Vitamin C prevents hyperoxia-mediated coronary vasoconstriction and impairment of myocardial function in healthy subjects

Penn State Heart and Vascular Institute, H047, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Arbeitsphysiologie (Impact Factor: 2.19). 05/2011; 112(2):483-92. DOI: 10.1007/s00421-011-1997-x
Source: PubMed


Supplementary oxygen is commonly administered in current medical practice. Recently it has been suggested that hyperoxia causes acute oxidative stress and produces prompt and substantial changes in coronary resistance in patients with ischemic heart disease. In this report, we examined whether the effects of hyperoxia on coronary blood velocity (CBV) would be associated with a reduction in myocardial function. We were also interested in determining if the postulated changes in left ventricular (LV) function seen with tissue Doppler imaging (TDI) could be reversed with intravenous vitamin C, a potent, acute anti-oxidant. LV function was determined in eight healthy subjects with transthoracic echocardiography and TDI before and after hyperoxia and with and without infusing vitamin C. Hyperoxia compared with room air promptly reduced CBV by 28 ± 3% (from 23.50 ± 2.31 cm/s down to 17.00 ± 1.79 cm/s) and increased relative coronary resistance by 34 ± 5% (from 5.63 ± 0.88 up to 7.32 ± 0.94). Meanwhile, LV myocardial systolic velocity decreased by 11 ± 6% (TDI). These effects on flow and function were eliminated by the infusion of vitamin C, suggesting that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation.

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    • "These results indicate the potential pivotal role of ˙NO in vascular dysfunction after hyperoxia. Use of different antioxidants, such as intravenous application of vitamin C (Mak et al., 2002; McNulty et al., 2007; Gao et al., 2012) or food-induced, indirect elevation of plasma uric acid (Vukovic et al., 2009) showed protective effects against hyperoxia-induced deterioration of vascular reactivity. These findings support the hypothesis that hyperoxia-induced oxidative stress is responsible for vascular dysfunction. "
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    ABSTRACT: We investigated the effects of acute intake of antioxidants on hyperoxia-induced oxidative stress, reduction of plasma nitrite and change in arterial stiffness. Twelve healthy males randomly consumed either placebo or an oral antioxidant cocktail (vitamin C, 1000 mg; vitamin E, 600 IU; alpha-lipoic acid, 600 mg). Every therapy was consumed once, a week apart, in a cross-over design, 30 min before the experiment. The volunteers breathed 100% normobaric oxygen between 30th and 60th min of 1-h study protocol. Plasma levels of nitrite, lipid peroxides (LOOH) and vitamin C, arterial stiffness (indicated by augmentation index, AIx) and arterial oxygen (PtcO2) pressure were measured before and after hyperoxia. Exposure to oxygen caused a similar increase of PtcO2 in both placebo and antioxidants groups, confirming comparable exposure to hyperoxia (438 ± 100 versus 455 ± 83 mm Hg). Vitamin C was increased in the antioxidants group confirming successful application of antioxidants (69 ± 14 versus 57 ± 15 μm). Hyperoxia resulted in increased AIx and LOOH and decreased nitrite in placebo (−32 ± 11 versus −47 ± 13%, 72 ± 7 versus 62 ± 6 μm H2O2 and 758 ± 184 versus 920 ± 191 nm, respectively), but not in the antioxidants group (−42 ± 13 versus −50 ± 13%, 64 ± 9 versus 61 ± 8 μm H2O2 and 847 ± 156 versus 936 ± 201 nm, respectively). The acute intake of selected antioxidants was effective in preserving bioavailabity of ˙NO and vascular function, against hyperoxia-induced oxidative stress.
    Clinical Physiology and Functional Imaging 05/2014; 35(1). DOI:10.1111/cpf.12169 · 1.44 Impact Factor
    • "Venous blood samples were obtained before and after each bout of hyperoxia (four samples total) to determine ascorbic acid levels. The rationale for these additional studies was based on prior work from our laboratory (Crawford et al. 1997; McNulty et al. 2005, 2007; Gao et al. 2012) and others (Narkowicz et al. 1993; Milone et al. 1999; Mak et al. 2002). Along with BP (Finometer), HR (ECG), and respiratory parameters (respiratory gas monitor, Ohmeda 5250), FBF was measured by duplex ultrasound (HDI 5000, ATL). "
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    ABSTRACT: Reactive oxygen species (ROS), produced acutely during skeletal muscle contraction, are known to stimulate group IV muscle afferents and accentuate the exercise pressor reflex (EPR) in rodents. The effect of ROS on the EPR in humans is unknown. We conducted a series of studies using ischemic fatiguing rhythmic handgrip to acutely increase ROS within skeletal muscle, ascorbic acid infusion to scavenge free radicals, and hyperoxia inhalation to further increase ROS production. We hypothesized that ascorbic acid would attenuate the EPR and that hyperoxia would accentuate the EPR. Ten young healthy subjects participated in two or three experimental trials on separate days. Beat-by-beat measurements of heart rate (HR), mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and renal vascular resistance index (RVRI) were measured and compared between treatments (saline and ascorbic acid; room air and hyperoxia). At fatigue, the reflex increases in MAP (31 ± 3 versus 29 ± 2 mmHg), HR (19 ± 3 versus 20 ± 3 bpm), MSNA burst rate (21 ± 4 versus 23 ± 4 burst/min), and RVRI (39 ± 12 versus 44 ± 13%) were not different between saline and ascorbic acid. Relative to room air, hyperoxia did not augment the reflex increases in MAP, HR, MSNA, or RVRI in response to exercise. Muscle metaboreflex activation and time/volume control experiments similarly showed no treatment effects. While contrary to our initial hypotheses, these findings suggest that ROS do not play a significant role in the normal reflex adjustments to ischemic exercise in young healthy humans.
    08/2013; 1(3). DOI:10.1002/phy2.47
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    • "It is well accepted that healthy tissue responds to hyperoxia with consistent vasoconstriction [27]. How the CBF changes in ischemic tissue in response to NBO therapy is an important question. "
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    ABSTRACT: Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO's neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore "buy time" for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke.
    01/2013; 3(1):2. DOI:10.1186/2045-9912-3-2
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