Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle Joseph Nanobashvili, MD, Christoph Neumayer,

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Presentation transcript:

Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle Joseph Nanobashvili, MD, Christoph Neumayer, MD, Alexander Fuegl, MD, Andreas Punz, PhD, Roland Blumer, PhD, Martina Mittlböck, PhD, Manfred Prager, MD, Peter Polterauer, MD, Lawrence W Dobrucki, PhD, Ihor Huk, MD, Tadeusz Malinski, PhD Journal of Vascular Surgery Volume 39, Issue 4, Pages 868-877 (April 2004) DOI: 10.1016/j.jvs.2003.10.060

Fig 1 A, Typical recordings of in vivo measurement of nitric oxide (NO) release in rabbit hind limb muscle in untreated animals (IR), animals with l-arginine treatment alone (AR), and animals with combined treatment with l-arginine plus antioxidative vitamins (AV). Baseline recording (CO group) not shown. B, Peak NO concentrations (solid bars) and NO concentration at the end of reperfusion (striped bars) recorded in rabbit hind limb muscle in IR, AR, and AV groups and in animals treated with antioxidative vitamins alone (OX). *P < .005 vs IR. **P < .05 vs AR. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)

Fig 1 A, Typical recordings of in vivo measurement of nitric oxide (NO) release in rabbit hind limb muscle in untreated animals (IR), animals with l-arginine treatment alone (AR), and animals with combined treatment with l-arginine plus antioxidative vitamins (AV). Baseline recording (CO group) not shown. B, Peak NO concentrations (solid bars) and NO concentration at the end of reperfusion (striped bars) recorded in rabbit hind limb muscle in IR, AR, and AV groups and in animals treated with antioxidative vitamins alone (OX). *P < .005 vs IR. **P < .05 vs AR. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)

Fig 2 Microvessel blood flow during ischemia-reperfusion injury of adductor magnus muscle in control animals (CO; open circles), untreated animals (IR; open squares), animals treated with antioxidative vitamins alone (OX; black squares) or l-arginine alone (AR; black triangles), and animals treated with a combination of L-arginine plus antioxidative vitamins (AV; black circles). *P < .005 vs preischemic level, and vs CO, AR, and AV groups at the same time point. **P < .05 vs AR animals at the same time point. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)

Fig 3 Changes in muscle interfiber area (%MIFA) in sham-operated animals (CO), untreated animals (IR), animals treated with antioxidative vitamins (OX) or l-arginine alone (AR), and animals treated with a combination of l-arginine plus antioxidative vitamins (AV) at time t0, before ischemia (black squares); ti, end of ischemia (open squares); and tr2, 2 hours after reperfusion (shaded squares). *P < .005, IR vs CO, OX, AR, and AV at tr2. **P < .05 vs CO at tr2. ***P < .05 vs CO, and P < .01 vs OX at tr2. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)

Fig 4 Microvessel plugging per 50 microvessels in sham-operated animals (CO), untreated animals (IR), animals treated with antioxidative vitamins (OX) or l-arginine alone (AR), and animals treated with a combination of l-arginine plus antioxidative vitamins (AV) at time t0, before ischemia (black squares); ti, end of ischemia (open squares); and tr2, 2 hours after reperfusion (shaded squares). *P < .005 vs CO and all treatment groups at tr2. **P < .005 vs CO, AR, and AV groups at tr2. ***P < .05 vs CO and AV groups at tr2. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)

Fig 5 A, Ultrathin cross-section through muscle fibers of animal in the CO group shows normal anatomy. Bar = 1 μm. B, Ultrathin cross-section through muscle fibers of animal in the IR group. Note severe damage to sarcolemma (arrow) and basal lamina (arrowhead). Sarcoplasmic reticulum (SR) and mitochondria (M) are swollen, and cristae in mitochondria are damaged. Myonuclei (N) appear pyknotic, and myofibrils are partly dissolved. Bar = 1 μm. C, Ultrathin cross-section through muscle fiber of animal in the OX group. The sarcolemma (arrow) of the muscle fiber is damaged, and the basal lamina (arrowhead) is partially damaged. The sarcoplasmatic reticulum (SR) is swollen, but swelling was less than in the IR group. The cristae of the mitochondria (M) are fragmented. Bar = 1 μm. D, Ultrathin cross-section through muscle fiber of animal in the AR group. Most areas of sarcolemma (arrow) of muscle fibers appear normal. Only single damage to the sarcolemma is observed. Myofibrils and sarcoplasatic reticulum are without significant pathologic changes. Bar = 1 μm. E, Ultrathin cross-section through muscle fiber of animal in the AV group. Myonuclei (N), sarcolemma (arrow), and sarcoplasmic reticulum (SR) are well-preserved; mitochondria (M) are partially damaged. Bar = 1 μm. Journal of Vascular Surgery 2004 39, 868-877DOI: (10.1016/j.jvs.2003.10.060)