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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


Understanding Cardiac Metabolism in Normal and Ischemic States


GOAL
To provide cardiologists with information on cardiac metabolism in patients with and without ischemic disease.

TARGET AUDIENCE
This activity is designed for cardiologists. No prerequisites required.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Discuss cardiac metabolism in both the normal and ischemic state.
  • Identify the risks of reperfusion in the ischemic patient.
  • Identify and compare potential cardioprotective agents.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

The estimated time to complete this educational activity:  2 hours.
Release date: June 15, 2004. Expiration date: June 15, 2006.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an unrestricted educational grant from CV Therapeutics, Inc.

Full Disclosure Policy Affecting CME Activities:
As a sponsor accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

PROGRAM DIRECTOR

Roger S. Blumenthal, MD, FACC, FCCP, FAHA
Associate Professor of Medicine
Director, Preventive Cardiology
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease
Johns Hopkins University
School of Medicine
Baltimore, Maryland
Dr Blumenthal reports receiving grants/research support and honoraria from AstraZeneca LP, Kos Pharmaceuticals, Inc, Merck & Co, Inc, and Pfizer Inc.

PARTICIPATING FACULTY

Gary Gerstenblith, MD
Professor of Medicine
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Gerstenblith reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Mikhail Maslov, PhD
Research Fellow
Cardiology Division
Department of Medicine and MRI Research Division
Department of Radiology
Johns Hopkins Hospital
Baltimore, Maryland
Dr Maslov reports having no significant financial or advisory relationships with corporate organizations related to this activity.

William C. Stanley, PhD
Associate Professor
Department of Physiology and Biophysics
Case Western Reserve University
School of Medicine
Cleveland, Ohio
• Dr Stanley reports receiving grants/research support and serving as a consultant to CV Therapeutics and Chugai Pharma USA, LLC; and receiving honoraria from Servier.

Robert G. Weiss, MD
Professor of Medicine
Cardiology Division
Johns Hopkins University School of Medicine
Baltimore, Maryland
• Dr Weiss reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Notice
In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:

Dr Stanley—antioxidants, L-carnitine, oxfenicine, perhexiline, propionyl L-carnitine, ranolazine, trimetazidine

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Understanding Cardiac Metabolism In Normal And Ischemic States
Roger S. Blumenthal, MD, FACC, FCCP, FAHA*

Acute myocardial ischemia and acute coronary syndrome are included in the classification of coronary heart disease (CHD) and represent the single largest cause of death of adults in the United States. Treatment of cardiovascular disease is multifaceted and individualized and generally includes lifestyle changes, pharmacologic intervention, or surgical intervention. Traditional pharmacologic treatments for ischemic heart disease focus on a hemodynamic approach to relieving symptoms of angina. However, data suggest that CHD is a consequence of abnormalities in cardiac metabolic pathways brought about by decreased oxygen. A basic understanding of cardiac metabolism was established several decades ago. More recent research has allowed for a greater appreciation of the importance of metabolism in the heart as it relates to pathologic conditions. The manipulation of cardiac metabolism is at the root of many novel treatment approaches for the management of CHD in patients. In this series, an overview of cardiac metabolism in the normal well-oxygenated state and in the pathologic ischemic state is provided.

Mikhail Maslov, PhD, Research Fellow, Cardiology Division, Department of Medicine and MRI Research Division, Department of Radiology, Johns Hopkins Hospital, and Robert G. Weiss, MD, Professor of Medicine, Cardiology Division, Johns Hopkins University School of Medicine, provide the groundwork for understanding cardiac metabolism by detailing the process of fueling cardiac contraction under normal conditions. The metabolic demands of the heart are very large and require a balance between substrates for metabolism and energy production over a wide range of workloads. The concept of adenosine triphosphate (ATP) as a chemical form of energy to meet divergent energy needs is explained. The major pathways for the production of ATP from 3 main substratesÑfatty acids, carbohydrates, and ketone bodiesÑare provided. Drs Maslov and Weiss offer a well-balanced discussion of the extremely complex and varied mechanisms involved in myocardial energy metabolism.

The subsequent article outlines derangements in cardiac metabolism during ischemia. The well-oxygenated heart generates the majority of its energy requirements via oxidation of lipids followed by glucose oxidation and glycolysis. The utilization of fatty acids requires more oxygen than that of glucose to produce the same amount of ATP. This preference for fatty acids becomes problematic when oxygen supply is diminished, such as during ischemia. Gary Gerstenblith, MD, Professor of Medicine, Johns Hopkins University School of Medicine, describes biochemical changes in the heart that occur as a consequence of decreased oxygen supply and reperfusion. When levels of oxygen are diminished, the primary source of ATP in the heart remains fatty acids, but the importance of glycolysis increases as glucose oxidation is decreased. The sequential intracellular acidosis and alterations in ionic homeostasis are associated with damage to mitochondria and myocardial cell death. The phenomenon of additional myocyte injury associated with reperfusion is also described.

William C. Stanley, PhD, Associate Professor, Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, ties the previous presentations together in a review of potential agents for the provision of cardioprotection in the patient with CHD. Optimization of therapy is described as are traditional and novel pharmacologic approaches. The mechanisms of action, efficacy, and safety are presented for nitroglycerin, calcium-channel blockers, beta blockers, and angiotensin-converting enzyme inhibitors, which represent traditional pharmacologic treatments. Novel therapies that exert an effect on the metabolism of  cardiac energy are also reviewed. Included in this discussion is an overview of carnitine derivatives, antioxidants, and fatty acid oxidation inhibitors.

This is an exciting time to be involved in the practice of contemporary cardiovascular medicine. Not only are we building upon our understanding of basic cardiac energy metabolism, we are also observing an emergence in novel treatment agents aimed toward the manipulation of ischemic heart disease as a metabolic problem. New agents utilizing nonhemodynamic mechanisms offer promise for the more effective management of patients with CHD.

*Associate Professor of Medicine, Director, Preventive Cardiology, Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Address correspondence to: Roger S. Blumenthal, MD, FACC, FCCP, FAHA, Johns Hopkins Ciccarone Center, 600 N Wolfe Street - Blalock 524-C, Baltimore, MD 21287. E-mail: rblument@jhmi.edu.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.