Clinical characteristics of current COVID-19 rehabilitation outpatients in China.

To understand the clinical characteristics of omicron in COVID-19 Rehabilitation Clinic after the current shift of dynamic zeroing policy, we consecutively collected the patients' data who visited in COVID-19 Rehabilitation Clinic of a Grade-A tertiary hospital in Hangzhou, Zhejiang Province, from January 3 to January 10, 2023, analyzed related data and then compared the pneumonia between elderly and non-elderly groups. The results showed that 95.68% of the patients in COVID-19 Rehabilitation Clinic had symptoms, 70.10% had a dry cough, 12.36% had abnormal complete blood count or C-reactive protein, 19.35% had electrolyte disorder, and 2% had abnormal troponin or creatine kinase-MB. 40.45% of patients had abnormal lung CT findings, among them 86.49% of elderly patients had abnormal lung CT findings, and the utilization rate of glucocorticoids in COVID-19 Rehabilitation Clinic was only 5.98%, although people are all susceptible to getting the COVID-19 infection, the elderly are more prone to getting pneumonia, and the glucocorticoids utilization rate is relatively insufficient. It is needed to be stressed that Chinese medical staff should pay more attention to the elderly patients who are vulnerable to getting pneumonia during this period.

Exercise-Induced Tachycardia-Dependent Atrioventricular Block with Narrow QRS Complexes: A Case Report and Review of Literature.

Exercise-induced tachycardia-dependent atrioventricular block with a normal electrocardiogram at rest is rare. Herein, we present a case of a 65-year-old woman with exercise-related chest suppression and treadmill exercise test-induced second- and third-degree atrioventricular blocks with narrow QRS wave and normal resting electrocardiogram. High atrioventricular block leads to tissue and organ insufficiency, resulting in exercise intolerance, dyspnea, dizziness, and syncope. Ths diagnosis was exercise-induced high-degree atrioventricular block. For lack of effective medicines, the patient received a permanent dual chamber pacemaker to ensure atrioventricular sequential pacing during exercise. No exercise-related discomfort occurred during follow up.

R-I subtype single right coronary artery with congenital absence of left coronary system: A case report.

BACKGROUND: Isolated single coronary artery is a rare congenital anomaly. R-I subtype single coronary artery is even rarer. In this subtype, a very large right coronary artery extends in the coronary sulcus to the anterior base of the heart where it produces the left anterior descending coronary artery. Currently, only a few case reports are available in the literature for this anomaly. CASE SUMMARY: Here, we report the case of a 62-year-old woman who presented to the cardiology clinic with decreased exercise tolerance and poor blood pressure control. The patient underwent coronary angiography (CAG) and emission computed tomography (ECT). CAG images revealed a single gigantic right coronary artery (R-I type) arising from the right coronary sinus with branches supplying the left coronary territory. The ECT results confirmed myocardial ischemia at the location of the absent left coronary artery. The ECT findings confirmed that ischemia was consistent with the vascular loss location in CAG images. In such anomalies, there is a compensatory widening of the coronary artery lumen. Medical treatment was administered, and the patient was discharged. CONCLUSION: Isolated single coronary arteries are associated with ischemia and potentially fatal acute coronary events. Hence, controlling risk factors is critical.

Cardiac Shock Wave Therapy in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Objective: Coronary artery disease (CAD) has been one of the leading causes of morbidity and mortality worldwide. Cardiac shock wave therapy (CSWT) is a novel and non-invasive therapy for CAD. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of CSWT on CAD. Methods and results: We performed a comprehensive search of electronic databases such as PubMed, Embase, the Cochrane Library, and Wanfang Data in October 2021. The results were reported as weighted mean difference (WMD) with a 95% confidence interval (CI). Statistical heterogeneity scores were assessed with the standard Cochran's Q test and the I 2 statistic. A total of 8 randomized trials and 2 prospective cohort studies, together involving 643 patients (n = 336 CSWT and n = 307 control), were included in our study. Eight studies with 371 patients showed significantly improved rest left ventricular ejection fraction (LVEF) with CSWT as compared to that of the control group (WMD 3.88, 95% CI 1.53-6.23, p = 0.001, I 2 = 51.2%). Seven studies with 312 patients reported left ventricular internal diameter in diastole (LVIDd) were markedly decreased in the CSWT group compared to the control group (WMD -1.81, 95% CI -3.23 to -0.39, p = 0.012, I 2 = 20.3%). The summed stress score significantly favored the CSWT group (WMD -3.76, 95% CI -6.15 to -1.37, p = 0.002, I 2 = 56.8%), but there was no significant difference for the summed rest score. Our data were acquired from studies without a perceived high risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. Conclusion: Based on data from our present meta-analysis, CSWT was shown to moderately improve myocardial perfusion and cardiac function among patients with CAD, which would provide the clinicians with a meaningful and valuable option. Systematic Review Registration: The meta-analysis was registered on the Open Science Framework (OSF) (https://osf.io/r2xf9).

De Winter electrocardiogram pattern due to type A aortic dissection: a case report.

BACKGROUND: De Winter electrocardiograph (ECG) pattern is an atypical presentation of acute myocardial infarction (AMI) due to severe stenosis of the left anterior descending (LAD). Complications of acute aortic dissection (AD) in the setting of acute myocardial infarction (AMI) with de Winter sign are relatively rare and physicians may easily miss the diagnosis of AD. We report a case of patient with acute chest pain and de Winter ECG pattern due to AD involving the left main coronary artery (LM), LAD and left circumflex artery (LCX). CASE PRESENTATION: A 57-year-old male patient was initially diagnosed with AMI and then the diagnosis of acute AD was supported by transthoracic echocardiograph (TTE). After two stents were implanted respectively into the proximal LM-LAD and LM-LCX, he recovered from cardiogenic shock. Two months later, the patient underwent the surgery of ascending aorta replacement. After the surgery, there was no obvious chest discomfort during follow-up. CONCLUSIONS: When an ECG shows a "de Winter pattern", we should also consider the possibility of AD which result in LAD occlusion. TTE is a useful tool in screening for AD. Further research is needed to prove that percutaneous coronary intervention (PCI) may be a useful treatment strategy in the case of AD leading to severe LAD occlusion and unstable hemodynamics when there's no condition to perform aortic replacement surgery immediately.

Comparative Efficacy of Statins for Prevention of Contrast-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease: A Network Meta-Analysis.

Contrast-induced acute kidney injury (CI-AKI) is a common complication of iodinated contrast medium administration during cardiac catheterization. Statin treatment has been shown to be associated with reduced risk of CI-AKI; however, the results are inconsistent, especially for patients with chronic kidney disease (CKD). Thus, we conducted a network meta-analysis to evaluate the effects of statins in the prevention of CI-AKI. We systematically searched several databases (including, Embase, PubMed, the Cochrane Library, and ClinicalTrials.gov ) from inception to January 31, 2018. The primary outcome was occurrence of CI-AKI in patients with CKD undergoing cardiac catheterization. Both pairwise and network meta-analysis were performed. Finally, 21 randomized controlled trials with a total of 6385 patients were included. Results showed that statin loading before contrast administration was associated with a significantly reduced risk of CI-AKI in patients with CKD undergoing cardiac catheterization (odds ratio: 0.46; P < .05). Atorvastatin and rosuvastatin administered at high dose may be the most effective treatments to reduce incidence of CI-AKI, with no difference between these 2 agents.

The Role of RhoA in Neovascular-Related Functions of Endothelial Progenitor Cells Induced by Angiotensinâ ¡.

BACKGROUND/AIMS: Interference with endothelial progenitor cell (EPC) neovascularization is a novel therapeutic target for neovascular-related diseases. Angiotensin Ⅱ (Ang Ⅱ) was found to enhance new vessel formation and aggravated neovascular-related diseases. In this study, we investigated the effects of Ang Ⅱ on EPC neovascular-related functions and explored the underlying mechanisms. METHODS: EPCs were cultured from bone marrow derived mononuclear cells. The effects of Ang Ⅱ on EPC proliferation, adhesion, migration, and in vitro tube formation were investigated using the MTT assay, adhesion assay, transwell chamber assay, and in vitro tube formation assay respectively. The underlying mechanisms were explored using Western blotting assay. RESULTS: EPC adhesion, migration and in vitro tube formation were promoted by Ang Ⅱ, and the effects were reversed by RhoA/Rho-associated kinases (ROCK) signaling pathway inhibitors including C3 exoenzyme, GGTI-286 and Y-27632. The active form of RhoA was up-regulated by Ang Ⅱ and this effect was abolished by C3 exoenzyme. Moreover, RhoA silencing resulted in a notable inhibition of EPC adhesion, migration and in vitro tube formation, suggesting that RhoA activation played a pivotal role in Ang Ⅱ angiogenic effect. The results also demonstrated that phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun-NH2 kinase was elevated by Ang Ⅱ and attenuated by C3 exoenzyme, GGTI-286 and Y-27632. The enhancing effects of Ang Ⅱ on EPC adhesion, migration and in vitro vasculogenesis were reversed by p38 inhibitor SB202190 and JNK inhibitor SP600125. CONCLUSION: Ang Ⅱ may enhance EPC neovascular-related functions through activating RhoA/ ROCK and MAPK signaling pathway.

Endothelial progenitor cells in age-related vascular remodeling.

Accumulating evidence has demonstrated that endothelial progenitor cells (EPCs) could facilitate the reendothelialization of injured arteries by replacing the dysfunctional endothelial cells, thereby suppressing the formation of neointima. Meanwhile, other findings suggest that EPCs may be involved in the pathogenesis of age-related vascular remodeling. This review is presented to summarize the characteristics of EPCs and age-related vascular remodeling. In addition, the role of EPCs in age-related vascular remodeling and possible solutions for improving the therapeutic effects of EPCs in the treatment of age-related diseases are discussed.

Protection of Luteolin-7-O-glucoside against apoptosis induced by hypoxia/reoxygenation through the MAPK pathways in H9c2 cells.

Myocardial hypertrophy is often associated with myocardial infarction. Luteolin-7-O-glucoside (LUTG) has the prosperity of preventing cardiomyocyte injury. The current study aimed to explore the potential protective effect of LUTG and its relevant mechanisms in the heart. To establish the cardiac hypertrophy model in vitro, Angiotensin II (Ang II) was used to stimuli H9c2 cells in this study. The CCK­8 assay showed that LUTG pretreatment improved cell viability of cardiomyocytes co­treated with Ang II and ischemia/reperfusion. LUTG decreased the reactive oxygen species levels. Furthermore, it was demonstrated LUTG could reduce the release amount of lactate dehydrogenase and recover the catalase activity according to the flow cytometry analysis, and activity detection, respectively in Ang II­H/R­treated H9c2 cells. In addition, the flow cytometry analysis showed that the pretreatment of LUTG mitigated cell apoptosis induced by hypoxia/reoxygenation in the cardiac hypertrophy model. Meanwhile, reverse transcription­quantitative polymerase chain reaction and western blot assays showed that the apoptosis­related genes, including poly (ADP­ribose) polymerase, Fas, Fasl and Caspase­3 were downregulated at the transcriptional and translational levels. Notably, the protien expression of phosphorylated (p)­extracellular signal­regulated kinas (ERK) 1/2, p­janus kinase and p­P38 were reduced, while the expression of p­ERK5 was elevated in the LUTG pretreatment groups compared with the hypoxia/reoxygenation treatment group. Based on these results, it was suggested that the anti­apoptosis effect of LUTG may be associated with regulating the activation of mitogen­activated protein kinases signaling pathways.

Different Effects of Thiazolidinediones on In-Stent Restenosis and Target Lesion Revascularization after PCI: A Meta-Analysis of Randomized Controlled Trials.

In-stent restenosis (ISR) remains the leading problem encountered after percutaneous coronary intervention (PCI). Thiazolidinediones (TZDs) has been shown to be associated with reduced ISR and target lesion revascularization (TLR); however, the results are inconsistent, especially between rosiglitazone and pioglitazone. In this study, fourteen RCTs with a total of 1350 patients were finally included through a systematical literature search of Embase, Pubmed, the Cochrane Library, and ClinicalTrials.gov from inception to January 31, 2017. The follow-up duration of the included trials ranged from 6 months to 18 months. The results demonstrated that TZDs treatment is associated with significantly reduced risk of TLR (RR:0.45, 95%CI 0.30 to 0.67 for pioglitazone, RR:0.68, 95%CI 0.46 to 1.00 for rosiglitazone). Pioglitazone is associated with significantly reduced risks of ISR (RR:0.47, 95%CI 0.27 to 0.81), major adverse cardiac events (MACE) (RR:0.44, 95%CI 0.30 to 0.64) and neointimal area (SMD: -0.585, 95%CI -0.910 to -0.261). No significant relationship was observed between rosiglitazone and ISR (RR:0.91, 95%CI 0.39 to 2.12), MACE (RR:0.73, 95%CI 0.53 to 1.00) and neointimal area (SMD: -0.164, 95%CI -1.146 to 0.818). This meta-analysis demonstrated that TZDs treatment is associated with significant reduction in ISR, TLR and MACE for patients after PCI. Pioglitazone treatment seems to have more beneficial effects than rosiglitazone and no significantly increased cardiovascular risk was detected for both agents.

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB.

BACKGROUND/AIMS: Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α)-induced endothelial progenitor cells (EPCs). METHODS: EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1 (ICAM-1) and activation of Nuclear factor κB (NF-κB) signaling pathway were measured. RESULTS: The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/ß in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount. CONCLUSION: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/ß pathway in EPCs.

Perindopril for the prevention of atrial fibrillation recurrence after radiofrequency catheter ablation: One-year experience.

BACKGROUND: Recurrence of atrial fibrillation (AF) after ablation is still high. Perindopril plays an essential role in AF induction and maintenance. OBJECTIVE: We aimed to prove that perindopril (8 mg) could prevent recurrence after pulmonary vein isolation. METHODS: Patients with paroxysmal AF who received radiofrequency ablation were randomized to a 3-month course of perindopril 8 mg once daily (perindopril group) or placebo (placebo group). Angiotensin-II (Ang-II) therapy and standard transthoracic echocardiography were performed. All 256 patients with paroxysmal AF who received radiofrequency ablation were randomized. And we followed them for complete 1 year. The 3-month recurrence and the 1-year recurrence were compared between the 2 groups. RESULTS: The 3-month recurrence of AF was observed in 33 (26.19%) of 126 patients in the placebo group vs 19 (14.62%) of 130 patients who received perindopril 8 mg once daily (χ2, P = .021). One-year recurrence of AF was observed in 36 (28.5%) of 126 patients in the placebo group as compared with 21 (16.2%) of 130 patients who received perindopril after 1 year (P = .017). The κ value was 0.94 in the control group (P < .001) and 0.96 in the perindopril group (P < .001) between 3-month and 1-year recurrence. The Ang-II level was related to the left atrial distance with the reduction in AF recurrence (r = 0.17, P = .005 at 3 months; r = 0.25, P < .001 at 1 year). CONCLUSION: Perindopril is an effective and safe treatment for the prevention of AF recurrence after radiofrequency catheter ablation. This effect seems to be strongly associated with a significant decrease in Ang-II level and left atrial distance.

Improvements in the primary culture of neonate rat myocardial cells by study of the mechanism of endoplasmic reticulum stress.

We previously found that endoplasmic reticulum stress (ERS) might be exhibited in the conventional protocol of the primary culture of neonate rat myocardial cells (NRMCs) and that the high glucose concentration (25 mmol/L) in the culture medium might be the cause. Here, we investigated if the high concentration of glucose might influence ERS in myocardial cells during culture. GRP78 expression (ERS marker) was similar in groups with tunicamycin (TM) and without TM in high glucose cultured cells (p > 0.01). Different glucose concentrations elicited different GRP78 expressions according to analyses of protein and RNA levels, which showed ERS in H/H groups. Finally, we found that GRP78 expression was higher in TM groups compared with M/M groups (p < 0.01). The conventional high-glucose culture media during primary culture of NRMCs induced ERS. We propose that medium-glucose culture media should be used and describe an improved protocol for the primary culture of NRMCs.

Inhibition of TNF-α by cyclophosphamide reduces myocardial injury after ischemia-reperfusion.

PURPOSE: The purpose of this study was to determine whether cyclophosphamide (CP) can decrease myocardial and systemic TNF-α expression and thus protects myocardial I/R injury. METHODS: Open chest rats were subjected to 30 min of ischemia followed by 3h, 12h or 24h of reperfusion. Rats were divided into sham group, I/R group and CP group, and each group included 3 timepoint subgroups (3h, 12h and 24h). Plasma TNF-α was measured by cytometric bead array (CBA) and immunohistochemistry was used to detect TNF-α in myocardium. RESULTS: Compared with I/R group, rats treated with CP showed a significant difference with decreased plasma TNF-α (13.31 ± 2.62 vs 14.13 ± 5.95 pg/mL at 3 h reperfusion, 10.1 ± 2.73 vs 12.54 ± 5.00 pg/mL at 12 h reperfusion, 10.38 ± 5.59 vs 13.00 ± 3.59 pg/mL at 24 h reperfusion, p <0.05 respectively). Immunostaining was less intense with CP injection at each reperfusion time. The score of the intensity of myocardial TNF-α staining was down regulated. CONCLUSIONS: TNF-α is expressed in the myocardium and plasma after myocardial I/R injury. CP might be a feasible strategy for anti-TNF-α to protect myocardial I/R injury.

Investigation of cystatin C and cystatin C based estimated glomerular filtration rate in pregnant patients with heart failure.

BACKGROUND: Impaired cardiac function leads to impaired renal function. We assessed renal function in pregnant patients with heart failure. METHODS: This was a retrospective study. From 1999 to 2010, 42 pregnant patients with heart failure were classified into the single-pregnancy group and the twin or multifetation group. Clinical manifestations were assessed. Serum concentrations of creatinine and cystatin C were assessed. Estimated glomerular filtration rate (eGFR) based on serum concentrations of creatinine or cystatin C was completed. RESULTS: There were 29 single pregnancies, 12 twin pregnancies, and one multifetation. Ten patients in the twin pregnancy or multifetation group had in-vitro fertilization. The concentration of creatinine was 84.6±33.8 µmol/L and the creatinine-based eGFR was 87.2±34.9 mL/min per 1.73 m2. The percentage of patients with a creatinine based eGFR<60 mL/min per 1.73 m2was 23.8%. The concentration of cystatin C was 1.5±0.7 mg/L and the cystatin C-based eGFR was 65.2±45.8 mL/min per 1.73 m2. The percentage of patients with a cystatin C-based eGFR<60 mL/min per 1.73 m2was 52.4%. CONCLUSIONS: Serum concentrations of cystatin C and cystatin C-based eGFR are important indicators of renal impairment in pregnant patients with heart failure.

Cardiac injury in patients with pandemic 2009 influenza A (H1N1) infection.

BACKGROUND: In March 2009, the novel 2009 influenza A (H1N1) was first reported in the southwest of Mexico, and rapidly spread worldwide. We investigated the clinical features of cardiovascular involvement of patients infected with the 2009 influenza A (H1N1) virus in China. METHODS: This retrospective study recruited one hundred and seventy-two patients with 2009 influenza A (H1N1) of different severity (non-severe, severe, critically severe) and 21 patients who were influenza A (H1N1)-negative but who had an influenza-like illness. Blood was obtained for measurement of the concentration of creatine kinase (CK), creatine kinase-MB (CK-MB) and high sensitivity C-reactive protein (hs-CRP) in plasma. Chest radiography was also undertaken to calculate the cardiothoracic ratio (CTR). RESULTS: influenza A (H1N1) caused more illness in middle-aged people. The patients in the non-severe group were younger than in the severe group (P < 0.05) and the non-influenza A (H1N1) group (P < 0.01). The level of CK, CK-MB, hs-CRP and the CTR was higher in the critically severe group than in the other three groups (P < 0.001, P < 0.05, P < 0.01, P < 0.01, respectively). CONCLUSIONS: Myocardial injury was quite serious in severe infection by the influenza A (H1N1) virus, particularly in critically severe patients. Patients with 2009 influenza A (H1N1) had injury and dilation of the heart, which may be a potential cause of death.

[Study on the efficiency of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) in predicting in-hospital mortality of the patients with percutaneous coronary intervention].

OBJECTIVE: To investigate the efficiency of European System for Cardiac Operative Risk Evaluation (EuroSCORE) in predicting in-hospital mortality for the patients after percutaneous coronary intervention (PCI). METHODS: Retrospective analysis was conducted on the patients who had undergone PCI in our hospital since year 2005 to 2007. We used both cumulative EuroSCORE score and logistic EuroSCORE to predict the in-hospital morality and to analyze the correlation between the predicted mortality and the actual mortality. RESULTS: According to the additive EuroSCORE, we divided the patients into three groups, the additive EuroSCORE 0-2 were divided into low-risk group, 3-5 were divided into mid-risk group and ≥ 6 into high-risk group. The actual in-hospital mortality rates were 0%, 0.47% and 6.09% respectively. The EuroSCORE model demonstrated an overall relation between the EuroSCORE ranking and the incidence of in-hospital mortality (P<0.001). Results from the multivariable logistic regression analysis showed that the EuroSCORE was an independent in-hospital mortality predictor (P<0.01). CONCLUSION: The EuroSCORE risk model and the in-hospital mortality were significantly correlated, indicating that the model was a promising method for predicting the in-hospital mortality of PCI patients.

The influence of influenza A (H1N1) virus on creatinine and cystatin C.

BACKGROUND: In March 2009, the novel 2009 influenza A (H1N1) virus was first reported in the southwestern USA and Mexico. It rapidly spread to China and worldwide. We investigated possible kidney injury in patients with the 2009 influenza A (H1N1) virus in China. METHODS: This study was a retrospective cohort investigation of the potential renal injury in patients of influenza. One hundred and seventy-two patients confirmed to have the 2009 influenza A (H1N1) virus but who had different levels of severity (non-severe, severe, and critically severe) and 21 cases who were influenza A (H1N1)-negative but who had an influenza-like illness were investigated. Blood samples were obtained for the measurement of creatinine (Cr) and cystatin C (Cy-C). RESULTS: The influenza A (H1N1) virus caused more illness in middle-aged people in all groups. The patients in the non-severe group were younger than those in the severe group (p<0.05) and the non-influenza A (H1N1) group (p<0.01). Four subjects in the critically severe group died (3 due to respiratory failure, 1 heart injury). A significant difference in the levels of Cr and Cy-C between the groups was not observed (p>0.05). CONCLUSION: The 2009 influenza A (H1N1) virus did not cause severe kidney injury in the acute phase in adult patients.

[Interleukin-1beta upregulates matrix metalloproteinase-2 expression and activity in cardiac fibroblasts via nitric oxide synthase pathway].

OBJECTIVE: To investigate the effect of interleukin-1beta (IL-1beta) on expression and activity of matrix metalloproteinase-2 (MMP-2) of cultured human cardiac fibroblasts and related signaling pathway. METHODS: Primary human cardiac fibroblasts seeded in 6-well tissue culture plates and cultured to 80% to 90% confluence were harvested at passage 3 to 6 and exposed to IL-1beta at various concentrations for 24 h, culture supernatant and cell protein were obtained. MMP-2 mRNA was determined by RT-PCR. The activity of MMP-2 was analyzed by zymography and the expression of inducible nitric oxide synthase (iNOS) protein level was detected by Western blot analysis. Assessment of NO production in the culture supernatant was performed using the Griess method. RESULTS: IL-1beta (4 ng/ml) significantly increased MMP-2 activity of cultured fibroblasts in a time-dependent manner. MMP-2 mRNA expression was significantly upregulated by IL-1beta (4 ng/ml and 10 ng/ml, all P<0.01). Moreover, IL-1beta also significantly increased NO production in supernatant (P<0.01) and these effects could be significantly blocked by cotreatment with L-NMMA (10(-3) mol/L, all P<0.01). Western blot analysis showed that iNOS could not be detected in unstimulated human cardiac fibroblasts but could be detected in cardiac fibroblasts exposed to IL-1beta. CONCLUSION: IL-1beta increased MMP-2 activity and transcription of human cardiac fibroblasts via iNOS-NO pathway.

Cyclophosphamide protects against myocardial ischemia/reperfusion injury in rats: one of the therapeutic targets is high sensitivity C-reactive protein.

OBJECTIVE: Cyclophosphamide has a role of decreasing high-sensitivity C-reactive protein in the treatment of autoimmune disorders. The effect of cyclophosphasmide on high-sensitivity C-reactive protein was investigated in myocardial ischemia/reperfusion rat. METHODS: Open-chest rats were submitted to 30 minutes of ischemia and followed for 3, 12, or 24 hours of reperfusion. All 72 rats survived and were divided into sham, ischemia/reperfusion (I/R) and cyclophosphamide groups, and each group included 3 time-point subgroups (3, 12, and 24 hours; n = 8 for each subgroup). Cyclophosphamide (0.75 g/m(2)) or saline was intraperitoneally administrated in the cyclophosphamide or I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure, left ventricular end-diastolic pressure, and maximum rate of rise or fall of left ventricular pressure. In the end, blood was collected for detection of high-sensitivity C-reactive protein, and hearts were harvested for histopathologic assessment and infarct size determination. RESULTS: Compared with the I/R group, rats treated with cyclophosphamide showed a significant recovery in myocardial function with improved left ventricular systolic pressure (88.27 +/- 3.78 vs 68.62 +/- 3.78 mm Hg at 3 hours, 92.04 +/- 3.77 vs 63.74 +/- 4.87 mm Hg at 12 hours, and 90.41 +/- 3.98 vs 64.21 +/- 4.88 mm Hg at 24 hours; P < .05, respectively). Left ventricular end-diastolic pressure and maximum rate of rise or fall of left ventricular pressure also had similar trends. Infarct size was reduced (26.1% +/- 0.4% vs 40.4% +/- 0.4% at 3 hours, 21.6% +/- 0.4% vs 49.9% +/- 0.4% at 12 hours, and 21.6% +/- 0.4% vs 40.0% +/- 0.4% at 24 hours; P < .01, respectively). Histopathologic damage score was attenuated (1.83 +/- 0.14 vs 2.17 +/- 0.14 at 3 hours, 2.33 +/- 0.14 vs 3.17 +/- 0.14 at 12 hours, and 2.83 +/- 0.14 vs 3.83 +/- 0.14 at 24 hours; P < .01, respectively). Plasma high-sensitivity C-reactive protein concentration was significantly reduced (29.28 +/- 0.51 vs 32.26 +/- 0.51 ng/mL at 3 hours, 29.06 +/- 0.50 vs 31.8 +/- 0.51 ng/mL at 12 hours, and 28.61 +/- 0.51 vs 31.86 +/- 0.51 ng/mL at 24 h; P < .01, respectively). CONCLUSION: Cyclophosphamide protects myocardial ischemia/reperfusion injury in the rat with a decrease in plasma concentration of high-sensitivity C-reactive protein.