The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion (<2 vs 2 to 3 vs >3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p=0.026), trends for better myocardial blush (p=0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p=0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p=0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p=0.23, p=0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.

Context Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. Objective To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size.Design, Setting, and Patients Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis.Interventions Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection.Main Outcome Measures Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events.Results Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73 % (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/2391, respectively; absolute difference, 1.4% [95% confidence interval, -7.7% to 10.5%; P=.781), and left ventricular infarct size was similar in both groups (median, 12.0% [n=2291 vs9.5% [n=2081, respectively; P=.15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P=.66).Conclusions A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.

We examined endothelium-dependent vasodilator responses in well-developed coronary collateral vessels. Collateral vessels and size-matched normal epicardial coronary arteries were isolated from canine hearts 6 months after a hollow plug had been introduced into the left anterior descending coronary artery (LAD) to stimulate collateral vessel growth. Vessel segments were isolated and studied in organ chambers. After preconstriction with prostaglandin F2 alpha, (PGF2 alpha) responses to the endothelium-dependent vasodilators, acetylcholine (ACh), substance P, and bradykinin (BK), as well as the endothelium-independent vasodilator nitroglycerin (NTG), were measured. The maximum relaxation to ACh was greater in collateral vessels (129 +/- 3.6% of the preconstricted tension) than in normal vessels (110 +/- 6.2%, p < 0.001), although the EC50 value for ACh was not significantly different between collateral and normal vessels. Collateral vessels demonstrated sensitivity to BK similar to that of normal vessels, but the maximal vasodilation achieved was greater in collaterals (138 +/- 4.6% of preconstricted tension) than in normal vessels (108 +/- 5.0%, p < 0.05). Both substance P and NTG produced dose-related relaxation that was similar in collateral vessels and normal arteries. These findings demonstrate that endothelium-dependent relaxation is intact in well-developed coronary collateral vessels.

We examined the effects of the alpha-adrenergic blocking agent urapidil on coronary blood flow (CBF) and myocardial O2 consumption during exercise in 11 dogs trained to run on a motor-driven treadmill. Left circumflex coronary artery (LCX) BF was measured with an electromagnetic flowmeter, and aortic and coronary sinus electromagnetic flowmeter, and aortic and coronary sinus catheters allowed determination of myocardial arteriovenous O2 extraction. During control conditions, graded treadmill exercise caused progressive increases in myocardial O2 consumption, which resulted from regular increases in CBF as well as increased O2 extraction by myocardium. Urapidil 3 mg/kg blocked the response to the selective alpha 1-adrenergic agonist phenylephrine (PE 5 micrograms/kg intravenously, i.v.), and significantly decreased arterial blood pressure (BP) at rest and during exercise. Heart rate (HR) was significantly faster than control during the lightest level of exercise after urapidil. Similarly, CBF was significantly increased during light and moderate exercise after urapidil administration. Urapidil caused a slight decrease in myocardial O2 extraction, with an increase in coronary sinus O2 tension. These data indicate that urapidil antagonized adrenergic coronary vasoconstriction, which acted to limit the increase in CBF that occurred during exercise.