The Impact of the Cold Pressor Test on Inter-arm Differences in Blood Pressure.

A large inter-arm difference (IAD+; ≥10mmHg between arms at rest) in blood pressure (BP) at rest is linked to cardiovascular risk, and exercise can change this difference. As mechanisms for IAD are elusive, unique physiological stimuli may provide insight towards a better understanding of this phenomenon. The cold pressor test (CPT) has a potent effect on BP and acts primarily through sympathetic nervous system (SNS) stimulation, though the effects of SNS stimulation on IAD are unknown. Therefore, the purpose of the present study was to examine the effects of the CPT on IAD. BP was monitored simultaneously using two automated, auscultatory monitors (SunTech Tango) and a non-invasive hemodynamic device (Physioflow). Participants completed a CPT test, including a 15-minute rest, three pre-test BP measurements (averaged), and a three-minute water immersion (3°C; measurements at 30-sec and 2-min). Descriptive statistics were calculated, and a repeated measures ANOVA test used to compare both the absolute and relative IAD responses. The CPT induced an average absolute increase in IAD of 4.0 mmHg at 30-sec and 6.7mmHg at 2-min across all participants (P<0.05). Differences in both the absolute and relative IAD responses to the CPT were noted between IAD- and IAD+ individuals (P<0.05). Despite a consistent HR response to the CPT between groups, stroke volume was lower in IAD+ participants at 30-sec and 2-min. Sympathetic stimulation via the CPT induced changes in both the inter-arm difference in blood pressure and hemodynamics in young, apparently-healthy individuals.

Magnitude and significance of interarm blood pressure differences in children and adolescents.

BACKGROUND: An interarm difference (IAD) in blood pressure (BP) of 10 mmHg or more is a potential cardiovascular risk factor in adults, given its association with cardiovascular events/mortality. In children and adolescents, accurate BP assessment is critical for identifying risk of end organ damage. However, IAD has not been systematically studied in paediatric patients; if present and of significant magnitude, measuring BP in only one arm could lead to misclassification of hypertensive status. METHOD: In 95 children/adolescents with a normal aorta (including 15 with a history of tetralogy of Fallot) aged 7-18 years attending the Royal Children's Hospital, Melbourne, we aimed to determine the magnitude of IAD, frequency of IAD of at least 10 mmHg, difference in BP classification between arms, and influence of repeat measures on IAD in a single visit. After 5 min rest, simultaneous bilateral BP was measured in triplicate with an automated device. RESULTS: Absolute systolic IAD was 5.0 mmHg (median, interquartile range 2-8 mmHg) and was 10 mmHg or more in 14%, with no change on repeat measures. In patients with a history of aortic surgery, IAD of 10 mmHg or more occurred in 27% (transposition of the great arteries, n = 15) and 75% (aortic coarctation, n = 8). Differences in BP classification, based on initial left vs. right arm measures, occurred in 25% (normal aorta) and 40%/63% (aortic surgery), or 17% and 33%/50%, respectively if second and third measurements were averaged. CONCLUSION: Substantial interarm BP differences were common, even in apparently healthy children and adolescents: evaluation of IAD may, therefore, be important for BP classification in the paediatric setting.

Sex differences in the association between PTSD symptoms with cardiac autonomic function and subclinical atherosclerotic risk.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a public health concern that may elevate the risk for cardiovascular disease (CVD). There are established sex differences in both PTSD risk and CVD risk. PURPOSE: To examine sex-specific associations between subclinical PTSD symptom severity and subclinical CVD risk in young men and women. METHODS: A total of 61 young adults (women: n = 29, mean age: 26 ± 7 years) completed the post-traumatic stress disorder civilian checklist (PCL) and the Center for Epidemiologic Studies Depression Scale (CES-D). Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV). Peripheral vasomotor function was measured as flow-mediated slowing (FMS) of carotid-radial PWV following 5-min forearm occlusion. Heart rate variability was used to assess sympathovagal balance as LF/HF ratio. RESULTS: PCL score was positively correlated with CES-D score (r = 0.79, p < .001), cfPWV (r = 0.33, p = .03) and LF/HF ratio (r = 0.42, p = .009) in men. PCL score was positively correlated to CES-D score (r = 0.80, p < .001) in women, but was inversely correlated to cfPWV (r = -0.38, p = .02) and LF/HF ratio (r = -0.34, p = .04). PCL score was also inversely associated with FMS in women (r = -0.49, p = .01). CONCLUSION: There are sex differences in the association of PTSD symptoms and subclinical atherosclerosis. In men, increased PTSD symptoms may increase CVD risk by increasing sympathovagal balance and aortic stiffness. In women, increased PTSD symptoms may increase CVD risk via reducing vasomotor function.

Characterization of resting and exercise inter-arm differences in SBP to isometric handgrip exercise in males and females.

A large inter-arm difference (IAD; ≥10 mmHg) in SBP is linked to cardiovascular and peripheral vascular disease, hypertension, and premature mortality. Exercise-induced IAD (eIAD) is related to resting IAD, and acute aerobic activity alters eIAD and reduces IAD in recovery. Isometric handgrip exercise (IHE) affects blood pressure (BP), though the eIAD response to IHE is unknown. Further, the eIAD response may differ between males and females. OBJECTIVES: To characterize the eIAD response to IHE in males and females. METHODS: On visit 1, participants (16 females and 15 males, aged 18-35 years) completed three maximal voluntary isometric contractions (MVIC) per arm. On visit 2, before IHE, a series of three simultaneous, bilateral BP measures were averaged at rest. During IHE, participants maintained handgrip at 20% of MVIC for 2 minutes (arm randomly assigned), at which time bilateral BP was measured (IHE) during exercise and subsequent recovery (REC1 and REC2). Repeated-measures analysis of variance assessed eIAD and SBP (time × sex). RESULTS: IHE increased absolute eIAD (4 mmHg). Differences in relative eIAD were observed at IHE and REC2 based on resting IAD status (P < 0.05). Females only had an exaggerated SBP and pulse pressure response in the working arm. CONCLUSION: Acute IHE was shown to augment eIAD. Further eIAD and resting IAD were related. Acute IHE induced different bilateral responses between males and females, though the impact of sex on eIAD warrants further investigation. Future studies should address the effects of repeated bouts of IHE, which may benefit individuals with a large resting IAD.

An acute bout of aerobic exercise alters interarm systolic blood pressure difference.

BACKGROUND: Clinically, when a difference of at least 10 mmHg in systolic blood pressure (SBP) between arms exists, it is identified as an interarm systolic blood pressure difference (ISBPD). At rest, ISBPD is linked with hypertension, peripheral vascular disease, and increased premature mortality. Exercise may reveal underlying cardiovascular pathologies otherwise absent at rest. However, there have been no investigations to examine the effect of exercise on ISBPD. AIM: The aim of this investigation was to determine whether exercise may alter ISBPD when detected at rest or reveal ISBPD when it was not observed in the resting condition. METHODS: An experienced investigator sequentially measured SBP using standard auscultation in each arm (alternating order) in 85 normotensive individuals (22±6 years, 39 male, 46 female). ISBPD was quantified before exercise (PRE). Participants then completed a three-stage protocol on a cycle ergometer. A cadence of 50 rpm was maintained at a workload of 3 (EX-3; light) and 6 (EX-6; moderate) METS and during an active recovery (REC). At each stage, SBP was measured upon achieving steady-state heart rate. A logistic regression analysis was used to determine the change in odds ratio of ISBPD when exposed to exercise. RESULTS: Thirteen percent (n=11) of patients presented with ISBPD during PRE and the degree of ISBPD was lower (3.81 mmHg; P<0.05) in REC than PRE. In individuals who did not present with ISBPD during PRE (n=74), progression from EX-3 to EX-6 significantly increased the odds of developing ISBPD (4.31; P<0.05). CONCLUSION: In individuals with ISBPD at PRE, active recovery from exercise attenuated the difference between interarm SBP. Moderate-intensity exercise resulted in ISBPD not otherwise present at rest.

Eight Weeks of Kettlebell Swing Training Does not Improve Sprint Performance in Recreationally Active Females.

The kettlebell swing (KBS), emphasizing cyclical, explosive hip extension in the horizontal plane, aligns with movement- and velocity-specificity of sprinting. The present study examined the effect of an eight-week KBS intervention on sprinting in recreationally-active females, in comparison to an eight-week intervention using the stiff-legged deadlift (SDL). Following a pre-testing session measuring 30 meter sprint and countermovement vertical jump performance, participants were divided evenly by sprint time into KBS (n=8) and SDL (n=10) cohorts. Following familiarization with the exercises, KBS met twice weekly to perform swings using the Tabata interval (20s work, 10s rest, 8 rounds), stressing a rapid, explosive tempo. In contrast, the SDL group performed their Tabata stiff-legged deadlifts at a conventional resistance training tempo (2 seconds concentric, 2 seconds eccentric). Following eight weeks and greater than 95% training adherence, the SDL group only had a slightly greater average training volume (~3%) than KBS. No significant differences in pre-test values, or changes were noted in sprint performance from pre- to post-intervention in either group. An improvement in vertical jump performance was noted across groups. Potential explanations for the lack of sprint improvement compared to previous studies include differences between recreationally-active and athletic females, and low exercise volume (~46% of a comparable study with improvements in vertical jump). Future studies should seek to determine the appropriate volume and intensity for KBS components of sprint programming.

Electrocardiographic Responses to Deer Hunting in Men and Women.

OBJECTIVE: Deer hunting includes various stimuli resulting in augmented sympathetic activity, increased heart rate (HR) response, and rhythm changes. Collectively, these superimposed stresses may increase an individual's risk for cardiovascular events. We undertook this study to evaluate HR and rhythm responses in multiple phases of deer hunting in men and women with and without cardiovascular disease (CVD). METHODS: Nineteen participants age 38.3 ± 13.8 years (mean ± SD) with body mass index 29.2 ± 6.9 kg/m(2) followed their normal hunting routine. HR and rhythm were recorded continuously during the hunt using a small leadless electrocardiogram (ECG) patch monitor. RESULTS: Data were collected on 13 of 19 hunters while hiking. Three hunters recorded HR ≥85% of their age-predicted heart rate maximum (HRmax) for 1 to 2 minutes. Arrhythmias were detected in both participants with CVD and in 8 without CVD. Recorded rhythms included premature atrial, junctional, and ventricular complexes. Six hunters climbed a tree stand; 3 of them recorded HR ≥85% HRmax with sustained elevated HR response for 2 to 3 minutes with premature junctional contractions. Four of 19 participants dragged deer carcasses. During the drag, 1 male hunter recorded an HR of 91% HRmax, and another male hunter without CVD recorded an exercise-induced ischemic ECG. Fifteen of 19 hunters experienced "buck fever" (acute extreme excitation), with 7 reaching ≥85% HRmax for up to 1 minute. Ventricular bigeminy and trigeminy and ventricular couplets were observed in 1 subject during buck fever. CONCLUSIONS: Men and women with and without CVD recorded substantial increases in HR and clinically relevant arrhythmias while deer hunting.

Short-term exercise training attenuates acute doxorubicin cardiotoxicity.

Doxorubicin (DOX) is a potent and widely used antineoplastic agent. Despite the efficacy of DOX, its clinical use is limited by a dose-dependent cardiotoxicity. Chronic exercise training has been shown to protect against DOX-induced cardiotoxicity. It is less clear whether short-term exercise can attenuate DOX-induced dysfunction. The purposes of this study were to determine if short-term wheel running and treadmill exercise training can attenuate the cardiac dysfunction that accompanies DOX treatment and to investigate possible mechanisms that may be involved with any protective effects of exercise. Male Sprague-Dawley rats engaged in a short-term 5-day voluntary wheel running (WR) or treadmill exercise (TM) regimen. Following the exercise preconditioning period, animals received either 10 or 15 mg/kg of DOX or an equivalent volume of saline (SAL). Five days after DOX/SAL exposure, cardiac function was examined. Western immunoblotting was used to quantify left ventricular sarcoendoplasmic reticulum calcium-ATPase 2a (SERCA2a) protein expression. Exercise preconditioning attenuated in vivo and ex vivo cardiac dysfunction observed with DOX treatment alone. Specifically, short-term treadmill exercise (TM + DOX10, 56 ± 4%; TM + DOX15, 48 ± 5%) and voluntary wheel running (WR + DOX10, 51 ± 5%; WR + DOX15, 45 ± 3%) consistently preserved fractional shortening when compared to sedentary (SED) animals treated with DOX (SED + DOX10, 48 ± 4%; SED + DOX15, 39 ± 6%). Likewise, both exercise protocols preserved left ventricular developed pressure (TM + DOX10, 115 ± 6 mmHg; TM + DOX15, 85 ± 5 mmHg; WR + DOX10, 92 ± 12 mmHg; WR + DOX15, 91 ± 8 mmHg) when compared to SED animals treated with DOX (SED + DOX10, 79 ± 6 mmHg; SED + DOX15, 69 ± 7 mmHg). SERCA2a expression was also preserved in TM + DOX and WR + DOX. These findings suggest that short-term exercise prior to DOX treatment may be a valuable adjuvant therapy to offset acute cardiotoxicities and that maintaining calcium handling in cardiomyocytes may be responsible, in part, for the preservation in cardiac function.

Endurance exercise attenuates cardiotoxicity induced by androgen deprivation and doxorubicin.

Doxorubicin (DOX) is associated with cardiac dysfunction and irreversible testicular damage. Androgen deprivation therapy (ADT) is administered prior to DOX treatment to preserve testicular function. However, ADT may exacerbate DOX-induced cardiac dysfunction. Exercise is cardioprotective, but the effects of exercise on cardiac function during combined ADT and DOX treatment are currently unknown. In this study, male Sprague-Dawley rats were randomly assigned to experimental groups: control (CON), ADT, DOX, or ADT+DOX. Animals received ADT or control implants on days 1 and 29 of the 56-day protocol. Animals remained sedentary (SED) or engaged in treadmill endurance exercise (TM) beginning on day 1. On day 15, the animals received DOX at 1 mg·(kg body mass)(-1)·d(-1) by intraperitoneal injection for 10 consecutive days, or an equivalent volume of saline. On day 57, cardiac function was assessed in vivo and ex vivo. Animals treated with DOX alone, or with combined ADT+DOX, showed significant (P < 0.05) reductions in left ventricular developed pressure (-21% and -27%), maximal rate of pressure development (-29% and -32%), and maximal rate of pressure decline (25% and 31%), respectively when compared with the sedentary control animals. Endurance exercise training attenuated (P > 0.05) cardiac dysfunction associated with combined ADT+DOX treatment, indicating that exercise during simultaneous ADT+DOX treatment is cardioprotective.

Exercise mitigates cardiac doxorubicin accumulation and preserves function in the rat.

PURPOSE: Doxorubicin (DOX) is an effective antineoplastic agent with well-characterized cardiotoxic effects. Although exercise has been shown to protect against DOX cardiotoxicity, a clear and concise mechanism to explain its cardioprotective effects is lacking. The purpose of this study was to determine if exercise training reduces cardiac DOX accumulation, thereby providing a possible mechanism to explain the cardioprotective effects of exercise against DOX toxicity. METHODS: Sprague-Dawley rats were randomly assigned to 1 of 3 primary experimental groups: sedentary (n = 77), wheel running (n = 65), or treadmill (n = 65). Animals in wheel running and treadmill groups completed 10 weeks of exercise before DOX treatment. DOX was administered 24 hours after the last training session as a bolus intraperitoneal injection at 10 mg/kg. Subgroups of rats from each primary group were killed at 1, 3, 5, 7, and 9 days after DOX exposure to assess cardiac function and DOX accumulation. RESULTS: Ten weeks of exercise preconditioning reduced myocardial DOX accumulation, and this reduction in accumulation was associated with preserved cardiac function. CONCLUSIONS: These data suggest that the cardioprotective effects of exercise against DOX-induced injury may be due, in part, to a reduction in myocardial DOX accumulation.

Switching to a low-fat diet attenuates the intensified doxorubicin cardiotoxicity associated with high-fat feeding.

PURPOSE: A high-fat diet has been shown to exacerbate the cardiotoxicity associated with the chemotherapy drug doxorubicin (DOX); however, it is unknown whether switching from a high-fat diet to a low-fat diet can attenuate the intensified DOX cardiotoxicity. The purpose of this study was to investigate the effects of a low-fat diet on DOX-induced cardiotoxicity in rats previously fed a high-fat diet. METHODS: Male rats were randomly assigned to consume a Western diet or a low-fat diet for 6 weeks. Western diet-fed rats were then further randomized to switch to the low-fat diet (WD-LF) or continue with the Western diet (WD). One week later, WD-LF and WD received 1 mg/kg DOX per day for 10 consecutive days and continued with their diets (WD-LF + DOX, WD + DOX). LF was further randomized to receive 1 mg/kg DOX per day for 10 consecutive days (LF + DOX) or saline injections as a control (LF + SAL). Four weeks following the first injection, cardiac function was analyzed, and left ventricles were analyzed for cardiotoxicity indices. RESULTS: When compared to LF + SAL and LF + DOX, WD + DOX exhibited an enhanced cardiotoxicity as evidenced by reduced septal wall thickness, fractional shortening, and sarco-endoplasmic reticulum Ca(2+) ATPase expression as well as increased left ventricular cavity dimensions, lipid peroxidation, and ß-myosin heavy-chain expression. This exacerbated cardiotoxicity was not observed in WD-LF + DOX. CONCLUSIONS: Switching to a low-fat diet 1 week prior to, during, and following DOX treatment attenuated the exacerbated cardiotoxicity observed in the previously Western diet-fed rats.

Voluntary wheel running in growing rats does not protect against doxorubicin-induced osteopenia.

There is growing concern regarding the long-term negative side effects of chemotherapy in childhood cancer survivors. Doxorubicin (DOX) is commonly used in the treatment of childhood cancers and has been shown to be both cardiotoxic and osteotoxic. It is unclear whether exercise can attenuate the negative skeletal effects of this chemotherapy. Rat pups were treated with saline or DOX. Animals remained sedentary or voluntarily exercised. After 10 weeks, femoral bone mineral content and bone mineral density were measured using dual-energy x-ray absorptiometry. Cortical and cancellous bone architecture was then evaluated by microcomputed tomography. DOX had a profound negative effect on all measures of bone mass and cortical and cancellous bone architecture. Treatment with DOX resulted in shorter femora and lower femoral bone mineral content and bone mineral density, lower cross-sectional volume, cortical volume, marrow volume, cortical thickness, and principal (IMAX, IMIN) and polar (IPOLAR) moments of inertia in the femur diaphysis, and lower cancellous bone volume/tissue volume, trabecular number, and trabecular thickness in the distal femur metaphysis. Exercise failed to protect bones from the damaging effects of DOX. Other modalities may be necessary to mitigate the deleterious skeletal effects that occur in juveniles undergoing treatment with anthracyclines.

Rehabilitative exercise in a rat model of doxorubicin cardiotoxicity.

The use of exercise to minimize doxorubicin (DOX)-induced cardiotoxicity is gaining attention. However, very few clinically relevant reports exist investigating the effects of exercise performed during and following DOX treatments. The purpose of this study, therefore, was to examine the effects of voluntary wheel running during and following DOX treatment using two models of late-onset DOX cardiotoxicity in the rat. Female Sprague-Dawley rats received either DOX or saline injections using one of two separate treatment regimens. These regimens involved either daily or weekly DOX injections with cumulative doses for both protocols totaling 15 mg/kg. Daily DOX injections were 1 mg/kg and lasted for 15 consecutive days while weekly DOX injections were 2.5 mg/kg and lasted for six consecutive weeks with control animals receiving matched saline injection regimens. Immediately following the initial DOX/saline injection, animals were randomly housed in cages with voluntary running wheels or standard rat cages throughout DOX/saline treatments and continued until reaching 10 weeks. Cardiac function was then assessed using echocardiography and an isolated working heart model, and myosin heavy chain (MHC) isoform distribution was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When compared wth controls, daily DOX treatment resulted in reduced running wheel distances at weeks 2-10 (P < 0.05), and weekly DOX treatment resulted in reduced running wheel distances at weeks 2, 6 and 10 (P < 0.05). Nonetheless, wheel running during and following daily and weekly DOX dosing protected against DOX-induced cardiotoxicity by preserving maximal mitral and aortic blood flow velocities, left ventricular developed pressure and MHC isoform expression. In conclusion, the overall reduced volume of activity during and following daily and weekly DOX treatments attenuated DOX-induced cardiac dysfunction suggesting that low-volume endurance training may be an effective rehabilitative approach in minimizing DOX cardiotoxicity in cancer patients.

Exercise training mitigates anthracycline-induced chronic cardiotoxicity in a juvenile rat model.

BACKGROUND: Childhood cancer survivors are at greater risk of cardiovascular complications once they reach adulthood. Anthracyclines may be a major contributor to these delayed-onset complications, yet their use continues because of favorable clinical outcomes. Exercise has been shown to protect against anthracycline cardiotoxicity, yet it is unclear whether exercise can protect against delayed-onset cardiotoxicity when treatment is initiated in childhood. The aim of the present study was to determine if exercise training provides cardioprotection in a juvenile rat model of delayed-onset anthracycline cardiotoxicity. PROCEDURE: At 25 days of age, male Sprague-Dawley rat pups were subjected to a treatment regimen with the anthracycline doxorubicin (DOX). Pups received DOX at 2 mg/kg on 7 consecutive days (cumulative dose 14 mg/kg) or saline as a control. At the time DOX treatment began, pups remained sedentary or were allowed to voluntarily exercise. Ten weeks after the initiation of exercise, cardiac function was assessed both in vivo and ex vivo. RESULTS: DOX treatment stunted normal growth and significantly impaired cardiac function. While voluntary exercise did not offset changes in the growth curve, it did provide significant cardioprotection against DOX-induced cardiotoxicity. CONCLUSIONS: Exercise training, initiated at the time treatment begins, can protect against delayed-onset anthracycline-induced cardiotoxicity in adult rats that were treated with anthracyclines as juveniles.

Characterization of the effect of in vivo doxorubicin treatment on skeletal muscle function in the rat.

UNLABELLED: Doxorubicin (DOX)-induced muscle dysfunction may contribute to patient fatigue, but the nature of this myotoxicity remains unclear. The purpose of this study was to characterize the muscle function dose-response to DOX. A secondary purpose was to compare the degree of DOX-induced muscle dysfunction to the observed cardiac dysfunction. MATERIALS AND METHODS: Rats received DOX at 10 mg/kg (DOX1), 12.5 mg/kg (DOX2), or 15 mg/kg (DOX3). Muscle and cardiac function were assessed 5 days, post injection. RESULTS: Compared to controls, DOX2 and DOX3 soleus and DOX3 extensor digitorum longus (EDL) had lower maximal twitch force (p<0.05). Soleus fatigue rate was altered by DOX, but EDL fatigue rate was not. Additionally, fractional shortening was lower in DOX2 and DOX3 compared to controls (p<0.05). CONCLUSION: DOX impaired muscle function in a dose-dependent manner. The degree of dysfunction was greater in the soleus and was consistent with the observed cardiac dysfunction.

Exercise preconditioning provides long-term protection against early chronic doxorubicin cardiotoxicity.

Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated in a progressive treadmill training protocol or voluntary wheel running, respectively, for 10 weeks. Following the intervention, animals were further randomized to receive either DOX (sedentary + DOX, treadmill + DOX, wheel running + DOX) or saline (sedentary + saline, treadmill + saline, wheel running + saline). All animals then remained sedentary for 4 weeks. A 22% reduction in fractional shortening was observed in left ventricles from previously sedentary animals receiving DOX when compared with sedentary + saline. This degree of decline was not observed in treadmill + DOX and wheel running + DOX. Sedentary + DOX possessed significantly depressed mitral and aortic valve blood flow velocities when compared with sedentary + saline, but these decrements were not observed in treadmill + DOX and wheel running + DOX. Ex vivo analysis revealed that left ventricular developed pressure and maximal rate of pressure development were significantly lower in sedentary + DOX when compared to sedentary + saline. Treadmill and wheel running prior to DOX treatment protected against these decrements. Exercise cardioprotection was associated with preserved myosin heavy chain but not sarcoendoplasmic reticulum Ca(2+) ATPase 2a expression. In conclusion, 10 weeks of prior exercise protected against early chronic DOX cardiotoxicity suggesting that training status may be a determining factor in the degree of late-onset cardiotoxicity experienced by cancer patients undergoing treatment with DOX.

Effects of endurance training on combined goserelin acetate and doxorubicin treatment-induced cardiac dysfunction.

PURPOSE: Doxorubicin (DOX) and goserelin acetate (GA), when administered individually, can lead to impaired cardiac function via different mechanisms. Combining GA and DOX (GA + DOX), however, could potentially exacerbate cardiac dysfunction when compared to GA and DOX treatments administered individually. Therefore, the first purpose of this study was to investigate the effects of GA + DOX on cardiac function. Additionally, since exercise training has been shown to protect against GA- and DOX-induced cardiac dysfunction when administered individually, the second purpose of this study was to examine the effects of exercise during GA + DOX on cardiac function. METHODS: Female rats were randomly assigned to control (CON), GA, DOX, GA + DOX, or exercise training during GA + DOX (EX GA + DOX). Following 56 days, cardiac function was analyzed in vivo using echocardiography and ex vivo using an isolated working heart model. RESULTS: GA + DOX had significantly lower mitral valve maximal and mean blood flow velocities and aortic valve maximal blood flow velocity than CON (in vivo analysis, P < 0.05), but these differences were not observed between EX GA + DOX and CON. In the isolated working heart, GA + DOX hearts had significantly different left ventricular developed pressures and maximal rates of pressure development and decline than CON (P < 0.05), but these differences were not observed in EX GA + DOX. CONCLUSIONS: GA + DOX resulted in significantly impaired in vivo and ex vivo cardiac function, but exercise training during GA + DOX was cardioprotective.

Effects of voluntary wheel running on goserelin acetate-induced bone degeneration.

A common treatment option for many breast and prostate cancer patients is the use of a luteinizing hormone-releasing hormone agonist such as goserelin acetate (GA) which reduces sex hormone levels. This treatment, however, is associated with bone degeneration, and exercise has been suggested as a means of preventing this side effect. Little is known about the effects of low intensity, low volume exercise on GA-induced bone loss. The purpose of this study, therefore, was to investigate the effects of voluntary wheel running on bone architecture in growing male (M) and female (F) rats receiving GA treatment. Rats received an 8-week GA treatment or placebo (CON) and were either housed in cages equipped with voluntary running wheels (WR) or remained sedentary (SED) in standard cages throughout the experimental period. Following treatments, tibiae were excised and analyzed for cortical bone (cross-sectional volume, cortical volume, marrow volume, cortical thickness) and cancellous bone (bone volume/total volume, trabecular number, trabecular thickness, trabecular spacing) using micro-computed tomography. Treatment with GA resulted in a significant reduction in running wheel distances in both sexes throughout the study period (P<0.05). GA treatment had no effect on cortical bone architecture in neither sex (P>0.05). Cancellous bone degeneration, however, was observed in M and F SED+GA (P<0.05). No significant differences were observed in M WR+GA animals in bone volume/total volume, trabecular number and trabecular spacing when compared to M SED+CON (P>0.05). In F WR+GA, trabecular thickness did not differ from that of F SED+CON (P>0.05), and trabecular spacing was found to be significantly lower than F SED+GA (P<0.05). The current report indicates that 8 weeks of GA treatment promotes cancellous bone degeneration, and voluntary wheel running provides no clear osteoprotection in growing male and female rats.