The effect of tezosentan after cold ischemia and renal artery clamping as a model of reperfusion injury in newborn piglets.

BACKGROUND: Cold ischemia and clamping of the renal artery contribute to acute tubular necrosis and renal dysfunction of transplant grafts. The mechanism of ischemic injury is not fully understood, but endothelin (ET)-1 and -2 have been found to participate in reperfusion injury. ET receptor blockade has been shown to have renoprotective effects in both warm and cold reperfusion injury. OBJECTIVE: We sought to assess the effect of tezosentan, a competitive ET antagonist, on piglet renal function during cold ischemia and renal artery clamping. DESIGN/METHODS: Sixteen piglets (7 to 10 days old) were prepped and assigned to three experimental groups: piglets with kidneys clamped (KCLAMP), with kidneys wrapped in ice (KICE), and piglets treated with tezosentan injected after 45 minutes of clamping and ice (KTEZO). Preexperiment parameters including vital signs, urine volume, glomerular filtration rate (GFR), paraaminohippuric acid clearance (CPAH), fractional excretion of sodium and potassium (FeNa, FeK), and renal blood flow (RBF) were measured at baseline, then at 1- and 2-hour intervals. RESULTS: The decrease in urine volume was comparable in both KCLAMP and KICE groups, but no UV decrease was observed in KTEZO group. RBF and GFR were similar (26% to 52% decrease) in all three groups. FeNa decreased by >50% in KICE, whereas it increased by 60% in KTEZO when compared with baseline. A similar increase in FeK was observed in all three groups. CONCLUSIONS: Cold ischemia and clamping have deleterious effects on RBF, GFR, and FeNa. ET blockade did not have a renoprotective effect except on urine volume when given soon after the injury.

[Quality of life and associated factors in asthma in a Primary Care Center. Application of the reduced version of the Asthma Quality of Life Questionnaire]. / Calidad de vida y factores asociados en asmáticos de un centro de Atención Primaria. Aplicación de la versión reducida del Asthma Quality of Life Questionnaire.

INTRODUCTION: Asthma is a highly prevalent disease that can affect the quality of life (QoL). The objective of this study is to determine the QoL in patients with asthma and its relationship with different factors in a Primary Care centre. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted in an urban health centre. The study included a total of 243 patients between 17 to 70 years who had a diagnosis of asthma in their medical records. The QoL was measured using the Spanish version of the Mini-Asthma Quality of Life Questionnaire, with age, sex, smoking, anxiety, depression, severity and control of asthma as associated variables. RESULTS: The mean age was 44.5 years and 71.2% were women. More than half (54.3%) had intermittent asthma, and 45.7% persistent asthma. The overall score in the Mini-Asthma Quality of Life Questionnaire was 5.4 out of 7. The scores by dimensions were: symptoms 5.4; limitation of activities 5.8; emotional function 5.7, and environmental stimuli 4.7. The variables with a worse QoL score that remained statistically significant (P<.05) in the multivariate analysis were poor control of asthma (in all dimensions), history of depression (in all except environmental stimuli), educated to less than secondary level (symptoms and emotional function), and patients admitted to hospital in the past 3 years (symptoms) and who used long-term beta-adrenergics (emotional function). CONCLUSIONS: Patients with intermittent, mild and moderate asthma have a good QoL. Poor control of the asthma and a history of depression negatively affect the QoL.

Incidence of cancer among Swedish military and civil personnel involved in UN missions in the Balkans 1989-99.

Leukaemia cases among European UN soldiers in the Balkans have been related hypothetically to exposure to depleted uranium. This study was performed to investigate the risk of cancer among Swedish personnel (8750 men and 438 women) involved in UN missions in the Balkans 1989-99. The overall incidence of cancer was slightly higher than expected; 34 cancers were observed and 28.1 were expected based on national cancer rates. Among military men, there were eight cases of testicular cancer versus 4.6 expected. There was one case of chronic myeloid leukaemia, and no cases of acute leukaemia. The overall risk of cancer was increased in a subgroup of 648 men taking part in convoy operations, based on only five cancers at four different sites. The study gives no support for the hypothesis that UN service in the Balkans could lead to haematolymphatic malignancies after short latency. However, no exposure assessment was performed, and future follow up is necessary for evaluation of long term risks.

New animal model to evaluate testicular blood flow during testicular torsion.

BACKGROUND/PURPOSE: Unilateral testicular torsion is known to cause infertility because of damage to the contralateral testis. Testicular damage has been attributed to many different mechanisms, one of which is altered contralateral blood flow. In our experiment, in an effort to identify the reason for contralateral testicular injury, the authors developed an accurate method of measuring blood flow in both testes before, during, and after unilateral torsion. METHODS: Four- to 6-week-old piglets weighing 4 to 6 kg were studied. The animals were anesthetized, intubated, ventilated, and catheterized for vascular access. Piglets were assigned randomly to a sham group or a group undergoing 360 degrees or 720 degrees torsion of the left testis (n = 5 per group) for 8 hours, after which it was untwisted. Data were collected at baseline (T = 0), 8 hours of torsion (T = 8), and 1 hour after detorsion (T = 9). Mean arterial blood pressure and heart rate were monitored continuously. Testicular blood flow was determined using radiolabeled microspheres. Blood flow data were evaluated by analysis of variance. RESULTS: In the 360 degrees torsion group, blood flow changes were insignificant during torsion and after detorsion. In the 720 degrees torsion group, blood flow to the twisted testis was reduced significantly, whereas the contralateral testis was unaffected. One hour after detorsion, blood flow to both testes was increased significantly. CONCLUSIONS: The authors describe a new animal model to evaluate testicular blood flow during and after testicular torsion. Increased blood flow after detorsion may be the cause of testicular damage in patients with unilateral testicular torsion.

Significance of fractional excretion of sodium and endothelin levels in the early diagnosis of renal failure in septic neonatal piglets.

PURPOSE: This experiment was designed to help understand the cascade of events that end in renal impairment in septic animals. METHODS: Twenty 3- to 8-day-old piglets were anesthetized and the femoral artery, jugular and femoral veins, and bladder were catheterized. After stabilization under anesthesia with ventilatory support, they were divided into a control group and three groups that received endotoxin (ETX) in doses of 0.01 mg/kg, 0.025 mg/kg, and 0.05 mg/kg. Blood pressure and blood gases were monitored continuously. Blood and urine samples were obtained before (B), 1 hour (E1), and 3 hours (E3) after the bolus of ETX to determine glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tumor necrosis factor (TNF), and endothelin-1 (ET-1) levels. RESULTS: Incremental doses of ETX induce greater release of ET-1 with an early proportionate increase in FENa (P< .05) and late decrease in GFR (P< .05). TNF release is dose and time dependent after ETX injection (P < .05). CONCLUSION: ET-1 and FENa are the best tests to evaluate renal failure during early sepsis in neonatal piglets.

Renal effects of low to moderate doses of dopamine in newborn piglets.

PURPOSE: Administration of dopamine to adult animal and human subjects results in increased renal blood flow, and it may also enhance the glomerular filtration rate. However, renal hemodynamic effects of exogenous dopamine in the neonate are unclear. In this study, we examined the renal actions of low to moderate doses of exogenous dopamine in newborn piglets. METHODS: The animals were anesthetized, catheterized for vascular access and urine collection, and assigned randomly to a control group or treatment groups receiving dopamine infusion at 2, 5, or 10 microg/kg/min. Data were collected at baseline, during dopamine infusion, and 1 hour after cessation of infusion. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored. Glomerular filtration rate (GFR), cardiac index (CI), and renal blood flow (RBF) were determined. Fractional excretion of sodium (FENa) was calculated. RESULTS: Dopamine did not alter renal blood flow nor did it significantly alter CI in spite of a modest increase in heart rate and mean arterial blood pressure. There was a statistically significant increase in GFR at 10 microg/kg/min and in FENa at all doses. CONCLUSIONS: Low doses of dopamine produce significant natriuresis probably by direct action on renal tubules and at moderate doses via, both, increase in GFR and a direct tubular effect. Low and moderate doses of dopamine do not increase RBF as seen in adult animals, possibly because of immaturity of dopaminergic receptors in newborn piglets.

The effect of prostaglandin E1 analog misoprostol on chronic cyclosporin nephrotoxicity.

Cyclosporin A has markedly improved graft survival in transplant patients but its side effects, such as renal toxicity and hypertension, pose management problems in transplant recipients. This toxicity has been attributed to prostaglandin inhibition. Concurrent administration of misoprostol (a prostaglandin E1 analog) prevents chronic cyclosporin A-induced nephrotoxicity but not hypertension in rats.

Effect of unilateral testicular torsion on blood flow and histology of contralateral testes.

BACKGROUND/PURPOSE: Infertility occurs in 25% of patients after unilateral testicular torsion; hence, the authors examined hemodynamic and histological changes in both testes after acute testicular torsion in neonatal piglets. METHODS: The animals were anesthetized, intubated, ventilated, catheterized, and assigned randomly to a sham group or one of three experimental groups undergoing 720 degrees torsion of the left testis for 8 hours after which it was untwisted in group I and removed in group II. In group III, both testes were removed. Data were collected at baseline (T = 0), 4 hours (T = 4), and 8 hours of torsion (T = 8) and at the ninth hour of the experiment (T = 9). Testicular blood flow was determined by using radiolabeled microspheres. The testes also were examined blindly with routine and electron microscopy. RESULTS: In group I, testicular blood flow decreased in the affected testis during torsion and increased significantly after detorsion, whereas blood flow to the contralateral testis increased significantly after detorsion. Sham-operated animals showed no histological abnormality in either testis. In all torsion groups, the affected testis showed extensive changes caused by hemorrhagic necrosis. The contralateral testis only showed changes in group I. CONCLUSION: Unilateral testicular torsion resulted in ipsilateral damage caused by a decrease and subsequent increase in blood flow while in the contralateral testis; damage was the result of a significant increase in blood flow after detorsion.

Body electrolytes in bronchopulmonary dysplasia and the effects of diuretic therapy.

Body electrolytes and their regulatory hormones were studied in preterm infants who suffered from bronchopulmonary dysplasia under two groups: those who were not treated with diuretics (Group II), and those who were treated with diuretics (Group III). The values were compared with a group of matched healthy controls (Group I). Lower serum Na levels, a need of higher Na intake, and higher urinary Na concentrations and urinary specific gravity were found in Group II infants. FeNa was normal and the urinary flow rate was lower than the controls. These data suggest an inability of these infants to dilute urine. Group III infants who were treated with diuretics showed higher serum Na levels and lower urinary specific gravity than Group II infants. These values, as well as water and Na intake/output ratios, were all similar to the control values. Serum aldosterone level was highest in Group II but did not reach significance. Intracellular K concentration was not different between the groups indicating an optimum total body K balance. A significant negative correlation between serum Na and aldosterone levels was found in Group II infants, which was not noted in the controls. Significant correlations were also found between FeNa and plasma aldosterone level in the BPD groups, unlike the controls. The control group of infants showed significant positive correlation between Na balance and serum Na levels. Our results suggest that inability to dilute urine appropriately might be the reason for the BPD patients to retain body water. Water restriction and diuretic therapy therefore are reasonable therapeutic approaches in such cases.

Fecal sodium and potassium losses in low birth weight infants.

We measured 24-hour fecal losses of sodium (Na) and potassium (K) in immediate post natal period of preterm neonates to determine the role of this route in the electrolyte imbalances seen in such infants. The values from preterm infants were compared to a group of age matched term infants. Eleven studies were done on unfed extremely low birth weight infants (group I, birth weight < 1200 gms), seven on fed preterm infants (group II, birth weight 1201-2500 gms) and nine on fed term infants (group III, birth weight 2501-4000 gms). Measured and derived variables compared between the groups were 24 hour fecal volume, total fecal electrolyte contents, Na or K lost per kg of body weight and per gm. of stool and Na or K losses as percent of intake. Although 24 hour fecal volume was lowest in group I, none of the variables related to Na differed between groups I and II whereas all of them were significantly lower in group I when compared with group III. Groups II and III differed only in terms of Na loss/gm stool which was lower in the previous group. Conversely K loss/gm of stool was significantly higher in group I when compared with both groups II and III and the only variable that differed between groups II and III was a higher fecal K content as fraction of intake. Fecal K/Na ratio was highest in group I, and decreased progressively with advancing gestational age, whereas creatinine clearance was lowest in group I and increased along with gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Calidad de vida y factores asociados en asmáticos de un centro de Atención Primaria. Aplicación de la versión reducida del Asthma Quality of Life Questionnaire / Quality of life and associated factors in asthma in a Primary Care Center. Application of the reduced version of the Asthma Quality of Life Questionnaire

Introducción. El asma es una enfermedad de elevada prevalencia y que puede afectar a la calidad de vida (CV). Nuestro objetivo ha sido conocer la CV en pacientes con asma y su relación con diferentes variables en un centro de Atención Primaria. Material y métodos. Estudio descriptivo transversal, realizado en un centro de salud urbano. Se seleccionaron 243 pacientes de entre 17-70 años en los que constaba el diagnóstico de asma en su historia clínica. La CV se estudió mediante la versión española reducida del Asthma Quality of Life Questionnaire, analizándose como variables asociadas la edad, el sexo, el tabaquismo, la ansiedad, la depresión, la gravedad y el control del asma. Resultados. La edad media fue de 44,5 años, con un 71,2% de mujeres. El 54,3% tenían asma intermitente y el 45,7% asma persistente. La puntuación global del Mini-Asthma Quality of Life Questionnaire fue de 5,4 sobre 7. Por dimensiones fueron las siguientes: síntomas 5,4; limitación de actividades 5,8; función emocional 5,7; estímulos ambientales 4,7. Las variables con peor puntación de CV que mantuvieron la significación estadística (p<0,05) en el análisis multivariado fueron el peor control del asma (en todas las dimensiones), el antecedente de depresión (en todas excepto estímulos ambientales), los estudios inferiores a secundarios (síntomas y función emocional) y los pacientes con ingresos hospitalarios los últimos 3 años (síntomas) y que utilizaron betaadrenérgicos de larga duración (función emocional). Conclusiones. Los pacientes con asma intermitente, persistente leve y moderada tenían una buena CV. El peor control del asma y el antecedente de depresión afectaron negativamente sobre la CV (AU)

Introduction. Asthma is a highly prevalent disease that can affect the quality of life (QoL). The objective of this study is to determine the QoL in patients with asthma and its relationship with different factors in a Primary Care centre. Material and methods. A descriptive, cross-sectional study was conducted in an urban health centre. The study included a total of 243 patients between 17 to 70 years who had a diagnosis of asthma in their medical records. The QoL was measured using the Spanish version of the Mini-Asthma Quality of Life Questionnaire, with age, sex, smoking, anxiety, depression, severity and control of asthma as associated variables. Results. The mean age was 44.5 years and 71.2% were women. More than half (54.3%) had intermittent asthma, and 45.7% persistent asthma. The overall score in the Mini-Asthma Quality of Life Questionnaire was 5.4 out of 7. The scores by dimensions were: symptoms 5.4; limitation of activities 5.8; emotional function 5.7, and environmental stimuli 4.7. The variables with a worse QoL score that remained statistically significant (P<.05) in the multivariate analysis were poor control of asthma (in all dimensions), history of depression (in all except environmental stimuli), educated to less than secondary level (symptoms and emotional function), and patients admitted to hospital in the past 3 years (symptoms) and who used long-term beta-adrenergics (emotional function). Conclusions. Patients with intermittent, mild and moderate asthma have a good QoL. Poor control of the asthma and a history of depression negatively affect the QoL (AU)

Effects of tezosentan, a dual endothelin receptor antagonist, on the cardiovascular and renal systems of neonatal piglets.

BACKGROUND/PURPOSE: Endothelin is a potent biological vasoactive mediator in the cardiovascular and renal systems. Little is known of the effects of endothelin antagonism on the developing heart and kidney, and we hope to show that endothelin does have an important role in the cardiovascular and renal systems of the developing neonate. In this study the authors have examined the effects of tezosentan, a nonselective endothelin-A and endothelin-B receptor antagonist designed for parenteral use, on the cardiovascular and renal systems of healthy neonatal piglets. METHODS: Eight, 7- to 10-day old domestic piglets weighing 2.5 to 3.0 kg were anesthetized, intubated, and ventilated with catheters placed into the jugular vein, left ventricle, and femoral artery. Urine output was monitored via a suprapubic cystostomy. After baseline data were obtained the piglets received tezosentan (1 mg/kg/h) for 1 hour. A set of data was collected just before discontinuation of the 1-hour infusion of tezosentan and another set was collected 1 hour after the discontinuation of the drug. Mean arterial pressure (MAP), heart rate (HR), and urine output (UV) were monitored continuously and cardiac index (CI), systemic vascular resistance (SVR), renal blood flow (RBF), and renal vascular resistance (RVR) were calculated from gamma counts obtained from injections of radio-labeled microspheres at end of the different time periods. Glomerular filtration rate (GFR) was obtained by the sodium iothalamate method. Data were averaged and plotted versus time and analyzed statistically by a Student's t test. RESULTS: (P <.05 versus baseline*). In our experimental animals the infusion of tezosentan diminished MAP and SVR from baseline values of 94 +/- 7 mm Hg and 0.14 +/- 0.03 mm Hg/mL/min, respectively to TEZO values of 62 +/- 4* mm Hg and 0.07 +/- 0.02* mm Hg/mL/min. CI increased from 278 +/- 58 to 367 +/- 75* mL/min/kg with tezosentan. There also was a statistically significant increase in RBF from 1.16 +/- 0.38 to 1.86 +/- 0.37* mL/min/kg, an increase in UV from 0.57 +/- 0.24 to 0.64 +/- 0.12* mL/min, a decrease in RVR from 4.60 +/- 1.47 to 2.03 +/- 0.36* mm Hg/mL/min, and no change in the GFR. CONCLUSIONS: The inhibition of endothelin receptors with tezosentan produced a statistically significant effect on the piglet cardiovascular system with a drop in MAP and SVR and an increase in CI and HR. It also produced a statistically significant increase in RBF and UV and a decrease in RVR without affecting GFR. J Pediatr Surg 36:1824-1828.

Surfactant therapy and spontaneous diuresis.

The effect of artificial surfactant therapy on renal function and the onset of spontaneous diuresis was prospectively evaluated in 19 infants with hyaline membrane disease in a double-blind, controlled study. Twelve infants were in the surfactant group; seven infants received placebo (0.9% saline solution). There was no difference in the time of onset of spontaneous diuresis (as defined by output greater than or equal to 80% of intake). The glomerular filtration rate, determined by endogenous creatinine clearance, was also similar in the surfactant- and placebo-treated infants during the first 3 days of life. The fractional excretion of sodium was significantly higher in the placebo group at 24 hours and 36 hours. Infants in the placebo group had a higher negative sodium balance than those in the surfactant group. Ventilatory status improved significantly soon after surfactant treatment, as evidenced by improvement in the alveolar/arterial oxygen pressure ratio and by a lower mean airway pressure. These data suggest that ventilatory status can be improved without diuresis; the factors that regulate diuresis are multiple and not fully understood.

Effect of ultrafiltration on peritoneal dialysis drug clearances.

To determine the effect of dialysate osmolarity on peritoneal dialysis drug transfer, peritoneal dialysis clearances of theophylline, phenobarbital, and tobramycin were determined in 10 rabbits using dialysate containing 1.5 and 4.25% glucose. Urea and creatinine clearances were also obtained for comparison. Under similar dialysis conditions, the peritoneal clearances of the three drugs remained unchanged for the two types of dialysate. In contrast, the peritoneal clearances of urea and creatinine were significantly higher with the use of 4.25% glucose dialysate (p less than 0.001). Thus, peritoneal dialysis clearances of theophylline, phenobarbital and tobramycin are not significantly affected by hypertonicity-induced ultrafiltration during acute peritoneal dialysis.

Beta 2-microglobulin clearance in neonates: index of tubular maturation.

Serum and urinary beta 2-microglobulin (beta 2M) were studied by enzyme immunoassay in 28 normal neonates at day 1 and day 4 of life in relation to gestational age (GA) and postnatal age (PNA). The infants were grouped according to GA; 10 with GA ranging from 32 to 35 weeks (mean 33.5 weeks) and 18 with GA ranging from 36 to 41 weeks (mean 38.3 weeks). Serum beta 2M varied directly with both GA and PNA. When values for serum beta 2M were related to conceptional age (CA), a significant positive correlation was present for all the infants studied (r = 0.68, P less than 0.01). Fractional excretion of beta 2M (FE beta 2M) decreased as a function of both GA and PNA. When a comparison of FE beta 2M was made in infants of all CA, a significant inverse correlation was noted for infants with CA less than or equal to 35 weeks (r = -0.89, P less than 0.001). The fall in FE beta 2M reached a plateau by 36 weeks. The highest FE beta 2M (33%) was observed in infants of 32 weeks CA who had the lowest filtered beta 2M (F beta 2M). No statistically significant relationship between changes in FE beta 2M and fractional urine flow rate was observed within each of the CA categories (infants less than or equal to 35 weeks, r = 0.21, P = 0.28; infants greater than or equal to 36 weeks, r = 0.25, P = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of tolazoline on renal function in newborn puppies.

Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

Renal actions of endothelin-1 in newborn piglets: dose-effect relation and the effects of receptor antagonist (BQ-123) and cyclooxygenase inhibitor (indomethacin).

Although the effects of endothelin-1 (ET-1) on intact or perfused adult kidney are well understood, its effects in the fetus and the newborn have not been well studied. We examined the effects of infusions of 25, 50, and 100 ng/kg of ET-1 per minute on mean blood pressure (MBP), cardiac index (CI), renal blood flow (RBF), glomerular filtration rate (GFR), and urine volume (UV) in 7- to 10-day-old piglets (n = 24). In addition, the effects of pretreatment with a receptor antagonist (BQ-123) and with a cyclooxygenase inhibitor (indomethacin) were studied in 12 separate piglets. ET-1 produced a dose- and level-dependent decrease in CI (60%), RBF (50% to 75%), GFR (66% to 80%) and MBP 15% to 17%. These changes returned to 75% to 80% of baseline 60 minutes after discontinuation of ET-1. Low-dose infusion (25 ng/kg) did not result in any changes in systemic or renal hemodynamics. Plasma half-life of ET-1 in piglets was 2.1 +/- 0.4 minutes. Pretreatment with the specific ETA receptor antagonist BQ-123 completely blocked the ET-1-induced systemic and renal hemodynamic changes. Indomethacin blocked the ET-1-induced rise in MBP but failed to block any renal changes. In fact, indomethacin accentuated the changes induced by ET-1, especially the changes in RBF, RVR, and GFR. Studies of receptor binding in the renal cortex and medulla showed that, in the cortex, the Ki value for ET-1 was 6.32 +/- 1.57, and for ET-3 it was 20.05 +/- 4.38 (p < 0.05); in the medulla, the Ki values were similar for both ET-1 and ET-3. These results indicate that in piglets the renal vascular bed is highly sensitive to ET-1, and its effects are predominantly mediated through ETA receptors.

Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.

Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as 5 micrograms kg-1 bolus followed by 0.1 microgram kg-1 min-1 continuous infusion for 105 min in six piglets, while the same treatment was repeated in five animals without preceding HI insult. At third group of six served as sham operated controls. In the HI insult group by 105 min of nimodipine infusion the mean BP dropped by 30% and the cardiac output dropped by 23% of respective baseline. In this group, the renal blood flow dropped between 65% and 77% of baseline and regional cerebral blood flow dropped between 28% and 55% of respective baseline by 45 min and 105 min of nimodipine fashion. In the group with no prior HI insult, 105 min of nimodipine infusion caused no significant changes in these variables. Despite nimodipine infusion, HI insult caused a significant increase in the mean brain water content compared to the two control groups: 89 +/- 3.2% compared to 82.7 +/- 0.5% in the nimodipine control group, and 83.7 +/- 1.7% in the sham group (P < 0.0001). We conclude that while nimodipine therapy without prior asphyxial insult does not cause significant adverse haemodynamic effects, its infusion after even a mild HI insult could cause reduction in renal blood flow and moderate reduction in regional cerebral blood flow, BP, and cardiac output, suggesting a differential effect. A 15 min lag between HI insult and nimodipine therapy may be too long to prevent cerebral oedema.

Correlation of flow probe determinations of common carotid artery blood flow and internal carotid artery blood flow with microsphere determinations of cerebral blood flow in piglets.

We investigated whether blood flow determined by a flow probe situated on one common carotid artery provided an accurate estimation of unilateral cerebral blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated piglets, blood flow determined by an ultrasonic flow probe placed on the right common carotid artery was correlated with CBF determined by microspheres under two experimental conditions: 1) before ligation of the right external carotid artery with both the right external and internal carotid circulations intact [common carotid artery blood flow (CCABF) condition], and 2) after ligation of the right external carotid artery (ipsilateral to the flow probe) with all residual right-sided carotid artery blood flow directed through the right internal carotid artery [internal carotid artery blood flow (ICABF) condition]. The left carotid artery was not manipulated in any way in either protocol. Independent correlations of unilateral CCABF and ICABF with microsphere-determined unilateral CBF were highly significant over a 5-fold range of CBF induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p < 0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF was 1.68 +/- 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The slope of the correlation of unilateral ICABF versus unilateral CBF did not differ significantly from unity (1.06 +/- 0.15), and the y intercept did not differ significantly from zero [-1.3 +/- 5.2 (SEM) mL]. Consequently, unilateral ICABF determined by flow probe accurately reflected unilateral CBF determined by microspheres under these conditions. Flow probe assessments of CCABF and ICABF in piglets may provide information about dynamic aspects of vascular control in the cerebral circulation that has heretofore been unavailable.