Biomedical subjects

Reid Hayward

Publications and source records attributed to Reid Hayward.

8 recordsLinked to original sources

PubMed2006

Exercise training attenuates acute doxorubicin-induced cardiac dysfunction.

The use of doxorubicin, a highly effective antitumor antibiotic, is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether chronic exercise training (ET) prior to doxorubicin treatment would preserve cardiac function and reduce myocardial oxidative stress following treatment. Rats were exercise trained on a motorized treadmill or confined to sedentary cage activity for 12 weeks, then administered an intraperitoneal injection of doxorubicin (15 mg/kg) or 0.9% saline. Five days following the injections, hearts were isolated and Langendorf perfused to assess cardiac function and then processed for biochemical analyses. Doxorubicin treatment induced significant inotropic, lusitropic, and chronotropic cardiac dysfunction, reduced coronary flow, and increased cardiac lipid peroxidation in the sedentary animals. Doxorubicin treatment was also associated with a decrease in cardiac manganese superoxide dismutase protein expression and an increase in heat shock protein-72 (Hsp72) compared with saline-treated animals. Exercise training attenuated doxorubicin-induced cardiac dysfunction, and lipid peroxidation, and led to a greater cardiac expression of Hsp72 compared with the sedentary animals. The results of this study demonstrate for the first time that chronic exercise training before doxorubicin treatment protects against cardiac dysfunction following treatment, and provide evidence for a sustained increase in myocardial Hsp72 following exercise training and doxorubicin treatment in vivo.

Animals↗

PubMed2006

Resistance exercise training attenuates alcohol-induced cardiac oxidative stress.

BACKGROUND: Myocardial oxidative stress is believed to play an important role in the pathogenesis of alcoholic cardiomyopathy. Strenuous physical exercise has been shown to increase or decrease myocardial oxidative stress depending on the mode and duration of the exercise intervention. Given the possibility of individuals to engage in both alcohol consumption and weight-training exercise, we have examined the effect of resistance exercise training and chronic alcohol consumption on myocardial oxidative stress in rats. METHODS: Forty Sprague-Dawley rats were randomly assigned to one of four experimental groups: sedentary, sedentary plus alcohol treatment, resistance training, or resistance training plus alcohol treatment. Rats in the alcohol groups received a liquid diet containing alcohol (35% of kilocalorie intake) for 6 weeks. Non-alcohol groups were pair-fed the same liquid diet supplemented with a maltose dextrin caloric substitute. Rats in the resistance training groups were trained to rise onto their hind limbs while wearing lead-weighted vests 30 times per training session, 3 days per week during the 6 week experimental period. RESULTS: Alcohol treatment in the sedentary animals resulted in greater levels of cardiac malondialdehyde, a marker of lipid peroxidation, and a depressed index of myocardial antioxidant potential compared with all other groups (P<0.05). Hearts from the resistance training plus alcohol animals exhibited malondialdehyde and antioxidant levels similar to sedentary controls, suggesting that resistance training protected against the alcohol-induced myocardial stress. CONCLUSION: These results suggest that resistance training may attenuate the damaging effects of alcohol on the heart and preserve myocardial antioxidant capacity.

Adaptation, Physiological↗

PubMed2005

Low-intensity exercise training during doxorubicin treatment protects against cardiotoxicity.

Doxorubicin (Dox) is a highly effective antineoplastic antibiotic associated with a dose-limiting cardiotoxicity that may result in irreversible cardiomyopathy and heart failure. The purpose of this study was to examine the effects of low-intensity exercise training (LIET) during the course of Dox treatment on cardiac function, myosin heavy chain expression, oxidative stress, and apoptosis activation following treatment. Male Sprague-Dawley rats either remained sedentary or were exercise trained on a motorized treadmill at 15 m/min, 20 min/day, 5 days/wk (Monday through Friday) for 2 wk. During the same 2-wk period, Dox (2.5 mg/kg) or saline was administered intraperitoneally to sedentary and exercised rats 3 days/wk (Monday, Wednesday, Friday) 1-2 h following the exercise training sessions (cumulative Dox dose: 15 mg/kg). Five days following the final injections, hearts were isolated for determination of left ventricular (LV) function, lipid peroxidation, antioxidant enzyme protein expression, 72-kDa heat shock protein expression, caspase-3 activity, and myosin heavy chain isoform expression. Dox treatment significantly impaired LV function and increased caspase-3 activity in sedentary animals (P < 0.05). LIET attenuated the LV dysfunction and apoptotic signal activation induced by Dox treatment and increased glutathione peroxidase expression, but it had no significant effect on lipid peroxidation, protein expression of myosin heavy chain isoforms, 72-kDa heat shock protein, or superoxide dismutase isoforms. In conclusion, our data suggest that LIET applied during chronic Dox treatment protects against cardiac dysfunction following treatment, possibly by enhancing antioxidant defenses and inhibiting apoptosis.

Animals↗

PubMed2005

Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart.

The clinical use of doxorubicin (DOX) is limited by a dose-dependent cardiotoxicity. The purpose of this study was to determine whether voluntary exercise training would confer protection against DOX cardiotoxicity in the isolated perfused rat heart. Female Sprague-Dawley rats were randomly assigned to standard holding cages or cages with running wheels for 8 wk. Twenty-four hours after the sedentary (SED) or voluntary exercise (VEX) running period, rats were anesthetized with pentobarbital sodium, and hearts were isolated and perfused with oxygenated Krebs-Henseleit (KH) buffer at a constant flow of 15 ml/min. After a 20-min stabilization period, hearts were paced at 300 beats per minute and perfused with KH buffer containing 10 microM DOX for 60 min. A set of control hearts from SED and VEX rats were perfused under identical conditions without DOX for the same period. DOX perfusion led to significant decreases in left ventricular developed pressure, +dP/dt, and -dP/dt, and significant increases in LV lipid peroxidation in sedentary rats compared with non-DOX controls (P < 0.05). Prior voluntary exercise training attenuated these DOX-induced effects and was associated with a significant increase (78%, P < 0.05) in heat shock protein (HSP72), but not mitochondrial isoform of SOD (MnSOD) or CuZnSOD protein expression in the hearts of wheel-run animals. These data indicate that chronic physical activity may provide resistance against the cardiac dysfunction and oxidative damage associated with DOX exposure and provide novel evidence of HSP72 induction in the heart after voluntary exercise.

Animals↗

PubMed2004

Training enhances vascular relaxation after chemotherapy-induced vasoconstriction.

PURPOSE: Although evidence is accumulating that suggests regular moderate physical activity improves physiological and psychological well-being of cancer patients undergoing chemotherapy, the mechanisms involved remain unclear. Therefore, the purpose of this study was to determine if exercise training improves endothelium-dependent vasodilation after exposure to the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS: Rats were injected with N-methyl-N-nitrosourea (MNU) and assigned to either exercise (EX; treadmill running, 20-25 m.min(-1) grade, 30 min.d(-1), 5 d.wk(-1) for 8 wk) or sedentary (SED) groups. After the exercise training period, aortic rings were obtained and used to assess contractile and relaxation characteristics. In addition, endothelial nitric oxide synthase (eNOS) protein content and eNOS enzyme activity was determined. RESULTS: Exercise training resulted in increased maximal endothelium-dependent vasorelaxation to acetylcholine (ACh, 1 x 10(-5) M) (SED, 56 +/- 3%; exercise, 71 +/- 5%; P < 0.05) after norepinephrine-induced (1 x 10(-7) M) vasoconstriction. Exposure of aortic rings from each group to increasing concentrations of 5-FU (7 x 10(-5) x 10 M(-3)) resulted in vasoconstriction. Rings obtained from exercise-trained animals demonstrated enhanced vasorelaxation to ACh (1 x 10(-5) M) after 5-FU-induced vasoconstriction compared with rings obtained from SED animals (P < 0.05). In addition, exercise training enhanced eNOS protein content and eNOS activity. CONCLUSION: Exercise training enhances endothelium-dependent vasorelaxation after 5-FU-induced vasoconstriction, and this may be due, at least in part, to an increase in aortic eNOS protein content and activity. Such exercise-induced adaptations may help alleviate chemotherapy-related fatigue observed in cancer patients.

Animals↗

PubMed2003

Influence of acute resistance exercise on cardiac biomarkers in untrained women.

This study was conducted to determine if an initial bout of resistance (weight lifting) exercise by untrained women results in any alterations in indicators of acute myocardial infarction (AMI). Untrained women performed 4 resistance exercises at 70% of their 1 repetition maximum. Blood samples were obtained during the 12 h post-exercise and analyzed for total creatine kinase (CK)-MB, CK-MB subforms 1 and 2, and the relative lymphocyte percentage. Exercise resulted in significant increases in total CK-MB, CK-MB(1), CK-MB(2), and the CK-MB(2)/CK-MB(1) ratio, total leukocyte count, and lymphocyte count. Using several criteria for the assessment of AMI, 22-25% of subjects completing the protocol demonstrated increases in CK-MB(2), CK-MB(2)/CK-MB(1) ratio, and relative lymphocyte percentages that were suggestive of AMI. Thus, our data suggest that moderate resistance exercise can significantly alter blood indicators of AMI, emphasizing the need to determine recent exercise history in patients with possible AMI.

Adult↗

PubMed2003

Attenuation of homocysteine-induced endothelial dysfunction by exercise training.

Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular disease. Exposure of endothelial cells to elevated levels of homocysteine (HCY) results in decreased availability of nitric oxide (NO) and impaired vascular function, both of which are early events in atherogenesis. Exercise training improves vascular function by increasing endothelial NO production secondary to an increase in the enzyme responsible for its synthesis, endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training would increase endothelial NO production, which would attenuate the endothelial dysfunction associated with HCY exposure. Rats were randomly assigned to either sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of treadmill running at 20-25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks. Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY for 120 min, then exposed to norepinephrine (NE 100 nM) to induce vasoconstriction. Once a stable contraction plateau was achieved, rings were exposed to increasing concentrations of the receptor-mediated endothelium-dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187 (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO(2) (0.1, 1, 10, 100 muM). In addition, eNOS protein content and eNOS enzyme activity were determined. Aortic rings obtained from exercise trained rats demonstrated significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison to aortic rings obtained from SED rats following exposure to HCY. Additionally, exercise training increased aortic eNOS protein content and activity. Our data demonstrate that exercise training improves endothelium-dependent vasorelaxation following HCY exposure and this may be due, at least in part, to elevated levels of eNOS protein and an increase in eNOS activity. These results suggest the possible role exercise may play in attenuating the endothelial dysfunction associated with hyperhomocysteinemia.

Journal Article↗

PubMed2003

A case study: prescriptive exercise intervention after bilateral mastectomies.

Exercise for cancer patients is gaining support. In the current case study, a female breast cancer patient was diagnosed with breast cancer at the age of 29 years; she underwent a left modified radical mastectomy. She developed cancer again in the opposite breast at the age of 57 years and had a right modified radical mastectomy. After the second mastectomy (the right breast), the patient received chemotherapy and radiation. Following her cancer treatments, she participated in an exercise intervention for 6 months at the University of Northern Colorado's Rocky Mountain Cancer Rehabilitation Institute. A 6-month reassessment showed that she increased her muscular strength and cardiovascular function in addition to attenuating her cancer-related fatigue and depression. It is recommended that health professionals work together to ensure that a collaborative effort is undertaken to increase functional work capacity that will significantly improve patients' quality of life.

Adult↗