Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease

Iraklis I Pipinos, Victor G. Sharov, Alexander D. Shepard, Petros V. Anagnostopoulos, Asterios Katsamouris, Anastasia Todor, Konstantinos A. Filis, Hani N. Sabbah

Research output: Contribution to journalArticle

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Abstract

Objective: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. Methods: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V0), after addition of substrates (malate and glutamate; (VSUB), after addition of adenosine diphosphate (ADP) (VADP), and finally, after adenine nucleotide translocase inhibition with atractyloside (VAT). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V ADP/VAT). Results. Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 ± 0.06 vs 0.55 ± 0.12; P = .09), but Vsub was significantly lower in patients with PAD compared with control subjects (0.43 ± 0.07 vs 0.89 ± 0.20; P < .05), as was VADP (0.69 ± 0.13 vs 1.24 ± 0.20; P < .05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 ± 0.07 vs 0.45 ± P=.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 ± 0.10 vs 2.90 ± 0.20; P < .001). Conclusion: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.

Original languageEnglish (US)
Pages (from-to)827-832
Number of pages6
JournalJournal of vascular surgery
Volume38
Issue number4
DOIs
StatePublished - Oct 2003

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Peripheral Arterial Disease
Respiration
Skeletal Muscle
Respiratory Rate
Atractyloside
ATP Translocases Mitochondrial ADP
Adenosine Diphosphate
Muscle Mitochondrion
Mitochondria
Muscles
Leg
Saponins
Glutamic Acid
Lower Extremity
Electrodes
Oxygen

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Pipinos, I. I., Sharov, V. G., Shepard, A. D., Anagnostopoulos, P. V., Katsamouris, A., Todor, A., ... Sabbah, H. N. (2003). Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease. Journal of vascular surgery, 38(4), 827-832. https://doi.org/10.1016/S0741-5214(03)00602-5

Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease. / Pipinos, Iraklis I; Sharov, Victor G.; Shepard, Alexander D.; Anagnostopoulos, Petros V.; Katsamouris, Asterios; Todor, Anastasia; Filis, Konstantinos A.; Sabbah, Hani N.

In: Journal of vascular surgery, Vol. 38, No. 4, 10.2003, p. 827-832.

Research output: Contribution to journalArticle

Pipinos, II, Sharov, VG, Shepard, AD, Anagnostopoulos, PV, Katsamouris, A, Todor, A, Filis, KA & Sabbah, HN 2003, 'Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease', Journal of vascular surgery, vol. 38, no. 4, pp. 827-832. https://doi.org/10.1016/S0741-5214(03)00602-5
Pipinos, Iraklis I ; Sharov, Victor G. ; Shepard, Alexander D. ; Anagnostopoulos, Petros V. ; Katsamouris, Asterios ; Todor, Anastasia ; Filis, Konstantinos A. ; Sabbah, Hani N. / Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease. In: Journal of vascular surgery. 2003 ; Vol. 38, No. 4. pp. 827-832.
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abstract = "Objective: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. Methods: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V0), after addition of substrates (malate and glutamate; (VSUB), after addition of adenosine diphosphate (ADP) (VADP), and finally, after adenine nucleotide translocase inhibition with atractyloside (VAT). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V ADP/VAT). Results. Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 ± 0.06 vs 0.55 ± 0.12; P = .09), but Vsub was significantly lower in patients with PAD compared with control subjects (0.43 ± 0.07 vs 0.89 ± 0.20; P < .05), as was VADP (0.69 ± 0.13 vs 1.24 ± 0.20; P < .05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 ± 0.07 vs 0.45 ± P=.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 ± 0.10 vs 2.90 ± 0.20; P < .001). Conclusion: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.",
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T1 - Abnormal mitochondrial respiration in skeletal muscle in patients with peripheral arterial disease

AU - Pipinos, Iraklis I

AU - Sharov, Victor G.

AU - Shepard, Alexander D.

AU - Anagnostopoulos, Petros V.

AU - Katsamouris, Asterios

AU - Todor, Anastasia

AU - Filis, Konstantinos A.

AU - Sabbah, Hani N.

PY - 2003/10

Y1 - 2003/10

N2 - Objective: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. Methods: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V0), after addition of substrates (malate and glutamate; (VSUB), after addition of adenosine diphosphate (ADP) (VADP), and finally, after adenine nucleotide translocase inhibition with atractyloside (VAT). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V ADP/VAT). Results. Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 ± 0.06 vs 0.55 ± 0.12; P = .09), but Vsub was significantly lower in patients with PAD compared with control subjects (0.43 ± 0.07 vs 0.89 ± 0.20; P < .05), as was VADP (0.69 ± 0.13 vs 1.24 ± 0.20; P < .05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 ± 0.07 vs 0.45 ± P=.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 ± 0.10 vs 2.90 ± 0.20; P < .001). Conclusion: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.

AB - Objective: Discrete morphologic, enzymatic and functional changes in skeletal muscle mitochondria have been demonstrated in patients with peripheral arterial disease (PAD). We examined mitochondrial respiration in the gastrocnemius muscle of nine patients (10 legs) with advanced PAD and in nine control patients (nine legs) without evidence of PAD. Methods: Mitochondrial respiratory rates were determined with a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles. Muscle samples were obtained from the anteromedial aspect of the gastrocnemius muscle, at a level 10 cm distal to the tibial tuberosity. Mitochondria respiratory rate, calculated as nanoatoms of oxygen consumed per minute per milligram of noncollagen protein, were measured at baseline (V0), after addition of substrates (malate and glutamate; (VSUB), after addition of adenosine diphosphate (ADP) (VADP), and finally, after adenine nucleotide translocase inhibition with atractyloside (VAT). The acceptor control ratio, a sensitive indicator of overall mitochondrial function, was calculated as the ratio of the respiratory rate after the addition of ADP to the respiratory rate after adenine nucleotide translocase inhibition with atractyloside (V ADP/VAT). Results. Respiratory rate in muscle mitochondria from patients with PAD were not significantly different from control values at baseline (0.31 ± 0.06 vs 0.55 ± 0.12; P = .09), but Vsub was significantly lower in patients with PAD compared with control subjects (0.43 ± 0.07 vs 0.89 ± 0.20; P < .05), as was VADP (0.69 ± 0.13 vs 1.24 ± 0.20; P < .05). Respiratory rates after atractyloside inhibition in patients with PAD were no different from those in control patients (0.47 ± 0.07 vs 0.45 ± P=.08). Compared with control values, mitochondria from patients with PAD had a significantly lower acceptor control ratio (1.41 ± 0.10 vs 2.90 ± 0.20; P < .001). Conclusion: Mitochondrial respiratory activity is abnormal in lower extremity skeletal muscle in patients with PAD. When considered in concert with the ultrastructural and enzymatic abnormalities previously documented in mitochondria of chronically ischemic muscle, these data support the concept of defective mitochondrial function as a pathophysiologic component of PAD.

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