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

AbstractObjectiveDiscrete 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.MethodsMitochondrial 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 (VADP/ VAT).ResultsRespiratory 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).ConclusionMitochondrial 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

Effects of Isoflurane Anesthesia on Aortic Compliance and Systemic Hemodynamics in Compliant and Noncompliant Aortas

Objectives: To investigate the effect of general anesthesia on aortic compliance and other cardiovascular hemodynamics in chronically instrumented pigs with compliant and noncompliant (stiff) aortas. Design: Experimental study. Setting: University animal laboratory. Participants: Twelve adult Yucatan miniature pigs. Interventions: Chronic instrumentation of a compliant (control; n = 7) and noncompliant (n = 5) group to measure pressure and flow in the ascending aorta. A Teflon prosthesis was wrapped around the aorta (noncompliant group) to limit wall compliance. Measurements and Main Results: Hemodynamic parameters were recorded on the 15th postoperative day, both awake and after general anesthesia. Banding the aorta caused a significant decrease in arterial compliance (-49%, p < 0.001) and increases in systolic blood pressure (SBP: +38%, p = 0.001) and pulse pressure (+107%, p < 0.01). Induction of anesthesia in the control group produced a 15% increase in arterial compliance (p < 0.05), resulting in a subtle decrease in SBP (-12%), diastolic blood pressure (DBP: -13%) and mean blood pressure (MBP; -12%). Induction of anesthesia in the noncompliant group also caused a significant increase in arterial compliance (17%, p < 0.001), but caused significant decreases in SBP (21%, p < 0.01), DBP (23%, p < 0.01) and MBP (22%, p < 0.01) as compared with controls. Conclusions: Induction of general anesthesia caused a similar increase in total arterial compliance and was associated with a decrease in SBP that was more pronounced in animals with noncompliant aortas. These results indicated that anesthesia caused a greater hemodynamic effect on noncompliant (stiff) aortas and may explain the extensive hemodynamic fluctuation and instability often observed in atherosclerotic, elderly patients with stiff aortas. (C) 2013 Elsevier Inc. All rights reserved

Total occlusion of the common carotid artery: A modified classification and its relation to clinical status

To investigate the hemodynamics and clinical presentation of common carotid artery occlusion (CCAO), we reviewed 6,415 patients with suspected carotid artery disease in whom a color Duplex imaging (CDI) examination was performed. According to distal vessel patency, the following CDI classification of CCAO was adopted: type I (patent both distal vessels); type II (isolated patency of external carotid artery); type III (isolated patency of internal carotid artery); and type IV (both distal vessels occluded). Thirty-five (0.5%) cases met the CDI criteria for CCAO. Twenty-nine of those (83%) had at least one patent distal vessel. Ten patients (29%) presented with stroke, 20 (57%) with transient ischemic attacks (TIAs) and five (14%) were asymptomatic. The incidence of stroke was higher in type IV (50%) vs. type II (30%) and in type II vs. type I (10%) lesions. Similarly, TIAs presented more often in type II (67%) and IV (50%) vs. in type I (40%) lesions (p = 0.002). Retrograde flow in the ophthalmic artery and concomitant severe contralateral carotid artery stenosis were more often related with type II and IV lesions (p = 0.02 and 0.04, respectively). CCAO is usually accompanied by patent distal vessel(s). The proposed CCAO classification correlates well with the patients’ clinical status and may help to better clarify the outcome of this rare entity. Among the main arteries of the developed collateral circulation, only the flow direction in the ophthalmic artery may be of clinical value. (E-mail: [email protected]) (c) 2008 World Federation for Ultrasound in Medicine &amp; Biology