The study aimed to evaluate the therapeutic effect of nilotinib-loaded biocompatible gelatin methacryloyl (GelMA) microneedles patch on cardiac dysfunction after myocardial infarction(MI), and provide a new clinical perspective of myocardial fibrosis therapies. The GelMA microneedles patches were attached to the epicardial surface of the infarct and peri-infarct zone in order to deliver the anti-fibrosis drug nilotinib on the 10th day after MI, when the scar had matured. Cardiac function and left ventricular remodeling were assessed by such as echocardiography, BNP (brain natriuretic peptide) and the heart weight/body weight ratio (HW/BW). Myocardial hypertrophy and fibrosis were examined by WGA (wheat germ agglutinin) staining, HE (hematoxylin-eosin staining) staining and Sirius Red staining. The results showed that the nilotinib-loaded microneedles patch could effectively attenuate fibrosis expansion in the peri-infarct zone and myocardial hypertrophy, prevent adverse ventricular remodeling and finally improve cardiac function. This treatment strategy is a beneficial attempt to correct the cardiac dysfunction after myocardial infarction, which is expected to become a new strategy to correct the cardiac dysfunction after MI. This is of great clinical significance for improving the long-term prognosis of MI patients.
Humans ; Myocardial Infarction/drug therapy* ; Cardiomegaly ; Natriuretic Peptide, Brain/therapeutic use* ; Fibrosis ; Myocardium/pathology*

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Hypertension ; drug therapy ; pathology ; physiopathology ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Phytotherapy ; Ventricular Remodeling ; drug effects

OBJECTIVETo compare the acute myocardial infarction models in Beagle dogs and mongrel dogs, and study whether the Beagle dog model is sensitive to drug intervention.

METHODThe acute myocardial infarction model of dog was set up through ligation of anterior descending branch of coronary artery in dogs, in order to observe morphological changes of the heart and determine artery length and heart coefficient of exposed anterior descending branch of coronary artery. The epicardium electrocardiogram (sigmaST, N-ST) was used to measure the degree of myocardial ischemia. The quantitative histological assay (nitroblue tetrazolium, N-BT stain) was adopted to determine the area of myocardial infarction.

RESULTThere was no significant difference between Beagle dogs and mongrel dogs in terms of sigmaST, N-ST and ischemia area. The diltiazem group of Beagle dogs showed obvious reduction in the ischemia area (P < 0.05 and P < 0.01), with notable decline in sigmaST and N-ST, however, it had no statistical difference compared with the Beagle dog model group. Beagle dogs had clear coronary branches, longer exposed arteries and less difference in organ coefficient, which were suitable for the preparation of the myocardial infarction model, whereas mongrel dogs had irregular coronary branches and exposed arteries, with greater individual difference.

CONCLUSIONBeagle dogs are superior to mongrel dogs in the preparation of the acute myocardial infarction model, which is sensitive to for drug intervention.

Acute Disease ; Animals ; Disease Models, Animal ; Dogs ; Electrocardiography ; Female ; Male ; Myocardial Infarction ; drug therapy ; pathology ; Myocardium ; pathology

BACKGROUNDA growing volume of data suggests that simple manual thrombus aspiration followed by direct stenting improves myocardial reperfusion and clinical outcome compared with conventional primary PCI, but there is still limited data comparing the in vivo performance among different devices. This study aimed to compare the efficacy and operability of thrombus aspiration by the Diver CE (Invatec, Brescia, Italy) and ZEEK (Zeon Medical Inc., Tokyo, Japan) aspiration catheters in ST-segment elevation myocardial infarction (STEMI) and their impact on 3-month outcome.

METHODSFrom September 2004 to June 2008, 298 consecutive patients with STEMI who received manual thrombus aspiration were involved in a single center retrospective analysis. Of them, 229 and 69 were treated with Diver CE and ZEEK aspiration catheters, respectively. Primary endpoints were myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade, ST-segment elevation resolution (STR), device pushability and trackability as judged by the frequency of usage of dual guide wires and aspiration efficacy as indicated by size distribution of aspirated thrombi. Secondary endpoints were 3-month outcome including left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), as well as cardiac death, target lesion revascularization (TLR), re-infarction and their combination as major adverse cardiac events (MACE).

RESULTSBaseline characteristics were not different between the two groups expect for a higher frequency of temporary cardiac pacing in the ZEEK group (ZEEK) than in the Diver CE group (Diver CE) (0.44% vs 5.8%, P = 0.002). Visible retrieved thrombi were achieved in 65.9% of the Diver CE and 68.1% of the ZEEK (P = 0.74). Aspirated thrombi were categorized as small thrombi (< 3.5 mm), moderate thrombi (3.5-7.0 mm) and large thrombi (> 7.0 mm). Small thrombi were more frequently seen in the Diver CE (61.6% vs 42.6%), whereas moderate and larger thrombi were more frequently found in the ZEEK (38.4% vs 57.4%) (P = 0.021). Rates of dual wire utilization were 1.7% of the Diver CE and 7.2% of the ZEEK (P = 0.052). There were no differences in MBG, STR and TIMI flow grade between the two groups. No differences were found in cardiac death, TLR, re-infarction, MACE, LVEDD and LVEF between the Diver CE and the ZEEK during 3-month follow-up.

CONCLUSIONSBoth Diver CE and ZEEK manual aspiration catheters are effective for thrombectomy in STEMI. In clinical practice, ZEEK presents a stronger aspiration capacity for moderate to large thrombi compared with Diver CE, but Diver CE displays a trend towards better pushability and trackability than ZEEK. Differences in aspiration capacity and operability between Diver CE and ZEEK in this setting do not influence myocardial reperfusion and 3-month outcome.

Coronary Angiography ; Echocardiography ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; pathology ; surgery ; Thrombectomy ; instrumentation ; methods ; Treatment Outcome

BACKGROUNDCurrent guidelines support primary percutaneous coronary intervention (primary PCI) as the first treatment of choice (as opposed to thrombolytic therapy) for patients with acute ST-segment elevation myocardial infarction (STEMI) especially when delivered within 12 hours of symptom onset. We aimed to evaluate the impact of different clinical pathways on reduction of reperfusion delay and subsequent improvement in outcomes in patients with STEMI.

METHODSFrom November 2005 to November 2007, 546 consecutive patients with definite STEMI, who upon arrival at the emergency room were triaged to undergo primary PCI, were included. Of them, 271 patients were brought directly to catheterization laboratory (rapid group), and 275 patients were admitted to the coronary care unit (CCU) or cardiac ward first, and then transferred to the catheterization laboratory (non-rapid group). Primary endpoint was door-to-balloon (D2B) time, and secondary endpoints included infarct size assessed by peak CK-MB level and rates of major cardiac adverse events (MACE) including death, reinfarction, or target-vessel revascularization during hospitalization and at 30-day clinical follow-up.

RESULTSBaseline clinical characteristics, angiographic features and procedural success rates were comparable between the two groups, except that more patients received glycoprotein IIb/IIIa receptor inhibitors before angiography (84.0% and 77.1, P = 0.042) and had TIMI 3 flow in the culprit vessel at initial angiogram (17.1% and 9.2%, P = 0.007) in the non-rapid group. The D2B time was shortened ((108 +/- 44) minutes and (138 +/- 31) minutes, P < 0.0001), and number of patients with D2B time < 90 minutes was greater (22.6% and 10.9%, P < 0.0001) in the rapid group. The advantages associated with rapid intra-hospital transfer were enhanced if the patients presented to the hospital at regular hours. Peak CK-MB level was significantly reduced in the rapid group. In-hospital mortality (4.1% and 5.8%) and cumulative MACE rate (7.0% and 9.8%) did not significantly differ between rapid and non-rapid groups. At 30 days, cumulative death- and MACE-free survival rates were improved in the rapid group (94.5% and 89.5%, P = 0.035; 90.1% and 84.0%, P = 0.034, respectively).

CONCLUSIONSClinical pathway with bypass of CCU/cardiac ward admission was associated with rapid reperfusion, smaller infarct size, and improved short-term survival for patients with STEMI undergoing primary PCI. In the future, it is essential to reduce the time delay for patients presenting at off-hours.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Critical Pathways ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; mortality ; pathology ; therapy ; Prognosis ; Survival Analysis ; Time Factors ; Treatment Outcome

Prinzmetal's variant angina describes chest pain secondary to reversible coronary artery vasospasm in the context of both diseased and non-diseased coronary arteries. Symptoms typically occur when the patient is at rest and are associated with transient ST-segment elevation. Acute episodes respond to glyceryl trinitrate, but myocardial infarction and other potentially fatal complications can occur, and long-term management can be challenging. Although it is not well understood, the underlying mechanism appears to involve a combination of endothelial damage and vasoactive mediators. In this case, a 35-year-old woman with myocardial infarction secondary to coronary artery vasospasm experienced recurrent chest pain. Coronary angiography revealed severe focal stenosis in the mid left anterior descending artery, which completely resolved after administration of intracoronary glyceryl trinitrate. The patient was discharged on nitrates and calcium channel blockers. The patient re-presented with another myocardial infarction, requiring up-titration of medical therapy.
Adult ; Angina Pectoris, Variant ; complications ; drug therapy ; Constriction, Pathologic ; drug therapy ; pathology ; Coronary Angiography ; Coronary Vasospasm ; Coronary Vessels ; physiopathology ; Electrocardiography ; Female ; Humans ; Myocardial Infarction ; complications ; drug therapy ; pathology ; Nitroglycerin ; therapeutic use ; Recurrence ; Vasodilator Agents ; therapeutic use

BACKGROUNDIt has been reported that osteopontin has an important role in cardiac fibrosis and remodeling. However, its direct mechanisms remain unclear. The purpose of this study was to investigate the role of angiotensin and aldosterone blockades in cardiac osteopontin expression associated with cardiac remodeling in myocardial infarcted (MI) rats.

METHODSFifty SD rats that survived 24 hours after ligating left anterior descending coronary artery were randomly divided into three groups: MI-saline group (n = 15, 5 ml/d), MI-perindopril group (n = 18, perindopril 2 mgxkg(-1)d(-1)) and MI-spironolacton (n = 17, spironolacton 20 mgxkg(-1)xd(-1)). A sham operation group (n = 15) was selected as non-infarcted control. At 6 weeks after treatment, hemodynamic pararmeters and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameters were evaluated histologically. Myocardium osteopontin protein expression level in the non-infarcted myocardium was detected by Western blotting.

RESULTSNo osteopontin protein was detected in the myocardium of sham-operation rats. High levels of osteopontin protein expression were detected in the MI-saline rats, but the levels were suppressed in the MI-perindopril and MI-spironolacton rats at 6 weeks following MI (P < 0.01, respectively). Compared with the sham operation group, all rats in the MI group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter (P < 0.01, respectively), and developed significant systolic and diastolic dysfunction as indicated by decreased left ventricular systolic pressure (LVSP) and +/-dp/dt, as well as increased left ventricular end-diastolic pressure (LVEDP) (P < 0.01, respectively). Angiotensin and aldosterone blockades partly prevented cardiac fibrosis and systolic and diastolic dysfunction (P < 0.01, respectively).

CONCLUSIONTreatment with angiotensin and aldosterone blockades inhibits expression of osteopontin in the non-infarcted myocardium and prevents cardiac remodeling following MI.

Angiotensins ; antagonists & inhibitors ; Animals ; Fibrosis ; Hemodynamics ; Male ; Mineralocorticoid Receptor Antagonists ; pharmacology ; Myocardial Infarction ; drug therapy ; pathology ; physiopathology ; Myocardium ; chemistry ; pathology ; Osteopontin ; analysis ; Rats ; Rats, Sprague-Dawley

One of the leading causes of death worldwide is cardiovascular disease, hence searching for a cure is an important endeavor. The totally safe, edible, and inexpensive Boswellia plant exudate, known as olibanum or frankincense, is considered to possess diverse medicinal values in traditional medicine and from recent biological studies. Investigating the cardioprotective and antioxidant activities of olibanum from a Boswellia species, family Bursearaceae, namely Boswellia carteri Birdw. was the aim of this study. Cardioprotective activity was evaluated using a model of myocardial infarction induced by isoprenaline (ISO), while antioxidant activity was tested adopting nitric oxide scavenging (NOS) and azino-bis-3-ethyl benzthiazoline-6-sulfonic acid (ABTS) assays. The results revealed a mild cardioprotective effect and weak antioxidant activity.
Animals ; Antioxidants ; administration & dosage ; analysis ; Boswellia ; chemistry ; Frankincense ; administration & dosage ; analysis ; Humans ; Male ; Myocardial Infarction ; drug therapy ; pathology ; Myocardium ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo observe the protective effect of combined administration of blood-activating drug and sedative drug on myocardial injury of acute myocardial infarction (AMI) rats.

METHODThe acute myocardial infarction (AMI) model was established by occluding the left descending coronary artery of Wistar rats. These rats were further divided into four groups (n = 15 per group): the sham-operated group, the AMI model group, the blood-activating drug group and the combined administration group.

RESULTCompared with the sham-operated group, the AMI model group showed significant decrease in ejection fraction (EF) and fractional shortening (FS) (P < 0.001) and notable increase in the left ventricular end-diastolic internal diameter (LVIDd) and left ventricular end-systolic internal diameter (LVIDs) (P < 0.01), with the infarct area of left ventricular front wall up to about 70%-90%. Besides, tissue was severely replaced by collagen deposition and fibrosis, the sarcomeres disorganized and mitochondrial abnormalized. Compared with the AMI model group, the blood-activating drug group and the combined administration group showed significant increase in the values of EF and FS (P < 0.05 or P < 0.01) and obvious reduction in LVIDd and LVIDs (P < 0.05 or P < 0.01), with the infarction area of left ventricular front wall up to about 40%-60%. The collagen deposition and myocardium fibrosis, the disorganized sarcomeres and mitochondrial abnormalities relieved significantly. And compared with blood-activating drug group, the combined administration group demonstrated further increase in the values of EF and FS and further decrease in LVIDd and LVIDs (P < 0.05), the collagen deposition and myocardium fibrosis, the disorganized sarcomeres and mitochondrial abnormalities relieved even more in Huoxue plus Anshen prescription group.

CONCLUSIONThe combined administration of blood-activating drug and sedative drug can further improve cardiac structure and function after myocardial ischemia infarction and have an obvious synergistic effect which may be related to sedative drug's effect of resisting lipid peroxide, stabling myocardial cell membrane and mitochondrial membrane and relieving cardiac cell injury.

Animals ; Drugs, Chinese Herbal ; therapeutic use ; Hypnotics and Sedatives ; therapeutic use ; Lipid Peroxidation ; drug effects ; Male ; Myocardial Infarction ; drug therapy ; pathology ; Rats ; Rats, Wistar

OBJECTIVETo test whether postconditioning could inhibit the expression of phospho-JNK (P-JNK) mitogen activated protein kinase (MAPK) and study its relation to apoptosis of cardiocyte.

METHODSSixty rats were randomly divided into six groups: sham, reperfusion injury (R/I), postconditioning (Post), SP600125 (I_JNK), anisomycin and postconditioning (Ani+Post) and anisomycin (Ani) groups. After acute myocardial infarction was induced in rats, placebo solution (DMSO), SP600125 (6 mg/kg) or anisomycin (2 mg/kg) was injected through jugular vein 5 min before reperfusion; 6 h later 3 rats of each group were executed and the hearts were separated to measure the signaling molecules (phospho-JNK, TNF alpha, Caspase-8, Bcl-2/Bax, cytochrome-c). Twenty-two hours later hemodynamic data were measured in the left rats, and then blood samples were taken to determine serum markers of cardiac damage, and hearts were separated to measure the infarction area and cardiocyte apoptosis.

RESULTPostconditioning improved +/-DP/DTmax of left ventricle, limited infarct area, relieved apoptosis and necrosis of cardiocytes, and inhibited the expression of P-JNK (1.12 +/-0.21 Compared with 1.90 +/-0.32, P<0.05). At the same time the levels of TNFalpha Caspase-8, Bax and Cyt-c were lower in Post group than those in R/I group, but Bcl-2 expression levels were higher. I_JNK group presented the similar protection effect of postconditioning [TUNEL index: (6.23 +/-2.43)% Compared with (18.22 +/-5.10)%, P<0.05; Infarct area: (23.44 +/-6.34)% Compared with (42.31 +/-8.21)%, P<0.05]. On the other hand, Ani+Post group partially lost cardioprotection effect [TUNEL index: (14.12 +/-2.00)% Compared with (18.22 +/-5.10)%,P>0.05; Infarct area: (35.27 +/-5.28)% Compared with (42.31+/-8.21)%,P>0.05], because of the activation of JNK MAPK.

CONCLUSIONPostconditioning can inhibit phosphorylation of JNK MAPK, which attenuates cardiocyte apoptosis by both extrinsic and mitochondria pathway.

Animals ; Apoptosis ; drug effects ; Ischemic Preconditioning, Myocardial ; JNK Mitogen-Activated Protein Kinases ; metabolism ; pharmacology ; Male ; Myocardial Infarction ; enzymology ; pathology ; therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; enzymology ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley