G. Mellgren

Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion

BACKGROUND Hemorrhage is a major complication experienced in 10% to 35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS-induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of nitric oxide on the ECLS-induced platelet consumption and activation. METHODS Two identical in vitro ECLS circuits were primed with fresh, heparin-treated human blood and circulated for 24 hours. Nitric oxide (15, 40, or 77 ppm) was added to one of the oxygenators in each pair. Eight paired experiments were performed. Platelet count, plasma beta-thromboglobulin, platelet serotonin content, plasma nitrate, plasma cyclic guanosine monophosphate, and platelet membrane glycoprotein Ib were assayed before the start and at 0.5, 1, 3, 12, and 24 hours of perfusion. RESULTS Plasma nitrate and plasma cyclic guanosine monophosphate levels were significantly higher in the nitric oxide circuits than in the control circuits (p < 0.01). Higher platelet counts (p < 0.01) and lower beta-thromboglobulin levels (p < 0.01) were observed in the nitric oxide circuits compared with the control circuits. However, no significant differences in platelet serotonin content or platelet membrane glycoprotein Ib density were noted between the circuits. CONCLUSIONS Nitric oxide probably reduces platelet consumption and platelet activation during ECLS.

The effect of albumin priming solution on platelet activation during experimental long-term perfusion.

The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer’s solution containing human serum albumin, the other with Ringer’s solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37°C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts (p = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.

Influence of hemofiltration on plasma cytokine levels and platelet activation during extra corporeal membrane oxygenation.

OBJECTIVE Extra corporeal circulation of human blood is used daily in lifesaving procedures such as open-heart surgery and extracorporeal membrane oxygenation (ECMO). But extracorporeal circulation also induces activation of various cascade reactions in the blood. The objective of this study was to evaluate the effects of hemofiltration on cytokine release and removal as well as on platelet activation and consumption. MATERIAL AND METHODS Two complete ECMO systems, each of them holding a hollow fiber oxygenator, a bladder box, PVC tubing and a roller pump were perfused for 24 h with fresh, heparinized human blood. A hemofilter was added to one of the paired systems. Blood samples were collected from both circuits before start, and at 0.5, 1, 3, 12 and 24 h of perfusion. A total of 8 paired experiments was performed. RESULTS The plasma concentration of interleukin (IL)1beta, IL-6 and IL-8, as well as of IL-1 receptor antagonist (IL-1ra) increased over time in both systems, but consistently lower levels were observed in the filter circuits compared to the controls. Only minor parts of these cytokines could be assayed in the ultrafiltrate. No significant difference in platelet count and platelet membrane expression of glycoprotein Ib was observed between the circuits. CONCLUSIONS By adding a hemofilter to the ECMO circuit, it is possible to reduce the plasma concentration of interleukins without significantly affecting platelet activation and consumption.

Single Doppler Detection of Left to Right Shunt through the Ductus Arteriosus

ABSTRACT. Forty‐two infants and children were examined with unguided continuous and pulsed Doppler echocardiography before and/or after surgical closure of ductus arteriosus or in connection with cardiac catheterization. Presence or absence of diastolic reverse flow in the main pulmonary artery was evaluated for sensitivity and specificity to detect left to right ductus shunt. Diastolic reverse flow was detected in 15 of 16 patients with such a shunt and in 3 of 38 patients without a left to right ductus shunt. This corresponds to 94% sensitivity and 92% specifcity. It is concluded that the accuracy of a single Doppler system in diagnosing patent ductus arteriosus is comparable to the results obtained with a Doppler interfaced to M‐mode or cross‐sectional echocardiography.

Glucose metabolism and insulin secretion in children with cyanotic congenital heart disease

The aim of the study was to reveal differences in carbohydrate metabolism in children with cyanotic congenital heart diseases (CHD). Thirteen children with diseases of these kinds were investigated with regard to glucose tolerance and insulin secretion and comparisons were made with healthy controls of the same age. Investigations included an intravenous glucose tolerance test, insulin response to the glucose load in plasma and insulin secretion rate. The results reveal lower fasting glucose levels and signs of a higher insulin secretion rate in the relatively few patients in the CHD group where C‐peptide measurements were performed, but no differences in glucose tolerance. The reasons for the differences are unclear, but the chronic increases in circulating catecholamines in combination with the impaired nutritional status of these children with CHD are probably the most important factors. We conclude that these divergences in carbohydrate metabolism should be emphasized in the care of children with CHD.

Subclavian flap angioplasty with absorbable suture polydioxanone (PDS): an experimental study in growing piglets

The fate of the subclavian flap in aortoplasty was studied and a new synthetic monofilament, absorbable vascular suture (polydioxanone, PDS) was evaluated. In 11 piglets submitted to the aortic repair, the diameter of the aortic arch and descending aorta and the length and width of the subclavian flap were measured. The aortoplasty was performed with a continuous running suture of 6/0 PDS. All the animals survived and grew normally. They were sacrificed 6-26 weeks postoperatively, when the mentioned variables were reestimated. No aortic narrowing was found and no suture material was detectable in the lumen. The subclavian flap had grown uniformly in length and width. Histologic examination showed evening of the inner surface by intimal proliferation and healing of the anastomoses. There was no sign of flap destruction and tissue reaction to PDS suture was minimal, indicating normal growth and viability in all parts of the flap. The suture material was absorbed 26 weeks postoperatively. Continuous suture with absorbable PDS seems to be a good alternative for repair of aortic coarctation in early infancy.

Glucose metabolism and insulin secretion in infants with symptomatic ventricular septal defect.

ABSTRACT. Nineteen infants with symptomatic ventricular septal defect (VSD) were examined on, altogether, 26 occasions, when each was given an intravenous glucose tolerance test (IVGTT); concentrations of insulin‐ and C‐peptide in plasma were determined. Comparisons were made with 14 healthy infants of the same age. The VSD infants were growth retarded with lower weight/age and length/age ratios. Glucose tolerance as indicated by glucose fasting levels and response to intravenous glucose tolerance test, including glucose disappearance rate, did not differ between the two groups. In response to the glucose load, insulin in plasma was significantly less in VSD infants. In response to the IVGTT, insulin secretion rate calculated from C‐peptide levels in plasma was significantly elevated in the VSD group. We conclude that compared to healthy infants, those with symptomatic VSD have normal glucose tolerance, increased secretion rate of insulin, but decreased levels of circulating insulin in response to an intravenous glucose load. We suggest this is so because binding of insulin to peripheral receptors and/or insulin extraction in the liver somehow increases.

RESECTION + CAROTID FLAP PLASTY A New Surgical Technique for Newborn Children with Coarctation of the Aorta and Critical Hypoplasia of the Aortic Arch

Coarctation of the aorta with critical hypoplasia of the aortic arch is a ductus dependent malformation-complex often combined with severe intracardiac malformations with a common denominator: there is a predominance of the pulmonary circulation and a flow restriction through the ascending aorta. Coarctation of the aorta with critical hypoplasia of the aortic arch may be looked upon as a malformation bordering on hypoplastic left heart syndrome. The degree of aortic arch hypoplasia seems to mirror the severity of the intracardiac malformation. The first objective in reconstructing these hearts is to create an unobstructed flow through the aortic arch. Resection of the coarcted segment combined with carotid flap plasty is a surgical alternative which fulfils this objective. We have used the technique in premature-born and severely ill neonates where one-step total correction was considered contraindicated. Thirteen neonates were operated upon, there were no cerebral consequences referable to the carotid artery ligation and no recoarctations.

The effect of prolonged perfusion with a membrane oxygenator (PPMO) on white blood cells

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% ± 9, 72% ± 2 and 76% ± 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 ± 1.5, 32.6 ± 2.2 and 40.3 ± 8.3 x 102%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 ± 1.5, 9.7 ± 1.2 and 13.9 ± 2.1 x 106/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% ± 0.3, 23% ± 0.2 and 14% ± 0.1 at 24,48 and 72 hours respectively (p < 0.001). This study showed a serious loss in white cell rheology during PPMO, which may contribute to the plugging effect of the microvessels in clinical use and may explain the organ dysfunction seen during ECMO on the basis of inadequate tissue oxygenation and nutrition due to areas of reduced perfusion, which results in increased frequency of morbidity.

Blood cell rheologic deterioration by complement activation during experimental prolonged perfusion with membrane oxygenation

In order to understand the microcirculatory disturbances during clinical ECMO, the relation of complement activation to blood cell rheologic parameters during prolonged perfusion with membrane oxygenation was studied in 10 experiments using fresh human donor blood. The perfusion set-up was a standard ECMO circuit without a patient. Blood rheologic parameters reflecting the fluidity of blood in the microcirculation were analysed by a St Georges Filtrometer. Changes in complement fractions C3a and C5a were measured by the radio-immunoassay (RIA) technique and the TCC (terminal complement complex) by ELISA technique. Samples for complement activation and blood rheological analysis were taken at 24 hours for correlation. There were strong and significant correlations between red and white cell rheologic parameters with all complement fractions. These observations indicate that complement activation plays a significant role in the deterioration of blood rheology during extracorporeal circulation. Improvements in biocompatibility and blood protection are required if this technology is to be made safer.