Pressure support ventilation with the ProSeal (R) laryngeal mask airway. A comparison of sevoflurane, isoflurane and propofol

Background and objective: There are no data about the influence of anaesthetics on cardiovascular variables during pressure support ventilation of the lungs through the laryngeal mask airway. We compared propofol, sevoflurane and isoflurane for maintenance of anaesthesia with the ProSeal (R) laryngeal mask airway during pressure support ventilation. Methods: Sixty healthy adults undergoing peripheral musculo-skeletal surgery were randomized for maintenance with sevoflurane end-tidal 29%, isoflurane end-tidal 1.1% or propofol 6 mg kg(-1) h(-1) in oxygen 33% and air. Pressure support ventilation comprised positive end-expiratory pressure set at 5 cmH(2)O, and pressure support set 5 cmH(2)O above positive end-expiratory pressure. Pressure support was initiated when inspiration produced a 2 cmH(2)O reduction in airway pressure. A blinded observer recorded cardiorespiratory variables (heart rate, mean blood pressure, oxygen saturation, air-way occlusion pressure, respiratory rate, expired tidal volume, expired minute volume and end-tidal CO2), adverse events and emergence times. Results: Respiratory rate and minute volume were 10-21% lower, and end-tidal CO2 6-11% higher with the propofol group compared with the sevoflurane or isoflurane groups, but otherwise cardiorespiratory variables were similar among groups. No adverse events occurred in any group. Emergence times were longer with the propofol group compared with the sevoflurane or isoflurane groups (10 vs. 7 vs. 7 min). Conclusion: Lung ventilation is less effective and emergence times are longer with propofol than sevoflurane or isoflurane for maintenance of anaesthesia during pressure support ventilation with the ProSeal (R) laryngeal mask airway. However, these differences are small and of doubtful clinical importance.

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region - An overview of 26 cohorts involving 306,620 participants

Background and Purpose - The cause of subarachnoid hemorrhage ( SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian ( predominantly white) populations. Methods - Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Results - Individual participant data from 26 prospective cohort studies ( total number of participants 306 620) that reported incident cases of SAH ( fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP > 140 mm Hg ( HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP ( similar to 140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Conclusions - Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

Simulation of Brugada syndrome using cellular and three-dimensional whole-heart modeling approaches

Brugada syndrome (BS) is a genetic disease identified by an abnormal electrocardiogram ( ECG) ( mainly abnormal ECGs associated with right bundle branch block and ST-elevation in right precordial leads). BS can lead to increased risk of sudden cardiac death. Experimental studies on human ventricular myocardium with BS have been limited due to difficulties in obtaining data. Thus, the use of computer simulation is an important alternative. Most previous BS simulations were based on animal heart cell models. However, due to species differences, the use of human heart cell models, especially a model with three-dimensional whole-heart anatomical structure, is needed. In this study, we developed a model of the human ventricular action potential (AP) based on refining the ten Tusscher et al (2004 Am. J. Physiol. Heart Circ. Physiol. 286 H1573 - 89) model to incorporate newly available experimental data of some major ionic currents of human ventricular myocytes. These modified channels include the L-type calcium current (ICaL), fast sodium current (I-Na), transient outward potassium current (I-to), rapidly and slowly delayed rectifier potassium currents (I-Kr and I-Ks) and inward rectifier potassium current (I-Ki). Transmural heterogeneity of APs for epicardial, endocardial and mid-myocardial (M) cells was simulated by varying the maximum conductance of IKs and Ito. The modified AP models were then used to simulate the effects of BS on cellular AP and body surface potentials using a three-dimensional dynamic heart - torso model. Our main findings are as follows. (1) BS has little effect on the AP of endocardial or mid-myocardial cells, but has a large impact on the AP of epicardial cells. (2) A likely region of BS with abnormal cell AP is near the right ventricular outflow track, and the resulting ST-segment elevation is located in the median precordium area. These simulation results are consistent with experimental findings reported in the literature. The model can reproduce a variety of electrophysiological behaviors and provides a good basis for understanding the genesis of abnormal ECG under the condition of BS disease.

Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

Exercise brachial blood pressure ( BP) predicts mortality, but because of wave reflection, central ( ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56 +/- 9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20 +/- 10 mm Hg and 15 +/- 7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/- SD) for central systolic BP of -1.3 +/- 3.2 mm Hg at rest and -4.7 +/- 3.3 mm Hg at peak exercise ( for both r=0.995; P < 0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155 +/- 33 versus 138 +/- 32mm Hg; mean difference, -16.3 +/- 9.4mm Hg) and during exercise (180 +/- 34 versus 164 +/- 33 mm Hg; mean difference, -15.5 +/- 10.4 mm Hg; for both P < 0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Contribution of changes in risk factors to the decline of coronary heart disease mortality in Australia over three decades

BACKGROUND: Coronary heart disease has been a major cause of mortality in Australian adults, but the rate has declined by 83% from the 1968 peak by the year 2000. The study objective is to determine the contribution of changes in population risk factors - mean serum cholesterol and diastolic blood pressure and tobacco smoking prevalence - to the decline in coronary heart disease mortality in Australia over three decades. METHODS: Coronary heart disease deaths (International Classification of Disease-9, 410-414) and population by year, age group and sex were obtained from the Australian Bureau of Statistics. Risk factor levels were obtained from population surveys and estimated average annual changes by period were used to calculate average annual 'attributable' proportional declines in CHD mortality by period (age 35-64 years). RESULTS: Over the period 1968-2000, 74% of male decline and 81% of the female decline in coronary heart disease mortality rate was accounted for by the combined effect of reductions in the three risk factors. In males 36% of the decline was contributed by reductions in diastolic blood pressure, 22% by cholesterol and 16% by smoking. For females 56% was from diastolic blood pressure reduction, 20% from cholesterol and 5% from smoking. Effects of reductions in serum cholesterol on coronary heart disease mortality occurred mainly in the 1970s. Declines in diastolic blood pressure had effects on coronary heart disease mortality over the three decades, and declines in tobacco smoking had a significant effect in males in the 1980s. CONCLUSION: Most of the spectacular decline in coronary heart disease mortality over the last three decades in Australia can be ascribed to reductions in population risk factors from primary and secondary prevention.

Motion analysis of right ventricular wall based on an electromechanical biventricular model

Based on our previously developed electrical heart model, an electromechanical biventricular model, which couples the electrical property and mechanical property of the heart, was constructed and the right ventricular wall motion and deformation was simulated using this model. The model was developed on the basis of composite material theory and finite element method. The excitation propagation was simulated by electrical heart model, and the resultant active forces were used to study the ventricular wall motion during systole. The simulation results show that: (1) The right ventricular free wall moves towards the septum, and at the same time, the base and middle of free wall move towards the apex, which reduce the volume of right ventricle; (2) The minimum principle strain (E3) is largest at the apex, then at the middle of free wall, and its direction is in the approximate direction of epicardial muscle fibers. These results are in good accordance with solutions obtained from MR tagging images. It suggests that such electromechanical biventricular model can be used to assess the mechanical function of two ventricles.

Transient cardiac ischaemia and abnormal variations in systemic blood pressure in unselected primary open angle glaucoma patients

To investigate the relationship between the occurrence of transient cardiac ischaemic episodes and variations in the ambulatory 24-h blood pressure and heart rate measurements in a group of unselected glaucoma patients.

The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy

BACKGROUND: Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability. METHODS: In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo. RESULTS: Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management. CONCLUSIONS: There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction. (C) 2009 Lippincott Williams & Wilkins, Inc.

Evaluation of the Heart of Birmingham teaching Primary Care Trust (HoBtPCT): My Choice Weight Management Programme:report commissioned by Heart of Birmingham teaching Primary Care Trust

This report details an evaluation of the My Choice Weight Management Programme undertaken by a research team from the School of Pharmacy at Aston University. The My Choice Weight Management Programme is delivered through community pharmacies and general practitioners (GPs) contracted to provide services by the Heart of Birmingham teaching Primary Care Trust. It is designed to support individuals who are ‘ready to change’ by enabling the individual to work with a trained healthcare worker (for example, a healthcare assistant, practice nurse or pharmacy assistant) to develop a care plan designed to enable the individual to lose 5-10% of their current weight. The Programme aims to reduce adult obesity levels; improve access to overweight and obesity management services in primary care; improve diet and nutrition; promote healthy weight and increased levels of physical activity in overweight or obese patients; and support patients to make lifestyle changes to enable them to lose weight. The Programme is available for obese patients over 18 years old who have a Body Mass Index (BMI) greater than 30 kg/m2 (greater than 25 kg/m2 in Asian patients) or greater than 28 kg/m2 (greater than 23.5 kg/m2 in Asian patients) in patients with co-morbidities (diabetes, high blood pressure, cardiovascular disease). Each participant attends weekly consultations over a twelve session period (the final iteration of these weekly sessions is referred to as ‘session twelve’ in this report). They are then offered up to three follow up appointments for up to six months at two monthly intervals (the final of these follow ups, taking place at approximately nine months post recruitment, is referred to as ‘session fifteen’ in this report). A review of the literature highlights the dearth of published research on the effectiveness of primary care- or community-based weight management interventions. This report may help to address this knowledge deficit. A total of 451 individuals were recruited on to the My Choice Weight Management Programme. More participants were recruited at GP surgeries (n=268) than at community pharmacies (n=183). In total, 204 participants (GP n=102; pharmacy n=102) attended session twelve and 82 participants (GP n=22; pharmacy 60) attended session fifteen. The unique demographic characteristics of My Choice Weight Management Programme participants – participants were recruited from areas with high levels of socioeconomic deprivation and over four-fifths of participants were from Black and Minority Ethnic groups; populations which are traditionally underserved by healthcare interventions – make the achievements of the Programme particularly notable. The mean weight loss at session 12 was 3.8 kg (equivalent to a reduction of 4.0% of initial weight) among GP surgery participants and 2.4 kg (2.8%) among pharmacy participants. At session 15 mean weight loss was 2.3 kg (2.2%) among GP surgery participants and 3.4 kg (4.0%) among pharmacy participants. The My Choice Weight Management Programme improved the general health status of participants between recruitment and session twelve as measured by the validated SF-12 questionnaire. While cost data is presented in this report, it is unclear which provider type delivered the Programme more cost-effectively. Attendance rates on the Programme were consistently better among pharmacy participants than among GP participants. The opinions of programme participants (both those who attended regularly and those who failed to attend as expected) and programme providers were explored via semi-structured interviews and, in the case of the participants, a selfcompletion postal questionnaire. These data suggest that the Programme was almost uniformly popular with both the deliverers of the Programme and participants on the Programme with 83% of questionnaire respondents indicating that they would be happy to recommend the Programme to other people looking to lose weight. Our recommendations, based on the evidence provided in this report, include: a. Any consideration of an extension to the study also giving comparable consideration to an extension of the Programme evaluation. The feasibility of assigning participants to a pharmacy provider or a GP provider via a central allocation system should also be examined. This would address imbalances in participant recruitment levels between provider type and allow for more accurate comparison of the effectiveness in the delivery of the Programme between GP surgeries and community pharmacies by increasing the homogeneity of participants at each type of site and increasing the number of Programme participants overall. b. Widespread dissemination of the findings from this review of the My Choice Weight Management Project should be undertaken through a variety of channels. c. Consideration of the inclusion of the following key aspects of the My Choice Weight Management Project in any extension to the Programme: i. The provision of training to staff in GP surgeries and community pharmacies responsible for delivery of the Programme prior to patient recruitment. ii. Maintaining the level of healthcare staff input to the Programme. iii. The regular schedule of appointments with Programme participants. iv. The provision of an increased variety of printed material. d. A simplification of the data collection method used by the Programme commissioners at the individual Programme delivery sites.

The development and investigation of a novel pulsatile heart assist device

Cardiovascular diseases (CVD) contributed to almost 30% of worldwide mortality; with heart failure being one class of CVD. One popular and widely available treatment for heart failure is the intra-aortic balloon pump (IABP). This heart assist device is used in counterpulsation to improve myocardial function by increasing coronary perfusion, and decreasing aortic end-diastolic pressure (i.e. the resistance to blood ejection from the heart). However, this device can only be used acutely, and patients are bedridden. The subject of this research is a novel heart assist treatment called the Chronic Intermittent Mechanical Support (CIMS) which was conceived to offer advantages of the IABP device chronically, whilst overcoming its disadvantages. The CIMS device comprises an implantable balloon pump, a percutaneous drive line, and a wearable driver console. The research here aims to determine the haemodynamic effect of balloon pump activation under in vitro conditions. A human mock circulatory loop (MCL) with systemic and coronary perfusion was constructed, capable of simulating various degrees of heart failure. Two prototypes of the CIMS balloon pump were made with varying stiffness. Several experimental factors (balloon inflation/deflation timing, Helium gas volume, arterial compliance, balloon pump stiffness and heart valve type) form the factorial design experiments. A simple modification to the MCL allowed flow visualisation experiments using video recording. Suitable statistical tests were used to analyse the data obtained from all experiments. Balloon inflation and deflation in the ascending aorta of the MCL yielded favourable results. The sudden balloon deflation caused the heart valve to open earlier, thus causing longer valve opening duration in a cardiac cycle. It was also found that pressure augmentation in diastole was significantly correlated with increased cardiac output and coronary flowrate. With an optimum combination (low arterial compliance and low balloon pump stiffness), systemic and coronary perfusions were increased by 18% and 21% respectively, while the aortic end-diastolic pressure (forward flow resistance) decreased by 17%. Consequently, the ratio of oxygen supply and demand to myocardium (endocardial viability ratio, EVR) increased between 33% and 75%. The increase was mostly attributed to diastolic augmentation rather than systolic unloading.

The relationship between measurement method and corneal structure on apparent intraocular pressure in glaucoma and ocular hypertension

Purpose: To analyse the relationship between measured intraocular pressure (IOP) and central corneal thickness (CCT), corneal hysteresis (CH) and corneal resistance factor (CRF) in ocular hypertension (OHT), primary open-angle (POAG) and normal tension glaucoma (NTG) eyes using multiple tonometry devices. Methods: Right eyes of patients diagnosed with OHT (n=47), normal tension glaucoma (n=17) and POAG (n=50) were assessed, IOP was measured in random order with four devices: Goldmann applanation tonometry (GAT); Pascal(R) dynamic contour tonometer (DCT); Reichert(R) ocular response analyser (ORA); and Tono-Pen(R) XL. CCT was then measured using a hand-held ultrasonic pachymeter. CH and CRF were derived from the air pressure to corneal reflectance relationship of the ORA data. Results: Compared to the GAT, the Tonopen and ORA Goldmann equivalent (IOPg) and corneal compensated (IOPcc) measured higher IOP readings (F=19.351, p<0.001), particularly in NTG (F=12.604, p<0.001). DCT was closest to Goldmann IOP and had the lowest variance. CCT was significantly different (F=8.305, p<0.001) between the 3 conditions as was CH (F=6.854, p=0.002) and CRF (F=19.653, p<0.001). IOPcc measures were not affected by CCT. The DCT was generally not affected by corneal biomechanical factors. Conclusion: This study suggests that as the true pressure of the eye cannot be determined non-invasively, measurements from any tonometer should be interpreted with care, particularly when alterations in the corneal tissue are suspected.

Does rebound tonometry probe misalignment modify intraocular pressure measurements in human eyes?

Purpose. To examine the influence of positional misalignments on intraocular pressure (IOP) measurement with a rebound tonometer. Methods. Using the iCare rebound tonometer, IOP readings were taken from the right eye of 36 healthy subjects at the central corneal apex (CC) and compared to IOP measures using the Goldmann applanation tonometer (GAT). Using a bespoke rig, iCare IOP readings were also taken 2 mm laterally from CC, both nasally and temporally, along with angular deviations of 5 and 10 degrees, both nasally and temporally to the visual axis. Results. Mean IOP ± SD, as measured by GAT, was 14.7±2.5 mmHg versus iCare tonometer readings of 17.4±3.6 mmHg at CC, representing an iCare IOP overestimation of 2.7±2.8 mmHg (P<0.001), which increased at higher average IOPs. IOP at CC using the iCare tonometer was not significantly different to values at lateral displacements. IOP was marginally underestimated with angular deviation of the probe but only reaching significance at 10 degrees nasally. Conclusions. As shown previously, the iCare tonometer overestimates IOP compared to GAT. However, IOP measurement in normal, healthy subjects using the iCare rebound tonometer appears insensitive to misalignments. An IOP underestimation of <1 mmHg with the probe deviated 10 degrees nasally reached statistical but not clinical significance levels. © 2013 Ian G. Beasley et al.

Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo

Objective- Increased reactive oxygen species (ROS) production is involved in the pathophysiology of endothelial dysfunction. NADPH oxidase-4 (Nox4) is a ROS-generating enzyme expressed in the endothelium, levels of which increase in pathological settings. Recent studies indicate that it generates predominantly hydrogen peroxide (H O ), but its role in vivo remains unclear. Methods and Results- We generated transgenic mice with endothelium-targeted Nox4 overexpression (Tg) to study the in vivo role of Nox4. Tg demonstrated significantly greater acetylcholine- or histamine-induced vasodilatation than wild-type littermates. This resulted from increased H O production and H O -induced hyperpolarization but not altered nitric oxide bioactivity. Tg had lower systemic blood pressure than wild-type littermates, which was normalized by antioxidants. Conclusion- Endothelial Nox4 exerts potentially beneficial effects on vasodilator function and blood pressure that are attributable to H O production. These effects contrast markedly with those reported for Nox1 and Nox2, which involve superoxide-mediated inactivation of nitric oxide. Our results suggest that therapeutic strategies to modulate ROS production in vascular disease may need to separately target individual Nox isoforms. © 2011 American Heart Association, Inc.