Hydroxyethylstarch and gelatin solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: Colloids are often used after cardiac surgery as intravascular volume replacement therapy. Cardiac surgical patients have an increased risk of bleeding. Both hydroxyethylstarch (HES) and gelatin solutions impair haemostasis. We examined the impact and dose effect on coagulation of HES 130/0.4, gelatin, or Ringer's acetate solutions after cardiac surgery. METHODS: Forty-five patients received three boluses (each 7 ml kg(-1)) of either 6% HES 130/0.4, 4% gelatin, or Ringer's acetate solution after elective cardiac surgery. The infusion of study solution was continued in the dose 7 ml kg(-1) over the following 12 h. The total dose of study solution was 28 ml kg(-1). Hypovolaemia was treated with Ringer's acetate. Modified thromboelastometry was performed to detect coagulation disorders. RESULTS: Clot formation time was prolonged and clot strength decreased after infusion of 7, 14, and 21 ml kg(-1) of either colloid compared with the Ringer's acetate group. After infusion of 14 and 21 ml kg(-1) of Ringer's acetate, clot strength was slightly, but significantly, increased. On the first postoperative morning, clot strength was still decreased in the gelatin group in comparison with the Ringer's acetate group. Neither HES nor gelatin induced fibrinolysis. Chest tube drainage was comparable between all groups. CONCLUSIONS: Even a small dose of HES 130/0.4 or gelatin impaired clot strength after cardiac surgery in a dose-dependent fashion, but neither colloid increased blood loss.

Whole blood hypercoagulability despite anticoagulation during mechanical cardiac assist.

We report hypercoagulability despite activated partial thromboplastin time (APTT)-guided heparin treatment during Berlin Heart-supported circulation in a 38-year-old man with heart failure for 19 days. The patient was anticoagulated using unfractionated heparin, acetylsalicylic acid and dipyridamole. Contact and tissue factor-activated thromboelastometry revealed increased clot firmness, although anticoagulation assessed by APTT was in accordance with the treatment protocol. Strength of polymerized fibrin was also increased. We saw no clinical signs of thrombosis. Thromboelastometry normalized after heart transplantation. Our results suggest that hypercoagulability is due to excess fibrin formation. Monitoring anticoagulation using APTT may, therefore, be misleading during mechanical cardiac assist.

Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin.

BACKGROUND: Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients. MATERIALS AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 6% HES (mW 130 kDa, n = 15), 6% HES (MW 200 kDa, n = 15) or 4% HA (MW 69 kDa, n = 15) after on-pump cardiac surgery. RESULTS: Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. mean (SD) cardiac index was higher in HES130 [3.5 l min(-1) m(-2) (0.7) ] and HES200 [3.5 l min(-1) m(-2) (0.5)] than in HA [2.8 l min(-1) m(-2) (0.6)] group after completion of infusion (P = 0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in Ha group. At 2 hours mean (SD) base excess was higher in HES130 [0 (1.32)] than in HES200 [-1.32 (2.27) ] and HA [-2.3 (1.3)] group (P = 0.002, between the groups). CONCLUSIONS: We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion.

A comparison of the haemodynamic effects of 4% succinylated gelatin, 6% hydroxyethyl starch (200/0.5) and 4% human albumin after cardiac surgery.

BACKGROUND AND AIMS: The goal for volume replacement therapy is to maintain stable haemodynamics after cardiac surgery. We hypothesized that a short term infusion of hydroxyethyl starch results in better haemodynamic response than an infusion of lower molecular weight gelatin. MATERIAL AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 4% succinylated gelatin (GEL) or 6% hydroxyethyl starch (HES) or 4% human albumin (HA) after cardiac surgery. RESULTS AND CONCLUSIONS: Pulmonary capillary wedge pressure was more increased in GEL and HES groups [mean (SD) 153% (54) and 168% (57) of pre-infusion value] than in HA group [122% (23)] (P = 0.031) after completion of infusion, but no differences in cardiac index (CI) and stroke volume index (SVI) were observed. At 2 and 18 hours after end of study infusions SVI was more increased in HES [143% (38) and 148% (41) of pre-infusion values] and HA [143% (35) and 163% (42) of pre-infusion values] groups than in GEL [116% (23) and 125% (30)] group (P = 0.047 at 2 hours and P = 0.033 at 18 hours). In early postoperative phase after cardiac surgery, HES and HA infusions improve haemodynamics more and longer period than GEL infusion.

Vasopressin, when added to norepinephrine, was not associated with increased predicted mortality after cardiac surgery.

BACKGROUND AND AIMS: Arginin vasopressin (AVP) is a potent vasoconstrictor which has been used in vasodilatory shock when therapy with catecholamines and fluids has failed. In this study we evaluated the association of AVP with organ failure and mortality in cardiac surgical patients suffering from vasodilatory shock refractory to norepinephrine (NE) treatment. MATERIAL AND METHODS: Cardiac surgical patients who received AVP in addition to NE (N=33, AVP-group) and 33 control patients (NE group) who were treated with an equal dose of NE compared with AVP patients when AVP infusion started. Data on preoperative risk factors according to EuroSCORE and predicted mortality calculated by logistic EuroSCORE were collected preoperatively. Data on hemodynamics, organ dysfunctions, length of intensive care unit stay and mortality were collected. RESULTS: EuroSCORE did not differ between the groups, AVP:10.4 +/- 3.9 vs. NE 8.9 +/- 4.0. Observed 30 day mortality was lower than predicted in both groups, AVP: 7 (21.7%) vs. predicted mortality 25.9% and NE: 2 (6.1%) vs. 16.0%, respectively. There were more renal complications (36.4% vs. 9.1%, p = 0.008) and infections (30.3% vs. 3.0%, p = 0.003) in patients receiving AVP. Cardiovascular complications did not differ between the groups. CONCLUSIONS: In this prospectively observed cohort of cardiac surgical patients, AVP did not increase mortality predicted by Euroscore. Anyhow renal and infection complications were common.

Mycotrophy of crops in rotation and soil amendment with peat influence the abundance and effectiveness of indigenous arbuscular mycorrhizal fungi in field soil.

Mycotrophy of previous crops has been shown to have an impact on arbuscular mycorrhizal fungi (AMF), and the growth and productivity of succeeding crops. We studied the impact of 3 years of cultivation of eight crops with different degrees of mycotrophy, including mycorrhizal (strawberry, rye, timothy, onion, caraway) and non-mycorrhizal (turnip rape, buckwheat, fiddleneck) hosts, as well as the impact of peat amendment, on the effectiveness, amount and diversity of indigenous AMF. A field experiment having a split-plot design with peat amendment as the main plot, crop cultivation as a sub-plot and three replications, was carried out on silt clay mineral soil in 1999-2001. A well-humified dark peat was applied immediately before establishment of the field experiment. Each year, the relative mycorrhizal effectiveness of soil collected in September, in terms of shoot dry weight (RME(DW)), was determined in a bioassay. In the 3rd year of the experiment, AMF spores were also extracted and identified from the field soil. Expressed as the mean of 3 years of cropping in unamended soil, the mycorrhizal crops strawberry and caraway maintained RME(DW) most effectively, while the values were lower in the non-host crops buckwheat, turnip rape and fiddleneck. In addition, the numbers of AM spores detected in soil were considerably greater during 3 years of strawberry cultivation. In soil under caraway, there were high numbers of AM spores compared to the other crops. In soil amended with peat, the situation was in some cases opposite of that of unamended soil; RME(DW) was highest in rye and onion and lowest in strawberry and caraway. The reasons behind the negative impact of peat on mycorrhizal effectiveness in strawberry soil may be due to the microbiological properties of peat. The importance of including mycotrophic species in crop rotations for maintaining high soil quality and for increasing yields of subsequent crops is discussed.

L protein, the RNA-dependent RNA polymerase of hantaviruses.

L protein of hantaviruses is the RNA transcriptase and replicase that transcribes mRNAs and replicates the genomic RNA using antigenomic RNA as an intermediate. It also appears to have endonuclease activity. In this review, the current knowledge on the hantavirus L protein is presented including sequence motifs conserved in RNA polymerases, mechanisms of RNA synthesis and also the most recent findings on homologous RNA recombination and membrane association.

L-Arginine in lung graft preservation and reperfusion.

BACKGROUND: Inhaled nitric oxide has been shown to ameliorate early lung graft dysfunction. It improves oxygenation by inducing pulmonary vasodilatation in well-ventilated lung areas, and it also modulates leukocyte-endothelium interactions. We used a porcine, single lung transplantation model to evaluate whether the benefits of exogenously administered gas could be achieved easier by adding L-arginine, the substrate of endogenous nitric oxide synthesis, as an additive to the flush solution and intravenously during reperfusion. METHODS: Six pig lungs were flushed with modified Euro-Collins solutions containing L-arginine (2 g/liter). After cold (4 degrees C) storage, the left lung was transplanted. Ischemic time was 260 minutes. The recipients received intravenous boluses of L-arginine (30 mg/kg), followed by infusion (20 mg/kg/min) during the first 30 minutes of reperfusion. Six control animals received saline as placebo. We measured the blood flow and pulmonary vascular resistance (PVR) in the transplanted and in the native lung using a right heart bypass model. We measured blood gases, leukocyte counts, plasma free-radical trapping capacity, and diene conjugates in pulmonary venous blood and myeloperoxidase activity of the lung tissue. RESULTS: Pulmonary vascular resistance was 4 to 5-fold higher in the transplanted lung than in the native lung, which received 80% of the total blood flow. L-arginine reduced PVR by 30% in the native lung (p < 0.001), but not in the transplanted lung. L-arginine had no effect on oxygenation or carbon dioxide exchange of the transplanted lung. Nor did L-arginine treatment have any effect on leukocyte sequestration or myeloperoxidase activity in the transplanted lung. The plasma antioxidant capacity in venous blood of the transplanted lung almost doubled shortly during early reperfusion without influence of L-arginine. CONCLUSIONS: L-arginine reduced PVR in the native lung but did not improve pulmonary hemodynamics, gas exchange, or reduce leukocyte sequestration of the transplanted lung.

Inhaled NO and prostacyclin during porcine single lung transplantation.

BACKGROUND: Increased pulmonary vascular resistance (PVR) and decreased arterial oxygenation frequently complicate lung transplantation. Inhaled nitric oxide (NO) and aerosolized prostacyclin (PGI2) both dilate the pulmonary vasculature and improve oxygenation in adult respiratory distress syndrome. We investigated whether similar effects would occur during early reperfusion of a lung graft. METHODS: Eighteen pigs underwent left lung transplantation. We measured blood flow distribution, mean pulmonary artery pressure, PVR, and gas exchange in each lung separately. Animals were randomized into three groups to receive NO (10 ppm/30 minutes, 40 ppm/30 minutes), nebulized PGI2 (25 microg/mL/30 minutes, 50 microg/mL/30 minutes), or no drugs (control). RESULTS: In the transplanted lung, PVR was significantly higher than in the native lung. Pulmonary vascular resistance of the transplanted lung was lower in the NO and PGI2 groups in comparison with the control group. During the first hour of inhalation, NO decreased PVR more than PGI2. Neither drug improved oxygenation in the graft. CONCLUSIONS: Nitric oxide and PGI2 decreased PVR of the transplanted lung slightly, but the effect did not produce a normal pressure in pulmonary vasculature.

Donor lung pretreatment with prostaglandin E(1) does not improve lung graft preservation.

Prostaglandin E(1) (PGE(1)) is widely used to improve early graft function after lung transplantation, but some studies have questioned its benefits. Therefore we evaluated the effect of donor pretreatment with PGE(1) in our porcine model of single lung transplantation. Donors received PGE(1) or placebo intravenously before flushing the pulmonary artery with modified Euro-Collins solution. After cold storage, the excised left lung was transplanted. Ischemic time was 4 h. We used our right side heart bypass model to measure standardized pulmonary vascular resistance and to study blood flow distribution between recipient's native and transplanted lung. Systemic and pulmonary hemodynamics and gas exchange were also measured. After transplantation, pulmonary vascular resistance was significantly higher in the transplanted lung, which received only one fourth of the total pulmonary blood flow. PGE(1) pretreatment did not improve pulmonary hemodynamic parameters, or gas exchange.

Completion of the Tula hantavirus genome sequence: properties of the L segment and heterogeneity found in the 3' termini of S and L genome RNAs.

In this study the L segment and the 5' and 3' termini of the S, M and L segments of the prototype Tula hantavirus (TUL) were sequenced, thus completing the first determination of the genome sequence of a hantavirus that has not been linked to any human disease. The TUL L segment comprises 6541 nt with one ORF of 6459 nt in the antigenome sense. This ORF potentially encodes a 2153 aa protein with a predicted molecular mass of 247 kDa. The amino acid sequence includes all the motifs conserved in RNA-dependent RNA polymerases. The 5' termini of all three genome RNAs (vRNAs) had the expected sequences conserved in hantaviruses. The 3' termini of M vRNAs were also conserved. However, the 3' termini of S and L vRNAs were heterogeneous as most of the sequenced 3' termini had either deletions of 1 to 22 nt or an extra 1 to 3 nt. No increase in the level of heterogeneity was seen in vRNAs of virions collected 3, 6, 9 and 12 days post-infection, suggesting that the heterogeneity already exists at the early stages of infection. The S and L vRNAs from infected cells had more truncated 3' termini than vRNAs from pelleted virus. Heterogeneity of the 3' termini of genome RNAs could decrease the efficiency of antigenome and mRNA syntheses and contribute to the slow growth observed for TUL and other hantaviruses in cell culture.

Puumala hantavirus genome in patients with nephropathia epidemica: correlation of PCR positivity with HLA haplotype and link to viral sequences in local rodents.

Reverse transcription-PCR was used to analyze specimens from 20 Finnish nephropathia epidemica (NE) patients hospitalized during the period from October 1994 to January 1995. Blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of Puumala hantavirus (PUU). PCR positivity of the specimens from the patients correlated well with the HLA-DRB1*0301 and HLA B8 alleles, which previously were shown to associate with severe courses of NE. Genetic analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.

In vitro pulmonary arterial relaxation after experimental lung transplantation with extracorporeal circulation.

OBJECTIVE: In search of an agent to attenuate the increased pulmonary vascular resistance after lung transplantation with extracorporeal circulation, we investigated contractions and relaxations of isolated porcine pulmonary arterial rings in organ chambers. METHODS: Rings of arteries from three groups were studied. Rings from the heart-lung block were studied immediately after Euro-Collins flush (n = 6). Rings from the recipient's native (n = 5) and transplanted (n = 5) lung were studied after 3 h of right heart bypass following transplantation. The duration of cold ischemia of the transplanted lung was 3-4 h. Contractions to potassium chloride and phenylephrine were measured. In order to study relaxations, the rings were preconstricted with phenylephrine. Relaxations to acetylcholine, adenosine diphosphate and isoproterenol were determined in rings with endothelium, and relaxations to sodium nitroprusside in rings without endothelium. RESULTS: Sodium nitroprusside induced complete relaxations (100%) in rings of arteries from all three groups. Relaxations to acetylcholine and adenosine diphosphate were comparable among the three groups, but relaxations to isoproterenol were significantly depressed in pulmonary artery rings from the transplanted lung, compared with those from the native lung. CONCLUSIONS: Lung transplantation with extracorporeal circulation is associated with depressed beta-receptor-mediated vasodilation, but the pulmonary vascular smooth muscle cell's ability to relax is not affected.

Isolation and characterization of Tula virus, a distinct serotype in the genus Hantavirus, family Bunyaviridae.

A Vero E6 cell culture isolate of Tula virus (TUL), a hantavirus first detected in European common voles (Microtus arvalis and M. rossiaemeridionalis) by RT-PCR was obtained after initial passaging of TUL-infected vole lung samples in laboratory-colonized M. arvalis. TUL was defined as a classical serotype by a cross-focus-reduction neutralization test (FRNT) and was also shown to be distinct from other hantaviruses by haemagglutination inhibition assay. The sequences of S, M and partial L genome segments of the isolate were determined: the S segment was 99.9% identical to the original rodent-derived sequence. Serological evidence for a previous TUL infection was obtained from the serum of a blood donor living near a TUL focus in Moravia, Czech Republic, showing at least a 16-fold higher FRNT titre to TUL as compared to Puumala or other hantaviruses.

Abnormal in vivo response to sodium nitroprusside after porcine single lung transplantation.

The chronic increase of pulmonary vascular resistance after lung transplantation is only partly due to an active increase in baseline vasomotor tone, but the nature of the acute pulmonary hypertension after ischemia and reperfusion is not known. We studied the effects of sodium nitroprusside on pulmonary hemodynamics during reperfusion in porcine left lung allotransplants. In twelve pigs (weight: 18 to 24 kg) pulmonary arteries of the native and the transplanted lung were cannulated for right-heart bypass. The total blood flow was 2 L/min. Flow distribution between the lungs was measured at equal mean pulmonary artery pressure, and pulmonary vascular resistance at equal and constant flow-i.e., 1 L/min to each lung. After baseline measurements sodium nitroprusside (1, 3, and 9 microg/kg/min) was administered to six animals (SNP group). The control group (n=6) received an equal amount of the vehicle. After 30 min of discontinuation of the drug infusion, the schedule was repeated. In the transplanted lung, pulmonary vascular resistance decreased in all animals during the first hour of reperfusion. During the second drug infusion pulmonary vascular resistance was significantly lower in the SNP group compared with the control group only at the highest infusion rate of the drug (9 microg/kg/min), which also induced a 44% decrease in systemic vascular resistance. Arterial oxygen tension remained comparable in the two groups throughout the study. Our data suggest that other factors besides active vasoconstriction may contribute to the acute increase of pulmonary vascular resistance after lung transplantation.

Thromboxane receptor blockade does not attenuate pulmonary pressor response in porcine single lung transplantation.

BACKGROUND: The ischemia-reperfusion lung injury is characterized by increased pulmonary vascular resistance, edema, and subsequent deterioration of oxygenation. Other models of acute lung injury suggest that thromboxane A2 may contribute to the pulmonary hypertension after transplantation. METHODS: We studied the effects of the selective thromboxane A2 receptor antagonist SQ 30741 on pulmonary hemodynamics and gas exchange in porcine single lung transplantation using extracorporeal circulation (right heart bypass) with separate cannulations of the right and left pulmonary arteries. Pulmonary vascular resistance was measured at equal and constant flow to each lung. Flow distribution between the lungs was registered at equal pulmonary artery pressures. Twelve pigs (weight 17 to 23 kg) were studied. At the onset of reperfusion a bolus dose of the drug (5 mg/kg) was injected into both pulmonary arteries followed by an infusion (5 mg/kg/hr) for 1 hour (SQ group, n = 6). The control group (n = 6) received an equal amount of vehicle. The systemic and pulmonary hemodynamics and blood gas values were registered during 2 hours of reperfusion. RESULTS: The pulmonary vascular resistance of the transplanted lung was significantly higher compared with the native lung (p < 0.001). Administration of SQ 30741 failed to ameliorate the pulmonary pressor response of the graft in comparison with the control group. No difference was found in the systemic arterial oxygen tension between the two groups. CONCLUSIONS: Thromboxane does not seem to be among the principal mediators in the pulmonary hypertension after transplantation.

Prostaglandin E1 or prostacyclin in Euro-Collins solution fails to improve lung preservation.

BACKGROUND: In search of the ideal composition of the flush solution for pulmonary preservation, we studied the effects of prostaglandin E1 (PGE1) and prostacyclin as an additive to Euro-Collins solution (ECS) on pulmonary hemodynamics and gas exchange in a porcine single lung transplantation model using extracorporeal circulation and right heart bypass. METHODS: Twenty-two pigs served as donors. The animals were randomized to receive either modified ECS alone (control group, n = 8), ECS with 100 micrograms/L of PGE1 (PGE1 group, n = 6), or ECS with 200 micrograms/L of prostacyclin (prostacyclin group, n = 8). Left lung transplantation was performed in 22 recipients after approximately 4 hours of cold ischemia. RESULTS: Carbon dioxide elimination was significantly depressed in the two prostaglandin groups, and the use of PGE1 was associated with a significant decrease in arterial oxygen tension compared with the control group. Both drugs were inefficient in alleviating the increase in pulmonary vascular resistance after transplantation. CONCLUSION: The use of prostaglandins as constituents of the flush solution was not followed by any improvement of early graft function after cold ischemia.

Pulmonary vasodilatory properties of prostaglandin E1 are blunted after experimental single lung transplantation.

BACKGROUND: Pulmonary dysfunction and right heart failure are still a common clinical problem after single lung transplantation. METHODS: In this study we investigated the pulmonary vasodilatory properties of prostaglandin E1 in pigs during the first 4 hours after left lung allotransplantation. With the use of extracorporeal circulation and total right heart bypass, the right and left pulmonary arteries could be individually perfused and the drug effect in each lung separately analyzed either at equal blood pressures or at equal blood flows in the pulmonary arteries. Twelve animals received in a randomized double-blind fashion either saline solution or an increasing prostaglandin E1 infusion (10, 25, 50, and 100 ng/kg/min; 15 minutes each). After a drug-free period of 75 minutes, the infusion schedule with 25, 50, and 100 ng/kg/min was repeated. RESULTS: During the first part of the study the highest dose of prostaglandin E1 decreased the mean systemic arterial pressure by 25%, but an almost similar decrease occurred in the control animals. During the second infusion period a 28% decrease was observed only in the animals treated with prostaglandin E1. None of the infusions was able to decrease pulmonary vascular resistance. Instead prostaglandin E1 diverted two thirds of the pulmonary blood flow toward the native lung, and this diversion manifested itself as an earlier improvement of the arterial oxygen tension in the drug-treated animals. The end-tidal carbon dioxide values measured from each lung corresponded to those from the common expiratory limb of the system, but there was a distinct gradient in the range of 14 to 20 mm Hg between the arterial and end-tidal carbon dioxide values. CONCLUSIONS: We conclude that prostaglandin E1, in doses tolerated by the systemic circulation, is ineffective in the treatment of the increased pulmonary vascular resistance after single lung transplantation.

Successful treatment of ARDS with two doses of synthetic surfactant.

A 50-year-old man with adult respiratory distress syndrome (ARDS) was successfully treated with synthetic surfactant. The therapy rapidly improved the respiratory function; it also increased the release of endogenous surfactant. Synthetic surfactant may thus be of value in the treatment of ARDS.