Medical High Dependency Unit series, Article 4: Tracheostomy management.

The number of patients with tracheostomies managed within high dependency units is increasing. National audits have suggested that the care of these patients could have been improved upon with a significant minority of cases resulting in death or serious adverse events. Because of this, it is crucial that staff working within medical high dependency units have a good understanding of the indications for and techniques of insertion of tracheostomies. In addition, knowledge of the various tube types and ancillary equipment is mandatory. Ideally, care should be standardised across hospital sites and all staff trained to deal with routine and basic emergency care using national guidelines. It is fundamental that medical staff without expertise in the advanced management of emergencies are aware of the equipment required and who to contact within their hospital should such procedures be necessary. Temporary tracheostomies should be removed at the earliest opportunity under the guidance of the teams responsible for their insertion.

Progressing care in the Medical High Dependency Unit: unit configurations, staffing, standards, and daily routine.

There are currently various models of care for provision of high dependency care for acutely ill medical patients across the UK. Acute Physicians are integral to the development and progression of this both challenging and rewarding area of medicine. This article outlines current standards, best evidence, and our own experience of both setting up and developing a medical high dependency unit (MHDU).

Medical High Dependency Series 2: Haemodynamics and Shock: Assessment, Interventions and Support.

Shock is a life-threatening state commonly encountered by the acute physician. As such those practicing and training in the specialty should strive to become true experts in this field by going beyond even the learning provided by generic life support courses when involved with identifying and managing the shocked state. This article explores the current evidence, where it exists and provides a framework for approaching such patients along with common pitfalls.

Medical High Dependency Unit series, Article 3: Respiratory Support in the MHDU.

Acute respiratory failure is a life threatening condition encountered by Acute Physicians; additional non-invasive support can be provided within the medical high dependency unit (MHDU). Acute Physicians should strive to be experts in the investigation, management and support of patients with acute severe respiratory failure. This article outlines key management principles in these areas and explores common pitfalls.

Problem-based review: A patient with metabolic acidosis.

Metabolic acidosis is a common metabolic derangement present in the acute medical patient. A thorough and structured investigative approach is required as there are many causes and management is reliant on identifying these. In particular calculation of the anion gap with correction for albumin level and use of the delta ratio can be helpful in complex cases especially in patients where a combination of metabolic derangements may be present.

ATP consumption by sarcoplasmic reticulum Ca2+ pumps accounts for 50% of resting metabolic rate in mouse fast and slow twitch skeletal muscle.

In this study, we aimed to directly quantify the relative contribution of Ca(2+) cycling to resting metabolic rate in mouse fast-twitch (extensor digitorum longus, EDL) and slow-twitch (soleus) skeletal muscle. Resting oxygen consumption of isolated muscles (Vo(2), microl.g wet wt(-1).s(-1)) measured polarographically at 30 degrees C was approximately 25% higher in soleus (0.61 +/- .03) than in EDL (0.46 +/- .03). To quantify the specific contribution of Ca(2+) cycling to resting metabolic rate, cyclopiazonic acid (CPA), a highly specific inhibitor of sarco(endo)plasmic reticulum Ca(2+) ATPases (SERCAs), was added to the bath at different concentrations (1, 5, 10, and 15 microM). There was a concentration-dependent effect of CPA on Vo(2), with increasing CPA concentrations up to 10 microM resulting in progressively greater reductions in muscle Vo(2). There were no differences between 10 and 15 microM CPA, indicating that 10 microM CPA induces maximal inhibition of SERCAs in isolated muscle preparations. Relative reduction in muscle Vo(2) in response to CPA was nearly identical in EDL (1 microM, 10.6 +/- 3.0%; 5 microM, 33.2 +/- 3.4%; 10 microM, 49.2 +/- 2.9%; 15 microM, 50.9 +/- 2.1%) and soleus (1 microM, 11.2 +/- 1.5%; 5 microM, 37.7 +/- 2.4%; 10 microM, 50.0 +/- 1.3%; 15 microM, 49.9 +/- 1.6%). The results indicate that ATP consumption by SERCAs is responsible for approximately 50% of resting metabolic rate in both mouse fast- and slow-twitch muscles at 30 degrees C. Thus SERCA pumps in skeletal muscle could represent an important control point for energy balance regulation and a potential target for metabolic alterations to oppose obesity.

Posttetanic potentiation in mdx muscle.

X-linked muscular dystrophy of the mouse (mdx) has been reported to progressively remodel skeletal muscle to preferentially reduce fast fiber composition. Despite this, mdx muscle displays normal levels of posttetanic potentiation (PTP). Since PTP may primarily depend on phosphorylation of the myosin regulatory light chain (RLC) in fast muscle fibers, maintenance of PTP with mdx disease progression is paradoxical and may represent an adaptation of the diseased muscle. This study assesses the role of RLC phosphorylation during PTP of mdx muscle. Extensor digitorum longus muscles were isolated from mdx and from C57BL/10 (control) mice at ~50 (young) and ~300 (adult) days and stimulated in vitro (25°C) to induce PTP. During potentiation, muscles were harvested for subsequent determination of RLC phosphorylation levels. Immunofluorescence was used to assess muscle fiber type composition and no age effects were found. The magnitude of PTP was higher (P < 0.05) in mdx than control muscles at both young (mdx: 21.9 ± 1.6%; control: 17.7 ± 1.2%) and adult (mdx: 30.4 ± 1.8%; control: 23.2 ± 2.2%) ages. However, RLC phosphate content was similar between all groups both at rest and following stimulation. Our results are consistent with a model where the sensitivity of mdx muscle to RLC phosphorylation-induced force potentiation is increased by disease- and age-dependent alterations in excitation-contraction coupling noted for mdx and aging muscle.

Diaphragm assessment in mice overexpressing phospholamban in slow-twitch type I muscle fibers.

AIMS: Phospholamban (PLN) and sarcolipin (SLN) are small inhibitory proteins that regulate the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pump. Previous work from our laboratory revealed that in the soleus and gluteus minimus muscles of mice overexpressing PLN (Pln (OE)), SERCA function was impaired, dynamin 2 (3-5 fold) and SLN (7-9 fold) were upregulated, and features of human centronuclear myopathy (CNM) were observed. Here, we performed structural and functional experiments to evaluate whether the diaphragm muscles of the Pln (OE) mouse would exhibit CNM pathology and muscle weakness. METHODS: Diaphragm muscles from Pln (OE) and WT mice were subjected to histological/histochemical/immunofluorescent staining, Ca(2+)-ATPase and Ca(2+) uptake assays, Western blotting, and in vitro electrical stimulation. RESULTS: Our results demonstrate that PLN overexpression reduced SERCA's apparent affinity for Ca(2+) but did not reduce maximal SERCA activity or rates of Ca(2+) uptake. SLN was upregulated 2.5-fold, whereas no changes in dynamin 2 expression were found. With respect to CNM, we did not observe type I fiber predominance, central nuclei, or central aggregation of oxidative activity in diaphragm, although type I fiber hypotrophy was present. Furthermore, in vitro contractility assessment of Pln (OE) diaphragm strips revealed no reductions in force-generating capacity, maximal rates of relaxation or force development, but did indicate that ½ relaxation time was prolonged. CONCLUSIONS: Therefore, the effects of PLN overexpression on skeletal muscle phenotype differ between diaphragm and the postural soleus and gluteus minimus muscles. Our findings here point to differences in SLN expression and type I fiber distribution as potential contributing factors.