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PubMed1997

Effects of anoxia, acidosis and temperature on the contractile properties of turtle cardiac muscle strips.

The responses to anoxia and acidosis of cardiac ventricular muscle strips from the anoxia-tolerant turtle Chrysemys picta bellii were investigated at 10 degrees C and 20 degrees C. Force-velocity curves were determined by quick isotonic releases at 85% of the time to peak isometric force under control, anoxia, lactate acidosis and anoxic lactate acidosis conditions. The isotonic forces during quick releases spanned 5-95% of the measured isometric force at each conditions. Superfusion solution pH was 7.8 and 7.95 for non-acidosis experiments, and 7.0 and 7.15 for acidosis experiments, at 20 degrees C and 10 degrees C, respectively. After normalizing force data to control isometric force, the values of maximum isometric force (P0), maximum velocity of shortening (Vmax) and maximal power output (Powermax) were evaluated by fitting the curves using the hyperbolic Hill equation. The maximum rate of force development (dF/dtmax), time-to-peak force (TPF) and half-relaxation time (T1/2) were also determined. At 20 degrees C, during acidosis, anoxia and anoxic acidosis, P0 decreased significantly to 81%, 40% and 24% of control values, dF/dtmax decreased significantly to 67%, 53% and 23% of control values, and Powermax decreased significantly to 75%, 40% and 14% of control values, respectively. Vmax, however, was not significantly affected by acidosis, anoxia or even anoxia acidosis. TPF was significantly shortened by anoxia, but prolonged by acidosis. The effects were similar at 10 degrees C, Temperature did not affect P0, but Vmax decreased by a factor of 1.6-1.8 at all corresponding conditions when temperature was reduced from 20 degrees C to 10 degrees C. We conclude that acidosis and anoxia inhibit isometric force production and Powermax of turtle cardiac muscle, but have no effect on Vmax, and the insensitivity of Vmax indicates that the rate of cross-bridge cycling is not affected by these conditions. Our observations indicate that the reduced power outputs of the hearts of submerged anoxic turtles at low temperature are due in part to inhibition of force production by anoxia and acidosis, and to a reduction of contraction velocity at low temperature.

Acidosis, Lactic↗
PubMed1995

Influence of acidosis, hypoxemia, and hypotension on neurodevelopmental outcome in very low birth weight infants.

OBJECTIVE: We previously demonstrated that acidosis (pH < 7.15) predicts poor motor outcome in very low birth weight (VLBW) infants. The present study was undertaken to examine the association between acidosis and developmental outcome in more detail and to better understand the interrelationship of acidosis with related factors such as hypoxemia and hypotension. METHODS: The nursery records of 191 infants enrolled in our VLBW follow-up study were reviewed to identify the type of acidosis (metabolic or respiratory) present, measure the duration of single and cumulative episodes, and examine the interaction of acidosis with hypoxemia and hypotension. The Bayley Scales of Infant Development and a detailed neurologic examination were performed at 6 (n = 158) and 24 (n = 106) months corrected age. RESULTS: At 6 months, both respiratory and metabolic acidosis as well as the total duration and longest single episode of acidosis were significantly correlated with cognitive, motor, and neurologic outcome (P < .0001). By 24 months, only the association of the metabolic component of acidosis with all three outcome measures remained significant. Duration of hypotension independently correlated with outcome at both testing periods (P < .002) but isolated hypoxemia did not. The metabolic component of acidosis and isolated hypotension contributed significantly to the variance in all three outcome measures (P < .05). Duration of hypoxemia, but not hypotension, contributed significantly (53%) to the variance in the metabolic component of acidosis. CONCLUSION: We conclude that it is the metabolic component of acidosis that is important in predicting poor developmental outcome in VLBW infants. The detrimental effect of hypoxemia appears to be closely related to the occurrence of metabolic acidosis while hypotension has an independent effect on outcome.

Acidosis↗
PubMedDate not supplied

Influence of acidosis on protein metabolism.

Acidosis is a common clinical condition with both chronic and acute forms. Chronic metabolic acidosis induces an increase in protein degradation; however, its effects on protein synthesis are less clear. Metabolic acidosis increases net whole-body proteolysis by a massive increase in protein degradation and only a moderate increase in protein synthesis. Most studies in humans on the relation between acidosis and protein metabolism have concentrated on patients with chronic renal failure with metabolic acidosis. However, because chronic renal failure is associated with other abnormal metabolic conditions such as malnutrition, it is difficult to separate out the effects on protein metabolism solely due to acidosis. Data on the influence of other forms of acidosis, e.g., respiratory acidosis, diabetic ketoacidosis, and lactic acidosis, on protein turnover are sparse. Similarly, data about the influence of acidosis on the metabolism of other proteins, such as the liver-produced secretory proteins, are lacking. Future research should more vigorously investigate the influence of acidosis on protein metabolism in various clinical conditions and the potential regulatory effects on the metabolism of secretory proteins. The reversal of acidosis might prove to have beneficial effects on protein wasting, and thus decrease morbidity and possibly mortality.

Acid-Base Equilibrium↗
PubMed2006

Unexplained acidosis of malnutrition: a study by ion-exchange chromatography/mass spectrometry.

Keto-acidosis is usually associated with uncontrolled diabetes and typically poses few diagnostic problems when presenting as hyperglycaemia, metabolic acidosis and a high anion gap. An emaciated patient suffering from Duchenne Muscular Dystrophy and volume depletion presented with acidosis of unknown origin. Preliminary investigations appeared to rule out lactic acidosis, diabetic keto-acidosis and acidosis due to base loss. We have previously reported a technique utilizing liquid chromatography coupled to mass spectrometry (LC-MS) which can be used to characterize the underlying aetiology of acidosis and applied it to ultrafiltrate derived from a blood sample taken from this patient. The anion profile obtained on the chromatogram showed elevated levels of acetoacetate and hydroxybutyrate but no evidence of lactic acidosis, nor was the profile typical of that seen in 'unexplained' acidosis. We concluded that the patient was suffering from keto-acidosis associated with starvation and dehydration, the biochemical features being obscured by both the patient's chronic malnutrition and minimal muscle mass. A combination of enteral feeding and rehydration led to prompt resolution of the patient's metabolic acidosis.

Acetoacetates↗
PubMed1993

Hypoxia and metabolic acidosis in the isolated heart: evidence for synergistic injury.

Although hypoxia and metabolic acidosis have both been shown to impair cardiac function, some workers have suggested that acidosis during a period of hypoxia will actually accelerate physiologic recovery from this insult. To address the interactions of metabolic acidosis and hypoxia further, isolated isovolumic rat hearts were exposed to normal perfusion conditions for 30 min to establish baseline conditions, then either continued normal conditions, metabolic acidosis, hypoxia, or combined acidosis and hypoxia for 30 min and subsequently reperfused under normal perfusion conditions for an additional 30 min. We observed that acidosis + hypoxia impaired recovery of cardiac contraction more than acidosis or hypoxia alone following experimental perfusion. The combination of acidosis and and hypoxia also impaired cardiac energy metabolism more than acidosis or hypoxia alone as assessed by increases in tissue inorganic phosphate during experimental perfusion as well as during reperfusion. These data suggest that during hypoxia, acidosis appears to primarily impair cardiac energy production as we have previously observed in the normoxic isolated rat heart. Therefore, in the intact beating heart, acidosis may not protect from hypoxic injury as has been suggested in simpler systems but may not protect from hypoxic injury as has been suggested in simpler systems but rather may exacerbate at.

Acidosis↗
PubMed1999

Growth hormone corrects acidosis-induced renal nitrogen wasting and renal phosphate depletion and attenuates renal magnesium wasting in humans.

We have shown previously that chronic hyperchloremic metabolic acidosis (CMA) induces severe negative nitrogen balance and renal phosphate depletion and decreases serum insulin-like growth factor-1 (IGF-1) in association with growth hormone (GH) insensitivity in humans. The present study investigated whether acidosis-induced renal nitrogen wasting and renal phosphate depletion are mediated by GH insensitivity/low IGF-1 and thereby responsive to GH treatment. The effects of GH on acidosis-induced changes in divalent cation metabolism and acidosis-induced hypothyroidism were also investigated. CMA (delta[HCO3], -10.5 mmol/L) was induced in six healthy male subjects ingesting 4.2 mmol NH4Cl/kg body weight [BW]/d for 7 days. Recombinant human GH (0.1 U/kg BW/12 h subcutaneously) was administered for 7 days while acid feeding was continued. GH increased serum IGF-1 from 22.1 +/- 1.4 to 87 +/- 8.4 nmol/L (control level, 36.4 +/- 2.2). GH decreased urinary nitrogen excretion, resulting in a cumulative nitrogen retention of 2,404 mmol, thereby correcting the acidosis-induced cumulative increase in nitrogen excretion (2,506 mmol) despite continued acid feeding. GH attenuated the acidosis-induced hyperphosphaturia (cumulative phosphate retention, 91 mmol) and corrected the hypophosphatemia. GH did not affect acidosis-induced ionized hypercalcemia, but further exacerbated acidosis-induced hypercalciuria (cumulative loss, 27.3 mmol). GH significantly further increased serum 1,25-dihydroxyvitamin D (1,25(OH)2D) and further decreased intact PTH (from 10 +/- 1 to 6 +/- 1 pg/mL). Acidosis also induced hypomagnesemia and hypermagnesuria (cumulative loss, 9.4 mmol, ie, renal magnesium wasting), a novel finding, which was significantly attenuated by GH (cumulative retention, 5.0 mmol). In conclusion, GH corrected acidosis-induced renal nitrogen wasting, which may be caused, at least in part, by decreased IGF-1 levels. GH further increased serum 1,25(OH)2D and the systemic calcium load, which account for the suppression of parathyroid hormone (PTH) despite renal PO4 retention and correction of hypophosphatemia. GH attenuated acidosis-induced renal magnesium wasting.

Acidosis, Renal Tubular↗
PubMed2002

[Hyperchloremic acidosis druing plasma volume replacement].

OBJECTIVES: Review of the physiological and clinical consequences of hyperchloraemic acidosis observed during plasma volume replacement using crystalloids and colloids. DATA SOURCES: Data were searched in the Medline database after 1990 using the following key words: metabolic acidosis, crystalloids, colloids, albumin, gelatin, hydroxyethyl starch. DATA EXTRACTION: Publications before 1990 were selected for their historical value. Most of articles published after 1990 and all types including case report were accepted. DATA SYNTHESIS: Large volume infusion of isotonic solution can cause hyperchloraemic acidosis. Colloid plasma substitutes using saline solvent may be responsible for the same kind of acidosis with acidaemia. The anion gap is not modified in this case because of chloride increase. Physiological mechanism may be described using the Henderson-Hasselbach equation or the strong ion difference decrease (Stewart concept). Excessive chloride infusion is a major factor in this acid-base disorder and the term hyperchloraemic acidosis should be preferred to dilutional acidosis. When perioperative acidosis occurs, careful and complete analysis of acid-base disturbance should be made. The association of a normal anion gap, normal lactatemia, hyperchloraemia and acidaemia does not need specific treatment. Acidosis corrects spontaneously and slowly following chloride normalization. But any factor that may increase acidosis should be avoided. CONCLUSION: The use of balanced solution like lactated-Ringer solution instead of isotonic saline solution for fluid resuscitation, except for specific contra-indication as intracranial hypertension, may avoid hyperchloraemic acidosis. Potential risk of this acidosis led to the conception of a new colloid using balanced crystalloids solution as the solvent (Hextend).

Acidosis↗
PubMed2002

Lactic acidosis and status asthmaticus: how common in pediatrics?

BACKGROUND: Lactic acidosis is a well described phenomenon in adult patients with severe asthma. However, this entity is rarely reported in children with status asthmaticus. OBJECTIVE: To report our experience in a 13-year-old girl who developed lactic acidosis as a complication of status asthmaticus and to investigate the prevalence of this complication of severe asthma. We sought to determine the frequency of lactic acidosis in such patients and to review etiologies of lactic acidosis. METHODS: 1) Observations on the clinical and laboratory findings in an adolescent girl with status asthmaticus who developed lactic acidosis were recorded. 2) The medical records of 100 children and adolescents with status asthmaticus admitted to an intensive care unit were reviewed for laboratory evidence of lactic acidosis. 3) We also reviewed our own previous experience of status asthmaticus with respiratory failure. RESULTS: Among 100 patients admitted to a pediatric intensive care unit for status asthmaticus, a single case of isolated metabolic acidosis was identified. This proved to be attributable to lactic acidosis. When records of patients with severe respiratory failure were examined, no cases of metabolic acidosis were found. CONCLUSIONS: Although rare, lactic acidosis does occur in pediatric-aged patients during status asthmaticus. It is important that this complication be recognized and treated because acidosis may inhibit the effectiveness of bronchodilator therapy, produce electrolyte disturbances, and cause serious adverse effects on the patient's cardiovascular system.

Acidosis, Lactic↗
PubMed2003

Stimulation of the plasma membrane Na+/H+ exchanger NHE1 by sustained intracellular acidosis. Evidence for a novel mechanism mediated by the ERK pathway.

Activity of the Na+/H+ exchanger (NHE) isoform 1 (NHE1) is increased by intracellular acidosis through the interaction of intracellular H+ with an allosteric modifier site in the transport domain. Additional regulation is achieved via kinase-mediated modulation of the NHE1 regulatory domain. To determine if intracellular acidosis stimulates NHE1 activity solely by the allosteric mechanism, we subjected cultured neonatal rat ventricular myocytes (NRVM) with native NHE1 expression to intracellular acidosis (pHi approximately 6.6) for up to 6 min by transient exposure to NH4Cl and its washout in the presence of NHE inhibition (by zero [Na+]o or the NHE1 inhibitor cariporide) in HCO3- -free medium. After the desired duration of acidosis, NHE was reactivated (by reintroduction of [Na+]o or removal of cariporide), and the rate of recovery of pHi (dpHi/dt) was measured as the index of NHE activity. Regardless of the method used when intracellular acidosis was sustained for > or =3 min, subsequent NHE activity was significantly increased (>4-fold). Similar NHE stimulatory effects of sustained acidosis were observed in adult rat ventricular myocytes and COS-7 cells. Sustained (3 min) intracellular acidosis activated several NHE1 kinases in NRVM, in an in-gel kinase assay using as substrate a glutathione S-transferase fusion protein of the NHE1 regulatory domain. Detailed investigation of ERK and its downstream effector p90RSK, two putative NHE1 kinases, revealed time-dependent activation of both by intracellular acidosis in NRVM. Furthermore, inhibition of MEK1/2 by pretreatment of NRVM with two structurally distinct inhibitors, PD98059 (30 microM) or UO126 (3 microM), inhibited the activation of ERK and p90RSK and abolished the stimulation of NHE activity by sustained (3 min) intracellular acidosis. Our data show that not only the extent but also the duration of intracellular acidosis regulates NHE1 activity and suggest that the stimulatory effect of sustained intracellular acidosis occurs through a novel mechanism mediated by activation of the ERK pathway.

Acidosis↗
PubMed1991

31P-NMR study of normoxic and anoxic perfused turtle heart during graded CO2 and lactic acidosis.

We studied the effects of graded acidosis (both CO2 and lactic acid) and anoxia on intracellular pH (pHi) regulation, high-energy phosphates, and mechanical function of isolated perfused hearts of the turtle (Chrysemys picta bellii) at 20 degrees C using 31P-nuclear magnetic resonance (NMR) spectroscopy. During CO2 acidosis, anoxia had no effect on apparent nonbicarbonate buffer value (d[HCO3-]/dpHi = 71 and 89 mM/pH in normoxia and anoxia, respectively) or on pHi regulation (dpHi/dpHe = 0.52 and 0.43 in normoxia and anoxia, respectively, where pHe is extracellular pH). During normoxic lactic acidosis, dpHi/dpHe was similar to the values observed in CO2 acidosis and averaged 0.55 overall. During anoxic lactic acidosis, however, similar regulation occurred over only a narrow range of pHe, and then dpHi/dpHe increased to greater than 1.0 at pHe less than 7.1. Creatine phosphate (CP), calculated as the area of the NMR peak, fell more in response to normoxic CO2 acidosis than to normoxic lactic acidosis; in anoxia, the fall in CP was further increased but to similar extreme levels (10-20% of control) in both acid perfusions. Cardiac output and maximum rate of pressure development each fell during acidosis in similar fashion in all protocols, and the responses were similar in normoxic and anoxic hearts. Heart rate, in contrast, decreased during acidosis, but this effect was more pronounced when hearts were anoxic. We conclude that the effect of acidosis on cardiac function can depend on the type of acidosis imposed. Based on the heart's insensitivity to anoxia alone, we suggest that anoxia may normally depress function indirectly via its effect on intracellular acid-base state.

Acidosis, Lactic↗
PubMed1983

Synergistic effects of acute hypoxemia and hypercapnic acidosis in conscious dogs. Renal dysfunction and activation of the renin-angiotensin system.

The effects of acute hypoxemia and hypercapnic acidosis were examined in five unanesthetized dogs in which sodium intake was controlled at 80 mEq/24 hours for 4 days prior to study. Each animal was studied during combined acute hypoxemia and hypercapnic acidosis (Pao2 = 36 +/- 1 mm Hg, Paco2 = 52 +/- 1 mm Hg, pH = 7.18 +/- 0.02), acute hypoxemia alone (Pao2 = 32 +/- 1 mm Hg, Paco2 = 32 +/- 1mm Hg, pH = 7.34 +/- 0.01), and acute hypercapnic acidosis alone (Pao2 = 82 +/- 2 mm Hg, Paco2 = 51 +/- 1 mm Hg, pH = 7.18 +/- 0.02). Although mean arterial pressure, cardiac output, and heart rate increased during combined hypoxemia and hypercapnic acidosis, effective renal plasma flow and glomerular filtration rate decreased. In addition, filtered sodium load and urinary sodium excretion decreased during combined hypoxemia and hypercapnic acidosis. Either acute hypoxemia or hypercapnic acidosis alone resulted in increased mean arterial pressure, cardiac output, and heart rate. However, in contrast to their combined effects, renal hemodynamic function was unchanged and natriuresis was observed. Measurement of plasma renin activity and angiotensin II concentrations indicated that hypoxemia or hypercapnic acidosis alone resulted in moderate activation of the renin-angiotensin system. Moreover, combined hypoxemia and hypercapnic acidosis acted synergistically resulting in major renin-angiotensin activation. Systemic angiotensin II blockade using 1-sarcosine, 8-alanine, angiotensin II (2 micrograms/kg per min) during combined acute hypoxemia and hypercapnic acidosis resulted in decreased renal hemodynamic function. We conclude that acute hypoxemia and hypercapnic acidosis act synergistically to increase mean arterial pressure, diminish renal hemodynamic function and activate the renin-angiotensin system. Systemic angiotensin inhibition studies suggest activation of the renin-angiotensin system maintains renal hemodynamic function during combined hypoxemia and hypercapnic acidosis, instead of mediating the renal vasoconstriction.

Acidosis, Respiratory↗
PubMed1994

Stunned myocardium after rapid correction of acidosis. Increased oxygen cost of contractility and the role of the Na(+)-H+ exchange system.

Left ventricular (LV) contractile dysfunction during acidosis has been reported to be almost reversible in crystalloid-perfused hearts after correction of acidosis. In contrast, we have found that, in blood-perfused hearts, contractile function is paradoxically depressed after correction of acidosis with a transient overshoot of contractility during the recovery of pH. To clarify the mechanism of this phenomenon, we measured the LV contractility index (Emax) and the relation between myocardial oxygen consumption (VO2) and systolic pressure-volume area (PVA, a measure of the LV total mechanical energy) before and after induction and rapid correction of acidosis by CO2 loading (pH 7.00) and unloading in 13 excised cross-circulated canine hearts. During the rapid correction of acidosis in six control hearts, a severe transient overshoot of Emax (404% of acidosis) occurred. However, after correction of acidosis, Emax and PVA were lower than the preacidosis values by 46% (P < .01) and 44% (P < .01) at the same LV volume. When the preacidosis Emax level was restored by Ca2+ infusion, the VO2 intercept (PVA-independent VO2) of the linear VO2-PVA relation exceeded the control value by 18% (P < .05) with an unchanged slope. In addition, the oxygen cost of contractility, defined as the slope of the relation between PVA-independent VO2 and Emax, increased by 83% (P < .01) after correction of acidosis, indicating that postacidosis myocardium requires higher VO2 for nonmechanical activities for a unit increase in Emax. Then, we hypothesized that these mechanoenergetic disorders after rapid correction of acidosis would result from Ca2+ overload via accelerated Na(+)-Ca2+ exchange due to the heavily operating Na(+)-H+ exchange system at the time of rapid pH recovery. To examine this hypothesis, dimethylamiloride, a selective Na(+)-H+ exchange inhibitor, was administered just before the correction of acidosis in the other seven hearts. The administration of dimethylamiloride completely prevented both the mechanical and energetic disorders after correction of acidosis. We conclude that rapid recovery of pH paradoxically depresses myocardial contractility and increases the oxygen cost of contractility through an activation of the Na(+)-H+ exchange system.

Acidosis↗
PubMed1986

Effect of acidosis on chloride transport in the cortical thick ascending limb of Henle perfused in vitro.

The present studies examined the effect of acute in vitro acidosis on chloride reabsorption in the rabbit cortical thick ascending limb of Henle (cTALH). Four protocols were used: hypercapnic acidosis; "isocapnic" peritubular acidosis (bath bicarbonate reduction to 10 mM); isocapnic luminal acidosis (luminal bicarbonate reduction to 10 mM); isocapnic peritubular acidosis in the absence of luminal potassium. Transepithelial voltage (VT) decreased during hypercapnic acidosis and increased with recovery. Chloride reabsorption (pmol X mm-1 X min-1) decreased from 50.3 +/- 8.4 to 15.7 +/- 5.6, then increased to 45.6 +/- 11.1 with recovery. Likewise, VT was decreased reversibly during isocapnic peritubular acidosis, and chloride reabsorption decreased by 60%. Chloride reabsorption was greater (28.3 +/- 3.6) when tubules were perfused at normal luminal pH than at an acidotic luminal pH (11.4 +/- 4.5; P less than 0.05). Luminal potassium removal reduced chloride transport, and acidosis had no significant additional effect. Decreased chloride reabsorption in the cTALH during acidosis could contribute to the chloruresis associated with systemic acidosis. The symmetrical nature of this effect suggests that acidosis inhibits chloride reabsorption through an effect on cytosolic pH.

Acidosis↗
PubMed2006

Contractile recovery from acidosis in toad ventricle is independent of intracellular pH and relies upon Ca2+ influx.

Hypercapnic acidosis produces a negative inotropic effect on myocardial contractility followed by a partial recovery that occurs in spite of the persistent extracellular acidosis. The underlying mechanisms of this recovery are far from understood, especially in those species in which excitation-contraction coupling differs from that of the mammalian heart. The main goal of the present experiments was to obtain a better understanding of these mechanisms in the toad heart. Hypercapnic acidosis, induced by switching from a bicarbonate-buffered solution equilibrated with 5% CO2 to the same solution equilibrated with 12% CO2, evoked a decrease in contractility followed by a recovery that reached values higher than controls after 30 min of continued acidosis. This contractile pattern was associated with an initial decrease in intracellular pH (pHi) that recovered to control values in spite of the persistent extracellular acidosis. Blockade of the Na+/H+ exchanger (NHE) with cariporide (5 micromol l-1) produced a complete inhibition of pHi restitution, without affecting the mechanical recovery. Hypercapnic acidosis also produced a gradual increase of diastolic and peak Ca2+i transient values, which occurred immediately after the acidosis was settled and persisted during the mechanical recovery phase. Inhibition of Ca2+ influx through the reverse mode of the Na+/Ca2+ exchanger (NCX) by KB-R (1 micromol l-1 for myocytes and 20 micromol l-1 for ventricular strips), or of L-type Ca2+ channels by nifedipine (0.5 micromol l-1), completely abolished the mechanical recovery. Acidosis also produced an increase in the action potential duration. This prolongation persisted throughout the acidosis period. Our results show that in toad ventricular myocardium, acidosis produces a decrease in contractility, due to a decrease in Ca2+ myofilament responsiveness, followed by a contractile recovery, which is independent of pHi recovery and relies on an increase in the influx of Ca2+. The results further indicate that both the reverse mode NCX and the L-type Ca2+ channels, appear to be involved in the increase in intracellular Ca2+ concentration that mediates the contractile recovery from acidosis.

Acidosis↗
PubMed1998

The role of adenosine in rat coronary flow regulation during respiratory and metabolic acidosis.

The role of adenosine in rat coronary flow regulation during acidosis was evaluated in isolated, perfused, Langendorff rat heart preparations exposed to brief periods of hypercapnic or metabolic acidosis. Acidosis resulted in increases in coronary flow rate, in conjunction with decreases in ventricular contractile tensions. Heart rates were non-significantly increased. Two non-selective adenosine antagonists, caffeine and 8-phenyltheophylline, markedly attenuated the increases in coronary flow during hypercapnic acidosis without affecting the decline in contractile tension or the heart rate. ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a]triazin-5-ylami no]ethyl)phenol), a selective adenosine A2A receptor antagonist, also blocked hypercapnic acidosis-evoked coronary flow rate increases. The adenosine A1 selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine, did not affect flow rate increases during hypercapnic acidosis. SCH 58261 (5-amino-7-(2-phenyl ethyl)-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine, a selective adenosine A2A receptor antagonist, blocked the increases in coronary flow rate evoked by metabolic acidosis. An adenosine transport inhibitor, dipyridamole, doubled coronary flow rates during hypercapnic acidosis. When taken in conjunction with previous reports that acidosis enhances adenosine release from cardiac preparations, these results suggest that adenosine is a significant contributor to acidosis-evoked increases in coronary flow.

Acidosis↗
PubMed1976

The acute effects of respiratory and metabolic acidosis on renal function in the dog.

1. Effective renal plasma flow, glomerular filtration rate and cardiac output were measured in osmotically loaded dogs before and during comparable acute respiratory and metabolic acidosis. 2. Urine output increased in control dogs and in animals with metabolic acidosis, but declined with respiratory acidosis. Effective renal plasma flow and glomerular filtration rate declined with respiratory and metabolic acidosis. 3. When respiratory acidosis was buffered with sodium bicarbonate, urine volume increased and glomerular filtration rate and effective renal plasma flow were unchanged; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate and effective renal plasma flow fell. 4. When metabolic acidosis was buffered with sodium bicarbonate, urine volume increased; with trihydroxymethylaminomethane, urine volume increased but glomerular filtration rate fell. Cardiac output declined only during metabolic acidosis, both buffered and unbuffered. 5. These studies demonstrate that, even with osmotic loading: (1) respiratory acidosis caused a decrease in glomerular filtration rate, effective renal plasma flow and urine volume; (2) metabolic acidosis depresses glomerular filtration rate and effective renal plasma flow but does not change urine volume even though cardiac output falls; (3) sodium bicarbonate is mor effective than trihydroxymethylaminomethane in preserving renal function during respiratory and metabolic acidosis.

Acidosis↗
PubMed1991

Myocardial uptake and pharmacodynamics of quinidine and propafenone in isolated rabbit hearts: metabolic versus respiratory acidosis.

The influence of metabolic and respiratory acidosis on the myocardial accumulation and pharmacodynamics of quinidine and propafenone was studied in isolated perfused rabbit hearts. Three pH groups were evaluated: physiologic buffer, pH 7.4; metabolic acidosis, pH 7.0; and respiratory acidosis, pH 7.0. Myocardial accumulation of quinidine and propafenone was significantly reduced during acidosis. Although myocardial quinidine concentrations were similar in the metabolic acidosis group (14.4 +/- 1.2 micrograms/g) and the respiratory acidosis group (14.5 +/- 1.3 micrograms/g), the myocardial propafenone concentration was significantly less during metabolic acidosis (8.9 +/- 2.0 micrograms/g) as compared with respiratory acidosis (12.7 +/- 2.4 micrograms/g, p less than 0.05). The myocardial concentration-effect relationships were linear over the observed myocardial concentration ranges. The slopes of the linear concentration-effect relationships describing QRS duration were increased twofold by both types of acidosis as compared with normal pH (p less than 0.05). In contrast, the slopes of the concentration-effect relationships describing changes in ventricular repolarization and refractoriness were increased only during metabolic acidosis as compared with pH 7.4 (p less than 0.05). Thus, for any given concentration of drugs, the effects of quinidine and propafenone on ventricular conduction time are dependent on the pH of the perfusate, whereas these drug effects on ventricular repolarization and refractoriness are dependent on the buffer composition.

Acidosis↗
PubMed2001

Metabolic, but not respiratory, acidosis increases bone PGE(2) levels and calcium release.

A decrease in blood pH may be due to either a reduction in bicarbonate concentration ([HCO(3)(-)]; metabolic acidosis) or to an increase in PCO(2) (respiratory acidosis). In mammals, metabolic, but not respiratory, acidosis increases urine calcium excretion without altering intestinal calcium absorption, indicating that the additional urinary calcium is derived from bone. In cultured bone, chronic metabolic, but not respiratory, acidosis increases net calcium efflux (J(Ca)), decreases osteoblastic collagen synthesis, and increases osteoclastic bone resorption. Metabolic acidosis increases bone PGE(2) production, which is correlated with J(Ca), and inhibition of PGE(2) production inhibits this acid-induced J(Ca). Given the marked differences in the osseous response to metabolic and respiratory acidosis, we hypothesized that incubation of neonatal mouse calvariae in medium simulating respiratory acidosis would not increase medium PGE(2) levels, as observed during metabolic acidosis. To test this hypothesis, we determined medium PGE(2) levels and J(Ca) from calvariae incubated at pH approximately 7.1 to model either metabolic (Met; [HCO(3)(-)] approximately 11 mM) or respiratory (Resp; PCO(2) approximately 83 Torr) acidosis, or at pH approximately 7.5 as a control (Ntl). We found that after 24-48 and 48-51 h in culture, periods when cell-mediated J(Ca) predominates, medium PGE(2) levels and J(Ca) were increased with Met, but not Resp, compared with Ntl, and there was a direct correlation between medium PGE(2) levels and J(Ca). Thus metabolic, but not respiratory, acidosis induces the release of bone PGE(2), which mediates J(Ca) from bone.

Acidosis↗