Effects of Positive Pressure Ventilation on Intrarenal Blood Flow in Infant Primates
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Pediat. Res. 8: 792-796 (1974) Antidiuretic hormone intrarenal blood flow developmental physiology kidney intermittent positive pressure ventilation Effects of Positive Pressure Ventilation on Intrarenal Blood Flow in Infant Primates EDDIE S. MOO RE,(^^) MAURINA B. GALVEZ, JOHN B. PATON, DAVID E. FISHER, AND RICHARD E. BEHRMAN Department of Pediatvics, University of Illinois College of Medicine, Chicago, Illinois, USA Extract cortical flow rates in patients with acute failure. Horster and Thurau (9) found that superficial cortical and juxtamedullary Measurement of intrarenal distribution of renal blood flow nephrons in adult rats have different functional capacities. It by injection of radionuclides in 3-5-day-old infant monkeys can be speculated that the occurrence of decreased urine flow showed a preponderance of outer cortical over inner cortical might result from redistribution of blood to inner cortical " flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. nephrons with possible greater reabsorptive capacity. The Intermit tent positive pressure ventilation (IPPV) causes a extent and character of overall renal function may therefore reversal of this flow pattern. The theoretical difference in be in part dependent upon intrarenal distribution as well as on nephron function in these two areas suggests that this reversal total renal blood flow. Although the studies of Jose et al. (1 1) in intrarenal flow induced by IPPV may have important demonstrated a low cortical flow and low total renal blood clinical implications. flow in infant puppies, few studies have been done in infants to measure the effect on intrarenal flow to various stimuli and Speculation how this would affect overall renal function. Intermittent positive pressure ventilation is an extensively used therapeutic Extrarenal stimuli such as IPPV causes a redistribution of procedure in pediatrics. Decreased urine flow is known to intrarenal blood flow in infant primates. Any stimuli that occur in some patients receiving IPPV (13, 20). We speculated results in increased production of epinephrine or similar that this decreased urine flow might result from redistribution compounds may be responsible for this redistribution by a of renal blood flow as discussed previously. The purpose of local effect on outer cortical blood vessels. Our data further this study, therefore, was to measure basal intrarenal suggest that antidiuretic hormone may influence intrarenal distribution of renal blood flow in infant primates and to blood flow in addition to altering tubular membrane permea- study changes in distribution of response to the stress of IPPV. bility. Our findings demonstrate that the pattern of intrarenal blood flow distribution in resting infant monkeys is similar to the adult with a preponderance of outer cortical over inner INTRODUCTION cortical flow. Assisted ventilation was found to result in a redistribution of this flow which theoretically would affect Recent studies have demonstrated that renal blood flow in renal function. early infancy is low when compared with that in the older child and adult. Gruskin et al. (7) have shown in infant piglets MATERIALS AND METHODS that this low renal blood flow increases by a fall in intrinsic renal vascular resistance which results in a greater percentage Seventeen infant Macacca sp. monkeys born in the caged of the cardiac output going to the kidneys. Jose and colleagues primate breeding facility at the University of Illinois College of (11) subsequently demonstrated by using 33~ewashout Medicine were used in this study. The infants were born by techniques, that cortical flow (component I) was low when spontaneous vaginal delivery and were studied between 3 and compared with medullary flow (component 11) in puppies up 5 days of age. All infants were mature by weight and to 4 months of age. After 4 months of age, component I flow gestational age. and total renal blood flow increased markedly. These authors For surgery each infant was restrained comfortably on a concluded that there is relative underperfusion of the renal padded frame in the supine position. A catheter (PV 3) was cortex in infant puppies and this is a major factor for the low inserted into a femoral artery and advanced to the left renal blood flow in that age group. ventricle. The placement of this catheter was confirmed by The importance of intrarenal distribution of renal blood pressure recordings and/or fluoroscopy. A second arterial flow is controversial. Hollenberg and Herd (8) have noted that catheter was advanced from the femoral artery and placed although total renal blood flow may be reduced severely in with its tip at the level of the diaphragm. This catheter was chronic renal disease, adequate renal function may persist, used for arterial blood sampling and aortic pressure recordings. whereas a similar decrease in total renal blood flow in acute An additional catheter was inserted into the inferior vena cava renal failure may be associated with oliguria and renal via a femoral vein for infusion and venous blood sampling. insufficiency. The difference in renal function in these After repair of skin incisions, the infant was secured in the conditions may be explained in part by the presence of normal prone position on a toweling roll and placed in an incubator rates of blood flow and glomerular filtration in some portions with room air at constant temperature and humidity. The of the cortex in chronic renal failure but abnormally low period of recovery was from 18 to 24 hr; 100 ml/kg/24 hr of INTRARENAL BLOOD FLOW IN INFANT PRIMATES 79 3 10% glucose in water was given intravenously. Penicillin microscope (23). Careful dissection was done to avoid (1 00,000 unitslkg) and Kanamycin (15 mg/kg) were given as a including any medullary tissue with the inner cortical slices. single injection to each infant after surgery. The tissue slices were weighed on a Mettler balance and the On the following day, the catheters were flushed with saline radioactivity for each isotope in the slices counted. Slices were and control blood gases and flow measurements were taken from both kidneys for comparison of results. The blood obtained. A modification of the radionuclide microsphere flow to the total cortex and segments of the cortex were method described by Rudolph and Heymann (191, 20-25,000 calculated based on weight and radioactivity. The theoretical microspheres, 50 ,um in diameter, were injected slowly into the consideration as to whether or not selected sections of the left ventricle, was utilized to estimate cardiac output and cortex obtained in the described manner represents flow to the organ blood flow. Simultaneously, approximately 1 ml blood kidney as a whole has been discussed by Katz et al. (12). was withdrawn over 1 min from the descending aorta using a The radioactivity due to each isotope in each kidney was constant speed pump. Inasmuch as adequate mixing of calculated using the method of Rudolph and Heymann (18). microspheres and blood has been shown to take place in the Cardiac output, total kidney, and regional cortical blood flows left ventricle, the withdrawn sample of blood which contains were calculated from the following equations microspheres can be quantitated and is directly proportional to cardiac output. Cardiac output Control measurements of cardiac output and distribution of y Activity of blood renal blood flow were done by injection of microspheres Rate aortic blood withdrawal (ml/min) --withdrawn from aorta (I) labeled with 46Sc. Injection of three different nucleotides over Cardiac output (ml/min) Total body y activity 4 days into six control infants showed no significant affect on renal flow by this procedure. After determination of control Renal blood flow values, an endotracheal tube was passed and the infant was Renal blood flow (ml/min) - Kidney y activity placed on a mechanical respirator with IPPV at less than 10 (2) Cardiac output (ml/min) - Total body y activity mm Hg but sufficient to cause expansion of the chest without significant change in blood gases. The IPPV was continued for 6 hr. Arterial pH, Pco,, and base excess were monitored frequently during ventilation. After ventilation, a second Regional cortical flow injection of a different labeled nucleotide (l 1) was made to Renal blood flow (ml/min) - Regioflal cortical flow (ml/min/g) measure any changes in cardiac output and distribution of Renal y activity (dpm/g) - Regional cortical y activity (dpm/g) (3) cortical flow. Blood pressure was measured using a Statham pressure transducer and recorded on a Sanborn recorder. After each experiment the monkeys were killed by injection Statistical analysis of mean values was by means of the of sodium pentobarbital. All organs ezcept the kidneys were Student paired t test. removed, weighed, and ashed at 375 for determination of RESULTS total body radioactivity. Separate experiments were performed to assure that there was no loss of radioactivity at this The mean control arterial pH, base excess and standard temperature. The ashed tissues were then placed in glass vials bicarbonate were 7.385, 3.60, and 20.47, respectively. These and radioactivity measured in a y counter (22). After counting control values indicated the stability of the infants before total kidney radioactivity, the kidneys were dissected along ventilation. The mean control Po, was 97.86 mm Hg and the the sagittal plane according to the method of Katz et al. (12). mean PCO2 was 35.20 mm Hg. These arterial blood gases are The capsule was removed and the cortex divided into equal similar to those reported previously in unstressed Macacca sp. portions of outer and inner cortex using a dissecting monkeys (1). The mean weight of these infants was 502 g Table 1. Control flow measurements1 Cardiac output Total RBF, Cardiac Study Weight, g ml/min ml/min/kg ml/min/gm output, % 2.62 2.62 1.76 4.69 2.1 1 2.81 4.22 1.01 2.26 2.54 1.54 1.99 1.92 2.43 1.53 ' RBF: renal blood flow; OC: outer cortex; IC: inner cortex.