Delays to Hospital Presentation in Women and Men with ST-Segment Elevation Myocardial Infarction: A Multi-Center Analysis of Patients Hospitalized in New York City.

PURPOSE: Previous studies have shown longer delays from symptom onset to hospital presentation (S2P time) in women than men with acute myocardial infarction. The aim of this study is to understand the reasons for delays in seeking care among women and men presenting with an ST-Segment Elevation Myocardial Infarction (STEMI) through a detailed assessment of the thoughts, perceptions and patterns of behavior. PATIENTS/METHODS AND RESULTS: A total of 218 patients with STEMI treated with primary angioplasty at four New York City Hospitals were interviewed (24% female; Women: 68.7 ± 13.1 years and men: 60.7 ± 13.8 years) between January 2009 and August 2012. A significantly larger percentage of women than men had no chest pain (62% vs 36%, p<0.01). Compared to men, a smaller proportion of women thought they were having a myocardial infarction (15% vs 34%, p=0.01). A larger proportion of women than men had S2P time >90 minutes (72% of women vs 54% of men, p= 0.03). Women were more likely than men to hesitate before seeking help, and more women than men hesitated because they did not think they were having an AMI (91% vs 83%, p=0.04). Multivariate regression analysis showed that female sex (Odds Ratio: 2.46, 95% CI 1.10-5.60 P=0.03), subjective opinion it was not an AMI (Odds Ratio 2.44, 95% CI 1.20-5.0, P=0.01) and level of education less than high school (Odds ratio 7.21 95% CI 1.59-32.75 P=0.01) were independent predictors for S2P >90 minutes. CONCLUSION: Women with STEMI have longer pre-hospital delays than men, which are associated with a higher prevalence of atypical symptoms and a lack of belief in women that they are having an AMI. Greater focus should be made on educating women (and men) regarding the symptoms of STEMI, and the importance of a timely response to these symptoms.

Cangrelor in STEMI as a bridge to CABG- a mini-case series.

Background: Patients with STEMI receive dual antiplatelet therapy as soon as possible with aspirin and a P2Y12 receptor antagonist prior to PCI. A fraction of these patients may have multi-vessel disease needing emergent CABG surgery. The choice of a P2Y12 receptor antagonist plays a role in the timing of CABG surgery as it poses a bleeding risk until it is completely eliminated from the system. Oral P2Y12 receptor antagonists have a long duration of platelet inhibition which is difficult to reverse. Cangrelor is an intravenous P2Y12 receptor antagonist with a short half-life and rapid cessation of its effect after discontinuation. Methods: Three patients who presented to our emergency department with STEMI were started on cangrelor infusion prior to cardiac catheterization instead of other P2Y12 receptor antagonists like clopidogrel or ticagrelor. The study received ethical approval as it is part of the current standard of care for STEMI patients. Results: All three patients were found to have multi-vessel disease during coronary angiography requiring CABG surgery. As cangrelor was used in these patients they were able to have their surgery within 24-48 h. Intravenous cangrelor was stopped about an hour before surgery. No bleeding complications occurred and all three patients made a speedy recovery in the ICU. Conclusion: Cangrelor is a potent P2Y12 receptor antagonist which can be used in patients presenting with STEMI as one of the two anti-platelet agents along with aspirin without any dilemma that it would cause a delay in CABG surgery if the patients need one.

Meta-Analysis of Randomized Controlled Trials Comparing Multivessel Versus Culprit-Only Revascularization for Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention.

Current guidelines recommend against revascularization of the noninfarct artery during the index percutaneous coronary intervention (PCI) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI). This was based largely on observational studies with few data coming from randomized controlled trials (RCTs). Recently, several small-to-moderate sized RCTs have provided data, suggesting that a multivessel revascularization approach may be appropriate. We performed a meta-analysis of RCTs comparing multivessel percutaneous coronary intervention (MV PCI) versus culprit vessel-only revascularization (COR) during primary PCI in patients with STEMI and multivessel coronary disease (MVCD). We searched Medline, PubMed, and Scopus databases for RCTs comparing MV PCI versus COR in patients with STEMI and MVCD. The incidence of all-cause death, cardiac death, recurrent myocardial infarction, and revascularization during follow-up were extracted. Four RCTs fit our primary selection criteria. Among these, 566 patients underwent MV PCI (either at the time of the primary PCI or as a staged procedure) and 478 patients underwent COR. During long-term follow-up (range 1 to 2.5 years), combined data indicated a significant reduction in all-cause mortality (relative risk [RR] 0.57, 95% confidence interval [CI] 0.36 to 0.92, p = 0.02) and in cardiac death (RR 0.38, 95% CI 0.20 to 0.73, p = 0.004) with MV PCI. In addition, there was a significantly lower risk of recurrent myocardial infarction (RR 0.41, 95% CI 0.23 to 0.75; p = 0.004) and future revascularization (RR 0.37, 95% CI 0.27 to 0.52; p <0.00001). In conclusion, from the RCT data, MV PCI appears to improve outcomes in patients with STEMI and MVCD.

High dose statin loading prior to percutaneous coronary intervention decreases cardiovascular events: a meta-analysis of randomized controlled trials.

OBJECTIVE: We performed a meta-analysis of randomized controlled trials of statin loading prior to percutaneous coronary intervention (PCI). BACKGROUND: Statin loading prior to PCI has been shown to decrease peri-procedural myocardial infarction (pMI) but less is known regarding the clinical benefit of pre-procedural statin loading. METHODS: We searched for trials of statin naïve patients presenting with stable angina or NSTE-ACS and treated with statins prior to PCI. We evaluated the incidence of pMI and major cardiac events including spontaneous myocardial infarction, death, and target vessel revascularization. RESULTS: Out of 1,210 articles, 14 randomized controlled trials were included in this meta-analysis. Among 3,146 patients, 1,591 patients were randomized to a loading dose of statin before PCI and 1,555 patients were given statin therapy initiated only after the PCI. Statin loading prior to PCI was associated with a 56% relative reduction in pMI (OR: 0.44, 95% CI: 0.35-0.56; P < 0.00001). There was a 41% reduction in clinical events in follow-up in the group of patients treated with statin loading prior to PCI (OR: 0.59, 95% CI: 0.38-0.92, P = 0.02). When stratified according to the clinical presentation, the results were only significant for those patients with NSTE-ACS (OR: 0.18, 95% CI: 0.07-0.47; P = 0.0005) and was not noted in the group of patients who underwent PCI for stable angina (OR: 0.92, 95% CI: 0.53-1.61; P = 0.78). CONCLUSIONS: High dose statin therapy given prior to PCI in patients with NSTE-ACS is associated with a reduction in pMI and short-term clinical events. © 2013 Wiley Periodicals, Inc.

Meta-analysis of randomized clinical trials comparing short-term versus long-term dual antiplatelet therapy following drug-eluting stents.

Current guidelines recommend 12 months of dual antiplatelet therapy (DAPT) after drug-eluting stent (DES) implantation in the absence of increased bleeding risk. Studies have suggested that early discontinuation of DAPT can result in an increased risk of stent thrombosis. However, given the potential for major bleeding, the optimal duration of DAPT after DES implantation remains uncertain. We searched PubMed, EMBASE, Scopus, and ClinicalTrials.gov databases from inception until October 2013 for randomized controlled trials that compared shorter versus longer DAPT duration after DES implantation. Four randomized controlled trials were included. A total of 4,081 patients received DAPT for 3 to 6 months, and 4,076 patients were treated with DAPT for 12 to 24 months. Oral DAPT consisted of aspirin and clopidogrel. There was no significant difference in the rate of the composite outcome of cardiac death or myocardial infarction between the short (3.3%) and prolonged (3.0%) DAPT groups (odds ratio 1.11, 95% confidence interval 0.87 to 1.43, p=0.41). A landmark analysis performed at the time of discontinuation of DAPT in the short DAPT group demonstrated a nonsignificant higher rate of stent thrombosis in patients treated with a short course of DAPT (0.35% vs 0.20%, p=0.22). Major bleeding was significantly higher in the group of patients treated with prolonged DAPT (0.29% vs 0.71%, p=0.01). In conclusion, prolonged DAPT compared with short-term treatment is associated with increased major bleeding but is not associated with a decrease in the composite rates of death or myocardial infarction.

A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction.

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9% ± 8.5% vs 1.6% ± 7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105).

Safety and feasibility of intra-arterial bivalirudin bolus administration during primary angioplasty.

AIM: We investigated the feasibility and safety of intra-arterial bivalirudin bolus during primary angioplasty. BACKGROUND: Bivalirudin has been shown to be an effective and safe anticoagulant during angioplasty. However, in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, the bivalirudin group experienced higher acute stent thrombosis rate compared with the heparin and glycoprotein IIb/IIIa inhibitor group. One possible explanation is suboptimal systemic administration. METHODS: To prevent this possibility and to potentially prevent acute stent thrombosis, we administered intra-arterial bivalirudin bolus during primary angioplasty in 100 consecutive patients. RESULTS: Our observational study suggests safety with no bleeding episode and no observed acute stent thrombosis. CONCLUSION: We conclude that intra-arterial bivalirudin bolus during primary angioplasty is safe and could ensure effective systemic delivery of bivalirudin.

Evaluation of microvascular angina with TIMI frame count using nitroprusside induced hyperemia.

TIMI frame count (TFC) provides a quantitative index of coronary microvascular dysfunction. Previous studies suggested the degree of frame count reserve (FCR) and slow coronary flow (SCF) correlated with microvascular dysfunction. We investigated the clinical implication of FCR and SCF for the evaluation of microvascular angina (MA). We included consecutive 77 patients with the complaint of chest pain, who subsequently had normal coronary angiography. TFC was obtained from left anterior descending artery. Intracoronary nitroprusside (15 µg) was infused to induce hyperemia, and repeat angiogram was performed after 30s. FCR was calculated by dividing basal TFC by hyperemic TFC. SCF was defined as being present when TFC was more than 28. All patients underwent a treadmill test without medication after angiography. After the treadmill test, patients were divided into a MA group (40 patients) and a control group (37 patients). FCR was similar in both groups (2.0±1.0 and 2.1±0.9, MA and control group, respectively). However, hyperemic TFC induced by nitroprusside was significantly higher in the MA group (10.9±4.7) than in the control group (9.0±3.5, p<0.05). Patients who showed SCF had a significantly greater incidence of MA (78.5%; 11/14 patients) than that with normal coronary flow (46.0%; 29/63 patients, p<0.05). The higher hyperemic TFC and presence of SCF were found to have a diagnostic value for MA.

Unilateral pulmonary edema: a rare initial presentation of cardiogenic shock due to acute myocardial infarction.

Cardiogenic unilateral pulmonary edema (UPE) is a rare clinical entity that is often misdiagnosed at first. Most cases of cardiogenic UPE occur in the right upper lobe and are caused by severe mitral regurgitation (MR). We present an unusual case of right-sided UPE in a patient with cardiogenic shock due to acute myocardial infarction (AMI) without severe MR. The patient was successfully treated by percutaneous coronary intervention and medical therapy for heart failure. Follow-up chest Radiography showed complete resolution of the UPE. This case reminds us that AMI can present as UPE even in patients without severe MR or any preexisting pulmonary disease affecting the vasculature or parenchyma of the lung.

Recent Advances in the Treatment of ST-Segment Elevation Myocardial Infarction.

ST-segment elevation myocardial infarction (STEMI) represents the most urgent condition for patients with coronary artery disease. Prompt diagnosis and therapy, mainly with primary angioplasty using stents, are important in improving not only acute survival but also long-term prognosis. Recent advances in angioplasty devices, including manual aspiration catheters and drug-eluting stents, and pharmacologic therapy, such as potent antiplatelet and anticoagulant agents, have significantly enhanced the acute outcome for these patients. Continuing efforts to educate the public and to decrease the door-to-balloon time are essential to further improve the outcome for these high-risk patients. Future research to normalize the left ventricular function by autologous stem cell therapy may also contribute to the quality of life and longevity of the patients surviving STEMI.

Implementing a pathway for the management of acute coronary syndrome leads to improved compliance with guidelines and a decrease in angina symptoms.

We describe our experience with the Advanced Cardiac Admission Program (ACAP) at our institution. The ACAP program is a hospital-wide implementation of critical pathways-based management of all cardiac patients. Data review of patients admitted for acute coronary syndromes from the ACAP-PAIN database and a comparative study of outcomes before and after implementation of the pathways-based assessment and treatment protocols. In the pre-ACAP and post-ACAP patient groups, antiplatelet use at admission improved from 50% to 75% (p<.01), ACE-I use improved from 32% to 54% (p<.0001), statins use increased from 35% to 62% (p<.0001), and smoking cessation awareness increased from 15% to 86% (p<.0001). At 1-year follow-up, 84% of patients with CAD were treated with statins, and 47% had LDL cholesterol <100 mg/dL, compared with 20% and 9%, respectively, with conventional treatment before ACAP implementation (p<.0001). Recurrent angina symptoms and nonfatal myocardial infarction rates decreased from 28.5% to 13% (p = .02), and 15% to 5% (p = 0.03), respectively. Pathway-based programs like ACAP significantly enhance administration of guidelines-based cardioprotective medications both during hospital stay and at 1-year follow-up.

Success in implementing a hospital-wide evidence-based clinical pathways system for the management of cardiac patients: the ACAP program experience.

There is robust evidence to support the concept that critical pathways, derived from evidence-based guidelines, are an effective strategy for bridging the gap between published guidelines and clinical practice. It was with this idea in mind that in 2004 we developed an innovative novel program at our institution, that is, the "Advanced Cardiac Admission Program." The Advanced Cardiac Admission program consists of tools and strategies for implementing American College of Cardiology or American Heart Association guidelines into daily clinical practice. The program is composed of 8 novel critical pathways for the management of cardiac patients. In this article, we describe our experience in successfully implementing this program at our institutions.

Pathway for the management of survivors of out-of-hospital cardiac arrest.

The estimated number of out-of-hospital care arrest cases is about 300,000 per year in the United States. Two landmark studies published in 2002 demonstrated that the use of therapeutic hypothermia after cardiac arrest decreased mortality and improved neurologic outcome. Based on these studies, the International Liaison Committee on Resuscitation and the American Heart Association recommended the use of therapeutic hypothermia after cardiac arrest. Therapeutic hypothermia is defined as a controlled lowering of core body temperature to 32 degrees C to 34 degrees C. This temperature goal represents the optimal balance between clinical effect and cardiovascular toxicity. Therapeutic hypothermia does require resources to implement-including device, close nursing care, and monitoring. It is important to select patients who have potential for benefit from this technique which is a limited resource and carries potential complications. A collaborative team approach involving physicians and nurses is critical for successful development and implementation of this kind of a protocol. In 2004, the "Advanced Cardiac Admission Program" was launched at the St. Luke's Roosevelt Hospital Center of Columbia University in New York. The program consists of a series of projects, which have been developed to bridge the gap between published guidelines and implementation during "real world" patient care. In this article, we are reporting our latest project for the comprehensive management of survivors of out-of-hospital cardiac arrest. The pathway is divided into 3 steps: Step I, From the field through the emergency department into the cardiac catherization laboratory and to the critical care unit; Step II, Induced invasive hypothermia protocol in the critical care unit (this step is divided into 3 phases: 1, invasive cooling for the first 24 hours; 2, rewarming; 3, maintenance); Step III, Management post the rewarming phase including the recommendation for out-of-hospital therapy and the ethical decision to define goal of care. We hope that this novel pathway will bridge the gap between the complex guidelines and the actual clinical practice and will improve the survival and neurologic condition of patients suffering cardiac arrest.

Increased vascular access complications in patients with renal dysfunction undergoing percutaneous coronary procedures using arteriotomy closure devices.

BACKGROUND: Arteriotomy closure device (ACD) use has increased following percutaneous transfemoral coronary procedures (PTCP). However, their safety in patients with chronic kidney disease (CKD) is not known. Therefore, we evaluated the complication rates of ACD among patients with CKD. METHODS: Six-hundred ten consecutive patients who underwent PTCP and ACD were retrospectively studied. Patients were grouped according to their creatinine clearance (CrCl in ml/min/1.73 m2) calculated by the Cockcroft-Gault formula using the National Kidney Foundation classification system; Stage I (CrCl > or = 90); Stage II (60-89); Stage III (30-59); Stage IV (15-29); and Stage V (< or = 15). The primary endpoint was the combined incidence of pseudoaneurysm, retroperitoneal hematoma, femoral artery thrombosis, surgical vascular repair, and groin infection. RESULTS: Among 610 patients 283 (46%) underwent PCI. The primary endpoint was seen in 66 (10.8%) patients. Univariate predictors of primary outcome were lower CrCl (p < 0.001), and presence of peripheral vascular disease (p = 0.03). There was an inverse relationship between CrCl and complication rate. CKD was the strongest independent multivariate predictor for the primary endpoint (OR 1.032; 95% CI 1.019-1.046; p < 0.0001), driven by higher infection (p < 0.0001), thrombosis (p = 0.003) and hematoma (p = 0.007). CONCLUSIONS: Renal function appears to be significantly associated with vascular access-site complications. Worsening renal function is associated with higher vascular access site complications, largely driven by an increased infection rate.

The association of admission heart rate and in-hospital cardiovascular events in patients with non-ST-segment elevation acute coronary syndromes: results from 135 164 patients in the CRUSADE quality improvement initiative.

AIMS: To evaluate the relationship between presenting heart rate (HR) and in-hospital events in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: We evaluated 139 194 patients with NSTE-ACS in the CRUSADE quality improvement initiative. The presenting HR was summarized as 10 beat increments. Patients with systolic BP < 90 mm Hg (4030 patients) were excluded to avoid the confounding effect of cardiogenic shock. An adjusted odds ratio (OR) was calculated using a reference OR = 1 for HR of 60-69 b.p.m. after controlling for baseline variables. Primary outcome was a composite of in-hospital events all-cause mortality, non-fatal re-infarction, and stroke. Secondary outcomes were each of these considered separately. From the cohort of 135 164 patients, 8819 (6.52%) patients had a primary outcome (death/re-infarction or stroke) of which 5271 (3.90%) patients died, 3578 (2.65%) patients had re-infarction, and 1038 (0.77%) patients had a stroke during hospitalization. The relationship between presenting HR and primary outcome, all-cause mortality, and stroke followed a 'J-shaped' curve with an increased event rate at very low and high HR even after controlling for baseline variables. However, there was no relationship between presenting HR and risk of re-infarction. CONCLUSION: In contrast to patients with stable CAD, in the acute setting, the relationship between presenting HR and in-hospital cardiovascular outcomes has a 'J-shaped' curve (higher event rates at very low and high HRs). These associations should be considered in ACS prognostic models.

Low-dose spironolactone: effects on artery-to-artery vein grafts and percutaneous coronary intervention sites.

The efficacy of vein grafts used in coronary and peripheral artery bypass is limited by excessive hyperplasia and fibrosis that occur early after engraftment. In the present study, we sought to determine whether low-dose spironolactone alleviates maladaptive vein graft arterialization and alters intimal reaction to coronary artery stenting. Yorkshire pigs were randomized to treatment with oral spironolactone 25 mg daily or placebo. All animals underwent right carotid artery interposition grafting using a segment of external jugular vein and, 5 days later, underwent angiography of carotid and coronary arteries. At that time, a bare metal stent was placed in the left anterior descending artery and balloon angioplasty was performed on the circumflex coronary artery. Repeat carotid and coronary angiograms were performed before euthanasia and graft excision at 30 days. Angiography revealed that venous grafts of spironolactone-treated animals had lumen diameters twice the size of controls at 5 days, a finding that persisted at 30 days. However, neointima and total vessel wall areas also were 2- to 3-fold greater in spironolactone-treated animals, and there were no differences in vessel wall layer thicknesses or collagen and elastin densities. In the coronary circulation, there were no differences between treatment groups in any vessel wall parameters in either stented or unstented vessels. Taken together, these observations suggest that low-dose spironolactone may exert a novel protective effect on remodeling in venous arterial grafts that does not depend on the reduction of hyperplastic changes but may involve dilatation of the vessel wall.

Blood pressure paradox in patients with non-ST-segment elevation acute coronary syndromes: results from 139,194 patients in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) quality improvement initiative.

BACKGROUND: The relationship between systolic blood pressure (BP) and the risk of cardiovascular events is complex. In patients with chronic coronary artery disease, a J-shaped relationship has been shown, such that there is an increased risk of events both at high and low BP. The current coronary artery disease risk prediction models, however, considers a linear relationship between presenting BP and outcomes in patients presenting with acute coronary syndromes. METHODS: We evaluated 139,194 patients with non-ST-segment elevation acute coronary syndromes in the Can Rapid risk stratification of Unstable anigina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) quality improvement initiative. The presenting systolic BP was summarized as 10-unit increments. Primary outcome was a composite of in-hospital events all-cause mortality, reinfarction, and stroke. Secondary outcomes were each of these outcomes considered separately. RESULTS: From the cohort of 139,194 patients, 9,566 (6.87%) patients had a primary outcome (death/reinfarction or stroke) of which 5,910 (4.25%) patients died, 3,724 (2.68%) patients had reinfarction, and 1,079 (0.78%) patients had a stroke during hospitalization. There was an inverse association between presenting systolic BP and the risk of primary outcome, all-cause mortality, and reinfarction such that there was an exponential increase in the risk with lower presenting systolic BP even after controlling for baseline variables. However, there was no clear relationship between stroke and lower presenting systolic BP. CONCLUSIONS: In contrast to longitudinal impacts, there is a BP paradox on acute outcomes such that a lower presenting BP is associated with increased risk of in-hospital cardiovascular events. These associations should be considered in acute coronary syndrome prognostic models.

Can glycopyrrolate replace temporary pacemaker and atropine in patients at high risk for symptomatic bradycardia undergoing AngioJet mechanical thrombectomy?

We studied the feasibility and efficacy of glycopyrrolate, a synthetic anticholinergic agent with shorter half-life and without reflex tachycardia, in preventing symptomatic bradycardia in patients undergoing mechanical thrombectomy with the AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota). There was no need for temporary pacemaker insertion and no hemodynamically significant bradycardia in 10 consecutive patients. Additionally, there were no adverse effects from glycopyrrolate therapy. Our pilot study demonstrates that glycopyrrolate may replace temporary pacemaker insertion in these patients at high risk for symptomatic bradycardia.

Potent mitochondria-targeted peptides reduce myocardial infarction in rats.

OBJECTIVE: Previously, we demonstrated that a novel opiate peptide, 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2, provided cardioprotection against myocardial stunning in vivo. We subsequently showed that this peptide targeted mitochondria and can scavenge reactive oxygen species. The objective of this study was to determine the role of opioid versus antioxidant activity in cardioprotection. METHODS: We compared two mitochondria-targeted peptide analogs that lacked opioid activity: SS-31 (D-Arg-2',6'-dimethyl-tyrosine-Lys-Phe-NH2) and SS-20 (Phe-D-Arg-Phe-Lys-NH2). They differ in that only SS-31 has scavenging ability. Rats (n=8/group) were randomized to SS-31, SS-20 or placebo. The drugs (3 mg/kg) or saline was administered intraperitoneally 30 min before ligation of the left anterior descending artery for 60 min, and another dose given intraperitoneally 5 min before reperfusion for 60 min. Study endpoints included myocardial infarct size, cardiac arrhythmia and myocardial lipid peroxidation. RESULTS: The area at risk was similar among the groups. The infarct area/area at risk, however, was significantly smaller in the treatment groups (53.9+/-1.1% in SS-31 group, 47.1+/-1.4% in SS-20 group, versus 59.9+/-1% in the controls, P<0.01). Lipid peroxidation was significantly reduced by both SS-31 and SS-20 treatment. Arrhythmia occurred only during the early period of coronary occlusion and was less frequent and less severe in the peptide treatment groups than in the controls (Lambeth score 5 points, 3 points, versus 13 points in the controls, P<0.05). CONCLUSIONS: This study shows that pretreatment with both SS-31 and SS-20 significantly reduced myocardial lipid peroxidation and infarct size in ischemia-reperfusion injury, and suggests that the cardioprotective properties of 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it most likely reduces reactive oxygen species production during ischemia-reperfusion.