nNOS-expressing interneurons control basal and behaviorally evoked arterial dilation in somatosensory cortex of mice

Cortical neural activity is coupled to local arterial diameter and blood flow. However, which neurons control the dynamics of cerebral arteries is not well understood. We dissected the cellular mechanisms controlling the basal diameter and evoked dilation in cortical arteries in awake, head-fixed mice. Locomotion drove robust arterial dilation, increases in gamma band power in the local field potential (LFP), and increases calcium signals in pyramidal and neuronal nitric oxide synthase (nNOS)-expressing neurons. Chemogenetic or pharmocological modulation of overall neural activity up or down caused corresponding increases or decreases in basal arterial diameter. Modulation of pyramidal neuron activity alone had little effect on basal or evoked arterial dilation, despite pronounced changes in the LFP. Modulation of the activity of nNOS-expressing neurons drove changes in the basal and evoked arterial diameter without corresponding changes in population neural activity.

Impact of catheterization on shear-mediated arterial dilation in healthy young men

Purpose Animal studies have shown that endothelial denudation abolishes vasodilation in response to increased shear stress. Interestingly, shear-mediated dilation has been reported to be reduced, but not abolished, in coronary artery disease (CAD) patients following catheterization. However, it is not known whether this resulted from a priori endothelial dysfunction in this diseased population. In this study, we evaluated shear-mediated dilation following catheterization in healthy young men. Methods Twenty-six (age: 24.4 ± 3.8 years, BMI: 24.3 ± 2.8 kg m−2, VO2peak: 50.5 ± 8.8 ml/kg/min) healthy males underwent unilateral transradial catheterization. Shear-mediated dilation of both radial arteries was measured using flow-mediated dilation (FMD) pre-, and 7 days post-catheterization. Results FMD was reduced in the catheterized arm [9.3 ± 4.1% to 4.3 ± 4.1% (P < 0.001)] post-catheterization, whereas no change was observed in the control arm [8.4 ± 3.8% to 7.3 ± 3.8% (P = 0.168)]. FMD was completely abolished in the catheterized arm in five participants. Baseline diameter (P = 0.001) and peak diameter during FMD (P = 0.035) were increased in the catheterized arm 7 days post-catheterization (baseline: 2.3 ± 0.3 to 2.6 ± 0.2 mm, P < 0.001, peak: 2.5 ± 0.3 to 2.7 ± 0.3 mm, P = 0.001), with no change in the control arm (baseline: 2.3 ± 0.3 to 2.3 ± 0.3 mm, P = 0.288, peak: 2.5 ± 0.3 to 2.5 ± 0.3 mm, P = 0.608). Conclusion This is the first study in young healthy individuals with intact a priori endothelial function to provide evidence of impaired shear-mediated dilation following catheterization. When combined with earlier studies in CAD patients, our data suggest the catheterization impairs artery function in humans.

Association of Carboxyhemoglobin Levels with Peripheral Arterial Disease in Chronic Smokers Managed at Dr George Mukhari Academic Hospital

Chronic cigarette smokers (CCS) are known to have elevated levels of carboxyhemoglobin (COHb). However, it is not known whether increased levels of COHb are associated with endothelial dysfunction (ED), and therefore the development of peripheral arterial disease (PAD). The aim of the study was to investigate the association of blood COHb and plasma nitric oxide (NO) levels, and whether it is an independent risk factor in the development of PAD among CCS at Dr George Mukhari Academic Hospital (DGMAH). A sample of 120 CCS with PAD and a convenience sample of 100 CCS without PAD were recruited into the study. Blood COHb levels were measured using the ABL 90 FLEX CO-oximeter automated spectroscopy. Plasma nitric oxide (NO) levels were measure using ELISA. Logistic regression analysis was used to investigate the association of blood COHb and plasma NO with PAD. Blood COHb levels of CCS with PAD were significantly higher than those of CCS without PAD, and the NO levels of CCS with PAD were significantly lower than those of CCS without PAD. Although both the blood COHb and plasma NO in CCS were significantly associated with PAD in bivariate logistic analysis, only plasma NO was independently associated with PAD in multivariate logistic analysis. This finding is consistent with the hypothesis that COHb is a cause of arterial damage in PAD, leading to reduced NO, and therefore reduced arterial dilation.

Endothelial and left ventricular diastolic function in young adults exposed to tobacco

Smoking is associated with endothelial and left ventricular diastolic disfunction. We aimed to determine the endothelial and diastolic function in young adults exposed to tobacco smoke and the effects of acute exposure to it. Smokers were considered as cases and non-smokers as controls. Brachial artery diameter, brachial artery flow velocity, and echocardiographic variables were measured. Mean age of the participants was 21 years. Smokers showed significant endothelial dysfunction compared with non-smokers. Arterial dilation mediated by the endothelium was significantly higher in non-smokers than in smokers (p = 0.005). Non-endothelium-mediated arterial dilation was significantly impaired in smokers compared with non-smokers (p = 0.02). After reactive hyperaemia, there was a significant increase in blood flow in non-smokers (61%) compared with that in smokers (29%). Acute cigarette exposure showed a trend towards left ventricle diastolic disfunction in smokers. Left atrium diameter was significantly higher in smokers than in non-smokers. After acute exposure to cigarette smoke, arterial dilation and brachial flow velocity were lower than those achieved in the abstinence phase (p = 0.005). We concluded that endothelium-dependent arterial dilation is impaired in young smokers and it worsens even after acute exposure to cigarette smoke.

An oligarchy of NO-producing interneurons controls basal and evoked blood flow in the cortex

Changes in cortical neural activity are coupled to changes in local arterial diameter and blood flow. However, the neuronal types and the signaling mechanisms that control the basal diameter of cerebral arteries or their evoked dilations are not well understood. Using chronic two-photon microscopy, electrophysiology, chemogenetics, and pharmacology in awake, head-fixed mice, we dissected the cellular mechanisms controlling the basal diameter and evoked dilation in cortical arteries. We found that modulation of overall neural activity up or down caused corresponding increases or decreases in basal arterial diameter. Surprisingly, modulation of pyramidal neuron activity had minimal effects on basal or evoked arterial dilation. Instead, the neurally-mediated component of arterial dilation was largely regulated through nitric oxide released by neuronal nitric oxide synthase (nNOS)-expressing neurons, whose activity was not reflected in electrophysiological measures of population activity. Our results show that cortical hemodynamic signals are not controlled by the average activity of the neural population, but rather the activity of a small ‘oligarchy’ of neurons.

Acute Hemoptysis Redefined: A Deadly Presentation

An aortic aneurysm is a permanent localized arterial dilation with more than 50% of the artery diameter. Among the complications of an aortic aneurysm, one of the rarest is the aorto-bronchial fistula, which presents with massive hemoptysis; this condition is lethal if not treated surgically. We report a 90-year-old man with no significant medical history who presented to the emergency department with abrupt onset of hemoptysis; his chest X-ray displayed left upper lobe opacity with widened mediastinum. CT chest revealed aneurysmatic dilatation of the aorta, left upper lobe opacity suspicious of pulmonary aortic fistula. Thoracic surgery was consulted but due to his poor functional status surgery was deferred. On the second day of hospitalization, the patient developed another episode of massive hemoptysis resulting in hypovolemic shock and expired. This case epitomizes the relevance of broad differential diagnosis for hemoptysis and the prompt assessment and management of the patients with this condition.

Life-threatening complications of pulmonary hypertension

Pulmonary arterial hypertension is a severe disease with a 1-year mortality of over 10%. Since it is a rare disease, it is usually managed in expert centres. However, life-threatening complications can occur at any moment and place and should be adequately taken care of to prevent avoidable deaths. Therefore, based on an analysis of the causes of death, this chapter describes the most important complications and their management: right heart failure, arrhythmias, haemoptysis, pericardial effusion, pulmonary arterial dilation with as a consequence left main coronary artery compression, and pulmonary artery dissection, as well as treatment-related adverse events.