RESUMO
BACKGROUND: Preclinical studies have reported that a single treadmill session performed 24h prior to doxorubicin provides cardio-protection. We aimed to characterize the acute change in cardiac function following an initial doxorubicin treatment in humans and determine whether an exercise session performed 24h prior to treatment changes this response. METHODS: Breast cancer patients were randomized to either 30min of vigorous-intensity exercise 24h prior to the first doxorubicin treatment (n=13), or no vigorous exercise for 72h prior to treatment (control, n=11). Echocardiographically-derived left ventricular volumes, longitudinal strain, twist, E/A ratio, and circulating NT-proBNP, a marker of later cardiotoxicity, were measured before and 24-48h after the treatment. RESULTS: Following treatment in the control group, NT-proBNP, end-diastolic and stroke volumes, cardiac output, E/A ratio, strain, diastolic strain rate, twist, and untwist velocity significantly increased (all p≤0.01). Whereas systemic vascular resistance (p<0.01) decreased, and ejection fraction (p=0.02) and systolic strain rate (p<0.01) increased in the exercise group only. Relative to control, the exercise group had a significantly lower NT-proBNP (p<0.01) and a 46% risk reduction of exceeding the cut-point used to exclude acute heart failure. CONCLUSION: The first doxorubicin treatment is associated with acutely increased NT-proBNP, echocardiographic parameters of myocardial relaxation, left ventricular volume overload, and changes in longitudinal strain and twist opposite in direction to documented longer-term changes. An exercise session performed 24h prior to treatment attenuated NT-proBNP release and increased systolic function. Future investigations should verify these findings in a larger cohort and across multiple courses of doxorubicin.
Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Cardiotoxinas/uso terapêutico , Teste de Esforço/tendências , Treinamento Intervalado de Alta Intensidade/tendências , Estudo de Prova de Conceito , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Neoplasias da Mama/sangue , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Cardiotoxinas/efeitos adversos , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Exercício Físico/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologiaRESUMO
High-intensity exercise suppresses appetite partly through changes in peripheral appetite-regulating hormones. Lactate and IL-6 mediate the release of these hormones in animal/cell models and may provide a mechanistic link between exercise intensity and appetite regulation. The current study examined changes in appetite-regulating hormones, lactate, and IL-6 after different intensities of running. Eight males completed four experimental sessions: 1) moderate-intensity continuous training (MICT; 65% VÌo2max); 2) vigorous-intensity continuous training (VICT; 85% VÌo2max); 3) sprint interval training (SIT; repeated "all-out" sprints); and 4) Control (CTRL; no exercise). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), total peptide YY (PYY), lactate, IL-6, and appetite perceptions were measured pre-, immediately postexercise, 30 min postexercise, and 90 min postexercise. Energy intake was recorded over 3 days. VICT and SIT suppressed ghrelin (P < 0.001), although SIT elicited a greater (P = 0.016 vs. MICT) and more prolonged (P < 0.001 vs. all sessions) response. GLP-1 increased immediately after MICT (P < 0.001) and 30 min after VICT (P < 0.001) and SIT (P < 0.002), while VICT elicited a greater postexercise increase in PYY vs. MICT (P = 0.027). Postexercise changes in blood lactate and IL-6 correlated with the area under the curve values for ghrelin (r = -0.60, P < 0.001) and GLP-1 (r = 0.42, P = 0.017), respectively. Appetite was suppressed after exercise (P < 0.001), although more so after VICT (P < 0.027) and SIT (P < 0.001) vs. MICT, and energy intake was reduced on the day after VICT (P < 0.017 vs. MICT and CTRL) and SIT (P = 0.049 vs. MICT). These findings support an intensity-dependent paradigm for appetite regulation following exercise and highlight the potential involvement of lactate and IL-6.NEW & NOTEWORTHY This study examines the involvement of two potential mechanisms (lactate and IL-6) that may explain the intensity-dependent effects of acute exercise on appetite-related parameters. Our findings support a clear intensity-dependent paradigm for appetite regulation following exercise, as highlighted by the change in acylated ghrelin and the suppression of appetite and energy intake after vigorous exercise (continuous and intermittent). Further, our findings extend previous work in animal/cell models by providing evidence for the potential role of lactate and IL-6 in mediating changes in appetite-related parameters following exercise in humans.