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Published on: August 6, 2015
Myocardial ischemia: no supply/demand mismatch but reduced blood flow per beat
1Cardioprotection Unit, Institute for Pathophysiology, West German Heart and Vascular Center, University of Duisburg-Essen, Hufelandtsr. 55, 45122, Essen, Germany. Gerd.heusch@uk-essen.de.
Insights
Myocardial ischemia views are shifting. The study challenges the supply/demand mismatch model, highlighting that coronary blood flow, not hypothetical demand, dictates myocardial function and salvage in ischemic heart conditions.
Area of Science:
- Cardiology
- Physiology
- Pathophysiology
Background:
- Current understanding of myocardial ischemia is evolving, with increased focus on plaque vulnerability in acute coronary syndromes and coronary microcirculation in chronic conditions.
- The traditional supply/demand mismatch paradigm for myocardial ischemia, derived from animal studies, faces challenges in explaining clinical scenarios, particularly those involving coronary microvascular dysfunction.
Purpose of the Study:
- To critically evaluate the supply/demand mismatch paradigm for myocardial ischemia.
- To investigate the relationship between coronary blood flow and myocardial function in ischemic conditions.
- To propose an alternative framework for understanding myocardial ischemia based on perfusion-contraction matching.
Main Methods:
- Review of existing literature and experimental data on myocardial ischemia.
- Analysis of animal studies (dogs and pigs) examining regional myocardial contractile function and blood flow during ischemia.
- Examination of the effects of interventions like beta-blockade on myocardial function and blood flow.
Main Results:
- The supply/demand paradigm has fundamental limitations and is ill-suited for coronary microvascular dysfunction.
- A direct proportionality exists between reduced blood flow and reduced myocardial contractile function during ischemia (perfusion-contraction match).
- Beta-blockade increases myocardial blood flow and contractile function, contradicting the concept of reducing hypothetical demand.
Conclusions:
- The perfusion-contraction match, where coronary blood flow directly determines myocardial function, provides a more accurate model for ischemia than supply/demand mismatch.
- Restoration of coronary blood flow is paramount for salvaging ischemic myocardium in acute coronary syndromes.
- Understanding the flow-function relationship is crucial for developing effective therapeutic strategies for myocardial ischemia.
Abstract:
The views on myocardial ischemia are changing-with an increasing focus on plaque vulnerability in acute coronary syndromes and more attention to the coronary microcirculation in chronic coronary syndromes. The unifying paradigm of supply/demand mismatch to characterize myocardial ischemia was developed from experiments in dogs with coronary occlusion and reperfusion and later used to also characterize myocardial ischemia from stress- and exercise-induced ischemia in settings of epicardial coronary stenoses. However, the supply/demand paradigm of myocardial ischemia has fundamental problems and appears not well suited to explain clinical scenarios with coronary microvascular dysfunction. Demand is an anthropocentric/hypothetical parameter which cannot be measured. In fact, in detailed and extensive experiments in dogs and pigs, regional myocardial contractile function which largely determines energy consumption, is reduced proportionately with the reduction of blood flow during ischemia-there is a perfusion-contraction match. When coronary blood flow is expressed in µl/g per cardiac cycle, the relationships of flow and function in ischemic myocardium at rest and during exercise are superimposable. Supporting the view that flow determines function, beta-blockade increases blood flow per cardiac cycle and in consequence also increases contractile function of the ischemic myocardium rather than reducing its hypothetical demand. In acute coronary syndromes, again supporting the pivotal role of coronary blood flow, the only way to salvage ischemic myocardium is restoration of blood flow, and all maneuvers to protect ischemic myocardium such as ischemic conditioning work only in conjunction with reperfusion.
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