Mechanisms Regulating the Cardiac Output Response to Cyanide Infusion, a Model of Hypoxia

A 27-yr-old woman with lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia induced by trivial exercise was found to have a skeletal muscle respiratory chain defect characterized by low levels of reducible cytochromes a + a3 and b in muscle mitochondria and marked deficiency of cytochrome c oxidase (complex IV) as assessed biochemically and immunologically. Investigation of the pathophysiology of the exercise response in the patient revealed low maximal oxygen uptake (1/3 that of normal sedentary women) in cycle exercise and impaired muscle oxygen extraction as indicated by profoundly low maximal systemic arteriovenous oxygen difference (5.8 ml/dl; controls = 15.4±1.4, mean±SD). The increases in cardiac output and ventilation during exercise, normally closely coupled to muscle metabolic rate, were markedly exaggerated (more than two-to threefold normal) relative to oxygen uptake and carbon dioxide production accounting for prominent tachycardia and dyspnea at low workloads. Symptoms in our patient are similar to those reported in other human skeletal muscle respiratory chain defects involving complexes I and III, and the exaggerated circulatory response resembles that seen during experimental inhibition of the mitochondrial respiratory chain. These results suggest that impaired oxidative phosphorylation in working muscle disrupts the normal regulation of cardiac output and ventilation relative to muscle metabolic rate in exercise.

Section: Discussionsupporting

confidence: 58%

Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.

Haller¹,

Lewis²,

Estabrook³

et al. 1989

“…Similarly, it decreases during severe hypoxia, probably a result of adrenergic stimulation (40). The increases in cardiac output and myocardial contractility during hypoxia probably are related to autoregulation ofthe peripheral vascular beds (41) and stimulation of the sympathetic nervous system (1,28,42,43). Results of the present study suggest that the systemic hemodynamic effects of hypoxia probably are not causally related to the accumulation of glycolytic metabolites or of other metabolites which are also affected by fluoroacetate.…”

Section: Resultsmentioning

confidence: 60%

“…Cardiac output and coronary blood flow also may increase in the absence of any reduction in tissue oxygen tension when metabolic changes like those occurring in hypoxia are produced by cyanide (1,2). Thus, these hemodynamic changes could be attributed, at least in part, to alterations in metabolite contents typical ofhypoxia.…”

Section: Introductionmentioning

confidence: 99%

Metabolic control of circulation. Effects of iodoacetate and fluoroacetate.

Liang¹

1977

A B S T R A C T The circulatory effects of selective metabolic inhibition of glycolysis and of the tricarboxylic acid cycle by iodoacetate and fluoroacetate were studied in intact chloralose-anesthetized dogs. Pulmonary arterial blood pressure and vascular resistance increased after administration of both inhibitors, but neither systemic hemodynamics nor myocardial contractility changed significantly. Coronary blood flow did not change after iodoacetate administration but increased four-to fivefold after fluoroacetate. Administration of normal saline had no effect on any of the parameters. The changes in pulmonary arterial blood pressure and coronary blood flow after fluoroacetate were not mediated via the autonomic nerves or adrenergic neurohumors because they still occurred after autonomic nervous system inhibition. Neither myocardial oxygen consumption nor left ventricular work changed. A selective increase in myocardial blood flow also occurred in conscious dogs after fluoroacetate administration; hepatic artery flow was reduced, but other organ flows did not change significantly. These results indicate that pulmonary pressor and coronary dilator effects may be produced in intact dogs by selective metabolic blockade, in the absence of reduced oxygen supply or impairment in the electron transport system. These results also suggest that the increases in pulmonary arterial blood pressure, coronary blood flow, and cardiac output that occur during hypoxia probably are related to separate metabolic events in the tissue.

“…Dogs weighing from 15.5 to 30 kg were anesthetized and prepared as described in the preceding paper (1). The tracheal cannula was connected to a Douglas bag via a "J" valve system for determining oxygen consumption.…”

Section: Methodsmentioning

confidence: 99%

Effects of Splenectomy and Beta-Adrenoceptor Blockade on Cardiac Output Response to Acute Hypoxemia

Liang¹,

Huckabee²

1973

Self Cite

A B S T R A C T Acute hypoxemia produced by the inhalation of 8% and 5% oxygen increased cardiac output in intact anesthetized dogs by 38% and 62%, respectively. Although practolol, a cardioselective betaadrenergic blocking agent, reduced the increase in cardiac output in dogs subjected to severe hypoxemia (5% 02 breathing) from 62% to 43%, it only slightly reduced the cardiac output rise in dogs subjected to moderate hypoxemia (8% 02 breathing). Splenectomy, on the other hand, abolished the increase in cardiac output produced by moderate hypoxemia except for a small initial rise, but it reduced the increase in cardiac output during severe hypoxemia only to 37%. The entire increase, except for a small initial rise, disappeared only when splenectomized dogs were pretreated with practolol. Sham operation did not affect the cardiac output response to hypoxemia. It is concluded that an intact spleen is required for a significant portion of the increased cardiac output that occurs during both moderate and severe hypoxemia and that catecholamines do not participate in the regulation of cardiac output unless severe hypoxemia occurs.