Trials, tribulations and speculation! Report from the 7th Biennial Hatter Cardiovascular Institute Workshop

Bell, Robert M.; Beeuwkes, Reinier; Bøtker, Hans Erik; Davidson, Sean M.; Downey, James M.; Garcı́a-Dorado, David; Hausenloy, Derek J.; Heusch, Gerd; Ibáñez, Borja; Kitakaze, Masafumi; Lecour, Sandrine; Mentzer, Robert M.; Miura, Tetsuji; Opie, Lionel H.; Ovize, Michel; Ruiz‐Meana, Marisol; Schulz, Rainer; Shannon, Richard P.; Walker, John M.; Vinten‐Johansen, Jakob; Yellon, Derek M.

doi:10.1007/s00395-012-0300-6

Cited by 21 publications

(12 citation statements)

References 37 publications

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“…33 Huge resources have been dedicated to exploring novel therapies that might reduce infarct size but so far with little success. 34 Here, we show that an inexpensive medication already approved for STEMI treatment (intravenous metoprolol) can significantly reduce infarct size simply by being administered before reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

et al. 2013

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Background-The effect of β-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). Methods and Results-Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean±SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6±15.3 versus 32.0±22.2 g; adjusted difference, −6.52; 95% confidence interval, −11.39 to −1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was −8.13 (95% confidence interval, −13.10 to −3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). Conclusions-In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI.

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Section: Discussionmentioning

confidence: 99%

Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

et al. 2013

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“…This apparent failure can be attributed to a number of different factors. These include the use of animal models that do not adequately represent clinical reality, e.g., due to lack of comorbidities; and poor study design (Ludman et al, 2010;Ovize et al, 2010;SchwartzLongacre et al, 2011;Hausenloy et al, 2010Hausenloy et al, , 2013aBell et al, 2012).…”

Section: Pharmacologic Postconditioningmentioning

confidence: 99%

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Ferdinándy¹,

Hausenloy²,

Heusch³

et al. 2014

Pharmacol Rev

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“…63 Recently, it has been suggested that plasma exosomes are cardioprotective in a Langendorff-perfused heart system. 64 Given the many beneficial aspects of exosomes outlined here, their induction after hypoxia, 41,65 and their ability to transmit cardioprotective signals, an attractive hypothesis is that exosomes contribute to the humoral transmission of the cardioprotective state induced by cardioprotective modalities, such as remote ischemic preconditioning. If our hypothesis is validated, then this would suggest that exosomes may harbor novel cardioprotective molecules.…”

Section: Exosomes and Cardioprotectionmentioning

confidence: 99%

Exosomes

Yellon

Davidson

2014

Circulation Research

175

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Trials, tribulations and speculation! Report from the 7th Biennial Hatter Cardiovascular Institute Workshop

Cited by 21 publications

References 37 publications

Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Effect of Early Metoprolol on Infarct Size in ST-Segment–Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

Exosomes

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