Effect of pulsatility on the mathematical modeling of rotary blood pumps

In this study, the effect of time derivatives of flow rate and rotational speed was investigated on the mathematical modeling of a rotary blood pump (RBP). The basic model estimates the pressure head of the pump as a dependent variable using measured flow and speed as predictive variables. Performance of the model was evaluated by adding time derivative terms for flow and speed. First, to create a realistic working condition, the Levitronix CentriMag RBP was implanted in a sheep. All parameters from the model were physically measured and digitally acquired over a wide range of conditions, including pulsatile speed. Second, a statistical analysis of the different variables (flow, speed, and their time derivatives) based on multiple regression analysis was performed to determine the significant variables for pressure head estimation. Finally, different mathematical models were used to show the effect of time derivative terms on the performance of the models. In order to evaluate how well the estimated pressure head using different models fits the measured pressure head, root mean square error and correlation coefficient were used. The results indicate that inclusion of time derivatives of flow and speed can improve model accuracy, but only minimally.

Pulsatile control of rotary blood pumps: Does the modulation waveform matter?

Mechanical support of a failing heart is typically performed with rotary blood pumps running at constant speed, which results in a limited control on cardiac workload and nonpulsatile hemodynamics. A potential solution to overcome these limitations is to modulate the pump speed to create pulses. This study aims at developing a pulsatile control algorithm for rotary pumps, while investigating its effect on left ventricle unloading and the hemodynamics.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial

We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels.

Body composition and fuel metabolism after kidney grafting

Kidney transplant patients display decreased muscle mass and increased fat mass. Whether this altered body composition is due to glucocorticoid induced altered fuel metabolism is unclear. To answer this question, 16 kidney transplant patients were examined immediately after kidney transplantation (12 +/- 4 days, mean +/- SEM) and then during months 2, 5, 11 and 16, respectively, by whole body dual energy X-ray absorptiometry (Hologic QDR 1000W) and indirect calorimetry. Results were compared with those of 16 age, sex and body mass index matched healthy volunteers examined only once. All patients received dietary counselling with a step 1 diet of the American Heart Association and were advised to restrict their caloric intake to the resting energy expenditure plus 30%. Immediately after transplantation, lean mass of the trunk was higher by 7 +/- 1% (P < 0.05) and that of the limbs was lower by more than 10% (P < 0.01) in patients than in controls. In contrast, no difference in fat mass and resting energy expenditure could be detected between patients and controls. During the 16 months of observation, total fat mass increased in male (+4.9 +/- 1.5 kg), but not in female patients (0.1 +/- 0.8 kg). The change in fat mass observed in men was due to an increase in all subregions of the body analysed (trunk, arms+legs as well as head+neck), whereas in women only an increase in head+neck by 9 +/- 2% (P = 0.05) was detected. Body fat distribution remained unchanged in both sexes over the 16 months of observation. Lean mass of the trunk mainly decreased between days 11 and 42 (P < 0.01) and remained stable thereafter. After day 42, lean mass of arms and legs (mostly striated muscle) and head+neck progressively increased over the 14 months of observation by 1.6 +/- 0.6 kg (P < 0.05) and 0.4 +/- 0.1 kg (P < 0.01), respectively. Resting energy expenditure was similar in controls and patients at 42 days (30.0 +/- 0.7 vs. 31.0 +/- 0.9 kcal kg-1 lean mass) and did not change during the following 15 months of observation. However, composition of fuel used to sustain resting energy expenditure in the fasting state was altered in patients when compared with normal subjects, i.e. glucose oxidation was higher by more than 45% in patients (P < 0.01) during the second month after grafting, but gradually declined (P < 0.01) over the following 15 months to values similar to those observed in controls. Protein oxidation was elevated in renal transplant patients on prednisone at first measurement, a difference which tended to decline over the study period. In contrast to glucose and protein oxidation, fat oxidation was lower in patients 42 days after grafting (P < 0.01), but increased by more than 100% reaching values similar to those observed in controls after 16 months of study. Mean daily dose of prednisone per kg body weight correlated with the three components of fuel oxidation (r > 0.93, P < 0.01), i.e. protein, glucose and fat oxidation. These results indicate that in prednisone treated renal transplant patients fuel metabolism is regulated in a dose-dependent manner. Moreover, dietary measures, such as caloric and fat intake restriction as well as increase of protein intake, can prevent muscle wasting as well as part of the usually observed fat accumulation. Furthermore, the concept of preferential upper body fat accumulation as consequence of prednisone therapy in renal transplant patients has to be revised.

Physiologic and hematologic concerns of rotary blood pumps: what needs to be improved?

Over the past few decades, advances in ventricular assist device (VAD) technology have provided a promising therapeutic strategy to treat heart failure patients. Despite the improved performance and encouraging clinical outcomes of the new generation of VADs based on rotary blood pumps (RBPs), their physiologic and hematologic effects are controversial. Currently, clinically available RBPs run at constant speed, which results in limited control over cardiac workload and introduces blood flow with reduced pulsatility into the circulation. In this review, we first provide an update on the new challenges of mechanical circulatory support using rotary pumps including blood trauma, increased non-surgical bleeding rate, limited cardiac unloading, vascular malformations, end-organ function, and aortic valve insufficiency. Since the non-physiologic flow characteristic of these devices is one of the main subjects of scientific debate in the literature, we next emphasize the latest research regarding the development of a pulsatile RBP. Finally, we offer an outlook for future research in the field.

Analysis of Pressure Head-Flow Loops of Pulsatile Rotodynamic Blood Pumps

The clinical importance of pulsatility is a recurring topic of debate in mechanical circulatory support. Lack of pulsatility has been identified as a possible factor responsible for adverse events and has also demonstrated a role in myocardial perfusion and cardiac recovery. A commonly used method for restoring pulsatility with rotodynamic blood pumps (RBPs) is to modulate the speed profile, synchronized to the cardiac cycle. This introduces additional parameters that influence the (un)loading of the heart, including the timing (phase shift) between the native cardiac cycle and the pump pulses, and the amplitude of speed modulation. In this study, the impact of these parameters upon the heart-RBP interaction was examined in terms of the pressure head-flow (HQ) diagram. The measurements were conducted using a rotodynamic Deltastream DP2 pump in a validated hybrid mock circulation with baroreflex function. The pump was operated with a sinusoidal speed profile, synchronized to the native cardiac cycle. The simulated ventriculo-aortic cannulation showed that the level of (un)loading and the shape of the HQ loops strongly depend on the phase shift. The HQ loops displayed characteristic shapes depending on the phase shift. Increased contribution of native contraction (increased ventricular stroke work [WS ]) resulted in a broadening of the loops. It was found that the previously described linear relationship between WS and the area of the HQ loop for constant pump speeds becomes a family of linear relationships, whose slope depends on the phase shift.

Brain-borne IL-1 adjusts glucoregulation and provides fuel support to astrocytes and neurons in an autocrine/paracrine manner.

It is still controversial which mediators regulate energy provision to activated neural cells, as insulin does in peripheral tissues. Interleukin-1β (IL-1β) may mediate this effect as it can affect glucoregulation, it is overexpressed in the 'healthy' brain during increased neuronal activity, and it supports high-energy demanding processes such as long-term potentiation, memory and learning. Furthermore, the absence of sustained neuroendocrine and behavioral counterregulation suggests that brain glucose-sensing neurons do not perceive IL-1β-induced hypoglycemia. Here, we show that IL-1β adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein (MyD88)-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. Furthermore, we found that, opposite to insulin, IL-1β stimulates brain metabolism. This effect is absent in MyD88-deficient mice, which have neurobehavioral alterations associated to disorders in glucose homeostasis, as during several psychiatric diseases. IL-1β effects on brain metabolism are most likely maintained by IL-1β auto-induction and may reflect a compensatory increase in fuel supply to neural cells. We explore this possibility by directly blocking IL-1 receptors in neural cells. The results showed that, in an activity-dependent and paracrine/autocrine manner, endogenous IL-1 produced by neurons and astrocytes facilitates glucose uptake by these cells. This effect is exacerbated following glutamatergic stimulation and can be passively transferred between cell types. We conclude that the capacity of IL-1β to provide fuel to neural cells underlies its physiological effects on glucoregulation, synaptic plasticity, learning and memory. However, deregulation of IL-1β production could contribute to the alterations in brain glucose metabolism that are detected in several neurologic and psychiatric diseases.Molecular Psychiatry advance online publication, 8 December 2015; doi:10.1038/mp.2015.174.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

OBJECTIVE Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. DESIGN Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. RESULTS Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). CONCLUSION A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD.