Cardioprotective effect of nicorandil against myocardial injury following cardiac arrest in swine.

INTRODUCTION: Nicorandil, a vasodilatory drug used to treat angina, was reported to protect against myocardial ischemia-reperfusion injury in various animal models. However, its cardioprotective action following cardiac arrest is unknown. We examined the cardioprotective effects of nicorandil in a porcine model of cardiac arrest and resuscitation. METHODS: Ventricular fibrillation was induced electrically for 4min in anesthetized domestic swine, followed by cardiopulmonary resuscitation. Sixteen successfully resuscitated animals were randomized to saline control (n=8) or nicorandil (n=8) groups. Nicorandil (150µg/kg) was administered by central intravenous injection at onset of restoration of spontaneous circulation (ROSC), followed by 3µg/kg/min infusion until reperfusion end. Sham-operated animals received surgery only (n=4). Hemodynamic parameters were monitored continuously. Blood samples were taken at baseline, 5, 30, 180, and 360min after ROSC. Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. The animals were euthanized 6h after ROSC, and the cardiac tissue was removed for analysis. RESULTS: 6 h after ROSC, nicorandil had significantly improved all hemodynamic variables (all P<0.05) except the maximum rate of left ventricular pressure decline and heart rate (P>0.05) compared with the control group. Control animals showed elevated cardiac troponin I and lactate levels compared with sham animals, which were significantly decreased following nicorandil treatment (P<0.05). In the saline control group, the adenosine triphosphate (ATP) content was largely reduced but subsequently rescued by nicorandil (P<0.05). Histopathologic injury was reduced with nicorandil treatment. Nicorandil reduced cardiomyocyte apoptosis as evidenced by reduced terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, decreased Bax and caspase-3 expression, and increased Bcl-2 expression in the myocardium (all P<0.05). CONCLUSION: Nicorandil exhibited cardioprotective effects on myocardial injury following cardiac arrest via improvement in post-resuscitation myocardial dysfunction and energy metabolism, reduction in myocardial histopathologic injury, and antiapoptotic effects.

Effect of levosimendan on estimated glomerular filtration rate in hospitalized patients with decompensated heart failure and renal dysfunction.

BACKGROUND: Only limited data of the long-term effect of levosimendan on renal dysfunction in patients with decompensated heart failure (DHF) have been published previously. To date, there has been no similar study carried out in a Chinese population. DESIGN AND METHODS: A prospective, randomized, placebo-controlled, and double-blind study was performed to investigate the effect of levosimendan on estimated glomerular filtration rate (eGFR) in DHF patients with renal dysfunction during a 30-day period. Sixty-six patients with left ventricular ejection fraction (LVEF) ≤40% and eGFR 15-89 mL/min/1.73 m(2) were randomized in a 1:1 ratio to receive a 24-h infusion with levosimendan or placebo. The B-type natriuretic peptide (BNP) and eGFR were determined at baseline and day 1, 3, 7, 14, 30 after the start of treatment. RESULTS: The eGFR levels were obviously enhanced following levosimendan, peaked at 3 days, sustained for at least 14 days, and returned to baseline by day 30 after starting infusion. In contrast, placebo did not induce any significant changes in eGFR levels during the follow-up. In addition, levosimendan resulted in a distinct decrease in BNP levels in comparison with placebo, and the beneficial effect returned to baseline by day 14 and remained so at day 30 postinfusion. CONCLUSIONS: A 24-h infusion with levosimendan transiently improved the renal dysfunction compared with placebo in patients with DHF, and its beneficial effects persisted for at least 14 days after the initiation of treatment.

Effect of lipo-prostaglandin E1 on cystatin C, ß2-microglobulin, and estimated glomerular filtration rate in patients with decompensated heart failure and renal dysfunction: a single-center, nonrandomized controlled study.

A nonrandomized controlled study was conducted to evaluate the effect of lipo-prostaglandin E1 (lipo-PGE1) on cystatin C (CysC), ß2-microglobulin (B2MG), and estimated glomerular filtration rate (eGFR) in patients with decompensated heart failure (DHF) and renal dysfunction. A total of 286 enrolled patients with DHF and renal dysfunction were nonrandomly assigned a 7-day standard treatment without (n = 146) or with (n = 140) lipo-PGE1 intervention. According to the baseline eGFR, patients were further classified into mild, moderate, and severe renal dysfunction subgroups. By the end of study period, there was no evidence of an immense improvement in B2MG, CysC, and eGFR in response to standard treatment (all P > 0.05). On the contrary, a noticeable decrease of B2MG and CysC was observed in patients receiving lipo-PGE1 intervention, as well as an increase in eGFR (all P < 0.05). Moreover, lipo-PGE1 intervention led to greater changes in renal function variables from baseline than with standard management (all P < 0.05). Most important, the favorable renal protective effects of lipo-PGE1 were maintained in three subgroups. Lipo-PGE1 intervention brought a substantial renoprotective benefit to hospitalized DHF patients as compared with standard therapy, suggesting it might offer a promising therapeutic option for the management of renal dysfunction associated with DHF.

Association of serum omentin-1 levels with coronary artery disease.

AIM: Omentin-1, a novel adipokine expressed in visceral adipose tissue, is negatively correlated with insulin resistance and obesity. Decreased omentin-1 expression has been found in many chronic inflammatory diseases. However, the role of omentin-1 in coronary artery disease (CAD) has not been elucidated. The aim of the present study was to determine whether serum concentration of omentin-1 was independently associated with CAD. METHODS: One hundred and fifty five patients with CAD were divided into two groups: acute coronary syndrome (ACS) and stable angina pectoris (SAP). A total of 52 healthy participants served as controls. Serum concentrations of omentin-1 and interleukin-6 (IL-6) were measured using ELISA. The association of omentin-1 with CAD and cardiovascular disease risk factors was evaluated. RESULTS: Serum omentin-1 levels were lower in patients with ACS or SAP compared with controls (ACS, 113.08±61.43 ng/mL; SAP, 155.41±66.89 ng/mL; control, 254.00±72.9 ng/mL; P<0.01). Patients with ACS also had lower serum concentrations of omentin-1 compared with patients with SAP (P<0.01). Serum concentration of omentin-1 was negatively correlated with body mass index (r=-0.17, P<0.05) and serum IL-6 concentration (r=-0.19, P<0.05). Furthermore, multiple logistic regression analysis showed that serum omentin-1 concentrations were independently correlated with CAD. CONCLUSION: The findings suggest that serum concentrations of omentin-1 are related to CAD.

[Arterial remodeling at the reference site after angioplasty and the effect of granulocyte-macrophage colony-stimulating factor on remodeling].

OBJECTIVE: To observe the correlation of the arterial remodeling at the reference site and the lesion site and the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on arterial remodeling. METHODS: 28 healthy New Zealand White rabbits were randomized to 2 equal groups: GM-CSF group receiving subcutaneous injection of GM-CSF (10 microg x kg(-1)xd(-1)) for 7 days, and pure damage group given subcutaneous injection of equivalent normal saline foe 7 days. Seven days later the iliac arteries of all animals were damaged by balloon. The levels of nitrogen monoxide (NO) were detected before and 4 weeks after angioplasty. Histological sections of iliac from rabbits killed 4 weeks after angioplasty were analyzed. Lumen area (LA), external elastic lamina area (EELA), and intimal plus medial areas (I + M) were measured at the lesion(L) and reference(R) sites. RESULTS: The NO levels 4 weeks later of the GM-CSF group was 98 +/- 10 micromol/L, significantly higher than that of the pure damage group (83 +/- 12 micromol/L, P < 0.05). Morphometric analysis showed that the LA(L) of the pure damage group was (0.87 +/- 0.40) mm2, significantly smaller than that of the GM-CSF group [(1.34 +/- 0.52) mm2, P < 0.05]. The I + M(L) of the pure damage group was (2.62 +/- 0.48) mm2, significantly greater than that of the GM-CSF group [(2.26 +/- 0.43) mm2, P < 0.05]. There was no statistical significance in the EEL(L) between the 2 groups [(3.48 +/- 0.80) mm2 versus (3.60 +/- 0.91) mm2, P > 0.05]. Morphometric analysis showed that the LA(R) of the pure damage group was (1.60 +/- 0.48) mm2, significantly smaller than that of the GM-CSF group [(1.99 +/- 0.54) mm2, P < 0.05], whereas there was no statistical significance in the I + M(R) between the 2 groups. In both groups, LA(R) was significantly correlated with LA(L) (r = 0.919, P < 0.001); and EELA(R) was significantly correlated with EELA(L) (r = 0.909, P < 0.001) and I + M(R) (r = 0.685; P < 0.001). CONCLUSION: Remodeling affects both the lesion and the reference sites and appears to occur in parallel and proportionately at both sites. GM-CSF treatment increases re-endothelialization of the injured artery and inhibits unfavorable remodeling.

[Atorvastatin inhibits scavenger receptor A and monocyte chemoattractant protein-1 expressions in foam cell].

OBJECTIVE: To investigate the effects of atorvastatin on expressions of scavenger receptor A and secretion of monocyte chemoattractant protein-1 (MCP-1) in foam cells. METHODS: THP-1 cells were induced to differentiate into macrophages by PMA and treated with 0.1% BSA (control), ox-LDL (100 mg/L) or ox-LDL plus atorvastatin (5, 10, 20 micromol/L) for 24 hours. MCP-1 concentration in cell substratum was measured by ELISA. Scavenger receptor A expression was observed under fluorescent microscope after incubated with DiI-Ac-LDL. The relationship between concentration of MCP-1 and the activity of scavenger receptor A was also analyzed. RESULTS: Compared to the control cells, MCP-1 concentration in ox-LDL treated cells was significantly increased after 6 hours, peaked at 12 hours and was still significantly increased after 24 hours (all P < 0.05 vs. baseline). The activity of scavenger receptor A was also significantly increased in ox-LDL treated cells (P < 0.01 vs. control). The activity of scavenger receptor A proteins correlated positively to the concentration of MCP-1 in ox-LDL treated cells (r = 0.683, P < 0.01). Atorvastatin significantly attenuated these changes in a dose-dependent manner. CONCLUSIONS: Scavenger receptor A and MCP-1 expressions were significantly increased in the course of monocyte lines THP-1 differentiating into macrophages and foam cells. The anti-atherosclerosis effect of atorvastatin might be partly achieved by inhibiting the secretion of MCP-1 and expression of scavenger receptor A in foam cells.