Lactic acidosis following heart transplantation: a common phenomenon?

BACKGROUND: Lactic acidosis (LAc) is a common form of metabolic acidosis early after heart transplantation (HTX). The mechanism remains unclear. This study analyzed 13 patients who developed severe LAc after HTX. METHODS: From a series of 60 consecutive heart transplant patients, we identified 13 patients with LAc in the first hours following HTX. Nine patients with normal or mildly elevated lactate levels (<5.0 mmol/l) were investigated as controls. RESULTS: Thirteen patients developed a moderate or severe LAc (up to 14.6 mmol/l) after HTX. Serum lactate levels increased immediately following surgery with a peak after 6.3+/-1.4 h, spontaneously returning to normal values within 24 h. In contrast to the control group, a significant correlation was found between the maximal serum lactate level and the maximal dosage of inotropic drugs (r=0.93, P<0.02), administered during the reperfusion phase and continued for 12-24 h postoperatively. No correlation was found between LAc and blood gas analysis during extracorporeal perfusion period. CONCLUSION: LAc can occur after HTX and seems to be related to the inotropic support of the graft. In contrast to other forms, LAc after HTX has an excellent prognosis and resolves rapidly and spontaneously without treatment. The fact that inotropic support during and immediately after cardiac transplantation can enhance preexisting severe peripheral metabolic cellular dysfunction remains hypothetical.     

Blood lactate levels are superior to oxygen-derived variables in predicting outcome in human septic shock

Recent reports have shown that oxygen delivery (Do2) and oxygen uptake (Vo2) could be related to outcome of critically ill patients. In this study, we examined measurements of cardiac output, oxygen-derived variables, and blood lactate levels in 48 patients with documented septic shock. There were 27 survivors and 21 nonsurvivors from the shock episode. For all 174 observations, there was a significant linear relationship between Vo2 and Do2 (Vo2 = 79 + 0.17 x Do2, r = 0.64, p less than 0.001). There were no significant differences in Do2 between survivors and nonsurvivors at the onset of septic shock (mean +/- SD, 540 +/- 219 vs 484 +/- 222 ml/min.m2, NS) or in the final phase of septic shock (506 +/- 163 vs 443 +/- 187 ml/min.m2, NS). Also, no significant differences were found in Vo2 and oxygen extraction between survivors and nonsurvivors. However, survivors had significantly lower blood lactate levels both initially (5.1 +/- 2.7 vs 8.2 +/- 5.4 mmol/L, p less than 0.05) and in the final phase of septic shock (2.6 +/- 1.9 vs 7.7 +/- 5.6 mmol/L, p less than 0.001). Only the survivors had a significant decrease in blood lactate levels during the course of septic shock (p less than 0.001). We conclude that the oxygen-derived variables, Do2 and Vo2, cannot be used as prognostic indicators in human septic shock. In contrast, blood lactate levels are closely related to ultimate survival from septic shock. Furthermore, decreases in blood lactate levels during the course of septic shock could indicate a favorable outcome. Therefore, blood lactate levels can serve as a reliable clinical guide to therapy.     

Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction

PURPOSE: The purpose of our study was to ascertain the safety of rapidly correcting acute symptomatic hyponatremia in psychogenic water drinkers, particularly in regard to any delayed adverse neurologic sequelae. PATIENTS AND METHODS: We reviewed the medical records of all known psychogenic water drinkers (34) in our hospital from 1977 to 1989. Using seizure as a marker of severity, we identified 13 patients having a total of 27 episodes associated with severe hyponatremia. We evaluated the charts of those patients in detail to assess the mode of treatment, rate of correction, and long-term neurologic outcome. None of the patients experienced respiratory arrest before treatment, which was initiated within 2 hours of seizure. RESULTS: For all 27 episodes, the initial serum sodium level (mean +/- SE) was 110.9 +/- 1.2 mmol/L, and the rate of correction (mean +/- SE) was 1.65 +/- 0.2 mmol/L/hour. All but one episode were corrected "rapidly" (initial correction rate of 0.7 or more mmol/L/hour) to 120 to 130 mmol/L within 12 hours. The absolute change in the serum sodium level was 15.1 +/- 1.2 mmol/L in 12 hours, 21.6 +/- 1.4 mmol/L in 24 hours, and 25.9 +/- 1.4 mmol/L in 48 hours. In no instance did therapy induce hypernatremia. All patients recovered immediately after treatment. There was no clinical or radiologic evidence of adverse neurologic sequelae immediately after treatment or after 6 years of follow-up. CONCLUSION: In this series of male psychogenic water drinkers, early "rapid" correction of acute symptomatic hyponatremia by raising the serum sodium level 15 mmol/L in 12 hours while maintaining an absolute change in the serum sodium level of 26 mmol/L within 48 hours produced no long-term neurologic sequelae.     

Altered purine and glycogen metabolism in skeletal muscle during exercise in patients with heart failure

Plasma levels of ammonia and hypoxanthine (HX) can be indices of purine nucleotide degradation. The present study determined if patients with heart failure (HF) have altered exercise plasma ammonia and HX levels relative to the peak work rate performed. Blood lactate, plasma ammonia, and plasma HX levels were measured in 59 patients with HF (New York Heart Association [NYHA] classes I:20, II:21, and III:18) and 21 controls at rest and after a maximal cardiopulmonary exercise test. The peak work rate (normal and NYHA I, II, and III, 163+/-11, 152+/-9, 94+/-5, and 69+/-5 W) and peak oxygen uptake ([VO2] 32.3+/-1.7, 25.1+/-0.9, 18.6+/-0.5, and 14.1+/-0.6 mL/min/kg) decreased as the NYHA functional class increased. The increment from rest to peak exercise (delta) for lactate ([(delta)lactate] 6.1+/-0.3, 4.8+/-0.4, 4.6+/-0.3, and 2.9+/-0.3 mmol/L), (delta)ammonia (132+/-14, 119+/-20, 94+/-13, and 32+/-6 microg/dL), and (delta)HX (33.5+/-3.4, 24.9+/-4.7, 20.6+/-3.0, and 9.9+/-1.2 micromol/L) was progressively smaller as HF worsened. The ratio for (delta)lactate to peak work rate (0.037+/-0.003, 0.032+/-0.004, 0.049+/-0.003, and 0.042+/-0.005) was higher in classes II to III HF, while the ratio for (delta)ammonia to peak work rate (0.81+/-0.14, 0.78+/-0.16, 0.99+/-0.11, and 0.47+/-0.11) was significantly lower in class III HF. In summary, patients with HF exhibited a smaller ammonia response with a higher lactate response to exercise when normalized with the peak work rate. These results suggest there may be an altered purine and glycogen metabolism during exercise in skeletal muscle in patients with HF.     

Mechanisms by which systemic salbutamol increases ventilation

BACKGROUND AND OBJECTIVE: Salbutamol (SAL) has systemic effects that may adversely influence ventilation in asthmatic patients. The authors sought to determine the magnitude of this effect and mechanisms by which i.v. SAL affects ventilation. METHODS: A prospective study of nine healthy subjects (eight men, one woman; age 23 +/- 1.4 years (SD)) was undertaken. Each subject received i.v. SAL at 5, 10 and 20 microg/min each for 30 min at each dose and was observed for 1 h post infusion. Minute ventilation ((VE)), oxygen consumption (VO(2)), CO(2) production (VCO(2)), occlusion pressure (P(0.1)), heart rate, blood pressure, respiratory rate, glucose, arterial blood gases, lactate and potassium (K(+)) were recorded at baseline and at 30-min intervals. The effect of 100% oxygen on (VE) and P(0.1) during SAL infusion at 20 microg/min was observed. Results are expressed as mean +/- SEM. RESULTS: V(E) was significantly increased at 20 microg/min SAL (37.8 +/- 12.1%, P = 0.01), as were VO(2) (22.5 +/- 5.1%, P < 0.01) and VCO(2) (40.9 +/- 10.6%, P < 0.01). Ventilation was in excess of metabolic needs as demonstrated by a rise in the respiratory exchange ratio (0.87 +/- 0.03 to 0.99 +/- 0.04, P < 0.05). Serum lactate rose by 124 +/- 30.4% from baseline to 20 microg/min (1.1 +/- 0.1 to 2.3 +/- 0.25 mmol/L, P < 0.01) and base excess decreased (0.89 +/- 0.56 to vs. -1.75 +/- 0.52 mmol/L, P < 0.01) consistent with a lactic acidosis contributing to the excess ventilation. There was no significant differences in (VE) or P(0.1) with F(I)O(2) = 1.0, suggesting peripheral chemoreceptor stimulation was not responsible for the rise in (VE). At 20 microg/min SAL, K(+) fell significantly from baseline (3.8 +/- 0.06 to 2.8 +/- 0.09 mmol/L, P < 0.001). CONCLUSION: Systemic SAL imposes ventilatory demands by increasing metabolic rate and serum lactate. This may adversely affect patients with severe asthma with limited ventilatory reserve.     

Use of maximal bicycle exercise testing with respiratory gas analysis to assess exercise performance in patients with congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy

Analysis of respiratory gases during maximal treadmill exercise testing has been used in patients with congestive heart failure (CHF) to detect the lactate threshold, presumed to reflect the onset of skeletal muscle underperfusion, and maximal oxygen consumption (VO2), the point at which VO2 plateaus with increasing work due to exhaustion of peripheral oxygen delivery capacity. To determine if this approach is also useful during maximal bicycle exercise testing, ventilatory, hemodynamic and systemic lactate responses to bicycle exercise were measured in 48 patients with CHF. Ventilatory responses also were assessed in 12 normal subjects. Exercise increased VO2 to 24.8 +/- 3.9 ml/min/kg in normal subjects and 13.9 +/- 3.7 ml/min/kg in patients with CHF (p less than 0.001). In all but 1 patient the VO2 increment over the last 3 minutes of exercise was comparable to that in normal subjects exercising over identical work times, suggesting that maximal VO2 was not achieved. Moreover, in patients who exercised for less than 6 minutes, a ventilatory lactate threshold could not be identified. In the 33 patients who exercised longer, a ventilatory lactate threshold was identified in 31 and correlated well (r = 0.81) with blood lactate threshold, as defined by the VO2 at which lactate increased 5 mg/dl over rest levels. However, the 95% confidence limit for predicting blood lactate threshold from ventilatory data was +/- 200 ml/min, a large range relative to the measured ventilatory threshold (570 +/- 132 ml/min). These data suggest that in patients with CHF, respiratory gas analysis during maximal bicycle exercise cannot be used to measure maximal VO2 and provides only a general index of blood lactate behavior.     

Fluid loading increases oxygen consumption in septic patients with lactic acidosis

We prospectively evaluated 20 patients with systemic sepsis and signs of circulatory failure to determine if fluid loading was associated with increases in systemic oxygen delivery (DO2) and consumption (VO2). Fluid loading led to an increase in DO2 in 14 patients (70%). Patients who demonstrated increased DO2 with a corresponding increase in VO2 (Group A, n = 8) had significantly higher (p less than 0.05) initial blood lactate levels (4.9 +/- 2.9 mmol/L, mean +/- SD) than did patients without an increase in VO2 (Group B, n = 6, 1.9 +/- 1.0 mmol/L). A decrease in DO2 that was attributed to hemodilution was noted in the remaining 6 patients (Group C). Group C exhibited elevated lactate levels (5.1 +/- 2.4 mmol/L) and no significant changes in VO2. We conclude that lactic acidosis, a marker of anaerobic metabolism, predicts increases in VO2 in septic patients who respond to fluid loading with an increase in DO2.     

Study of the correlation between blood lipid levels and the severity of coronary atherosclerosis in a Chinese population sample

OBJECTIVE: To investigate the relationship between blood lipid levels with severity of coronary artery atherosclerosis in a Chinese population sample. METHODS AND RESULTS: According to coronary angiography results, 363 patients (287 men and 76 women) with coronary artery atherosclerosis were divided into four groups: the single-vessel group (I, n = 125), the double-vessel group (II, n = 113), the triple-vessel group (III, n = 107) and the multi-vessel group (IV, n = 18).The severity of coronary artery atherosclerosis was quantified with a modified Gensini score on the basis of angiographic imaging. Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL-C) were measured before angiography in all groups. Levels of serum TC, LDL-C and non-HDL-C of the II, III and IV group were significantly higher than those of the I group (4.78 +/- 0.82 mmol/L and 4.87 +/- 1.50 mmol/L and 4.73 +/- 0.99 mmol/L vs. 4.38 +/- 0.93 mmol/L, 2.91 +/- 0.68 mmol/L and 2.74 +/- 1.23 mmol/L and 2.64 +/- 0.84 mmol/L vs. 2.30 +/- 0.77 mmol/L, 3.58 +/- 0.75 mmol/L and 3.59 +/- 1.41 mmol/L and 3.43 +/- 0.94 mmol/L vs. 3.17 +/- 0.91 mmol/L; p < 0.05); the mean levels of TC, LDL-C and non-HDL-C associated positively with the Gensini score. CONCLUSION: Serum lipid levels correlate positively with the severity of coronary artery atherosclerosis in a Chinese population sample. Patients with higher levels of serum TC, LDL-C and non-HDL-C have more severe coronary atherosclerosis, compared with those with low levels of serum TC, LDL-C and non-HDL-C.     

Steroids, hypoxemia, and oxygen transport.

This study investigated the effects of administration of methylprednisolone on oxygen transport in ten stable hypoxemic (mean arterial oxygen pressure, 54 +/- 3 mm Hg) patients with chronic obstructive pulmonary disease (COPD). At 24 hours (after four injections of a bolus of 30 mg of methylprednisolone sodium succinate per kilogram of body weight, given intravenously every six hours), significant differences (P less than 0.05) were an increased cardiac index (3.0 +/- 0.2 to 4.1 +/- 0.2 L/min/sq m), a decreased peripheral vascular resistance (1,186 +/- 100 to 849 +/- 60 dynes/sec/cm-5), an increased flow of oxygen to tissue (0.90 +/- 0.07 to 1.16 +/- 0.09 L/min), a decreased arteriovenous oxygen content difference (49 +/- 3 to 43 +/- 2 ml/L), a decreased concentration of hydrogen ions in the arterial blood (38 +/- 1 to 35 +/- 1 nmol/L) and arterial carbon dioxide tension (39 +/- 2 to 32 +/- 1 mm Hg), and increased levels of lactate (1.1 +/- 0.2 to 3.7 +/- 1.0 mmol/L) and pyruvate (0.14 +/- 0.04 to 0.37 +/- 0.08 mmol/L). Fractional oxygen utilization, oxygen consumption, the partial pressure of oxygen at which hemoglobin was 50 percent saturated, and the level of 2,3-diphosphoglyceric acid remained unchanged. In vitro studies showed that these patients' red blood cells responded with a significant (more than 35 percent) increase in the level of 2.3-diphosphoglyceric acid when incubated for ten hours with concentrations of methylprednisolone that were much higher (1.0 mg/ml) than those attained in vivo (12.5 microgram/ml). These studies demonstrate that repeated infusions of high doses of steroids in a bolus in stable hypoxemic patients with COPD produce significant physiologic changes but no apparent net gain in the oxygenation of tissues.     

Chronic heart failure. The relationship between increased activity of skeletal muscle ergoreceptors and reduced exercise tolerance

BACKGROUND: In chronic heart failure (CHF), skeletal muscle abnormalities may lead to the overactivation of ergoreceptors which in turn may cause sympathetic overactivation and increased ventilatory response to exercise. AIM: To assess ergoreceptor reflex response to exercise and to evaluate whether ergoreceptor overactivity is related to the progression of CHF. METHODS: In 69 patients with CHF (66 males, mean age 62.7+/-11.6 years, NYHA class I/II/III/IV - 11/32/24/2 patients, respectively) and 24 controls without CHF (22 males, mean age 59+/-4.6 years) the ergoreflex contribution to the ventilatory and haemodynamic responses to exercise was evaluated. Moreover, in 13 patients with CHF, reproducibility of the measurements was assessed by repeating the test 1 to 7 days later. RESULTS: Enhanced ergoreflex effects on ventilation (1.9+/-1.6 vs 0.14+/-0.7 l/min, p<0.05) and systolic blood pressure (19.2+/-14.9 vs 6.1+/-5.9 mmHg, p<0.05) were found in patients with CHF compared with control subjects. Ergoreceptor overactivity was associated with a worse symptomatic state (NYHA class I vs II vs III, IV: 0.9 vs 1.5 vs 2.9 l/min, p<0.05) and lower exercise tolerance (peak V0(2): r=-0.51, p<0.0001; VE/VC0(2): r=0.50, p<0.0001). The mean values of the ergoreceptor reflex did not differ significantly between the two tests (t=1.5, p=0.14; variability coefficient = 21.5%). CONCLUSIONS: In CHF, overactivation of the ergoreflex is associated with the progression of the syndrome and may be responsible for reduced exercise tolerance. Reproducibility of ergoreflex measurements is satisfactory.     

Airway pressure release ventilation in severe acute respiratory failure

Airway pressure release ventilation (APRV), a new ventilatory support technique, was compared with conventional intermittent positive-pressure ventilation plus PEEP (CPPV) in 18 patients with severe acute respiratory failure. Patients were initially stabilized on CPPV and then switched to APRV. The APRV provided effective ventilatory support in 17 of 18 patients; APRV achieved similar levels of alveolar ventilation as CPPV (for APRV, mean PaCO2 = 45.0 +/- 6.2 mm Hg; vs for CPPV, mean PaCO2 = 43.3 +/- 5.7 mm Hg), with significantly lower mean maximum airway pressures (38.9 +/- 10.1 cm H2O vs 64.6 +/- 15.4 cm H2O; p = 0.0001) and mean VT (0.79 +/- 0.11 L vs 1.05 +/- 0.15 L; p = 0.0002). No significant differences in mean airway pressure, end-expiratory pressure, FIO2, ventilator rate, arterial blood gas levels, and hemodynamic function were noted between APRV and CPPV.     

Cytokine response to pulmonary thromboendarterectomy

BACKGROUND: Pulmonary thromboendarterectomy (PTE) is an effective but challenging treatment for chronic thromboembolic pulmonary hypertension (CTEPH). PTE is associated with marked hemodynamic instability in the perioperative course, suggesting the involvement of circulating mediators. The aim of this study was to characterize the expression of proinflammatory and anti-inflammatory cytokines in patients undergoing PTE. METHODS: Fourteen patients with CTEPH (mean [+/- SD] pulmonary vascular resistance, 1,056 +/- 399 dyne.s.cm(-5)) underwent PTE using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Peripheral arterial blood samples were drawn prior to patients undergoing sternotomy, during CPB, before and after DHCA, and 0, 8, 16, 24, and 48 h after surgery. An enzyme-linked-immunosorbent assay was used to analyze the plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Seven patients undergoing aortic arch replacement (ARCH) in DHCA served as a control group. RESULTS: Prior to and during PTE, the CTEPH patients exhibited elevated TNF-alpha levels, which decreased within the first 24 postoperative hours (p = 0.02). There was no TNF-alpha release among patients in the ARCH group. IL-6 levels were similar in both groups throughout the perioperative course. A profound anti-inflammatory response was observed in the PTE group, which was reflected by elevated IL-10 levels prior to surgery and a marked peak level immediately after surgery. A positive correlation was found between maximum vasopressor support and peak levels of IL-6 (r = 0.82) in the PTE patients. CONCLUSION: Heart failure due to CTEPH appears to generate a pronounced inflammatory response with the release of proinflammatory and anti-inflammatory cytokines. PTE results in the rapid normalization of preoperatively elevated TNF-alpha levels. IL-6-mediated systemic inflammatory cascades may be involved in the regulation of peripheral vascular tone after PTE.     

Assessment of basal insulin requirement using fasting tests in insulin-treated patients with type 2 diabetes mellitus.

AIMS: Characterizing the time course of the rise of blood glucose concentrations in the fasting state during the day and night in patients with type 2 diabetes. METHODS: 40 consecutive insulin-treated patients with type 2 diabetes underwent fasting tests on two different days with either no breakfast and lunch (fasting time of 20 hours) or no dinner (fasting time of 21 hours). Glucose-lowering medication was stopped prior to the test according to the half-life of the medication prescribed. At the start of the fasting tests, blood glucose concentrations were lowered to below 7 mmol/L using an insulin infusion. RESULTS: 26 men and 14 women were included in the study. Mean (+/-SD) age was 61+/-10 years, BMI 31+/-7 kg/m (2), and HbA1c 7.5+/-1%. Diabetes duration was 14+/-8 years and duration of insulin therapy had been prescribed for a mean of 6+/-6 years. During the daytime fast, plasma glucose concentrations rose by a mean of 0.8+/-1.6 mmol/L. During the nighttime fast, plasma glucose concentrations increased particularly after midnight, by 4.3+/-2.1 mmol/L, i.e. significantly more than during the daytime fast. CONCLUSIONS: Fasting blood glucose concentrations in the majority of insulin-treated patients with type 2 diabetes increase markedly after midnight. No similar increase is observed during the day. Thus, for most patients with type 2 diabetes, an intermediate- or long-acting insulin injected at bedtime with a peak action six to eight hours after injection should be appropriate.     

Altered purine nucleotide degradation during exercise in patients with essential hypertension

Purine degradation occurs during strenuous muscle exercise and plasma levels of hypoxanthine (HX), purine degradation intermediate, increase. Purine nucleotide degradation has not been investigated in patients with essential hypertension (HTN). The present study determined whether purine nucleotide degradation is altered in patients with HTN. Cardiopulmonary exercise test was performed with serial measurements in blood lactate and plasma HX in 24 patients (14 men and 10 women) with essential HTN (World Health Organization [WHO] class I to II; mean age, 57.7 +/- 2.1 years) and 24 age-, sex-matched normal subjects. Exercise was terminated either by severe fatigue or excess blood pressure increase. Peak work rate (WR) (normal v HTN, 151 +/- 10 v 135 +/- 8 W, not significant [NS]) was not different, but peak oxygen uptake (peak Vo(2), 26.3 +/- 1.5 v 22.2 +/- 0.9 mL/min/kg, P <.05) and anaerobic threshold were lower in patients with HTN. Resting levels of blood lactate and plasma HX were similar, but the increment from rest to peak exercise (Delta) for lactate (Delta lactate: 4.4 +/- 0.4 v 3.4 +/- 0.4 mmol/L, P <.05) and for HX (Delta HX, 15.9 +/- 2.2 v 9.1 +/- 1.1 micromol/L, P <.05) were significantly smaller in patients with HTN. When normalized by the peak WR, Delta HX/peak WR (0.105 +/- 0.013 v 0.069 +/- 0.007 micromol/L/W, P <.05) was significantly lower in patients with HTN. Patients with HTN exhibited reduced HX response to exercise with impaired exercise capacity. The exercise-induced changes in plasma HX were smaller in patients with HT when normalized with peak WR. These results suggest that the purine nucleotide degradation is reduced in patients with HTN.     

Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance

We have recently demonstrated that exercise training can induce important hemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examines the accompanying changes in submaximal exercise performance and the ventilatory response to exercise in these patients. Before and after 16-24 weeks of exercise training, subjects underwent two symptom-limited bicycle exercise tests, one with an incremental graded workload, and one with a constant workload that represented 79 +/- 11% of the pretraining peak oxygen consumption. Breath-by-breath expired gas analysis was performed continuously during each test, and central hemodynamic, leg blood flow, and blood lactate measurements were obtained during the incremental protocol. The ventilatory anaerobic threshold was determined during the incremental exercise study from coplotted breath-by-breath ventilatory data with standard criteria by observers who were unaware of patient identity or training status. As previously reported, exercise training increased peak oxygen consumption by 23% from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min and reduced blood lactate levels during submaximal exercise. The training-induced decrease in lactate accumulation was accompanied by a decrease in carbon dioxide production, respiratory exchange ratio, and ventilation during submaximal exercise. The ventilatory anaerobic threshold was delayed from 284 +/- 43 to 352 +/- 91 seconds of exercise (p = 0.02), and it occurred at an increased oxygen consumption (10.1 +/- 1.2 vs. 12.1 +/- 2.6 ml/kg/min, p = 0.01). Exercise duration during the constant workload protocol increased from 938 +/- 410 to 1,429 +/- 691 seconds (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal and metabolic responses in brittle diabetic patients during feedback intravenous insulin infusion

Twenty-four hour profiles of blood hormones and intermediary metabolites were obtained in seven 'brittle' diabetic subjects during their usual insulin therapy and during feedback intravenous insulin infusion from an artificial pancreas (GCIIS). The results were compared to those in matched stable diabetics and normal controls. Although routine insulin doses were higher in the brittle group than in the stable group (164 +/- 32 (mean +/- SE) vs. 58 +/- 8 U/day, P less than 0.005) during routine therapy, plasma free insulin levels were equal (35 +/- 12 vs. 31 +/- 6 mU/l). In the brittle group feedback i.v. insulin infusion reduced daily requirements to normal levels (80 +/- 13 U/day, P less than 0.025; stable group 71 +/- 4 U/day, NS). On routine therapy blood glucose levels were not different in the two groups (brittle 10.5 +/- 1.6, stable 10.8 +/- 0.6 mmol/l) and were similarly corrected by the GCIIS (6.9 +/- 0.3 and 6.9 +/- 0.3 mmol/l, respectively). Blood lactate and pyruvate levels were markedly abnormal in the brittle group during routine therapy (lactate: brittle group 1.93 +/- 0.27 mmol/l, stable group 0.91 +/- 0.07 mmol/l, P less than 0.025), and this abnormality was not corrected by the GCIIS (1.75 +/- 0.32 and 0.88 +/- 0.08 mmol/l, P less than 0.005). Abnormalities were also found in profiles of blood alanine and glycerol, and serum cortisol. Blood ketone body levels did not differ between the two groups of patients. The results suggest a defect in insulin delivery from subcutaneous tissue into the plasma. These patients have a characteristic metabolic abnormality, unresponsive to short-term normoglycaemia, either as the result of long-term disturbance of diabetic control, or as a marker for the underlying hormonal or biochemical abnormality.     

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.     

Cholesterol and glucose levels belong to independent predictors of death and hospitalizations in patients with chronic systolic heart failure

PURPOSE: To elucidate relationship of total cholesterol (TC) level to results of follow-up of patients (pts) with systolic chronic heart failure (CHF). METHODS: In a framework of various international and local trials we prospectively followed up 130 patients (pts) with stable NYHA class II-IV HF and ejection fraction (EF) 40% or less. Criterion of inclusion in this analysis was presence of TC value obtained at baseline examination for a given trial. Mean age of pts was 65 +/- 9 years, 78% were men. During follow-up (mean 1.3 +/- 0.8, median 1.4 years) we registered all deaths and hospitalizations for heart failure worsening. RESULTS: During follow up 31 pts died and 38 were hospitalized. Compared to the group of pts without these events, pts who died had higher baseline fasting glucose (7.8 +/- 3.6 vs. 6.7 +/- 2.1 mmol/L; p=0.026) and lower TC (5.09 +/- 1.57 vs. 5.50 +/- 1.31 mmol/L; p=0.052) levels. Compared to event-free group, those who were hospitalized had significantly lower hemoglobin (Hb) (135 +/- 17 vs. 143 +/- 15 g/L; p=0.010). Cox proportionate hazards model included age, sex, EF, NYHA class, BMI, hemoglobin, glucose, creatinine, TC, history of hypertension, smoking, presence of disturbances of cardiac rhythm and conduction, medications. Mortality risk correlated with glucose and TC levels; each 1-mmol/L increase in glucose concentration was associated with 17% increase of mortality risk [hazard ratio (HR) 1.17; 95% confidence interval (CI) 1.05 to 1.31, p=0.005], and each 1-mmol/L decrease in TC - with 26% increase of mortality risk (HR 0.74, 95%CI 0.55 to 1.00, p=0.052). Left bundle branch block (LBBB) was an independent predictor of mortality (HR 2.51, 95%CI 1.02 to 6.18, p=0.045). Heart failure hospitalizations were linked to hemoglobin level and NYHA class. Each 10-g/L decrease in hemoglobin was associated with 31% elevation of risk of hospitalization (HR 0.69, 95%CI 0.51 to 0.92, p=0.011). There was almost 5-fold difference in risk of hospitalization between NYHA class II and IV (HR 4.80, 95%CI 2.64 to 8.73, p < 0.001). Pts with glucose > 7.4 mmol/L, or TC < 4.0 mmol/L, or hemoglobin < 130 g/L (optimal specificity/sensitivity derived from ROC curves) were at higher risk of an event. Kaplan-Meier survival analysis revealed that pts with glucose > 7.4 mmol/L, TC < 4.0 mmol/L, hemoglobin < 130 g/L had significantly reduced survival: p=0.050, p=0.006, p=0.016, respectively. CONCLUSION: In a homogeneous group of pts with chronic heart failure and low EF characterized by usual relationships between established factors of prognosis (NYHA class, hemoglobin, LBBB) and development of events lower TC and higher glucose levels were each associated with worse outcome.     

Factors for successful weaning from a percutaneous cardiopulmonary support system (PCPS) in patients with low cardiac output syndrome after cardiovascular surgery

The objective of this study was to analyze the early predictive factors for successful weaning from a percutaneous cardiopulmonary support system (PCPS) in patients with low cardiac output syndrome after cardiovascular surgery. A total of 938 patients underwent cardiovascular surgery with cardiopulmonary bypass (CPB) from January 1991 to September 2006 at Gunma University Hospital. Of these 938 patients, 13 (1.4%) required PCPS to maintain hemodynamics within 48 hours after surgery. The mean age of the 13 patients was 66 years (range, 45 to 86 years). Nine patients underwent open-heart surgery, 3 repair of a thoracic aortic aneurysm, and 1 a pericardiectomy. The patients were divided into 2 groups; group A (n = 4) who were removed from PCPS and group B (n = 9) who were not removed from PCPS. The conditions during the operation and after PCPS support were compared between the 2 groups. The mean age was higher, and operation time, CPB time, and aortic cross-clamping time were significantly (P < 0.05) longer in patients with PCPS than in those without PCPS. The mean PCPS time in all 13 patients was 190 +/- 122 hours. The mean age was higher, and CPB time and the aortic cross-clamping time were longer in group B than in group A (NS). The mean duration of PCPS support was significantly (P < 0.05) shorter in group A than in group B (117 +/- 42 hours versus 235 +/- 136 hours). PCPS flow in group A could be reduced from 48 hours after PCPS induction. However, PCPC flow in group B could not be reduced, and there were significant (P < 0.05) differences in PCPS flow at 72 and 96 hours after starting PCPS. Significant (P < 0.05) differences in the absolute values of the APACHE II score, serum lactate levels, administered epinephrine dose, and levels of total bilirubin (T-Bil), serum creatinine (sCr), and lactate dehydrogenase (LDH) were found between the 2 groups within 96 hours after PCPS induction. In addition, there were significant (P < 0.05) differences in the rate of change compared with the baseline control value obtained prior to PCPS use in PCPS flow, APACHE II score, and levels of T-Bil, sCr, and LDH within 96 hours after PCPS induction. Significant differences in the rate of change of sCr and LDH were found, especially from the early phase after PCPS use, compared with other parameters. In the patients removed from PCPS, PCPS flow could be reduced within 48 hours after commencement of PCPS. Improvements in the APACHE II score and biochemical variables within 96 hours appear to be reliable prognostic factors for PCPS patients.