Heart rate fluctuation predicts mortality in critically ill patients in the intensive care unit: a retrospective cohort study.

BACKGROUND: To evaluate the association between heart rate (HR) fluctuation and mortality in critically ill patients in the intensive care unit (ICU). METHODS: A total of 27,814 patients were enrolled from the Medical Information Mart for Intensive Care database and were divided into 3 groups: low HR fluctuation [<25 beats per minute (bpm)], control (25-34 bpm), and high HR fluctuation (≥35 bpm), based on the initial 24-hour HR fluctuation (calculated as the maximum HR minus minimum HR). Multivariate Cox regression and restricted cubic spline models were used. RESULTS: Compared to the control group, higher risk of 28-day and 1-year mortality remained significant in an adjusted model, with hazard ratios of 1.210 [95% confidence interval (CI), 1.103-1.327] and 1.150 (95% CI, 1.078-1.227), respectively, in the high HR fluctuation group, as well as hazard ratios of 1.130 (95% CI, 1.035-1.232) and 1.087 (95% CI, 1.022-1.157), respectively, in the low HR fluctuation group. Restricted cubic splines showed a U-type curve, with the lowest risk of mortality at an HR fluctuation of 30 bpm. CONCLUSIONS: This retrospective cohort study revealed that both high and low HR fluctuation correlated with increased mortality in critically ill ICU patients, providing new insights for optimizing HR control strategies.

Carotid Artery Stenting Versus Carotid Endarterectomy for Treatment of Asymptomatic Carotid Artery Stenosis.

Asymptomatic carotid stenosis is common and is associated with increased risk of stroke. The relative efficacy and safety of carotid endarterectomy (CEA) and carotid stenting (CAS) in patients with asymptomatic carotid stenosis remain unclear. Five studies that recruited patients with asymptomatic but significant carotid stenosis, who underwent CEA or CAS, were included in this systematic review and meta-analysis. The analyzed outcomes included risks of stroke, myocardial infarction (MI), and death. Risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled for meta-analysis. Pooled analysis demonstrated that compared with CEA, CAS was associated with a decreased risk of MI (RR = 0.49, 95%CI = 0.26-0.91, P = 0.023) and slightly increased risk of stroke, although not significant (RR = 1.69, 95% CI = 0.97-2.92, P = 0.063). There was no difference in the death rates between the groups (RR = 0.60, 95% CI = 0.17-2.18, P = 0.436). In the subgroup analysis, CAS was associated with a decreased risk of MI in mixed patients (RR = 0.45, 95% CI = 0.26-0.78, P = 0.005), but not in asymptomatic patients (RR = 0.549, 95% CI = 0.26-1.17, P = 0.119). Compared with CAS, CEA was associated with decreased risk of perioperative stroke and increased risk of MI; it did not affect the risk of death in patients with asymptomatic carotid stenosis. In the subgroup analysis, the decreased risk of MI after CAS was significant only in the mixed patients group. CAS was associated with higher risk of stroke but lower risk of MI than those with CEA. Both procedures appeared equivalent in terms of the risk of death.

Stretch-activated channel Piezo1 is up-regulated in failure heart and cardiomyocyte stimulated by AngII.

Mechanotransduction is the conversion of extracellular mechanical stimuli into intracellular biochemical signals, and plays an important role in heart responses to its own mechanical environment. Piezo1 as a distinct stretch-activated channel (SAC) in mammal involves in not only vascular remodeling during embryonic development but also arterial remodeling upon to hypertension at adult stage. In the present study, the expression of Piezo1 was up-regulated in failure heart induced by myocardial infarction (MI) by real-time PCR, Western blot and immunohistochemistry analysis. Expression of Piezo1 mRNA and protein was enhanced by AngiotensinII (AngII) in neonatal rat ventricular myocytes via AT1 receptor depended methods. Furthermore, the Piezo1 expression was attenuated by Erk1/2 chemical inhibitor (U0126) only, but not by p38 MAPK inhibitor (SB203580), or JNK inhibitor (SP600125). Finally, systolic function improvement followed by chronic treatment with angiotensin receptor blocker (ARB) losartan prevented Piezo1 up-regulation in failure heart in vivo. In conclusion, our studies linked mechanotransduction which involved renin-angiotensin system that mediated up-regulation of Piezo1 to a clinically relevant heart failure.

Fosinopril improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats.

This study investigated the effects of fosinopril on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHRs). Twenty-four 10-week-old male SHRs were divided into fosinopril and non-fosinopril groups (n = 12 each). Twelve 10-week-old Wistar-Kyoto rats were used a control group. Left ventricular mass index and ventricular fibrillation threshold (VFT) were measured after 8 weeks of fosinopril or saline treatment. L-type calcium current (I CaL), sodium current (I Na), and transient outward potassium current (I to) were measured in left ventricular myocytes after 8 weeks of fosinopril or saline treatment using the whole-cell patch-clamp technique. VFT was higher in the fosinopril group than in the non-fosinopril group (17.5 ± 1.2 mA vs. 15.6 ± 1.1 mA, P < 0.01). The density of I CaL was lower in the fosinopril group than in the non-fosinopril group (-7.17 ± 0.13 pA/pF vs. -7.87 ± 0.13 pA/pF, P < 0.05). The density of I to was higher in the fosinopril group than in the non-fosinopril group (14.46 ± 0.28 pA/pF vs. 12.66 ± 0.25 pA/pF, P < 0.05). I to was positively correlated with VFT (r = 0.90, P < 0.001) and was found to be associated independently with VFT (P < 0.001). Fosinopril improves the electrophysiological characteristics of the left ventricular hypertrophic myocardium in SHRs.

Effect of fosinopril on the transient outward potassium current of hypertrophied left ventricular myocardium in the spontaneously hypertensive rat.

To investigate fosinopril's effect on the transient outward potassium current (Ito) of differing degrees of hypertrophied myocytes in the spontaneously hypertensive rat (SHR). Ten- and 24-week-old SHRs were used as models for cardiac hypertrophy. Hypertrophied ventricular myocytes were exposed to 1, 10, and 100 µmol/L fosinopril; the whole-cell patch-clamp technique was used to study the effects on the transient outward potassium current. Ito current density was decreased in SHR myocytes relative to controls (14.17 ± 0.31 and 11.62 ± 0.08 pA/pF in 10- and 24-week-old SHR versus 16.73 ± 0.15 pA/pF, p < 0.01). Higher concentrations of fosinopril (10 and 100 µmol/L) increased Ito peak current density in 10-week-old SHR myocytes compared with controls (14.92 ± 0.14 and 15.27 ± 0.13 pA/pF versus 14.17 ± 0.31 pA/pF, p < 0.01). Fosinopril increased Ito peak current density in 24-week-old SHR myocytes at all doses (12.70 ± 0.07, 13.74 ± 0.10, and 14.53 ± 0.13 versus 11.62 ± 0.08 pA/pF for controls, p < 0.01). Fosinopril had a greater Ito elevation potential on hypertrophied myocytes in 24-week-old compared with 10-week-old SHR for each dose (1.08 ± 0.09 versus 0.37 ± 0.26 pA/pF, p < 0.01; 2.13 ± 0.05 versus 0.75 ± 0.35 pA/pF, p < 0.01; 2.92 ± 0.07 versus 1.10 ± 0.40 pA/pF, p < 0.01). Fosinopril increased Ito current density in hypertrophied myocytes. This effect was more pronounced in myocytes with a greater degree of hypertrophy.

Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension.

BACKGROUND: Some studies have shown that serum resistin levels increase in hypertensive patients. Whether the increase of resistin is related to inflammatory or vascular endothelial function is still unknown. We investigated the relationship of increased resistin levels to inflammatory factors and circulating biomarkers of vascular endothelial function in hypertensive patients. METHODS: One hundred and forty-four nondiabetic patients with new onset, hypertension were recruited. Blood pressure, blood glucose, insulin, resistin, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), von Willebrand factor (vWF), endothelin-1 (ET-1) and nitric oxide (NO) were measured. The homeostasis model assessment, insulin resistance index (HOMA-IR) was calculated. Patients were divided into two groups according to the median level of resistin. Cytokine levels and indicators of vascular endothelial function were compared. Multiple linear regression was used to determine factors influencing resistin. RESULTS: Serum resistin ranged from 2.57 ng/ml to 20.18 ng/ml in hypertensive patients. High resistin group (> 8.36 ng/ml) had higher levels of TNF-α, IL-6, vWF and ET-1 but lower level of NO compared with low resistin group (P < 0.01). Resistin was positively correlated with body mass index, systolic blood pressure, HOMA-IR, low-density lipoprotein cholesterol, TNF-α and ET-1 but negatively correlated with NO (all P < 0.05). Multiple linear regression analysis revealed that HOMA-IR, TNF-α, NO and ET-1 are independent predictors of resistin with standardized regression coefficients of 0.625, 0.368, -0.260 and 0.222, respectively (all P < 0.01). CONCLUSIONS: We conclude that higher resistin levels are associated with inflammatory activation and endothelial dysfunction, because patients with essential hypertension have increased TNF-α, IL-6, vWF and ET-1 and decreased NO. Moreover, the statistical association of resistin with TNF-α, NO and ET-1 suggests involvement of resistin in the progression of hypertension by influencing inflammation and endothelial function.

Sdc1 overexpression inhibits the p38 MAPK pathway and lessens fibrotic ventricular remodeling in MI rats.

Expression of the proteoglycan syndecan-1 (Sdc1) is increased in rats with myocardial infarction (MI). This study investigated the effects of Sdc1 overexpression on ventricular remodeling and cardiac function in MI and explored the possible mechanism through in vivo transfection of rats with recombinant adenovirus-carrying rat Sdc1 cDNA. Sprague-Dawley rats (n = 48) underwent intramyocardial injection in the marginal zone of the infarcted area immediately after ligation of the left anterior descending artery. The rats were divided into four groups according to the solution injected: MI Ad-GFP-Sdc1 transfection group, MI Ad-GFP control group, MI saline group, and sham operation group. Cardiac function and collagen expression of each group were examined, and the roles of inflammation, apoptosis, and p38 MAKP signal transduction pathway were investigated. Compared with the rats in the sham operation group, ventricular weight and collagen content increased in MI rats, and cardiac function declined. Substantial inflammatory cell infiltration was seen in the marginal zone of the infarction area, and a great number of myocardial cells were apoptotic. The p38 MAPK signaling pathway was clearly activated. Rats in the MI Ad-GFP-Sdc1 transfection group showed decreased ventricular weight, reduced collagen synthesis, and significant improvement of ventricular remodeling and cardiac function. Post-MI inflammatory cell infiltration and apoptosis was reduced, and the p38 MAPK signaling pathway was inhibited. Overexpression of Sdc1 can improve post-MI ventricular remodeling, and it is possible that the improvement is achieved through reducing apoptosis and suppressing inflammatory response and through the p38 MAPK signal transduction pathway.

Blockades of angiotensin and aldosterone reduce osteopontin expression and interstitial fibrosis infiltration in rats with myocardial infarction.

BACKGROUND: It has been reported that osteopontin has an important role in cardiac fibrosis and remodeling. However, its direct mechanisms remain unclear. The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats. METHODS: Fifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups: MI-saline group (n = 15, 5 ml/d), MI-perindopril group (n = 18, perindopril 2 mgxkg(-1)d(-1)) and MI-spironolacton (n = 17, spironolacton 20 mgxkg(-1)xd(-1)). A sham operation group (n = 15) was selected as non-infarcted control. At 6 weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically. Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting. RESULTS: No osteopontin protein was detected in the myocardium of sham-operation rats. High levels of osteopontin protein expression were detected in the MI-saline rats, but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI (P < 0.01, respectively). Compared with the sham operation group, all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter (P < 0.01, respectively), and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure (LVSP) and +/-dp/dt, as well as increased left ventricular end-diastolic pressure (LVEDP) (P < 0.01, respectively). Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction (P < 0.01, respectively). CONCLUSION: Treatment with angiotensin and aldosterone blockades inhibits expression of osteopontin in the non-infarcted myocardium and prevents cardiac remodeling following MI.