Impaired Spontaneous Baroreceptor Reflex Sensitivity in Patients With COPD Compared to Healthy Controls: The Role of Lung Hyperinflation

Background and Objectives: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular disease. This study aimed to investigate the relationship between pulmonary hyperinflation and baroreceptor reflex sensitivity (BRS), a surrogate for cardiovascular risk.Methods: 33 patients with COPD, free from clinical cardiovascular disease, and 12 healthy controls were studied. Participants underwent pulmonary function and non-invasive hemodynamic measurements. BRS was evaluated using the sequence method during resting conditions and mental arithmetic stress testing.Results: Patients with COPD had evidence of airflow obstruction [forced expiratory volume in 1 s predicted (FEV1%) 26.5 (23.3–29.1) vs. 91.5 (82.8–100.8); P < 0.001; geometric means (GM) with 95% confidence interval (CI)] and lung hyperinflation [residual volume/total lung capacity (RV/TLC) 67.7 (64.3–71.3) vs. 41.0 (38.8–44.3); P < 0.001; GM with 95% CI] compared to controls. Spontaneous mean BRS (BRSmean) was significantly lower in COPD, both during rest [5.6 (4.2–6.9) vs. 12.0 (9.1–17.6); P = 0.003; GM with 95% CI] and stress testing [4.4 (3.7–5.3) vs. 9.6 (7.7–12.2); P < 0.001; GM with 95% CI]. Stroke volume (SV) was significantly lower in the patient group [−21.0 ml (−29.4 to −12.6); P < 0.001; difference of the means with 95% CI]. RV/TLC was found to be a predictor of BRS and SV (P < 0.05 for both), independent of resting heart rate.Conclusion: We herewith provide evidence of impaired BRS in patients with COPD. Hyperinflation may influence BRS through alteration of mechanosensitive vagal nerve activity.

Autonomic and cardiac evaluation upon sub-therapeutic doxorubicin administration

Doxorubicin (DOX) is a chemotherapeutic agent that improves the survival and quality of life of patients with solid tumours. However, these improvements are counterbalanced by various dose-dependent side effects including cardiac dysfunction, which may occur in a subset of patients leading to treatment discontinuation. In addition, despite overall insufficiently studied, available data clearly show that women are more susceptible to drugs toxicity due to sex differences in drug metabolism or sensitivity. Regarding doxorubicin, apart its acute toxicity, women are also more vulnerable to late cardiotoxicity. Currently, there are no robust clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline and, despite treatment personalization, subclinical signs of toxicity are not yet well identified. Thus, in the present work, we sought to characterize the toxic effects of a sub-therapeutic dose of doxorubicin upon cardiovascular and autonomic function. For that, adult healthy female wistar rats (n=14), aged >3 months, were intraperitoneally treated with doxorubicin (2 mg/kg) at weekly intervals for up to 4 weeks. A control (Ctrl, n=7) group received saline solution 0,9% NaCl as a vehicle. Rats underwent an echocardiographic evaluation at 4 weeks. Blood pressure, heart rate and respiratory frequency were assessed in an acute experiment. Cardiovascular variability studies in the time-frequency domain (LF, HF and LF/HF calculation) and cardiorespiratory reflexes assessment were performed. T-Student test for paired observations was applied (level significance p<0.05) DOX-treated animals showed a severe bradypnea and hypotension, significant decrease in ejection fraction and fractional shortening, sympatho-inhibition and reduced baroreceptor reflex gain and chemoreflex sensitivity. Our functional results might be due to cellular respiratory dysfunction and vascular adaptations induced by doxorubicin via TNF alpha actions at central nervous system (CNS) and peripheral level. In fact, peripheral TNF alpha release elicits NO production, which through vasodilation will induce hypotension and baroreceptor reflex adjustments. Reinforcing these actions, and despite doxorubicin low ability to pass BBB, TNF alpha acting at CNS induces neuronal apoptosis and impairment of mitochondrial function which might also contribute to affect autonomic and respiratory function, expressed by a decreased chemoreflex sensitivity and sympathetic tone. In conclusion, sub-therapeutic doses of doxorubicin are able to produce per se the impairment of autonomic and cardiac functions. Thus, a tight monitoring of these functions in patients treated with therapeutic doses of doxorubicin is highly recommended. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fundação para a Ciência e a Tecnologia

Blood pressure variability — regular and irregular waves

The review presents data on regular and irregular waves of blood pressure (BP) recorded during its invasive (intra-arterial) and non-invasive registration. Regular pulse waves, Traube-Hering waves (second-order waves) and Mayer waves (third-order waves) are described. The characteristic of circadian and ultradian super slow waves is given. The role of the sympathetic nervous system in the origin of regular waves of BP and their relationship with the magnitude of the baroreceptor reflex are shown. Attention is drawn to the role of changes in the minute volume of blood circulation and peripheral resistance to blood flow in the occurrence of fluctuations in BP. We also review the methods and features of BP registration, which enable identification and analysis of irregular high-frequency fluctuations in BP, the relationship of these fluctuations with the magnitude of the baroreceptor reflex and the activity of the sympathetic nervous system. The data on the amplitude of high-frequency irregular fluctuations in BP in animals with simulated hypertension are presented. The review draws attention to the possibility of recording regular fluctuations in BP during its constant non-invasive registration.

Carotid Body Baroreceptor Preservation and Control of Arterial Pressure in Eversion Carotid Endarterectomy

The technique of the eversion carotid endarterectomy (ECEA), as an alternative to the conventional endarterectomy with primary or patch angioplasty, is an established technique for managing internal carotid artery stenoses and recently its application has been upgraded through the European Society for Vascular Surgery guidelines (Recommendation 55: Class 1, Level A). However, the typical eversion method has been associated with postoperative hypertension due to loss of the baroreceptor reflex; the standard oblique transection at the bulb performed in the eversion endarterectomy interrupts either the baroreceptor sensoring tissue, which is mostly located in the adventitia at the medial portion of the proximal internal carotid artery, or even the proper Hering nerve, a branch of the glossopharyngeal nerve. These actions deregulate the natural negative feedback of the carotid baroreceptor. Guided by the anatomical location of the baroreceptor sensor we have elaborated a slight modification of the classical ECEA to maintain as much as possible of the viable carotid baroreceptor sensoring surface. By extending the oblique incision distal to the carotid bifurcation in the medial part of the internal carotid artery stem, an eyebrow-like part of the proximal internal carotid artery is maintained and the axis from the sensoring tissue to the nerve of Hering is protected and following the endarterectomy, postoperative arterial blood pressure levels are lower than in the classical ECEA due to the maintenance of the efficiency of the baroreceptor reflex. During the period from September 2016 to November 2018, carotid endarterectomy was performed in 57 patients. Twenty-eight of them underwent the typical ECEA and 29 patients had the modified eyebrow eversion carotid endarterectomy (me-ECEA). The changes of blood pressure baseline during the postoperative course in ECEA and me-ECEA group were analyzed and compared. Postoperative hypertension was defined as an elevation of systolic blood pressure (SBP) greater than 140 mm Hg. Patients who underwent typical ECEA had significantly higher postoperative blood pressure values compared with those who underwent me-ECEA. Actually, the mean postoperative SBP was 172.67 ± 24.59 mm Hg in the typical ECEA group compared with 160.86 ± 12.83 mm Hg in the me-ECEA group (p = 0.023). The mean diastolic blood pressure in the ECEA group was 65.42 ± 11.39 mm Hg compared with 58.06 ± 9.06 mm Hg in the me-ECEA group (p = 0.009). Our proposed me-ECEA technique seems to be related to lower rates of postoperative hypertension compared with the typical ECEA, probably due to the sparing of the main mass of the baroreceptor apparatus; this improved modification (me-ECEA) of the typical eversion procedure could represent an alternative ECEA technique with its inherent advantages.