Gastric cooling and menthol cause an increase in cardiac parasympathetic efferent activity in healthy adult human volunteers.

NEW FINDINGS: What is the central question of this study? How do gastric stretch and gastric cooling stimuli affect cardiac autonomic control? What is the main finding and its importance? Gastric stretch causes an increase in cardiac sympathetic activity. Stretch combined with cold stimulation result in an elimination of the sympathetic response to stretch and an increase in cardiac parasympathetic activity, in turn resulting in a reduction in heart rate. Gastric cold stimulation causes a shift in sympathovagal balance towards parasympathetic dominance. The cold-induced bradycardia has the potential to decrease cardiac workload, which might be significant in individuals with cardiovascular pathologies. ABSTRACT: Gastric distension increases blood pressure and heart rate in young, healthy humans, but little is known about the effect of gastric stretch combined with cooling. We used a randomized crossover study to assess the cardiovascular responses to drinking 300 ml of ispaghula husk solution at either 6 or 37°C in nine healthy humans (age 24.08 ± 9.36 years) to establish the effect of gastric stretch with and without cooling. The effect of consuming peppermint oil capsules to activate cold thermoreceptors was also investigated. The ECG, respiratory movements and continuous blood pressure were recorded during a 5 min baseline period, followed by a 115 min post-drink period, during which 5 min epochs of data were recorded. Cardiac autonomic activity was assessed using time and frequency domain analyses of respiratory sinus arrhythmia to quantify parasympathetic autonomic activity, and corrected QT (QTc) interval analysis to quantify sympathetic autonomic activity. Gastric stretch only caused a significant reduction in QTc interval lasting up to 15 min, with a concomitant but non-significant increase in heart rate, indicating an increased sympathetic cardiac tone. The additional effect of gastric cold stimulation was significantly to reduce heart rate for up to 15 min, elevate indicators of cardiac parasympathetic tone and eliminate the reduction in QTc interval seen with gastric stretch only. Stimulation of gastric cold thermoreceptors with menthol also caused a significant reduction in heart rate and concomitant increase in the root mean square of successive differences. These findings indicate that gastric cold stimulation causes a shift in the sympathovagal balance of cardiac control towards a more parasympathetic dominant pattern.

Collaborative care for depression: a cumulative meta-analysis and review of longer-term outcomes.

BACKGROUND: Depression is common in primary care but is suboptimally managed. Collaborative care, that is, structured care involving a greater role of nonmedical specialists to augment primary care, has emerged as a potentially effective candidate intervention to improve quality of primary care and patient outcomes. METHODS: To quantify the short-term and longer-term effectiveness of collaborative care compared with standard care and to understand mechanisms of action by exploring between-study heterogeneity, we conducted a systematic review of randomized controlled trials that compared collaborative care with usual primary care in patients with depression. We searched MEDLINE (from the beginning of 1966), EMBASE (from the beginning of 1980), CINAHL (from the beginning of 1980), PsycINFO (from the beginning of 1980), the Cochrane Library (from the beginning of 1966), and DARE (Database of Abstracts of Reviews of Effectiveness) (from the beginning of 1985) databases from study inception to February 6, 2006. RESULTS: We found 37 randomized studies including 12 355 patients with depression receiving primary care. Random effects meta-analysis showed that depression outcomes were improved at 6 months (standardized mean difference, 0.25; 95% confidence interval, 0.18-0.32), and evidence of longer-term benefit was found for up to 5 years (standardized mean difference, 0.15; 95% confidence interval, 0.001-0.31). When exploring determinants of effectiveness, effect size was directly related to medication compliance and to the professional background and method of supervision of case managers. The addition of brief psychotherapy did not substantially improve outcome, nor did increased numbers of sessions. Cumulative meta-analysis showed that sufficient evidence had emerged by 2000 to demonstrate the statistically significant benefit of collaborative care. CONCLUSIONS: Collaborative care is more effective than standard care in improving depression outcomes in the short and longer terms. Future research needs to address the implementation of collaborative care, particularly in settings other than the United States.

NO-cGMP pathway at ventrolateral medullary cardiac inhibitory sites enhances the baroreceptor reflex bradycardia in the rat.

The neuronal isoform of the enzyme nitric oxide synthase (nNOS) has been identified in the caudal ventrolateral medulla of the rat close to the location of cardiac vagal motoneurones. Therefore in this study we tested identified ventral medulla cardioinhibitory sites for the involvement of nitric oxide (NO) in the baroreceptor-heart rate reflex pathway. In rats anaesthetised with a mixture of urethane (650 mg kg(-1)) and chloralose (50 mg kg(-1)) i.v., blood pressure and heart rate were monitored continuously and using stereotaxic coordinates the ventrolateral caudal brainstem within and around the nucleus ambiguus was systematically explored for sites producing a bradycardia of >50 bpm, without a change in blood pressure, using D,L homocysteic acid (DLH, 0.2 M) microinjections (50 nl) from a glass micropipette. Identified sites were marked with pontamine sky blue. Microinjection of the NO donor sodium nitroprusside (SNP, 1 mM, 50 nl) at a cardioinhibitory site also produced a significant bradycardia (68+/-14 bpm) while the NOS inhibitor N(G)-nitro-l-arginine (l-NNA) (3 mM, 50 nl) caused a small significant increase in heart rate (5+/-1 bpm). Baroreceptor reflex gain measured by the response in heart rate to a change in blood pressure induced by phenylephrine i.v. was significantly increased (610+/-171%, p<0.05) during the steady state of the response to SNP, whereas it was significantly reduced (73+/-5%, p<0.01) by l-NNA injection at a medullary cardioinhibitory site. An inhibitor of soluble guanylyl cyclase, (1)H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 1 mM, 50 nl) also significantly reduced the baroreceptor reflex gain (63+/-8%, p<0.05). The results suggest that a NOS-cGMP signalling system in the baroreceptor reflex pathway distal to the NTS and closer to cardiac vagal motoneurones in the caudal ventral medulla contributes to enhancement of cardiac vagal tone.

Developing a U.K. protocol for collaborative care: a qualitative study.

OBJECTIVE: This study aimed to explore the views of stakeholders including patients, general practitioners (GPs) and mental health workers on the feasibility, acceptability and barriers to a collaborative care model for treatment of depression within the context of U.K. primary health care. METHOD: We used semistructured interviews and focus groups with a purposive sample of 11 patients and 38 professionals from a wide selection of primary and secondary care mental health services, as well as framework analysis using a "constant comparative" approach to identify key concepts and themes. RESULTS: Regular contact for patients with depression is acceptable and valued by both patients and professionals. However, patients value support, whereas professionals focus on information. To be acceptable to patients, contacts about medication or psychosocial support must minimize the potential for patient disempowerment. The use of the telephone is convenient and lends anonymity, but established mental health workers think it will impair their judgments. While patients merely identified the need for skilled case managers, GPs preferred established professionals; however, these workers did not see themselves in this role. All involved were cautious about deploying new workers. Additional barriers included practical and organizational issues. CONCLUSIONS: Although a telephone-delivered mix of medication support and low-intensity psychological intervention is generally acceptable, significant issues to be addressed include the values of the current mental health workforce, fears about new workers' experience and competence, the balance of face-to-face and telephone contacts and case manager education in nonspecific skills necessary to develop a therapeutic alliance, as well as the knowledge and skills required for education, medication support and behavioral activation. Qualitative research can add value to careful modeling of collaborative care prior to international implementation.

Acute aldosterone antagonism improves cardiac vagal control in humans.

OBJECTIVES: We have examined the acute effects (<45 min) of aldosterone antagonism on heart rate variability and baroreflex sensitivity, markers of cardiac vagal control, in 13 healthy subjects. BACKGROUND: Evidence for the beneficial effects of aldosterone antagonists comes from studies showing increased survival rates following their addition to standard heart failure therapy. Many mechanisms have been suggested for this action, including effects upon the autonomic nervous system. METHODS: Heart rate variability and baroreflex sensitivity were examined 30 min following the administration of potassium canrenoate (intravenous) (aldosterone antagonist) or saline (control). RESULTS: Active treatment reduced resting heart rate (-6 +/- 1 beats/min [mean +/- standard error mean]) compared to control (0 +/- 1 beat/min) (p < 0.001) and increased measures of high frequency (HF) heart rate variability. Root mean square of successive RR interval differences increased by 21 +/- 5 ms versus -6 +/- 5 ms control (p < 0.001); HF power increased by 1,369 +/- 674 ms(2)with aldosterone antagonism compared to -255 +/- 431 ms(2) following saline infusion (p < 0.01). Baroreflex sensitivity (alpha-HF) was increased after active treatment (+4 +/- 2 ms/mm Hg vs. 0 +/- 1 ms/mm Hg control [p < 0.05]). No changes in plasma potassium levels were observed. CONCLUSIONS: These results provide evidence that aldosterone antagonists acutely improve cardiac vagal control, irrespective of any diuretic effects, and may in part explain their beneficial effects in treatment of heart failure.

Prognostic significance of early short-term measurements of heart rate variability following acute myocardial infarction.

This study of 164 subjects demonstrates that short-term (5-minute) recordings of heart rate variability, performed within 48 hours of admission, identify those who survive acute myocardial infarction but have an adverse prognosis.

A collaborative approach to embedding graduate primary care mental health workers in the UK National Health Service.

The UK National Health Service (NHS) workforce has recently seen the arrival of the Graduate Mental Health Worker (GMHW) in primary care. We established a Quality Improvement Collaborative to assist in embedding this new workforce in one Strategic Health Authority Area of England. The intervention utilised 'collaborative' technology which involves bringing together groups of practitioners from different organizations to work in a structured way to improve the quality of their service. The process was evaluated by an action research project in which all stakeholders participated. Data collection was primarily qualitative. During the project, there was an increase in throughput of new patients seen by the GMHWs and increased workforce satisfaction with a sense that the collaborative aided the change process within the organizations. Involvement of managers and commissioners from the Primary Care Trusts where the GMHWs were employed appeared to be important in achieving change. This was not, however, sufficient to combat significant attrition of the first cohort of workers. The project identified several barriers to the successful implementation of a new workforce for mental health problems in primary care, including widespread variation in the level and quality of supervision and in payment and terms of service of workers. A collaborative approach can be used to support the development of new roles in health care; however, full engagement from management is particularly necessary for success in implementation. The problems faced by GMHWs reflect those faced by other new workers in healthcare settings, yet in some ways are even more disturbing given the lack of governance arrangements put in place to oversee these developments and the apparent use of relatively unsupported and inexperienced novices as agents of change in the NHS.

Collaborative care for depression in primary care. Making sense of a complex intervention: systematic review and meta-regression.

BACKGROUND: The management of depression in primary care is a significant issue for health services worldwide. "Collaborative care" interventions are effective, but little is known about which aspects of these complex interventions are essential. AIMS: To use meta-regression to identify "active ingredients" in collaborative care models for depression in primary care. METHOD: Studies were identified using systematic searches of electronic databases. The content of collaborative care interventions was coded, together with outcome data on antidepressant use and depressive symptoms. Meta-regression was used to examine relationships between intervention content and outcomes. RESULTS: There was no significant predictor of the effect of collaborative care on antidepressant use. Key predictors of depressive symptom outcomes included systematic identification of patients, professional background of staff and specialist supervision. CONCLUSIONS: Meta-regression may be useful in examining "active ingredients" in complex interventions in mental health.

The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction.

AIMS: Heart rate variability (HRV) is a measure of cardiac autonomic control and is therefore subject to regulation by the renin-angiotensin system. The primary objective of this study was to determine the effect of an insertion/deletion polymorphism within the angiotensin-converting enzyme (ACE) gene on HRV in the early stages after a myocardial infarction at a time when cardiac autonomic control is deranged. The secondary objective was to determine whether this polymorphism affected the HRV response to inhibition of ACE. MAJOR FINDINGS: 149 Caucasian subjects were studied 25 +/- 16 h following MI using time and frequency domain measures of HRV derived from two 5-minute ECG recordings. Recordings were repeated at 182 +/- 65 h following MI, when subjects had been stabilised on ramipril 2.5 mg bd. The study included 46 subjects with the DD genotype, 69 with the ID genotype, and 34 with the II genotype. No effect of the I/D polymorphism on short-term recordings of HRV was found. There was no difference in HRV response to the introduction of ramipril according to the genotypes. PRINCIPAL CONCLUSIONS: The I/D polymorphism within the ACE gene does not influence HRV after MI or the HRV response to ACE inhibitor therapy with ramipril. These findings may reflect the relative lack of importance of the I/D polymorphism and ACE activity in determining plasma and tissue angiotensin II concentration after a major stimulus to the renin-angiotensin system as occurs after myocardial infarction.