High-dose methylprednisolone and endothelial glycocalyx in paediatric heart surgery.

BACKGROUND: Corticosteroids are used in paediatric heart surgery to attenuate systemic inflammatory response. Glycocalyx regulates vascular permeability, shear stress and cell adhesion on the endothelium. Syndecan-1 serves as a biomarker of glycocalyx degradation. Hydrocortisone decreased endothelial glycocalyx degradation in an experimental model. Our hypothesis was that high-dose methylprednisolone decreases glycocalyx degradation as measured by plasma sydecan-1 concentration in children undergoing cardiac surgery. METHODS: Two double-blinded, randomized, placebo-controlled trials were conducted. In the first trial ('neonatal trial'), 40 neonates undergoing open heart surgery received either 30 mg/kg intravenous methylprednisolone (n = 20) or placebo (n = 20). In the second trial ('VSD trial'), 45 infants and very young children, undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone intravenously after anaesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15) or placebo (n = 15). Plasma syndecan-1 concentrations were measured. Results were expressed both as absolute concentrations and in relative concentrations as multiples of the baseline values of syndecan-1. RESULTS: There were no statistically significant differences between the neonate trial groups for absolute syndecan-1 concentrations. However, operative administration of methylprednisolone to neonates significantly reduced the relative increases of syndecan-1 at weaning from cardiopulmonary bypass (P = 0.008) and at 6 h post-operatively (P = 0.018). There were no statistically significant differences in absolute or relative increases of syndecan-1 between the VSD trial study groups. CONCLUSION: High-dose methylprednisolone reduces shedding of glycocalyx in neonates after complex cardiac surgery but not in older infants after repair of VSD/AVSD with shorter ischaemia times.

The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

Echocardiographic prediction of patent ductus arteriosus in need of therapeutic intervention.

AIM: To evaluate the efficacy of various echocardiographic markers in predicting a patent ductus arteriosus (PDA) in need of treatment. METHODS: Forty-five preterm infants with a mean (SD) gestational age of 27.7 (1.9) weeks underwent echocardiography at a postnatal age of 24 ± 6 and 72 ± 6 h. Four echocardiographic markers were studied: ductus diameter, ductal flow Doppler curves, the left atrial to aortic root (LA/Ao) ratio and Doppler pixels representing ductal shunting. RESULTS: Twenty-eight infants had a PDA with a detectable left-to-right shunt. Of these, 12 (43%) were treated for a shunt through the PDA. Ductal diameter was the most accurate echocardiographic marker when it came to predicting a significant shunt, with a sensitivity of 89%, a specificity of 70%, a positive likelihood ratio of 2.97 and a negative likelihood ratio of 0.16 at the age of 72 h. The efficacy of the method at 72 h of age was 84%. The corresponding efficacy of the pulsatile Doppler curve was 72%, percentage of green colour pixels 63% and the LA/Ao ratio 53%. CONCLUSION: Ductus diameter appears to be the most important variable in determining the need for therapeutic intervention for PDA in preterm infants.

Hepatic neutrophil activation during reperfusion may not contribute to initial graft function after short cold ischemia in human liver transplantation.

BACKGROUND: Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear. METHODS: In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated. RESULTS: Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7-1.0]; 1.4 [0.9-1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2-0.5]; 1.7 [1.3-3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation. CONCLUSIONS: Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.

Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation.

BACKGROUND: Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. METHODS: In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Δ) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). RESULTS: Positive transrenal gradients of tPA antigen occurred at 1 minute [Δ = 14 (3-46) ng/mL, P < .01] and 5 minutes [Δ = 5 (-3 to 27) ng/mL, P < .01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Δ = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P < .001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P = .006). CONCLUSIONS: The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation.

Respiratory infection recurrence and passive smoking in early atherosclerosis in children and adolescents with type 1 diabetes.

BACKGROUND: Optimal glucose control in juvenile type 1 diabetes mellitus is necessary but not sufficient to reduce the burden of cardiovascular events in later life. This emphasizes the importance of searching for other possible risk factors associated with diabetes. We investigated whether recurrent episodes of acute respiratory infections and exposure to tobacco smoke could influence vascular phenotypes for early atherosclerosis in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: Common carotid artery elasticity and intima-media thickness along with circulating markers of lipid, inflammatory and glycaemic profiles were investigated in up to 98 children and adolescents with type 1 diabetes. The number of clinically manifest acute respiratory tract infections (RTI) during the past year, and the degree of exposure to environmental tobacco smoke (ETS), were assessed by separate questionnaires. RESULTS: Carotid artery compliance (CAC) was decreased in patients with high (>or= 4/year; n = 22) recurrence of RTI compared to the remaining patients (n = 40; P < 0.05). In a multivariate analysis, the number of RTI during the past year and HbA(1C) were independently associated with decreased CAC (P < 0.05 for both). The inverse relationship between RTI recurrence and CAC was strengthened by frequent exposure to ETS. CONCLUSIONS: High recurrence of respiratory infections in young type 1 diabetics is associated with increased stiffening of the carotid artery particularly in those often exposed to tobacco smoke.

Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice.

BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05 and P:<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.

Elucidation of the natural history of ventricular septal defects by serial Doppler color flow mapping studies.

Two-dimensional echocardiography has provided information to aid in the diagnosis and management of infants with ventricular septal defect, but its inability to resolve very small ventricular septal defects and problems with defining ventricular septal defect orifice size (because of overlying muscle or tricuspid tissue) have made it unsuitable as a standard for defining the natural history of ventricular septal defect. In this study, 114 serial two-dimensional Doppler color flow mapping studies were performed to define ventricular septal defect anatomy, location and color flow diameter as an indicator of shunt size in 66 patients (over a 40 month period). Twenty-five patients first studied at 6 months of age (mean age at most recent study 15.9 months) had congestive heart failure and 41 (mean age 45 months) did not. In the congestive heart failure group, there were 24 perimembranous and 1 muscular ventricular septal defect and aneurysm formation was present in 17. Mean (+/- SD) color flow diameter was 8.2 +/- 1.9 mm and color flow diameter/aortic root diameter ratio was 0.63. In the 30 patients who underwent cardiac catheterization, color flow diameter bore a close relation to angiographic diameter (r = 0.96) and pulmonary/systemic flow ratio (Qp/Qs) (r = 0.88). In the patients with congestive heart failure, 4 of the 25 ventricular septal defects, all with aneurysm present or positioned adjacent to the tricuspid valve, became smaller but none closed. Of the 41 patients without congestive heart failure, 21 had a perimembranous defect (15 with aneurysm), 18 had a muscular ventricular septal defect and 2 had a supracristal ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Matrix Metalloproteinase-9 and Graft Preservation Injury in Clinical Renal Transplantation.

BACKGROUND: Deleterious effects of matrix metalloproteinase-9 (MMP-9) have been established in experimental renal ischemia-reperfusion models but not in clinical renal transplantation thus far. METHODS: We studied MMP-9 and its physiological inhibitor tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in 45 consecutive patients of a larger trial in renal transplantation: perioperative anti-thymocyte globulin (group A, n = 15), perioperative basiliximab (group B, n = 16), and conventional triple therapy (group C, n = 14). In addition to systemic blood samples, local blood samples were obtained simultaneously at 1 and 5 minutes after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because anti-thymocyte globulin activates inflammation, group A was analyzed separately. Groups B and C were pooled (group BC). RESULTS: Anti-thymocyte globulin infusion caused a robust rise of MMP-9 in the systemic circulation in group A. No significant transrenal difference of MMP-9 or TIMP-1 occurred in either group during graft reperfusion. In group BC, strong transrenal release of MMP-9 at 1 minute after reperfusion correlated with cold ischemia time (R = 0.66, P = .0001) and was associated with delayed graft function (P = .052). CONCLUSIONS: Renal production of MMP-9 on graft reperfusion is associated with cold ischemia time and emergence of delayed graft function. MMP inhibition may offer a means to reduce reperfusion injury in renal transplantation.

Serum fatty acids in 8-year-old Finnish boys: correlations with qualitative dietary data and other serum lipids.

To survey risk factors in coronary heart disease in Finnish children, fasting serum specimens from 244 healthy 8-yr-old boys were analyzed for the fatty acid composition of cholesterol esters (CE), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL). A qualitative dietary survey was made by asking parents to answer a questionnaire including, among others, a question on the kind of fat usually used on bread by the child. The mean percentages of linoleate (18:2) in serum cholesterol esters, triglycerides, free fatty acids, and phospholipids were 53.1, 13.5, 11.5, and 22.7%, respectively, which represent an international average. The quality of dietary fat had a clear influence on serum fatty acids, eg, the content of 18:2 in CE was 56.8 +/- 3.6% in boys using soft vegetable margarine and 50.5 +/- 3.6% in those using butter. The former had also a marginally lower serum total cholesterol (4.87 +/- 0.86 mmol/l) than the latter (5.08 +/- 0.80 mmol/l). Serum total cholesterol showed significant negative correlations with the percentage of 18:2 in all four lipid fractions, the highest r values being with PL-18:2 (-0.41) and CE-18:2 (-0.24). Accordingly, serum cholesterol was lower in the highest CE-18:2 quartile (4.67 +/- 0.76 mmol/l) compared with the lowest (5.30 +/- 0.70 mmol/l; p less than 0.001). The results indicate that when serum fatty acids are used as indicators of the quality of dietary fat, a negative association between polyunsaturated fat and serum cholesterol may be demonstrable even within a free-living population.

Myocardial function in children and adolescents after therapy with anthracyclines and chest irradiation.

Cardiotoxicity is a potential adverse effect of anthracycline (A) therapy. Radiotherapy (XRT) may also cause a variety of cardiac complications. The purpose of the present study was to evaluate these cardiac side-effects in children and adolescents treated for cancer. We assessed the cardiac status of 91 patients, divided into three groups: Group A (n = 53) had anthracyclines at a mean cumulative dose of 410 mg/m2, group A+XRT (n = 26) had both chest irradiation (XRT) and A (mean 360 mg/m2), and group XRT (n = 12) had XRT alone. The patients differed from the controls in both systolic and diastolic indices of myocardial function. In echocardiography, the left ventricular (LV) contractility was abnormal in 32% in group A, in 50% in group A+XRT, and in 8% in group XRT. In radionuclide cineangiography, the LV ejection fraction was subnormal in 19% in group A, in 24% in group A+XRT, and in 1 patient in group XRT. A higher cumulative dose of A predicted decreased contractility. Treatment with A and/or XRT often leads to cardiotoxicity. Although in most cases this cardiotoxicity seems to be mild and subclinical, the long-term clinical sequelae merit further evaluation.

Infection-associated intimal thickening in the coronary arteries of children.

OBJECTIVES: based on autopsy material from children this study investigated the possible relationship of clinically evident infection prior to death with intimal thickening of the coronary arteries. BACKGROUND: viral infections are suggested to be associated with intimal thickening in the coronary arteries both in animals and man. METHODS: the coronary arteries were examined in 175 autopsied children 0-15 years of age (median 7 days). Semi-serial cross sections of the coronary arteries were screened for maximal intimal thickening at 0.2 mm intervals. The length of the internal elastic lamina, the areas of arterial media and intima were measured from cross-sections. Irregular linings of the arteries were mathematically transformed to circles. The percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was calculated. RESULTS: intimal thickening increased with age but was also associated with the presence of infectious disease at death. Already in the newborn children, who died shortly after the birth, the percentage of intimal and musculoelastic layer area to luminal area encircled by arterial media was big, maximally 55%. In the left coronary artery the mean percentages were 32 and 21% in the groups with viral and bacterial infections, respectively as compared to 16% in the group with no evidence of infection. CONCLUSION: infections in general and viral infections in particular, seem to be associated with intimal thickening, which may predispose coronary arteries to atherosclerosis. Atherogenesis might have a rapid dynamic component.

Endothelial cell damage in piglet coronary artery after intravenous administration of E. coli endotoxin. A scanning and transmission electron-microscopic study.

E. Coli endotoxin was administered to 6 piglets from a litter of 10. Three days after the endotoxin stimulus 3 piglets showed definitive morphological evidence of endothelial damage to their left coronary artery. The proximal parts of the coronary artery were severely damaged. In scanning electron microscopy, the changes varied from disappearance of the microvilli to complete exfoliation of the endothelial cells. In cases of severe endothelial cell damage transmission electron microscopy revealed severe changes or even signs of cell death in the inner medial smooth muscle cells. Only of the piglets died prematurely. We are sufficiently encouraged to continue testing the theory that repeated endothelial cell damage initiates stenosing lesions in the coronary arteries.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part 1. Scanning and transmission electron microscopic study.

Endothelial cell damage is considered to be the primary event in atherogenesis. In this study we compared the effects of mild hypercholesterolemia and repeated E. coli endotoxin infusions on the endothelial cells of the coronary arteries of the pig. We divided 24 pigs into 4 groups: I: controls on normal diet; II: normal diet and endotoxin treatment; III: fat-supplemented diet; IV: fat-supplemented diet and endotoxin treatment. The animals on a fat-supplemented diet showed the most frequent and most severe endothelial cell damage. The damage was less when this diet was combined with endotoxin treatment. Endotoxin reduced the serum total cholesterol level (P less than 0.01). The cholesterol level correlated very significantly (P less than 0.001) with endothelial damage of the coronary arteries. Mild hypercholesterolemia (s-cholesterol 5.68 mmol/l, controls 2.28 mmol/l) was thus associated with toxic effects in the endothelial cells. The E. coli endotoxin infusions did not have any cumulative effect on the lesions.

Plasma cholesteryl ester fatty acids in 3- and 12-year-old Finnish children.

Risk factors associated with coronary heart disease were surveyed in a multicentre study carried out in 1979 among children living in different parts of Finland. The survey included analyses of plasma lipids and cholesteryl ester (CE) fatty acids as well as a dietary interview by a 48-hour recall method. The present report gives the plasma fatty acid compositions obtained from 181 3-year-old and 226 12-year-old children and their relations to dietary factors and other plasma lipids. The mean percentages (+/- SD) of CE linoleate in the 3- and 12-year-old children were 49.2 +/- 5.2 and 5.10 +/- 51.0%, respectively. Differences in CE fatty acid composition between the various regions of Finland were relatively small, but there was a trend to higher proportions of polyunsaturated fatty acids in western and urban compared with eastern and rural communities. Among different dietary constituents the daily intake of margarine + oils or butter had the greatest effect on plasma CE fatty acid composition. There was a highly significant positive correlation between the dietary P/S ratio and the percentage of CE linoleate in plasma.

Transhepatic neutrophil and monocyte activation during clinical liver transplantation.

BACKGROUND: During experimental liver transplantation, neutrophil sequestration results in increased oxygen free radical production and correlates inversely with graft viability. Neutrophil activation in clinical liver transplantation is poorly understood. METHODS: We assessed leukocyte sequestration and transhepatic differences of neutrophil and monocyte CD11b expression, neutrophil free radical production, and plasma concentrations of interleukin 6 and interleukin 8 in nine patients during liver transplantation. RESULTS: Significant hepatic neutrophil sequestration occurred during initial graft rewarming with portal blood, after inferior vena cava declamping, and after hepatic artery declamping (all P<0.05). A positive transhepatic difference (i.e., outcoming - ingoing) in CD11b expression of neutrophils was observed after portal vein declamping (51+/-32 relative fluorescence unit [RFU]) and in CD11b expression of monocytes during initial graft rewarming (67+/-86 RFU, both P<0.05). A transcoronary increase in both unstimulated (74+/-80 RFU) and N-formyl-methionyl-leucylphenylalanine-stimulated (112+/-168 RFU) neutrophil free radical production took place after hepatic artery declamping (both P<0.05). A negative transcoronary difference of interleukin 6 occurred during initial graft rewarming (-192+/-176 pg/ml) and a positive difference of interleukin 8 occurred after hepatic artery declamping (17+/-23 pg/ml, both P<0.05). CONCLUSIONS: Hepatic sequestration and transhepatic activation of neutrophils, and hepatic production of interleukin 8 occur during clinical liver transplantation. A splanchnic influx of interleukin 6 occurs to the graft, possibly modulating neutrophil-mediated graft reperfusion injury.

Cardiopulmonary evaluation of exercise tolerance after chest irradiation and anticancer chemotherapy in children and adolescents.

OBJECTIVE: The aim of the study was to evaluate the cardiopulmonary exercise tolerance in children and adolescents after chest irradiation and anticancer chemotherapy. METHODS: We studied 30 subjectively asymptomatic patients aged 8 to 25 years treated for pediatric malignancies with chest irradiation (XRT) +/- chemotherapy. The median interval since XRT was 7 (range, 2 to 13) years. The median XRT dose for mediastinum and/or lungs was 2550 (range, 1000 to 5100) cGy. The median cumulative dose of anthracyclines was 250 (range, 0 to 480) mg/m2. Cardiac function and exercise tolerance were evaluated by electrocardiography, echocardiography, radionuclide cineangiography, and exercise test with gas exchange analysis. RESULTS: The patients differed from normal controls in systolic indices of myocardial function. In echocardiography, the left ventricular contractility was abnormal in 14/30 patients. In radionuclide cineangiography, the left ventricular ejection fraction was subnormal in 6/30 patients, and in 9/30 patients the rise in ejection fraction during exercise was inadequate (< 5%). In exercise testing, the mean (+/- SD) maximum workload attained was 2.7 (+/- 0.7) watts/kg, and the mean (+/- SD) maximum oxygen consumption was 35.4 (+/- 9.7) mL/min/kg. Both variables were < 80% of predicted values in 11 patients. CONCLUSIONS: XRT and anticancer chemotherapy very often lead to late cardiopulmonary toxicity and impaired exercise tolerance. Although in most cases this toxicity seemed to be mild and subclinical, the long-term clinical sequels merit further evaluation.

Radiation-related chronic heart disease.

Three cases of radiation-related chronic heart disease are reported. All three patients had been treated for Hodgkin's disease with a mantle technique six to ten years earlier. Ten years after radiation treatment, a 34-year-old woman had dyspnea during exercise. Her heart was enlarged, and an ECG showed a RBBB. An echocardiogram showed pericardial effusion. Right-sided catheterization revealed an infundibular stenosis. A 31-year-old man had chest pain nine years after radiation. An ECG showed complete RBBB and an exercise stress test signs of ischemia; a coronary angiogram showed three proximal stenoses; and an echocardiogram revealed pericardial effusion. A 12-year-old boy had angina pectoris six years after radiation; one year later, he suffered an acute posterior infarction. Two weeks later he died suddenly. An autopsy showed a severe fibrotic and calcified narrowing of the proximal part of the left main coronary artery. Regardless of the patient's age, radiation-related cardiac complications must be kept in mind. Echocardiograms and, in cases of chest pain, exercise stress tests should be a part of routine postradiation follow-up.