Late remote ischemic preconditioning in children undergoing cardiopulmonary bypass: A randomized controlled trial

Objective: Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction. Methods: This was a prospective, randomized, single-blind, controlled trial. Children allocated to remote ischemic preconditioning underwent 4 periods of 5 minutes of lower limb ischemia by a blood pressure cuff intercalated with 5 minutes of reperfusion. Blood samples were collected 4, 12, 24, and 48 hours after cardiopulmonary bypass to evaluate nuclear factor kappa B activation in leukocytes by quantification of mRNA of I kappa B alpha by real-time quantitative polymerase chain reaction and for interleukin-8 and 10 plasma concentration measurements by enzyme-linked immunosorbent assay. Myocardial dysfunction was assessed by N-terminal pro-B-type natriuretic peptide and cardiac troponin I plasma concentrations, measured by chemiluminescence, and clinical parameters of low cardiac output syndrome. Results: Twelve children were allocated to remote ischemic preconditioning, and 10 children were allocated to the control group. Demographic data and Risk Adjustment for Congenital Heart Surgery 1 classification were comparable in both groups. Remote ischemic preconditioning group had lower postoperative values of N-terminal pro-B-type natriuretic peptide, but cardiac troponin I levels were not significantly different between groups. Interleukin-8 and 10 concentrations and I kappa B alpha gene expression were similar in both groups. Postoperative morbidity was similar in both groups; there were no postoperative deaths in either group. Conclusions: Late remote ischemic preconditioning did not provide clinically relevant cardioprotection to children undergoing cardiopulmonary bypass. (J Thorac Cardiovasc Surg 2012;144:178-83)

Air to muscle O2 delivery during exercise at altitude

[EN] Hypoxia-induced hyperventilation is critical to improve blood oxygenation, particularly when the arterial Po2 lies in the steep region of the O2 dissociation curve of the hemoglobin (ODC). Hyperventilation increases alveolar Po2 and, by increasing pH, left shifts the ODC, increasing arterial saturation (Sao2) 6 to 12 percentage units. Pulmonary gas exchange (PGE) is efficient at rest and, hence, the alveolar-arterial Po2 difference (Pao2-Pao2) remains close to 0 to 5mm Hg. The (Pao2-Pao2) increases with exercise duration and intensity and the level of hypoxia. During exercise in hypoxia, diffusion limitation explains most of the additional Pao2-Pao2. With altitude, acclimatization exercise (Pao2-Pao2) is reduced, but does not reach the low values observed in high altitude natives, who possess an exceptionally high DLo2. Convective O2 transport depends on arterial O2 content (Cao2), cardiac output (Q), and muscle blood flow (LBF). During whole-body exercise in severe acute hypoxia and in chronic hypoxia, peak Q and LBF are blunted, contributing to the limitation of maximal oxygen uptake (Vo2max). During small-muscle exercise in hypoxia, PGE is less perturbed, Cao2 is higher, and peak Q and LBF achieve values similar to normoxia. Although the Po2 gradient driving O2 diffusion into the muscles is reduced in hypoxia, similar levels of muscle O2 diffusion are observed during small-mass exercise in chronic hypoxia and in normoxia, indicating that humans have a functional reserve in muscle O2 diffusing capacity, which is likely utilized during exercise in hypoxia. In summary, hypoxia reduces Vo2max because it limits O2 diffusion in the lung.

Effect of blood haemoglobin concentration on V(O2,max) and cardiovascular function in lowlanders acclimatised to 5260 m

[EN] The principal aim of this investigation was to determine the influence of blood haemoglobin concentration ([Hb]) on maximal exercise capacity and maximal O(2) consumption (V(O(2),max)) in healthy subjects acclimatised to high altitude. Secondarily, we examined the effects of [Hb] on the regulation of cardiac output (CO), blood pressure and muscular blood flow (LBF) during exercise. Eight Danish lowlanders (three females and five males; 24 +/- 0.6 years, mean +/- S.E.M.) performed submaximal and maximal exercise on a cycle ergometer after 9 weeks at an altitude of 5260 m (Mt Chacaltaya, Bolivia). This was done first with the high [Hb] resulting from acclimatisation and again 2-4 days later, 1 h after isovolaemic haemodilution with Dextran 70 to near sea level [Hb]. After measurements at maximal exercise while breathing air at each [Hb], subjects were switched to hyperoxia (55 % O(2) in N(2)) and the measurements were repeated, increasing the work rate as tolerated. Hyperoxia increased maximal power output and leg V(O(2),max), showing that breathing ambient air at 5260 m, V(O(2),max) is limited by the availability of O(2) rather than by muscular oxidative capacity. Altitude increased [Hb] by 36 % from 136 +/- 5 to 185 +/- 5 g l(-1) (P < 0.001), while haemodilution (replacing 1 l of blood with 1 l of 6 % Dextran) lowered [Hb] by 24 % to 142 +/- 6 g l(-1) (P < 0.001). Haemodilution had no effect on maximal pulmonary or leg V(O(2),max), or power output. Despite higher LBF, leg O(2) delivery was reduced and maximal V(O(2)) was thus maintained by higher O(2) extraction. While CO increased linearly with work rate irrespective of [Hb] or inspired oxygen fraction (F(I,O(2))), both LBF and leg vascular conductance were systematically higher when [Hb] was low. Close and significant relationships were seen between LBF (and CO) and both plasma noradrenaline and K(+) concentrations, independently of [Hb] and F(I,O(2)). In summary, under conditions where O(2) supply limits maximal exercise, the increase in [Hb] with altitude acclimatisation does not improve maximal exercise capacity or V(O(2),max), and does not alter peak CO. However, LBF and vascular conductance are higher at altitude when [Hb] is lowered to sea level values, with both relating closely to catecholamine and potassium concentrations. This suggests that the lack of effect of [Hb] on V(O(2),max) may involve reciprocal changes in LBF via local metabolic control of the muscle vasculature.

Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?

[EN] Acute hypoxia (AH) reduces maximal O2 consumption (VO2 max), but after acclimatization, and despite increases in both hemoglobin concentration and arterial O2 saturation that can normalize arterial O2 concentration ([O2]), VO2 max remains low. To determine why, seven lowlanders were studied at VO2 max (cycle ergometry) at sea level (SL), after 9-10 wk at 5,260 m [chronic hypoxia (CH)], and 6 mo later at SL in AH (FiO2 = 0.105) equivalent to 5,260 m. Pulmonary and leg indexes of O2 transport were measured in each condition. Both cardiac output and leg blood flow were reduced by approximately 15% in both AH and CH (P < 0.05). At maximal exercise, arterial [O2] in AH was 31% lower than at SL (P < 0.05), whereas in CH it was the same as at SL due to both polycythemia and hyperventilation. O2 extraction by the legs, however, remained at SL values in both AH and CH. Although at both SL and in AH, 76% of the cardiac output perfused the legs, in CH the legs received only 67%. Pulmonary VO2 max (4.1 +/- 0.3 l/min at SL) fell to 2.2 +/- 0.1 l/min in AH (P < 0.05) and was only 2.4 +/- 0.2 l/min in CH (P < 0.05). These data suggest that the failure to recover VO2 max after acclimatization despite normalization of arterial [O2] is explained by two circulatory effects of altitude: 1) failure of cardiac output to normalize and 2) preferential redistribution of cardiac output to nonexercising tissues. Oxygen transport from blood to muscle mitochondria, on the other hand, appears unaffected by CH.

Cardiovascular responses to dynamic exercise with acute anemia in humans

[EN] We hypothesized that reducing arterial O2 content (CaO2) by lowering the hemoglobin concentration ([Hb]) would result in a higher blood flow, as observed with a low PO2, and maintenance of O2 delivery. Seven young healthy men were studied twice, at rest and during two-legged submaximal and peak dynamic knee extensor exercise in a control condition (mean control [Hb] 144 g/l) and after 1-1.5 liters of whole blood had been withdrawn and replaced with albumin [mean drop in [Hb] 29 g/l (range 19-38 g/l); low [Hb]]. Limb blood flow (LBF) was higher (P < 0.01) with low [Hb] during submaximal exercise (i.e., at 30 W, LBF was 2.5 +/- 0.1 and 3.0 +/- 0.1 l/min for control [Hb] and low [Hb], respectively; P < 0.01), resulting in a maintained O2 delivery and O2 uptake for a given workload. However, at peak exercise, LBF was unaltered (6.5 +/- 0.4 and 6.6 +/- 0.6 l/min for control [Hb] and low [Hb], respectively), which resulted in an 18% reduction in O2 delivery (P < 0.01). This occurred despite peak cardiac output in neither condition reaching >75% of maximal cardiac output (approximately 26 l/min). It is concluded that a low CaO2 induces an elevation in submaximal muscle blood flow and that O2 delivery to contracting muscles is tightly regulated.

Progettazione ed implementazione di un dispositivo portabile per l'acquisizione ed il filtraggio di segnali biomedici

The use of wearable devices for the monitoring of biological potentials is an ever-growing area of research. Wearable devices for the monitoring of vital signs such as heart-rate, respiratory rate, cardiac output and blood oxygenation are necessary in determining the overall health of a patient and allowing earlier detection of adverse events such as heart attacks and strokes and earlier diagnosis of disease. This thesis describes a bio-potential acquisition embedded system designed with an innovative analog front-end, showing the performance in EMG and ECG applications and the comparison between different noise reduction algorithms. We demonstrate that the proposed system is able to acquire bio-potentials with a signal quality equivalent to state of the art bench-top biomedical devices and can be therefore used for monitoring purpose, with the advantages of a low-cost low-power wearable device.

Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.

Sonographic Assessment of Fetal Cardiac Function: Indirect Measurements of Fetal Cardiac Function, Newer Techniques and Clinical Applications

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status of fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and in particular clinical situations such as severe growth restriction or volume overload also of venous vessels close to the heart or of flow patterns in the heart is being used to gauge the level of compensation in a fetus. However, quantitative assessment of the driving force of the fetal circulation, the cardiac output remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measurements of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

Sonographic Assessment of Fetal Cardiac Function: Introduction and Direct Measurement of Cardiac Function

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status in fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and, in particular clinical situations such as severe growth restriction or volume overload, also of venous vessels close to the heart or of flow patterns in the heart are being used to gauge the level of compensation in a fetus. Quantitative assessment of the driving force of the fetal circulation, the cardiac output, however, remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measures of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

In situ cardiac performance of Atlantic cod (Gadus morhua) at cold temperatures: long-term acclimation, acute thermal challenge and the role of adrenaline

The resting and maximum in situ cardiac performance of Newfoundland Atlantic cod (Gadus morhua) acclimated to 10, 4 and 0°C were measured at their respective acclimation temperatures, and when acutely exposed to temperature changes: i.e. hearts from 10°C fish cooled to 4°C, and hearts from 4°C fish measured at 10 and 0°C. Intrinsic heart rate (f(H)) decreased from 41 beats min(-1) at 10°C to 33 beats min(-1) at 4°C and 25 beats min(-1) at 0°C. However, this degree of thermal dependency was not reflected in maximal cardiac output (Q(max) values were ~44, ~37 and ~34 ml min(-1) kg(-1) at 10, 4 and 0°C, respectively). Further, cardiac scope showed a slight positive compensation between 4 and 0°C (Q(10)=1.7), and full, if not a slight over compensation between 10 and 4°C (Q(10)=0.9). The maximal performance of hearts exposed to an acute decrease in temperature (i.e. from 10 to 4°C and 4 to 0°C) was comparable to that measured for hearts from 4°C- and 0°C-acclimated fish, respectively. In contrast, 4°C-acclimated hearts significantly out-performed 10°C-acclimated hearts when tested at a common temperature of 10°C (in terms of both Q(max) and power output). Only minimal differences in cardiac function were seen between hearts stimulated with basal (5 nmol l(-1)) versus maximal (200 nmol l(-1)) levels of adrenaline, the effects of which were not temperature dependent. These results: (1) show that maximum performance of the isolated cod heart is not compromised by exposure to cold temperatures; and (2) support data from other studies, which show that, in contrast to salmonids, cod cardiac performance/myocardial contractility is not dependent upon humoral adrenergic stimulation.

Efficiency and safety of bosentan in child C cirrhosis with portopulmonary hypertension and renal insufficiency

Bosentan has lately been described as a successful therapeutic agent for portopulmonary hypertension consecutive to child A cirrhosis. This is the first report of the effect of this substance with advanced liver cirrhosis (child C) and renal insufficiency. Low doses of bosentan (initially twice 31.25 mg/day and then 62.5 mg/day) increased cardiac output and allowed correction of renal insufficiency; it allowed one to stop the requirement of oxygen and not only improved the 6-min walking test by more than 400 m, but also decreased the severity of the liver cirrhosis to child B stadium. This suggests that patients, who would be excluded from a liver transplantation program because of their portopulmonary hypertension, could profit from a careful therapy with bosentan.

Vasopressin in vasodilatory shock: ensure organ blood flow, but take care of the heart!

Supplementary arginine vasopressin infusion in advanced vasodilatory shock may be accompanied by a decrease in cardiac index and systemic oxygen transport capacity in approximately 40% of patients. While a reduction of cardiac output most frequently occurs in patients with hyperdynamic circulation, it is less often observed in patients with low cardiac index. Infusion of inotropes, such as dobutamine, may be an effective strategy to restore systemic blood flow. However, when administering inotropic drugs, systemic blood flow should be increased to adequately meet systemic demands (assessed by central or mixed venous oxygen saturation) without putting an excessive beta-adrenergic stress on the heart. Overcorrection of cardiac index to hyperdynamic values with inotropes places myocardial oxygen supply at significant risk.

Arterio-venous gradients of free energy change for assessment of systemic and splanchnic perfusion in cardiac surgery patients

OBJECTIVE: Adequacy of organ perfusion depends on sufficient oxygen supply in relation to the metabolic needs. The aim of this study was to evaluate the relationship between gradients of free energy change, and the more commonly used parameter for the evaluation of the adequacy of organ perfusion, such as oxygen-extraction in patients undergoing valve replacement surgery using normothermic cardiopulmonary bypass (CPB). METHODS: In 43 cardiac patients, arterial, mixed venous, and hepato-venous blood samples were taken synchronously after induction of anaesthesia (preCPB), during CPB, and 2 and 7 h after admission to the intensive care unit (ICU+2, ICU+7). Blood gas analysis, cardiac output, and hepato-splanchnic blood flow were measured. Free energy change gradients between mixed venous and arterial (-deltadeltaG(v - a)) and hepato-venous and arterial (-deltadeltaG(hv - a)) compartments were calculated. MEASUREMENTS AND RESULTS: Cardiac index (CI) increased from 1.9 (0.7) to 2.8 (1.3) L/min/m (median, inter-quartile range) (p = 0.001), and hepato-splanchnic blood flow index (HBFI) from 0.6 (0.22) to 0.8 (0.53) L/min/m (p = 0.001). Despite increasing flow, systemic oxygen extraction increased after CPB from 24 (10)% to 35 (10)% at ICU+2 (p = 0.002), and splanchnic oxygen extraction increased during CPB from 37 (19)% to 52 (14)% (p = 0.001), and remained high thereafter. After CPB, high splanchnic and systemic gradients of free energy change gradients were associated with high splanchnic and systemic oxygen extraction, respectively (p = 0.001, 0.033, respectively). CONCLUSION: Gradients of free energy change may be helpful in characterising adequacy of perfusion in cardiac surgery patients independently from measurements or calculations of data from oxygen transport.

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

Cyclical recruitment of atelectasis with each breath is thought to contribute to ventilator-associated lung injury. Extrinsic positive end-expiratory pressure (PEEPe) can maintain alveolar recruitment at end exhalation, but PEEPe depresses cardiac output and increases overdistension. Short exhalation times can also maintain end-expiratory recruitment, but if the mechanism of this recruitment is generation of intrinsic PEEP (PEEPi), there would be little advantage compared with PEEPe. In seven New Zealand White rabbits, we compared recruitment from increased respiratory rate (RR) to recruitment from increased PEEPe after saline lavage. Rabbits were ventilated in pressure control mode with a fraction of inspired O(2) (Fi(O(2))) of 1.0, inspiratory-to-expiratory ratio of 2:1, and plateau pressure of 28 cmH(2)O, and either 1) high RR (24) and low PEEPe (3.5) or 2) low RR (7) and high PEEPe (14). We assessed cyclical lung recruitment with a fast arterial Po(2) probe, and we assessed average recruitment with blood gas data. We measured PEEPi, cardiac output, and mixed venous saturation at each ventilator setting. Recruitment achieved by increased RR and short exhalation time was nearly equivalent to recruitment achieved by increased PEEPe. The short exhalation time at increased RR, however, did not generate PEEPi. Cardiac output was increased on average 13% in the high RR group compared with the high PEEPe group (P < 0.001), and mixed venous saturation was consistently greater in the high RR group (P < 0.001). Prevention of end-expiratory derecruitment without increased end-expiratory pressure suggests that another mechanism, distinct from intrinsic PEEP, plays a role in the dynamic behavior of atelectasis.

Influence of exertional oscillatory ventilation on exercise performance in heart failure

BACKGROUND: Exertional oscillatory ventilation (EOV) in heart failure may potentiate the negative effects of low cardiac output and high ventilation on exercise performance. We hypothesized that the presence of EOV might, per se, influence exercise capacity as evaluated by maximal cardiopulmonary exercise test. METHODS AND RESULTS: We identified 78 severe chronic heart failure patient pairs with and without EOV. Patients were matched for sex, age and peak oxygen consumption (VO2). Patients with EOV showed, for the same peak VO2, a lower workload (WL) at peak (DeltaWatts=5.8+/-23.0, P=0.027), a less efficient ventilation (higher VE/VCO2 slope: 38.0+/-8.3 vs. 32.8+/-6.3, P<0.001), lower peak exercise tidal volume (1.49+/-0.36 L vs. 1.61+/-0.46 L, P=0.015) and higher peak respiratory rate (34+/-7/min vs. 31+/-6/min, P=0.002). In 33 patients, EOV disappeared during exercise, whereas in 45 patients EOV persisted. Fifty percent of EOV disappearing patients had an increase in the VO2/WL relationship after EOV regression, consistent with a more efficient oxygen delivery to muscles. No cardiopulmonary exercise test parameter was associated with the different behaviour of VO2/WL. CONCLUSION: The presence of EOV negatively influences exercise performance of chronic heart failure patients likely because of an increased cost of breathing. EOV disappearance during exercise is associated with a more efficient oxygen delivery in several cases.