Metabolic acidosis-induced retinopathy in the neonatal rat.
PURPOSE: Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), was previously described by our group. In this model, it is possible that CO2-associated acidosis provides a biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis on the developing retinal vasculature of the neonatal rat was investigated. METHODS: A preliminary study of arterial blood pH was performed to confirm acidosis in our model. In neonatal rats with preplaced left carotid artery catheters, acute blood gas samples were taken 1 to 24 hours after gavage with either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25 and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100 g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of recovery, rats were killed, and retinal vasculature was assessed using fluorescein perfusion and ADPase staining techniques. RESULTS: In the preliminary pH study, the minimum pH after NH4Cl gavage was 7.10+/-0.10 at 3 hours (versus 7.37+/-0.03 in controls, mean +/- SD, P < 0.01). In the formal retinopathy study, preretinal neovascularization occurred in 36% of acidotic rats versus 5% of controls (P < 0.001). Acidotic rats showed growth retardation (final weight 16.5+/-3.0 g versus 20.2+/-2.6 g, P < 0.001). The ratio of vascularized to total retinal area was smaller in acidotic rats (94%+/-4% versus 96%+/-2%, P < 0.001). CONCLUSIONS: Metabolic acidosis alone induces neovascularization similar to ROP in the neonatal rat. This suggests a possible biochemical mechanism by which high levels of CO2 induce neovascularization and supports the suggestion that acidosis may be an independent risk factor for ROP. (+info)
Arteriovenous differences for amino acids and lactate across kidneys of normal and acidotic rats.
1. Arteriovenous differences fro amino acids across kidneys of normal and chronically acidotic rats were measured. Glutamine was the only amino acid extracted in increased amounts in acidosis. There was a considerable production of serine by kidneys from both normal and acidotic rats. 2. The arterial blood concentration of glutamine was significantly decreased in acidotic animals. 3. The glutamine extracted by kidneys of acidotic rats was largely and probably exclusively derived from the plasma. 4. The blood lactate concentration was unchanged in acidosis, as was the uptake of lactate by the kidney. (+info)
Abnormal ductus venosus blood flow: a clue to umbilical cord complication.
We report a case of umbilical cord complication causing, fetal hypoxemia and acidemia. At 30 weeks of gestation, the patient was referred because of slightly increased amniotic fluid volume and a non-reactive cardiotocogram. Biometry was appropriate for gestational age. Umbilical artery and fetal aortic Doppler findings were normal, whereas diastolic blood flow velocities in the middle cerebral artery were increased and the ductus venosus showed severely abnormal flow velocity waveforms with reversal of flow during atrial contraction. Since other reasons for fetal hypoxemia could be excluded, careful examination of the umbilical cord was performed. Traction of the hypercoiled umbilical cord due to its course around the fetal neck and shoulders was suspected. Cesarean section confirmed the sonographic findings and fetal blood gases revealed fetal acidemia. This case indicates that investigation of fetal venous blood flow may also help to identify fetal jeopardy due to reasons other than increased placental vascular resistance. (+info)
Epidural analgesia with bupivacaine does not improve splanchnic tissue perfusion after aortic reconstruction surgery.
Inadequate splanchnic tissue perfusion is relatively common during and after aortic surgery. We hypothesized that vasodilation caused by thoracic epidural analgesia improves splanchnic blood flow and tissue perfusion after aortic surgery. In this prospective, randomized, controlled study, we studied 20 patients undergoing elective aortic-femoral or aortic-iliac reconstruction surgery. Gastric and sigmoid colon mucosal PCO2 and pH were measured during surgery. An epidural bolus of bupivacaine 40 mg followed by infusion of 15 mg h-1 was started after operation in 10 patients. After operation, splanchnic blood flow and gastric and sigmoid colon mucosal PCO2 and pH were measured before and 2 h after the start of epidural analgesia. During surgery, the gastric mucosal-arterial PCO2 difference remained stable, whereas the sigmoid mucosal-arterial PCO2 difference increased during aortic clamping but returned to pre-clamping values after declamping. After operation, epidural analgesia had no effect on gastric or sigmoid mucosal-arterial PCO2 differences or on splanchnic blood flow. (+info)
Temporal differences in actions of calcium channel blockers on K+ accumulation, cardiac function, and high-energy phosphate levels in ischemic guinea pig hearts.
We investigated temporal differences in the protective action of three types of Ca2+ channel blockers in myocardial ischemia, focusing particularly on the blocking ability under depolarizing conditions. The effects of diltiazem, verapamil, and nifedipine on extracellular potassium concentration ([K+]e), acidosis, and level of metabolic markers were examined during 30-min global ischemia and postischemic left ventricular (LV) function in isolated guinea pig hearts. Diltiazem and verapamil, but not nifedipine, inhibited the late phase (15-30 min) of [K+]e elevation, whereas all three blockers delayed the onset of the early phase (0-8 min) of [K+]e elevation. Diltiazem and verapamil inhibited ischemic contracture and improved postischemic LV function to a greater extent. These differences appeared to be linked to preservation of ATP and creatine phosphate and delay of cessation of anaerobic glycolytic activity. Maneuvers to preserve energy sources during ischemia (decrease in external Ca2+ concentration or pacing at a lower frequency) attenuated the late phase of [K+]e elevation. Inhibition of LV pressure was potentiated 12- and 8.2-fold by diltiazem and verapamil, respectively, at 8.9 mM K+ as compared with 2.9 mM K+, whereas that by nifedipine was unchanged. These results indicate that the differential cardioprotection of Ca2+ channel blockers in the late period of ischemia correlates with preservation of high-energy phosphates as a result of different Ca2+ channel blocking abilities under high [K+]e conditions. (+info)
BACKGROUND: Changes in acid-base balance caused by infusion of a 0.9% saline solution during anesthesia and surgery are poorly characterized. Therefore, the authors evaluated these phenomena in a dose-response study. METHODS: Two groups of 12 patients each who were undergoing major intraabdominal gynecologic surgery were assigned randomly to receive 0.9% saline or lactated Ringer's solution in a dosage of 30 ml x kg(-1) x h(-1). The pH, arterial carbon dioxide tension, and serum concentrations of sodium, potassium, chloride, lactate, and total protein were measured in 30-min intervals. The serum bicarbonate concentration was calculated using the Henderson-Hasselbalch equation and also using the Stewart approach from the strong ion difference and the amount of weak plasma acid. The strong ion difference was calculated as serum sodium + serum potassium - serum chloride - serum lactate. The amount of weak plasma acid was calculated as the serum total protein concentration in g/dl x 2.43. RESULTS: Infusion of 0.9% saline, but not lactated Ringer's solution, caused a metabolic acidosis with hyperchloremia and a concomitant decrease in the strong ion difference. Calculating the serum bicarbonate concentration using the Henderson-Hasselbalch equation or the Stewart approach produced equivalent results. CONCLUSIONS: Infusion of approximately 30 ml x kg(-1) x h(-1) saline during anesthesia and surgery inevitably leads to metabolic acidosis, which is not observed after administration of lactated Ringer's solution. The acidosis is associated with hyperchloremia. (+info)
Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting.
The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system. (+info)
Changes in intracellular Na+ and pH in rat heart during ischemia: role of Na+/H+ exchanger.
The role of the Na+/H+ exchanger in rat hearts during ischemia and reperfusion was investigated by measurements of intracellular Na+ concentration ([Na+]i) and intracellular and extracellular pH. Under our standard conditions (2-Hz stimulation), 10 min of ischemia caused no significant rise in [Na+]i but an acidosis of 1.0 pH unit, suggesting that the Na+/H+ exchanger was inactive during ischemia. This was confirmed by showing that the Na+/H+ exchange inhibitor methylisobutyl amiloride (MIA) had no effect on [Na+]i or on intracellular pH during ischemia. However, there was a short-lived increase in [Na+]i of 8.2 +/- 0.6 mM on reperfusion, which was reduced by MIA, showing that the Na+/H+ exchanger became active on reperfusion. To investigate the role of metabolic changes, we measured [Na+]i during anoxia. The [Na+]i did not change during 10 min of anoxia, but there was a small, transient rise of [Na+]i on reoxygenation, which was inhibited by MIA. In addition, we show that the Na+/H+ exchanger, tested by sodium lactate exposure, was inhibited during anoxia. These results show that the Na+/H+ exchanger is inhibited during ischemia and anoxia, probably by an intracellular metabolic mechanism. The exchanger activates rapidly on reperfusion and can cause a rapid rise in [Na+]i. (+info)