There was no difference in vascular reactivity at baseline and following acute mental stress, as measured by EndoPAT or BIOPAC systems (p > 0·05). Mental stress ratios measured by EndoPAT were significantly different than those measured by BIOPAC (p < 0·01). These data suggest that EndoPAT measurements of vascular responses to acute mental stress may be more specific and sensitive than measurements using the BIOPAC system. Copyright

Thyroid Nodules in a Veterans Affairs Population

Objective: 1) Determine if follicular thyroid lesions in a Veteran Affairs (VA) population are at increased risk of harboring malignancy compared to the general population. 2) Analyze imaging modalities leading to diagnosis. Method: Retrospective analysis of 107 patients undergoing partial or total thyroidectomy from 2005 to 2010 at a single Veteran Affairs hospital. Outcome measures included age, sex, method of nodule detection, fine needle aspiration (FNA) cytopathology, final histopathology, associated 2deoxy-2[18F]fluoro-D-glucose positron emission tomography (FDG-PET) uptake, and incidence of cancer compared with previously published data. Results: Age range was 27 to 84 years (mean, 60 years). Fine needle aspiration (FNA) cytopathology results were benign in 31% (n = 33), follicular lesion in 41% (n = 46); suspicious for malignancy or malignant in 11.2% (n = 12). The overall malignancy rate was 36.4% (n = 39). Of the indeterminant FNA lesions, 41% (n = 19) had malignancy confirmed histopathologically. This is higher compared to recently published rates of malignancy in follicular lesions (15%-30%). In 9 of the 10 patients who underwent 2deoxy-2[18F]fluoro-D-glucose positron emission tomography (FDG-PET), focal thyroid uptake was identified and was significantly (P < .01) associated with malignancy. This percentage is also much higher prevalence than the approximately 33% reported. Conclusion: Follicular thyroid nodules of undetermined significance on FNA may harbor malignancy more frequently in the VA population compared to the general population. Focal FDG-PET uptake is significantly associated with malignancy.

Reassessment of CD62L as a marker of pre-effector T cells in the tumor draining lymph nodes of head and neck cancer patients☆

OBJECTIVES : CD62L was evaluated as a determinant of human pre-effector T cells. STUDY DESIGN AND SETTING : Phenotype and cytokine secretion profiles of CD62L cells were determined based on activation status. RESULTS : CD62LLow T cells demonstrated significantly higher secretion of interleukin (IL)-10 and interferon (IFN)-Γ than did CD62LHigh T cells. After activation, the majority of cells expressed high levels of the CD62L surface marker. Postactivation levels of IL-10 production remained elevated or unchanged. In a murine B16 melanoma model, freshly isolated CD62LLow tumor draining lymph nodes (TDLN) T cells showed increased secretion of IL-2 and IL-4 but not of IL-10 or IFN-γ. The surface expression of CD62L and cytokine secretion patterns were maintained after activation with concomitant increases in IL-10. CONCLUSION : Our results provide evidence that CD62LLow T cells in TDLNs of progressively growing squamous cell carcinoma of the head and neck differ phenotypically and functionally from those of mouse origin. SIGNIFICANCE : Characterization of this human CD62LLow T cell population provides initial insight regarding novel surface markers in TDLN T cells that might correlate with antitumor reactivity.