Asif Machhada

• MBPhD, PGcert(Surg) MRCS, MEd, MAcadMEd
• Imperial College London

Key points: The strength, functional significance and origins of parasympathetic innervation of the left ventricle remain controversial. This study tested the hypothesis that parasympathetic control of left ventricular contractility is provided by vagal preganglionic neurones of the dorsal motor nucleus (DVMN). Under β-adrenoceptor blockade combin...

Indirect measures of cardiac vagal activity are strongly associated with exercise capacity, yet a causal relationship has not been established. Here we show that in rats, genetic silencing of the largest population of brainstem vagal preganglionic neurons residing in the brainstem’s dorsal vagal motor nucleus dramatically impairs exercise capacity,...

JACC Basic to Translational Science (In Press) Large clinical trials designed to test the efficacy of vagus nerve stimulation (VNS) in heart failure patients did not demonstrate benefits with respect to the primary endpoints. Non-selective nature of VNS may account for the failure to translate promising results of preclinical and earlier clinical...

Deceased. The glymphatic system, that is aquaporin 4 (AQP4) facilitated exchange of CSF with interstitial fluid (ISF), may provide a clearance pathway for protein species such as amyloid-b and tau, which accumulate in the brain in Alzheimer's disease. Further, tau protein transference via the extracellular space, the compartment that is cleared by...

Objectives: To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective during the early phases of the pandemic. Design Systematic review. Methods: Two parallel searches of academic bibliographic databases and grey literature were undertaken until 8 May 2020. Governments were also contacted for further informa...

Background : Clinical outcome data in the United Kingdom, Europe, and the United States have yet to facilitate appropriately specific surveillance for liposarcoma histological subtypes, despite being one of the most common soft tissue sarcomas. Therefore, this study aims to demonstrate histologic-specific differences in liposarcoma recurrence, dise...

Introduction Open lower extremity fractures pose a challenge for treating surgeons. All surgical strategies have the common aim to facilitate fracture healing. Fracture union, however, should be critically considered in the context of functional recovery and not in isolation. Both local and free tissue transfer have benefits and drawbacks. Aim Thi...

Objectives To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective. Design Scoping review. Methods Two parallel searches of academic bibliographic databases and grey literature were undertaken. Governments were also contacted for further information where possible. Due to the time-sensitive nature of the re...

Neuronal cell groups residing within the retrotrapezoid nucleus (RTN) and C1 area of the rostral ventrolateral medulla oblongata contribute to the maintenance of resting respiratory activity and arterial blood pressure, and play an important role in the development of cardiorespiratory responses to metabolic challenges (such as hypercapnia and hypo...

Supplementary Figures and Supplementary Tables.

OBJECTIVES: Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in...

The autonomic nervous system controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic and sympathetic activities. These activities are generated by groups of sympathoexcitatory and vagal preganglionic neurones residing in a close proximity to each other within well-defined structures of the brainstem. This short essay pro...

Synopsis The ‘glymphatic’ clearance system is a brain-wide pathway for removal of waste solutes from the brain. It has recently been implicated in Alzheimer’s disease (AD), due to discovery that both amyloid and tau, accumulations of which lead to AD development, can be cleared from the brain via this pathway. We therefore hypothesise that an impai...

Introduction. The ‘glymphatic’ clearance system is a brain-wide pathway for removal of waste solutes from the brain. It has recently been implicated in Alzheimer’s disease (AD), due to discovery that both amyloid and tau can be cleared from the brain via this pathway. We therefore hypothesise that an impairment of ‘glymphatic’ clearance of amyloid...

The strength, functional significance and origins of parasympathetic (vagal) control of left ventricular function remain controversial. Experimental studies conducted on rats and mice using methods of genetic neuronal targeting, functional neuroanatomical mapping, and pharmaco- and optogenetics were employed to test the hypothesis that parasympathe...

Sleep disturbances are associated with Alzheimer's disease (AD). Correspondingly, it has recently been suggested that during sleep, the extra-cellular space increases in volume, allowing clearance of waste solutes from the brain parenchyma via interstitial fluid (ISF) into surrounding cerebrospinal fluid (CSF): a process known as glymphatic clearan...

The central nervous origin(s) of functional parasympathetic innervation of cardiac ventricles remain controversial. This study aimed to identify a population of vagal preganglionic neurones which contribute to the control of ventricular excitability. An animal model of synuclein pathology relevant to Parkinson's disease was used to determine whethe...

Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to h...

Introduction: Electrical stimulation of the vagus nerve has been shown to protect against ventricular tachyarrhythmia (VT). The exact mechanism of this effect is unknown and it also remains unclear whether acute or chronic withdrawal of tonic vagal efferent activity to the heart predisposes the heart to VT. To investigate this, we acutely silenced...

The Parkinson's disease (PD) gene, PARK6, encodes the PTEN-induced putative kinase 1 (PINK1) mitochondrial kinase, which provides protection against oxidative stress-induced apoptosis. Given the link between glucose metabolism, mitochondrial function and insulin secretion in β-cells, and the reported association of PD with type 2 diabetes, we inves...

The role of the parasympathetic innervation of the left ventricle remains controversial, although there is some evidence that vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart. The aim of this study was to identify the anatomical location of vagal preganglionic neurones that control ventricular cont...

Introduction Finding an accurate and convenient biomarker for cancer progression in Barrett's (BE) is of high clinical importance. DNA ploidy abnormalities (DNA-PA) are a reliable predictor of cancer risk in BE, but measurement is expensive and scarcely available. We have shown polo-like kinase-1 (PLK1) may act as a surrogate marker of DNA-PA in oe...