冠状动脉内应用国产替罗非班对急性ST段抬高心肌梗死急诊介入治疗后心肌灌注和临床预后的影响

目的 探讨急性ST段抬高心肌梗死急诊PCI时国产替罗非班的不同应用途径（静脉内／冠状动脉内）对心肌组织水平灌注与临床预后影响的差异。方法 连续选择60例急性ST段抬高心肌梗死拟行急诊PCI的患者,随机分为替罗非班静脉内应用组（静脉组,n=30）与替罗非班冠状动脉内应用组（冠状动脉组,n=30）,比较两组术后即刻造影结果、住院期间以及随访期间主要不良心脏事件（MACE）发生的差异。结果共有54例完成试验,其中男性43例,女性11例,年龄29～75（58．80±12．57）岁,冠状动脉组在术后心外膜TIMI分级、TIMI心肌灌注分级（TIMI Myocardial Perfusion,TMP）、心电图ST段回落、梗死相关血管远端末梢栓塞、以及治疗后5～7天的心脏彩超射血分数值、左室舒张末期容积（LVEDV）、左室收缩末期容积（LVESV）等方面均显著优于静脉组,虽然心脏肌钙蛋白I（cTnI）与肌酸激酶同工酶（CK-MB）峰值浓度两组无差异,但是冠状动脉组CK-MB达峰值的时间显著缩短,两组院内MACE事件发生未达到统计学差异,平均住院日亦相同,但是30～90（平均57±21）天随访期间冠状动脉组总的MACE事件发生显著少于静脉组（7．1％与30．8％,P=0．02）。应用Cox回归比例风险模型在校正年龄、性别、高血压、糖尿病、家族史、吸烟等危险因素以及心肌梗死部位、胸痛至球囊扩张时间后,计算冠状动脉组在平均57天随访期间发生总的MACE事件的相对危险度为0．14（P=0．03）。冠状动脉组发生轻度出血与严重出血并发症有增多的趋势,但未达到统计学差异。结论 对于急性ST段抬高心肌梗死行急诊PCI治疗的患者,冠状动脉内应用替罗非班安全、有效,与静脉内应用相比可以进一步改善心肌水平再灌注状态并能提高临床预后,这对于在急诊室因为各种原因未能提前应用替罗非班的患者来说具有特殊的临床意义。     

Effects of intracoronary dipyridamole infusion on regional myocardial blood flow and intrinsic thallium-201 washout in dogs with a critical coronary stenosis.

Intravenous dipyridamole (DP) infusion produces a significant endocardial-to-epicardial flow gradient distal to a critical coronary stenosis, resulting in diminished regional thallium-201 (Tl-201) uptake and washout. Intravenous DP can also produce a significant decrease in arterial blood pressure and therefore in coronary perfusion pressure. We determined to further clarify the mechanism of this transmural coronary "steal" employing intracoronary DP administration, thereby avoiding systemic hypotension. In five of eight dogs with a critical left anterior descending (LAD) stenosis, intracoronary DP caused no significant fall in systemic arterial pressure, a rise in epicardial flow from 1.15 +/- 0.2 to 1.75 +/- 0.2 ml/min/gm, and a slight fall in subendocardial flow from 1.15 +/- 0.2 to 1.03 +/- 0.5 ml/min/gm. Intracoronary DP caused no prolongation of the intrinsic Tl-201 washout rate. In three dogs that developed systemic hypotension after intracoronary DP, endocardial flow fell from 1.14 to 0.63 ml/min/gm, the epicardial/endocardial flow ratio fell to 0.35, and Tl-201 washout became more prolonged. Thus intracoronary DP in the setting of a critical LAD stenosis caused minimal endocardial-to-epicardial steal and had no effect on the intrinsic Tl-201 washout rate unless it was accompanied by a fall in systemic arterial pressure. The magnitude of the transmural steal was substantially less than reported in our previous experiments utilizing intravenous DP infusion. This study provides a further insight into the mechanism of DP-induced subendocardial ischemia and suggests that systemic hemodynamic alterations play an important role in the effects of the vasodilator on myocardial blood flow and Tl-201 kinetics.     

Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting.

There have been animal and human studies looking at intracoronary (IC) use of abciximab with good short-term clinical outcomes. There exists no data comparing intracoronary with intravenous (IV) administration of abciximab beyond 30 days. We compared the clinical outcomes between the IC (n = 101) and IV (n = 72) group of patients. Patients who had coronary stenting and received abciximab were included in the study. All the patients received the standard systemic bolus dose of abciximab 0.25 mg/kg either via the IC or IV route, followed by a 12-hr IV infusion at 0.125 microg/kg/min. The 6-month composite endpoint of death or myocardial infarction was slightly higher in the IV (13.9%) than in the IC group (5.9%; P = 0.04). The frequency of bleeding complications was similar in both groups. The IC bolus route of abciximab may be superior to the intravenous route. Prospective randomized trials are warranted to validate these findings.     

Prostanoids and cardiac reflexes of sympathetic and vagal origin

Prostaglandins in concentrations too low to stimulate afferent nerve endings in the heart may sensitize them to chemical or mechanical stimuli that activate cardiac reflexes during myocardial ischemia. Bradykinin, which is released from the heart during ischemia, elicits sympathetically mediated reflex pressor effects and tachycardia when applied in low doses (0.1 to 1 microgram) to the epicardium of the left ventricle in open-chest, anesthetized dogs. The reflex pressor effects evoked by bradykinin are reduced after inhibition of prostaglandins biosynthesis with indomethacin and potentiated by concomitant topical application of low doses (0.1 to 0.3 microgram/min) of PGE1 or PGE2 and prostacyclin (PGI2). The pressor and tachycardic responses to bradykinin are also enhanced after temporary (10-minute) coronary occlusion; this potentiation is abolished by indomethacin treatment and can be restored by superfusing the ventricle with prostaglandins. Nicotine is known to excite mechanosensitive vagal receptors with afferent C fibers, which supply the left ventricle, and to elicit reflex hypotension and bradycardia. This depressor vagal reflex evoked by epicardial or intracoronary administration of nicotine (10 to 50 micrograms) was not affected by either indomethacin or by topical application of PGE1, PGE2, or PGI2. Also, intracoronary infusion of PGE2 (0.1 to 0.3 microgram/min), which enhanced the pressor reflex effects of bradykinin, was without effect on nicotine-induced depressor reflex. However, intracoronary infusion of PGI2 (0.1 to 0.3 microgram/min) significantly enhanced the hypotensive and bradycardic responses to nicotine and, at the same time, reduced sympathetically mediated reflex effects of bradykinin. The hypotensive effects induced by epicardial or intracoronary administration of nicotine were also significantly enhanced during intravenous infusion of subdepressor doses of PGI2 (5 to 20 ng/kg/min). Treatment with captopril, which enhances the endogenous production of prostaglandins, greatly enhanced the reflex depressor effects of nicotine; this potentiating effect of captopril was completely abolished by indomethacin treatment. An increase in the magnitude of nicotine-induced reflex depressor effects was also observed after intravenous injection (1 microgram/kg) or infusion (25 to 50 ng/kg/min) of prostaglandin D2. A working hypothesis is proposed to account for the role of prostanoids in activation of cardiac reflexes during myocardial ischemia.     

Effects of adenosine on human coronary arterial circulation

Adenosine is a potent vasodilator used extensively to study the coronary circulation of animals. Its use in humans, however, has been hampered by lack of knowledge about its effects on the human coronary circulation and by concern about its safety. We investigated in humans the effects of adenosine, administered by intracoronary bolus (2-16 micrograms), intracoronary infusion (10-240 micrograms/min), or intravenous infusion (35-140 micrograms/kg/min) on coronary and systemic hemodynamics and the electrocardiogram. Coronary blood flow velocity (CBFV) was measured with a 3F coronary Doppler catheter. The maximal CBFV was determined with intracoronary papaverine (4.5 +/- 0.2.resting CBFV). In normal left coronary arteries (n = 20), 16-micrograms boluses of adenosine caused coronary hyperemia similar to that caused by papaverine (4.6 +/- 0.7.resting CBFV). In the right coronary artery (n = 5), 12-micrograms boluses caused maximal hyperemia (4.4 +/- 1.0.resting CBFV). Intracoronary boluses caused a small, brief decrease in arterial pressure (similar to that caused by papaverine) and no changes in heart rate or in the electrocardiogram. The duration of hyperemia was much shorter after adenosine than after papaverine administration. Intracoronary infusions of 80 micrograms/min or more into the left coronary artery (n = 6) also caused maximal hyperemia (4.4 +/- 0.1.resting CBFV), and doses up to 240 micrograms/min caused a minimal decrease in arterial pressure (-6 +/- 2 mm Hg) and no significant change in heart rate or in electrocardiographic variables. Intravenous infusions in normal patients (n = 25) at 140 micrograms/kg/min caused coronary vasodilation similar to that caused by papaverine in 84% of patients (4.4 +/- 0.9.resting CBFV). At submaximal infusion rates, however, CBFV often fluctuated widely. During the 140-micrograms/kg/min infusion, arterial pressure decreased 6 +/- 7 mm Hg, and heart rate increased 24 +/- 14 beats/min. One patient developed 1 cycle of 2:1 atrioventricular block, but otherwise, the electrocardiogram did not change. In eight patients with microvascular vasodilator dysfunction (delta CBFV, less than 3.5 peak/resting velocity after a maximally vasodilating dose of intracoronary papaverine), the dose-response characteristics to intracoronary boluses and intravenous infusions of adenosine were similar to those found in normal patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Randomized, double-blind, placebo-controlled trial of tissue plasminogen activator in unstable angina

Angiographic, angioscopic and pathologic reports have recently demonstrated a high incidence of intracoronary thrombus in patients with unstable angina. To determine if thrombolysis could be beneficial when combined with maximal medical therapy, 40 patients with rest angina, angiographically documented coronary artery disease and pacing-induced ischemia were randomly assigned to intravenous recombinant tissue-type plasminogen activator (rt-PA, 150 mg/8 h) or placebo in a prospective double-blind trial. All patients received nitrates, a beta-adrenergic blocking agent, a calcium channel blocker, aspirin and heparin. Pacing thresholds for ischemia and quantitative coronary stenosis were measured before and after infusion of the study medication. Intracoronary thrombus was identified angiographically before infusion of the study medication in 16 patients; 7 received rt-PA and 9 received placebo. The ischemic pacing threshold in patients treated with rt-PA increased from 112 +/- 4 beats/min at baseline to 127 +/- 5 beats/min (p = 0.007) by the end of the infusion versus an insignificant change in patients who received placebo (from 116 +/- 4 to 119 +/- 4 beats/min, p = NS). In patients with intracoronary thrombus, the ischemic pacing threshold increased 26 +/- 7 beats/min with rt-PA treatment versus 0 +/- 3 beats/min with placebo (p = 0.004). In contrast, in patients without thrombus, there was no difference in ischemic pacing threshold increments between treatment groups (7 +/- 11 beats/min for rt-PA versus 6 +/- 5 beats/min for placebo, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

重组腺相关病毒2型载体-血管内皮生长因子165改善小型猪慢性心肌缺血的研究

目的应用重组腺相关病毒2型载体(recombinant adenovirus-associated virus2,rAAV2)介导血管内皮生长因子165(vascular endothelial growth factor,VEGF165)基因转染,观察其促进小型猪慢性缺血心肌血管生成并改善心肌血流灌注和心功能的有效性。方法小型猪左冠状动脉回旋支(LCX)放置血管缩窄环,建立慢性心肌缺血模型。5周后行心电图、冠状动脉造影和心脏核磁共振成像检查确认LCX闭塞或相应心肌的缺血。动物随机分为实验组和对照组,每组8只,分别在心肌内直接注射rAAV2-VEGF165(1×1012virus genome)或磷酸盐缓冲液。治疗后3个月和6个月,观察心肌VEGF mRNA和蛋白的表达;6个月后,观察心肌毛细血管和小动脉密度,行冠状动脉造影进行LCX血流分级,应用心脏核磁共振成像观察心肌灌注及左心室功能。结果放置血管缩窄环后5周,所有动物均出现LCX完全/次全闭塞或LCX支配区域的心肌缺血。基因治疗后3个月,实验组心肌VEGF mRNA和蛋白表达显著高于对照组;6个月时,实验组VEGF表达水平较3个月时下降。基因治疗后6个月,VEGF组心肌毛细血管密度和小动脉密度[分别为(1404.06±250.48)/mm2和(167.81±36.29)/mm2]均高于对照组[分别为(976.88±344.79)/mm2和(116.56±34.48)/mm2](P<0.05);潘生丁负荷后心肌灌注成像显示VEGF组心肌灌注明显优于对照组(P<0.05),且较治疗前有改善(P<0.05);两组左心室功能在治疗前后均无明显变化。结论在小型猪慢性心肌缺血模型中,心肌内注射rAAV2-VEGF165后外源VEGF基因的表达至少可持续3个月;rAAV2-VEGF165能够促进缺血心肌毛细血管和小动脉生成并改善心肌灌注。     

激光心肌血运重建术与VEGF基因治疗犬心肌缺血心功能的变化

目的　观察 TML R联合 VEGF1 65c DNA治疗心肌缺血犬后心功能的变化。方法　健康杂种犬 36只 ,随机分为 VEGF1 65基因组、空质粒组 ,激光心肌打孔为对照组 (n=12 ) ,结扎冠状动脉造成急性心肌缺血后 6 0 min分别行CO2 激光心肌打孔和基因转染。采用热稀释法和彩色多谱勒超声心动图检测心排量 (CO)和左心室射血分数(L VEF)。结果　治疗后 6周和 12周 VEGF1 65c DNA组 L VEF和 CO显著高于激光打孔组 (P<0 .0 5 ) ,以治疗后 12周最为显著。结论　犬急性心肌缺血后采用激光心肌打孔联合 VEGF1 65基因治疗可显著改善心功能。     

Clinical outcomes of intracoronary eptifibatide bolus only versus intracoronary bolus and intravenous infusion of eptifibatide in primary percutaneous coronary intervention

Intracoronary bolus of eptifibatide during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to result in higher local platelet glycoprotein IIb/IIIa receptor occupancy with improved microvascular perfusion. It is unclear whether intracoronary administration of eptifibatide in a larger patient population results in favourable clinical outcomes. We evaluated the safety and efficacy of two regimens of intracoronary eptifibatide (bolus only versus bolus followed by intravenous infusion) in patients undergoing primary PCI for ST-elevation MI. They were divided into two groups: Group A (n=67) who received fixed-dose intracoronary eptifibatide bolus only and Group B (n=88) who received intracoronary bolus and continuous intravenous infusion of eptifibatide for 18 h. The preliminary findings from our registry showed that both regimens were associated with good angiographic outcomes, few bleeding events and low in-hospital major adverse cardiac events. A large prospective randomized, multi-centre trial is needed to confirm our observation.     

The role of protein kinase C in left ventricular relaxation impaired by global ischemia

The role of protein kinase C (C kinase) in the left ventricular relaxation impaired by global ischemia was investigated in anesthetised dogs. Left ventricular global ischemia model was made by coronary blood flow reduction and atrial pacing (100-180 beats/min). By this maneuver, the time constant T and left ventricular end-diastolic pressure (LVEDP) were increased in a pacing-rate dependent manner. Intracoronary infusion of H-7, an inhibitor of C kinase, suppressed the magnitudes of the increments of T and LVEDP, while intracoronary infusion of 12-O-tetradecanoyl-phorbol-13-acetate, an activator of C kinase, enhanced the increases of T and LVEDP caused by ischemia. In non-ischemic group, H-7 did not influenced T and LVEDP. The results indicate that C kinase is activated by myocardial ischemia and enhances impairment of left ventricular relaxation.     

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.     

Assessment of the efficacy, optimal dosage, and safety of diltiazem in early treatment of unstable angina pectoris

BACKGROUND: The anti-ischemic benefits of diltiazem are well recognized; however, there are fewer studies of the use of intravenous diltiazem for early treatment of unstable angina pectoris (UAP). HYPOTHESIS: The present study prospectively evaluated the efficacy, optimal dosage, and safety of continuous intravenous diltiazem for initial management of UAP. METHODS: In all, 102 patients with UAP were recruited in this multicenter trial. Diltiazem was administered as a continuous intravenous infusion with a fixed incremental dosage of 1,3, and 5 microg/kg/min, titrated according to the patients' symptoms of angina, and then was maintained for a further 48 h at the angina-free dose. Episodes of angina, hemodynamic stability, and complications were observed. RESULTS: Angina was adequately controlled with continuous intravenous infusion of diltiazem in 64 patients (63%) at a dosage of 1 microg/kg/min, in 26 patients (25%) at dosage of 3 microg/kg/ min, and in 6 patients (6%) at dosage of 5 microg/kg/min, leading to a cumulative effective ratio of 94% in all patients. Additional anti-ischemic medications were required in six patients (6%) who had refractory angina. Bradyarrhythmias noted in only six patients (6%) were reversible after decreasing the dosage of diltiazem. No acute myocardial infarction or other severe side effects occurred. CONCLUSION: Continuous intravenous infusion of diltiazem is well tolerated and relieves symptoms rapidly and effectively in up to 94% patients with UAP, with the majority (63%) treated at the low dosage of 1 microg/kg/min. Diltiazem can be used as a first-line anti-ischemic agent for early conservation treatment of UAP.     

Coronary vascular K+ATP channels contribute to the maintenance of myocardial perfusion in dogs with pacing-induced heart failure

The functional role of coronary vascular ATP-sensitive potassium (K+ATP) channels in the regulation of coronary blood flow (CBF) has not been determined in chronic heart failure (CHF). To test the hypothesis that K+ATP channels contribute to myocardial perfusion in HF, we examined the effects of intracoronary infusion of glibenclamide, an inhibitor of K+ATP channels, on basal CBF in control and CHF dogs. CHF was produced in mongrel dogs by pacing the right ventricle for 4 weeks. Under anesthesia, CBF in the left anterior descending coronary artery, other hemodynamic and metabolic parameters, or regional myocardial blood flow were measured. Basal CBF was less in CHF dogs than in controls. Glibenclamide at the graded doses (5, 15 and 50 microg x kg(-1) x min(-1) decreased CBF in both control and CHF dogs. The percentage decrease in CBF with glibenclamide at 50 microg x kg(-1) x min(-1) was greater (p<0.01) in CHF dogs than in controls. The greater decrease in CBF with glibenclamide at 50microg x kg(-1) x min(-1) was associated with myocardial ischemia. Glibenclamide decreased myocardial blood flow in each sublayer of the myocardium in the 2 groups. These results suggest that the basal activity of coronary vascular K+ATP channels is increased in CHF dogs but not in controls. This may contribute to the maintenance of myocardial perfusion in CHF.     

Vascular endothelial growth factor-165 gene therapy promotes cardiomyogenesis in reperfused myocardial infarction

BACKGROUND: Vascular endothelial growth factor (VEGF)-165 promotes cardiomyogenesis in chronic myocardial ischemia and nonreperfused myocardial infarction (MI). It is unknown whether this effect is present in reperfused MI. We sought to investigate the effect of VEGF-165 gene therapy on cardiomyogenesis after reperfused MI. METHODS AND RESULTS: Twenty-four Yucatan minipigs underwent thoracotomy and a vascular clamp was placed in the left circumflex artery. Reperfusion was reestablished after 90 minutes, and VEGF-165 gene therapy or placebo was administered. A replication-deficient recombinant human adenovirus serotype 5 was used for gene transfer (Ad5-VEGF165). The same viral vector devoid of VEGF gene (Ad5-beta-galactosidase) was used as placebo. Two administration routes were tested, intramyocardial (IM) injection and circumflex intracoronary (IC) infusion. The pigs were assigned to one of the following groups: IM Ad5-VEGF165 (n = 6), IM Ad5-betaGal (n = 6), IC Ad5-VEGF165 (n = 6), and IC Ad5-betaGal (n = 6). All pigs received 5-bromo-2'-deoxyuridine (BrdU) 250 mg IV twice a week to label cells undergoing DNA replication. The hearts were explanted at 4 weeks. BrdU-labeled cardiomyocytes in the peri-infarct area were counted by a pathologist blinded to group assignment. The number of BrdU-labeled cardiomyocytes per million cells was 4-fold higher in the group receiving IM VEGF-165 (64 +/- 11.4) vs. IM placebo (16 +/- 10.6), P = 0.034. No difference in infarct size or ventricular function was observed between the groups. CONCLUSIONS: IM VEGF-165 gene therapy promotes cardiomyogenesis in reperfused MI. However, no benefit in infarct size or cardiac function was observed at 4 weeks. The origin of these cells remains unknown and needs to be determined.     

Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN).

AIMS: To evaluate the safety and efficacy of levosimendan in patients with left ventricular failure complicating acute myocardial infarction. METHODS AND RESULTS: Levosimendan at different doses (0.1-0.4 microg x kg(-1) x min(-1)) or placebo were administered intravenously for 6h to 504 patients in a randomised, placebo-controlled, double-blind study. The primary end-point was hypotension or myocardial ischaemia of clinical significance adjudicated by an independent Safety Committee. Secondary end-points included risk of death and worsening heart failure, symptoms of heart failure and all-cause mortality. The incidence of ischaemia and/or hypotension was similar in all treatment groups (P=0.319). A higher frequency of ischaemia and/or hypotension was only seen in the highest levosimendan dose group. Levosimendan-treated patients experienced lower risk of death and worsening heart failure than patients receiving placebo, during both the 6h infusion (2.0% vs 5.9%; P=0.033) and over 24h (4.0% vs 8.8%; P=0.044). Mortality was lower with levosimendan compared with placebo at 14 days (11.7% vs 19.6%; hazard ratio 0.56 [95% CI 0.33-0.95];P =0.031) and the reduction was maintained at the 180-day retrospective follow-up (22.6% vs 31.4%; 0.67 [0.45-1.00],P =0.053). CONCLUSION:s Levosimendan at doses 0.1-0.2 microg x kg(-1) x min(-1) did not induce hypotension or ischaemia and reduced the risk of worsening heart failure and death in patients with left ventricular failure complicating acute myocardial infarction.     

Prospective randomized trial of intravenous and intracoronary streptokinase in acute myocardial infarction

To evaluate the relative thrombolytic efficacy and complications of intracoronary vs high-dose, short-term intravenous streptokinase infusion in patients with acute myocardial infarction, we performed baseline coronary arteriography and then randomly allocated 51 patients with acute myocardial infarction to receive either intracoronary (n = 25) or intravenous (n = 26) streptokinase. Patients getting the drug by the intracoronary route received 240,000 IU of streptokinase into the infarct-related artery over 1 hr, whereas those getting the drug by the intravenous route received either 500,000 IU of streptokinase over 15 min (n = 10) or 1 million IU of streptokinase over 45 min (n = 16). Angiographically observed thrombolysis occurred in 76% (19/25) of the patients receiving intracoronary streptokinase, in 10% (1/10) of the patients receiving 500,000 IU of streptokinase intravenously, and in 44% (7/16) of the patients receiving 1 million IU of streptokinase intravenously. Among patients in whom thrombolysis was observed, mean elapsed time from onset of streptokinase infusion until lysis was 31 +/- 18 min in patients receiving intracoronary streptokinase and 38 +/- 20 min in those receiving intravenous streptokinase (p = NS). Among patients in whom intravenous streptokinase "failed," intracoronary streptokinase in combination with intracoronary guidewire manipulation recanalized only 7% (1/15). Fibrinogen levels within 6 hr after streptokinase were significantly lower in the patients receiving intravenous streptokinase (39 +/- 17 mg/dl) than the levels in those receiving intracoronary streptokinase (88 +/- 70 mg/dl) (p less than .05) but were similar 24 hr after streptokinase in the two groups. Bleeding requiring transfusion occurred in one patient in each group. Thus, in this prospective randomized trial of intracoronary vs intravenous streptokinase, hemorrhagic complications were few, although both regimens produced a systemic lytic state. Although the thrombolytic efficacy of intracoronary streptokinase was superior to that of high-dose, short-term intravenous streptokinase, the higher-dose intravenous regimen (1 million IU over 45 min) achieved thrombolysis in a significant minority (44%) of patients and might be useful therapy for patients not having access to emergency catheterization.     

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.     

Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique

To determine the relative contributions of milrinone's positive inotropic and vasodilator actions in patients with severe congestive heart failure, the drug was administered by constant infusion directly into the left main coronary artery of 11 patients with New York Heart Association functional class III or IV heart failure. Intracoronary infusion of milrinone at rates up to 50 micrograms/min had no effect on mean arterial pressure or systemic vascular resistance but resulted in dose-related increases in peak positive dP/dt (+21%), stroke volume index (+18%), and stroke work index (+21%) and decreases in heart rate (-3%), mean right atrial pressure (-25%), and left ventricular end-diastolic pressure (-17%). In eight patients, intravenous administration (75 micrograms/kg) after the intracoronary infusion resulted in significant decreases in mean arterial pressure (-14%) and systemic vascular resistance (-40%), further increase in stroke volume index compared with intracoronary administration, and further decreases in mean right atrial and left ventricular end-diastolic pressures compared with intracoronary administration. These data indicate that milrinone exerts both positive inotropic and vasodilator actions that contribute significantly to the drug's overall hemodynamic effect.     

多巴酚丁胺对心肌桥-壁冠状动脉血流动力学的作用

目的探讨运动对心肌桥患者血流动力学的影响。方法观察8例心肌桥患者在静脉滴注多巴酚丁胺前后壁冠状动脉受压程度的变化,并运用腔内多普勒技术观察壁冠状动脉的基础峰值血流速率(bAPV)、最大峰值血流速率(hAPV)、冠状动脉血流储备(CFR)的变化。结果多巴酚丁胺使壁冠状动脉受压程度由用药前的平均(51.7±21.4)%增加至(90.0±12.7)%,P<0.01;壁冠状动脉近段和远段的 hAPV 分别由(19.83±5.84)cm/s 和(20.75±4.91)cm/s 增加至(31.52±10.93)cm/s 和(30.46±9.01)cm/s;壁冠状动脉近段和远段的 CFR 分别由(2.91±0.62和2.46±0.82,P<0.05)下降至(2.17±0.66和1.83±0.51,P 均<0.01)。结论运动可能使壁冠状动脉受压程度增加,CFR 显著下降。     

Administration of atrial natriuretic peptide attenuates reperfusion phenomena and preserves left ventricular regional wall motion after direct coronary angioplasty for acute myocardial infarction.

To evaluate the effects of synthetic human atrial natriuretic peptide (hANP) on myocardial reperfusion injury and left ventricular remodeling, 19 patients within 12 h of a first attack of anterior myocardial infarction (AMI) underwent intracoronary injection of 25 microg of hANP immediately after coronary angioplasty, combined with intravenous infusion of 0.025 microg x kg(-1) x min(-1) of hANP initiated on admission for 1 week (hANP group); 18 similar patients had saline administered (control group). The incidences of premature ventricular contraction, ventricular tachycardia and/or fibrillation in the hANP group were significantly less than in the control group after coronary angioplasty. Left ventricular ejection fraction was significantly greater and left ventricular end-diastolic volume index was significantly smaller 6 months after coronary angioplasty. Left ventricular regional wall motion of the infarcted segments significantly increased. Thus, hANP remarkably suppressed reperfusion phenomena and preserved left ventricular function through improvement of regional wall motion of the infarcted segments after coronary angioplasty.