Ira Jacobs

Markers of inflammation in recipients of continuous-flow left ventricular assist devices.

Although the newer continuous-flow left ventricular assist devices (CF-LVADs) provide clinical advantages over the pulsatile pumps, the effects of low pulsatility on inflammation are incompletely understood. The objective of our study was to examine the levels of inflammatory mediators in CF-LVAD recipients compared with both healthy control subjects and heart failure patients who were candidates for CF-LVAD support. Plasma levels of chemokines, cytokines, and inflammatory markers were measured in 18 CF-LVAD recipients and compared with those of 14 healthy control subjects and 14 heart failure patients who were candidates for CF-LVADs. The levels of granulocyte macrophage-colony stimulating factor, macrophage inflammatory proteins-1&bgr;, and macrophage-derived chemokine were significantly higher in the CF-LVAD group compared with both the heart failure and the healthy control groups, whereas no significant differences were observed between the healthy control subjects and the heart failure groups. Compared with the healthy controls, C-reactive protein, interferon gamma-induced protein-10, monocyte chemotactic protein-1, and interleukin-8 levels were significantly higher in both the CF-LVAD and heart failure groups, but no significant differences were observed between the CF-LVAD recipients and the heart failure patients. Inflammatory markers were elevated in CF-LVAD recipients compared with healthy control subjects and the heart failure patients. Further studies should investigate the clinical implications of elevated levels of inflammation in CF-LVAD recipients.

Increased cyclic guanosine monophosphate levels and continuous-flow left-ventricular assist devices: Implications for gastrointestinal bleeding

OBJECTIVES We examine the hypothesis that cyclic guanosine monophosphate (cGMP) levels are elevated in recipients of continuous-flow left ventricular assist devices (CF-LVADs) and that elevated cGMP levels are associated with a risk of gastrointestinal (GI) bleeding events. METHODS The levels of cGMP, nitric oxide, platelet activation markers, platelet-derived growth factors (PDGF) AB/BB and AA, and the inflammatory mediator C-reactive protein (CRP) were examined in 19 CF-LVAD recipients, 21 patients who had heart failure, and 19 healthy control-group participants. RESULTS The median level of cGMP was significantly higher in CF-LVAD recipients, compared with healthy participants (6.6 vs 2.1 pmol/mL, u = 62.5; P = .001; r = -0.55). Median cGMP levels in the heart failure group (12.5 pmol/L) were higher, compared with both CF-LVAD recipients (u = 75.0; P = .001; r = -0.53) and healthy participants (u = 4.0; P < .001; r = -0.83). Compared with the healthy group, median CRP levels were significantly higher in CF-LVAD recipients (2.9 vs 8.0 mg/L; u = 58.0; P < .001; r = -0.63) and heart failure patients (2.9 vs 7.0 mg/L; u = 59.0; P < .001; r = -0.65). In the subgroup of patients supported with the HeartMate II (Thoratec Corporation, Pleasanton, Calif), pulsatility index was significantly negatively correlated with cGMP levels (r = -0.73; P < .05), indicating that low pulsatility index is associated with higher cGMP levels. High cGMP levels were significantly associated with GI bleeding events, but not with bleeding events in general. CONCLUSIONS The primary finding of this study is that GI bleeding in CF-LVAD recipients is associated with significantly elevated cGMP levels, despite high levels of CRP, which interfere with cGMP production. Further studies are required to determine whether elevated cGMP levels can be used as a clinical marker for increased risk of GI bleeding in CF-LVAD recipients.

New therapy, new challenges: The effects of long-term continuous flow left ventricular assist device on inflammation

Surgically implanted continuous flow left ventricular assist devices (CF-LVADs) are currently used in patients with end-stage heart failure (HF). However, CF-LVAD therapy introduces a new set of complications and adverse events in these patients. Major adverse events with the CF-LVAD include right heart failure, vascular dysfunction, stroke, hepatic failure, and multi-organ failure, complications that may have inflammation as a common etiology. Our aim was to review the current evidence showing a relationship between these adverse events and elevated levels of inflammatory biomarkers in CF-LVAD recipients.

Longitudinal Assessment of Inflammation in Recipients of Continuous-Flow Left Ventricular Assist Devices

BACKGROUND The long-term effects of continuous-flow left ventricular assist device (CF-LVAD) support on trends of inflammatory markers over time are unknown. We examined the hypothesis that the levels of inflammatory markers in CF-LVAD recipients are higher than in healthy controls and that these levels increase over time with long-term CF-LVAD support. METHODS We examined the levels of inflammatory markers longitudinally at baseline before CF-LVAD implantation and at 3, 6, and 9 months after implantation. We then compared the levels of inflammatory markers to those in a healthy control group. RESULTS Compared with baseline values before CF-LVAD implantation, left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd) decreased significantly at 3, 6, and 9 months after CF-LVAD implantation. Brain natriuretic peptide (BNP) levels dropped significantly after CF-LVAD implantation but did not normalize. Improvements in ejection fraction at 3, 6, and 9 months after CF-LVAD implantation did not reach significance. Monocyte chemoattractant protein-1, interferon γ-induced protein, and C-reactive protein levels were higher in the CF-LVAD recipients at each of the time points (baseline before CF-LVAD implantation and 3, 6, and 9 months after implantation) compared with levels in healthy controls. In CF-LVAD recipients, serum interleukin-8, tumour necrosis factor-α, and macrophage inflammatory protein-β increased significantly at 9 months, and macrophage-derived chemokine increased at 6 months after CF-LVAD implantation compared with baseline. CONCLUSIONS Despite improvements in LV dimensions and BNP levels, markers of inflammation remained higher in CF-LVAD recipients. High levels of inflammation in CF-LVAD recipients may result from heart failure preconditioning or the long-term device support, or both. Because inflammation may be detrimental to CF-LVAD recipients, future studies should determine whether inflammatory pathways are reversible.

Validation of a Tablet Application for Assessing Dietary Intakes Compared with the Measured Food Intake/Food Waste Method in Military Personnel Consuming Field Rations

The collection of accurate dietary intakes using traditional dietary assessment methods (e.g., food records) from military personnel is challenging due to the demanding physiological and psychological conditions of training or operations. In addition, these methods are burdensome, time consuming, and prone to measurement errors. Adopting smart-phone/tablet technology could overcome some of these barriers. The objective was to assess the validity of a tablet app, modified to contain detailed nutritional composition data, in comparison to a measured food intake/waste method. A sample of Canadian Armed Forces personnel, randomized to either a tablet app (n = 9) or a weighed food record (wFR) (n = 9), recorded the consumption of standard military rations for a total of 8 days. Compared to the gold standard measured food intake/waste method, the difference in mean energy intake was small (−73 kcal/day for tablet app and −108 kcal/day for wFR) (p > 0.05). Repeated Measures Bland-Altman plots indicated good agreement for both methods (tablet app and wFR) with the measured food intake/waste method. These findings demonstrate that the tablet app, with added nutritional composition data, is comparable to the traditional dietary assessment method (wFR) and performs satisfactorily in relation to the measured food intake/waste method to assess energy, macronutrient, and selected micronutrient intakes in a sample of military personnel.

Rate dependent influence of arterial desaturation on self-selected exercise intensity during cycling

The purpose of this study was to clarify if Ratings of Perceived Exertion (RPE) and self-selected exercise intensity are sensitive not only to alterations in the absolute level of arterial saturation (SPO2) but also the rate of change in SPO2. Twelve healthy participants (31.6 ± 3.9 y, 175.5 ± 7.7 cm, 73.3 ± 10.3 kg, 51 ± 7 mL·kg-1·min-1 V˙O2peak) exercised four times on a cycle ergometer, freely adjusting power output (PO) to maintain RPE at 5 on Borg’s 10-point scale with no external feedback to indicate their exercise intensity. The fraction of inspired oxygen (FIO2) was reduced during three of those trials such that SPO2 decreased during exercise from starting values (>98%) to 70%. These trials were differentiated by the time over which the desaturation occurred: 3.9 ± 1.4 min, -8.7 ± 4.2%•min-1 (FAST), 11.0 ± 3.7 min, -2.8 ± 1.3%•min-1 (MED), and 19.5 ± 5.8 min, -1.5 ± 0.8%•min-1 (SLOW) (P < 0.001). Compared to stable PO throughout the control condition (no SPO2 manipulation), PO significantly decreased across the experimental conditions (FAST = 2.8 ± 2.1 W•% SPO2-1; MED = 2.5 ± 1.8 W•% SPO2-1; SLOW = 1.8 ± 1.6 W•% SPO2-1; P < 0.001). The rates of decline in PO during FAST and MED were similar, with both greater than SLOW. Our results confirm that decreases in absolute SPO2 impair exercise performance and that a faster rate of oxygen desaturation magnifies that impairment.

Clamping end-tidal carbon dioxide during graded exercise with control of inspired oxygen

Exercise- and hypoxia-induced hyperventilation decreases the partial pressure of end-tidal carbon dioxide (PETCO2), which in turn exerts many physiological effects. Several breathing circuits that control PETCO2 have been previously described, but their designs are not satisfactory for exercise studies where changes in inspired oxygen (FIO2) may be desired. This study is the first report of a breathing system that can maintain PETCO2 constant within a single session of graded submaximal exercise and graded hypoxia. Thirteen fit and healthy subjects completed two bouts of exercise consisting of three 3min stages on a cycle ergometer with increasing exercise intensity in normoxia (Part A; 142±14, 167±14, 192±14W) or with decreasing FIO2 at a constant exercise intensity (Part B; 21, 18, and 14%). One bout was a control (CON) where PETCO2 was not manipulated, while during the other bout the investigator clamped PETCO2 within 2mmHg (CO2Clamp) using sequential gas delivery (SGD). During the final 30s of each exercise stage during CO2Clamp, PETCO2 was successfully maintained in Part A (43±4, 44±4, 44±3mmHg; P=0.44) and Part B (45±3, 46±3, 45±3mmHg; P=0.68) despite the increases in ventilation due to exercise. These findings demonstrate that this SGD circuit can be used to maintain isocapania in exercising humans during progressively increasing exercise intensities and changing FIO2.

The effect of alpha lipoic acid ingestion on glucose uptake in healthy males

Background There are reports that indicate dietary alpha lipoic acid (ALA) supplementation enhances glucose uptake. The research was done with animal models and diabetic humans, but the effects of ALA supplementation on glucose uptake in healthy humans are unknown. The present study was designed to test the hypothesis that acute ingestion of ALA would enhance glucose uptake in healthy male subjects. Methods