A recirculatory pharmacokinetic model describing the circulatory mixing, tissue distribution and elimination of antipyrine in dogs

A model of antipyrine disposition from the moment of its injection was developed incorporating the intravascular mixing component as determined by indocyanine green (ICG) kinetics. The simultaneous dispositions of antipyrine and ICG were characterized in five dogs anesthetized with halothane. After injecting antipyrine and ICG into the right atrium, femoral arterial blood samples were collected every 3 sec for the 1st min and less frequently to 20 min for ICG and to 360 min for antipyrine. ICG and antipyrine concentrations were measured by high-performance liquid chromatography and modeled with SAAM 30.1. A fully identifiable recirculatory compartmental model, incorporating the ICG recirculatory model with blood flows and time delays, was used to describe antipyrine disposition. Four distinct antipyrine pharmacokinetic tissue compartments and the distribution clearances assigned to them could be estimated: a pulmonary tissue (0.13 +/- 0.05 I, and 2.51 +/- 0.39 liters/min), a very fast equilibrating tissue (0.12 +/- 0.08 I, and 1.33 +/- 0.22 liters/min), a fast equilibrating tissue (3.21 +/- 0.45 I, and 0.74 +/- 0.09 liters/min) and a slow equilibrating tissue (15.94 +/- 1.8 I, and 0.44 +/- 0.13 liters/min). Although this recirculatory model retains the predominant attributes of traditional pharmacokinetic models, it also can describe completely drug concentrations during the mixing transient when many drugs reach peak effect as well as ascertain the role of cardiac output and its distribution in drug disposition.     

Studies on methods for determination of the distribution of cardiac output in the mouse

Different techniques for determining cardiac output distribution in the mouse have been studied. The soluble indicator technique using injection of rubidium on the right side of the heart was found to give a satisfactory reproducibility which made it possible to determine cardiac output fractions in the normal mouse. The use of radioactivity-labelled microspheres, which must be injected on the side of the heart, was found to give unreliable and non-reproducible results. This was due to difficulty in depositing the microspheres into the left ventricle both when a catheter was inserted via the right carotid artery, or by means of cardiac puncture.     

Comparison of the accuracy of the lithium dilution technique with the thermodilution technique for measurement of cardiac output

A new indicator dilution technique for measurement of cardiac output is described. Lithium chloride is injected via a central venous catheter and its dilution curve measured in arterial blood using a lithium-selective electrode. We assessed the lithium dilution cardiac output measurement (LiDCO) and a conventional thermodilution cardiac output measurement (ThDCO) by comparing the results of both with cardiac output determined by electromagnetic flowmetry (EMCO) under controlled laboratory conditions in 10 swine. They were monitored with a pulmonary artery catheter, femoral artery catheter and electromagnetic flowmeter placed around the ascending aorta. LiDCO, ThDCO and EMCO measurements were determined at baseline, in a hyperdynamic state produced by administration of dobutamine, at a second baseline and finally in a hypodynamic state induced by propranolol during deep anaesthesia. Data were analysed by linear regression analysis and the comparison method described by Bland and Altman; bias and precision of both LiDCO and ThDCO compared with EMCO were calculated by the method of Sheiner and Beal. The correlation coefficient between LiDCO and EMCO (0.95) was higher than that between ThDCO and EMCO (0.87). The precision value of LiDCO (0.04) was significantly less (i.e. better) than that of ThDCO (0.09). The results of this study indicated that LiDCO was more reliable compared with conventional ThDCO.     

Evaluation of a continuous cardiac output and mixed venous oxygen saturation catheter in critically ill surgical patients

OBJECTIVE: To evaluate the agreement of continuous cardiac output and mixed venous oxygen saturation measurements, obtained with a modified pulmonary artery catheter, with those values obtained by standard intermittent bolus thermodilution and cooximetry. DESIGN: Prospective, clinical investigation. SETTING: A surgical intensive care unit in a tertiary referral center. PATIENTS: Twenty-one adult critically ill surgical patients, requiring pulmonary artery catheter monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A modified pulmonary artery catheter capable of continuous monitoring of cardiac output and mixed venous oxygen saturation was used with either an 8.5-Fr or a 9-Fr introducer. At random intervals, the continuous cardiac output measurement was compared with the cardiac output obtained using standard intermittent bolus thermodilution. The system was calibrated every 24 hrs for mixed venous oxygen saturation monitoring. Each saturation obtained by the laboratory cooximeter was compared with that value recorded using the catheter. Data points for 202 pairs of cardiac output (21 patients, 31 catheters) and 65 pairs of mixed venous oxygen saturation (20 patients, 28 catheters) were obtained. The bias and precision of the cardiac output data were 0.49 and 1.01 L/min, respectively. The agreement between the continuous and bolus values decreased as the cardiac output increased. Heart rate did not affect the agreement between the continuous and bolus techniques. The bias and precision of the mixed venous oxygen saturation data were -0.57% and 3.76%, respectively. The hematocrit did not affect the bias or precision of the venous saturation data over the hematocrit range observed (23.2% to 44.6%). Fewer catheter malfunctions were observed when the catheter was used with a 9-Fr introducer than with an 8.5-Fr introducer. CONCLUSIONS: The test catheter adequately measures continuous cardiac output and mixed venous oxygen saturation in the clinical setting. Because intermittent bolus thermodilution is not a true "gold standard" for cardiac output determination, new techniques compared with bolus thermodilution may fail to achieve accuracy expectations. A 9-Fr introducer is recommended, as fiberoptic damage may have occurred when the 8.5-Fr introducer was used.     

Determination of heart time volume using the Fick principle in the early postoperative phase after correction of congenital heart defects. Comparison of the calculation of arterio-mixed venous oxygen differences and pulmonary oxygen uptake with the calculation of arterial-central venous oxygen differences and pulmonary oxygen uptake

Comparison of the calculation by means of the arterio-mixed venous oxygen difference and the oxygen uptake with the calculation by means of the arterio-central venous oxygen difference and the oxygen uptake. OBJECTIVE: How reliable is the measurement of cardiac output on Fick's principle without a pulmonary artery catheter? SETTING: PICU in an University hospital. DESIGN: In the postoperative period following complete repair of congenital heart disease we carried out 91 simultaneous measurements of blood gases in 45 infants and children (mean age 18.6 months, mean body weight 8.9 kg) from a systemic artery, the A. pulmonalis, and the V. cava superior. We also determined the pulmonary oxygen uptake in 24 patients (48 measurements). Cardiac output was calculated on Fick's principle using the arterio-mixed venous oxygen difference and the pulmonary oxygen uptake (HZV a-pa) and compared to the cardiac output derived from the central venous values (HZV a-zv). We differentiated between patients with a left to right shunt of 10% or more postoperatively (group A, n = 18) and all others (group B, n = 27). RESULTS: In both groups the correlation coefficient between HZV a-zv and HZV a-pa was high (group A: r = 0.97, group B: r = 0.94). In group A HZV a-pa (mean: 1958 ml/min) was higher than HZV a-zv (mean: 1340 ml/min), group B showed the opposite situation (mean HZV a-pa: 1136 ml/min, mean HZV a-zv: 1373 ml/min). With the Wilcoxon signet-rank test we found significant differences between the partial pressure of oxygen and the saturation of central venous and mixed venous blood samples in both groups, but HZV a-zv and HZV a-pa were different significantly on a level of p < or = 0.01 only in group A. CONCLUSIONS: In both groups HZV a-pa and HZV a-zv correlated well. Therefore, if a pulmonary artery catheter is not inserted; the course of the cardiac output can be calculated with acceptable reliability from the central venous blood gases. By means of Fick's principle the pulmonary blood flow is determined, which is higher than the systemic blood flow in cases of left to right shunting, because of the recirculation in the pulmonary blood circuit. Interpreting the results this has to be taken into account.     

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.     

Pre- and post-operative management of cesarean section in a parturient with severe preeclampsia accompanied by hyperdynamic state

A 37-year-old parturient with severe preeclampsia accompanied by pulmonary edema underwent emergency cesarean section. Pulmonary artery (PA) catheter inserted while the patient was awake revealed hyperdynamic state with increased cardiac index and preload, and decreased systemic vascular resistance. Epidural anesthesia and analgesia were provided with a satisfactory outcome. Monitoring of PA pressure and cardiac index was continued postoperatively in ICU for fluid management. We conclude that preoperative PA catheterization provides useful hemodynamic information in severe preeclamptic patients associated with persistent oliguria, pulmonary edema and hyperdynamic state.     

Systolic hypertension in critical aortic stenosis and the effect of valve replacement

Isradipine (lomir) is a new highly selective arteriolar vasodilator of the dihydropyridine group, characterized by a slight cardiodepressive effect. The drug effect on the central hemodynamics and oxygen transport was studied after cardiovascular surgery. Arterial pressure and total peripheral vascular resistance were reliably reduced at the peak of the drug action, as was the left-ventricular stroke work and oxygen consumption. A tendency to increase of cardiac output and cardiac index was observed. Pulmonary vascular resistance and pressure in the pulmonary artery did not reliably change. The drug increased the intrapulmonary shunt.     

Measurement of cardiac output with continuous thermodilution. b1 Clinical experience with the Intellicath-Vigilans system

BACKGROUND: Thermodilution cardiac output measurements are commonly obtained by a manual bolus technique with a pulmonary artery catheter. METHODS: A new thermodilution catheter has been developed which utilizes an integral thermal filament and provides semicontinuous online cardiac output. The response of this new device in 25 patients undergoing coronary artery bypass grafting was examined. A total of 250 data pairs was obtained; the cardiac outputs ranged from 2.2 to 11.9 lts.min. RESULTS: The linear regression is represented by the following equation: continuous thermodilution = 0.7196 bolus thermodilution +1.038. The correlation coefficient was 0.75; the mean bias was 0.493 +/- 1.034. CONCLUSIONS: The new technique provides acceptable accuracy in many clinical situations except when sudden haemodynamic changes occur.     

Regional pharmacokinetics of 5-fluorouracil in dogs: role of the liver, gastrointestinal tract, and lungs

The purpose of this study was to determine the presence and extent of pulmonary elimination for 5-fluorouracil (FUra). A secondary aim was to characterize the relative importance of the liver, gastrointestinal tract, splanchnic region, and lungs toward the overall elimination of FUra. A total of 10 mixed-breed male and female dogs were used in these acute studies in which FUra was administered through a cephalic vein. Six dogs were studied at sequentially escalated dose rates of 0.125, 0.250, 0.500, 0.750, and 1.00 micromol/min/kg (8-fold range); four dogs were studied at sequentially escalated dose rates of 0.0625, 0.250, 0.750, 1.50, and 2.00 micromol/min/kg (32-fold range). Each infusion lasted 2 h, at which time steady-state plasma concentrations were obtained (i.e., portal vein, carotid artery, hepatic vein, and pulmonary artery), perfusion rates were measured (hepatic artery, portal vein, and cardiac output), and pharmacokinetic parameters were directly assessed. Pulmonary elimination of FUra was conclusively demonstrated. Although only 17% of the drug was extracted by the lungs at the lowest dose rate, pulmonary clearance (16.0 ml/min/kg) was on the order of splanchnic clearance (13.5 ml/min/kg), or larger. As the dose rate increased, pulmonary clearance was more easily saturated than splanchnic clearance. Thus, it appears that at increasing dose rates, the splanchnic region becomes a more significant pathway, whereas the lungs have a reduced role in the overall elimination of FUra.     

Timing variability in children with early-treated congenital hypothyroidism

Hypertonic acetate solution in small volumes greatly improves cardiac output and corrects acid-base disturbances in hemorrhaged animals. We hypothesized that the combination of alpha alpha-crosslinked human hemoglobin (alpha alpha Hb), an oxygen carrier and vasoconstrictor, with hypertonic sodium acetate (HAHb), a vasodilator, may be effective for small volume resuscitation of hemorrhagic shock. Six pigs hemorrhaged to a mean arterial pressure of 40 mmHg for 60 min (bled volume: 23.6 +/- 2.5 ml.kg-1) received a single bolus of 4 ml.kg-1 of HAHb infused over two min. HAHb restored arterial pressure, increased systemic vascular resistance and caused a modest increase in cardiac output and SvO2, while pulmonary arterial pressure and vascular resistance were markedly increased. In two animals, transient severe hypotension and low cardiac output may have been due to acute pulmonary hypertension during injection. Compared to our previous study, in which animals received 4 ml-kg-1 of alpha alpha Hb alone, HAHb produced higher cardiac output and a smaller increase in systemic and pulmonary vascular resistance. However, slower, titrated infusions may be needed when hemoglobin solutions are combined with drugs or solutions that cause vasodilation in order to decrease the likelihood of acute hemodynamic instability.     

Cardiac flow after fetal blood sampling in normally grown and growth-retarded fetuses

The objective of this study was to evaluate the effect of fetal blood sampling on cardiac flow velocity waveforms. Flow velocity waveforms were measured from the ascending aorta and pulmonary artery immediately before and after fetal blood sampling in 29 normally grown and 12 growth-retarded fetuses. The latter group was characterized by abnormal Doppler indices in the umbilical artery and middle cerebral artery suggestive of uteroplacental insufficiency as the causative factor of the impaired growth. The flow velocity parameters studied were the peak velocity, the time to peak velocity, and the left and right cardiac output and their ratio. In normally grown fetuses, the peak velocity and right and left cardiac output values increased significantly after fetal blood sampling, while no significant changes were observed in the other indices considered. The gestational age at the time of the procedure was positively related to the amplitude of these changes. In growth-retarded fetuses, fetal blood sampling did not induce any significant increase in cardiac output or peak velocities, while in more than 50 per cent of the fetuses these Doppler indices decreased. The amplitude of the decrease was significantly related to the severity of acidosis in the umbilical vein. In conclusion, the cardiac haemodynamic response to fetal blood sampling differs between normally grown and growth-retarded fetuses. This difference may explain the higher rate of complications occurring in the latter group of fetuses after blood sampling.     

Single injection thermodilution. A flow-corrected method

BACKGROUND: Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output. METHODS: To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle. RESULTS: A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction. CONCLUSION: It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.     

Different ancestor alleles: a reason for the bimodal fragment size distribution in the minisatellite D2S44 (YNH24)

The aim of this study was to evaluate whether MR could depict pulmonary arterial anatomy in more detail than routine angiography in patients with congenital interruption or acquired occlusion of the left pulmonary artery or pulmonary atresia. This study included 10 patients with tetralogy of Fallot (n=6) or pulmonary atresia with ventricular septal defect (n=3) or aorticopulmonary window (n=1) diagnosed by cardiac angiography and MR. Surgical confirmation was made in seven patients. Interruption of the proximal left pulmonary artery, diagnosed at the time of evaluation, was found in seven patients and acquired obstruction of the hilar pulmonary artery (PA) was found in two at cardiac angiography. In the remaining one patient with pulmonary atresia and an occluded palliative shunt, the central PA was not visualized at angiography. MR showed 3-6 mm-sized hilar PAs in five and a central PA in a patient with pulmonary atresia. In 4 of 6 (67%) surgically-proven patients with congenital or acquired left PA obstruction, the status of the PA distal to the obstruction was correctly diagnosed with MR. In conclusion, MR is an effective modality in depicting sizable PAs when routine angiography fails to visualize the PA anatomy.     

Milrinone improves pulmonary hemodynamics and right ventricular function in chronic pulmonary hypertension

BACKGROUND: Right ventricular failure after cardiac transplantation is commonly related to preexisting recipient pulmonary hypertension. This study was designed to investigate the effects of intravenous milrinone on pulmonary hemodynamic indices and right ventricular function in a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. METHODS: Eight mongrel dogs underwent pulmonary artery catheterization to measure right-sided hemodynamic indices before and 6 weeks after a right atrial injection of monocrotaline pyrrole. Six weeks after injection, all hearts were instrumented with a pulmonary artery flow probe, ultrasonic dimension transducers, and micromanometers. Data were collected at baseline and after milrinone infusion. RESULTS: Six weeks after monocrotaline pyrrole injection, significant increases in the pulmonary artery pressure and pulmonary vascular resistance were observed. Milrinone led to significant increases in right ventricular function as well as significant improvements in pulmonary vascular resistance, pulmonary blood flow, and left ventricular filling. CONCLUSIONS: This investigation demonstrates the well-known hemodynamic and inotropic effects of milrinone which, in the setting of monocrotaline pyrrole-induced pulmonary hypertension, were also associated with significant increases in pulmonary blood flow and left ventricular filling.     

Immediate increase in circulating hepatocyte growth factor/scatter factor by heparin

Circulating levels of hepatocyte growth factor (HGF)/scatter factor have been recently found to be increased in the early phase of myocardial infarction, and it has been hypothesized that HGF plays a role in angiogenesis and collateral vessel growth. Heparin has also been shown to enhance angiogenesis and to improve collateral blood flow. This study was designed to study the effect of heparin on the release of HGF. In an experimental study, heparin was given to rats intravenously and plasma was collected for measurements of HGF by enzyme-linked immunosorbent assay. A dose-dependent increase in circulating HGF was measured with peak levels occurring 10 min after injection of 300 units/kg of heparin (15.4+/-2.0 ng/ml after v 0. 17+/-0.14 ng/ml before injection,P<0.0001). In a subsequent clinical study, 12 patients received 3000 units of heparin during cardiac catheterization. Circulating HGF increased steeply within 3 min of the injection. Comparable changes in plasma concentrations were measured in samples obtained from femoral vein (8.7+/-3.5 after v 0. 33+/-0.07 before injection P<0.05) or artery (10.5+/-3.2 ng/mlv 0. 27+/-0.05 P<0.01), pulmonary artery (9.1+/-2.0 ng/mlv 0.36+/-0.06 ng/ml,P=0.07 ) or right atrium (8.5+/-1.6 ng/mlv 0.42+/-0.11,P<0.01). This study suggests that heparin-induced effects such as the promotion of angiogenesis may be at least partly due to the release of HGF.     

Paradoxical cerebral embolism during fibrinolysis therapy in deep vein thrombosis and pulmonary embolism

A 37-year-old woman with increasing dyspnoea over several months suddenly developed severe ortho- and tachypnoea as well as cyanosis of the lips and acrocyanosis. Pulmonary angiography revealed massive bilateral pulmonary emboli with a systolic pulmonary artery pressure of 75 mm Hg. Phlebography demonstrated a thrombotic occlusion of the deep veins of the left leg extending to the distal femoral vein. Thrombolysis treatment was started via an indwelling pulmonary artery catheter (500,000 IU urokinase and 10,000 IU heparin as bolus, then 1 mill. IU urokinase and 1,000 IU heparin per hour). After two hours an incomplete left-sided paresis occurred (involving ocular and facial muscles, dysarthria, left arm and left leg) and the thrombolytic infusion was stopped. But cerebral computed tomography (CT) did not demonstrate any intracerebral haemorrhage. The heparin infusion was restarted (partial thromboplastin time between 70 and 90 s). CT examinations during the next few days showed the development of an ischaemic infarction in the distribution of the right medial cerebral artery. Angiography demonstrated occlusion of the right internal carotid artery. The diagnosis of a paradoxical embolus was supported by easy cardiac catheter passage through a patent foramen ovale. Subsequent pulmonary angiography demonstrated a thrombus-free pulmonary arterial circulation with a normal pulmonary arterial pressure. There was gradual and extensive regression of the incomplete hemiparesis.     

Successful outcome in Swan-Ganz catheter-induced rupture of pulmonary artery

Swan-Ganz catheter-induced pulmonary artery (PA) rupture is rare, with an incidence of 0.016 to 0.2 per cent, but it remains the most dreaded complication in the placement of these catheters with a mortality above 50 per cent. We report two cases of PA rupture after catheter placement. Both patients were managed nonoperatively and without any invasive procedure. They both stopped bleeding after the initial episode and were discharged a few days later. We believe that in the absence of high-risk factors, such as pulmonary hypertension and systemic anticoagulation, PA rupture from a Swan-Ganz catheter can be successfully treated by withdrawal of the catheter and supportive care.     

Histological and urographic findings in the autotransplanted ureter without kidney in dogs: preliminary report

To ascertain whether isoflurane produces a peripheral splanchnic sympathectomy as compared to fentanyl or pentobarbital anesthesia, 12 mongrel dogs (30-45 kg) were allocated randomly to one of three anesthetic test groups, tracheally intubated, surgically prepared, and subjected to unilateral electrical stimulation of the greater splanchnic nerve. Anesthetically, Group 1 animals (n = 4) received pentobarbital, Group 2 animals (n = 4) were administered fentanyl, and Group 3 animals (n = 4) received isoflurane. Stimulation continued for 90 min. Each second of stimulation consisted of 20 stimuli of 0.5 minimum alveolar anesthetic concentration duration and 5 V intensity, delivered during a 0.2-s interval, followed by an 0.8-s pause. To assess splanchnic sympathetic responses, mean arterial blood pressure, heart rate, pulmonary artery diastolic, cardiac output, adrenal blood flow, adrenal and arterial norepinephrine (N) and epinephrine (E) were obtained before and at 5, 10, 15, 30, 45, 60, and 90 min during stimulation. In Group 1 animals (pentobarbital), electrical stimulation elicited marked increases in mean arterial blood pressure, pulmonary artery diastolic, and cardiac output (P < 0.001). Examination of the adrenal effluent, which was exteriorized from the animal during the protocol, revealed that adrenal blood flow, adrenal vein N and E concentrations dramatically increased (P < 0.0001). Arterial N and E concentrations remained unchanged. Results of Group 2 animals (fentanyl) were similar to those of Group 1; mean arterial blood pressure, pulmonary artery diastolic, and cardiac output increased (P < 0.005). Adrenal blood flow, adrenal vein N and E increased dramatically (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Total cavopulmonary connection for grown diminutive pulmonary artery after staged Blalock-Taussig shunt

We report a two-year-old girl with asplenia, [A, L, L] DORV, pulmonary atresia, common AV valve, PDA, and TAPVC, who successfully underwent total cavo pulmonary connection (TCPC). Deep cyanosis was pointed out since birth. Cardiac catheterization performed on the sixth day after birth revealed a diminutive pulmonary artery tree of which PA index was 41 mm2/m2. Left modified Blalock-Taussig shunt was created at 27 days of age. The PA index increased to 282 mm2/mm2, but disparity in diameter between the left and the right pulmonary artery was yielded by PDA subsidence. Therefore additional contralateral B-T shunt was made at one year of age. Follow-up cardiac catheterization at 28 months of age showed well developed pulmonary artery; PA index of 460 mm2/m2, right pulmonary resistance (Rp) of 3.49 units, left Rp of 2.33 units, and estimated total Rp was 1.39. According to study, bidirectional Glenn procedure or TCPC was indicated. Considering necessity of urgent repair of common pulmonary vein obstruction, regurgitation of the common atrio-ventricular valve and pulmonary artery stenosis, TCPC was performed with concomitant repair of the associated lesions. Severe butterfly-figure stenosis of the central PA was augmented by anastomosing both the left SVC and the left-sided atrium. In conclusion, diminutive pulmonary artery could be adequately grown by phase-in Blalock-Taussig shunts. Pulmonary blood flow scintigraphy was thought to be useful for estimation of pulmonary resistance in such cases with different pulmonary resistance between right and left PA.