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ANIMAL PRODUCTION |

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Departments of Animal Science and
and
* Anatomy, Physiological Sciences, and Radiology, North Carolina State University, Raleigh 27695
| Abstract |
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Key Words: Acid-Base Balance Blood Variables Gastric Ulcers Sodium Bicarbonate Swine Water Consumption
| Introduction |
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The primary cause of ulcerogenesis in swine is bile and acid reflux into the proximal stomach. Reflux is enhanced when the contents are made highly fluidic owing to consumption of a finely ground diet or as time after feeding increases (Lang et al., 1998
). In a normal, highly acidic stomach, glycocholic acid will primarily be in the uncharged, protonated form, increasing the capacity for membrane disruption (Narain et al., 1999
). Ideally, buffer consumption will maintain gastric pH above 4.0, which Lang et al. (1998)
demonstrated to be the threshold pH for preventing in vitro bile acid damage to the pars esophagea.
Ange et al. (2000)
demonstrated that consumption of 200 mOsm NaHCO3 buffer in the water supply maintained gastric pH above 4.0. However, any potentially deleterious effects related to consumption of increased amounts of NaHCO3, which could include toxic levels of sodium in the blood, severe disruptions of the acid-base balance, and genitourinary problems associated with elevated urine pH, have not yet been investigated. Therefore, the present study was conducted to evaluate systemic acid-base and electrolyte balance and urinary variables in response to consumption of a buffer treatment through the drinking water.
| Materials and Methods |
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Experiment 1
Animals.
Eight barrows weighing 40.7 ± 3.0 kg were obtained from a crossbred herd (Landrace, Duroc, Large White, Hampshire). Six of the animals were then used in a single reversal-design experiment, with two treatments. Animals were housed individually in metabolism crates (0.48 m x 1.61 m) fitted with urine drip trays and fecal screens, in a room with a 12 h light:12 h dark cycle. The animals were weighed immediately before surgery to determine initial weight, and again at the completion of the study to determine final weight.
Surgical Procedures.
All animals were fitted with jugular catheters to allow repeated blood sample collection. Animals were fasted a minimum of 12 h before anesthesia, which was induced via injection of ketamine (11.0 mg/kg BW, i.m.) and xylazine (1.5 mg/kg BW, i.m.) and maintained with isofluorane delivered via mask. To insert the catheter into the jugular vein, a ventral incision approximately 2.5 cm from the midline of the animal was made. Blunt dissection exposed the vein; after making a small incision in the vein, the catheter (i.d. 0.102 cm, o.d. 0.203 cm, micro-renathane) was inserted (approximately 10 cm) and sutured into place. A 45-cm probe allowed exteriorization at the dorsal base of the neck, where a patch secured the catheter. A minimum of 10 d was allowed for recovery following the surgical procedure, before the 24-h period of treatment administration and sample collection.
Water and Diet.
Animals were monitored throughout the day to ensure adequate feed and water availability, as well as overall health of the animal. Water was available ad libitum and delivered via an Arato water nipple (Aratowerk GmbH & Co., Cologne, Germany). Individual 25-L Nalgene water containers provided each animals water supply. Gravity-fed water flow rate averaged 460 mL/min. Water spillage was collected separately from excreted urine and was quantified to more accurately estimate each animals daily water intake.
In this study of the acute effects of buffer administration, the water containers were weighed before administration of the treatment, filled with a measured amount of fresh or buffered water, and suspended above each metabolism crate. Following the collection of the last sample of the 24-h period, the containers were again weighed, and the water intake determined.
A finely ground and pelleted corn/soybean mealbased diet was used (Table 1
). Before pelleting, particle size was determined to be 398 ± 2.35 µm. Animals were fed ad libitum; however, feed intake was monitored daily. Each day at 0800, remaining feed from the previous day was measured and animals were refed at 110% of each animals previous days intake. Animals were fed this diet from the time of catheter insertion to the completion of the sampling period.
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Blood and urine samples were taken throughout the 24-h period. The experimental design allowed animals receiving the treated water in the first period to receive the control in the second period and vice versa. The six animals selected for experimentation were randomly separated into two groups of three, which went through the protocol sequentially for logistical reasons. Each group was randomly divided into two subgroups, designated to receive buffer-treated or control water, and then switched between periods to the other treatment, so that all six pigs would receive both treatments. Between periods, all animals received untreated water for 48 h to eliminate any carryover effect from consuming buffer-treated water.
Sample Collection.
Blood samples were taken at 0730, 0900, 1000, 1200, 1400, 1600, and 0730 the following day. The initial samples collected at 0730 determined the baseline values and were taken before administration of the treatment. Before each collection, a blood volume equivalent to twice the catheter volume was drawn and discarded to prevent contamination of the ensuing sample by the solution used to seal the catheter between samplings. At each collection, 3 mL of blood was collected and sealed immediately to prevent atmospheric exposure and subsequent alteration of blood gas values. Samples were immediately placed on ice and transported to a blood gas analyzer (GEM Premier Plus; Instrumentation Laboratory, Lexington, MA), which quantified pO2, pCO2, HCO3, K+, Na+, and hematocrit. Samples were analyzed within 60 min of collection. Voided urine was collected at 1030, 1230, 1430, 1630, and the following day at 0830. The entire amount voided was immediately weighed and a pH value determined using a pH meter (Acumet; Fischer Scientific, Pittsburgh, PA). Subsamples (
50 mL) were frozen for later determination of Na+, Cl, and K+ on an electrolyte content analyzer (Hitachi 912; Roche Diagnostics, Indianapolis, IN).
Experiment 2
Animals, Water, and Diet.
Ten crossbred barrows weighing 33.8 ± 3.0 kg were obtained and fitted with jugular catheters. Eight of the animals were used in the experiment, which had a single reversal design, although this experiment lasted for 10 d. Barrows were from the same herd as those in Exp 1. They were housed, fed, and watered as described above, with the same procedure used to determine intake of both feed and water. The animals were weighed immediately before surgery to determine an initial weight, and again at the completion of the study to determine a final weight.
Surgical Procedures.
Animals were fitted with jugular catheters, as described for Exp. 1, with the following exceptions. Anesthesia was induced by injection of Telazol (a combination of tiletamine and zolazepam, 3 mg/kg BW), instead of ketamine/xylazine. Anesthesia was maintained with isofluorane administered via orotracheal intubation.
Treatments.
Treatments were initiated at 0800 of d 1 and consisted of either untreated water (control) or water containing sufficient sodium bicarbonate to obtain a calculated 200 mOsm solution. The experimental design allowed the animals to receive one of the two randomly assigned treatments in the first period and then receive the other treatment in the second period. Periods lasted 10 d, with all animals receiving untreated water for 72 h between periods. This allowed elimination of any carryover effect from consumption of treated water in the previous period. Additionally, the animals were randomly divided into two groups, which went through the protocol sequentially.
Sample Collection.
Blood was collected for analysis on d 5 and 10 of each period at 1100, 1300, 1500, and 1700. Blood samples were collected and analyzed as described above. Urine samples were collected daily, following the morning feeding. Samples were weighed and pH was measured. Subsamples were taken and stored for analysis as described above. Water samples were taken daily and frozen for later analysis, as described above. Aliquots of the daily water samples for each animal were later pooled, combining an equal amount of water from each day on which the animal received the buffer treatment, and, separately, received the control treatment. Thus, two samples were measured, in duplicate, for each pig: one untreated sample and one treated sample. These aliquots were then analyzed for osmolality (Micro-osmette; Precision Instruments, Natick, MA).
Statistical Analysis
In both Exp. 1 and 2, data were analyzed using the Proc Mixed procedure of SAS (SAS Inst., Inc., Cary, NC). The repeated factor used was (TIME), representing the time at which each sample was collected. Blood variables were analyzed using a model consisting of treatment, animal(treatment), time, time x treatment, day x treatment, as well as day, and treatment x time x day in Exp. 2 only. In Exp. 1, the initial 0730 samples were analyzed separately from those collected after treatment initiation. Variables were analyzed via the same methods, excepting time inclusive statements. The fixed effects were treatment, time, and day. Random effects included animal within treatment and the interactions. Each animal was an experimental unit. Urine and water variable analysis used the same model, without the time terms. Significance was declared at P < 0.05.
| Results |
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One pigs catheter came out after the first period, so no data were obtained from that pig in the second period. This pig received the control water treatment in the first period, and did not receive the treated water in the second period. Therefore, there were only two animals on the treated water in the second period, leaving only five animals to receive the buffered water treatment, compared with six consuming the untreated water.
Water intake was not affected by treatment. Pigs consuming water treated with bicarbonate consumed 4.34 ± 1.35 kg of water in 24 h, whereas those receiving untreated water consumed 5.05 ± 1.20 kg. Feed intake was monitored from the day animals were acquired until the completion of the study, to assist monitoring the health status of the animals following surgery. From the day the animals were obtained until the conclusion of the study, barrows consumed 1.72 ± 0.20 kg/d; during the two sampling periods the barrows consumed 1.63 ± 0.34 kg/d.
Despite being assigned randomly to treatment groups, pigs in the BUF group demonstrated elevated values (P < 0.05) for blood pH, HCO3, and pCO2 before receiving any treatments (data not shown). In pigs consuming the buffer-treated water, pH remained constant, whereas mean values for HCO3 and pCO2 were increased (Table 2
; P < 0.05). Blood sodium measurements showed an effect (P < 0.05) of treatment, with higher levels seen in BUF pigs (Table 2
). However, the magnitude of these changes is clinically irrelevant because it did not exceed normal ranges for these variables (Nagai et al., 1994
). Blood potassium and hematocrit (Table 2
) were not affected by treatment.
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Experiment 2
Initial body weights of the pigs were 33.6 ± 3.21 kg. Final body weights, taken 43 d later at the completion of the study, were 81.9 ± 8.59 kg. Feed intake was not altered by water treatment; BUF pigs consumed 2.35 ± 0.27 kg/d, and control pigs consumed 2.36 ± 0.38 kg/d.
Bicarbonate was added at a calculated osmolality of 200 mOsm; however, the measured osmolarity of the treated water was 176.6 mOsm/L compared with 6.1 mOsm/L for the untreated water. Water intake (Figure 1
) was monitored daily. Due to a system to divert and account for spillage, water consumption was quantified accurately. Pigs receiving the BUF treatment consumed more (P < 0.001) water (10.10 ± 0.23 kg/d) than the control pigs (6.95 ± 0.23 kg/d).
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Urine electrolyte concentrations (Na+, K+, Cl), pH, and output were also analyzed, with the aim of determining the fate of the excess Na+ intake, or any pH alterations attributable to the bicarbonate treatment. Consumption of NaHCO3 caused an increased urine Na+ concentration within 24 h of treatment initiation (Figure 2
). Overall mean sodium concentration in urine was higher (P < 0.01) in pigs consuming bicarbonate-treated water than in control animals. Overall mean urine K+ concentration (Figure 3
) was lower (P < 0.01) in pigs consuming the BUF treatment. The total amount of potassium excreted was unchanged; BUF pigs excreted 10.8 ± 2.8 g K+/d; control pigs excreted 11.7 ± 3.2 g K+/d.
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| Discussion |
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In Exp. 2, the expected water intake based on feed consumption ranged from 9.13 to 11.7 kg/d. Control animals consumed 6.95 ± 0.42 kg water/d and the BUF pigs consumed 10.10 ± 0.86 kg water/d. The intake values in the second experiment were higher than those in the first experiment owing to the greater feed intake and growth rate of the animals. At the completion of the second experiment, the animals were approximately 27 kg heavier than at the completion of the first experiment. In comparison, Ange et al. (2000)
, using pigs of weights similar to those in the second experiment, reported water disappearance levels for a 200 mOsm water treatment of 13.56 kg/d; however, wastage was not quantified in that study.
The increase in water intake by pigs consuming the BUF treatments may be due to numerous factors. Possibly, the consumption of 200 mOsm water may increase plasma osmolarity, activating hypothalamic thirst sensors, and stimulating increased intake (Vander, 1991
). An alternative explanation may be due to a "salt appetite, thirst analogue." In addition to having a regulatory appetite for salt to ensure adequate intake, many mammalian species have a hedonistic appetite causing ingestion of much higher salt quantities than is required to meet their physiological needs (Vander, 1991
).
The decrease in hematocrit following NaHCO3 administration suggests an extracellular fluid volume expansion owing to Na+ retention. However, this increase is within normal values and thus of limited clinical relevance (Nagai et al., 1994
).
It was theorized that the consumption of such high levels of NaHCO3 (in some cases more than 100 g/d) may alter blood acid-base balance and induce a mild alkalosis. In neither experiment did the BUF treatment result in an increase in blood pH, indicating rapid compensation for excess base intake. Hannon et al. (1990)
reported a mean venous pH value for healthy, untreated pigs of 7.42, with a range of 7.38 to 7.48. The values obtained in this study in pigs consuming NaHCO3 for 10 d (7.43 pH) were well within physiologically tolerable ranges.
Despite the consumption of large quantities of NaHCO3, neither blood K+ concentration nor urine K+ excretion levels were altered. Urine concentration of K+ decreased with the BUF treatment, but, owing to the increased urine output, the total amount of K+ excreted did not change.
Comparison of blood HCO3 levels between Exp. 1 and 2 showed a similar pattern, with the bicarbonate-induced increase being greater in Exp. 1 than in Exp. 2, indicating physiological adaptation. In a study characterizing various blood variables in pigs, Hannon et al. (1990)
observed venous HCO3 levels of 31 mEq/L, which is much lower than even the control pigs in these trials.
Acid-base balance in mammals is regulated primarily by two mechanisms: 1) respiratory control of blood pCO2 and 2) urinary HCO3 excretion (Rose, 1989
). Blood pH is maintained at an optimal level by a 20:1 ratio of HCO3 to CO2 (Hannon et al., 1990
). In these studies, the BUF treatment elevated circulatory HCO3 levels, with no alteration of blood pH. To maintain the optimal 20:1 ratio, the animals hypoventilated, thereby increasing pCO2 levels. Calculating the Henderson-Hasselbach equation, pH = 6.1 + log[HCO3]/[CO2], using values obtained in this study confirm that the consumption of large amounts of NaHCO3 did not cause any disturbance in acid-base balance because the 20:1 ratio was maintained.
Despite the consumption of nearly 25 g/d of Na+ from both feed and water intake, there was little effect on blood levels. Values never approached a concentration of 150 mEq/L, which is considered the minimal threshold for hypernatremia (Fraser et al., 1991
). Pigs consuming 20 g of Na+ from the BUF treatment, in addition to the approximately 5 g/d of Na+ intake in the diet, excreted almost 19 g of Na+ daily in the urine.
As these studies indicate, the consumption of moderate levels of buffer (NaHCO3) may induce a short-term, clinically insignificant alkalotic state, for which the body rapidly compensates. One concern with the elevated urine pH is the development of uroliths. To the best of the authors knowledge, the only report of uroliths in swine was by Manning and Blaney (1986)
. In other species with this problem, such as cats, castration and increased urine pH (typically secondary to bacterial infection) are the two primary risk factors for the development of uroliths (Osborne et al., 1990
). Normal urine pH levels in swine range from 5.5 to 7.7 (Schenkman et al., 1999
). During the 10-d study, both groups of animals produced urine with an elevated pH; however, animals consuming NaHCO3 generated more alkaline urine, with a maximal value of 9.1 seen at d 9. Although this would seem to put the typical commercial animal at risk for the development of urinary tract problems, the increase in urine output following consumption of buffer-treated water, should decrease the likelihood of urinary tract problems associated with increased urine pH. Additionally, if the buffers are used prophylactically during anorexigenic illness, the short-term consumption of buffers would likely eliminate the possibility of urolith formation.
| Implications |
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| Footnotes |
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2 The authors express their appreciation to R. Palmitier, D. Hardin, and C. McLamb for their excellent assistance. ![]()
3 Correspondence: Box 7621 (phone: 919-515-4044; fax: 919-515-7780; e-mail: joan_eisemann{at}ncsu.edu).
Received for publication July 21, 2003. Accepted for publication May 12, 2004.
| Literature Cited |
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