The importance of 'place' and its influence on rural and remote health and well-being in Australia.

AIMS: This article explores the crucial role of 'place' as an ecological, social and cultural determinant of health and well-being, with a focus on the benefits and challenges of living rurally and remotely in Australia. CONTEXT: The health system, including health promotion, can contribute actively to creating supportive environments and places that foster health and well-being among individuals residing in rural and remote locations. For First Nations peoples, living on Country, and caring for Country and its people, are core to Indigenous worldviews, and the promotion of Aboriginal and Torres Strait Islander health and well-being. Their forced removal from ancestral lands has been catastrophic. For all people, living in rural and remote areas can deliver an abundance of the elements that contribute to a 'liveable' community, including access to fresh air, green and blue space, agricultural employment, tight-knit communities, a sense of belonging and identity, and social capital. However, living remotely also can limit access to employment opportunities, clean water, affordable food, reliable transport, social infrastructure, social networks and preventive health services. 'Place' is a critical enabler of maintaining a healthy life. However, current trends have led to a reduction in local services and resources, and increased exposure to the impacts of climate change. APPROACH: This commentary suggests ideas and strategies through which people in rural and remote locations can strengthen the liveability, resilience and identity of their communities, and regain access to essential health care and health promotion services and resources. CONCLUSION: Recommended strategies include online access to education, employment and telehealth; flexible provision of social infrastructure; and meaningful and responsive university-health service partnerships.

Neural substrate for atrial fibrillation: implications for targeted parasympathetic blockade in the posterior left atrium.

The parasympathetic (P) nervous system is thought to contribute significantly to focal atrial fibrillation (AF). Thus we hypothesized that P nerve fibers [and related muscarinic (M(2)) receptors] are preferentially located in the posterior left atrium (PLA) and that selective cholinergic blockade in the PLA can be successfully performed to alter vagal AF substrate. The PLA, pulmonary veins (PVs), and left atrial appendage (LAA) from six dogs were immunostained for sympathetic (S) nerves, P nerves, and M(2) receptors. Epicardial electrophysiological mapping was performed in seven additional dogs. The PLA was the most richly innervated, with nerve bundles containing P and S fibers (0.9 +/- 1, 3.2 +/- 2.5, and 0.17 +/- 0.3/cm(2) in the PV, PLA, and LAA, respectively, P < 0.001); nerve bundles were located in fibrofatty tissue as well as in surrounding myocardium. P fibers predominated over S fibers within bundles (P-to-S ratio = 4.4, 7.2, and 5.8 in PV, PLA, and LAA, respectively). M(2) distribution was also most pronounced in the PLA (17.8 +/- 8.3, 14.3 +/- 7.3, and 14.5 +/- 8 M(2)-stained cells/cm(2) in the PLA, PV, and LAA, respectively, P = 0.012). Left cervical vagal stimulation (VS) caused significant effective refractory period shortening in all regions, with easily inducible AF. Topical application of 1% tropicamide to the PLA significantly attenuated VS-induced effective refractory period shortening in the PLA, PV, and LAA and decreased AF inducibility by 92% (P < 0.001). We conclude that 1) P fibers and M(2) receptors are preferentially located in the PLA, suggesting an important role for this region in creation of vagal AF substrate and 2) targeted P blockade in the PLA is feasible and results in attenuation of vagal responses in the entire left atrium and, consequently, a change in AF substrate.

Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach.

OBJECTIVES: The purpose of this study was to investigate whether a novel fibroblast growth factor-2 gene formulation, providing a localized and sustained availability of the adenoviral vector from a collagen-based matrix, in combination with CO 2 transmyocardial laser revascularization would lead to an enhanced angiogenic response and improved myocardial function. METHODS: Fibroblast growth factor-2 gene was delivered by means of an adenoviral vector (adenoviral fibroblast growth factor-2) formulated in a collagen-based matrix. The ischemic areas of 33 animals were then treated. Group 1 was treated with CO 2 transmyocardial laser revascularization; group 2 was treated with intramyocardial injections of adenoviral fibroblast growth factor-2 in a collagen-based matrix; group 3 had a combination treatment of matrix adenoviral fibroblast growth factor-2 and CO 2 transmyocardial laser revascularization; and group 4 received injections with saline-formulated adenoviral fibroblast growth factor-2. Baseline left ventricular function was assessed by echocardiography and cine magnetic resonance imaging. Studies were repeated 6 weeks after treatment. Vascular development was assessed using anti-alpha-actin immunohistochemistry. RESULTS: Matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas had a 105% increase in arteriolar development versus either treatment alone ( P < .05) and a 390% increase compared with saline-formulated adenoviral fibroblast growth factor-2 treatment alone ( P < .05). Contractility was significantly improved in matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas as measured by myocardial wall thickening. This functional improvement was confirmed by cine magnetic resonance imaging, in which a 90% increase in the contractility of the treated segments was demonstrated after matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularation. The other treatments provided significantly less restoration of myocardial function. CONCLUSIONS: The increase in angiogenesis as a result of matrix adenoviral fibroblast growth factor-2 gene therapy in combination with CO 2 transmyocardial laser revascularization is greater than that seen in either therapy alone. A concomitant improvement in myocardial function was seen as a result of this angiogenic response.

What is the optimal channel density for transmyocardial laser revascularization?

BACKGROUND: Transmyocardial laser revascularization (TMR) has demonstrated reproducible relief of angina in patients with end-stage coronary disease. However, the optimum dose or channel density has not been elucidated. METHODS: Using a porcine model of chronic myocardial ischemia, 14 animals were treated with CO2 TMR and randomized as follows: group 1 was 1 channel per 2 cm2; group 2 was 1 channel per 1 cm2; and group 3 was 2 channels per 1 cm2. Left ventricular myocardial viability and function were assessed by magnetic resonance imaging (MRI) and echocardiography pretreatment, and repeated 6 weeks later. RESULTS: The MRI assessment of group 1 (1 channel/2 cm2) and group 2 (1 channel/cm2) demonstrated similar improvement in segmental contractility posttreatment of 12.11% +/- 5.15% and 12.47% +/- 9.51%, respectively. In contrast, group 3 (2 channels/cm2) showed significantly worse segmental contractility posttreatment: -18.52% +/- 7.16% (p = 0.01). Echocardiographic imaging revealed significant improvements in wall thickening in the ischemic zone for group 1 at 0.91 +/- 0.07 cm pretreatment versus 1.30 +/- 0.09 cm posttreatment, (p = 0.01); and for group 2 at 0.93 +/- 0.11 cm versus 1.42 +/- 0.18 cm, (p = 0.01). No significant improvement in wall thickening was seen in group 3 (0.84 +/- 0.06 cm versus 0.88 +/- 0.09 cm, p = n.s.). CONCLUSIONS: These data corroborate the empiric finding of an effective therapeutic dose range for TMR, 1 channel per 1 to 2 cm2. These results also demonstrate a detrimental effect when channel density is increased above the clinical standard of 1 channel per cm2 to a density of 2 channels per 1 cm2.

Myocardial functional recovery after fibroblast growth factor 2 gene therapy as assessed by echocardiography and magnetic resonance imaging.

BACKGROUND: Although it has been shown that gene therapy is capable of inducing neovascularization in ischemic myocardium, the functional significance of such therapeutic angiogenesis remains less certain. The purpose of this study was to investigate whether an experimental link could be made between the ability of a novel fibroblast growth factor 2 (FGF2) gene formulation to promote neovascularization, and its ability to restore myocardial function. METHODS: Fibroblast growth factor 2 gene was delivered by means of an adenovirus vector formulated in a collagen-based matrix to provide localized and sustained gene activity. Using a model of chronic myocardial ischemia, animals were randomized to either treatment of the ischemic area by injections of adenovirus vector-FGF2 or no treatment. Left ventricular function was assessed by rest and dobutamine stress echocardiography as well as contrast-enhanced and cine magnetic resonance imaging scans. Studies were repeated 6 weeks after treatment. Arteriogenesis was assessed by quantifying the total arteriolar wall area present in treated areas, using anti-alpha-actin immunohistochemistry and subsequent morphometric analyses. RESULTS: Echocardiographic results demonstrated a significant restoration of myocardial function in FGF2 gene-treated areas as measured by myocardial wall thickening (0.38 +/- 0.08 cm pretreatment versus 0.76 +/- 0.09 cm posttreatment; p < 0.05). This was demonstrated by comparing the ischemic zones of FGF2 gene-treated versus control-treated animals, as well as by comparing ischemic with nonischemic zones in individual animals This functional improvement was confirmed by cine magnetic resonance imaging, in which 68% (147 of 216) of the treated segments showed improvement in wall motion and there was no change in the untreated segments. Fibroblast growth factor 2 gene treatment also enhanced arteriogenesis within the ischemic zone, as FGF2 gene-treated animals showed a 340% increase in the total arteriolar wall area present versus control-treated animals. CONCLUSIONS: The function of ischemic myocardium can be restored by a novel FGF2 gene delivery method using a gene-activated matrix. The increased arteriogenesis as a result of FGF2 gene therapy leads to restoration of this myocardial function.