BACKGROUND: Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients. METHODS: A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up. DISCUSSION This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504).
Angina, Stable ; drug therapy ; physiopathology ; Coronary Circulation ; Double-Blind Method ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Exercise Test ; Exercise Tolerance ; physiology ; Humans ; Placebos ; Sample Size

OBJECTIVE: To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. METHODS: Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. RESULTS: There was a significant difference in CTFC between groups (P<0.05). The average CTFC values of the vessels with slow blood flow in CSF patients were, respectively, 49.98 ± 10.01 and 40.42 ± 11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values (frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00 ± 13.32 and 41.80 ± 15.38, 59.00 ± 4.69 and 50.00 ± 9.04, and 51.90 ± 8.40 and 40.09 ± 10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow flow before treatment were significantly decreased after treatment (P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP (all P>0.05). CONCLUSIONS The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.
Blood Pressure ; drug effects ; Coronary Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; No-Reflow Phenomenon ; drug therapy ; physiopathology

OBJECTIVETo evaluate the effect of treatment with Qishen Yiqi Dripping Pills (, QSYQ) on myocardial injury and myocardial microvascular function in patients undergoing elective percutaneous coronary intervention (PCI).

METHODSEighty patients undergoing elective PCI were randomly assigned to QSYQ and control groups. The QSYQ group received QSYQ at a dosage of 0.5 g 3 times daily (3-7 days before PCI and then daily for 1 month) and regular medication, which comprised of aspirin, clopidogrel, statin, β-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the absence of contradiction. The control group received only the regular medication. The index of microcirculatory resistance (IMR) was measured at maximal hyperemia after PCI. The fractional flow reserve was measured before and after the procedure. Troponin I levels were obtained at baseline and 20-24 h after the procedure.

RESULTSPre-PCI troponin I levels between the two groups were similar (0.028±0.05 vs. 0.022±0.04 ng/mL, P=0.55). However, post- PCI troponin I levels in the QSYQ group were significantly lower than that in the control group (0.11±0.02 vs. 0.16±0.09 ng/mL, P<0.01). IMR values were significantly lower in the QSYQ group as compared to the control group (16.5±6.1 vs. 31.2±16.0, P<0.01). Multivariate analysis identified QSYQ treatment as the only independent protective factor against IMR >32 (odds ratio=0.29, 95% confidence interval: 0.11-0.74, P=0.01).

CONCLUSIONSThe present study demonstrated the benefit of QSYQ in reducing myocardial injury and preserving microvascular function during elective PCI.

Aged ; Coronary Angiography ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Male ; Microvessels ; diagnostic imaging ; drug effects ; physiopathology ; Middle Aged ; Multivariate Analysis ; Myocardium ; pathology ; Percutaneous Coronary Intervention ; Pilot Projects ; Troponin I ; blood

OBJECTIVETo investigate the effects of Chinese herbs for supplementing qi, nourishing yin and activating blood circulation on heart function of patients with acute coronary syndrome (ACS) after successful percutaneous coronary intervention (PCI).

METHODSOne hundred patients with ACS after successful PCI were randomly assigned to a Western medicine (WM) treatment group (WMG) and a combined treatment group (CMG) treated by Chinese herbs for supplementing qi, nourishing yin and activating blood circulation, besides Western medicine treatment, with 50 cases in each group. Both treatment courses were 6 months. The followup was scheduled at baseline, 6 months and 1 year after PCI, and New York Heart Association (NYHA) functional class, Chinese medicine (CM) symptom scores, blood stasis syndrome scores, and major adverse cardiovascular events (MACE) were observed, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and hyper-sensitivity C-reactive protein (Hs-CRP) were measured, an echocardiogram was conducted to examine left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), and ventricular wall motion index (VWMI).

RESULTSCompared with the baseline, LVEF significantly increased (P<0.01), and CM symptom scores, blood stasis syndrome scores, VWMI, LVEDV, LVESV, NT-proBNP, and Hs-CRP all decreased (P<0.01) in both groups at 6 months and at 1 year after PCI. There were no significant differences in all the above parameters at 1 year vs those at 6 months after PCI (P>0.05). VWMI, LVEDV, LVESV, NT-proBNP, Hs-CRP, LVEF, and CM symptom and blood stasis syndrome scores were all improved obviously in CMG than those in WMG (P<0.05 or P<0.01) at 6 months and at 1 year after PCI. There were no significant differences in NYHA functional class between CMG and WMG at different follow-up timepoints; it was notable that value was 0.054 when comparing the cases of NYHA functional class between the two groups at 1-year follow-up. During the 1-year follow-up, 3 MACE and 11 MACE occurred in CMG and WMG, respectively; the MACE rate in CMG was lower than that in WMG (6% vs 22%, P<0.05).

CONCLUSIONChinese herbs for supplementing qi, nourishing yin and activating blood circulation could improve heart function, reduce the CM symptom scores and blood stasis syndrome scores, and decrease the incidence of MACE in patients with ACS after successful PCI.

Acute Coronary Syndrome ; blood ; drug therapy ; physiopathology ; surgery ; C-Reactive Protein ; metabolism ; Cardiotonic Agents ; adverse effects ; pharmacology ; therapeutic use ; China ; epidemiology ; Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Heart Function Tests ; drug effects ; Humans ; Incidence ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; New York ; Peptide Fragments ; blood ; Percutaneous Coronary Intervention ; adverse effects ; Postoperative Complications ; epidemiology ; etiology ; Qi ; Societies, Medical ; Syndrome ; Ultrasonography ; Yin-Yang

It has been found that in case of targeted for coronary microvascular dysfunction and myocardial cell apoptosis, the anti-apoptosis effect of Guanxin No. 2, a Chinese herbal composite for activating blood and removing stasis (ABRS), is identical to that of its three absorption components (ferulic acid, Danshensu and hydroxylcarthamin yellow), and there exists a dose/myocardial flow-dependent direct or indirect acting path. Based on which, a hypothesis regarding the dose/myocardial flow related direct/indirect action of Chinese ABRS composite, with the same targets as before, was put forward by the authors in this paper, that is, the myocardial protective effect of acute high dose administration of the composite is acted through indirectly path by increasing the myocardial flow (MF); while that of chronic low dose administration is realized directly without change of MF. The evidence and significance of this hypothesis were discussed.
Animals ; Apoptosis ; drug effects ; Coronary Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Male ; Microcirculation ; physiology ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Myocytes, Cardiac ; pathology ; Phytotherapy ; Rats

BACKGROUNDReal-time perfusion imaging (RTPI) using ultrasound contrast agents has shown good "accuracy" in detecting myocardial infarction, however its accuracy in the assessment of peri-infarct ischemia and stress echocardiography are not known. The aim of this study was to determine the accuracy of RTPI in assessment of peri-infarct ischemia during dobutamine and adenosine stress.

METHODSWe employed the RTPI modality (Agilent and ATL Philips) in a canine model (18 dogs) of distal coronary occlusion and proximal coronary stenosis. Using coronary flow probe recordings, the physiologic significance of proximal coronary stenosis was established by confirming abolition of the coronary reserve. The contrast agent Optison was given as a slow bolus injection at baseline, during prolonged distal coronary occlusion, during adenosine bolus stress and during dobutamine stress. Triphenyltetrazolium chloride (TTC) staining was used to verify a distal infarction. RTPI recordings at baseline, the distal coronary occlusion and stress protocols were randomly mixed and reviewed blindly.

RESULTSIn all but one dog, RTPI detected a distal infarct as small as 9% of the left ventricle. The sensitivity, specificity and overall diagnostic accuracy of RTPI in the detection of distal infarcts were: 94%, 89% and 92%, respectively. The sensitivity, specificity, and overall diagnostic accuracy of RTPI in the assessment of peri-infarction ischemia were 83%, 92% and 88% for adenosine stress and 95%, 86% and 91% for dobutamine stress, respectively.

CONCLUSIONSEven small distal infarcts can be detected by RTPI; peri-infarct ischemia can be accurately recognized by RTPI during stress; adenosine and dobutamine stress appear equally reliable in the RTPI evaluation of peri-infarct ischemia.

Adenosine ; toxicity ; Animals ; Coronary Circulation ; drug effects ; Dobutamine ; toxicity ; Dogs ; Echocardiography ; methods ; Female ; Hemodynamics ; drug effects ; Male ; Myocardial Infarction ; diagnostic imaging

OBJECTIVETo observe the effects of Chinese drugs for supplementing qi, nourishing yin and activating blood circulation on the myocardial perfusion in acute myocardial infarction (AMI) patients after revascularization.

METHODSEighty patients with anterior or inferior ventricular wall AMI, who had received revascularization by intravenous thrombolysis or coronary bypass, were randomized into the treated group and the control group equally, both treated with conventional Western medical treatment, but combined, respectively, with Xinyue Capsule (, XYC) plus Composite Salvia Tablet (CST) and placebo for 3 months. Dobutamine stress echocardiography (DSE) was performed 14 days and 3 months after revascularization, respectively on every patient to observe blood perfusion extent (b value), myocardial perfusion velocity (k value) and local blood fl ow volume (k x b) in left ventricular infarction-related vascular segments under stressed state.

RESULTSWith 5 cases dropping out in the observation period (3 in the treated group and 2 in the control group), the trial was completed in 75 patients in total. The 14-day DSE shows that the b value and k x b value of left anterior ventricular wall mid segment and apex segment, and the k value of apex segment in patients with anterior wall AMI, as well as the b value and k x b of basal segment in patients with inferior wall AMI in the treated group were significantly higher than those in the control group (P<0.05 or P<0.01). The 3-month DSE shows that the b value of apex segment, k x b value of basal segment, mid segment and apex segment of left anterior ventricular wall in patients with anterior wall AMI as well as the b value and k x b value of basal segment of left inferior ventricular wall in patients with inferior wall AMI were all higher in the treated group than those in the control group, respectively (P<0.05). The comparison between 14-day DSE and 3-month DSE in the treated group showed that the b value of apex segment of left anterior ventricular wall in patients with anterior wall AMI and the k x b value of apex segment and mid segment of left inferior ventricular wall in patients with inferior wall AMI significantly increased along with the on-going treatment (P<0.05).

CONCLUSIONTherapy with Chinese drugs for supplementing qi, nourishing yin and activating blood circulation in combination with conventional Western medical treatment could obviously improve the blood perfusion at the myocardial tissue level in infarction-related vascular segments.

Coronary Circulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Ventricles ; diagnostic imaging ; drug effects ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnostic imaging ; drug therapy ; Myocardial Reperfusion ; Myocardial Revascularization ; Qi ; Ultrasonography ; Yin-Yang

BACKGROUNDThere are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.

METHODSThe hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n = 10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment. The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.

RESULTSThe cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1, the cardiac function variables and coronary flow at all the observed points were significantly improved in Group 2. The cardiac function variables and coronary flow were better in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO contents and NOS activity in the myocardium were significantly higher in Group 2 than in Group 1. However, NOS contents in the myocardium did not significantly differ between Groups 1 and 2.

CONCLUSIONSIn isolated rat hearts, propofol can improve cardiac functional recovery after ischemia-reperfusion by upregulating NOS activity in the myocardium. The NO system may play an important role in the preservation of myocardial ischemia-reperfusion injury produced by propofol.

Animals ; Coronary Circulation ; drug effects ; Enzyme Activation ; drug effects ; Heart ; drug effects ; Heart Function Tests ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Immunohistochemistry ; In Vitro Techniques ; Male ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; Myocardium ; enzymology ; Nitric Oxide Synthase ; metabolism ; Propofol ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley

BACKGROUNDMyocardial perfusion associates with clinical syndromes and prognosis. Adenosine could improve myocardial perfusion of acute myocardial infarction within 6 hours, but few data are available on late perfusion of myocardial infarction (MI). This study aimed at quantitatively evaluating the value of intracoronary adenosine improving myocardial perfusion in late reperfused MI with myocardial contrast echocardiography (MCE).

METHODSTwenty-six patients with anterior wall infarcts were divided randomly into 2 groups: adenosine group (n = 12) and normal saline group (n = 14). Their history of myocardial infarction was about 3 - 12 weeks. Adenosine or normal saline was given when the guiding wire crossed the lesion through percutaneous coronary intervention (PCI), then the balloon was dilated and stent (Cypher/Cypher select) was implanted at the lesion. Contrast pulse sequencing MCE with Sonovue contrast via the coronary route was done before PCI and 30 minutes after PCI. Video densitometry and contrast filled-blank area were calculated with the CUSQ off-line software. Heart function and cardiac events were followed up within 30 days.

RESULTSPerfusion in the segments of the criminal occlusive coronary artery in the adenosine group was better than that in the saline group (5.71 +/- 0.29 vs 4.95 +/- 1.22, P < 0.05). Ischemic myocardial segment was deminished significantly after PCI, but the meliorated area was bigger in the adenosine group than in the saline group ((1.56 +/- 0.60) cm(2) vs (1.02 +/- 0.56) cm(2), P < 0.05). The video densitometry in critical segments was also improved significantly in the adenosine group (5.53 +/- 0.36 vs 5.26 +/- 0.35, P < 0.05). Left ventricular ejection fraction (LVEF) was improved in all patients after PCI, but EF was not significant between the two groups ((67 +/- 6)% vs (62 +/- 7)%, P > 0.05). There was no in-hospital or 30-day major adverse cardiac event (MACE) in the adenosine group but 3 MACE in the saline group in 30 days after PCI.

CONCLUSIONSAdenosine could improve myocardial microvascular perfusion in the late reopening of an occluded infarct related artery (3 to 12 weeks after AMI) and clinical outcome in the follow-up period, and myocardial microvascular perfusion is a powerful predictor of clinical events.

Adenosine ; administration & dosage ; Coronary Angiography ; Coronary Circulation ; drug effects ; Echocardiography ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; physiopathology ; Myocardial Reperfusion ; Ventricular Function, Left

OBJECTIVETo evaluate the direct effects of dobutamine as compared to adenosine on the coronary microcirculation in both normal and stenotic segments using myocardial contrast echocardiography (MCE).

METHODSLeft anterior descending (LAD) coronary artery stenosis, which was not flow limiting at rest, was established in 9 dogs. At the baseline and during intracoronary infusion of dobutamine (2 mg.kg(-1).min(-1)) and adenosine (5 mg.kg(-1).min(-1)), the radiolabeled microsphere (RM)-derived myocardial blood flow (MBF) were determined, and the double product (DP) and myocardial vascular resistance (MVR) were calculated. MCE was performed to determine the myocardial blood volume (MBV, represented by A) and microbubble velocity (beta).

RESULTSAs compared to the baseline level, the MBF increased and MVR decreased significantly in both the normal and abnormal beds during infusion of both drugs (P<0.05). In the normal bed, adenosine had no effect on MBV, the decrease in MVR was the result of decreased arteriolar (plus venular) resistance, and the increase in MBF was predominately due to the increase in b (deltabeta/ deltaA=13.6). Dobutamine caused a 28% increase in MBV, responsible for 32% of the decrease in the total MVR, but the increase in MBF arose mainly from the increase in b (deltabeta/deltaA=5.9). In the abnormal bed, both the drugs caused a similar increase in MBF entirely by increasing b, and 14% and 15% of the increases in capillary resistance were associated with the capillary derecruitment during administration of dobutamine and adenosine, respectively.

CONCLUSIONThe direct effects of intracoronary dobutamine infusion on the coronary microcirculation are similar to that of adenosine, and the increase in MBF occurs mostly as the result of increased myocardial blood velocity.

Adenosine ; pharmacology ; Adrenergic beta-Agonists ; pharmacology ; Animals ; Blood Flow Velocity ; drug effects ; Coronary Circulation ; drug effects ; Coronary Stenosis ; diagnostic imaging ; Coronary Vessels ; diagnostic imaging ; Dobutamine ; pharmacology ; Dogs ; Echocardiography ; methods ; Microcirculation ; drug effects ; Vasodilator Agents ; pharmacology