A haptic training environment for the heart myoblast cell injection procedure

The heart muscle of a cardiac arrest victim continues to accumulate damage throughout its lifetime. This reduces the heart's ability to pump sufficient oxygen and nutrient blood to meet the body's needs. Medical researchers have shown that direct injection of pre-harvested skeletal myoblast cells into the heart can restore some muscle function [1]. This operative procedure usually necessitates the surgeon to open a patient's chest. The open chest procedure is usually a lengthy process and often extends the recovery time of the patient. Alternatively, a high accuracy surgical aid robotic system can be used to assist the thoracoscopic surgery [2][3]. While the robotic surgical method aids faster patient recovery, a less experienced surgeon can potentially cause damage to surrounding tissue.

This paper presents a study into the development of a virtual haptically-enabled heart myoblast injection simulation environment, which can be used to train new surgeons to get hands on experience with the process. The paper also discusses the development of a generic constraint motion technique for needle insertion. Experiments on human performance measures and efficacy, while interacting with haptic feedback training models, are also presented. The experiment involved 10 operators, with each person repeating the needle insertion and injection 10 times. A notable improvement in the task execution time with the number of repetitions was observed. Operators improved their time by up to 300% compared to their first training attempt for a static heart scenario. Under a dynamic heart motion, operator's performance was slightly lower, with the successful rate of completing the experiment reduced from 84% to 75%.

Problem-based learning and masculinities : unique opportunities for Mr. Fix It? Well, maybe

I watched a smoker of 30 years being admitted to the Coronary Care unit following an acute Myocardial Infarction (heart attack). The message from the male clinician was simple, accurate, but somewhat behaviourist: " the death of part of your heart muscle is the result of your smoking, if you don’t stop smoking the damage will continue and you will die." A global, proactive and humanistic consultation demonstrating an understanding of the man’s addiction to a legal and accessible drug and illuminating prevention strategies may have been more appropriate. Maybe the interaction was about competing masculinities, the risk taker and the problem solver. The irony? As I left the hospital that night I observed the same clinician strategically positioned in a secluded hospital doorway drawing heavily on a cigarette. Hypocrite? No, invincible late 20’s male? Maybe. Smoking was someone else’s problem – at least today.

In my 16 years as a clinician such scenarios are common. Clinical practice based predominantly on problem solving potentiates hegemonic masculine approaches to treating men in clinical practice, often justified by limited health resources and increasing patient acuity. Ironically, Problem-based Learning (PBL) curriculums commonly used in health sciences higher education encourages, nurtures and rewards such problem solving approaches. As a teaching academic with current clinical practice it occurs to me that health science education and PBL has an opportunity if not obligation to empower clinicians to establish holistic approaches to male health presentations.

This paper explores the interconnections of Problem-based Learning (PBL) curriculums, health promotion, male nurses’ health-related behaviours and the implications and specificities of masculinity. The pilot study offers an insight into the perceptions of three male nurses that completed undergraduate nursing studies in PBL curriculums. The data obtained introduces some connections that could be illuminated by further research.

The long life of birds : the rat-pigeon comparison revisited

The most studied comparison of aging and maximum lifespan potential (MLSP) among endotherms involves the 7-fold longevity difference between rats (MLSP 5y) and pigeons (MLSP 35y). A widely accepted theory explaining MLSP differences between species is the oxidative stress theory, which purports that reactive oxygen species (ROS) produced during mitochondrial respiration damage bio-molecules and eventually lead to the breakdown of regulatory systems and consequent death. Previous rat-pigeon studies compared only aspects of the oxidative stress theory and most concluded that the lower mitochondrial superoxide production of pigeons compared to rats was responsible for their much greater longevity. This conclusion is based mainly on data from one tissue (the heart) using one mitochondrial substrate (succinate). Studies on heart mitochondria using pyruvate as a mitochondrial substrate gave contradictory results. We believe the conclusion that birds produce less mitochondrial superoxide than mammals is unwarranted. We have revisited the rat-pigeon comparison in the most comprehensive manner to date. We have measured superoxide production (by heart, skeletal muscle and liver mitochondria), five different antioxidants in plasma, three tissues and mitochondria, membrane fatty acid composition (in seven tissues and three mitochondria), and biomarkers of oxidative damage. The only substantial and consistent difference that we have observed between rats and pigeons is their membrane fatty acid composition, with rats having membranes that are more susceptible to damage. This suggests that, although there was no difference in superoxide production, there is likely a much greater production of lipid-based ROS in the rat. We conclude that the differences in superoxide production reported previously were due to the arbitrary selection of heart muscle to source mitochondria and the provision of succinate. Had mitochondria been harvested from other tissues or other relevant mitochondrial metabolic substrates been used, then very different conclusions regarding differences in oxidative stress would have been reached. ©

Mechanisms and treatment of cardiac atrophy secondary to cancer cachexia

 This project found that oxidative stress and activation of pro-inflammatory molecules is a feature of heart protein loss secondary to cancer wasting. Treatment with an omega-3 fatty acid is able to protect against heart muscle loss in cancer by reducing gene transcripts of both pro-inflammatory and oxidative molecules.

Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate—A randomized controlled trial

Background : We aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF).

Methods and Results : Thirteen CHF patients (New York Heart Association functional class 2.3 ± 0.5; Left ventricular ejection fraction 26 ± 8%; age 70 ± 8 years) underwent testing for peak total body oxygen consumption (VO_2peak), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO_2peak and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO_2peak, P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO_2peak) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO_2peak.

Conclusions : These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.

Respiratory muscle dysfunction and training in chronic heart failure

A characteristic feature of chronic heart failure (CHF) is reduced exercise tolerance. Several factors contributing to this have been identified, including alterations in central haemodynamics, skeletal muscle oxygen utilisation and respiratory muscle dysfunction. This review focuses on abnormalities identified in respiratory muscle structure and function in CHF and recent evidence for the benefit of selective inspiratory muscle training in CHF. Included in this review are findings from original investigations, with a specific focus on recent published data.

Local nitric oxide synthase inhibition reduces skeletal muscle glucose uptake but not capillary blood flow during in situ muscle contraction in rats

OBJECTIVE: We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats.

RESEARCH DESIGN AND METHODS: Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (arterial concentration of 5 µmol/l) or saline was infused into the epigastric artery of the contracting leg.

RESULTS: Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P < 0.05) skeletal muscle NOS activity, and this was prevented by L-NAME infusion. NOS inhibition caused a modest significant (P < 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P < 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ~35%, without affecting AMP-activated protein kinase (AMPK) activation.

CONCLUSIONS: NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.

Reliability of isokinetic strength and aerobic power testing for patients with chronic heart failure

PURPOSE: The objective of this study was to assess the reliability of testing skeletal muscle strength and peak aerobic power in a clinical population of patients with chronic heart failure (CHF).

METHODS: Thirty-three patients with CHF (New York Heart Association (NYHA) Functional Class 2.3 ± 0.5; left ventricular ejection fraction 27% ± 7%; age 65 ± 9 years; 28:5 male-female ratio) underwent two identical series of tests (T1 and T2), 1 week apart, for strength and endurance of the muscle groups responsible for knee extension/flexion and elbow extension/flexion. The patients also underwent two graded exercise tests on a bicycle ergometer to measure peak oxygen consumption (VO_2peak). Three months later, 18 of the patients underwent a third test (T3) for each of the measures. Means were compared using MANOVA with repeated measures for strength and endurance, and ANOVA with repeated measures for VO_2peak.

RESULTS: Combining data for all four movement patterns, the expression of strength increased from T1 to T2 by 12% ± 25% (P < .001; intraclass correlation coefficient [ICC] = 0.89). Correspondingly, endurance increased by 13% ± 23% (P = .004; ICC = 0.87). Peak oxygen consumption was not significantly different (16.2 ± 0.8 and 16.1 ± 0.8 mL·kg^-1·min^-1 for T1 and T2, respectively;P = .686; ICC = 0.91). There were no significant differences between T2 and T3 for strength (2% ± 17%;P = .736; ICC = 0.92) or muscle endurance (-1% ± 15%;P = .812; ICC = 0.96), but VO_2peak decreased from 16.7 ± 1.2 to 14.9 ± 0.9 mL·kg^-1·min^-1 (-10% ± 18%;P = .021; ICC = 0.89).

CONCLUSIONS: These data suggest that in a population of patients with CHF, a familiarization trial for skeletal muscle strength testing is necessary. Although familiarization is not required for assessing oxygen consumption as a single measurement, VO_2peak declined markedly in the 3-month period for which these patients were followed. Internal consistency within patients was high for the second and third strength trials and the first and second tests of VO_2peak.

Exercise and Sports Science Australia position statement on exercise training and chronic heart failure

Chronic heart failure (CHF) is a complex syndrome characterised by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Regular exercise participation has been shown to be a safe and effective treatment modality in the majority of CHF patients, partially reversing some of the maladaptations evident in myocardial and skeletal muscle function, and resulting in improvements in physical fitness and quality of life, and perhaps reduced mortality. The volume and intensity of exercise that is recommended depends on the syndrome severity, however in most patients it should consist of a combination of low-to-moderate intensity aerobic (endurance) exercise on most days of the week and individually prescribed low-to-moderate intensity resistance (strength) training at least twice per week. Additionally, all patients should be closely monitored prior to and during exercise for contraindications by an appropriately trained health professional. The purpose of this statement is to inform and guide exercise practitioners and health professionals in the safe and effective prescription and supervision of exercise for patients with CHF.

Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity

Background : We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance.

Methods and results : Total body O₂ uptake (VO_2peak) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO_2peak (15.1±1.1 versus 28.1±2.3 mL·kg⁻¹·min⁻¹, P<.001) and capillary to fiber ratio (1.09±0.05 versus 1.40±0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups.

Conclusions : Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO_2peak observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.

Growth restriction before and after birth increases kinase signaling pathways in the adult rat heart

To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control). In males, Reduced Litter offspring had increased LV phosphorylation of AMPKa, p38 MAPK and Akt compared with Restricted and Controls (P,0.05). In females, both Restricted and Reduced Litter adult offspring had increased LV phosphorylation of p38 MAPK and Akt, however, only Restricted offspring had increased phosphorylation of AMPKa (P,0.05). In addition, only Restricted male offspring displayed LV oxidative stress (P,0.05). Experiment two investigated in mothers exposed to uteroplacental insufficiency or sham surgery the effects of cross-fostering offspring at birth, and therefore the effects of the postnatal lactational environment. Surprisingly, the cross-fostering itself resulted in increased LV phosphorylation of AMPKa and Akt in females and increased phosphorylation of Akt in males compared with Control non-cross-fostered offspring (P,0.05). In conclusion, kinase signaling in the adult LV can be programmed by uteroplacental insufficiency induced growth restriction in a gender-specific manner. In addition, the heart of adult rats is also sensitive to programming following the postnatal intervention of cross-fostering alone as well as by postnatal growth restriction.

Insulin entry into muscle involves a saturable process in the vascular endothelium

Aims/hypothesis : Insulin's rate of entry into skeletal muscle appears to be the rate-limiting step for muscle insulin action and is slowed by insulin resistance. Despite its obvious importance, uncertainty remains as to whether the transport of insulin from plasma to muscle interstitium is a passive diffusional process or a saturable transport process regulated by the insulin receptor. Methods : To address this, here we directly measured the rate of 125I-labelled insulin uptake by rat hindlimb muscle and examined how that is affected by adding unlabelled insulin at high concentrations. We used mono-iodinated [125I]TyrA14-labelled insulin and short (5 min) exposure times, combined with trichloroacetic acid precipitation, to trace intact bioactive insulin. Results : Compared with saline, high concentrations of unlabelled insulin delivered either continuously (insulin clamp) or as a single bolus, significantly raised plasma 125I-labelled insulin, slowed the movement of 125I-labelled insulin from plasma into liver, spleen and heart (p < 0.05, for each) but increased kidney 125I-labelled insulin uptake. High concentrations of unlabelled insulin delivered either continuously (insulin clamp), or as a single bolus, significantly decreased skeletal muscle 125I-labelled insulin clearance (p < 0.01 for each). Increasing muscle perfusion by electrical stimulation did not prevent the inhibitory effect of unlabelled insulin on muscle 125I-labelled insulin clearance. Conclusions/interpretation : These results indicate that insulin's trans-endothelial movement within muscle is a saturable process, which is likely to involve the insulin receptor. Current findings, together with other recent reports, suggest that trans-endothelial insulin transport may be an important site at which muscle insulin action is modulated in clinical and pathological settings.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise

Cold water immersion (CWI) and active recovery (ACT) are frequently used as postexercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q̇), muscle oxygenation (SmO2), blood volume (tHb), muscle temperature (Tmuscle), and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q̇ (7.9 ± 2.7 l) and Tmuscle (2.2 ± 0.8°C) increased, whereas SmO2 (-21.5 ± 8.8%) and tHb (-10.1 ± 7.7 μM) decreased after exercise (P < 0.05). During CWI, Q̇ (-1.1 ± 0.7 l) and Tmuscle (-6.6 ± 5.3°C) decreased, while tHb (121 ± 77 μM) increased (P < 0.05). In the hour after CWI, Q̇ and Tmuscle remained low, while tHb also decreased (P < 0.05). By contrast, during ACT, Q̇ (3.9 ± 2.3 l), Tmuscle (2.2 ± 0.5°C), SmO2 (17.1 ± 5.7%), and tHb (91 ± 66 μM) all increased (P < 0.05). In the hour after ACT, Tmuscle, and tHb remained high (P < 0.05). Peak isometric strength during 10-s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; P < 0.05). Muscle deoxygenation time during MVCs increased after ACT (P < 0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (P = 0.052). These findings suggest first that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and second, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature.