Saving the brain initiative - Developing an effective hub-and-spoke model to improve the acute stroke management pathways in urban India.

OBJECTIVES: We aimed to develop and evaluate a hub-and-spoke model in the East Delhi by assessing knowledge and creating awareness through sensitization programs in target communities and among general physicians (GPs) along with implementation of a standard stroke management protocol (SMP) at our institute in order to extend the benefit of thrombolytic therapy. METHODS: We carried out a prospective interventional study using sensitization program comprising 1046 community participants and 101 GPs under "Saving the Brain Initiative" project. Network included one hub and six nearby spoke hospitals. The pre-awareness and post-awareness data along with clinical outcome of thrombolysis collected over 2012-2017 was analyzed. RESULTS: We observed lack of awareness in communities and among GPs regarding stroke symptomatology and treatment options. There was 17.3% increase in patients with stroke post-awareness programs. Door-to-door time improved as 49.3% of patients reached hospital within <2 h of onset as compared to 32.2% in pre-awareness period. 89.4% patients had good outcome and were discharged with improved NIHSS. In the post-awareness period, the rate of thrombolysis increased by 4.0%. CONCLUSIONS: Sensitization of primary physicians, paramedical and medical staff along with community dwellers and implementation of SMP through hub-and-stroke model is instrumental in improving the rate of thrombolysis and its outcome.

Angiotensin type 1a receptor-deficient mice develop diabetes-induced cardiac dysfunction, which is prevented by renin-angiotensin system inhibitors.

BACKGROUND: Diabetes-induced organ damage is significantly associated with the activation of the renin-angiotensin system (RAS). Recently, several studies have demonstrated a change in the RAS from an extracellular to an intracellular system, in several cell types, in response to high ambient glucose levels. In cardiac myocytes, intracellular angiotensin (ANG) II synthesis and actions are ACE and AT1 independent, respectively. However, a role of this system in diabetes-induced organ damage is not clear. METHODS: To determine a role of the intracellular ANG II in diabetic cardiomyopathy, we induced diabetes using streptozotocin in AT1a receptor deficient (AT1a-KO) mice to exclude any effects of extracellular ANG II. Further, diabetic animals were treated with a renin inhibitor aliskiren, an ACE inhibitor benazeprilat, and an AT1 receptor blocker valsartan. RESULTS: AT1a-KO mice developed significant diastolic and systolic dysfunction following 10 wks of diabetes, as determined by echocardiography. All three drugs prevented the development of cardiac dysfunction in these animals, without affecting blood pressure or glucose levels. A significant down regulation of components of the kallikrein-kinin system (KKS) was observed in diabetic animals, which was largely prevented by benazeprilat and valsartan, while aliskiren normalized kininogen expression. CONCLUSIONS: These data indicated that the AT1a receptor, thus extracellular ANG II, are not required for the development of diabetic cardiomyopathy. The KKS might contribute to the beneficial effects of benazeprilat and valsartan in diabetic cardiomyopathy. A role of intracellular ANG II is suggested by the inhibitory effects of aliskiren, which needs confirmation in future studies.

Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: comparison with an angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor.

Hyperglycaemia up-regulates intracellular AngII (angiotensin II) production in cardiac myocytes, effects of which are blocked more effectively by renin inhibition than ARBs (angiotensin receptor blockers) or ACEis (angiotensin-converting enzyme inhibitors). In the present study, we determined whether renin inhibition is more effective at preventing diabetic cardiomyopathy than an ARB or ACEi. Diabetes was induced in adult mice for 10 weeks by STZ (streptozotocin). Diabetic mice were treated with insulin, aliskiren (a renin inhibitor), benazeprilat (an ACEi) or valsartan (an ARB) via subcutaneous mini-pumps. Significant impairment in diastolic and systolic cardiac functions was observed in diabetic mice, which was completely prevented by all three RAS (renin-angiotensin system) inhibitors. Hyperglycaemia significantly increased cardiac oxidative stress and circulating inflammatory cytokines, which were blocked by aliskiren and benazeprilat, whereas valsartan was partially effective. Diabetes increased cardiac PRR (prorenin receptor) expression and nuclear translocation of PLZF (promyelocytic zinc finger protein), which was completely prevented by aliskiren and valsartan, and partially by benazeprilat. Renin inhibition provided similar protection of cardiac function to ARBs and ACEis. Activation of PLZF by PRR represented a novel mechanism in diabetic cardiomyopathy. Differential effects of the three agents on oxidative stress, cytokines and PRR expression suggested subtle differences in their mechanisms of action.