Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups (n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O(2) fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O(2) fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 +/- 3.6%) compared with N (26.1 +/- 2.8%) and control (21.7 +/- 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries.
Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B 4 is a lipid mediator involved in atherogenesis.In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB 4 production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB 4 production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB 4 production was also studied. An overnight sleep study was followed by firstmorning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB 4 production, which was measured by liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls.LTB 4 production was increased in OSA patients compared with controls. LTB 4 levels correlated with the mean and minimal arterial oxygen saturation (Sa,O 2 ). LTB 4 production correlated with luminal diameter data in patients with a mean Sa,O 2 of f94% but not with IMT. Lastly, CPAP significantly reduced LTB 4 production by 50%.Leukotriene B 4 production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B 4 could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
These data suggested that the contraction elicited by 2-AG resulted from the vascular smooth muscle cell uptake and conversion of 2-AG to constrictor prostanoid TXA2, which in turn caused vasoconstriction through the stimulation of TP receptor.
Background
It is unclear whether HIV infection affects the long‐term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV‐uninfected (HIV−) patients, and to identify determinants of cardiovascular prognosis.
Methods and Results
Consecutive PLHIV and matched HIV− patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36‐month follow‐up. A total of 103 PLHIV and 195 HIV− patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow‐up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− patients (17.8% and 15.1%,
P
=0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67–3.82 [
P
=0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32–30.21 [
P
=0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%;
P
=0.01) and had smaller total cholesterol decreases (–22.3 versus –35.0 mg/dL;
P
=0.04).
Conclusions
Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV− individuals, PLHIV had a higher rate of recurrent ACS.
Registration
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00139958.
These data suggested that 5-LO-derived products, through the activation of cysLT1 receptors, could be involved in the endothelium-dependent contraction to acetylcholine in aorta from SHR but not in the regulation of MABP in SHR.
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