Ion Codreanu

A high-fat diet impairs cardiac high-energy phosphate metabolism and cognitive function in healthy human subjects

BACKGROUND High-fat, low-carbohydrate diets are widely used for weight reduction, but they may also have detrimental effects via increased circulating free fatty acid concentrations. OBJECTIVE We tested whether raising plasma free fatty acids by using a high-fat, low-carbohydrate diet results in alterations in heart and brain in healthy subjects. DESIGN Men (n = 16) aged 22 ± 1 y (mean ± SE) were randomly assigned to 5 d of a high-fat, low-carbohydrate diet containing 75 ± 1% of calorie intake through fat consumption or to an isocaloric standard diet providing 23 ± 1% of calorie intake as fat. In a crossover design, subjects undertook the alternate diet after a 2-wk washout period, with results compared after the diet periods. Cardiac (31)P magnetic resonance (MR) spectroscopy and MR imaging, echocardiography, and computerized cognitive tests were used to assess cardiac phosphocreatine (PCr)/ATP, cardiac function, and cognitive function, respectively. RESULTS Compared with the standard diet, subjects who consumed the high-fat, low-carbohydrate diet had 44% higher plasma free fatty acids (P < 0.05), 9% lower cardiac PCr/ATP (P < 0.01), and no change in cardiac function. Cognitive tests showed impaired attention (P < 0.01), speed (P < 0.001), and mood (P < 0.01) after the high-fat, low-carbohydrate diet. CONCLUSION Raising plasma free fatty acids decreased myocardial PCr/ATP and reduced cognition, which suggests that a high-fat diet is detrimental to heart and brain in healthy subjects.

Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp

We postulated that changes in cardiac high‐energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17‐d trek to Mt. Everest Base Camp (5300 m). 31P magnetic resonance (MR) spectroscopy was used to measure cardiac phosphocreatine (PCr)/ATP, and MR imaging and echocardiography were used to assess cardiac volumes, mass, and function. Immediately after returning from Mt. Everest, total body weight had fallen by 3% (P<0.05), but left ventricular mass, adjusted for changes in body surface area, had disproportionately decreased by 11% (P<0.05). Alterations in diastolic function were also observed, with a reduction in peak left ventricular filling rates and mitral inflow E/A, by 17% (P<0.05) and 24% (P<0.01), respectively, with no change in hydration status. Compared with pretrek, cardiac PCr/ATP ratio had decreased by 18% (P<0.01). Whether the abnormalities were even greater at altitude is unknown, but all had returned to pretrek levels after 6 mo. The alterations in cardiac morphology, function, and energetics are similar to findings in patients with chronic hypoxia. Thus, a decrease in cardiac PCr/ATP may be a universal response to periods of sustained low oxygen availability, underlying hypoxia‐induced cardiac dysfunction in healthy human heart and in patients with cardiopulmonary diseases.—Holloway, C. J., Montgomery, H. U., Murray, A. J., Cochlin, L. E., Codreanu, I. Hopwood, N., Johnson, A. W., Rider, O. J., Levett, D. Z. H., Tyler, D. J., Francis, J. M., Neubauer, S., Grocott, M. P. W., Clarke, K., for the Caudwell Xtreme Everest Research Group. Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp. FASEB J. 25, 792–796 (2011). www.fasebj.org

Short-term consumption of a high-fat diet impairs whole-body efficiency and cognitive function in sedentary men

We recently showed that a short‐term high‐fat diet blunted exercise performance in rats, accompanied by increased uncoupling protein levels and greater respiratory uncoupling. In this study, we investigated the effects of a similar diet on physical and cognitive performance in humans. Twenty sedentary men were assessed when consuming a standardized, nutritionally balanced diet (control) and after7dof consuming a diet comprising 74% kcal from fat. Efficiency was measured during a standardized exercise task, and cognition was assessed using a computerized assessment battery. Skeletal muscle mitochondrial function was measured using 31P magnetic resonance spectroscopy. The diet increased mean ± se plasma free fatty acids by 44% (0.32±0.03 vs. 0.46±0.05 mM; P<0.05) and decreased whole‐body efficiency by 3% (21±1 vs. 18±1%;P<0.05), although muscle uncoupling protein (UCP3) content and maximal mitochondrial function were unchanged. High‐fat diet consumption also increased subjects’ simple reaction times (P<0.01) and decreased power of attention (P<0.01). Thus, we have shown that a high‐fat diet blunts whole‐body efficiency and cognition in sedentary men. We suggest that this effect may be due to increased respiratory uncoupling.—Edwards, L. M., Murray, A. J., Holloway, C. J., Carter, E. E., Kemp, G. J., Codreanu, I., Brooker, H., Tyler, D. J. Tyler, Robbins, P. A., Clarke, K. Short‐term consumption of a high‐fat diet impairs whole‐body efficiency and cognitive function in sedentary men. FASEB J. 25, 1088–1096 (2011). www.fasebj.org

Longitudinally and circumferentially directed movements of the left ventricle studied by cardiovascular magnetic resonance phase contrast velocity mapping

ObjectiveUsing high resolution cardiovascular magnetic resonance (CMR), we aimed to detect new details of left ventricular (LV) systolic and diastolic function, to explain the twisting and longitudinal movements of the left ventricle.MethodsUsing CMR phase contrast velocity mapping (also called Tissue Phase Mapping) regional wall motion patterns and longitudinally and circumferentially directed movements of the left ventricle were studied using a high temporal resolution technique in healthy male subjects (n = 14, age 23 ± 3 years).ResultsPreviously undescribed systolic and diastolic motion patterns were obtained for left ventricular segments (based on the AHA segmental) and for basal, mid and apical segments. The summation of segmental motion results in a complex pattern of ventricular twisting and longitudinal motion in the normal human heart which underlies systolic and diastolic function. As viewed from the apex, the entire LV initially rotates in a counter-clockwise direction at the beginning of ventricular systole, followed by opposing clockwise rotation of the base and counter-clockwise rotation at the apex, resulting in ventricular torsion. Simultaneously, as the entire LV moves in an apical direction during systole, the base and apex move towards each other, with little net apical displacement. The reverse of these motion patterns occur in diastole.ConclusionLeft ventricular function may be a consequence of the relative orientations and moments of torque of the sub-epicardial relative to the sub-endocardial myocyte layers, with influence from tethering of the heart to adjacent structures and the directional forces associated with blood flow. Understanding the complex mechanics of the left ventricle is vital to enable these techniques to be used for the evaluation of cardiac pathology.

Chasing the reflected wave back into the heart: a new hypothesis while the jury is still out

Background: Arterial stiffness directly influences cardiac function and is independently associated with cardiovascular risk. However, the influence of the aortic reflected pulse pressure wave on left ventricular function has not been well characterized. The aim of this study was to obtain detailed information on regional ventricular wall motion patterns corresponding to the propagation of the reflected aortic wave on ventricular segments. Methods: Left ventricular wall motion was investigated in a group of healthy volunteers (n = 14, age 23 ± 3 years), using cardiac magnetic resonance navigator-gated tissue phase mapping. The left ventricle was divided into 16 segments and regional wall motion was studied in high temporal detail. Results: Corresponding to the expected timing of the reflected aortic wave reaching the left ventricle, a characteristic “notch” of regional myocardial motion was seen in all radial, circumferential, and longitudinal velocity graphs. This notch was particularly prominent in septal segments adjacent to the left ventricular outflow tract on radial velocity graphs and in anterior and posterior left ventricular segments on circumferential velocity graphs. Similarly, longitudinal velocity graphs demonstrated a brief deceleration in the upward recoil motion of the entire ventricle at the beginning of diastole. Conclusion: These results provide new insights into the possible influence of the reflected aortic waves on ventricular segments. Although the association with the reflected wave appears to us to be unambiguous, it represents a novel research concept, and further studies enabling the actual recording of the pulse wave are required.

Effects of ventricular insertion sites on rotational motion of left ventricular segments studied by cardiac MR

OBJECTIVE Obtaining new details for rotational motion of left ventricular (LV) segments using velocity encoding cardiac MR and correlating the regional motion patterns to LV insertion sites. METHODS Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Peak rotational velocities and circumferential velocity curves were obtained for 16 ventricular segments. RESULTS Reduced peak clockwise velocities of anteroseptal segments (i.e. Segments 2 and 8) and peak counterclockwise velocities of inferoseptal segments (i.e. Segments 3 and 9) were the most prominent findings. The observations can be attributed to the LV insertion sites into the right ventricle, limiting the clockwise rotation of anteroseptal LV segments and the counterclockwise rotation of inferoseptal segments as viewed from the apex. Relatively lower clockwise velocities of Segment 5 and counterclockwise velocities of Segment 6 were also noted, suggesting a cardiac fixation point between these two segments, which is in close proximity to the lateral LV wall. CONCLUSION Apart from showing different rotational patterns of LV base, mid ventricle and apex, the study showed significant differences in the rotational velocities of individual LV segments. Correlating regional wall motion with known orientation of myocardial aggregates has also provided new insights into the mechanisms of LV rotational motions during a cardiac cycle. ADVANCES IN KNOWLEDGE LV insertion into the right ventricle limits the clockwise rotation of anteroseptal LV segments and the counterclockwise rotation of inferoseptal segments adjacent to the ventricular insertion sites. The pattern should be differentiated from wall motion abnormalities in cardiac pathology.

Oral Coenzyme Q10 supplementation does not prevent cardiac alterations during a high altitude trek to everest base cAMP.

Exposure to high altitude is associated with sustained, but reversible, changes in cardiac mass, diastolic function, and high-energy phosphate metabolism. Whilst the underlying mechanisms remain elusive, tissue hypoxia increases generation of reactive oxygen species (ROS), which can stabilize hypoxia-inducible factor (HIF) transcription factors, bringing about transcriptional changes that suppress oxidative phosphorylation and activate autophagy. We therefore investigated whether oral supplementation with an antioxidant, Coenzyme Q10, prevented the cardiac perturbations associated with altitude exposure. Twenty-three volunteers (10 male, 13 female, 46±3 years) were recruited from the 2009 Caudwell Xtreme Everest Research Treks and studied before, and within 48 h of return from, a 17-day trek to Everest Base Camp, with subjects receiving either no intervention (controls) or 300 mg Coenzyme Q10 per day throughout altitude exposure. Cardiac magnetic resonance imaging and echocardiography were used to assess cardiac morphology and function. Following altitude exposure, body mass fell by 3 kg in all subjects (p<0.001), associated with a loss of body fat and a fall in BMI. Post-trek, left ventricular mass had decreased by 11% in controls (p<0.05) and by 16% in Coenzyme Q10-treated subjects (p<0.001), whereas mitral inflow E/A had decreased by 18% in controls (p<0.05) and by 21% in Coenzyme Q10-treated subjects (p<0.05). Coenzyme Q10 supplementation did not, therefore, prevent the loss of left ventricular mass or change in diastolic function that occurred following a trek to Everest Base Camp.

Details of left ventricular radial wall motion supporting the ventricular theory of the third heart sound obtained by cardiac MR.

OBJECTIVE Obtaining new details of radial motion of left ventricular (LV) segments using velocity-encoding cardiac MRI. METHODS Cardiac MR examinations were performed on 14 healthy volunteers aged between 19 and 26 years. Cine images for navigator-gated phase contrast velocity mapping were acquired using a black blood segmented κ-space spoiled gradient echo sequence with a temporal resolution of 13.8 ms. Peak systolic and diastolic radial velocities as well as radial velocity curves were obtained for 16 ventricular segments. RESULTS Significant differences among peak radial velocities of basal and mid-ventricular segments have been recorded. Particular patterns of segmental radial velocity curves were also noted. An additional wave of outward radial movement during the phase of rapid ventricular filling, corresponding to the expected timing of the third heart sound, appeared of particular interest. CONCLUSION The technique has allowed visualization of new details of LV radial wall motion. In particular, higher peak systolic radial velocities of anterior and inferior segments are suggestive of a relatively higher dynamics of anteroposterior vs lateral radial motion in systole. Specific patterns of radial motion of other LV segments may provide additional insights into LV mechanics. ADVANCES IN KNOWLEDGE The outward radial movement of LV segments impacted by the blood flow during rapid ventricular filling provides a potential substrate for the third heart sound. A biphasic radial expansion of the basal anteroseptal segment in early diastole is likely to be related to the simultaneous longitudinal LV displacement by the stretched great vessels following repolarization and their close apposition to this segment.

Normobaric hypoxia elevates free fatty acids and impairs cardiac energetics and diastolic function in normal human volunteers

Methods Healthy males from the University of Oxford (n = 12, age 24 ± 2) underwent twenty hours of normobaric hypoxia in purpose-built hypoxia chambers. The partial pressure of oxygen during end tidal expiration (PETO2) was kept between 50 and 60 mmHg, whilst keeping peripheral oxygen saturation (SaO2) above 80%. Cardiac function was measured using magnetic resonance imaging (MRI) and echocardiography. High-energy phosphate metabolism was measured as the ratio of phosphocreatine to ATP (PCr/ATP) by 31Phosphorus magnetic resonance spectroscopy (MRS) before and after twenty hours of hypoxia. Additionally, four subjects had blood taken for biochemical analysis every four hours.

High-grade solitary extramedullary plasmacytoma arising in skeletal muscle of a kidney transplant recipient.

Extramedullary plasmacytomas (EMPs) comprise less than 3% f all plasma cell malignancies. Although rare, post-transplant lymhoproliferative disorders (PTLD) are known complications of solid rgan and bone marrow/stem cell transplantation. PTLD include a ast range of both lymphoid and plasma cell proliferations. Very ew cases of solitary EMP have been reported in kidney transplant ecipients. We report herein the first case of a high-grade solitary MP of skeletal muscle origin in a renal transplant recipient. A 38-year-old Hispanic female with history of allogeneic kidey transplant 18 months prior presented in November 2010 with one-month history of progressive right upper thigh discomfort. he denied fever, weight loss, or night sweats. Her medications ncluded prednisone, tacrolimus, colchicine and valganciclovir. She enied alcohol and tobacco use, and any occupational or other azards. Family history was unremarkable. Physical examination evealed an ill-defined mass, involving the right lateral proximal high that was tender to palpation. Aside from the thigh mass nd a moderate pallor, physical examination was unremarkable. here was no palpable lymphadenopathy. Laboratory data showed hemoglobin of 11.8 g/dL, a hematocrit of 34.9%, a white blood ell count of 35.5 × 109/L with a mature neutrophil predominance, nd platelet count of 185 × 109/L. Creatinine was 1.2 mg/dL, eGFR 8 ml/min, and electrolytes including calcium were normal. LDH as elevated at 818 U/L (normal, 180–616 U/L), alkaline phoshatase was elevated at 311 U/L (normal, 45–125 U/L), and ESR as 18 mm/hr. Beta-2-microglobulin was 4.58 mg/L (1.2–2.8 mg/L), otal serum protein 7.5 g/dL, albumin 3.9 g/dL. Serum protein elecrophoresis was essentially normal and no M-component was seen. uantitative immunoglobulin levels IgG, IgA and IgM, as well as ree light chains and ratio were also normal. A myeloma skeletal urvey showed no evidence of lytic lesions in the area of right emur or elswhere, and no soft tissues calcifications. An MRI of he right femur with and without gadolinium showed a complex .0 cm × 3.1 cm × 8.6 cm heterogeneous mass arising in the proxmal vastus intermedius muscle (Fig. 1). The lesion was T2 bright nd displayed T1 surrounding edema. Enhancement was apprecited along the muscle fibers. The patient underwent a right thigh ass core needle biopsy and a bone marrow biopsy. Morphologic nd phenotypic analysis by paraffin immunohistochemistry were onsistent with involvement by a monomorphic PTLD consistent ith plasmacytoma (Fig. 2A). The tumor cells were strongly positive or vimentin and CD138, and exhibited a preferential kappa light hain expression (Fig. 2B and C). The immunophenotypic analysis of he bone marrow and peripheral blood by flow cytometry showed o diagnostic immunophenotypic evidence of Bor T-cell lympho-