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[Hypertensive myocardial hypertrophy and rhythm disorders: 2 possible origins]
P Belichard1, D Pruneau, N L Brown
1Laboratoires Fournier, Daix, Fontaine-lès-Dijon.
Insights
Hypertension and left ventricular hypertrophy in spontaneously hypertensive rats (SHR) lead to significant cardiac electrical abnormalities and fibrosis. These changes increase the risk of ventricular arrhythmias, unlike in normotensive controls (WKY).
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Pathology
Background:
- Hypertension is linked to left ventricular hypertrophy (LVH) and complex ventricular arrhythmias.
- Previous studies showed increased ventricular fibrillation in spontaneously hypertensive rats (SHR) after coronary ligation.
- The current study investigates structural and electrophysiological changes in hypertrophied hearts contributing to arrhythmias.
Purpose of the Study:
- To characterize structural and electrophysiological abnormalities in hypertrophied rat hearts.
- To correlate these abnormalities with the occurrence of ventricular arrhythmias.
- To identify specific mechanisms underlying arrhythmogenesis in hypertensive hearts.
Main Methods:
- Utilized a double tissue bath to expose ventricular strips to normal and altered conditions (low pH, hypoxia, high potassium).
- Recorded electrical activity using micro-electrode techniques to assess conduction and action potential characteristics.
- Employed automated image analysis to quantify sub-endocardial collagen fibrosis.
- Measured action potential duration (APD90) in papillary muscles.
Main Results:
- Significant alterations in cardiac conduction and maximal upstroke velocity (Vmax) were observed in SHR compared to WKY rats.
- Hypertrophied ventricles in SHR exhibited marked sub-endocardial collagen fibrosis.
- Action potential duration (APD90) was significantly prolonged in SHR papillary muscles.
- Blocking potassium channels induced triggered activity from early afterdepolarizations in SHR, but not WKY, hearts.
Conclusions:
- Left ventricular hypertrophy in SHR is associated with significant electrophysiological abnormalities, including impaired conduction and prolonged action potentials.
- Increased collagen fibrosis in the sub-endocardium of SHR hearts may contribute to arrhythmogenesis.
- Early afterdepolarizations and triggered activity, exacerbated by potassium channel blockade, represent a mechanism for arrhythmias in hypertensive hearts.
Abstract:
It has been suggested that complex ventricular arrhythmias commonly occur in hypertensive patients with left ventricular hypertrophy. We have previously demonstrated that coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) resulted in a significantly increased incidence and duration of ventricular fibrillation in SHR compared with WKY. The object of the present study was to characterize the structural and electrophysiological abnormalities in hypertrophied hearts, associated with the occurrence of arrhythmias. We used a double tissue bath in which a ventricular strip was exposed simultaneously to normal and to altered conditions (low pH, hypoxia and high potassium). Electrical activity recorded using standard micro-electrode techniques showed the occurrence of arrhythmias in all preparations and the development of major alterations in conduction (a conduction block appeared at 11 +/- 1 mn in SHR vs 16 +/- 1 mn in WKY, p less than 0.05), and maximal upstroke velocity (Vmax values before and 3 mn after the beginning of ischemia were 229 +/- 12 to 46 +/- 7 v/s for the SHR and 227 +/- 10 to 106 +/- 12 v/s for the WKY; p less than 0.001). These changes were associated in hypertrophied ventricles with a marked sub-endocardial collagen fibrosis as estimated by the use of automated image analysis (subendocardial collagen density = 4.39 +/- 0.34 p. 100 in SHR vs 1.66 +/- 0.15 p. 100 in WKY; p less than 0.001). Action potential duration measured using conventional glass micro-electrodes in a single chamber tissue bath revealed a highly significant difference (p less than 0.001) in APD 90 p. 100 of papillary muscles between SHR (114.7 +/- 2.8 ms) and WKY (76.9 +/- 1.7 ms). The addition of tetra-ethylammonium to block potassium channels induced triggered activity arising from early afterdepolarizations only in muscles hypertrophied SHR hearts.(ABSTRACT TRUNCATED AT 250 WORDS)