Relocation of patients after cardiac surgery: is it worth the effort?

BACKGROUND: Fast-track protocols may facilitate early patient discharge from the site of surgery through the implementation of more expedient pathways. However, costs may merely be shifted towards other parts of the health care system. We aimed to investigate the consequence of patient transfers on overall hospitalisation, follow-up and readmission rate after cardiac surgery. METHODS: A single-centre descriptive cohort study using prospectively entered registry data. The study included 4,515 patients who underwent cardiac surgery at Aarhus University Hospital during the period 1 April 2006 to 31 December 2012. Patients were grouped and analysed based on type of discharge: Directly from site of surgery or after transfer to a regional hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register. RESULTS: Median overall length of stay was 9 days (7.0;14.4). Transferred patients had longer length of stay, median difference of 2.0 days, p < 0.001. Time to first outpatient consultation was 41(30;58) days in transferred patients vs. 45(29;74) days, p < 0.001. 18.6% was readmitted within 30 days. Mean time to readmission was 18.4 ± 6.4 days. Median length of readmission was 3(1,6) days. There was no difference in readmissions between groups. Leading cause of readmission was cardiovascular disease with 48%. CONCLUSION: Transfer of patients does not overtly reduce health care costs, but overall LOS and time to first outpatient consultation are substantially longer in patients transferred to secondary hospitals than in patients discharged directly. Readmission rate is high during the month after surgery, but with no difference between groups.

The neonatal but not the mature heart adapts to acute tachycardia by beneficial modification of the force-frequency relationship.

The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n = 8 neonate pigs in the 0.05 mg/kg group and n = 7 adult pigs in the 0.025 mg/kg group) and paced for 90 min at 25 bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30 bpm greater than baseline (P < 0.03). There was no vertical shift; thus, force at 150 bpm decreased (P < 0.03) and force at 300 beats/min increased (P < 0.08). In adult control pigs, FFR shifted downward (P < 0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses.

Infants with congenital heart defects have reduced brain volumes.

Children with congenital heart defects (CHDs) have increased risk of cognitive disabilities for reasons not fully understood. Previous studies have indicated signs of disrupted fetal brain growth from mid-gestation measured with ultrasound and magnetic resonance imaging (MRI) and infants with CHDs have decreased brain volumes at birth. We measured the total and regional brain volumes of infants with and without CHDs using MRI to investigate, if certain areas of the brain are at particular risk of disrupted growth. MRI brain volumetry analyses were performed on 20 infants; 10 with- (postmenstrual age 39-54 weeks, mean 44 weeks + 5 days) and 10 without CHDs (postmenstrual age 39-52 weeks, mean 43 weeks + 5 days). In six infants with- and eight infants without CHDs grey and white matter were also differentiated. Infants with CHDs had smaller brains (48 ml smaller; 95% CI, 6.1-90; p = 0.03), cerebrums (37.8 ml smaller; 95% CI, 0.8-74.8; p = 0.04), and cerebral grey matter (25.8 ml smaller; 95% CI, 3.5-48; p = 0.03) than infants without CHD. Brain volume differences observed within weeks after birth in children with CHDs confirm that the brain impact, which increase the risk of cognitive disabilities, may begin during pregnancy.

Chronic pain in adults after thoracotomy in childhood or youth.

BACKGROUND: Chronic pain is common after thoracotomy with reported prevalence rates of 20-60%. The pain may be caused by damage to the intercostal nerves during surgery. Some studies have suggested that young age at the time of surgery reduces the risk of developing chronic pain. So far, no studies have examined if children and adolescents develop chronic pain after thoracotomy. METHODS: Eighty-eight patients, mean (sd) age 39.3 (7.7) yr, who underwent thoracotomy between the age of 0 and 25 yr were asked to recall the duration of postoperative pain and-if pain was still present-to describe intensity and character of pain. In addition, all patients underwent quantitative sensory testing. RESULTS: Fourteen patients (16%) recalled that their postoperative pain had lasted for more than 3 months: one (3.2%) patient in the youngest group (0-6 yr), seven (19.4%) patients in the age group 7-12 yr, and six (28.5%) patients in the age group 13-25 yr (P=0.03). Three out of the 14 patients, who were 11, 11, and 18 yr of age at the time of surgery, still had pain at present. Quantitative sensory testing revealed hypo- and hyperphenomena in most patients, including those with persistent pain. Tactile detection thresholds and pressure detection thresholds were significantly higher on the operated side when compared with the contralateral side (n=88; P<0.001). CONCLUSIONS: The risk of developing chronic pain after thoracotomy seems to be lower if surgery is performed at a young age. Pain after thoracotomy is likely to be of neuropathic origin.

Clinical outcome in children with acute renal failure treated with peritoneal dialysis after surgery for congenital heart disease.

The present single-center cohort study was based on a clinical intensive care unit database containing data on 1128 consecutive children undergoing their first operation for congenital heart disease between 1993 and 2002 at Aarhus University Hospital, Skejby, Denmark. A total of 130 (11.5%) children developed postoperative acute renal failure (ARF) managed with peritoneal dialysis (PD). Logistic regression analysis was used to examine risk factors for complications related to PD and to compare mortality between ARF and non-ARF patients controlling for potential confounding factors. A total of 43 complications related to PD were registered in 27 (20.8%) patients. Major complications were seen in eight (6.2%) patients, and only two (1.5%) patients were switched to hemodialysis after peritonitis and hemicolectomy due to bowel perforation. The main risk factors for complications to PD were duration of PD, high RACHS-1 score (Risk Adjusted Classification for Congenital Heart Surgery), and hyperkalemia at initiation of PD. Overall, in-hospital mortality was 6.8% (76/1128). Mortality of ARF patients was 20.0% compared to 5.0% among non-ARF patients (adjusted odds ratio=1.91, 95% confidence interval=1.10-3.36). After stratification, ARF was strongly associated with increased mortality in the subgroups of patients with the lowest overall risk of dying (age> or =1 year, body weight> or =5 kg, RACHS-1 score <3, and no preoperative cyanosis). For patients at high risk of dying (age <1 year, body weight <5 kg, RACHS-1 score> or =3, cardiopulmonary bypass time> or =60 min, and preoperative cyanosis), the association between ARF and mortality was substantially weaker. In conclusion, postoperative ARF was associated with increased mortality in children operated for congenital heart disease. Major complications to PD were few, and our data strongly support that PD is a simple, safe, feasible, and robust dialysis modality for the management of ARF in children.

Effects of exercise and respiration on blood flow in total cavopulmonary connection: a real-time magnetic resonance flow study.

BACKGROUND: Little is known about blood flow and its relationship to respiration during exercise in patients with total cavopulmonary connection (TCPC). METHODS AND RESULTS: We studied 11 patients 12.4+/-4.6 years (mean+/-SD) of age 5.9+/-2.8 years (mean+/-SD) after TCPC operation. Real-time MRI was used to measure blood flow in the superior vena cava (SVC), inferior vena cava (IVC), and ascending aorta under inspiration and expiration during supine lower-limb exercise (rest, 0.5 and 1.0 W/kg) on an ergometer bicycle. IVC and aortic flow increased from 1.60+/-0.52 and 2.99+/-0.83 L/min per m2 at rest to 2.58+/-0.71 and 3.97+/-1.20 L/min per m2 at 0.5 W/kg and to 3.25+/-1.23 and 4.62+/-1.49 L/min per m2 at 1.0 W/kg (P< or =0.05). SVC flow remained unchanged. Resting flow in the IVC was greater during inspiration (2.99+/-1.25 L/min per m2) than during expiration (0.83+/-0.44 L/min per m2) (inspiratory/mean flow ratio, 1.9+/-0.5), and retrograde flow was present during expiration (11+/-12% of mean flow). The predominance of inspiratory flow in IVC diminished with exercise to an inspiratory/mean flow ratio of 1.5+/-0.2 (P< or =0.05) and 1.4+/-0.3 at 0.5 and 1.0 W/kg, respectively. CONCLUSIONS: In the TCPC, circulation IVC and aortic but not SVC flows increase with supine leg exercise. Inspiration facilitates IVC flow at rest but less so during exercise, when the peripheral pump seems to be more important.

Maternal hyperglycemia improves fetal cardiac function during tachycardia-induced heart failure in pigs.

BACKGROUND: Fetal tachycardia often leads to cardiac failure, which in experimental settings can be prevented by direct fetal glucose-insulin administration. In this study, we hypothesize that similar effects can be obtained indirectly by inducing maternal hyperglycemia. METHODS AND RESULTS: Systolic and diastolic indices (dP/dt(max) and tau) of left ventricular function were measured by use of high-fidelity catheters during 180 minutes of aggressive atrial pacing ( approximately 300 bpm) in 12 preterm porcine fetuses. In 6 fetuses, maternal hyperglycemia (15 mmol/L) was induced for the last 120 minutes of pacing. The remaining fetuses served as controls. Glucose, insulin, and free fatty acid levels were determined, as was fetal myocardial glycogen content. Maternal glucose infusion led to significant fetal hyperglycemia and hyperinsulinemia but did not change the inherently low fetal levels of free fatty acids. There were no differences between groups with regard to dP/dt(max) (1025+/-226 and 1037+/-207 mm Hg, P=NS) and tau (20.6+/-2.0 and 21.4+/-1.6 ms, P=NS) at baseline (100%). During the 180 minutes of pacing, systolic function (dP/dt(max)) and diastolic function (tau) deteriorated more in the control group than in the hyperglycemic group (P<0.001 for both). At 180 minutes, dP/dt(max) was 62+/-18% of baseline in controls and 85+/-11% in hyperglycemic fetuses (P=0.03), and tau was 117+/-12% and 98+/-4%, respectively (P=0.004). CONCLUSIONS: Induced maternal hyperglycemia improves fetal cardiac function during fetal tachycardia and suggests a possible additional therapeutic option to improve the function of the failing fetal heart before or during antiarrhythmic therapy. The findings may be relevant in fetal heart failure in general.

The effect of changing excitation frequency on parallel conductance in different sized hearts.

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.

Atrial fibrillation and stroke in adult patients with atrial septal defect and the long-term effect of closure.

OBJECTIVE: To estimate the risk of atrial fibrillation (AF) and stroke and the impact of closure in patients with atrial septal defect (ASD) compared with a general population cohort. METHODS: All adult Danish patients (>18 years) diagnosed with ASD from 1977 to 2009 (N=1168) were identified through population-based registries. Using Cox regression, we compared ASD patients' risk of AF and stroke with an age-matched and gender-matched comparison cohort. We computed prevalence proportions of anticoagulation and antiarrhythmic medicine use before and after closure and described stroke-related mortality. RESULTS: Median follow-up was 9.6 years (range 1-33 years). Patients with ASD had a higher risk of first-time AF (adjusted HR 8.2; 95% CI 6.6 to 10.2) after closure than the comparison cohort, but with no difference between transcatheter and surgical closure (HR 1.5, 95% CI 0.6 to 3.5). Patients without prevalent AF had a 10-year cumulative incidence of AF of 11% (95% CI 9% to 14%) after closure compared with 2% (95% CI 1.8% to 2.5%) in the comparison cohort. Patients with ASD with prevalent AF continued to use anticoagulation medicine after closure/diagnosis. Patients with ASD had increased risk of stroke without closure (adjusted HR 2.6; 95% CI 1.4 to 3.0) and with closure (adjusted HR 2.0; 95% CI 1.4 to 2.7). Risk of stroke after closure was related to AF (HR adjusted for AF 1.3; 95% CI 0.9 to 1.9). CONCLUSIONS: Patients with ASD had a higher risk of first-time AF after closure than the comparison cohort. There was no effect of closure on the use of AF-related medicine in patients with prevalent AF.

High pulse pressure is not associated with abnormal activation of the renin-angiotensin-aldosterone system in repaired aortic coarctation.

We investigated the relationship between pulse pressure (PP)--a surrogate marker of arterial stiffness-and activity of the renin-angiotensin-aldosterone system (RAAS) in adult patients with repaired coarctation and normal left ventricular (LV) function. A total of 114 patients (44 (26-74) years, 13 (0.1-40) years at repair) and 20 healthy controls were examined with 24-h ambulatory blood pressure monitoring, echocardiography, vasoactive hormone levels and magnetic resonance of the thoracic aorta. Forty-one patients (36%) were taking antihypertensives (28 RAAS inhibitors). Fifty-one had mean 24-h blood pressures >130/80 mm Hg. Hypertension was not associated with age at repair (P=0.257). Patients had higher PP and LV mass compared with controls (52±11 vs. 45±5 mm Hg and 221±71 vs. 154±55 g, respectively; both P<0.05). Differences were more pronounced in the presence of recoarctation, but independently of RAA levels. Even normotensive patients had higher LV mass than controls. LV mass and recoarctation were correlated with PP levels. In conclusion, adult patients with repaired coarctation have increased PP and LV mass compared with controls. PP increased with increasing recoarctation. Hypertension was present also in the absence of recoarctation. These changes could not be explained by abnormal activation of the RAAS.

A new model for evaluation of thrombosis and ischaemia/reperfusion injury.

BACKGROUND: The purpose of the present study was to describe infarct size and platelet accumulation when reperfusion injury was combined with a thrombogenic lesion in the coronary artery. The left anterior descending artery was damaged in 11 pigs and subsequently occluded proximal to the lesion for 50 min, followed by 4 h of reperfusion. RESULTS: The infarct size/area at risk was 40 (35 63)%. Infarct size correlated with troponin-T-3 h (p=0.85, p<0.002), but not with creatine kinase-3 h. Platelet aggregation decreased by 34% (p<0.01) at 15 min of reperfusion, but returned to baseline. Platelet accumulation in the left ventricle was significantly higher in the area at risk (194 (157-206)%) compared to the right ventricle (137 (120-142)%); p<0.05). CONCLUSION: A decreased platelet reactivity and increased accumulation of platelets in the area at risk indicates that activated platelets become entrapped in the myocardium. Troponin-T was a better marker of myocardial damage than creatine kinase in this in vivo model with pigs.

Differential release of endothelin in myocutaneous island flaps in response to gradually insetting venous stasis or arterial ischemia.

Endothelin (ET) provokes strong and sustained contraction in preparations of isolated vascular smooth muscle, and the production of ET is thought to increase secondary to increased wall shear stress and hypoxia. The release of ET and blood flow distribution between arteriovenous shunts and capillaries were studied in autoperfused myocutaneous pig island flaps during graded arterial or venous blood flow reduction (N = 12). A group comprising four flaps was not exposed to blood flow reduction and served as controls. Total flap blood flow (venous outflow [VO]) was reduced in 1-hour periods to 50%, 25%, and 0%. Downregulation of VO caused a lower capillary blood flow (CBF) at 25% (P < .05) and at 50% (P < .05) in flaps exposed to venous stasis as compared with flaps with arterial ischemia. The reduction in blood flow was paralleled by decreasing oxygen consumption, although flaps with venous stasis had lower oxygen consumption than flaps exposed to arterial ischemia (P < .05). ET was found to be released from these island flaps before blood flow was reduced. Gradual arterial clamping caused a statistically significant (P < .05) decrease in the release of ET from 8.7 +/- 1.3 fmol/min before ischemia to 4.1 +/- 1.7 at 50% blood flow and 4.1 +/- 1.0 at 25% blood flow. In contrast, the release of ET with venous stasis remained unchanged at a level of 7.5 +/- 1.6 fmol/min before blood flow reduction, 7.3 +/- 0.7 at 50% blood flow, and 8.5 +/- 1.6 at 25% blood flow. These data suggest a relationship between CBF, intravascular pressure, and ET production.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary and caval flow dynamics after total cavopulmonary connection.

OBJECTIVE: To assess flow dynamics after total cavopulmonary connection (TCPC). DESIGN: Cross-sectional study. SETTING: Aarhus University Hospital. PATIENTS: Seven patients (mean age 9 (4-18) years) who had previously undergone a lateral tunnel TCPC mean 2 (0. 3-5) years earlier. INTERVENTIONS: Pressure recordings (cardiac catheterisation), flow volume, and temporal changes of flow in the lateral tunnel, superior vena cava, and right and left pulmonary arteries (magnetic resonance velocity mapping). RESULTS: Superior vena cava flow was similar to lateral tunnel flow (1.7 (0.6-1.9) v 1. 3 (0.9-2.4) l/min*m2) (NS), and right pulmonary artery flow was higher than left pulmonary artery flow (1.7 (0.6-4.3) v 1.1 (0.8-2. 5) l/min*m2, p < 0.05). The flow pulsatility index was highest in the lateral tunnel (2.0 (1.1-8.5)), lowest in the superior vena cava (0.8 (0.5-2.4)), and intermediate in the left and right pulmonary arteries (1.6 (0.9-2.0) and 1.2 (0.4-1.9), respectively). Flow and pressure waveforms were biphasic with maxima in atrial systole and late ventricular systole. CONCLUSIONS: Following a standard lateral tunnel TCPC, flow returning via the superior vena cava is not lower than flow returning via the inferior vena cava as otherwise seen in healthy subjects; flow distribution to the pulmonary arteries is optimal; and some pulsatility is preserved primarily in the lateral tunnel and the corresponding pulmonary artery. This study provides in vivo data for future in vitro and computer model studies.

Intravenously and topically applied magnesium in the prevention of arterial thrombosis.

Magnesium (Mg) has been shown to reduce platelet aggregation both in vitro and ex vivo, and this antiplatelet effect may be advantageous in the prevention of arterial thrombosis. Previous animal studies have shown an antithrombotic effect of Mg also in vivo, but mainly with higher Mg concentrations ( approximately 3.0-4.0 mM). The objectives of the present study were to evaluate the antithrombotic effect of (1) intravenous Mg at a lower and clinically more relevant concentration and (2) topically applied Mg. The study comprised 30 male rats, randomly assigned into 3 groups: (1) placebo group, (2) intravenous Mg group, and (3) topical Mg group. A thrombogenic lesion was established by making a standardised arteriotomy in the right femoral artery. The vessel was transilluminated and thrombus formation was visualised dynamically by in vivo microscopy and recorded on videotapes. Thrombus area was measured after ended experiment by computer-assisted image analysis. Intravenously administered Mg, elevating the S-Mg level to 2.2 mmol/L, significantly reduced the mean thrombus area (p<0.05) compared to the control group. Topically applied Mg significantly decreased the maximum thrombus area, without any increase in S-Mg level (p<0.05). The Mg-treated groups showed no increase in bleeding complications. A transient fall in blood pressure was seen in the systemic Mg group, but blood pressures were not significantly different between any of the groups at the end of the experiment. In conclusion, topically as well as intravenously infused Mg reduce arterial thrombus formation in this in vivo rat model without compromising haemostasis.

Dietary fish oil reduces microvascular thrombosis in a porcine experimental model.

Microvascular thrombosis plays a significant role in the pathophysiology of ischaemic reperfusion injury. A fish oil-supplemented diet containing n-3 polyunsaturated fatty acids (PUFA) reduces thromboxane A(2) (TxA(2)) synthesis and, thus, vasoconstriction and platelet aggregation. The aim of this study was to elucidate whether n-3 PUFA in a porcine model of ischaemia and reperfusion injury 1) inhibit accumulation of platelets and fibrinogen in ischaemia-reperfusion injured tissue, 2) prolong the bleeding time, and 3) inhibit TxA(2) synthesis. Nine pigs were fed a standard diet supplemented with 7 g n-3 PUFA/day for 3 weeks. Nine pigs on the standard diet served as controls. Unilateral myocutaneous flaps were exposed to ischaemia for a period of 6 hours. Contralateral flaps were nonischaemic. Tissue contents of radioactive-labelled platelets and fibrinogen were measured after 4 hours of reperfusion. Platelet count, serum TxB(2), and the cutaneous bleeding time were measured before and after 3 weeks of diet. In the fish oil group, the accumulation of platelets was significantly reduced in all the myocutaneous flaps, except in the ischaemic skin part, when compared to control animals. Fibrinogen was significantly reduced in nonischaemic flaps, but not in ischaemic flaps. After the feeding period, the level of TxB(2) was significantly lowered in the fish oil group (p<0.01). No difference in the bleeding time was observed. Thus, dietary supplementation with n-3 PUFA inhibits the formation of microvasculatory thrombosis in this model.

[99mTc]diphosphonate uptake and hemodynamics in arthritis of the immature dog knee.

The relationship between [99mTc]diphosphonate uptake and bone hemodynamics was studied in canine carrageenan-induced juvenile chronic arthritis. Blood flow was determined with microspheres, plasma and red cell volumes were measured by labeled fibrinogen and red cells, and the microvascular volume and mean transit time of blood were calculated. Normal femoral epiphyses had lower central and higher subchondral blood flow and diphosphonate uptake values. Epiphyseal vascular volume was uniform, resulting in a greater transit time of blood centrally. In arthritis, blood flow and diphosphonate uptake were increased subchondrally and unaffected centrally, while epiphyseal vascular volume was increased throughout, leading to prolonged transit time centrally. The normal metaphyses had low blood flow and diphosphonate uptake values in cancellous bone and very high values in growth plates, but a large vascular volume throughout. The mean transit time therefore was low in growth plates and high in adjacent cancellous bone. Arthritis caused decreased blood flow and diphosphonate uptake in growth plates but increased vascular volume and transit time of blood. Diphosphonate uptake correlated positively with blood flow and plasma volume and negatively with red cell volume in a nonlinear fashion. Thus, changes in diphosphonate uptake and microvascular hemodynamics occur in both epiphyseal and metaphyseal bone in chronic synovitis of the immature knee. The [99mTc]diphosphonate bone scan seems to reflect blood flow, plasma volume, and red cell volume of bone.

Three-phase [99mTc]diphosphonate scintimetry in septic and nonseptic arthritis of the immature knee: an experimental investigation in dogs.

We compared the informative value of dynamic and static [99mTc]diphosphonate ([99mTc]DPD) scintimetry in early septic arthritis (SA) and chronic nonseptic arthritis (NSA) of the knee in puppies. SA (n = 10), induced by injection of Staphylococcus aureus into one knee, was examined after 48 h. NSA (n = 6) was induced by weekly intraarticular instillation of 1% carrageenan and examined at 2 and 12 weeks. Epiphyseal and metaphyseal count ratios (CRs) between experimental and control joint were calculated in an angiographic phase (0-20 s), a "blood pool" phase (20-256 s), and a bone uptake phase (2 hs). Control dogs (n = 4) had a CR of 1.0 in all regions and phases, the coefficients of variation being 0.06 and 0.03 in dynamic and static phases, respectively. In NSA, all scintimetric phases showed decreased metaphyseal uptake and largely unchanged epiphyseal uptake. Generally, SA exhibited vastly increased angiographic uptake in all regions and increased epiphyseal blood pool uptake, whereas delayed epiphyseal uptake varied and delayed metaphyseal uptake tended to decrease. Two septic joints had generalized reduction in dynamic uptake, probably owing to increased intraarticular pressure; in one of these, dynamic uptake in the distal femoral epiphysis (FE) was totally absent, suggesting temporary circulatory arrest during the dynamic scanning procedure. The use of regional dynamic and static [99mTc]DPD scintimetry increased the pathophysiologic and diagnostic value of joint scintigraphy, especially with respect to the early detection of SA and its avascular complications.

[99mTc]diphosphonate uptake and hemodynamics in experimental arthritis: effect of naproxen in the canine carrageenan injection model.

The impact of naproxen treatment on juxta-articular hemodynamics and bone metabolism in experimental juvenile arthritis was studied in the articular carrageenan injection model. Unilateral gonarthritis was induced for 12 weeks in eight dogs receiving naproxen (dosage, 2 mg/kg) and eight controls. Regional blood flow was assessed by the microsphere method, plasma volume by the distribution space of [125I]fibrinogen, and bone metabolism by the 2-h uptake of [99mTc]diphosphonate ([99mTc]DPD). Synovial effusion was less prominent with naproxen treatment as judged by joint fluid volume and pressure. Naproxen reduced the arthritic capsular hyperemia, almost normalized a severe blood flow increase in patella and both juxta-articular epiphyses, ameliorated an expansion of plasma volume in the patella and the distal femoral epiphysis, and normalized an increased [99mTc]DPD uptake in subchondral femoral bone and the tibial cortex. Significantly increased arteriovenous shunting in the arthritic extremity was unaffected by naproxen. The study suggests that long-term cyclooxygenase inhibition offers protection against hemodynamic and metabolic changes in juxta-articular bone secondary to synovial inflammation.

Intravenous acetylsalicylic acid, magnesium and their combination in experimental arterial thrombosis in rats.

Intravenous acetylsalicylic acid (ASA) and magnesium (Mg) both possess antiplatelet properties and are thus potential inhibitors of the formation of arterial thrombi. Their effect on the dynamic aspects of arterial thrombus formation was investigated following intravenous administration of both substances alone and in combination. A blinded, placebo-controlled, in-vivo study was performed in 71 rats. Thrombus formation was induced by a standardized arteriotomy in the right femoral artery with inversion of the vessel wall during subsequent closure. Thrombus formation was recorded on video tapes and analysed off-line for 30 min. Animals were randomly assigned to one of four groups: 20 mg bolus of ASA followed by 0.3 mmol/h Mg (ASA/Mg group); NaCl followed by 0.3 mmol/h Mg (Mg group); 20 mg bolus of ASA followed by NaCl (ASA group); or NaCl throughout the experiment (control group). In the ASA-treated groups, serum levels of thromboxane B2 were reduced significantly, and the Mg-treated groups reached a serum level of Mg just above 2.0 mmol/l. No significant differences were observed in initial or maximum thrombus area or in mean thrombus area during the study period. In the ASA/Mg group, a trend towards reduced thrombus formation was observed (P = 0.06). In the same group, seven of 22 animals developed an occlusive thrombus (P < 0.01), an unexpected adverse event possibly related to the combined administration of ASA and Mg.

Aprotinin attenuates platelet accumulation in ischaemia-reperfusion-injured porcine skeletal muscle.

This purpose of this study was to evaluate the effect of aprotinin, a serine protease inhibitor, in ischaemia- and reperfusion-injured myocutaneous flaps and skin flaps. Flap survival, microcirculatory platelet accumulation, and regional blood flow were investigated in seventeen pigs which had been subjected to 8 h of ischaemia and 18 h of reperfusion. The pigs were randomly assigned to aprotinin treatment (n = 9) or saline (n = 8). In-vitro studies were performed to investigate the influence of aprotinin on the activated partial thromboplastin time. The survival of skeletal muscle correlated positively with the concentration of aprotinin (P = 0.02) and could not be explained by regional changes in blood flow. Platelet accumulation was decreased in aprotinin-treated muscle (P = 0.04). In-vitro (n = 10), 100 kallikrein inactivator units/ml aprotinin prolonged the activated partial thromboplastin time both in plasma (P = 0.001) and in blood (P = 0.002), suggesting an anticoagulant rather than a procoagulant effect. In conclusion, aprotinin at high concentrations may be beneficial for the survival of skeletal muscle and provides protection from platelet accumulation in the microcirculation of skeletal muscle exposed to ischaemia and reperfusion injury.