| Chapter 1 Effect of Tirofiban Administered by Different Routes on Rabbit Myocardial Ischemia Reperfusion and Its MechanismObjective:To study the effect of tirofiban administered by different routes on myocardial ischemia reperfusion and its possible mechanism, so as to provide theoretical basis for clinical research and application.Methods:A total of 50 healthy male New Zealand white rabbits were randomly and equally divided into five groups. Models of myocardial ischemia reperfusion injury (MIRI) were constructed by ligaturing the left anterior descending (LAD) coronary artery. (1) Group A:Sham-operation was performed, in which the LAD was threaded without ligation. (2) Group B:Group B was the ischemia reperfusion group, the LAD of which was subjected to 60 min of myocardial ischemia followed by 120 min of reperfusion. (3) Group C:The LAD was subjected to 60 min of myocardial ischemia followed by 120 min of reperfusion, and the LAD was given tirofiban by intravenous injection at a dose of 50μg/kg 5 min before reperfusion. (4) Group D:The LAD was subjected to 60 min of myocardial ischemia followed by 120 min of reperfusion, and the LAD was given tirofiban by intracoronary injection at a dose of 50μg/kg 5 min before reperfusion. (5) Group E:The LAD was subjected to 60 min of myocardial ischemia followed by 120 min of reperfusion, and at the same time when reperfusion began, the LAD was given tirofiban by intracoronary injection at a dose of 50μg/kg. The ligation area (LA), infarct area (IA) and area of no reflow (ANR) were observed and compared among different groups. The activity of superoxide dismutase (SOD), the content of serum malondialdehyde (MDA), the concentration of Ca2+ in cardiac muscle cells, the activity of serum nitric oxide synthase (NOS), the contents of toll-like receptor-4 (TLR-4) and tumor necrosis factor-α (TNF-α) were also measured and compared among different groups.Results:The IA and ANR in group C, group D and group E were significantly reduced compared with those in group B (P<0.05), especially group E, which showed statistically significant difference compared with group C and group D (P<0.05), but there was no statistically significant difference between group C and group D (P>0.05).In group B, C, D and E, the activities of SOD and eNOS were significantly reduced, but the concentration of serum MDA, the concentration of Ca2+ in cardiac muscle cells, the activity of iNOS and the expressions of TLR-4 and TNF-α were all significantly increased, all of which had statistically significant difference compared with those in group A (P< 0.05).Conversely, in group C, D and E, the activities of SOD and eNOS were significantly increased, whereas the concentration of serum MDA, the concentration of Ca2+ in cardiac muscle cells, the activity of iNOS and the expressions of TLR-4 and TNF-α were all significantly reduced, all of which had statistically significant difference compared with group B (P<0.05).In group E, the activities of SOD and eNOS were both higher than those in group C and D (P<0.05), while the concentration of serum MDA and the concentration of Ca2+ in cardiac muscle cells, the activity of eNOS and the expressions of TLR-4 and TNF-α were all lower than those in group C and D, all of which had statistically significant difference (P<0.05). No statistically significant difference was found between group C and group D (P>0.05).Conclusion:Tirofiban can reduce myocardial infarction and ANR after myocardial ischemia reperfusion. Possible mechanisms include increasing SOD activity, reducing MDA content and effectively inhibiting the accumulation of oxygen free radicals; effectively reducing the concentration of Ca2+ and inhibiting the calcium overload in cardiac muscle cells; increasing tNOS activity, reducing iNOS activity and improving the vascular endothelial function; reducing the concentrations of TLR-4 and TNF-a, as well as inhibiting inflammatory reactions.Administration of tirofiban by intracoronary injection at the same time when reperfusion begins is the best route of administration compared with intravenous and intracoronary injection before reperfusion.Chapter 2 Curative Effect of Tirofiban Administered by Different Routes on Emergency PCI in Patients with STEMIObjective:To study the effect of tirofiban administered by different routes on emergency percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEM), so as to explore the optimal administration route of tirofiban in emergency PCI for patients with STEMMethods:A total of 96 patients with acute STEM who underwent emergency PCI and thrombus aspiration in our hospital from July 2012 to December 2014 were chosen and divided into three groups based on the administration routes of tirofiban, namely group A (intravenous injection group,27 cases), group B (intracoronary injection group,39 cases) and group C (modified intracoronary injection, 30 cases). Patients in three groups all underwent emergency PCI and thrombus aspiration combined with tirofiban administered by different routes. In group A, tirofiban was administered by intravenous injection at a loading dose of 10μg/kg 30 min before PCI. In group B, tirofiban was administered by intracoronary injection at a dose of 10μg/kg after the guiding catheter was placed. In group C, after the guidewire passed the lesion, the thrombus aspiration catheter was placed to the distal end of infarct-related artery to administer tirofiban at a dose of 10μg/kg. Then tirofiban was intravenously pumped at a dose of 6μg/kg/h for 24-36h in patients of all the groups. The corrected TIM frame count (CTFC), myocardial blush grade (MBG), ST segment resolution rate, peak value of blood TnI, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), perioperative hemorrhagic complications and major adverse cardiac events (MACE) in 1 month after discharge were also recorded and compared.Results:The incidence of reperfusion arrhythmia as well as the CTFC and TnI in goup C were significantly lower than those in group A and group B (P<0.05), whereas the MBG, ST segment resolution rate, LVEF and LVEDD in group C were all significantly higher than those in group A and group B (P<0.05). There was no statistically significant difference between group A and group B (P>0.05). In group A,2 cases had slightly bleeding and 1 case died from cardiac arrest during PCI, and no severe bleeding occurred. In group B and group C, no bleeding and death occurred. No MACE cases such as new myocardial infarction and repeated revascularization occurred in three groups. The CTFC and TnI in group C were significantly lower than those in group A and group B 1 month after discharge (P< 0.05), whereas the MBG, ST-segment resolution rate, LVEF and LVEDD were all significantly higher than those in group A and group B (P<0.05).Conclusion:Intracoronary injection of tirofiban at the distal end of IRA through the thrombus aspiration catheter is superior to traditional intravenous or intracoronary injection in improving the myocardial microcirculation and short-term left ventricular systolic function after PCI, and has good safety. |
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