Exercise-induced changes in myocardial glucose utilization during periods of active cardiac growth.

Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fate of carbon derived from dietary glucose in the heart during acute, active, and established phases of exercise-induced cardiac growth. Male and female FVB/NJ mice were subjected to treadmill running for up to 4 weeks and cardiac growth was assessed by gravimetry. Cardiac metabolic responses to exercise were assessed via in vivo tracing of [13C6]-glucose via mass spectrometry and nuclear magnetic resonance. We found that the half-maximal cardiac growth response was achieved by approximately 1 week of daily exercise training, with near maximal growth observed in male mice with 2 weeks of training; however, female mice were recalcitrant to exercise-induced cardiac growth and required a higher daily intensity of exercise training to achieve significant, albeit modest, increases in cardiac mass. We also found that increases in the energy charge of adenylate and guanylate nucleotide pools precede exercise-induced changes in cardiac size and were associated with higher glucose tracer enrichment in the TCA pool and in amino acids (aspartate, glutamate) sourced by TCA intermediates. Our data also indicate that the activity of collateral biosynthetic pathways of glucose metabolism may not be markedly altered by exercise. Overall, this study provides evidence that metabolic remodeling in the form of heightened energy charge and increased TCA cycle activity and cataplerosis precedes cardiac growth caused by exercise training in male mice.

Cardiac mitochondrial metabolism during pregnancy and the postpartum period.

The goal of the present study was to characterize changes in mitochondrial respiration in the maternal heart during pregnancy and after birth. Timed pregnancy studies were performed in 12-wk-old female FVB/NJ mice, and cardiac mitochondria were isolated from the following groups of mice: nonpregnant (NP), midpregnancy (MP), late pregnancy (LP), and 1-wk postbirth (PB). Similar to our previous studies, we observed increased heart size during all stages of pregnancy (e.g., MP and LP) and postbirth (e.g., PB) compared with NP mice. Differential cardiac gene and protein expression analyses revealed changes in several mitochondrial transcripts at LP and PB, including several mitochondrial complex subunits and members of the Slc family, important for mitochondrial substrate transport. Respirometry revealed that pyruvate- and glutamate-supported state 3 respiration was significantly higher in PB vs. LP mitochondria, with respiratory control ratio (RCR) values higher in PB mitochondria. In addition, we found that PB mitochondria respired more avidly when given 3-hydroxybutyrate (3-OHB) than mitochondria from NP, MP, and LP hearts, with no differences in RCR. These increases in respiration in PB hearts occurred independent of changes in mitochondrial yield but were associated with higher abundance of 3-hydroxybutyrate dehydrogenase 1. Collectively, these findings suggest that, after birth, maternal cardiac mitochondria have an increased capacity to use 3-OHB, pyruvate, and glutamate as energy sources; however, increases in mitochondrial efficiency in the postpartum heart appear limited to carbohydrate and amino acid metabolism.NEW & NOTEWORTHY Few studies have detailed the physiological adaptations that occur in the maternal heart. We and others have shown that pregnancy-induced cardiac growth is associated with significant changes in cardiac metabolism. Here, we examined mitochondrial respiration and substrate preference in isolated mitochondria from the maternal heart. We show that following birth, cardiac mitochondria are "primed" to respire on carbohydrate, amino acid, and ketone bodies. However, heightened respiratory efficiency is observed only with carbohydrate and amino acid sources. These results suggest that significant changes in mitochondrial respiration occur in the maternal heart in the postpartum period.

Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart.

Introduction: Branch-chain amino acids (BCAA) are markedly elevated in the heart following myocardial infarction (MI) in both humans and animal models. Nevertheless, it remains unclear whether dietary BCAA levels influence post-MI remodeling. We hypothesize that lowering dietary BCAA levels prevents adverse cardiac remodeling after MI. Methods and Results: To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. We found that mice fed the low BCAA diet had >2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies; notably, the high BCAA diet did not further increase BCAA levels over the normal chow diet. To investigate the impact of dietary BCAAs on cardiac remodeling and function after MI, male and female mice were fed either the low or high BCAA diet for 2 wk prior to MI and for 4 wk after MI. Although body weights or heart masses were not different in female mice fed the custom diets, male mice fed the high BCAA diet had significantly higher body and heart masses than those on the low BCAA diet. Echocardiographic assessments revealed that the low BCAA diet preserved stroke volume and cardiac output for the duration of the study, while the high BCAA diet led to progressive decreases in cardiac function. Although no discernible differences in cardiac fibrosis, scar collagen topography, or cardiomyocyte cross-sectional area were found between the dietary groups, male mice fed the high BCAA diet showed longer cardiomyocytes and higher capillary density compared with the low BCAA group. Conclusions: Provision of a diet low in BCAAs to mice mitigates eccentric cardiomyocyte remodeling and loss of cardiac function after MI, with dietary effects more prominent in males.

Randomized, controlled trial comparing the effects of anesthesia with propofol, isoflurane, desflurane and sevoflurane on pain after laparoscopic cholecystectomy / Estudo randômico controlado que compara os efeitos da anestesia com propofol, isoflurano, desflurano e sevoflurano sobre a dor pós-colecistectomia videolaparoscópica / Estudio aleatorizado controlado comparando los efectos de la anestesia con propofol, isoflurano, desflurano y sevoflurano sobre el dolor poscolecistectomía videolaparoscópica

Background: Pain is the primary complaint and the main reason for prolonged recovery after laparoscopic cholecystectomy. The authors hypothesized that patients undergoing laparoscopic cholecystectomy will have less pain four hours after surgery when receiving maintenance of anesthesia with propofol when compared to isoflurane, desflurane, or sevoflurane. Methods: In this prospective, randomized trial, 80 patients scheduled for laparoscopic cholecystectomy were assigned to propofol, isoflurane, desflurane, or sevoflurane for the maintenance of anesthesia. Our primary outcome was pain measured on the numeric analog scale four hours after surgery. We also recorded intraoperative use of opioids as well as analgesic consumption during the first 24 h after surgery. Results: There was no statistically significant difference in pain scores four hours after surgery (p = 0.72). There were also no statistically significant differences in pain scores between treatment groups during the 24 h after surgery (p = 0.45). Intraoperative use of fentanyl and morphine did not vary significantly among the groups (p = 0.21 and 0.24, respectively). There were no differences in total morphine and hydrocodone/APAP use during the first 24 h (p = 0.61 and 0.53, respectively). Conclusion: Patients receiving maintenance of general anesthesia with propofol do not have less pain after laparoscopic cholecystectomy when compared to isoflurane, desflurane, or sevoflurane. .

Justificativa e objetivo: a dor é a principal queixa e também o motivo principal de recuperação prolongada pós-colecistectomia laparoscópica. A nossa hipótese foi que os pacientes submetidos à colecistectomia laparoscópica apresentariam menos dor quatro horas após a cirurgia se recebessem manutenção anestésica com propofol em comparação com isoflurano, desflurano ou sevoflurano. Métodos: neste estudo prospectivo e randômico, 80 pacientes agendados para colecistectomia laparoscópica foram designados para receber propofol, isoflurano, desflurano ou sevoflurano para manutenção da anestesia. Nosso desfecho primário foi dor mensurada em escala analógica numérica quatro horas após a cirurgia. Também registramos o uso intraoperatório de opiáceos, bem como o consumo de analgésicos durante as primeiras 24 horas pós-cirúrgicas. Resultados: não houve diferença estatisticamente significante nos escores de dor quatro horas após a cirurgia (p = 0,72). Também não houve diferença estatisticamente significativa nos escores de dor entre os grupos de tratamento durante as 24 horas pós-cirúrgicas (p = 0,45). O uso intraoperatório de fentanil e morfina não variou significativamente entre os grupos (p = 0,21 e 0,24, respectivamente). Não houve diferença no consumo total de morfina e hidrocodona/APAP durante as primeiras 24 horas (p = 0,61 e 0,53, respectivamente). Conclusão: os pacientes que receberam propofol para manutenção da anestesia geral não apresentaram menos dor pós-colecistectomia videolaparoscópica em comparação com os que receberam isoflurano, desflurano ou sevoflurano. .

Justificación y objetivo: el dolor es el principal motivo de queja y también la principal razón de una prolongada recuperación tras una colecistectomía laparoscópica. Nuestra hipótesis fue que los pacientes sometidos a colecistectomía laparoscópica tenían menos dolor 4 h después de la cirugía cuando recibían propofol para la anestesia en comparación con isoflurano, desflurano o sevoflurano. Métodos: en este estudio prospectivo y aleatorizado, 80 pacientes programados para colecistectomía laparoscópica fueron designados para recibir propofol, isoflurano, desflurano o sevoflurano para el mantenimiento de la anestesia. Nuestro primer resultado fue el dolor medido en escala analógica numérica 4 h después de la cirugía. También registramos el uso intraoperatorio de opiáceos y el consumo de analgésicos durante las primeras 24 h del postoperatorio. Resultados: no hubo diferencias estadísticamente significativas en las puntuaciones del dolor 4 h después de la cirugía (p = 0,72). Tampoco hubo diferencias estadísticamente significativas en las puntuaciones del dolor entre los grupos de tratamiento durante las 24 h del postoperatorio (p = 0,45). El uso intraoperatorio de fentanilo y morfina no varió significativamente entre los grupos (p = 0,21 y 0,24 respectivamente). No hubo una diferencia en el consumo total de morfina e hidrocodona/APAP durante las primeras 24 h (p = 0,61 y 0,53 respectivamente). Conclusiones: los pacientes que recibieron propofol para el mantenimiento de la anestesia general no tenían menos dolor poscolecistectomía videolaparoscópica en comparación con los que recibieron isoflurano, desflurano o sevoflurano. .