Effects of acute lactic acidosis on left ventricular performance

Wildenthal, K.; Mierzwiak, DS; Myers, RE; Mitchell, J. H.

doi:10.1152/ajplegacy.1968.214.6.1352

Cited by 184 publications

(60 citation statements)

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“…Hypoglycemia causes CNS disorder. Hyperlactemia reportedly causes bradycardia, a marked reduction in the ventricular contractile force and irreversible nerve cell injury in the brain (25,26). Most previous reports indicate that the first clinical symptom is CNS involvement, such as disorientation, agitation, unconsciousness, and coma.…”

Section: Discussionmentioning

confidence: 99%

Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Toshina

Dote

Usuda

et al. 2004

Environ Health Prev Med

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Objective: Monochloroacetic acid (MCA) is corrosive to skin, and causes not only chemical injury but also fatal systemic poisoning. Little is known about the cause of death. We studied the acute toxicity of MCA before clinical symptoms appeared in fasting rats. Methods: Blood samples were analyzed 2 h after subcutaneous MCA injection (LD 90 : 162 mg/ml kg body weight). Control rats were injected with saline. Results: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were about 1.5-fold higher than in the controls, and mitochondrial AST (mAST) was 2-fold higher. Blood urea nitrogen and creatinine were significantly increased, while serum glucose was significantly decreased in the treated group. Lactate was 6-fold higher and pyruvate was 13-fold higher than in the controls. Conclusions: MCA caused injury to the liver and kidneys but these injuries were slight. However, the larger increase in mAST indicated that hepatocellular mitochondria were selectively targeted. Hepatocellular mitochondrial injury decreased gluconeogenesis and caused hypoglycemia and extremely high levels of lactate and pyruvate. Hypoglycemia and lactic acidosis were insidious before the critical symptoms appeared and this combination accelerated to death, affecting other organs such as the heart and brain. Nosotropic therapy of these abnormalities up to the appearance of symptoms may help to establish an early therapy for skin exposure to MCA.

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Section: Discussionmentioning

confidence: 99%

Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Toshina

Dote

Usuda

et al. 2004

Environ Health Prev Med

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“…As previous studies had demonstrated that administration of several different exogenous opioids may result in sinus bradycardia, we were particularly interested to determine if opioid inhibition would prevent the sinus bradycardia that we noted previously in some of the lambs during acidemia (6,23,24). The irregular occurrence of sinus bradycardia also had been noted previously during HC1-induced acidemia in mature dogs (10). For this reason, we temporarily discontinued the atrial pacing and measured the spontaneous heart rate of the lambs that had developed sinus bradycardia during HC1-induced metabolic acidemia.…”

Section: Effect Of Opioid Inhibition On Hemodynamic Effects Of Hc1-inmentioning

confidence: 75%

“…Endogenous opioids such as P-endorphin appear to be important mediators of the depression of cardiac output and left ventricular contractility that occurs in endotoxic or hemorrhagic shock in mature cats and dogs (7)(8)(9). To the best of our knowledge, endogenous opioids have not been examined as possible regulators of the hemodynamic depression that occurs during metabolic acidemia (10,11). On considering that metabolic acidemia occurs frequently in newborn humans with asphyxia1 cardiomyopathy, that umbilical cord arterial blood pH and @-endorphin concentrations are inversely correlated in asphyxiated human newborns, that metabolic acidemia depresses cardiovascular function in lambs, and that P-endorphins are present and may be increased by certain conditions in lambs (12, 13), we formulated the hypothesis that increased endogenous opioids mediate part or all of the hemodynamic depression that occurs in HClinduced metabolic acidemia in lambs.…”

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confidence: 99%

Endogenous Opioids Do Not Mediate HCl-Induced Myocardial Dysfunction

Tate

et al. 1988

Pediatr Res

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A B S T R A a . We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HC1-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial ap~endafze: a catheter mounted micromanometer Dressure iransdvucer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 f 0.01 to 6.97 f 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance. In contrast, restoration of a normal arterial pH was associated with increases in cardiac output, heart rate, stroke volume, and dP/dt to greater than control values, as well as a normalization of systemic vascular resistance. These hemodynamic changes were not attributable to direct effects of naloxone. Herein we suggest that although opioids may exert a small role in mediating the contractile dysfunction that occurs during HC-induced metabolic acidemia, there is no apparent influence of opioids on pump performance. Opioids participate very little in the myocardial dysfunction of this model of metabolic acidemia in lambs. (Pediatr Res 23: 643-646, 1988) Abbreviations IV, intravenous LVEDP, left ventricular end diastolic pressure dP/dt, first derivative of left ventricular maximal pressure Received October 23, 1987; accepted February 23, 1988 Supported by a grant from the American Heart Association, Texas Affiliate.Myocardial dysfunction has occurred in conjunction with the metabolic acidemia of birth asphyxia in human newborns (1-5). To examine the effects of metabolic acidemia on neonatal cardiovascular function, we recently used an IV HC1 infusion to produce a metabolic acidemia in unanesthetized lambs (6). In this model, metabolic acidemia was associated wi...

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“…This could have caused accumulation of buformin and subsequently lactic acidosis [6]. The acidosis may have caused cardiac failure [7,8], a further decrease of renal function [9] and a further increase of the severity of the lactic acidosis.…”

Section: Discussionmentioning

confidence: 99%

Buformin concentrations in a case of fatal lactic acidosis

Verdonck¹,

Sangster²,

Heijst³

et al. 1981

Diabetologia

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Summary. A fatal case of lactic acidosis in a 84 year old diabetic woman taking buformin is reported. Buformin concentrations in serum, other body fluids and tissues were measured by gas chromatography. Serum buformin concentration at admission was 5.5 mg/1. PoStmortem concentrations were: in serum 3.2 mg/l; in lung 2.8mg/kg wet weight; in heart 3.0mg/kg; in pericardial fluid 3.5 rag/l; in liver 5.2 mg/kg; in bile 6.3 rag/l; and in kidney 98 mg/kg.

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Effects of acute lactic acidosis on left ventricular performance

Cited by 184 publications

References 0 publications

Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Hepatic injury and gluconeogenesis after subcutaneous injection of monochloroacetic acid in rats

Endogenous Opioids Do Not Mediate HCl-Induced Myocardial Dysfunction

Buformin concentrations in a case of fatal lactic acidosis

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