Hydrogen sulfide improves cardiomyocytes electrical remodeling post ischemia/reperfusion injury in rats.

Hydrogen sulfide (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, is an endogenous gaseous mediator exerting pronounced physiological effects as the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). Accumulating evidence indicated that H2S could mediate the cardioprotective effects in myocardial ischemia model. Ventricular arrhythmia is the most important risk factor for cardiac mortality and sudden death after acute myocardial infarction (AMI). The potential impact of H2S on cardiomyocytes electrical remodeling post ischemic insult is not fully explored now. Present study investigated the role of H2S on cardiomyocytes electrical remodeling in rats with ischemia/reperfusion injury. H2S concentration was reduced and arrhythmia score was increased in this model. CSE mRNA level was also upregulated in the ischemic myocardium. Exposure to exogenous NaHS reduced the action potential duration (APD), inhibited L-type Ca(2+) channels and activated K(ATP) channels in cardiomyocytes isolated from ischemic myocardium Exogenous H2S application improves electrical remodeling in cardiomyocytes isolated from ischemic myocardium. These results indicated that reduced H2S level might be linked to ischemia/reperfusion induced arrhythmias.

Oxidized low-density lipoprotein and C-reactive protein have combined utility for better predicting prognosis after acute coronary syndrome.

It has been shown that the elevated concentrations of oxidized low-density lipoprotein (Ox-LDL) or high-sensitivity C-reactive protein (hs-CRP) are predictive of future cardiovascular events for acute coronary syndrome (ACS) patients. But, the combined value of Ox-LDL and hs-CRP for predicting cardiovascular events is still unknown. Serum concentrations of Ox-LDL, hs-CRP, and cTnT were measured in a prospective cohort of 425 selective ACS patients followed 3-5 years for the occurrence of acute myocardial infarction (AMI) or death (AMI/death). Among 425 enrolled patients, 124 patients demonstrated AMI/death. Baseline levels of Ox-LDL, hs-CRP, and cTnT were significantly higher in AMI/death group than the event-free survival group. Kaplan-Meier survival analyses supported that elevations in Ox-LDL or hs-CRP predicted increased cardiovascular events risks. However, the strongest risk prediction was achieved by assessing Ox-LDL and hs-CRP together. Patients with high levels of Ox-LDL and hs-CRP were more likely to experience AMI or death than those with either Ox-LDL or hs-CRP elevated. Receiver-operating characteristic curves showed that Ox-LDL and hs-CRP have higher sensitivity and specificity than those of cTnT for predicting AMI or death. This was reflected by the AUC values for Ox-LDL, hs-CRP, and cTnT, which were 0.891, 0.834, and 0.626, respectively. The combined use of Ox-LDL and hs-CRP may improve prognosis after ACS with high-sensitivity and specificity.

Fosinopril attenuates the doxorubicin-induced cardiomyopathy by restoring the function of sarcoplasmic reticulum.

Fosinopril, an angiotensin-converting enzyme inhibitor, is known to attenuate cardiomyopathy induced by doxorubicin (DOX); however, the mechanisms of this cardioprotection are not fully elucidated yet. In the present study, experimental cardiomyopathy was induced in rats by administration of DOX with or without co-treatment with fosinopril. Fosinopril was utilized on day 1 or 14 of the treatment with DOX to compare efficacies of early versus late co-treatments. We observed that fosinopril attenuated changes induced by DOX (e.g., less increased heart and left ventricular weights, diminished lung congestion and ascites, attenuated LVEDP and LVSP, and less decreased +dP/dt and -dP/dt). Further, fosinopril diminished the levels of markers of cardiac toxicity (i.e., plasma levels and activities of cardiac enzymes and proteins AST, LDH, CPK, cTnI, and BNP). Fosinopril also prevented DOX-induced decreases in Ca(2+) uptake and restored activity of Ca(2+)-stimulated ATPase in left ventricular sarcoplasmic reticulum. We next tested whether the improved Ca(2+) transport activity in sarcoplasmic reticulum was due to modulation of SERCA2 and phospholamban expressions by fosinopril. Fosinopril attenuated the decrease in SERCA2 and phospholamban expressions caused by DOX. In conclusion, cardioprotective effects of fosinopril in the DOX-induced cardiomyopathy appear to be due to its ability to prevent remodeling of the cardiac sarcoplasmic reticulum membrane.

Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention.

1. Inflammation is central to the pathogenesis of acute coronary syndrome (ACS) and is associated with adverse clinical outcomes after percutaneous coronary intervention (PCI). Recent in vitro work has demonstrated the anti-inflammatory effect of berberine, a primary component of the traditional Chinese medicine 'umbellatine'. In the present study, we further tested whether berberine had any beneficial effects on ACS patients following PCI. 2.In all, 130 ACS patients undergoing PCI were recruited to the present study. Sixty-one patients were treated with berberine (300 mg, t.i.d., for 30 days) in addition to standard therapy, whereas the remaining patients received standard therapy alone. Circulating inflammatory markers were measured by ELISA, whereas serum lipid profiles were measured by routine chemical assays. 3.In the berberine-treated group, matrix metalloproteinase (MMP)-9, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, C-reactive protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly reduced relative to baseline values. Furthermore, the changes in MMP-9, ICAM-1 and VCAM-1 from baseline to after 1 month of treatment differed significantly between the two patient groups. There was a tendency for berberine to induce a slightly greater reduction in low-density lipoprotein cholesterol and triglycerides than standard therapy alone, without affecting high-density lipoprotein cholesterol, but the differences failed to reach statistical significance. No severe adverse effects of berberine were observed. 4.The results of the present study provide the first clinical evidence of the anti-inflammatory action of berberine in ACS patients following PCI. Berberine may become adjunct therapy to further improve clinical outcomes via its anti-inflammatory effect in ACS patients.

Hydrogen sulphide is an inhibitor of L-type calcium channels and mechanical contraction in rat cardiomyocytes.

AIMS: Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2)S is a novel inhibitor of the L-type calcium channel current (I(Ca,L)). METHODS AND RESULTS: Electrophysiological measurements were performed in cardiomyocytes isolated from Wistar-Kyoto and spontaneously hypertensive rats. Bath application of 100 microM NaHS (a H(2)S donor) significantly reduced the time required for the repolarization of the action potential. Inhibition of the peak I(Ca,L) by NaHS was determined to be concentration-dependent (25, 50, 100, 200, and 400 microM). NaHS inhibited the recovery from depolarization-induced inactivation. Electric field-induced [Ca(2+)]i transients and contraction of single cardiomyocytes and isolated papillary muscles were reduced by NaHS treatment. In contrast, caffeine induced an increase in [Ca(2+)]i that was not altered by NaHS. NaHS had no effect on the K(ATP) current or on the levels of cAMP and cGMP in the current study. CONCLUSION: H(2)S is a novel inhibitor of L-type calcium channels in cardiomyocytes. Moreover, H(2)S-induced inhibition of [Ca(2+)]i appears to be a secondary effect owing to its initial action towards I(Ca,L). The inhibitory effect of H(2)S on I(Ca,L) requires further investigation, particularly in the exploration of new pathways involved in cardiac calcium homeostasis and disease pathology.

[Influence of inhibitors of nitric oxide synthase and L-arginine on the survival rate in a rat model of traumatic shock].

OBJECTIVE: To investigate the influence of inhibitors of nitric oxide synthase (NOS) and L-arginine on the survival rate in a rat model of traumatic shock. METHODS: A rat model of traumatic shock was established by fracturing the posterior limb of the rat. Nomega-nitro-L-arginine-methyl ester (L-NAME, non-selective NOS inhibitor, 10 mg/kg), amino- guanidine (AG, selective inducible nitric oxide synthase (iNOS) inhibitor, 100 mg/kg) and L-arginine (L-Arg, the precursor of nitric oxide (NO) synthesis 100 mg/kg) were injected intravenously during resuscitation,survival time and survival rate were observed. RESULTS: There were no significant changes in survival time and 24-hour survival rate between L-NAME ((23.80+/-9.09) hours and 40 percent) and control group (18.78+/-4.64)hours and 10 percent, both P>0.05); the survival time of AG group (28.72+/-6.25) hours and L-Arg group (30.64+/-8.77) hours prolonged apparently (both P<0.01), and 24-hour survival rate was also increased (both 80 percent, both P<0.01). CONCLUSION: Selective iNOS inhibitor AG and L-Arg exert beneficial effects on after traumatic shock rats.

[L-arginine decreases P-selectin expression in traumatic shock].

OBJECTIVE: To investigate the changes of P-selectin distribution in the vital organs and plasma during traumatic shock and explore the significance of these changes. METHODS: Twenty-four normal SD rats were randomly assigned into 3 groups (n=8), namely traumatic shock group, L-arginine (L-Arg) treatment and control group. The rats in the former 2 groups were subjected to traumatic shock with L-Arg treatment group given 100 mg/kg L-Arg during resuscitation while the other receiving no medication. The control group received only intubation without trauma or phlebotomy. P-selectin expression in the vital organs including the heart, lungs, spleen, liver and small intestine was determined by means of streptavidin-biotin (SABC) immunocytochemical staining technique and serum P-selectin level assayed by enzyme-linked immunosorbent assay. RESULTS: Before traumatic shock, P-selectin was scarcely detected in the vital organs except the lungs, and the serum was positive for P-selectin expression. Four hours after shock, intense P-selectin expression was observed in almost all the vital organs and the serum P-selectin level was significantly higher than that of the control group. In L-Arg treatment group, P-selectin levels were significantly lowered than those of shock group. CONCLUSIONS: P-selectin expression in the vital organs and serum is up-regulated during traumatic shock in rats, possibly due to severe microcirculatory disorder and endothelial dysfunction in this condition. L-Arg may decrease the expression of P-selectin very likely through promoting endothelial NO synthesis.

[Therapeutic efficiency of nitric oxide synthase inhibitor on traumatic shock in rats].

OBJECTIVE: To evaluate the effects of aminoguanidine (AG) used as a selective inhibitor of the inducible form of nitric oxide synthase (iNOS) and N-nitro-L-arginine methyl ester (L-NAME) used as a non-selective inhibitor of nitric oxide synthase (NOS) on traumatic shock. METHODS: Thirty SD (Sprague-Dawley) rats were used to create a animal model of traumatic shock. Both shaft of femurs were crashed and bled to mean arterial pressure of 35-45 mm Hg (1 mmHg=0.133 kPa) via femoral artery. Hypotension was maintained 30 minutes, the shed blood was then returned, followed by an infusion with Ringer's solutions. Animals were randomly divided into three groups: traumatic shock group (n=10), AG group (AG 8 mg/kg was infused at resuscitation, n=10), L-NAME group (L-NAME 8 mg/kg was infused at resuscitation, n=10). Plasma levels of nitric oxide (NO) were determined before and after shock, immediately after resuscitation and 0.5, 2 and 4 hours after resuscitation. The 24 hours survival rates were recorded. Lung, liver and kidney, intestine tissues were obtained 24 hours after shock for microscopic examination. RESULTS: The plasma level of NO markedly increased after shock. The plasma level of NO markedly decreased and less tissue damages with highly survival rates in AG group. Lower plasma level of NO and survival rates and highly tissue damages were seen in L-NAME group. CONCLUSION: NO plays an important role in development of pathologically traumatic shock. AG is beneficial of treatment in traumatic shock, but L-NAME can only decrease the plasma level of NO and can not improve the outcome of shock.

Intervention with nitric oxide synthase inhibitors for traumatic shock in rats.

OBJECTIVE: To evaluate the effects of a selective inhibitor of inducible nitric oxide synthase (iNOS) aminoguanidine (AG) and a non-selective inhibitor of nitric oxide synthase (NOS) N(G)-nitro-L-arginine methylester (L-NAME) on traumatic shock in rats. METHODS: Animal models of traumatic shock were established in 44 Sprague-Dawley rats following fractures in both femur shafts and subsequent depletion until the mean arterial pressure in the femoral artery dropped to 35 to 45 mmHg(4.67-6.00 kPa). Hypotension was maintained for 30 min before the collected blood was infused back into the rats supplemented with Ringer's solution of the same volume. The rat models were then randomly divided into 3 groups, namely traumatic shock group (n=10), AG group (which was subdivided into AGI, AGII, and AGIII groups, each consisting of 8 rats and receiving 2, 8, and 60 mg/kg x b.w AG infusion respectively during resuscitation), and L-NAME group (with 8 mg/kg x b.w L-NAME infusion during resuscitation, n=10). Plasma NO levels were determined before and after shock, immediately after resuscitation and 0.5, 2, 4 h after resuscitation, and the survival rates within 24 h were recorded with tissue samples of the lung, liver, kidney and intestine obtained 24 h after shock for microscopic examination. RESULTS: Plasma NO level was seen to increase markedly after traumatic shock in the rat models. In the 3 AG groups, the elevated NO levels following the shock were obviously reduced after resuscitation with less tissue damages and higher survival rates, as compared with the other 2 groups. The best protective effect against traumatic shock was observed in AGIII group. In spite of obvious plasma NO level-lowering effect after resuscitation, L-NAME exhibited little efficacy in alleviating the tissue damages in the organs and hence failed to improve the survival rate of the rats. CONCLUSIONS: NO plays an important role in the pathological process of traumatic shock, and the application of AG may improve the condition. L-NAME can decrease plasma NO level after resuscitation, but fail to improve the outcome of traumatic shock in rats.

[Therapeutic effect of L-arginine on traumatic shock in rats].

OBJECTIVE: To evaluate the therapeutic effect of L-arginine (L-Arg) on traumatic shock in rats and explore the possible mechanisms. METHODS: Rat models of traumatic shock were established in Sprague-Daulay rats, which were randomly divided into two groups either to receive L-Arg treatment or not. The plasma concentration of endothelin (ET) and oxygen partial pressure in the tissues from the skeletal muscles, liver and small intestine were measured before and after the shock and 1, 3, and 5 h after resuscitation. The hemodynamics of the rats and their survival rates at 12 and 24 h were recorded. RESULTS: The changes of plasma ET levels and oxygen partial pressure in tissues of both groups were statistically significant after traumatic shock (P<0.05). Plasma ET concentration at 5 h after resuscitation was significantly lower in the treatment group than in the non-treatment shock group (P<0.05), while oxygen partial pressure in the liver and small intestine after resuscitation were significantly higher in the treatment group (P<0.05). The survival rates at 12 and 24 h were also significantly different between the 2 groups. CONCLUSION: Adscititious L-Arg can decrease plasma ET levels, improve oxygen partial pressure of internal organs and significantly increase the survival rate of the rats with traumatic shock.

Dynamic changes in serum level of nitric oxide and its mechanisms in rats with traumatic shock.

OBJECTIVE: To investigate the dynamic changes of serum nitric oxide (NO) level and its mechanisms in rats in traumatic shock. METHODS: Rat models of traumatic shock were established by fracturing the posterior limb of the rats. Serum levels of nitrate/nitrite were measured with the method described by Griess. RESULTS: No significant changes in serum NO level took place during traumatic shock. One hour after resuscitation, however, serum NO level first underwent marked decline and then increased to the peak level at 6 h after resuscitation, retaining a high level till 24 h after resuscitation. No obvious changes of serum NO levels were observed in rats without resuscitation. CONCLUSION: Serum NO level does not significantly alter during traumatic shock, while after resuscitation, NO level increases after transient decrease, possibly due to reperfusion injury.

[Clinical observation of abdominal compartment syndrome: report of 11 cases].

Through clinical observation of 11 patients with abdominal compartment syndrome (ACS), the author explored the effects of acutely elevated abdominal pressure on systemic circulation, respiration and renal function. Based on the experience in diagnosis and treatment of ACS, the author suggests that early identification and timely surgical depressurization are essential to reduce mortality and improve the prognosis.