Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction.

Previous studies have shown that intracoronary (IC) nitroprusside (NTP) injection is a safe and effective strategy for the treatment of no-reflow (NR) during percutaneous coronary intervention (PCI). The present study tested the hypothesis that, on the basis of thrombus aspiration for the treatment of ST-segment elevation myocardial infarction (STEMI), the selective IC administration of a fixed dose of NTP (100 µg) plus tirofiban is a safe and superior treatment method compared with the IC administration of tirofiban alone for the prevention of NR during primary PCI. A total of 162 consecutive patients with STEMI, who underwent primary PCI within 12 h of onset, were randomly assigned to two groups: Group A, IC administration of a fixed dose of NTP (100 µg) plus tirofiban (10 µg/kg) and group B, IC administration of tirofiban (10 µg/kg) alone (n=80 and n=82, respectively). The drugs were selectively injected into the infarct-related artery (IRA) via a thrombus aspiration catheter advanced into the IRA. The primary end-point was post-procedural corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The proportion of complete (>70%) ST-segment resolution (STR); the TIMI myocardial perfusion grade (TMPG) 2-3 ratio following PCI; the peak value of creatine kinase (CK)-MB; the TIMI flow grade; the incidence of major adverse cardiac events (MACEs) and the left ventricular ejection fraction (LVEF) after 6 months of follow-up were observed as the secondary end-points. There were no significant differences in the baseline clinical and angiographic characteristics between the two groups. Compared with group B, group A had i) a lower CTFC (23±7 versus 29±11, P=0.000); ii) a higher proportion of complete STR (72.5 versus 55.9%, P=0.040); iii) an enhanced TMPG 2-3 ratio (71.3 versus 53.7%, P=0.030) and iv) a lower peak CK-MB value (170±56 versus 210±48 U/l, P=0.010). There were no statistically significant differences in the final TIMI grade-3 flow between the two groups (92.5 versus 91.5% for groups A and B, respectively; P=0.956). The LVEF at 6 months was higher in group A than group B (63±9 versus 53±11%, respectively; P=0.001); however, the incidence of MACEs was not statistically different between the two groups, although there was a trend indicating improvement in group A (log rank χ2=0.953, P=0.489). The selective IC administration of a fixed dose of NTP (100 µg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA is a safe and superior treatment method compared with tirofiban alone in patients with STEMI undergoing primary PCI. This novel therapeutic strategy improves the myocardial level perfusion, in addition to reducing the infarct size. Furthermore, it may improve the postoperative clinical prognosis following PCI.

The chronergy of recombinant streptokinase thrombolysis in acute myocardial infarction.

The aim of this study was to explore the chronergy of intravenous recombinant streptokinase (r-SK) in patients with acute myocardial infarction (AMI). A total of 114 patients were divided into two groups according to the time of AMI onset: the morning onset (6:01-12:00, n=53) and non-morning onset (12:01-06:00, n=61) groups. The recanalization rate was recorded, as well as anticoagulant and fibrinolytic indices. Statistical analysis was performed to evaluate the recanalization rate following thrombolysis, as well as the anticoagulant and fibrinolytic activities. The recanalization rates following thrombolysis in the morning onset and non-morning onset groups were 60.4 and 82.0%, respectively (P<0.05). The level of plasminogen activator inhibitor-1 (PAI-1) antigen was significantly higher in the morning onset group compared with that in the non-morning onset group (P<0.05). This indicated a resistance to r-SK thrombolysis in the morning at the early stage of AMI, which possibly correlates with increased PAI-1 antigen levels and activity.

Combination of fluvastatin and losartan relieves atherosclerosis and macrophage infiltration in atherosclerotic plaques in rabbits.

AIM: To investigate whether the combination of fluvastatin and losartan synergistically relieve atherosclerosis and plaque inflammation induced by a high-cholesterol diet in rabbits. METHODS: Atherosclerosis was induced with a high-cholesterol diet for 3 months in 36 New Zealand white rabbits. The animals were randomly divided into model group, fluvastatin (10 mg·kg(-1)·d(-1)) group, losartan (25 mg·kg(-1)·d(-1)) group, and fluvastatin plus losartan group. After the 16-week treatments, the blood samples the animals were collected, and the thoracic aortas were examined immunohistochemically. The mRNA and protein expression levels of monocyte chemotactic protein-1 (MCP-1) were measured using RT-PCR and Western blot. RESULTS: Compared to the treatment with losartan or fluvastatin alone, the combined treatment did not produce higher efficacy in reduction of blood cholesterol level. However, the combination did synergistically decrease the intimal and media thickness of thoracic aortas with significantly reduced macrophage infiltration and MCP-1 expression in the plaques. CONCLUSION: The combined treatment with losartan and fluvastatin significantly inhibited atherosclerotic progress and reduced inflammation associated with atherosclerotic plaques.

[Overexpression of angiotensin converting enzyme 2 inhibits inflammatory response of atherosclerotic plaques in hypercholesterolemic rabbits].

OBJECTIVE: Angiotensin converting enzyme 2 (ACE2) efficiently hydrolyses the potent vasoconstrictor angiotensin II to vasodilative angiotensin (1-7). We hypothesized that ACE2 overexpression may inhibit inflammation response in atherosclerotic plaque by degrading Ang II into Ang-(1-7). METHODS: Atherosclerosis (AS) plaques were induced in the abdominal aorta of 38 rabbits by endothelial injury and atherogenic diet for 3 months. Rabbits were then underwent injection of a recombinant adenovirus (2.5 x 10(9) pfu/ml) carrying a murine ACE2 gene (Ad-ACE2) through a catheter into the abdominal aortic segments rich in plaques (n = 19) or injection of a control vector Ad-EGFP (n = 19). One month later, all rabbits were sacrificed and plaques from aortic segments were analyzed. RESULTS: ACE2 expression in aortic tissues of the Ad-ACE2 group were confirmed by immunohistochemistry. Macrophage infiltration (13.6% +/- 4.2% vs. 23.6% +/- 6.9%, P < 0.01) and MCP-1 expression (13.2% +/- 0.4% vs. 25.0% +/- 7.4%, P < 0.01) were significantly reduced in Ad-ACE2 group compared to Ad-EGFP group. CONCLUSIONS: Overexpression of ACE2 inhibited atherosclerotic plaque inflammation response in hypercholesterolemic rabbits.

Overexpression of ACE2 enhances plaque stability in a rabbit model of atherosclerosis.

OBJECTIVE: The purpose of this study was to test the hypothesis that ACE2 overexpression may enhance atherosclerotic plaque stability by antagonizing ACE activity and converting angiotensin II to angiotensin 1-7. METHODS AND RESULTS: Atherosclerotic plaques were induced in the abdominal aorta of 114 rabbits by endothelial injury and atherogenic diet. Gene therapy was performed in group A at week 4 and in group B at week 12, respectively. Each group of rabbits were randomly divided into 3 subgroups which received, respectively, a recombinant ACE2 expressing vector (AdACE2), a control vector AdEGFP and AdACE2+A779, an antagonist of angiotensin 1-7 receptor. Local ACE2 overexpression attenuated the progression of lesions from week 4 to week 8, but not progression of plaque size from week 12 to week 16. In group B rabbits, local ACE2 overexpression resulted in stable plaque compositions, ie, fewer macrophages, less lipid deposition and more collagen contents, higher plaque stability scores, decreased angiotensin II levels, and increased angiotensin 1-7 levels in plaque tissues in the AdACE2 subgroup compared with those in the AdEGFP subgroup. CONCLUSIONS: Overexpression of ACE2 results in stabilized atherosclerotic plaques and the mechanism is probably the conversion of vasoconstrictive angiotensin II to vessel protective angiotensin 1-7.