The effects of ischaemic conditioning on lung ischaemia-reperfusion injury.

Ischaemia-reperfusion injury (IRI) encompasses the deleterious effects on cellular function and survival that result from the restoration of organ perfusion. Despite their unique tolerance to ischaemia and hypoxia, afforded by their dual (pulmonary and bronchial) circulation as well as direct oxygen diffusion from the airways, lungs are particularly susceptible to IRI (LIRI). LIRI may be observed in a variety of clinical settings, including lung transplantation, lung resections, cardiopulmonary bypass during cardiac surgery, aortic cross-clamping for abdominal aortic aneurysm repair, as well as tourniquet application for orthopaedic operations. It is a diagnosis of exclusion, manifesting clinically as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Ischaemic conditioning (IC) signifies the original paradigm of treating IRI. It entails the application of short, non-lethal ischemia and reperfusion manoeuvres to an organ, tissue, or arterial territory, which activates mechanisms that reduce IRI. Interestingly, there is accumulating experimental and preliminary clinical evidence that IC may ameliorate LIRI in various pathophysiological contexts. Considering the detrimental effects of LIRI, ranging from ALI following lung resections to primary graft dysfunction (PGD) after lung transplantation, the association of these entities with adverse outcomes, as well as the paucity of protective or therapeutic interventions, IC holds promise as a safe and effective strategy to protect the lung. This article aims to provide a narrative review of the existing experimental and clinical evidence regarding the effects of IC on LIRI and prompt further investigation to refine its clinical application.

Association of impaired arterial wall properties with the presence of coronary artery disease in patients with abdominal aortic aneurysms.

Pulse wave velocity (PWV) is a valid, clinically feasible marker of arterial stiffening, and a strong predictor of outcomes. The present study aimed to compare aortic elastic properties in patients with abdominal aortic aneurysms (AAA), with or without coronary artery disease (CAD), as well as healthy individuals. A total of 130 patients with AAA, eligible for interventional repair, and 30 healthy individuals, comprising the control group (HC), were enrolled. Presence of CAD was identified by coronary angiography. Aortic PWV (aPWV) was measured using the Arteriograph. aPWV was found considerably higher in AAA patients compared with HC group (11.5 ± 2.9 vs 7.3 ± 1.6 m/s, P < .001). Importantly, among patients with AAA, those with concomitant CAD (n = 41) had greater aPWV than those without CAD (12.5 ± 2.9 vs 11.0 ± 3.0 m/s, P = .03). In receiver operator curve (ROC) analysis, a value of aPWV above 12.8 m/s was identified to correlate with the presence of CAD in the AAA patient population. After adjustment for confounders, including hypertension which is one of the major risk factors for abdominal aneurysms, multivariate logistic regression analysis revealed that this aPWV cutoff remained independently associated with presence of CAD [odds ratio = 1.64, 95% confidence interval =1.19-4.08, P = .03]. The coexistence of CAD and AAA is characterized by a greater arterial stiffness. This finding should be taken into consideration when selecting endovascular stents with more favorable elastic properties. Moreover, AAA patients with high aPWV (>12.8 m/s) are more likely to also have CAD, and this may be considered by vascular surgeons when evaluating patients' cardiovascular risk.

Bilateral sphenopalatine ganglion block reduces blood pressure in never treated patients with essential hypertension. A randomized controlled single-blinded study.

BACKGROUND: Sympathetic fibers connect sphenopalatine ganglion (SPG) with the central nervous system. We aimed to study the effect of SPG block in blood pressure (BP) in never treated patients with stage I-II essential hypertension. METHODS: We performed bilateral SPG block with lidocaine 2% in 33 hypertensive patients (mean age 48±12years, 24 men) and a sham operation with water for injection in 11 patients who served as the control group (mean age 51±12years, 8 men). All patients have been subjected to 24h ambulatory blood pressure monitoring prior and a month after the SBG block in order to estimate any differences in blood pressure parameters. We defined as responders to SBG block those patients with a 24h SBP decrease ≥5mmHg. RESULTS: We found that 24h and daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the study group a month after SPG block. In addition, a significant response was noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding BP were found in the sham operation group. CONCLUSIONS: SPG block is a promising, minimally invasive option of BP decrease in hypertensives, probably through SNS modulation. Additionally, due to its anesthetic effect, SPG block might act as a method of selection for those hypertensive patients with an activated SNS before any other invasive antihypertensive procedure.

HDL cholesterol levels and endothelial glycocalyx integrity in treated hypertensive patients.

Endothelial dysfunction indicates target organ damage in hypertensive patients. The integrity of endothelial glycocalyx (EG) plays a vital role in vascular permeability, inflammation and elasticity, and finally to cardiovascular disease. The authors aimed to investigate the role of increased HDL cholesterol (HDL-C) levels, which usually are considered protective against cardiovascular disease, in EG integrity in older hypertensive patients. The authors studied 120 treated hypertensive patients older than 50 years were divided regarding HDL-C tertiles in group HDLH (HDL-C ≥ 71 mg/dL, upper HDL-C tertile) and group HDLL (HDL-C < 71 mg/dL, two lower HDL-C tertiles). Increased perfusion boundary region (PBR) of the sublingual arterial microvessels (ranging from 5 to 9 µm) using Sideview Darkfield imaging (Microscan, Glycocheck) was measured as a non-invasive accurate index of reduced EG thickness. PBR 5-9 was significantly decreased in group HDLH (P = 0.04). In the whole population, HDL-C was inversely but moderately related to PBR 5-9 (r = -0.22, P = 0.01). In a multiple linear regression analysis model, using age, BMI, smoking habit, HDL-C, LDL-C, and office SBP, as independent variables, the authors found that BMI (ß = 0.25, P = 0.006) independently predicted PBR 5-9 in the whole population. In older hypertensive patients, HDL-C ranging between 71 and 101 mg/dL might moderately protect EG and subsequently endothelial function. Future studies in several groups of low- or high-risk hypertensives are needed in order to evaluate the beneficial role of extremely elevated HDL-C regarding cardiovascular risk evaluation as well as endothelial glycocalyx as a novel index of target organ damage in essential hypertension.

Integrase Strand Transfer Inhibitors and the Emergence of Immune Reconstitution Inflammatory Syndrome (IRIS).

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk. METHODS: Retrospective single-centre study of HIV patients treated with HAART. RESULTS: A total of 417 patients were included. We identified 45 cases of IRIS in 37 patients; an incidence of 13.3 cases over 1000 person-years. In univariate analysis, IRIS development was significantly associated with CDC stage, the presence of an opportunistic infection (OI) at diagnosis, CD4 cell count and viral load at diagnosis and HAART initiation and the use of integrase strand inhibitors (INSTIs). In multivariate analysis, INSTIs use (OR 2.89; 95%CI 1.26-6.64; p=0.012), CD4≤200/mm3 (OR 5.56; 95%CI 2.2-13.98; p<0.001), and the presence of an OI (OR 4.74; 95%CI 2.13-10.23; p=0.012) were independent risk factors. Among INSTI regimens, dolutegravir (OR 4.99 vs. NNRTI; 95%CI 1.11-22.55; p=0.037) and elvitegravir (OR 4.82 vs. NNRTI; 95%CI 1.43-16.19; p=0.011) seem to carry increased risk. Mortality was 18.9% (7/37) for IRIS patients compared to 9.7% (37/380) in the non-IRIS group. Mortality at any given time during follow-up was significantly higher in the IRIS group (HR 3.2; 95%CI 1.39-7.36; p=0.006). CONCLUSION: The use of INSTIs and especially DTG and EVG is associated with a higher probability for the development of IRIS in the background of late presentation and the presence of OIs. These data highlight the need for further research.

Infiltration of the sphenopalatine ganglion decreases blood pressure in newly diagnosed and never treated patients with essential hypertension.

BACKGROUND: Sphenopalatine ganglion (SPG), an extracranial structure, is connected with the central nervous system (CNS) through sympathetic and parasympathetic nerves. We hypothesized that SPG block through sympathetic nerves anesthesia might decrease blood pressure (BP) in recently diagnosed and never treated middle-aged patients with essential hypertension. METHODS: We performed SBG block in 22 hypertensive patients (mean age 45±12years, 15 men). All patients have been subjected to 24hour ambulatory blood pressure monitoring a week prior the procedure as well as in a period of 21-30days after the SBG block in order to estimate differences in 24h average systolic (24h SBP) and diastolic blood pressure (24h DBP), daytime, nighttime, pre-awake and early morning SBP and DBP as well as BP load. RESULTS: We found that 24h SBP (p=0.001) and 24h DBP (p<0.001), daytime SBP and DBP (p<0.001) as well as daytime SBP and DBP load (p=0.002 and p<0.001, respectively) were decreased in total population at 21-30days after SPG block. In 11/22 responders (24h SBP decrease ≥5mmHg), SBP and DBP were reduced during overall 24h and daytime (p<0.001) and nighttime periods (p=0.01 and p=0.06, respectively) while pre-awake SBP (p=0.09) along with daytime SBP and DBP load (p=0.07 and p=0.06, respectively) were also almost decreased. CONCLUSIONS: SBG block might be a promising, non-invasive, safe, painless and easy to perform therapeutic option of BP decrease. As with renal denervation, SBG should be effective in those hypertensive patients with an activated SNS, so a period of patient selection should precede the application of this procedure.