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Background: Greater insight into sex-based differences in health status can lay the foundation for more equitable health care. This study compares differences in health status of women and men in the CPORT-E trial (Cardiovascular Patient Outcomes Research Team Non-Primary Percutaneous Coronary Intervention) undergoing nonprimary percutaneous coronary intervention. Methods: We compared Seattle Angina Questionnaire scores at baseline, 6 weeks, and 9 months for 6851 women and 12 016 men undergoing nonprimary percutaneous coronary intervention. Results: Proportions of angina-free patients increased from 26.2% and 29.8% at baseline to 71.6% and 78.7% at 6 weeks to 78.1% and 83.0% at 9 months in women and men, respectively ( P P P Conclusions: Although health status increased significantly after percutaneous coronary intervention in both women and men, women had poorer health status outcomes than men before and after percutaneous coronary intervention. Additional investigation into therapies that address the causes of poorer health status in women with coronary artery disease is needed. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00549796.

Historically, percutaneous coronary intervention (PCI) was relegated to hospitals with colocated cardiac surgery because of the potential need for emergent surgical treatment of PCI-related complications. In the current issue of Circulation , Lee and colleagues1 compare outcomes of PCI at hospitals with and without on-site cardiac surgery and show that emergency cardiac surgery is, in fact, rarely needed ( 1 million patients and demonstrates that the incidence of other PCI-related complications, including myocardial infarction, stroke, cardiogenic shock, aortic dissection, and tamponade, as well as early (within 30 days) and late (after 30 days) all-cause mortality, is not different at hospitals with and without colocated cardiac surgery.1 Article see p 388 Because of inconsistencies among the studies, other outcomes indicators of quality, including the need for target vessel revascularization, could not be evaluated in detail. However, when results from the 2 randomized, controlled trials reporting target vessel revascularization (Cardiovascular Patient Outcomes Research Team Trial [CPORT-E]2 and Percutaneous Coronary Intervention [PCI] Outcomes in Community Versus Tertiary Settings [MASS COMM]3) were combined, rates of target vessel revascularization were similar at hospitals with and without on-site cardiac surgery. This important contribution confirms and puts on a more solid evidence-based foundation current guideline recommendations that allow the performance of primary and nonprimary PCI at hospitals without on-site surgery.4 Like all important studies, this report raises a number of questions. Although PCI at hospitals without on-site cardiac surgery is safe and effective, what is the motivation for extending nonprimary PCI at these facilities? What are the consequences of extending PCI to more hospitals? How should the extensive research knowledge base summarized by Lee and colleagues be applied to the development of PCI programs at hospitals without on-site cardiac surgery? The cynical view is that …

Background— Primary percutaneous coronary intervention (PCI) is more effective on average than fibrinolytic therapy in the treatment of ST-segment–elevation myocardial infarction. Yet, most US hospitals are not equipped for PCI, and fibrinolytic therapy is still widely used. This study evaluated the comparative effectiveness of ST-segment–elevation myocardial infarction regionalization strategies to increase the use of PCI against standard emergency transport and care. Methods and Results— We estimated incremental treatment costs and quality-adjusted life expectancies of 2000 patients with ST-segment–elevation myocardial infarction who received PCI or fibrinolytic therapy in simulations of emergency care in a regional hospital system. To increase access to PCI across the system, we compared a base case strategy with 12 hospital-based strategies of building new PCI laboratories or extending the hours of existing laboratories and 1 emergency medical services–based strategy of transporting all patients with ST-segment–elevation myocardial infarction to existing PCI-capable hospitals. The base case resulted in 609 (95% CI, 569–647) patients getting PCI. Hospital-based strategies increased the number of patients receiving PCI, the costs of care, and quality-adjusted life years saved and were cost-effective under a variety of conditions. An emergency medical services–based strategy of transporting every patient to an existing PCI facility was less costly and more effective than all hospital expansion options. Conclusion— Our results suggest that new construction and staffing of PCI laboratories may not be warranted if an emergency medical services strategy is both available and feasible.

Preamble......83 Introduction......84 Purpose......85 Writing Group Composition......85 Literature Review......85 Percutaneous Coronary Intervention......85 Evolution of Competence and Training Standards......85 Evolution of Coronary Interventional Capabilities......86 Procedural Success and

> Discontent is the first necessity of progress. > > —Thomas Edison In November of 1993, 3 reports that published simultaneously in the New England Journal of Medicine demonstrated the superiority of primary percutaneous coronary intervention (PCI) over thrombolytic therapy for treatment of patients with acute ST-segment–elevation myocardial infarction (STEMI).1–3 At that time, within my hospital system, the Johns Hopkins Health System, there were 2 acute care hospitals: the Johns Hopkins Hospital, a tertiary center with both PCI and cardiac surgery capability, and the Bayview Medical Center, a community hospital that could provide neither revascularization modality. In 1993, ≈20 patients with acute STEMI presented to our tertiary facility annually, whereas our community hospital admitted >5× that number. Because State healthcare regulation prohibited performance of PCI at hospitals without colocated cardiac surgery, the superior therapy could be applied at the hospital where the minority of patients presented, whereas at the hospital where the overwhelming majority of patients with STEMI presented primary PCI was not available. Article see p 797 This situation was replicated in many areas around the country, essentially restricting access to the better form of therapy for many patients with STEMI. The rationalized solution to this dilemma offered 2 alternatives: (1) continue to simply offer the “community hospital standard of care,” thrombolytic therapy, to patients with STEMI presenting to non-PCI hospitals or (2) transfer patients from non-PCI–capable to PCI-capable facilities for primary PCI. We were not satisfied with these proposed solutions. In the first, an inferior therapy is offered to patients with STEMI simply because of an accident of geography: they presented to the “wrong” hospital. Furthermore, transfer was not practical. According to Goggle Maps, in the absence of traffic, the Hopkins tertiary and community hospitals are separated geographically by 3.1 miles and temporally by 11 minutes. Yet in …

Background This study was done to determine whether cardiovascular reactivity to mental stress is associated with exercise-induced occult ischemia in an asymptomatic population at high risk for premature coronary heart disease (CHD). Methods and Results One hundred fifty-two siblings of persons with premature CHD underwent mental stress testing. Exercise thallium tomography and 24-hour Holter monitoring were also performed. Hemodynamic changes were monitored during both stressors. Siblings positive for exercise-induced ischemia were offered cardiac catheterization. During mental stress, siblings with an abnormal exercise ECG and/or thallium scan (n=15) had greater maximal increases in systolic blood pressure (SBP, P =.0004) and diastolic blood pressure (DBP, P =.05) and had greater heart rate variability in the normalized low frequency domain of an analysis of Holter monitor recordings, compared with siblings without exercise-induced ischemia. Coronary arteriography confirmed coronary atherosclerosis in 85% of siblings with exercise-induced ischemia. Regression analyses showed that occult ischemia during exercise was a strong independent predictor of maximal change in SBP and DBP during mental stress. A multivariate logistic model demonstrated that siblings with exercise-induced occult ischemia were 21 times more likely to be “hot” responders (top quartile of change in SBP and DBP) during mental stress. Conclusions An exaggerated cardiovascular response to mental stress is associated with exercise-induced myocardial ischemia in persons with preclinical coronary heart disease.

Background In the EPIC trial, c7E3 Fab, an antiplatelet IIb/IIIa receptor antibody, reduced 30-day ischemic end points after high-risk coronary angioplasty by 35% and 6-month ischemic events by 23% but increased in-hospital bleeding episodes. Methods and Results Of the 2099 patients randomized in EPIC, data were collected on 2038 (97%) for prospective hospital cost and major resources. Physician fees were estimated from the Medicare Fee Schedule. Regression analysis was used to examine the economic tradeoff between reduced ischemic events and increased major bleeding during the initial hospitalization. A potential cost savings of $622 per patient during the initial hospitalization from reduced acute ischemic events with c7E3 Fab was offset by an equivalent rise ($521) in costs as the result of an increase in bleeding episodes. Baseline medical costs for the bolus and infusion c7E3 Fab arm averaged $13 577 (exclusive of drug cost) compared with $13 434 for placebo ( P =.42). During the 6-month follow-up, c7E3 Fab decreased repeat hospitalization rates by 23% ( P =.004) and repeat revascularization by 22% ( P =.04), producing a mean $1270 savings per patient (exclusive of drug cost) ( P =.018). With a cost of $1407 for the bolus and infusion c7E3 Fab regimen, the cumulative net 6-month cost to switch from standard care to routine c7E3 Fab averaged $293 per patient. Conclusions In high-risk coronary angioplasty, aggressive platelet inhibition with c7E3 Fab, by significantly reducing ischemic events and repeat revascularization, recoups most of the cost of therapy and has the potential to pay for itself.

Objectives.This study investigated whether an antibody against neutrophil adhesion protein CD18 could limit myocardial infarct size and preserve left ventricular function after prolonged reperfusion in a canine model.Background.Myocardial reperfusion injury is mediated in part by accumulation of activated neutrophils. Although antibodies against CD18 have been shown to reduce neutrophil influx and infarct size after ischemia and 3 to 4 h of reperfusion, it is unknown whether protection is sustained beyond this time or whether there is meaningful preservation of ventricular function.Methods.Dogs undergoing 90-min circumflex coronary artery occlusion and 48-h reperfusion were randomized to receive 1 mg/kg bodyweight of R15.7 (an anti-CD18 antibody, n = 12) or saline (control, n = 12) 10 min before reperfusion. Contrast left ventriculography was used to measure left ventricular ejection fraction and regional chord shortening at baseline, during occlusion and at 48 h. Microspheres injected during occlusion were used to measure collateral flow and risk region size. Postmortem infarct size was measured with triphenyltetrazolium chloride.Results.In the dose administered, R15.7 bound to neutrophils in vivo, with >85% saturation of CD18 for >24 h, with sustained antibody excess in the plasma. R15.7 significantly reduced infarct size after adjusting for the effect of collateral flow (p = 0.0002, analysis of covariance). In a subgroup of dogs with collateral flow

Objectives. This study sought to analyze the outcomes of revascularization procedures in the treatment of allograft coronary disease. Background. Allograft vasculopathy is the main factor limiting survival of heart transplant recipients. Because no medical therapy prevents allograft atherosclerosis, and retransplantation is associated with suboptimal allograft survival, palliative coronary revascularization has been attempted. Methods. Thirteen medical centers retrospectively analyzed their complete experience with percutaneous transluminal coronary angioplasty, directional coronary atherectomy and coronary bypass graft surgery in allograft coronary disease. Results. Sixty-six patients underwent coronary angioplasty. Angiographic success (≤ 50% residual stenosis) occurred in 153 (94%) of 162 lesions. Forty patients (61%) are alive without retransplantation at 19 ± 14 (mean ± SD) months after angioplasty. The consequences of failed revascularization were severe. Two patients sustained periprocedural myocardial infarction and died. Angiographic restenosis occurred in 42 (55%) of 76 lesions at 8 ± 5 months after angioplasty. Angiographic distal arteriopathy adversely affected allograft survival. Eleven patients underwent directional coronary atherectomy. Angiographic success occurred in 9 (82%) of 11 lesions. Two periprocedural deaths occurred. Nine patients are alive without transplantation at 7 ± 4 months after atherectomy. Bypass graft surgery was performed in 12 patients. Four patients died perioperatively. Seven patients are alive without retransplantation at 9 ± 7 months after operation. Conclusions. Coronary revascularization may be an effective palliative therapy in suitable cardiac transplant recipients. Angioplasty has an acceptable survival in patients without angiographic distal arteriopathy. Because few patients underwent atherectomy and coronary bypass surgery, assessment of these procedures is limited. Angiographic distal arteriopathy is associated with decreased allograft survival in patients requiring revascularization.

Whether non-primary PCI performed at hospitals without on-site cardiac surgery is safe and effective remains controversial. The Cardiovascular Patient Outcomes Research Team Trial (CPORT-E) compared outcomes of non-primary percutaneous coronary intervention (PCI) performed at hospitals with (SOS)

For coronary artery disease (CAD), female gender is ’protective’, so that women typically present with clinically apparent CAD a decade later than men. We examined the extent to which traditional cardiovascular risk factor influence the age at presentation with STEMI in men and women. The Cardiovascular Patient Outcomes Research Team (C-PORT) primary PCI registry includes 7197 patients (5070 males and 2109 females) who presented with STEMI at 33 participating hospitals. The table below depicts the average age at presentation with STEMI in males and females with and without diabetes, hypercholesterolemia, hypertension, a family history of coronary artery disease and smoking history (current or former). The effect of smoking, family history and hypertension on age at presentation remained significant in multivariate analysis in both men and women. In both males and females, a family history of CAD and a positive smoking history are associated with presentation with STEMI at a younger age. Both have a greater effect in females. This is particularly true of smoking with lowers the age of presentation by 9 years in women, compared with 3.8 years in men. Male and female patients with a history of hypertension are older at presentation with STEMI, perhaps because the anti-ischemic effects of anti-hypertensive medications. We conclude that while the effect of most traditional risk factors for CAD on age at presentation with STEMI are similar in men and women, smoking lowers the age at presentation to a much greater degree in women. In women who do not smoke, STEMI is delayed for a decade or more compared to men; for women who do, the protective effect of female gender is nearly obliterated.

Developers of systems to improve access to primary percutaneous intervention (PCI) must recognize that most ST-elevation myocardial infarction (STEMI) patients present to hospitals that do not have PCI capability. Indeed, only ≈25% of US hospitals are currently capable of delivering this intervention.1 These non-PCI-capable institutions are often located in rural areas and face real challenges related to distance from PCI centers. In addition, these institutions face significant financial challenges2 in pursuing any of the 3 potential strategies to increase timely access to primary PCI. These 3 strategies include the following3: (1) hospitals currently without PCI capability can develop primary PCI services without cardiac surgery on-site (SOS); (2) non-PCI-capable facilities can rapidly diagnose and transfer STEMI patients to primary PCI-capable hospitals and thereby serve as STEMI referral hospitals; or (3) communities can develop systems that bypass non-PCI-capable hospitals. Each of these strategies is addressed in this article. For each, we review the current status, the ideal system, gaps in and barriers to development of the ideal system, and recommendations. ### Current Status Early observational studies from single institutions demonstrated potential efficacy and safety of primary PCI without SOS. In the Myocardial Infarction, Triage and Intervention (MITI) trial, 233 of 441 primary PCIs were performed at hospitals without SOS. Emergency cardiac surgery was rare (1.4% of patients), and its presence or absence did not affect survival after myocardial infarction.4 In another observational study, among 334 patients undergoing primary PCI at a hospital without SOS, there were no deaths, and no patient required emergency coronary artery bypass grafting (CABG).5 In a nonrandomized comparison of patients undergoing primary PCI at hospitals without SOS with those undergoing primary PCI after transfer to a tertiary hospital, there was no difference in 30-day or 1-year mortality, although time to reperfusion was significantly shorter, and …

UNLABELLED It has been speculated but never proven that tachycardia-induced ischemia per se may lead to myocardial infarction. In 17 anesthetized dogs, the proximal left anterior descending (LAD) artery was cannulated and perfused via bypass from the left subclavian artery. Distal LAD pressure was reduced by a screw clamp to cause > or =20% decrease in wall thickening during pacing tachycardia but no decrease in resting heart rate (approximately 90 bpm). Dogs were randomly assigned to three groups: 1) control (n = 6) maintained at resting heart rate (approximately 90 bpm) and mean coronary pressure of 49+/-5 mm Hg for 4 h; 2) 4-h ischemia (n = 6), paced at 150 bpm and mean coronary pressure maintained at 59+/-6 mm Hg for 4 h; and 3) 1-h ischemia (n = 5), paced at 150 bpm and mean coronary pressure of 54+/-8 mm Hg for 1 h. Myocardial blood flow and infarct area were measured by radiolabeled microspheres and triphenyl-tetrazolium chloride staining, respectively. Despite the higher coronary pressure in the 4-h ischemia group (P = 0.02), patchy subendocardial necrosis occurred in all these dogs and in two of the 1-h ischemia dogs, and one control dog had minimal papillary muscle necrosis. Infarct area was largest in the 4-h ischemic group (15.5%+/-9.1%) compared with control and 1-h ischemia groups (0.09%+/-0.2% and 1.6%+/-2.1%, respectively) (P < 0.002). Relative (risk/ nonrisk areas) subendocardial flow was lower at the end of ischemia in the 4- and 1-h ischemia groups compared with the control group (0.3+/-0.1 and 0.4+/-0.1 vs 0.9+/-0.2; P = 0.008 and 0.01, respectively). Prolonged tachycardia-induced ischemia, in the face of fixed coronary stenosis causing no ischemia at the resting heart rate, leads to patchy subendocardial necrosis, despite anticoagulation and antiplatelet treatment. IMPLICATIONS Prolonged tachycardia-induced ischemia, in the face of fixed coronary stenosis causing no ischemia at the resting heart rate, leads to subendocardial infarction in dogs. These findings suggest a possible mechanism for postoperative myocardial infarction.

Analysis of high frequency (150–250 Hz) in the signal-averaged electrocardiogram (SAECG) is one of the emerging methods for detecting vessel patency in acute myocardial infarction following thrombolytic therapy and angioplasty. Root-mean-square voltage (RMSV) of the filtered QRS has been used in earlier studies to detect reperfusion; however, previous analysis indicated that RMSV is sensitive to residual noise in the SAECG and errors in QRS delineation (onset/offset). A new measurement is proposed, high-frequency energy (HFQE), and the robustness of the RMSV and HFQE was evaluated for simulated errors in QRS delineation. In this study, two measures (RMSV and HFQE) were tested on 24 control subjects and 21 patients undergoing thrombolytic therapy. Results indicate that unfiltered QRS duration is more stable than filtered QRS duration for the control subjects and patients and that HFQE had less fluctuation than RMSV in thrombolytic therapy patients. In the control group, HFQE was sensitive to the amplitude variation of the filtered SAECG. Therefore, another new measurement is proposed high-frequency integral of absolute value (HFAV), for reducing the sensitivity to amplitude changes in the filtered SAECG. This new feature was tested on control subjects and was found to be more stable than HFQE. In the thrombolytic therapy group, HFAV provided similar information as HFQE. These three measurements—RMSV, HFQE, and HFAV—provide a comprehensive analysis of the high-frequency SAECG for detecting vessel patency and reocclusion. Relative merits of these measures need to be evaluated on a larger database of patients undergoing thrombolysis and angioplasty for acute myocardial infarction.

The hypothesis that an increase in the amplitude (root-mean-square voltage) of the high frequency (150-250 Hz) components of the QRS complex occurs with successful reperfusion following thrombolytic therapy in acute myocardial infarction (AMI) and fails to occur when thrombolysis fails was tested. Clinical markers for successful or failed reperfusion following thrombolytic therapy for AMI are notoriously insensitive. The amplitude of the high-frequency components of the QRS complex decreases during ischemia and returns to normal with resolution of ischemia, but neither the variability in measurement of these potentials nor their patterns of change during the course of AMI have been described. In 32 control subjects, the average coefficient of variation for the amplitude of the highfrequency QRS complex was 10% or 0.3 uV. Based on these data, for the acute infarction population a significant change in this measurement was therefore defined as a change in amplitude > 20% or 0.6 uV on two consecutive recordings. In 30 patients with AMI treated with a thrombolytic agent, either cardiac catheterization, serial serum myoglobin, or complete resolution of ST-segment elevation were used to define successful or failed reperfusion. High-frequency QRS electrocardiograms were obtained at the start of treatment with a thrombolytic agent and for 3 h thereafter using a signal-averaging technique and digital filtering. Standard 12-lead electrocardiograms were obtained at the same time. In patients who reperfused successfully, the high-frequency QRS amplitude increased significantly (1.2 ± 0.9 uV above its nadir at 83 ± 36 min after initiation of thrombolytic therapy) in 23 of 25 patients. In contrast, the highfrequency QRS amplitude did not change or declined in all five patients who failed to reperfuse (-0.4 ± 0.4 uV, p < 0.05 compared with successful reperfusion). Traditional clinical markers such as resolution of chest pain and ST-segment elevation failed to distinguish successful and failed reperfusion. High-frequency QRS electrocardiography is a rapid, reliable bedside technique for discriminating between successful and failed reperfusion in patients treated with thrombolytic agents for AMI.

ContextTrials comparing primary percutaneous coronary intervention (PCI) and thrombolytic therapy for treatment of acute myocardial infarction (MI) suggest primary PCI is the superior therapy, although they differ with respect to the durability of benefit. Because PCI is often limited to hospitals that have on-site cardiac surgery programs, most acute MI patients do not have access to this therapy.ObjectiveTo determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without on-site cardiac surgery and, if so, whether superiority is durable.DesignThe Atlantic Cardiovascular Patient Outcomes Research Team (C-PORT) trial, a prospective, randomized trial conducted from July 1996 through December 1999.SettingEleven community hospitals in Massachusetts and Maryland without on-site cardiac surgery or extant PCI programs.PatientsFour hundred fifty-one thrombolytic-eligible patients with acute MI of less than 12 hours' duration associated with ST-segment elevation on electrocardiogram.InterventionsAfter a formal primary PCI development program was completed at all sites, patients were randomly assigned to receive primary PCI (n = 225) or accelerated tissue plasminogen activator (bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes; n = 226). After initiation of assigned treatment, all care was determined by treating physicians.Main Outcome MeasuresSix-month composite incidence of death, recurrent MI, and stroke; median hospital length of stay.ResultsThe incidence of the composite end point was reduced in the primary PCI group at 6 weeks (10.7% vs 17.7%; P = .03) and 6 months (12.4% vs 19.9%; P = .03) after index MI. Six-month rates for individual outcomes were 6.2% vs 7.1% for death (P = .72), 5.3% vs 10.6% for recurrent MI (P = .04), and 2.2% vs 4.0% for stroke (P = .28) for primary PCI vs thrombolytic therapy, respectively. Median length of stay was also reduced in the primary PCI group (4.5 vs 6.0 days; P = .02).ConclusionsCompared with thrombolytic therapy, treatment of patients with primary PCI at hospitals without on-site cardiac surgery is associated with better clinical outcomes for 6 months after index MI and a shorter hospital stay.

Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 micrograms/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to-1.9% in the nitroglycerin group (p less than .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5.1% after nitroglycerin (p less than .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -.73, p less than .001). Performance was unchanged in the control region despite similar augmentation of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimension change measures of regional ventricular function, such as absolute or percent wall thickening (delta T or % delta T) or segmental shortening (delta L or % delta L), are highly load dependent. In 16 anesthetized mongrel dogs we assessed use of the end-systolic pressure-thickness and end-systolic pressure-length relationships (ESPTR, ESPLR) as more load-independent measures of regional function. We found that the ESPTR and ESPLR could be measured without detectable baroreceptor-mediated reflex changes in cardiac contractile state. Systemic administration of dobutamine shifted the ESPTR to the right and the ESPLR to the left of control, mainly due to a change in the slope (Ees) of the relationships. Both delta T, % delta T and delta L, % delta L failed to detect the positive inotropic effect of dobutamine because of an associated reduction in preload. With systemic administration of propranolol, ESPTR, ESPLR, delta T, % delta T, and delta L, % delta L detected the negative inotropic effect. Thus systemic propranolol shifted the ESPTR to the left and the ESPLR to the right of control, mainly due to a change in Ees. Regional administration of dobutamine shifted the ESPTR and the ESPLR in the direction of positive contractility in the region receiving the drug, whereas simple dimension change measures of regional function failed to detect the inotropic effect because preload fell and the timing of regional end-systole was altered. With regional propranolol both the ESPTR, ESPLR and simple dimension change measures detected the negative inotropic effect. Thus the ESPTR, ESPLR is a reliable measure of regional ventricular function and may be better than simple dimension change measures of regional function, particularly when loading conditions or the timing of regional systole is altered by an intervention.

Objectives.This study attempted to determine whether neutrophil sequestration in reperfused myocardium can be inhibited and infarct size reduced by treatment with a chimeric, monoclonal IgG4 antibody (CLB54) directed against CD18 in a primate model of acute myocardial ischemia and reperfusion.Background.Reperfusion injury, in part mediated by neutrophils, may limit the potential benefit of reestablishing infarctrelated artery patency in patients with acute myocardial infarction.Methods.Nineteen closed-chest baboons (10 control, 9 treated with CLB54) had the left anterior descending coronary artery occluded for 90 min, followed by 4 h of reflow. CLB54 (mean [±SD] 11 ± 2 mg/kg body weight) or saline solution was administered intravenously 20 min before reflow. Coronary flow was determined using radiolabeled microspheres, infarct size by triphenyltetrazolium chloride staining, global and regional ventricular function by contrast ventriculography and neutrophil accumulation by a myeloperoxidase assay.Results.Risk region size was the same in both groups. CLB54 treatment reduced infarct size expressed as a percent of the risk region from 41 ± 20% in the saline-treated group to 19 ± 17% in the CLB54-treated group (p < 0.02). This was associated with diminished myeloperoxidase activity and greater postreperfusion coronary flow in the risk region in CLB54-treated than in control baboons. Ejection fraction declined to the same extent in both groups, whereas anterior wall regional cord shortening was better preserved in CLB54-treated baboons.Conclusions.Inhibition of neutrophil sequestration with CLB54 administered before reperfusion reduces infarct size, preserves ischemic zone microvascular perfusion and minimizes the decline of regional wall motion.

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last druginduced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.