Untapped resource: the simulation-based healthcare environment as a means to study human stress.

The effects of 'stress' within the healthcare professions are wide-reaching, not least of all within the field of simulation-based healthcare education. Whilst this popular method of experiential learning offers a 'safe space' for participants to develop their skillset, it also has a more surreptitious action; namely, the incubation of simulation-related stress. Currently, research concerning the complex relationship between stress, learning, and performance is ambiguous, leaving fertile ground for simulationists to debate what level of stress is appropriate for an optimised educational experience. In this narrative review, we examine the human response to stress and outline the various methods that have been used by researchers to measure stress in a quantifiable and standardised way. We then provide a brief overview of simulation-based healthcare education before describing why stress responses have been of interest to healthcare educationalists for some time. Finally, we outline how simulation education environments might provide an ideal environment for studying the human response to stress generally, with ramifications extending beyond the field of medical education.

Biological testing during acute psychological stress: A hindrance or an opportunity?

All humans deal with acute psychological stress periodically. Some individuals are affected by needle phobia in which a heightened sense of arousal is precipitated by venepuncture. Acute psychological stress invokes a range of physiological changes including activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes. In this review article, we first examine the human response to acute stress. We then provide an overview of how psychological stress in a subject is likely to be a source of pre-analytical variability for certain measurands, and the major biochemical markers that have been studied in research aiming to quantify stress. As such, we highlight how stress can be a hindrance to the accurate interpretation of certain laboratory results (particularly cortisol, prolactin, metanephrines and growth hormone), and point out the role that biochemical analysis might play in future studies looking at the effects of stress on human behaviour.

Wavelet entropy of Doppler ultrasound blood velocity flow waveforms distinguishes nitric oxide-modulated states.

Wavelet entropy assesses the degree of order or disorder in signals and presents this complex information in a simple metric. Relative wavelet entropy assesses the similarity between the spectral distributions of two signals, again in a simple metric. Wavelet entropy is therefore potentially a very attractive tool for waveform analysis. The ability of this method to track the effects of pharmacologic modulation of vascular function on Doppler blood velocity waveforms was assessed. Waveforms were captured from ophthalmic arteries of 10 healthy subjects at baseline, after the administration of glyceryl trinitrate (GTN) and after two doses of N(G)-nitro-L-arginine-methyl ester (L-NAME) to produce vasodilation and vasoconstriction, respectively. Wavelet entropy had a tendency to decrease from baseline in response to GTN, but significantly increased after the administration of L-NAME (mean: 1.60 ± 0.07 after 0.25 mg/kg and 1.72 ± 0.13 after 0.5 mg/kg vs. 1.50 ± 0.10 at baseline, p < 0.05). Relative wavelet entropy had a spectral distribution from increasing doses of L-NAME comparable to baseline, 0.07 ± 0.04 and 0.08 ± 0.03, respectively, whereas GTN had the most dissimilar spectral distribution compared with baseline (0.17 ± 0.08, p = 0.002). Wavelet entropy can detect subtle changes in Doppler blood velocity waveform structure in response to nitric-oxide-mediated changes in arteriolar smooth muscle tone.

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation.

OBJECTIVE: Quantification of Doppler flow velocity waveforms has been shown to predict adverse cardiovascular outcomes and identify altered downstream haemodynamics and vascular damage in a number of organ beds. We employed novel techniques to quantify Doppler flow velocity waveforms from the retro bulbar circulation. METHODS AND RESULTS: In total, 39 patients with uncomplicated Type 1 diabetes mellitus, and no other significant cardiovascular risk factors were compared with 30 control subjects. Flow velocity waveforms were captured from the ophthalmic artery (OA), central retinal artery (CRA) and the common carotid artery. The flow velocity profiles were analysed in the time domain to calculate the resistive index (RI), and time-frequency domain using novel discrete wavelet transform methods for comparison. Analysis of flow waveforms from the OA and CRA identified specific frequency band differences between groups, occurring independently of potential haemodynamic or metabolic confounding influences. No changes were identified in the calculated RI from any arterial site. CONCLUSION: Novel analysis of the arterial flow velocity waveforms recorded from the retro bulbar circulation identified quantifiable differences in Doppler flow velocity waveform morphology in patients with diabetes prior to the development of overt retinopathy. The technique may be useful as an additional marker of cardiovascular risk.

Ocular blood flow analysis detects microvascular abnormalities in impaired glucose tolerance.

OBJECTIVE: Waveform analysis has been used to assess vascular resistance and predict cardiovascular events. We aimed to identify microvascular abnormalities in patients with IGT using ocular waveform analysis. The effects of pioglitazone were also assessed. METHODS: Forty patients with IGT and 24 controls were studied. Doppler velocity recordings were obtained from the central retinal, ophthalmic, and common carotid arteries, and sampled at 200 Hz. A discrete wavelet-based analysis method was employed to quantify waveforms. The RI was also determined. Patients with IGT were randomized to pioglitazone or placebo, and measurements were repeated after 12-week treatment. RESULTS: In the ocular waveforms, significant differences in power spectra were observed in frequency band 4 (corresponding to frequencies between 6.25 and 12.50 Hz) between groups (p < 0.05). No differences in RI occurred. No association was observed between waveform parameters and fasting glucose or insulin resistance. Pioglitazone had no effect on waveform structure, despite significantly reducing insulin resistance, fasting glucose, and triglycerides (p < 0.05). CONCLUSIONS: Analysis of ocular Doppler flow waveforms using the discrete wavelet transform identified microvascular abnormalities that were not apparent using RI. Pioglitazone improved glucose, insulin sensitivity, and triglycerides without influencing the contour of the waveforms.

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

Statins have beneficial effects on platelet free radical activity and intracellular distribution of GTPases in hyperlipidaemia.

In addition to lowering cholesterol, statins may alter endothelial release of the vasodilator NO and harmful superoxide free radicals. Statins also reduce cholesterol intermediates including isoprenoids. These are important for post-translational modification of substances including the GTPases Rho and Rac. By altering the membrane association of these molecules, statins affect intracellular positioning and hence activity of a multitude of substances. These include eNOS(endothelial NO synthase), which produces NO (inhibited by Rho), and NADPH oxidase, which produces superoxide (dependent on Rac). Statins may improve endothelial function by enhancing production of NO while decreasing superoxide production. A total of 40 hypercholesterolaemic patients were randomized to treatment with either atorvastatin or placebo; 20 normolipidaemic patients were also studied. Platelet nitrite, NO and superoxide were examined as was the cellular distribution of the GTPases Rho and Rac at baseline and after 8 weeks of treatment.Following atorvastatin therapy, platelet NO was increased (3.2 pmol/10(8) platelets) and superoxide output was attenuated [-3.4 pmol min(-1) (10(8) platelets)(-1)] when compared with placebo. The detection of both Rho and Rac was significantly reduced in the membranes of platelets, implying reduced activity. In conclusion, the results of the present study show altered NO/superoxide production following statin therapy. A potential mechanism for this is the change in the distribution of intracellular GTPases, which was considered to be secondary to decreases in isoprenoid intermediates, suggesting that the activity of the former had been affected by atorvastatin.

End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation.

Risk factors for cardiovascular disease mediate their effects by altering the structure and function of wall and endothelial components of arterial blood vessels. A pathological change in the microcirculation plays a pivotal role in promoting end-organ dysfunction that not only predisposes to further organ damage, but also increases the risk for future macrovascular events. The microcirculation is recognized as the site where the earliest manifestations of cardiovascular disease, especially inflammatory responses, occur that may play a pivotal role in driving the atherosclerotic process in conduit vessels. Furthermore, the vast surface area of the endothelium compared with conduit vessels means that the vascular effects of endothelial dysfunction or activation will be most apparent in this section of the vasculature. Current techniques providing indices of vascular health focus on large arteries without providing insight into the structure and function of small vessels. Techniques capable of detecting microvascular damage and monitoring the response to therapeutic interventions, especially in vulnerable target organs of interest, may improve risk stratification and represent a valuable surrogate for future cardiovascular outcome.

A cardiologist view of vascular disease in diabetes.

Diabetes mellitus is a potent risk factor for the development of a wide spectrum of cardiovascular (CV) complications. The complex metabolic milieu accompanying diabetes alters blood rheology, the structure of arteries and disrupts the homeostatic functions of the endothelium. These changes act as the substrate for end-organ damage and the occurrence of CV events. In those who develop acute coronary syndromes, patients with diabetes are more likely to die, both in the acute phase and during follow-up. Patients with diabetes are also more likely to suffer from chronic cardiac failure, independently of the presence of large vessel disease, and also more likely to develop stroke, renal failure and peripheral vascular disease. Preventing vascular events is the primary goal of therapy. Optimal cardiac care for the patient with diabetes should focus on aggressive management of traditional CV risk factors to optimize blood glucose, lipid and blood pressure control. Targeting medical therapy to improve plaque stability and diminish platelet hyper-responsiveness reduces the frequency of events associated with atherosclerotic plaque burden. In patients with critical lesions, revascularization strategies, either percutaneous or surgical, will often be necessary to improve symptoms and prevent vascular events. Improved understanding of the vascular biology will be crucial for the development of new therapeutic agents to prevent CV events and improve outcomes in patients with diabetes.

Arterial stiffness: clinical relevance, measurement and treatment.

Most traditional cardiovascular risk factors alter the structure and/or function of arteries. An assessment of arterial wall integrity could therefore allow accurate prediction of cardiovascular risk in individuals. The term 'arterial stiffness' denotes alterations in the mechanical properties of arteries, and much effort has focused on how best to measure this. Pulse pressure, pulse wave velocity, pulse waveform analysis, localized assessment of blood vessel mechanics and other methods have all been used. We review the methodology underlying each of these measures, and present an evidence-based critique of their relative merits and limitations. An overview is also given of the drug therapies that may prove useful in the treatment of patients with altered arterial mechanics.

Evaluation of mechanical arterial properties: clinical, experimental and therapeutic aspects.

Ageing and disease states associated with an increase in cardiovascular events alter the physical characteristics of blood vessel walls and impair the pulsatile function of arteries. An accumulating body of evidence indicates that impaired pulsatile function of arteries provides important prognostic and therapeutic information beyond that provided by traditional blood pressure measurements. A variety of techniques are currently employed to evaluate the mechanical properties of arteries. All techniques have theoretical, technical and practical limitations that impact on their widespread application in the clinical setting and use as measurement tools to improve cardiovascular risk stratification. A detailed discussion of these issues forms the basis of this review.