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Cellular electrophysiology of coronary artery ligation in chronic pressure overload
Insights
Acute myocardial ischemia combined with chronic pressure overload causes unique cellular electrophysiologic abnormalities in ventricular myocardium. These findings reveal critical changes in heart muscle function under combined stress.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Myocardial Pathophysiology
Background:
- Chronic pressure overload leads to ventricular hypertrophy and fibrosis.
- Acute myocardial ischemia causes significant cellular dysfunction.
Purpose of the Study:
- To investigate cellular electrophysiologic abnormalities in ventricular myocardium under combined chronic pressure overload and acute ischemia.
- To compare these abnormalities with those seen in control, ischemia alone, or overload alone.
Main Methods:
- Induction of left ventricular systolic hypertension in cats via aortic constriction.
- Imposition of acute myocardial ischemia (2 hours) on pressure-overloaded hearts.
- In vitro electrophysiologic recordings of transmembrane action potentials from myocardial tissue.
Main Results:
- Combined ischemia/overload significantly increased spontaneous premature depolarizations and unique repetitive bursts.
- Border zones of fibrotic areas in ischemia/overload showed maintained but depressed resting potentials without action potentials.
- Non-fibrotic areas in ischemia/overload exhibited diminished electrophysiologic properties compared to ischemia or overload alone.
Conclusions:
- Acute myocardial ischemia superimposed on chronic pressure overload induces distinct and additional cellular electrophysiologic abnormalities.
- These abnormalities are particularly pronounced at the interface of fibrotic tissue.
- The study highlights the complex interplay between chronic and acute cardiac stressors on myocardial function.
Abstract:
We evaluated ischemia-induced cellular electrophysiologic abnormalities in chronic pressure overload ventricular myocardium in vitro. Left ventricular systolic hypertension was induced in cats via partial supracoronary aortic constriction (overload); at 1 1/2-3 months, resulting pressure overload was accompanied by ventricular hypertrophy (25-35% by weight) and patchy endocardial fibrosis. Two hours of subsequent acute myocardial ischemia (ischemia) was imposed on overload (ischemia/overload) via total occlusion of distal branches of the left coronary artery system. Spontaneous premature depolarizations in vitro were increased in ischemia/overload compared to control, ischemia or overload alone; bursts of spontaneous, repetitive depolarizations were also unique to these preparations. Multiple site recordings of endocardial transmembrane action potentials overlying the borders (interface) of fibrotic areas in ischemia/overload demonstrated numerous electrophysiologic abnormalities, including several not observed in control, ischemia or overload. Unique to the border areas of ischemia/overload preparations was the presence of maintained but depressed resting potential without action potentials; also, the incidence of depolarizations at the onset of the plateau phase was highest in these preparations. In non-fibrotic areas, electrophysiologic properties including resting potential and action potential amplitude and rate of rise were diminished in ischemia/overload compared to ischemia or overload preparations. These data demonstrate that acute myocardial ischemia in the setting of chronic pressure overload leads to additional cellular electrophysiologic abnormalities compared to ischemia or overload alone.