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Background/Objectives: Patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) often receive medical nutrition therapy (MNT) during intensive remission-induction treatment. Since little is known about changes in nutritional status, specifically body composition, in this patient population, these changes and their associations with physical and clinical outcomes were assessed. Subjects/Methods: In this multicenter prospective observational study, newly diagnosed AML/MDS patients who received intensive remission-induction chemotherapy, routine dietary counseling by a dietician and MNT immediately upon inadequate nutritional intake, were included. At treatment initiation and discharge, nutritional status, including Patient-Generated Subjective Global Assessment (PG-SGA)-scores and body composition, physical outcomes and fatigue were assessed. Associations of nutritional status/body composition with physical outcomes, fatigue, fever duration, number of complications, time to neutrophil engraftment and hospital length of stay (LOS) (collected from medical records) were examined using multiple regression analysis. Results: In >91% of the 126 AML/MDS patients included, nutritional intake was adequate, with 61% receiving MNT. Nevertheless, body weight decreased significantly (p< 0.001) and mainly consisted of a loss of muscle/fat-free mass (FFM) (p< 0.001), while fat mass (FM) remained unchanged (p-value range = 0.71–0.77). Body weight and waist circumference showed significant negative associations with fever duration and/or number of complications. Significant positive associations were found between mid-upper arm muscle circumference (MUAMC) and physical functioning and between PG-SGA-scores and fatigue. Body weight and MUAMC were also negatively associated with LOS. Conclusion: Despite MNT in AML/MDS patients undergoing intensive chemotherapy, muscle/FFM decreased while FM remained unchanged. Maintenance of nutritional status was associated with improved physical and clinical outcomes.

Ca2+sensitizers enhance systolic function, but may impair relaxation in vitro; these effects may differ in stunned and normal myocardium. We therefore studied the effect of EMD 57033 on systolic and diastolic function of normal and stunned porcine myocardium in vivo.Myocardial stunning by 15 min coronary occlusion and 30 min reperfusion abolished systolic shortening (SS) (baseline 13±1%) and decreased end‐systolic elastance (Ees) from 67±7 to 47±5 mmHg mm−1(both P<0.05). Maximum rate of fall of myocardial elastance (dE/dtmin) decreased from −850±100 to −320±30 mmHg mm−1s−1, while the time constant τeof the decay of elastance increased from 58±3 to 68±6 ms (both P<0.05). End‐diastolic elastance (Eed) was unchanged although the zero pressure intercept (L0,ed) had increased.In the stunned region, EMD 57033 (0.2 mg kg−1min−1for 60 min, i.v., n=7) increased SS to 19±2%, Eesto 287±40 mmHg mm−1, dE/dtminto −3630±640 mmHg mm−1s−1and decreased τeto 50±3 ms, while Eedremained unchanged. In the normal region, EMD 57033 increased SS from 14±2 to 18±3%, Eesfrom 59±4 to 263±23 mmHg mm−1, dE/dtminfrom −480±70 to −2280±700 mmHg mm−1s−1and decreased τefrom 91±12 to 61±3 ms (all P<0.05), while Eedremained unchanged. These responses were minimally affected by adrenoceptor blockade (n=7). Vehicle (n=7) had no effect on either region.EMD 57033 increased cardiac output (up to 27±8%) and LVdP/dtmax(86±19%). Mean aortic pressure decreased (19±7%) due to systemic vasodilation that was not amenable to blockade of adrenoceptors or NO synthesis.In conclusion, EMD 57033 restored systolic and diastolic function of stunned myocardium, and produced similar improvements in systolic and diastolic function in normal myocardium.

To study whether cardiac interstitial fluid levels of angiotensin I and II (Aug I and II) can be monitored in vivo, using the microdialysis technique, and to assess the contribution of plasma-derived angiotensins to the interstitial fluid levels of these peptides.

Ischemic preconditioning has not only received wide attention in heart research, but has also been a topic of extensive studies involving other organs. In several of these studies, it has been shown that in spite of differences in the endpoints used to assess protection, the same mediators as in myocardial ischemic preconditioning may be involved. However, several of the putative mediators do not require ischemia to become activated. This has guided us and others to investigate whether the myocardium can also be protected by brief ischemia in other organs and whether other non-pharmacological forms of stress, which do not produce ischemia but are capable of activating these potential mediators, are also cardioprotective.

Objectives: There is currently general agreement that adenosine is not involved in ischemic preconditioning (IP) in rat hearts. We hypothesized that the failure to show a role for adenosine is due to the use of brief preconditioning stimuli, and therefore investigated whether adenosine is involved when longer stimuli are employed and which receptor subtypes are involved. Methods and results: Infarct size (IS) was determined in anesthetized rats after 180 min of reperfusion (REP) following a 60-min coronary artery occlusion (CAO). IS was 69±2% (n=15) of the risk area in control rats and 45±2% (n=19; P<0.05) following IP by a single 15-min CAO. The non-selective adenosine receptor antagonist SPT, which itself had no effect on IS (74±1%), blunted the protection by IP (IS=57±2%, P<0.05) in a dose of 25 mg/kg i.v., and abolished the protection (IS=70±1%) at 225 mg/kg i.v. Following IP by three cycles of 3-min CAO and 3-min REP, IS was 24±6% (P<0.05), which was not affected by SPT in doses of 210 and 225 mg/kg i.v. The A₃ antagonist MRS-1191 (3.3 mg/kg, i.p.), which itself did not affect IS (70±2%), blunted the protection by IP with a 15-min CAO (IS=54±2%, P<0.05). When 25 mg/kg SPT (a dose selective for A₁-receptors, as it did not affect the protection by the A₃ selective agonist IB-MECA, 51±3%) and MRS 1191 were combined the protection by IP was abolished (IS=67±2%). Conclusions: Involvement of adenosine in IP in rats depends critically on the duration of the stimulus. Thus, whereas adenosine was not involved when stimuli of 3-min duration were employed, activation of both A₁ and A₃ receptors contributed when a stimulus of 15 min was used.

Objective: The aim was to investigate whether ischaemic preconditioning can be obtained by a partial coronary artery occlusion without intermittent reperfusion. Methods: In seven anaesthetised open chest pigs, the flow in the proximal left anterior descending coronary artery was reduced to 30% of baseline during 30 min before the vessel was occluded completely for 60 min (60 min total coronary occlusion, TCO). After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures. Infarct sizes were compared to those observed in control animals (n = 12), which were subjected to 60 min TCO and 2 h reperfusion, and to infarct sizes determined in animals preconditioned by 10 min TCO with either 15 min (n = 10) or 60 min (n = 5) of reperfusion before the 60 min TCO and 2 h reperfusion. In the last three groups of animals, area at risk was varied by occluding the coronary artery or its branches at different sites. Results: In the control animals infarct size was linearly related (r = 0.99, p< 0.001) to the area at risk with a positive intercept on the AR axis: IS/LV_mass (100%) = 0.88 AR/LV_mass (100%)–3.6. At comparable areas at risk, the infarct size of the animals preconditioned with a 10 min TCO was less than for the control animals. For the animals preconditioned with 10 min TCO and 15 min reperfusion, the relationship between infarct size and area at risk was again linear (r = 0.88) and also had a positive intercept on the AR axis: IS/LV_mass ( 100%) = 0.68 AR/LV_mass ( 100%)-4.8. All animals with the flow reduction to 30% of baseline immediately preceding the 60 min TCO had infarct sizes smaller (p < 0.05) than predicted from the regression equation for the control animals, but the infarct size limitation could not be simply related to variables such as changes in regional systolic and postsystolic segment length shortening, ATP, or ADP during the partial occlusion period. Conclusions: Myocardium can be preconditioned with a flow reduction to 30% of baseline for 30 min without intermittent reperfusion (two stage Harris model). The positive intercept on the AR axis of the IS-AR relationship warrants caution of the use of IS/AR as an index for infarct size limitation. Cardiovascular Research 1994;28:1146-1151