Exercise training combined with alprostadil improves myocardial infarction and coronary microcirculation disorder in aged rats by inhibiting mitogen-activated protein kinase (MAPK) signaling pathway activation.

Background: We aimed to explore the effects and mechanisms of exercise training combined with alprostadil (ALPR) treatment on myocardial infarction (MI) in aged rats. Methods: Male Wistar rats were randomly divided into five groups. One day after MI induction, an automatic biochemical analyzer was used to measure cardiac troponin I (cTnI), cardiac troponin T (cTnT), and creatine kinase MB isoenzyme (CK-MB) serum levels. One week after MI induction, echocardiography was performed to examine the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) rates of the rats. Parameters such as body weight (BW), heart mass index, and the heart weight (HW)/tibia length (TL) ratio of the rats were also calculated. Western blot was performed to assess angiogenesis and mitogen-activated protein kinase (MAPK) signal-related protein expression. Results: Compared with the MI group, the LVEDD and LVESD in the Trained + ALPR group were significantly decreased, while LVEF, LVFS, HW/BW, and HW/TL were significantly increased. Additionally, the Trained + ALPR group exhibited decreased levels of cTnI, cTnT, and CK-MB and significantly reduced MI size and myocardial injury. Moreover, compared with the Trained or ALPR group, the Trained + ALPR group showed upregulated energy metabolism, increased microvessel density, and better efficacy. Finally, the Trained + ALPR group showed a significant increase in angiogenesis-related proteins and a significant reduction in MAPK signaling pathway-related protein activity. Conclusions: Exercise training combined with ALPR improved MI in elderly rats by inhibiting MAPK signaling, promoting angiogenesis, and increasing metabolism.

The effectiveness of alprostadil in treating coronary microcirculation dysfunction following ST-segment elevation myocardial infarction in a pig model.

Though alprostadil has been reported to improve the impaired microcirculation of patients with pulmonary arterial hypertension, its effectiveness as a treatment for coronary microvasculature dysfunction (CMD) following ST-segment elevation myocardial infarction (STEMI) is unknown. A total of 18 miniature pigs with CMD following STEMI were randomized into three groups that received an intracoronary injection of 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil immediately after measurement of the index of microcirculatory resistance (IMR) and then an intravenous drip containing 5 ml of normal saline, 2 mg of nicorandil or 10 µg of alprostadil once a day for 6 days. The IMR, cardiac function using ultrasound, infarct areas and heparanase levels in infarct areas were measured and compared between the three groups. The IMR decreased markedly 10 min after alprostadil or nicorandil intracoronary injection (both P<0.05) but not following saline injection (P>0.05). After 7 days, the IMR was substantially lower in the alprostadil and nicorandil groups compared with the saline group (both P<0.05) and the ejection fraction was considerably higher in the alprostadil and nicorandil groups compared with the saline group (both P<0.05). Differences in infarct areas and the relative heparanase expression levels among the 3 groups were similar to the differences in the ejection fraction. No significant differences in the above assessment indexes were identified in the alprostadil and nicorandil groups. Alprostadil infusion improved coronary microcirculation function, reduced the infarct area and limited left ventricular dilatation in a pig coronary microvasculature dysfunction model following STEMI.

Effectiveness and safety of intracoronary papaverine, alprostadil, and high dosages of nicorandil and adenosine triphosphate for measurement of the index of coronary microcirculatory resistance in a pig model.

BACKGROUND: Papaverine is used to induce maximal hyperemia for index of coronary microcirculatory resistance (IMR) measurement in animal experiments, although it can lead to polymorphic ventricular tachycardia and ventricular fibrillation. OBJECTIVES: This study investigated the effect of an intracoronary (IC) bolus of high adenosine triphosphate (ATP) and nicorandil doses for IMR measurement and explored the possibility of inducing maximal hyperemia with an IC alprostadil bolus. MATERIAL AND METHODS: Index of coronary microcirculatory resistance was measured in a hyperemic state induced by 7 experimental conditions in 21 pigs (IC bolus of papaverine (18 mg), ATP (40 µg, 80 µg, 160 µg, and 240 µg), and nicorandil (2 mg and 4 mg)). The 7 conditions were induced sequentially, and the average IMR was calculated. Because of the long-term hyperemic condition in the pilot experiments, the IMR was measured 1, 3, 5, 8, and 10 min after an IC bolus of alprostadil (10 µg) in another 7 pigs. RESULTS: The IMR induced by 240 µg of ATP or 4 mg of nicorandil was not significantly different from that induced by 18 mg of papaverine (both p > 0.05). A strong linear correlation was observed between IMRs with papaverine (18 mg) and nicorandil (4 mg) (R2 = 0.936, p < 0.001) and with papaverine (18 mg) and ATP (240 µg) (R2 = 0.838, p < 0.05). The IC bolus of nicorandil (4 mg) produced the smallest changes, whereas papaverine caused the most significant changes in mean blood pressure and heart rate (p < 0.05). Tachypnea and transient ST depression were more common with increasing ATP dosages (especially 240 µg). Alprostadil (5 min) yielded a significant hyperemic response but reduced baseline blood pressure by almost 40% for a long time. CONCLUSIONS: Intracoronary bolus administration of 4 mg of nicorandil was better than 18 mg of papaverine or 240 µg of ATP for induction of maximal hyperemia and IMR measurement in a pig model, whereas alprostadil was not suitable for IMR measurement.

[Dynamic changes of brain natriuretic peptide concentration and its diagnostic value for heart failure in early phase of acute myocardial infarction].

OBJECTIVE: To explore the dynamic changes in brain natriuretic peptide (BNP) concentration and the diagnostic value of BNP for heart failure at different time points in the early phase of acute myocardial infarction (AMI). METHODS: AMI patients who were admitted in our department between January 1, 2016 and July 31, 2016 and underwent emergency percutaneous coronary intervention (PCI) within 12 h after onset were enrolled in this study. All the patients received bedside examinations of BNP concentration and clinical cardiac function within 1 h after PCI and at 12, 20, 24 and 48 h after the onset of AMI. According to the peak BNP concentration, the patients were divided into high peak BNP group (> 400 pg/mL) and normal peak BNP group (≤400 pg/mL). RESULTS: Seventy patients were enrolled in the study. Within 48 h after AMI onset, BNP concentration variations followed a pattern of an initial increase till reaching the peak concentration at 20 to 24 h, with subsequent gradual decrease. BNP concentrations differed significantly among the indicated time points (χ2=141.7, P < 0.05) except for those between 20 h and 24 h (χ2=0.173, P > 0.05). Compared with those in normal peak BNP group, the patients in high peak BNP group had an older age, a lower BMI, a longer time to perfusion, and a higher likeliness of anterior myocardial infarction and pulmonary infection (P < 0.05). Logistic regression analysis showed that age, BMI and anterior myocardial infarction were independently associated with the increase of peak BNP concentration. ROC curve analysis showed that BNP concentration within 1 h after emergency PCI was unable to diagnose heart failure at that time (P > 0.05), while BNP concentrations at 12, 20, 24 and 48 h after AMI onset had significant diagnostic values for heart failure (P < 0.05) with areas under ROC of 0.860, 0.786, 0.768 and 0.863, and optimal cutoff values of 156.5, 313.7, 240.9 and 285.9 pg/mL, respectively. CONCLUSIONS: BNP concentration increases first and then decreases in the early phase of AMI, and the peak concentration occurs at 20-24 h after the onset. The diagnostic values of BNP concentrations at different time points also vary.

[Impact of establishing regional collaborative network on reperfusion time and prognosis of patients with ST-segment elevated myocardial infarction admitting to community hospitals without percutaneous coronary intervention capacity].

OBJECTIVE: To investigate the impact of establishing regional collaborative network on reperfusion time and prognosis of patients with ST-segment elevated myocardial infarction (STEMI) admitting to community hospitals without percutaneous coronary intervention (PCI) capacity (Non-PCI hospital). METHODS: A regional collaborative network was developed, consisting of a PCI center and over 30 Non-PCI hospitals and connected by a tele-transmitted real-time 12-lead electrocardiogram system. This system enables the cardiologists on duty in PCI center to help the physicians in the Non-PCI hospitals (network hospital) to confirm the diagnosis and choose a reperfusion strategy for STEMI patients. All cardiologists in PCI center and physicians in Non-PCI hospitals were trained to follow the flowchart of reperfusion strategies for STEMI patients to shorten the reperfusion time. The mean time from door of Non-PCI hospital to needle of thrombolysis (D-to-N), the mean time from door of PCI center to balloon (D-to-B) and the mean time from the first medical contact to balloon (FMC-to-B) and the 1-year mortality were compared between the 20 months before and the 20 months after establishment of the regional collaborative network for patients with the first medical contact in three network hospitals. RESULTS: After establishment of the regional collaborative network, the mean D-to-N time was significantly shortened from (71 ± 62) min to (28 ± 9) min (P < 0.05), the rate of D-to-N below 30 min was increased from 11% (2/18) to 74% (26/35); the mean FMC-to-B and the mean D-to-B time were remarkably reduced in both complementary percutaneous coronary intervention and transfer percutaneous coronary intervention patients (all P < 0.05), the 1-year mortality post reperfusion was reduced from 15.1% (8/53) to 7.0% (10/142) (P < 0.05). CONCLUSION: The establishment of regional collaborative network could shorten the perfusion time and reduce the 1-year mortality for STEMI patients presenting to Non-PCI hospitals.

[Impacts of establishment of chest pain center on the door-to-balloon time and the short-term outcome after primary percutaneous coronary intervention of patients with ST segment elevated myocardial infarction].

OBJECTIVE: To investigate the impact of the establishment of chest pain center (CPC) model based on the pre-hospital real-time tele-12-lead electrocardiogram on the door-to-balloon (D-to-B) time and short-term outcome after primary percutaneous coronary intervention (PPCI) of patients with ST-segment elevated myocardial infarction (STEMI). METHODS: A regular CPC was established with pre-hospital transmitted real-time 12-lead electrocardiogram system for pre-hospital diagnosis of STEMI and enabled the STEMI patients to bypass the emergency room and directly treated in the catheter lab to shorten the D-to-B time. The mean D-to-B time, the short-term outcome and medical costs were compared in PPCI patients before (93 cases, group A) and after (149 cases, group B) the establishment of CPC. RESULTS: After the establishment of CPC, the annual mean D-to-B time was significantly shortened [(127 ± 79) min in group A vs.(72 ± 23 )min in group B, P < 0.01], the shortest monthly mean D-to-B time was remarkably reduced in group B than in group A [(56 ± 11) min vs. (73 ± 14) min, P < 0.01]. The annual ratio of D-to-B below 90 minutes was significantly increased from 62.4% (58/93) in group A to 91.9% (137/149) in group B (P < 0.05) . The in-hospital mortality rate tended to be lower and the incidence of heart failure during hospitalization was significantly reduced in group B compared with group A [3.4% (5/149) vs. 6.5% (6/93), P > 0.05; 14.1% (21/149) vs. 24.7% (23/93), P < 0.05]. The length of hospital stay was slightly shortened from (8.98 ± 4.89) days to (7.79 ± 5.43) days (P > 0.05). Corrected mean medical cost went down by 9.4% (P < 0.05). CONCLUSION: The establishment of CPC may significantly shorten the D-to-B time, improve the short-term outcome and reduce the hospitalization cost for PPCI patients with STEMI.