Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis.

OBJECTIVE: Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500 ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 out of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH. MATERIALS AND METHODS: fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 out of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500 ng/mL). RESULTS: Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2, 1 STX11, 1 UNC13D, and 1 PRF1. Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D, 1 PRF1. Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient. CONCLUSION: Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 out of the above 3 criteria.

Beneficial effects of iloprost during experimentally induced hemorrhagic shock.

BACKGROUND: The aim of the study was to evaluate the efficacy of iloprost on myocardial insufficiency associated with hypovolemic shock in dogs. We designed the study as a controlled randomized study. METHODS: Sixteen mixed-breed dogs were included into the study and divided into two equal groups as the control and iloprost groups. Mean arterial pressure was reduced to 45 mmHg by withdrawing the arterial blood into citrated bags. The control group did not receive any drug but the other group received iloprost at a rate of 20 ng/kg/min by an infusion pump. Iloprost infusion was started 30 min after the blood pressure was reduced to 45 mmHg. All measurements were made before removal of blood, 45 min after exsanguination and at 1 hour intervals for 3 hours. Left ventricular stroke work index was measured 72 hours after the study. The hemodynamic and biochemical parameters and blood gas analysis were obtained. RESULTS: After hemorrhage, cardiac index (CI) decreased significantly from 132 +/- 14 to 51 +/- 8 ml/kg/min in the control group and from 128 +/- 11 ml/kg/min to 47 +/- 13 ml/kg/min in the iloprost group, respectively but at the end of the third hour it was 81 +/- 8 ml/kg/min in the control group and 105 +/- 6 ml/kg/min in the iloprost group (p < 0.05). Tumor necrosis factor-alpha (TNF alpha) was 41 +/- 8 pg/ml in the control group and 18 +/- 6 in the iloprost group 3 hours after bleeding (p < 0.05). Tumor necrosis factor-alpha concentration was significantly higher in the control group than in the iloprost group. There was no significant difference in pH between the groups but actual bicarbonate concentrations were different between the groups (p < 0.05). At the end of the third hour total body oxygen consumption was 105 +/- 11 ml/min in the control group and 132 +/- 12 ml/min in the iloprost group (p < 0.05). Oxygen delivery 3 hours after hemorrhage was 201 +/- 19 ml/min in the control group and 252 +/- 24 ml/min in the iloprost group (p > 0.05). Left ventricular stroke work index was higher in the iloprost group (p < 0.05). CONCLUSIONS: Hemorrhagic shock causes tumor necrosis factor-alpha release which may lead to multiple organ failure. Organ dysfunction still persists even after the appropriate treatment. Iloprost attenuates the release of tumor necrosis factor-alpha which may improve the adverse effects of hemorrhagic shock.

Iloprost protects the spinal cord during aortic cross-clamping in a canine model.

BACKGROUND: Surgical procedures on the thoracoabdominal part of the aorta make the spinal cord vulnerable to ischemia. Paraplegia is the most severe complication following thoracoabdominal operations. In this study, iloprost was used as an agent to decrease the severity of ischemia and reperfusion injury to the spinal cord during aortic occlusion and declamping. METHODS: Twelve adult mongrel dogs weighing 17+/-2 kg were used in this study. The animals were randomly assigned to either group I, which received saline solution (6 dogs), or group II, which received prostacyclin. Group I was referred to as the control group and group II as the iloprost group. After baseline measurements were completed, the aorta was cross-clamped for sixty minutes distal to the left subclavian artery. No pharmacologic agents were used to control blood pressure in group I. Proximal and distal mean arterial pressures (DMAP) were monitored continuously. DMAP were considered as diastolic pressure in preocclusion and reperfusion periods. Iloprost administration was started at a rate of 5 ng/kg/minute five minutes before the aortic occlusion. This dosage was increased to 25 ng/kg/minute during aortic occlusion. RESULTS: Mean proximal arterial pressure was 147+/-12 mmHg in the control group and 116+/-13 mmHg in the iloprost group at occlusion (p<0.01). Mean distal arterial pressure was 19+/-7 in the control group and 37+/-5 in the iloprost group during clamping (p<0.05). Functional outcome was evaluated according to Tarlov scores 24 hours after the study. Although none of the animals recovered completely from the control group, 4 animals from the iloprost group recovered (p<0.05). Following the neurologic assessment, animals were sacrificed and specimens were taken for the electron microscopic study. Electron microscopic changes documented that severe mitochondrial damage and vacuolisation occurred in the control group. However these changes were more subtle in the iloprost group. CONCLUSIONS: As a result of this study we concluded that iloprost infused before and during clamping of the thoracic aorta mitigates the spinal cord injury due to ischemia and reperfusion following unclamping.

Reduction of the infarcted area with the use of simplified coronary sinus retroperfusion during experimental coronary artery occlusion.

This study examined if the use of simplified coronary sinus retroperfusion would lead to any reduction in the infarcted area associated with improved right and left ventricular function. Twelve mongrel dogs were entered in this study. Following anesthesia, a fast response thermistor was placed on the pulmonary artery via the jugular vein and aorta via the left ventricular apex. The left anterior descending artery (LAD) was separated from the vein. A retrograde cardioplegia catheter was inserted into the coronary sinus. Following these procedures, LAD was occluded for a period of 3.5 h. After 30 min ischemia, the aorta-coronary sinus connection was established. The animals were divided into two equal groups. One group was not treated and was considered the control group (six animals). In the remaining group (six animals), retroperfusion was used and was considered the retroperfusion group. At the end of the study, the left ventricular ejection fraction was 65+/-15% in the retroperfusion group and 48+/-5% in the control group (P<0.05). The left ventricular stroke work index was 0.44+/-0.04 (g m/kg) in the retroperfusion group and 0.31+/-0.05 (g m/kg) in the control group (P<0.05). Cardiac output was 1650+/-75 ml/min in the retroperfusion group and 1250+/-125 ml/min in the control group. The ratio of the infarct size to the area at risk was 49+/-5% in the control group and 7+/-3% in the retroperfusion group. In light of these studies, we conclude that simplified coronary sinus retroperfusion appears to be an effective method that must be taken into consideration.

Preservation of myocardial functions by pentoxyphylline cardioplegia during and after cardiopulmonary bypass.

BACKGROUND: The aim of the presented study was to evaluate the preservation effect of the pentoxyphylline-blood cardioplegia on myocardial functions during and after the cardiopulmonary bypass in an experimental dog model. METHODS: Central hemodynamics and metabolic variables such as creatine phosphokinase, myocardial oxygen extraction and myocardial lactate extraction were obtained during and following 4 hours after the cardiopulmonary bypass after the baseline scores were recorded. Twelve mongrel dogs were divided into two equal groups. The first group of animals served as controls. The second group of animals was treated with pentoxyphylline cardioplegia that was added to each blood cardioplegia as 15 mg/100 ml. RESULTS: After bypass, the hemodynamic parameters were better in the pentoxyphylline group. Cardiac index fell in all animals, but it was significantly less in the control group. Pulmonary capillary wedge pressure was lower in the pentoxyphylline group as an index of better preservation of ventricular filling pressure. CPK-MB was significantly higher in the control group both at 2 and 4 hours after the bypass. It was 79 +/- 13 iu/L in the control group and 41 +/- 9 iu/L in the pentoxyphylline group 4 hours after cardiopulmonary bypass. MLE was also higher both on bypass and following bypass in the control group. CONCLUSIONS: In conclusion, pentoxyphylline usage may reduce the risks of ischemic-reperfusion injury during and following cardiopulmonary bypass and aortic cross-clamping. It can be an administered drug during cardioplegia.

Effects of ATP-MgCl2 administration in hypovolemic dogs.

BACKGROUND: The aim of the study was to evaluate the efficacy of ATP-MgCl2 on myocardial insufficiency associated with hypovolemic shock in dogs. We designed the study as a controlled randomized study. METHODS: Six mixed-breed dogs weighing 22 +/- 3 kg were included in the control group and 20 +/- 3 kg in the ATP-MgCl2 group. After the animals were anesthetized 40 ml/kg of blood was withdrawn in 15 minutes. Animals were observed for 45 minutes after removal of blood. Six animals received 45 ml/kg of lactated Ringer's solution and the other animals were treated with 45 ml/kg of lactated Ringer's solution and ATP-MgCl2. All measurements were made before removal of blood, 45 min after exsanguination and at 1 hour intervals for 3 hours. The following parameters were measured; systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure, central venous pressure, cardiac output, rectal temperature, arterial pH, PCO2 and PO2 and mixed venous hemoglobin oxygen saturation. In addition blood samples were collected for the analysis of lactate and tumor necrosis factor (TNF) concentrations. RESULTS: After hemorrhage, cardiac index (CI) decreased significantly from 122 +/- 9 to 52 +/- 9 ml/kg/min in the control group (p < 0.0001) and from 124 +/- 11 ml/kg/min to 50 +/- 6 ml/kg/min in the ATP-MgCl2 group, respectively (p < 0.0001). After volume replacement, Cl was 93 +/- 6 ml/kg/min in the control group and 111 +/- 4 ml/kg/min in the ATP-MgCl2 group 3 hours after the onset of reinfusion, respectively (p < 0.05). TNF was 36 +/- 5 pg/ml in the control group and 21 +/- 3 pg/ml in the ATP-MgCl2 group (p < 0.05). Three hours after the onset of hemorrhagic shock, oxygen consumption and delivery were 126 +/- 14 and 206 +/- 19 ml/min in the control group and 198 +/- 16 and 305 +/- 27 ml/min in the ATP-MgCl2 group, respectively. At the same time point the oxygen extraction ratio was 0.49 +/- 0.04 in the control group and 0.61 +/- 0.03 in the ATP-MgCl2 group (p < 0.01). CONCLUSIONS: Hemorrhagic shock causes TNF release which may cause multiple organ failure. Organ dysfunction still persists even after the appropriate treatment. ATP-MgCl2 attenuates the release of TNF which may improve the adverse effects of hemorrhagic shock.

Hemodynamic effects of acute intestinal ischemia.

Twelve animals entered in this study with the aim of documenting that superior mesenteric artery small occlusions lasting for one hour have adverse effects on the myocardium. Three hours after cross clamp removal CO decreased to 1.07 +/- 0.11 from 1.99-0.09 a preoperative value (p < 0.01) and PCWP increased to 17 +/- 3 from 8 +/- 3 a preoperative value. MOE reduced to 40-5% 3 hours after cross clamp removal. MLE was -0.21 +/- 0.11 three hours after clamp removal. Changes in MOE and MLE were commented as a defect in myocardial aerobic metabolism. As a result of this study it was concluded that toxic mediators are released from the intestine being reperfused after temporary occlusions of the SMA impair myocardial metabolism, resulting in decreased hemodynamic functions.

Coronary sinus retroperfusion combined with intraaortic balloon pumping to perfuse the acutely ischemic myocardium.

This study was planned to show the effect of retroperfusion and intraaortic balloon pumping (IABP) on myocardial hemodynamic recovery. Twelve dogs entered this study. Half of them received IABP and coronary sinus retroperfusion (CSPR) combination (Group II) and the remaining received IABP alone (Group I). Left anterior descending artery was occluded for a period of three hours. 15 minutes after occlusion IABP and IABP + CSRP were initiated. The average cardiac output was 1.41 +/- 0.18 L/min in the group I and 1.72 +/- 0.24 L/min in the group II (p < 0.03) after 3 hours of occlusion. Mean arterial pressure was 82.1 +/- 4.8 mmHg in the group I and 89.7 +/- 2.6 mmHg in the group II (p < 0.03). On the basis of this study it was concluded that CSRP + IABP could be an alternative treatment to IABP alone during the acutely developing ischemia.