Mechanisms of cardiac contraction. What roles for preload, afterload and inotropic state in heart failure?
Insights
The failing heart
Area of Science:
- Cardiology
- Heart Failure Pathophysiology
- Cardiac Mechanics
Background:
- The Frank-Starling mechanism's role in cardiac failure is debated.
- Chronic cardiac enlargement may not alter maximal sarcomere length.
- Failing hearts may not operate on the true descending limb of the Frank-Starling curve.
Purpose of the Study:
- To investigate the functional significance of the Frank-Starling mechanism in heart failure.
- To explore the roles of preload reserve, afterload mismatch, and inotropic reserve in cardiac function during heart failure.
- To evaluate the hemodynamic effects of interventions like vasodilators and inotropic agents in experimental heart failure.
Main Methods:
- Analysis of sarcomere length dynamics during chronic cardiac enlargement.
- Assessment of ventricular end-diastolic volume's geometric role in maintaining stroke volume.
- Investigation of afterload mismatch and its impact on cardiac function.
- Experimental treatment of acute heart failure using nitroprusside (a mixed vasodilator).
- Evaluation of central blood volume shifts and their counterbalancing effects on venodilator action.
- Assessment of failing myocardium's response to positive inotropic agents.
Main Results:
- Sarcomere length remains near maximal and shows little change during chronic cardiac enlargement.
- Ventricular end-diastolic volume increases are geometrically important for stroke volume maintenance.
- Afterload mismatch can lead to apparent operation on a descending limb of cardiac function, especially under pressure loading.
- Nitroprusside's efficacy in acute heart failure is limited by significant peripheral blood volume shifts that counteract venodilation.
- Hemodynamic benefits of potent inotropic drugs in heart failure are largely attributed to their vasodilating properties.
- A degree of inotropic reserve is present even in severely failing myocardium.
Conclusions:
- The Frank-Starling mechanism has a limited role at the sarcomere level in heart failure.
- Afterload mismatch and its correction are crucial for improving cardiac function, contingent on increased venous return.
- Inotropic reserve exists in failing myocardium, but the risks and benefits of sustained stimulation require further research.
Abstract:
There is evidence that sarcomere length is maximal and changes little during chronic cardiac enlargement, and that the failing heart does not operate on a true descending limb of the Frank-Starling curve. However, increases of ventricular end-diastolic volume over time clearly are important at the geometrical level in maintaining stroke volume. When the preload reserve is fully utilized, afterload mismatch can exist in the steady state to produce operation of the heart on an apparent descending limb of cardiac function, and further afterload mismatch can be produced by pressure loading under these conditions. The treatment of acute experimental heart failure with a mixed vasodilator (nitroprusside) can lead to an increased cardiac output by afterload reduction only when the venous return curve does not shift downward; thus, the threefold larger shift of central blood volume to the periphery in heart failure (compared to normal) counter balances the venodilator action of nitroprusside. Whether or not the inotropic ceiling of failing myocardium can be reached by positive inotropic agents is unclear, but major hemodynamic benefits in heart failure with many potent inotropic drugs are associated with the direct vasodilating properties of these agents. Thus, there appears to be little role for the Frank-Starling mechanism at the sarcomere level, whereas afterload mismatch and its correction are of major importance provided the venous return can be increased. A degree of inotropic reserve also is available, even in the severely failing myocardium, but more research is needed on the potential costs and benefits of marked sustained inotropic stimulation.
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