Carotid Artery Doppler Flow Pattern After Deep Hypothermic Circulatory Arrest in Neonatal Piglets

The mechanisms of cerebral injury after cardiac surgery in neonates are not clear. The aim of the study was the analysis of flow changes in the carotid artery of neonatal piglets after deep hypothermic circulatory arrest (DHCA). Eight neonatal piglets were connected to cardiopulmonary bypass (CPB) and underwent (i) cooling to 18°C core temperature within 30 min, (ii) DHCA for 90 min, and finally (iii) rewarming to 37°C after cross‐clamp release (60 min of reperfusion). The blood flow was measured in the left carotid artery by an ultrasonic flow probe before CPB (baseline; T₀), immediately after termination of reperfusion on CPB (T₁), 30 min later (T₂), and 60 min later (T₃). Additionally, the pulsatility index and the resistance index were calculated and compared. Finally, the relationship between the carotid artery flow and the corresponding pressure at each time‐point was compared. After termination of CPB (T₁), the mean carotid artery flow was reduced from 45.26 ± 2.58 mL/min at baseline to 23.29 ± 2.58 mL/min (P < 0.001) and remained reduced 30 and 60 min later (P < 0.001 vs. baseline). Both the pulsatility index and the resistance index were increased after termination of reperfusion, with the maximum occurring 30 min after CPB end. In conclusion, the carotid artery Doppler flow in neonatal piglets was reduced after DHCA, while the indices of pulsatility and resistance increased.     

Effect of a Miniaturized Cardiopulmonary Bypass System on the Inflammatory Response and Cardiac Function in Neonatal Piglets

The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1‐week‐old piglets were placed on a mild hypothermic CPB (32°C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin‐6 (IL‐6) and thrombin‐antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL‐6 and TAT immediately after CPB (4370 ± 2346 vs. 9058 ± 2307 pg/mL, P < 0.01 and 9.9 ± 7.7 vs. 25.1 ± 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 ± 0.03 vs. 0.11 ± 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 ± 2860 vs. 28 620 ± 15 552 dynes/cm⁵/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates.     

The optimal flow rate for antegrade cerebral perfusion during deep hypothermic circulatory arrest

The aim of this study is to compare cerebral protection using antegrade cerebral perfusion (ACP) with various flow rates during deep hypothermic circulatory arrest (DHCA) in a piglet model. Twenty‐three piglets were randomized to five groups: the control group (n = 3), DHCA group (n = 5), ACP25 group (n = 5), ACP50 group (n = 5), and ACP80 group (n = 5). Three control piglets did not undergo operations. Twenty piglets underwent cardiopulmonary bypass (CPB) and DHCA for 60 min at 20°C. ACP was conducted at 0, 25, 50, and 80 mL/kg/min in the DHCA, ACP25, ACP50, and ACP80 group, respectively. Serum S‐100B protein and neuron‐specific enolase were monitored, and brain tissues were assayed for the activities of caspase‐3 and stained for the evidence of apoptotic cellular injury. Rise in serum S‐100B level (post‐CPB—pre‐CPB) in the ACP50 group was significantly lower than that in the ACP80 group (P = 0.001). Caspase‐3 levels were significantly elevated in the ACP80 group compared with the ACP25 (P = 0.041) and ACP50 group (P = 0.01), while positive terminal deoxyneucleotidyl transferase‐mediated biotin‐dUTP nick end labeling reaction scores in the ACP80 group were significantly higher than those in the ACP25 (P = 0.043) and ACP50 group (P = 0.023). Cerebral protection effects of ACP at 25 and 50 mL/kg/min were superior to that of ACP at 80 mL/kg/min as determined by cerebral markers, immunology, and histology.     

Low‐Output Is Not the Cause of Death of Neonatal Piglets Early After Cardiopulmonary Bypass

The mortality rate of neonatal piglets after heart surgery is high. Searching for a possible explanation for the death of neonatal piglets early after cardiopulmonary bypass, we analyzed hemodynamic parameters regarding survival and non‐survival. Initially, 10 neonatal piglets (younger than 7 days) were connected to cardiopulmonary bypass (CPB). The mean body weight was 2.98 ± 0.44 kg. Exposure of the heart was performed through a median sternotomy. After connection to the CPB, the piglets were cooled to 32°C core temperature before the ascending aorta was cross‐clamped and the heart arrested (90 min). Thereafter, piglets were re‐warmed to 37°C and separated from CPB. During follow‐up, the piglets did not receive inotropic support or vasopressors. Piglets who survived at least 2 h after termination of CPB were included in the study for further data analysis (n = 9). Five piglets died 2.5 to 4.0 h (median: 3.5 h) after CPB; these piglets formed the non‐survivors group. Four animals survived the complete follow‐up of 6 h after CPB and formed the survivors group. Regarding contractility (dP/dt_max, dP/dt_max/P, and wall thickening) there were not statistically significant differences between the groups. Non‐survivors showed prolonged decrease of mean arterial pressure of more than 20% of baseline values, corresponding with a value of below 30 mm Hg. In conclusion, the death of neonatal piglets early after cardiopulmonary bypass was not determined by low output.     

Dialysis Reduces Portal Pressure in Patients With Chronic Hepatitis C

The purpose of this study was to characterize changes in hepatic venous pressures in patients with chronic hepatitis C. The histology and laboratory data from patients with chronic hepatitis C who underwent a transjugular liver biopsy (TJLB) and hepatic venous pressure gradient measurement were analyzed. Portal hypertension was defined as hepatic venous pressure gradient ≥6 mm Hg. A single pathologist masked to hepatic venous pressure gradient scored liver sections for inflammation and fibrosis. The patients with high‐grade inflammation (relative risk [RR] 2.82, P = 0.027, multivariate analysis) and late‐stage fibrosis (RR 2.81, P = 0.022) were more likely to have a hepatic venous pressure gradient ≥6 mm Hg, while the patients on dialysis (RR 0.32, P = 0.01) were less likely to have a hepatic venous pressure gradient ≥6 mm Hg. The patients on dialysis (n = 58) had an elevated serum blood urea nitrogen and creatinine when compared with those who were not (n = 75) (47.6 ± 3.3 and 7.98 ± 0.4 vs. 25.9 ± 2.0 and 1.66 ± 0.22 mg/dL, respectively; P < 0.001). While the hepatic venous pressure gradient increased with the rising levels of liver fibrosis in the latter group (P < 0.01), it did not change in the patients on dialysis (P = 0.41). The median hepatic venous pressure gradient was especially low in late‐stage fibrosis patients on dialysis when compared with the latter group (5 vs. 10 mm Hg, P = 0.017). In patients on dialysis, serum transaminases were low across all levels of fibrosis. Twenty‐three of the 92 patients with early fibrosis had a hepatic venous pressure gradient ≥6 mm Hg. In patients with chronic hepatitis C, concomitant TJLB and hepatic venous pressure gradient measurement identify those who have early fibrosis and portal hypertension. Long‐term hemodialysis may reduce portal pressure in these patients.     

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Background: Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. Methods: After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27°C or DHCA at 18°C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. Results: COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 ± 8 vs 56 ± 13% and 35 ± 6 vs 58 ± 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 ± 0.1 vs 0.2 ± 0.1 mm ·l^?1, P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 ± 17 vs 6 ± 2 μm ·l^?1, P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 ± 1020 vs 70 ± 28, P < 0.01). Conclusions: In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.     

Iron Deficiency in Outdoor Pig Production

It has been claimed that outdoor‐reared suckling piglets do not need iron supplementation. According to practical experience, outdoor‐reared and non‐iron‐supplemented piglets show a lower performance in comparison with their iron‐supplemented counterparts. The purpose of the present study was to determine the effect of iron supplementation on outdoor‐reared suckling piglets. In a large Hungarian outdoor pig production unit, 4691 piglets were assigned to one of two treatment groups. Piglets in group 1 (n = 2344): received no iron supplementation, whereas piglets in group 2 (n = 2347) were intramuscularly injected in the neck on day 3 post‐ partum with 1.5 ml of Ferriphor^® 10% solution (TAD Pharmaceutical GmbH, Bremerhaven, Germany). Animal weights, morbidity, haemoglobin concentration and mortality were recorded and analysed. At weaning the iron‐injected piglets were significantly (P < 0.05) heavier. The iron‐supplemented piglets also revealed significantly (P < 0.01) less pre‐weaning morbidity and mortality and higher (P < 0.01) blood haemoglobin concentration compared with the non‐injected ones. This study suggests that in order to prevent pre‐weaning losses and support piglet health and weight performance, iron supplementation should be administered to piglets in outdoor pig production units.     

Combined treatment for facial rejuvenation using an optimized pulsed light source followed by a fractional non‐ablative laser

Background

Combination laser treatments can potentially increase the effectiveness of treatment without the additional downtime associated with another procedure.

Objective

To assess the effectiveness and safety of combining non‐ablative fractional treatments with optimized intense pulsed light.

Methods and Materials

Ten subjects (Group A) received full face treatments with a non‐ablative fractional either followed or preceded by an optimized intense pulsed light source. Twenty‐six subjects (Group B) received only full face treatments with the same non‐ablative, fractional laser device.

Results

For Group A, the overall average Fitzpatrick Wrinkle Scale for all patients improved from 6.3 ± 1.1 at baseline to 5.9 ± 0.8 one month following one treatment for an average improvement of 0.4 ± 0.6 (P < 0.10 paired t‐test n = 9). The average pigment improvement score was 1.8 ± 0.9 on a 4‐point scale. In Group B, the average Fitzpatrick Wrinkle Scale improved from 6.0 ± 1.6 at baseline to 5.2 ± 1.4 at 3 months for an average improvement of 0.8 ± 0.7 (P < 0.001, n = 26 paired t‐test). The average pigment improvement score was 1.4 ± 1.0 (P < 0.001, t‐test, n = 26). Adverse events were similar in the two groups.

Conclusion

The combination of an optimized intense pulsed light source with a non‐ablative fractional laser during the same treatment session is safe and effective. Lasers Surg. Med. 45:405–409, 2013. © 2013 Wiley Periodicals, Inc.     

Hemodiafiltration—A Technique for Physiological Correction of Priming Solution in Pediatric Cardiac Surgery: An In Vitro Study

Pediatric cardiopulmonary bypass (CPB) circuit invariably requires priming with packed red blood cells (PRBCs). Metabolic composition of stored PRBCs is unphysiological and becomes worse with increasing duration of storage. It is recommended to correct these abnormalities before initiation of CPB. We tested the hypothesis that hemodiafiltration of the prime with 0.45% saline is sufficient for reducing the metabolic load and reaching a physiologic state. In an in vitro study, 100 mL of blood each from 45 units of PRBCs stored for 3–20 days were used for priming the 45 neonatal CPB circuits. Based upon the method used for removal of excess crystalloid from the prime, circuits were divided into three groups. Group 1: Direct removal through manifold line. Group 2: Ultrafiltration of prime. Group 3: Hemodiafiltration of the prime. Blood gas analyses were obtained from the PRBCs and from the prime before and after removal of crystalloid. Both direct removal of crystalloid and ultrafiltration resulted in significant reduction in biochemical and metabolic load of blood (P < 0.001). However, the final composition of the prime was far from being physiological. Hemodiafiltration resulted in improvement of metabolic parameters to near physiological range (lactate: 33.8 ± 4.44 vs. 14 ± 2.53 mg/dL, pH: 7.05 ± 0.15 vs. 7.34 ± 0.06, bicarbonates: 4.83 ± 0.59 vs. 27.6 ± 2.94 meq/L; P < 0.001). Similarly, sodium (147.76 ± 12.73 vs. 144.6 ± 5.96 meq/L) and potassium (9.6 ± 2.83 vs. 4.23 ± 0.37 meq/L) also changed significantly (P < 0.001) to near physiologic range. Hemodiafiltraion of final prime is a simple, efficients and rapid method of correcting the biochemical parameters and reducing the metabolic load of stored PRBCs towards the physiological range before initiating the CPB.     

Hepatocellular Glycogen in Alleviation of Liver Ischemia-Reperfusion Injury During Partial Hepatectomy

Background Temporary occlusion of liver blood supply for complex liver operation is common in liver surgery. However, hepatic vascular occlusion will undoubtedly impair liver function. This study was designed to elucidate the effect of hepatocellular glycogen in alleviation of liver ischemia-reperfusion injury during hepatic vascular occlusion for partial hepatectomy. Methods Fifty-seven patients were randomly divided into an experimental group (n = 29) and a control group (n = 28). In the experimental group, patients were given high-concentration glucose intravenously during 24 h before the operation. The hepatic lesion was resected after portal triad clamping in the two groups. Noncancer liver tissue was biopsied to measure hepatic tissue ATP content and change of malondialdehyde (MDA) and superoxide dismutase (SOD). Liver function of all patients was assessed by using an automatic biochemical analysis apparatus before the operation and the first and fifth days after operation. Results The mean hepatic vascular occlusion time in the experimental group was 19.21 ± 4.54 min and in the control group it was 21.04 ± 5.11 min. Hepatic tissue ATP content of the experimental group was significantly higher than that of the control group at the end of hepatic vascular occlusion (2.15 ± 0.39 μmol/g wet tissue vs. 1.33 ± 0.44, p < 0.01) and at the point of 1-h reperfusion (2.19 ± 0.29 μmol/g wet tissue vs. 1.57 ± 0.35, p < 0.01). There was significant difference in SOD activity between the two groups at the end of hepatic vascular occlusion (130.69 ± 30.49 NU/mg pr vs. 97.83 ± 26.23, p < 0.01) and at the point of 1-h reperfusion (139.55 ± 39.88 NU/mg pr vs. 114.74 ± 25.93, p < 0.01). Significant difference was shown in MDA content between the two groups at the end of hepatic vascular occlusion (3.02 ± 0.30 nmol/mg pr vs. 3.99 ± 0.49, p < 0.01) and at the point of 1-h reperfusion (3.81 ± 0.69 nmol/mg pr vs. 5.75 ± 1.17, p < 0.01). In addition, the liver function of the experimental group was significantly better than that of the control group the first and fifth days after the operation (p < 0.01). Conclusions Abundant intracellular glycogen may reduce liver ischemia-reperfusion injury caused by hepatic vascular occlusion. It is beneficial to give a large amount of glucose before a complex liver operation during which temporary occlusion of hepatic blood flow is necessary.     

Quantification of Operational Learning in Minimal Invasive Extracorporeal Circulation

Minimal invasive extracorporeal circulation (MiECC) has initiated important new efforts within science and technology towards a more physiologic perfusion. In this study, we aim to investigate the learning curve of our center regarding MiECC. We studied a series of 150 consecutive patients who underwent elective coronary artery bypass grafting by the same surgical team during the initial phase of MiECC application. Patients were randomly assigned into two groups. Group A (n = 75) included patients operated on MiECC, while group B (n = 75) included patients operated with conventional cardiopulmonary bypass (cCPB). The primary end‐point of the study was to identify whether there is a learning curve when operating on MiECC. The following parameters were unrelated with increasing experience, even though the results favored MiECC use: reduced CPB duration (102.9 ± 25 vs. 122.2 ± 33 min, P <0.001), peak troponin release (0.07 ± 0.02 vs. 0.1 ± 0.04 ng/mL, P < 0.01), peak creatinine levels (0.97 ± 0.24 vs. 1.2 ± 0.3 mg/dL, P < 0.001), duration of mechanical ventilation (14.1 ± 7.2 vs. 36.9 ± 59.8 h, P < 0.01) and ICU stay (2.1 ± 0.7 vs. 4.4 ± 6.4 days, P < 0.01). However, need for intraoperative blood transfusion showed a trend towards a gradual decrease as experience with MiECC system was accumulating (R² = 0.094, P = 0.007). Subsequently, operational learning applied to postoperative hematocrit and hemoglobin levels (R² = 0.098, P = 0.006). We identified that advantages of MiECC technology in terms of reduced hemodilution and improved end‐organ protection and clinical outcome are evident from the first patient. Optimal results are obtained with 50 cases; this refers mainly to significant reduction in the need for intraoperative blood transfusion. Teamwork from surgeons, anesthesiologists, and perfusionists is of paramount importance in order to maximize the clinical benefits from this technology.     

Cardiopulmonary bypass and its direct effects on neonatal piglet kidney morphology

Renal failure after open heart surgery is a serious complication even in the pediatric population. The aim of the present study was to analyze morphological changes after cardiopulmonary bypass (CPB) surgery in a neonatal piglet model. The kidneys of newborn piglets sacrificed 6 h after CPB were examined (CPB; n = 4) regarding tubular dilatation, vacuole formation, leukocytic infiltration, epithelial destruction, and interstitial edema. Thereafter, the findings were compared with the morphology of normal (untreated) neonatal piglet kidneys (control; n = 4). All changes but the interstitial edema were statistically significant if compared with the normal renal tissue: tubular dilatation (CPB vs. control P < 0.05), vacuole formation (CPB vs. control P < .05), leukocytic infiltration (CPB vs. control P < 0.05), and epithelial destruction (CPB vs. control P < 0.001). In conclusion, CPB induces significant changes in the morphology of the neonatal piglet kidneys.     

Comparison Between D901 Lilliput 1 and Kids D100 Neonatal Oxygenators: Toward Bypass Circuit Miniaturization

Progress in biomaterial technology and improvements in surgical and perfusion strategy ameliorated morbidity and mortality in pediatric cardiac surgery. In this study, we describe our clinical experience comparing performance of two neonatal oxygenators. From January 2002 to March 2011, 159 infants with less than 5 kg body weight underwent heart surgery. Ninety‐four patients received a D901 Lilliput 1 oxygenator with standard bypass circuit (group A), while 65 received a D100 Kids with miniaturized bypass circuit (group B). Miniaturization consisted in shortened arterial, venous, cardioplegia, and pump‐master lines. Priming composition consisted in Ringer's acetate solution with addition of albumin and blood, with target hematocrit of 24% or greater. In group B cardiopulmonary bypass (CPB) was vacuum‐assisted and started with an empty venous line. Modified ultrafiltration and Cell‐Saver blood infusion was routinely applied in both groups. Average ± standard deviation (SD) age at repair was 37 ± 38 days in group A and 59 ± 60 days in group B (P = 0.005). Average ± SD weight, height, and body surface area were 3.5 ± 0.7 kg, 52 ± 4 cm, and 0.22 ± 0.03 m², respectively, in group A, and 3.7 ± 1 kg, 53 ± 5 cm, and 0.23 ± 0.02 m², respectively, in group B (P = not significant [NS]). Male sex was predominant (55 vs. 58%, P = NS). Priming volume was 524 ± 67 mL (group A) and 337 ± 53 mL (group B) (P = 0.001). There were no statistical differences in hemoglobin at the start, during, and at the end of CPB, but group A required higher blood volume added to the prime (111 ± 33 vs. 93 ± 31 mL, P = 0.001). In group B, two surgical procedures were completed in total hemodilution. In group B, CPB time and aortic cross‐clamp time were shorter than in group A (106 ± 52 vs. 142 ± 78 min and 44 ± 31 vs. 64 ± 31 min, respectively, P = 0.001). There were 16 hospital deaths in group A and 4 in group B (P = 0.04). Durations of mechanical ventilation and intensive care unit stay were 5.3 ± 3.2 vs. 4.1 ± 3.2 days (P = 0.02) and 6.5 ± 4.9 vs. 5.1 ± 3 days (P = 0.03), respectively. There were significant differences in inotropic score (1083 ± 1175 vs. 682 ± 938, P = 0.04) and blood postoperative transfusion (153 ± 226 vs. 90 ± 61 mL, P = 0.04). Twenty‐seven patients in group A and 10 in group B presented with major adverse postoperative complications (P = 0.04). Use of neonatal oxygenators with low priming volume, associated with a miniaturized bypass circuit, seems to be a favorable strategy to decrease postoperative morbidity after cardiac surgery in neonates and infants.     

Basic fibroblast growth factor accelerates and improves second‐degree burn wound healing

Second‐degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second‐degree burn patients (average 57.8 ± 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 ± 0.9 days from the burn injury, compared with non‐bFGF use (12.0 ± 2.2 vs. 15.0 ± 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF‐treated and non‐bFGF–treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF‐treated scars than non‐bFGF–treated scars (0.23 ± 0.10 vs. 0.14 ± 0.06 mm, 0.59 ± 0.20 vs. 0.49 ± 0.15 mm: scar extension, scar elasticity, bFGF vs. non‐bFGF, p<0.01). The durometer reading was significantly lower in bFGF‐treated scars than in non‐bFGF–treated scars (16.2 ± 3.8 vs. 29.3 ± 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF‐treated than in non‐bFGF–treated scars (p<0.01).     

1,25 dihydroxyvitamin d-induced inhibition of3H-25 hydroxyvitamin D production by the rachitic rat liverin vitro

Summary The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production of³H-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepatic³H-25 hydroxyvitamin D production in the liver perfusion (3.6 ± 0.4 vs 2.0 ± 0.5 pmol/liver,P<0.05) and in liver homogenates (11.9 ± 0.6 vs 10.1 ± 0.4 pmol/g liver protein/3 h,P<0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 ± 0.6 vs 9.2 ± 0.1 pmol/g liver protein/3 h,P<0.05) but not in the intact liver (3.6 ± 0.4 vs 3.4 ± 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition.     

Liposome‐Encapsulated Hemoglobin Ameliorates Ischemic Stroke in Nonhuman Primates: Longitudinal Observation

Liposome‐encapsulated hemoglobin (LEH) is protective early after brain ischemia in rats and nonhuman primates, but it remains unclear whether the protection persists and confers any benefits beyond the acute phase of brain ischemia and reperfusion. Ten monkeys underwent middle cerebral artery occlusion, received LEH (2 mL/kg, n = 5) or saline (2 mL/kg, n = 5) 5 min later, and reperfusion 3 h later. Positron emission tomography studies were repeated for the cerebral metabolic rate of O₂ (CMRO₂) as well as glucose (CMRglc) up to 8 days after reperfusion, when the animals were euthanized for morphological studies. There was no difference in O₂ metabolism until 3 h after reperfusion, when CMRO₂ was significantly better preserved in the cortex, but not in basal ganglia, on Day 0 in LEH‐treated monkeys. The extent of cortical infarction (saline 68 ± 10% vs. LEH 38 ± 9%, P < 0.05) and CMRO₂ (mild suppression: saline 34 ± 10% vs. LEH 14 ± 4%, P < 0.05) remained significantly better preserved 8 days later, when CMRglc showed a similar pattern of cortical protection (mild suppression: saline 49 ± 15% vs. LEH 37 ± 4%, P < 0.05) in LEH‐treated monkeys, together with regained body weight. Somatic weight control, morphological integrity, CMRO₂, and CMRglc were better preserved immediately, as well as 8 days after occlusion and reperfusion of the middle cerebral artery in monkeys receiving LEH early after onset of ischemia.     

Inhaled iloprost to control pulmonary artery hypertension in patients undergoing mitral valve surgery: a prospective, randomized-controlled trial

Background: Pulmonary hypertension (PHT) is common in patients undergoing mitral valve surgery and is an independent risk factor for the development of acute right ventricular (RV) failure. Inhaled iloprost was shown to improve RV function and decrease RV afterload in patients with primary PHT. However, no randomized‐controlled trials on the intraoperative use of iloprost in cardiac surgical patients are available. We therefore compared the effects of inhaled iloprost vs. intravenous standard therapy in cardiac surgical patients with chronic PHT. Methods: Twenty patients with chronic PHT undergoing mitral valve repair were randomized to receive inhaled iloprost (25 μg) or intravenous nitroglycerine. Iloprost was administered during weaning from cardiopulmonary bypass (CPB). Systemic and pulmonary haemodynamics were assessed with pulmonary artery catheterization and transoesophageal echocardiography. Milrinone and/or inhaled nitric oxide were available as rescue medication in case of failure to wean from CPB. Results: Inhaled iloprost selectively decreased the pulmonary vascular resistance index after weaning from CPB (208 ± 108 vs. 422 ± 62 dyn·s/cm⁵/m², P<0.05), increased the RV‐ejection fraction (29 ± 3% vs. 22 ± 5%, P<0.05), improved the stroke volume index (27 ± 7 vs. 18 ± 6 ml/m², P<0.05) and reduced the transpulmonary gradient (10 ± 4 vs. 16 ± 3 mmHg, P<0.05). In all patients receiving inhaled iloprost, weaning from CPB was successful during the first attempt. In contrast, three patients in the control group required re‐institution of CPB and had to be weaned from CPB using rescue medication. Conclusions: In patients with pre‐existing PHT undergoing mitral valve surgery, inhaled iloprost is superior to intravenous nitrogylycerine by acting as a selective pulmonary vasodilator, reducing RV afterload and moderately improving RV‐pump performance.     

Plasma levels of endothelin-1 in patients with the hepatorenal syndrome after successful liver transplantation

The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction leading to deterioration of renal function in patients with liver disease. A possible role of endothelin-1 (ET-1) in the pathogenesis of HRS has been suggested, but a correlation between ET-1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not been shown yet. We performed longitudinal measurements of ET-1 plasma levels in four groups of patients, 5 patients with HRS before and after orthotopic liver transplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients with chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET-1 were higher in patients with HRS (19.5 ± 8.6 ng/l, P < 0.001; n = 5) compared to patients without HRS (4.9 ± 1.1 ng/l; n = 10), normals (1.2 ± 0.18 ng/l; n = 12), and patients with chronic renal failure (2.4 ± 0.4 ng/l; n = 20). Patients with HRS compared to patients without HRS had higher levels for creatinine (2.42 ± 0.6 vs. 0.89 ± 0.05 mg/dl, P < 0.05), creatinine clearance (107 ± 9 ml/min vs. 44.6 ± 5.5 ml/min, P < 0.001), and bilirubin (11.4 ± 3.8 vs. 3.7 ± 1 mg/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid decrease in ET-1 levels in patients with HRS while creatinine and bilirubin levels decreased slower. Regression analysis revealed a weak correlation between serum creatinine and ET-1 (r = 0.192, P = 0.04) and a significant correlation between serum bilirubin and ET-1 (r = 0.395, P < 0.001). The means of the ET-1 levels decreases rapidly with improvement of liver function after OLT. Levels of ET-1 correlate with excretory liver function assessed by bilirubin. The fall in ET-1 levels preceding improvement of renal function further strengthens the concept of ET-1 being a causative factor in HRS. Received: 22 July 1999/Revised: 28 January 2000/Accepted: 11 May 2000     

Five‐Year Experience With Mini‐Volume Priming in Infants ≤5 kg: Safety of Significantly Smaller Transfusion Volumes

Reducing the cardiopulmonary bypass (CPB) priming volume in congenital cardiac surgery is important because it is associated with fewer transfusions. This retrospective study was designed to compare safety and transfusion volumes between the mini‐volume priming (MP) and conventional priming (CP) methods. Between 2007 and 2012, congenital heart surgery using CPB was performed on 480 infants (≤5 kg): the MP method was used in 331 infants (MP group, 69.0%), and the CP method was used in 149 infants (CP group, 31.0%). In the MP group, narrow‐caliber (3/16″) tubing was used, and the pump heads were vertically aligned to shorten the tubing lengths. The smallest possible oxygenators and hemofilters were used, and vacuum drainage was applied. Ultrafiltration was vigorously applied during CPB to avoid excessive hemodilution. The mean age and body weight of the patients were 48 ± 41 (0–306) days and 3.8 ± 0.8 (1.3–5.0) kg, respectively. The total priming and transfusion volumes during CPB were lower in the MP group than in the CP group (141 ± 24 mL vs. 292 ± 50 mL, P < 0.001, and 82 ± 40 mL vs. 162 ± 82 mL, P < 0.001, respectively). In the MP group, the smallest priming volume was 110 mL. However, there was no significant difference in the lowest hematocrit level during CPB between the two groups (22 ± 3% vs. 22 ± 3%, P = 0.724). The incidence of postoperative neurological complications was not significantly different between the MP and CP groups (1.8% vs. 2.7%, P = 0.509). After adjustment for the Risk Adjustment for Congenital Heart Surgery category, body surface area, and age, MP was not an independent risk factor of postoperative neurological complications or early mortality (P = 0.213 and P = 0.467, respectively). The MP method reduced the priming volume to approximately 140 mL without increasing the risk of morbidity or mortality in infants ≤5 kg. The total transfusion volume during CPB was reduced by 50% without compromising hematocrit levels. We recommend the use of mini‐volume priming, which is a safe and effective method for reducing transfusion volumes.     

Effects of buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were exposed to extreme hypercapnia (Paco_2-20 kPa) at Fio₂ 0.4 for 480 min, with (n = 6) or without (n = 6) continuous infusion of isotonic buffers (bicarbonate and trometamol). Arterial pH was higher in buffered animals than controls, 7.21 ±0.01 vs 7.01±0.01 (mean ± s.e.mean, P < 0.01). Serum osmolality and Paco₂ did not differ between groups throughout the experiment. The hemodynamic response to hypercapnia was attenuated in the buffered group, who had lower heart rate, 133 ± 6 vs 189±12 min^-1 (P < 0.01), mean arterial pressure (MAP) 109 ± 4 vs 124 ± 4 mmHg (14.5 ± 0.5 vs 16.5 ± 0.5 kPa) (P < 0.05), mean pulmonary arterial pressure 16±1 vs 23 ± 1 mmHg (2.1 ±0.1 vs 3.1 ±0.1 kPa) (P < 0.01), and pulmonary vascular resistance (PVR) 249 ± 21 vs 343 ± 20 dyn s-cm^-5 (2490±210 vs 3430±200 μN-s-cm^-5) (P < 0.01), compared with the control group. Subsequently, both groups were exposed to hypercapnic hypoxemia by stepwise increases in Fio₂ (0.15, 0.10, 0.05) at 30-min intervals, while Fico₂ was kept at 0.2. PVR increased in both groups (P < 0.05) but, except for heart rate, all hemodynamic differences between the groups disappeared during hypoxia. At Fio₂ 0.15, buffered animals had higher arterial oxygen saturation (73 ± 5%) than the controls (55 ± 5%), (P < 0.05). The control animals died after 1–29 min (mean 14 min) at Fio₂ 0.10, while all buffered animals survived Fio₂ 0.10 with stable MAP (122 ± 14 mmHg (16.3 ± 1.9 kPa). The buffered animals died after 4–22 min (mean 15 min) at Fio₂ 0.05. We conclude that buffering to a pH of 7.21 attenuates the observed hemodynamic response in extreme hypercapnia and improves survival in hypercapnic hypoxemia.