digoxin and Hypercapnia

This article reviews evidence that mild, but sustained, inhibition of breathing can affect blood pressure regulation via effects of increased PCO2 on sodium regulation. Experiments with micropigs are summarized which show that anticipation of the onset of a familiar avoidance task is accompanied by sustained increases in PCO2, increases in plasma hydrogen and bicarbonate ion concentrations, decreases in hematocrit, and increases in circulating levels of sodium pump inhibitors that are sensitive to plasma volume. Observational studies with humans using an ambulatory respiration monitor characterize episodes of inhibited breathing occurring in the natural environment. Experimental studies with human subjects show that voluntary maintenance of end-tidal CO2 near the upper end of the normal range results in decreases in renal sodium excretion, increases in plasma sodium pump inhibitors and inhibition of sodium pump activity. Together, these studies are consistent with the view that behavioral stress can influence blood pressure regulation via sustained inhibition of respiration which acidifies the plasma and increases sodium/hydrogen exchange in kidneys and blood vessels.

Topics: Arousal; Blood Pressure; Cardenolides; Digoxin; Humans; Hypercapnia; Hypoventilation; Kidney; Neural Inhibition; Psychophysiology; Saponins; Sodium; Sodium-Potassium-Exchanging ATPase

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnic acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 degrees C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS - PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; PCO2 = 37 mmHg; PO2 = 530 mmHg) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; PCO2 = 36 mmHg; PO2 = 122 mmHg), a hypercapnic gas mixture (pH = 7.08; PCO2 75 mmHg; PO2 = 485 mmHg), or a hypoxic-hypercapnic gas mixture (pH = 7.09; PCO2 = 73 mmHg; PO2 = 124 mmHg). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Gas Analysis; Blood Pressure; Carbon Dioxide; Coronary Circulation; Digoxin; Heart; Hydrogen-Ion Concentration; Hypercapnia; Hypoxia; In Vitro Techniques; Male; Myocardial Contraction; Oxygen Consumption; Rats; Rats, Inbred Strains

A recent study has shown in the conscious dog that hypoxia associated with respiratory acidosis could increase the in vivo distribution of digoxin in the myocardium. The aim of the present study was to evaluate in vitro the effects of hypoxia and (or) hypercapnic acidosis on the digoxin uptake. For this purpose, rat myocardium was incubated for 180 min with radiolabelled [3H]digoxin. The uptake of digoxin which was expressed in nanograms of digoxin bound per 100 mg of myocardium was decreased by hypoxia and increased by hypercapnic acidosis. The association of hypoxia and hypercapnic acidosis had no effect on the digoxin uptake, suggesting that in vitro hypoxia acts in an opposite way to hypercapnia.

Topics: Acidosis; Animals; Biological Transport; Digoxin; Hypercapnia; Hypoxia; In Vitro Techniques; Kinetics; Male; Myocardium; Rats; Rats, Inbred Strains

Topics: Adult; Chronic Disease; Digoxin; Humans; Hypercapnia; Hypoxia; Male; Middle Aged; Pulmonary Heart Disease

Topics: Brain Diseases; Chemoreceptor Cells; Chronic Disease; Diagnosis, Differential; Diazepam; Digoxin; Furosemide; Humans; Hydrochlorothiazide; Hypercapnia; Hypoventilation; Hypoxia; Lung Diseases, Obstructive; Male; Obesity; Respiratory Center; Respiratory Function Tests