Biochemical and immunological markers of insufficiency of blood circulation in children with cardiomyopathies

Complex clinical-laboratory investigation of children with congestive heart failure developed on the basis of dilated cardiomyopathy and hypertrophic cardiomyopathy has been carried out. The development of congestive heart failure in children with cardiomyopathy was accompanied by changes in activity of creatine phosphokinase, MB isoform of creatine phosphokinase, and also blood serum lactate, neopterin, TNF-α, interleukin-2 (IL-2), interleukin-6 (IL-6), and the soluble receptors for IL-2 and IL-6 (sIL-2R, sIL-6R). The energy deficit in patients with congestive heart failure is associated with pronounced impairments of expression of neopterin, TNF-α, IL-2, IL-6 and their receptors. The role of cytokines in formation of dysregulation processes is analyzed at the level of intercellular and organ local interactions. A cascade of multiple biochemical and molecular processes including impairments of membrane integrity and ion transport, apoptosis, proteolysis followed by fibrosis of myocardium finally cause myocardial remodeling, the development, chronization and progression of congestive heart failure in children with cardiomyopathy.     

The use of recombinant erythropoietin in the reduction of blood transfusion rates in craniosynostosis repair in infants and children

The vast majority of infants and children undergoing craniosynostosis correction receive a blood transfusion. The risks of blood transfusion include, but are not limited to, acute hemolytic reactions (approximately 1 of 250,000), human immunodeficiency virus (approximately 1 of 200,000), hepatitis B and C (approximately 1 of 30,000 each), and transfusion-related lung injuries (approximately 1 of 5000). This prospective, single-blinded, randomized study was undertaken to examine the safety and efficacy of preoperative single weekly dosing with erythropoietin (epoetin alfa) in reducing the rate of transfusion in infants and small children undergoing craniosynostosis repair. A total of 29 patients (<8 years) undergoing craniosynostosis repair were randomized into two groups: one received preoperative erythropoietin (600 U/kg) weekly for 3 weeks, and the other served as a control. All caregivers responsible for blood transfusions were blinded, and strict criteria for transfusion were established. A pediatric hematologist monitored both groups, and all patients received supplemental iron (4 mg/kg). Fourteen patients were randomized to receive erythropoietin, and eight of these 14 patients (57 percent) required transfusion (mean age, 17 months; mean weight, 10.1 kg). Of the six patients not requiring transfusion, three were younger than 12 months old (mean, 6 months). Fourteen of 15 patients (93 percent) in the control group (mean age, 13 months; mean weight, 9.3 kg) required a blood transfusion during the study. The only control patient not requiring transfusion was the eldest (5 years old). The difference between the two groups was statistically significant (Fisher's exact test = 0.03). The control group showed no change in hemoglobin levels from baseline to preoperative levels, but the erythropoietin group increased their average hemoglobin levels from 12.1 to 13.1 g/dl. There were no adverse effects noted among children receiving erythropoietin, nor were there any surgical complications. The authors conclude that the preoperative administration of erythropoietin significantly raised hemoglobin levels and reduced the need for a blood transfusion with craniosynostosis correction. More suggestions are made that may further reduce the need for blood transfusions, and a cost-benefit analysis is discussed.     

Blood loss in major liposuction procedures: a comparison study using suction-assisted versus ultrasonically assisted lipoplasty.

The blood loss that accompanies liposuction procedures has always been a concern. Tumescent injection of the targeted area of liposuction with dilute lidocaine and epinephrine solution has minimized intraoperative blood loss. Proponents of a newer ultrasonically assisted lipoplasty technique have claimed many benefits over traditional suction-assisted lipoplasty. However, few quantitative data are available on the intraoperative blood loss and the significance of postoperative anemia using the ultrasonic method. A prospective clinical observational design was used to investigate 38 patients undergoing suction-assisted lipoplasty and 37 patients undergoing ultrasound-assisted lipoplasty in whom the liposuction aspirate was expected to be more than 1000 ml. These patients were investigated with preoperative measurement of hemoglobin, platelet count, prothrombin time, partial thromboplastin time, and postoperative measurement of hemoglobin on the seventh postoperative day. In addition, hemoglobin concentration and whole blood volume were calculated from the infranatant portion of the liposuction aspirate. The mean +/- SD volume of the liposuction aspirate was 2901 +/- 1471 ml for suction-assisted compared with 2741 +/- 1086 ml for ultrasound-assisted lipoplasty. The mean +/- SD of whole blood volume in liposuction aspirate per case was 36 +/- 50.82 ml for suction-assisted lipoplasty and 36 +/- 28.62 ml for ultrasound-assisted lipoplasty. The mean +/- SD of the preoperative hemoglobin concentration was 13.93 +/- 0.99 g/dl for suction-assisted lipoplasty and 14.05 +/- 1.16 g/dl for ultrasound-assisted lipoplasty, whereas the mean +/- SD of the postoperative hemoglobin concentration was 13 +/- 1.42 g/dl for suction-assisted lipoplasty and 13.05 +/- 1.32 g/dl for ultrasound-assisted lipoplasty. The mean decrease in hemoglobin on the seventh postoperative day was 0.93 +/- 0.92 g/dl for suction-assisted lipoplasty and 1 +/- 0.64 g/dl for ultrasound-assisted lipoplasty. The volume of whole blood loss was estimated to be 12.4 ml in each 1000 ml of liposuction aspirate when using suction-assisted lipoplasty versus 13.1 ml when using ultrasound-assisted lipoplasty. All procedures were done under general anesthesia, and patients were discharged home on the same day. No blood transfusion was required. This study shows that blood loss using the ultrasonic technique is slightly higher, though insignificant, than when using suction. However, this study did not demonstrate a difference in the postoperative hemoglobin decrease between the two techniques.     

The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome

Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure. Our joint renal-cardiac heart failure team found that anemia was indeed very common in congestive heart failure and was associated with severe, medication-resistant cardiac failure. Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized. Subsequent investigations by others have confirmed many of our observations. We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure may prove vital in preventing progression of both the heart failure and the associated renal disease.     

Plasma glucose, insulin and free fatty acids in infants with congenital heart disease.

The effect of congestive cardiac failure, hypoxia and hypoglycaemia on glucose tolerance and insulin secretion were studied in selected groups of infants with congenital heart disease. Fasting blood glucose level was significantly decreased in patients with congestive heart failure and in cyanotic infants without congestive heart failure. In the former it seemed to be correlated with the degree of malnutrition, while in cyanotic infants it was independent of the nutritional state. Plasma insulin levels were reduced in infants, with congestive cardiac failure, although their glucose tolerance test and free fatty acid concentrations were normal. It is suggested that the decreased plasma insulin concentration was a consequence of adaptation to reduced requirements. Glucose tolerance and insulin secretion were not affected by hypoxia or hypoglycaemia.     

High Incidence of Tuberculosis in the Absence of Isoniazid and Cotrimoxazole Preventive Therapy in Children Living with HIV in Northern Ethiopia: A Retrospective Follow-Up Study

ObjectiveTo identify the incidence of and predictors for tuberculosis in children living with HIV in Northern Ethiopia.DesignObservational, retrospective follow-up study.MethodsA total of 645 HIV-infected children were observed between September 2009 and September 2014. Cox regression analysis was used to identify predictors for developing TB.ResultsThe incidence rate of tuberculosis was 4.2 per 100 child-years. Incidence of tuberculosis was higher for subjects who were not on cotrimoxazole preventive therapy, were not on isoniazid preventive therapy, had delayed motor development, had a CD4 cell count below the threshold, had hemoglobin level less than 10 mg/dl and were assessed as World Health Organization (WHO) clinical stage III or IV.ConclusionIncidence of TB in children living with HIV was high. This study reaffirmed that isoniazid preventive therapy is one of the best strategy to reduce incidence of TB in children living with HIV. All children living with HIV should be screened for TB but for children with delayed motor development, advanced WHO clinical stage, anemia or immune suppression, intensified screening is highly recommended.     

Elevation of taurine in human congestive heart failure

The concentration of taurine in the left ventricle of the heart was doubled in patients who had died of chronic congestive heart failure compared to patients who had died of other causes and had no cardiac pathology. In the absence of congestive heart failure, a similar elevation in taurine level was seen in patients with high blood pressure compared to patients with lower blood pressures. The levels of taurine in heart failure were not affected by digitalis treatment. The concentration of taurine in the aorta was almost the same in patients who had died of congestive heart failure and patients who had died of other causes, suggesting that the increase in concentration of taurine might be specific to the heart.     

Localization of the insulin-like growth factor system in a rat model of heart failure induced by myocardial infarction.

Although cardiac effects of growth hormone (GH) and insulin-like growth factor (IGF)-I have been reported in experimental models of heart failure and in human dilated cardiomyopathy, the IGF system has not been comprehensively assessed in the failing heart. We therefore localized the IGF system in the left ventricle during congestive heart failure after myocardial infarction (MI) in the rat. The left anterior descending coronary artery was ligated in adult female Sprague-Dawley rats and hearts were examined after 6 months when congestive heart failure had developed. In situ hybridization histochemistry was used to localize mRNA for the components of the IGF system in the left ventricle of sham and congestive heart failure animals. We were able to detect changes in the spatial distribution of mRNA for IGF-I and IGF binding proteins 3, 4, 5, and 6 in the left ventricle during congestive heart failure after MI. IGF-I and the binding proteins were predominantly increased in the infarct/peri-infarct area of the left ventricle. Other components of the IGF system were indistinguishable from the low to undetectable levels in sham-operated rats. These results demonstrate that the IGF system is altered in the failing heart and suggest that the IGF system plays an important role in the response of the heart to MI and consequent failure.     

Haemodynamic Studies with Peruvoside in Human Congestive Heart Failure

The immediate haemodynamic effects of peruvoside, a cardiac glycoside obtained from the Indian plant Thevetia neriifolia Juss, were studied in six patients with congestive heart failure. The drug was found to have an immediate and powerful positive inotropic and negative chronotropic effect, like ouabain, on the failing human heart. Oral peruvoside was also effective in the treatment of congestive heart failure when used on a short-term as well as a long-term basis. It therefore seems that peruvoside is a useful cardiac glycoside in the management of congestive heart failure in man as a quick-acting intravenous preparation. It is equally effective when used orally.     

Statement of the ad hoc committee on the laboratory diagnosis of infectious and serum hepatitis.

A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%.     

The diurnal rhythm of plasma aldosterone and plasma renin activity in patients with congestive heart failure

Study on a diurnal rhythm of plasma aldosterone (PA) and plasma renin activity (PRA) was performed in 8 patients with congestive heart failure. All patients had been digitalized and received diuretics under mild sodium restriction. An obvious diurnal rhythm of PA similar to the normal subjects, with the lowest value in the evening and the highest value in the morning, was observed in 7 of 8 cases, while a diurnal rhythm of PRA was obscure except in one case. The PA generally did not run parallel with PRA. Although the reason of the absence of PRA diurnal rhythm in congestive heart failure was not clear, it was considered that reninangiotensin system did not play a significant role for the development of PA diurnal rhythm in congestive heart failure. The determined PA values were entirely within normal range except in 2 cases, although they were administered the potent diuretics chronically. A high PA value was observed only in early morning in one case, while all determined PA values were extremely high in another case with severe congestive heart failure involved in cardiac liver cirrhosis. The PRA values were relatively low in 2 cases, normal in 5 and high in one.     

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aortocaval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.     

Alpha 1-adrenoceptor activity in arterial smooth muscle following congestive heart failure

The interactions between yohimbine (selective alpha 2-antagonist) with noradrenaline (mixed agonist) and phenylephrine (selective alpha 1-agonist) were studied in the canine dorsal pedal artery in an attempt to characterize the peripheral vascular response to adrenergic agents before and after the development of congestive heart failure in the dog. The contractile responses of the dorsal pedal artery to potassium chloride were also examined. Both noradrenaline and phenylephrine contracted the dorsal pedal artery in a concentration-dependent manner before and at peak heart failure, the responses to the agonists being enhanced at heart failure. The responses of the artery to potassium were not modified by congestive heart failure. Yohimbine caused concentration-dependent antagonism of noradrenaline, without altering the magnitude of the maximum response, providing pA2 values ranging from 8.26 to 7.06 against low and high concentrations of noradrenaline, respectively, before heart failure development. Following heart failure, the pA2 values for yohimbine against noradrenaline remained unchanged, but slopes from the Arunlakshana-Schild plots were significantly different from unity, implying a noncompetitive antagonism. The pA2 values of yohimbine against phenylephrine were at least 10 orders of magnitude lower than those against noradrenaline. After congestive heart failure, yohimbine was even less effective against high concentrations of phenylephrine. These findings suggest that enhanced vasoconstriction during heart failure results, in part, from increased alpha 1-adrenoceptor mechanisms in peripheral arterial smooth muscle.     

琥珀酸美托洛尔与美托洛尔对慢性充血性心衰患者心功能的影响

目的：探讨琥珀酸美托洛尔缓释片与美托洛尔片对慢性心力衰竭患者的心功能的影响。方法：选取慢性充血性心衰患者182例临床患者资料,排除67例不符合入选标准病例后,按照服用美托洛尔剂型（缓释片、平片）分为两组,两组均为常规利尿剂ACEI等治疗。美托洛尔组患者服用每日服用25mg-50mg的美托洛尔治疗,均分2次服用。琥珀酸美托洛尔组每日服用23．75-95mg琥珀酸美托洛尔缓释片进行治疗。评价治疗前和治疗12个月后的相关指标,包括：一日5次的平均心率（晨起前,8时,12时,16时,夜间休息前共5次平均心率）、LVDd、EF、BUN、Crea。结果：治疗12个月后,两组患者心率均下降．琥珀酸美托洛尔组与美托洛尔组相比下降更明显（64．0±5．4VS69．5±7．6,P〈0．05）、LVDd、EF、BUN、Crea等指标在两组之间没有差别。结论：慢性充血性心衰患者应用琥珀酸美托洛尔较美托洛尔平片相比可明显降低平均心率。但对于心功能肾功能的影响。琥珀酸关托洛尔较美托洛尔平片相比无明显差异。     

Losartan corrects abnormal frequency response of renal vasculature in congestive heart failure

In congestive heart failure, renal blood flow is decreased and renal vascular resistance is increased in a setting of increased activity of both the sympathetic nervous and renin-angiotensin systems. The renal vasoconstrictor response to renal nerve stimulation is enhanced. This is associated with an abnormality in the low-pass filter function of the renal vasculature wherein higher frequencies (> or =0.01 Hz) within renal sympathetic nerve activity are not normally attenuated and are passed into the renal blood flow signal. This study tested the hypothesis that excess angiotensin II action mediates the abnormal frequency response characteristics of the renal vasculature in congestive heart failure. In anesthetized rats, the renal vasoconstrictor response to graded frequency renal nerve stimulation was significantly greater in congestive heart failure than in control rats. Losartan attenuated the renal vasoconstrictor response to a significantly greater degree in congestive heart failure than in control rats. In control rats, the frequency response of the renal vasculature was that of a first order (-20 dB/frequency decade) low-pass filter with a corner frequency (-3 dB, 30% attenuation) of 0.002 Hz and 97% attenuation (-30 dB) at > or =0.1 Hz. In congestive heart failure rats, attenuation did not exceed 45% (-5 dB) over the frequency range of 0.001-0.6 Hz. The frequency response of the renal vasculature was not affected by losartan treatment in control rats but was completely restored to normal by losartan treatment in congestive heart failure rats. The enhanced renal vasoconstrictor response to renal nerve stimulation and the associated abnormality in the frequency response characteristics of the renal vasculature seen in congestive heart failure are mediated by the action of angiotensin II on renal angiotensin II AT1 receptors.     

Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid-pregnancy.

We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl), serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and 2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy.     

Experiences with High Doses of Furosemide in Renal Disease and Resistant Edematous States

Six cases of edema, three due to the nephrotic syndrome, one to congestive heart failure and two to chronic renal failure, are reported in which furosemide was administered in oral doses higher than those usually prescribed (up to 720 mg. a day), in order to obtain a satisfactory diuresis. In one case of severe prerenal failure secondary to cardiogenic shock and in one case of acute tubular necrosis secondary to hypotension at the time of operation, intravenous doses up to 990 and 1400 mg. per day respectively were able to reverse the oliguria. In eight additional patients who were on chronic hemodialysis, furosemide was administered to the amount of 1000 mg. per day orally in divided doses for two weeks, and produced a moderate diuretic response.The use of high doses of furosemide in edema and renal failure resistant to the usual therapeutic measures appears to be safe and effective.     

Insulin,Glucose, and Potassium in the Treatment of Congestive Heart Failure

A daily infusion of 500-1,000 ml of 50% glucose containing 100-120 units of soluble insulin and 100-120 mEq of potassium chloride per litre was given to six patients suffering from hyponatraemia and congestive cardiac failure resistant to digoxin and diuretic therapy. In two patients there was no response, but four showed a striking improvement with a sodium and water diuresis, a rise in plasma sodium level, and in two cases a reversion from atrial fibrillation to sinus rhythm. It is suggested that insulin, glucose, and potassium given by the intravenous route in adequate dosage forms a useful adjunct to the management of severe congestive heart failure.     

Red blood cell transfusion in patients with ST-elevation myocardial infarction—a meta-analysis of more than 21,000 patients

Background

Red blood cell transfusion remains controversial in patients with acute coronary syndromes and particularly in patients with ST-elevation myocardial infarction (STEMI).

Methods

We systematically searched PubMed, Cochrane, EMBASE, and Web of Science for studies published until January 2017 describing the outcomes in patients with STEMI who received red blood cell transfusion, compared with patients who did not.

Results

A total of 21,770 patients with STEMI from 5 cohort studies were included in the meta-analysis, 984 (4.5%) received red blood cell transfusion and 20,786 (95.4%) did not. Red blood cell transfusion was associated with a higher risk of in-hospital and long-term mortality, emergency repeated percutaneous coronary intervention (PCI), reinfarction rate, stroke rate, and heart failure. The group with red blood cell transfusion had a slightly higher incidence of diabetes mellitus and hypertension, but a lower incidence of smoking. The two groups had the same incidence of prior myocardial infarction, prior coronary artery bypass graft surgery and malignancy. Prior heart failure, prior stroke and prior PCI were more frequent in the group that had received red blood cell transfusion. The mean nadir haemoglobin was 8.5?±?0.1?g/dl in the group with red blood cell transfusion and 12.5?±?0.4?g/dl in the control group, p?<?0.001.

Conclusions

Red blood cell transfusion increases the morbidity and mortality in patients with STEMI. This difference could not be explained by the higher morbidity in the red blood cell transfusion group alone. Further randomised controlled trials are required to provide a reliable haemoglobin threshold for these patients.