Efficacy of Shexiang Tongxin Dropping Pills in a Swine Model of Coronary Slow Flow.

Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms. Methods: SF was induced by coronary injection of 40 µ m microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting. Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group. Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression.

A simple method of placing a coronary sinus catheter through the femoral vein in miniature swine.

The aim of the present study was to evaluate the feasibility of placing a coronary sinus (CS) catheter through the femoral veins of miniature swine. A total of 16 male domestic pigs (3-4 months old, 25±2 kg) were used. Firstly, the anatomic structure of the CS ostium of swine heart was observed at different angles under X-ray. The guide wire and Cobara catheter were subsequently advanced into the right atrium through the femoral vein. Subsequently, the guide wire was retracted behind the fix curve of the Cobara catheter and the catheter bent spontaneously in the absence of supporting guide wire following retraction. The catheter was then gently rotated clockwise to direct the catheter tip to the left allowing the catheter to easily be placed in the CS ostium. This method was associated with a short procedure time: The time on separation of the blood vessels was 15.5±5.8 min and the time of radiation exposure was 112±20 sec. The success rate of placing the catheter to CS ostium was 100%. Only one pig experienced a hematoma after the sheath was pulled out. All swine recovered without serious complications, such as perforation of coronary vein and pericardial tamponade. Therefore, this method of placing CS catheter is simple, safe and reliable, which may offer help for related research.

Evolution of Coronary Flow in an Experimental Slow Flow Model in Swines: Angiographic and Pathological Insights.

OBJECTIVE: Pathomechanism of coronary slow flow phenomenon remains largely unclear now. Present study observed the pathological and angiographic evolution in a pig model of coronary slow flow. METHODS: Coronary slow flow was induced by repeat coronary injection of small doses of 40 µm microspheres in 18 male domestic pigs and angiographic and pathological changes were determined at 3 hours, 7 days, and 28 days after microspheres injection. RESULTS: Compared to control group treated with coronary saline injection (n = 6) and baseline level, coronary flow was significantly reduced at 3 hours and 7 days but completely recovered at 28 days after coronary microsphere injection in slow flow group. Despite normal coronary flow at 28 days after microsphere injection, enhanced myocardial cytokine expression, left ventricular dysfunction, adverse remodelling, and ischemia/microembolism related pathological changes still persisted or even progressed from 3 hours to 28 days after coronary microsphere injection. CONCLUSIONS: Our results show that this large animal slow flow model could partly reflect the chronic angiographic, hemodynamic, and pathological changes of coronary slow flow and could be used to test new therapy strategies against the slow flow phenomenon.

Effects of intravenous diltiazem in a rat model of experimental coronary thrombotic microembolism.

The aim of this study was to assess the feasibility of evaluating the therapeutic effects of intravenous diltiazem in a newly established rat model of coronary thrombotic micro-embolism (CME). CME was induced by injecting 0.199 ml saline containing 5 mg of automicrothrombotic particulates (∼10 µm) into the aorta of Sprague Dawley rats. The injection was carried out over 10 sec using a tuberculin syringe with a 28-gauge needle. The CME model rats were randomly divided into untreated (CME, n=38) and diltiazem-treated (CME+DIL, n=38) groups. Diltiazem (1 mg/ml, 50 µg/min/kg) was intravenously injected using an infusion pump through the tail vein for 175 min, 5 min following the injection of the automicrothrombotic particulates. Hemodynamic measurements, echocardiography and pathohistological examinations were performed at various time-points (3 h, 24 h and 7 and 28 days) postoperatively. Arteriolar thrombosis, multifocal myocardial necrosis, inflammatory cell infiltration with markedly increased myocardial tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) expression, reduced left ventricular (LV) systolic function and increased plasma von Willebrand factor (vWF), endothelin-1 (ET-1) and serum c-troponin I (c-TnI) levels (indicating vascular endothelial injury and myocardial necrosis) were observed in the CME model rats. These pathological responses in CME rats were partly attenuated by intravenous diltiazem treatment. The present CME model is suitable for evaluating the therapeutic effects of intravenous diltiazem; intravenous diltiazem treatment significantly improved cardiac function through alleviating inflammatory responses and microvascular thrombotic injury in this rat model of CME.

A randomized, single-center double-blinded trial on the effects of diltiazem sustained-release capsules in patients with coronary slow flow phenomenon at 6-month follow-up.

OBJECTIVE: The aim of this study is to observe the chronic effects of diltiazem release capsules on patients with coronary slow flow (CSF) phenomenon. METHODS: From 2004 to 2009, 80 consecutive patients with chest pain and normal coronary arteries evidenced by coronary angiography and CSF were included in this randomized, double-blind, placebo-controlled trial. CSF patterns were evaluated by the corrected TIMI frame count. Patients were randomly assigned at 1:1 ratio to diltiazem sustained-release capsules treatment group (Dil, 90 mg twice daily) or placebo control group. Holter, liver and kidney function, treadmill exercise test, coronary angiography and left ventricular angiography were measured at baseline and after 6 months. The incidence of cardiovascular events (re-admission or progress in coronary heart disease, myocardial infarction, malignant arrhythmia or cardiac death) was evaluated during the 6 months follow up. RESULTS: Thirty-nine patients in control and 40 patients in Dil group completed the 6 months follow-up. There was no medication induced drug withdraw during follow up. Left ventricular ejection fraction was similar between the 2 groups at baseline and during follow up. Heart rate was significantly lower in Dil group than in control group and there was no symptomatic bradycardia and II and III degree atrioventricular conduction block in both groups. Significant improvement was observed in the onset of chest pain, treadmill exercise test and coronary blood flow in Dil group while these parameters remained unchanged in control group at the end of 6 months follow up. The incidence of cardiovascular events was similar between the two groups. CONCLUSION: Diltiazem slow-release capsules improved coronary blood flow and alleviated angina in patients with CSF. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TCC-11001864.

[Effect of scopolamine on the acute severe chlorphenamidine poisoning patients].

OBJECTIVE: To investigate effectiveness of scopolamine on the acute severe chlorphenamidine poisoning patients. METHODS: 72 cases of acute severe chlorphenamidine poisoning patients were divided into I and II groups by the principle of a 1:1 sampling according to the order of admission. The I group (36 cases) were treated with traditional multimodality therapy, including gastrolavage, catharsis, using reductant-oxidant (methylthioninium chloride and vitamin C), and symptomatic treatment. The II group were treated with traditional multimodality therapy and scopolamine at the same times. Blood methemoglobin were measured at 0, third, seventh, twelfth, twenty-fourth hour, serum troponin I (CTnI) and creatine kinase isoenzyme (CK-MB) levels at third, seventh, twenty-fourth, forty-eighth hour, hepatic and renal functions at third, twenty-fourth, forty-eighth hour, and electrocardiogram (ECG) were evaluated every 4 hours in 3 days after hospitalization on all patients. The two groups of patients were compared the efficacy and change detection of targets. RESULTS: 31 patients (86.11%) recovered and 5 patients (13.89%) died in I group. All 36 cases recovered in II group. The recovery rate of II group was distinctively higher than that in I group (P < 0.05) and the difference was statistically significant (P < 0.05). The average recovery time and the length of hospital stay in II group were sharply shorter than those in I group (P < 0.01) and the difference was statistically significant (P < 0.05). Serum CTnI levels between seventh hour and forty-eighth hour, serum CK-MB levels between third hour and forty-eighth hour and methemoglobin concentration at third, seventh, twelfth, twenty-fourth hour were apparently lower in II group, and the difference was statistically significant (P < 0.05). The abnormal rates of hepatic and renal functions in II group were distinctively lower than those in I group and the difference was statistically significant (P < 0.05). The abnormal rates of ECG in the second and third day in II group were respectively 38.89% and 11.11%, and were lower than those in I group (64.71%, 38.71%). The difference was statistically significant (P < 0.05). CONCLUSION: Scopolamine has the excellent treatment effect on acute severe chlorphenamidine poisoning patients and protec their hearts, livers, and kidneys. It complements the deficiency of reductant-oxidants, and combination of the two drugs can form the synergy effect.

Establishment and characterization of an experimental model of coronary thrombotic microembolism in rats.

To establish a model of coronary thrombotic microembolism in rats, either automicrothrombotic particulates (CM group) or saline control (SHAM group) was injected into temporarily clamped aortas of male Sprague-Dawley rats. After automicrothrombotic particulate injection, serum c-troponin I and von Willebrand factor levels, the no-flow area as evaluated by Thioflavin S, myocardial leukocyte infiltration levels, myocardial expressions of tumor necrosis factor alpha and interleukin-6, the percentage of arterioles obstructed by thrombosis, and myocardial fibrosis were all significantly increased whereas cardiac function as evaluated by echocardiography and hemodynamic measurements were significantly reduced compared with the sham group. Thus, aortic automicrothrombotic particulate injection could induce coronary microembolism in rats, and this model could be of value in improving the understanding of pathophysiology of coronary microembolism.

[Effects of treatment with redox agent, blood transfusion and scopolamine on 200 patients with severe chlorphenamidine poisoning].

OBJECTIVE: To verify the effects of treatment with blood transfusion and scopolamine on severe chlorphenamidine poisoning (SCP). METHODS: 400 patients with severe oral chlorphenamidine poisoning were randomly divided into two groups. 200 patients (Group I) were treated with the traditional combined therapy including gastrolavage, purgation and taking redox agent (methylene blue and vitamin C) while the other 200 patients (Group II) in addition to the above mentioned therapy, received blood transfusion and scopolamine injection. RESULTS: The cure rate of Group II was 99.5% and significantly higher than that of Group I (91.0%, P < 0.01). The average time of improving in health in Group II [(8.71 +/- 1.49) h] was obviously shorter than those in Group I [(10.65 +/- 1.72) h, P < 0.01]. Blood methemoglobin concentrations in Group II at 3, 7, 12, 24 h after admission [(43.58 +/- 2.69), (34.21 +/- 2.30), (20.60 +/- 4.03), (13.50 +/- 1.65) g/L respectively] were obviously lower than those in Group I [(54.42 +/- 12.79), (42.17 +/- 22.34), (30.66 +/- 17.67), (19.01 +/- 0.61) g/L respectively, P < 0.01]. CONCLUSION: Blood transfusion and scopolamine had distinctive therapeutic effect on SCP to makeup the deficiency of redox agent. Combination of three therapies may potentiate the detoxication for chlorphenamidine.