Prodromal Angina Limits Infarct Size

Ottani, Filippo; Galvani, Marcello; Ferrini, Donatella; F, Sorbello; Limonetti, P; Pantoli, Denis; Rusticali, F

doi:10.1161/01.cir.91.2.291

Cited by 352 publications

(65 citation statements)

References 24 publications

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“…First, despite inclusion and exclusion criteria in DELTA MI that were designed to define a very specific, homogeneous patient population, factors that significantly influence biomarker end points (including total ischemia time before reperfusion, diabetes mellitus, prodromal angina before presentation, and collaterals to the LAD distribution) varied substantially among active study drug versus concurrent placebo across dosing cohorts and influenced the evaluation of drug activity with the biomarker results. [12][13][14][15][16][17][18][19] Second, we observed a wide variability in the interquartile ranges of the quantitative biomarker results because of the small sample sizes of the dosing cohorts, and this variability influenced the statistical comparisons between active study drug versus concurrent placebo within dosing cohorts and prevented definitive conclusions on the impact of active study drug. Finally, we demonstrated consistent but nonsignificant improvements with active study drug with biomarkers collected during the first 24 to 36 hours such as ST recovery and CK-MB AUC values.…”

Section: Use Of Biomarkers Of Reperfusion Successmentioning

confidence: 92%

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

Bates

Bode²,

Costa³

et al. 2008

Circulation

162

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Background-KAI-9803, a ␦-protein kinase C inhibitor, has been shown to ameliorate injury associated with ischemia and reperfusion in animal models of acute myocardial infarction (MI). Methods and Results-Direct Inhibition of ␦-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) was a "first-in-human," dose-escalation study that evaluated the safety, tolerability, and activity of KAI-9803 for patients with acute anterior ST-segment elevation MI undergoing primary percutaneous coronary intervention. Patients who presented within 6 hours of symptom onset and had an occluded left anterior descending infarct artery on angiography were randomized in a 2:1 fashion to receive 1 of 4 doses of KAI-9803 (cohort 1, 0.05 mg; cohort 2, 0.5 mg; cohort 3, 1.25 mg; cohort 4, 5.0 mg) versus blinded concurrent placebo delivered in 2 divided doses via intracoronary injection before and after reestablishment of antegrade epicardial flow with percutaneous coronary intervention. Safety and biomarker end points were assessed. Overall, 154 patients were randomized and treated with study drug (37 in cohort 1, 38 in cohort 2, 38 in cohort 3, 41 in cohort 4). The incidence of serious adverse events was similar between patients treated with KAI-9803 versus placebo. Other safety end points, including changes in QT intervals and standard laboratory values after study drug administration, were similar between treatment groups. Although the study was not powered to demonstrate efficacy with the biomarker end points assessed, signs of drug activity with KAI-9803 were suggested by trends for consistent, nonsignificant reductions in creatine kinase-MB area under the curve and ST-recovery area under the curve values across all dosing cohorts with KAI-9803 compared with concurrent placebo, and similar trends were demonstrated for improvements in 99m technetium sestamibi infarct size values with active study drug in cohorts 1, 2, and 3. Conclusions-KAI-9803 had an acceptable safety and tolerability profile when delivered via intracoronary injection during primary percutaneous coronary intervention for ST-segment elevation MI. Signs of potential drug activity were demonstrated with biomarker end points in this small exploratory study, indicating that further testing of KAI-9803 as an adjunctive therapy for ST-segment elevation MI is warranted. (Circulation. 2008;117:886-896.)

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Section: Use Of Biomarkers Of Reperfusion Successmentioning

confidence: 92%

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

Bates

Bode²,

Costa³

et al. 2008

Circulation

162

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“…[1][2][3][4] The myocardial protection that results from ischemic preconditioning (IP) is characterized by reduced infarct size, decreased incidence of fatal arrhythmias, and reduced postischemic contractile cardiac dysfunction. 4 -6 Multiple mechanisms have been suggested to play a role in IP, [7][8][9][10] including vascular endothelial growth factor (VEGF)-mediated neovascularization during myocardial ischemia [11][12][13] protein kinase C activation, 2,4,[13][14][15][16] and nitric oxide synthase (NOS) activity, [17][18][19] among others.…”

mentioning

confidence: 99%

Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via “Imported” Nitric Oxide Synthase Activity

et al. 2005

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Background-The function of bone marrow-derived endothelial progenitor cells (EPCs) in repair of ischemic tissue has been the subject of intense scrutiny, and the capacity of these cells to contribute significantly to new blood vessels remains controversial. The possibility that EPCs could act as reservoirs of cytokines has been implied by several observations; however, a specific role for cytokine delivery has not been identified. Methods and Results-We performed a series of experiments that revealed the rapid recruitment of EPCs to the myocardium by very short periods of ischemia, so-called ischemic preconditioning. The recruited EPCs express an array of potentially cardioprotective cytokines including nitric oxide synthase isoforms. Bone marrow transplantation studies, using donor marrow null for nitric oxide synthase isoforms, revealed that both endothelial and inducible nitric oxide synthase derived from bone marrow cells play essential roles in the cardioprotective effect that normally occurs after ischemic preconditioning. Conclusions-These findings provide novel insights about the role of bone marrow-derived cells in ischemic preconditioning and also reveal that distinct mechanisms regulate recovery after ischemia-reperfusion and chronic ischemic injury.

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“…The presence of PIA was associated with better clinical course after AMI and reduction in infarct size, as assessed indirectly by measurement of myocardial necrosis markers 3 or quantitative SPECT (single-photon emission computed tomography) 4 . Other authors have found a decrease in ventricular remodeling 5 , as well as in the incidence of ventricular arrhythmias, congestive heart failure (CHF), cardiogenic shock, and death [6][7][8] .…”

Section: Introductionmentioning

confidence: 98%

“…These patients report angina symptoms that are more severe in the morning and subside during the course of the day, providing evidence that myocardial metabolism becomes more efficient during subsequent efforts 2 . Angina pectoris prior to acute myocardial infarction (AMI), called preinfarction angina (PIA), is likely to be a marker of IPC [3][4][5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Angina pré-infarto na evolução intra-hospitalar de pacientes idosos com infarto agudo do miocárdio

Shian

Lima

Filho

2007

Arq. Bras. Cardiol.

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Prodromal Angina Limits Infarct Size

Cited by 352 publications

References 24 publications

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

Intracoronary KAI-9803 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

Endothelial Progenitor Cells Are Rapidly Recruited to Myocardium and Mediate Protective Effect of Ischemic Preconditioning via “Imported” Nitric Oxide Synthase Activity

Angina pré-infarto na evolução intra-hospitalar de pacientes idosos com infarto agudo do miocárdio

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