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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used intracellular microelectrodes to study the electrophysiological effects of combinations of components of ischemia and their relation to the occurrence of ventricular arrhythmias in the specialized conducting system of isolated canine right ventricles. The middle area of the free wall was exposed to various test solutions in the center compartment of a three-chambered bath; the base and apex of the preparation were superfused with normal Tyrode's solution in the outer control compartments. Hypoxia (Po2 40 mm Hg), lactic acidosis (pH 6.5), and orciprenaline (10(-6) M), either alone or combined, failed to affect the action potential amplitude or the conduction velocity of the subendocardial fibers, and no arrhythmias occurred. The action potential duration and the effective refractory period were markedly prolonged by lactic acidosis. Exposure of the test regions to 15 mM K+ plus orciprenaline resulted in marked decreases in action potential amplitude and conduction velocity. Abnormalities of impulse transmission through the depressed area included high degrees of rate-dependent block, one-way block, warming-up phenomenon, and the Wenckebach phenomenon. Such conditions regularly provoked the appearance of single, sustained, or concealed reentrant depolarizations. The combined effects of hypoxia, 15 mM K+, and orciprenaline resulted in further depression of the already depressed action potential in the depolarized fibers. Our results indicate that regional increases of extracellular K+ may be the predominant factor of the components of ischemia we studied which facilitates the initiation of reentrant arrhythmias.
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PMID:Effects of some components of ischemia on electrical activity and reentry in the canine ventricular conducting system. 42 79

Acute alterations in plasma bicarbonate concentration have minimal effects on intracerebral pH and cerebral blood flow, perhaps due to blood-brain barrier mechanisms. To test this hypothesis, the consequences of an acute rise in the plasma bicarbonate concentration were studied in anesthetized rats previously subjected to an acute pressure pulse in the carotid system with unilateral damage to the blood-brain barrier. In rats subjected to a "heavy" hypertensive insult, the hemisphere on the side of the lesion showed a lactic acidosis, edema, and a depression of cerebral blood flow. An increase in the plasma bicarbonate concentrations of 15--20 mEq/1 during 35 minutes provoked a marked rise in the total CO2 content of this hemisphere, and a further increase in the lactate concentration, but did not later the brain edema nor affect further the already very low cerebral blood flow. An increase in the lactate concentration and a decrease of cerebral blood flow in the "reference" hemisphere indicated that the lesion was not completely unilateral. In rats subjected to a "moderate" hypertensive insult the changes were less pronounced and statistically not significant for all the parameters. There results illustrate the importance of an intact blood-brain barrier for the maintenance of intracerebral pH in the face of acute alterations in plasma [HCO3]. The impaired cerebral blood flow after an acute hypertensive insult did not appear to be influenced by the intracerebral [HCO3].
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PMID:Effect of non-respiratory alkalosis on brain tissue and cerebral blood flow in rats with damaged blood-brain barrier. 67 46

Cardiac beriberi is considered a rare disease in western society. A patient with fulminant Shoshin-type beriberi was studied in the acute phase and found to have severe metabolic acidosis, high output biventricular failure, and markedly low systemic vascular resistance. Red blood cell transketolase activity was abnormally low. Following treatment with thiamine, diuretics, digitalis and oxygen, all abnormalities disappeared. The historical background of the disease is reviewed along with a discussion of pathophysiologic mechanisms responsible for the hemodynamic profile and lactic acidosis. Angiographic and hemodynamic data on the patient presented suggest relative depression of left ventricular function in the acute phase of beriberi. Since beriberi is uncommonly encountered, emphasis is placed on diagnostic and therapeutic implications of the disease which may not be widely appreciated.
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PMID:Fulminant beriberi heart disease with lactic acidosis: presentation of a case with evaluation of left ventricular function and review of pathophysiologic mechanisms. 67 49

The growing number of drugs used to treat various diseases and the growing number of invasive procedures used for diagnosis and therapy have generated many iatrogenic diseases. Elderly patients are more likely than the young to react adversely to drugs since the physiological functions of the organs, especially of the kidneys, decrease and pharmacokinetic characteristics altered. In addition, multiple disease states are common in the elderly, and multiple drugs are consequently prescribed. In the present study, adverse effects of so-called "cerebroactive drugs" and "cerebral vasodilators" are discussed. More than 30 kinds of these drugs are on the market in Japan and are widely prescribed for "chronic cerebrovascular diseases" and "dementia syndromes" in the elderly. In contrast, they are rarely used in Western Europe and not on the market in the United States. Among them, calcium hopantenate was the first of "cerebral activators" and was the most popular. In 1986, however, the first cases of toxic encephalopathy induced by calcium hopantenate were reported. It resembled Reye syndrome, showing coma, hepatic failure, lactic acidosis and hypoglycemia and was frequently fatal. More than 47 victims including 11 fatal cases have been reported since. Flunarizine, a cerebral vasodilator, produced high rates of parkinsonism and depression. Multicenter studies have revealed that these side effects occurred in 10-30% of the elderly patients who had taken it. These symptoms usually appeared several months after flunarizine was started. Some of the adverse effects of the drugs may be unpredictable and inevitable, but most of them can be prevented or reduced if physicians are more careful with their patients, and drugs and their adverse effects.2
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PMID:[Iatrogenic diseases in the elderly]. 194 29

This review article examines the pathophysiology of septic shock, with special attention to the concept of supply-dependent consumption and the implications this concept has for therapy. Patients with septic shock require higher levels of oxygen delivery (DO2) to maintain aerobic metabolism. When DO2 is inadequate, peripheral tissues switch to anaerobic metabolism and oxygen consumption decreases. The lactic acidosis that occurs is a reasonable clinical marker of supply dependency and inadequate tissue perfusion. Maximizing DO2 is an important part of the hemodynamic resuscitation of patients with septic shock. To achieve this goal, intravascular volume must be restored and the myocardial depression associated with sepsis must be treated to optimize cardiac output. The normalization of arterial lactate concentration is a reasonable goal of resuscitative efforts.
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PMID:Oxygen consumption in sepsis and septic shock. 202 29

The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection.
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PMID:Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. 205 98

Widespread utilization of short-chain alcohols in solvents and alcoholic beverages provides small animals with numerous opportunities for exposure. Toxicosis most commonly occurs following ingestion but may also arise from inhalation and/or dermal absorption. The actions of short-chain alcohols are believed to result from nonspecific interactions with biomembranes altering the function of membrane-bound proteins, including the GABAA receptor. Mortality in alcohol toxicosis typically occurs because of respiratory and cardiac arrest as a result of profound CNS depression; therefore, general measures for resuscitation prevail in the initial treatment of severe alcohol toxicosis. Metabolism of alcohols alters the redox state in the liver, leading to hypoglycemia and lactic acidosis in some cases. In primates, treatment for methanol toxicosis is aimed at reducing accumulation of formate, thereby diminishing the metabolic acidosis and ocular damage characteristic in these species.
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PMID:Toxicology of selected pesticides, drugs, and chemicals. Short-chain alcohols. 218 Jan 93

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.
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PMID:Effect of lactic acidosis on canine hemodynamics and left ventricular function. 233 Oct 7

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.
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PMID:CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression. 313 17

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.
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PMID:Role of brain lactic acidosis in hypoxic depression of respiration. 318 2


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