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Alterations in small arterioles precede changes in limb skeletal muscle after myocardial infarction
D P Thomas1, O Hudlicka, M D Brown
1Department of Physiology, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Abstract:
We tested the hypothesis that alterations in arterioles in locomotor skeletal muscles in rats with myocardial infarction (MI), but before development of congestive heart failure (CHF), precede structural and functional changes commonly observed in limb muscle in association with CHF. Resting diameters of third- (A3) and fourth-order arterioles (A4) in extensor digitorum longus (EDL) muscle were significantly smaller in rats with nonfailing small and medium-sized MI compared with control animals. Dilation of A4 in response to 10(-4) M adenosine was significantly attenuated in both groups (P < 0.05), whereas dilation of A3 was unaltered. Microvessels from both groups of infarcted rats constricted to all doses of acetylcholine (10(-9), 10(-8), and 10(-7) M) and showed a significantly exaggerated vasoconstrictor response to norepinephrine (10(-9), 10(-8), and 10(-7) M) compared with microvessels in control rats (P < 0.05). Peak isometric tension of combined tibialis anterior and EDL muscles and muscle fatigue (final/peak tension x 100), measured during 5-min isometric supramaximal twitch contractions at 4 Hz, were similar in control and MI rats (218 +/- 7 vs. 213 +/- 15 g/g muscle and 52 +/- 1 vs. 51 +/- 9%, respectively; n = 5 for both). There was also no difference with respect to the proportion of oxidative fibers or capillary-to-fiber ratios. Our results indicate that, in rats with left ventricular dysfunction but without failure, decreased diameter and perturbations in reactivity of small arterioles precede alterations in skeletal muscle performance often seen at a later date in association with CHF. These findings are consistent with the notion of aberrant endothelial and smooth muscle function and may contribute to the maintenance of blood pressure after MI but before CHF.
Insights
In rats with heart dysfunction but no heart failure, small blood vessels in leg muscles shrink and react abnormally before muscle performance declines. These changes in arterioles may impact blood pressure post-heart attack.
Area of Science:
- Cardiovascular Physiology
- Skeletal Muscle Biology
- Vascular Biology
Background:
- Myocardial infarction (MI) can lead to congestive heart failure (CHF), often associated with skeletal muscle dysfunction.
- The early vascular changes in locomotor muscles preceding CHF are not well understood.
Purpose of the Study:
- To investigate if arteriolar alterations in locomotor skeletal muscles occur before the development of CHF in rats with myocardial infarction (MI).
- To determine if these early vascular changes precede functional deficits in skeletal muscle.
Main Methods:
- Rats with nonfailing MI were compared to control rats.
- Resting diameters of third- (A3) and fourth-order arterioles (A4) in the extensor digitorum longus (EDL) muscle were measured.
- Vascular reactivity to adenosine, acetylcholine, and norepinephrine was assessed.
- Skeletal muscle performance (peak tension and fatigue) and fiber type proportion were evaluated.
Main Results:
- Rats with MI showed smaller resting diameters of A3 and A4 arterioles compared to controls.
- Dilation to adenosine was attenuated in A4 arterioles, while constriction to acetylcholine and exaggerated vasoconstriction to norepinephrine were observed in both A3 and A4 arterioles.
- Skeletal muscle peak tension, fatigue, oxidative fiber proportion, and capillary-to-fiber ratios were similar between MI and control rats.
- These vascular changes occurred before any detectable decline in skeletal muscle performance.
Conclusions:
- Decreased arteriolar diameter and altered vascular reactivity in locomotor muscles precede skeletal muscle performance deficits in rats with left ventricular dysfunction before CHF.
- These findings suggest aberrant endothelial and smooth muscle function early after MI.
- These vascular alterations may play a role in maintaining blood pressure in the pre-CHF stage following MI.