S. Evans Downing

Cardiovascular Responses to Hypoxic Stimulation of the Carotid Bodies

The hemodynamic responses to hypoxic stimulation of the carotid bodies were investigated in the dog with controlled respiration. A dual, rotating disc oxygenator system was utilized to perfuse the vascularly isolated carotid region alternately with blood of high or low pO2. Perfusion of the carotid bodies with hypoxic blood caused a large reduction of heart rate. The bradycardia response was reduced, but not abolished, by vagotomy. However, the subsequent administration of hexamethonium completely abolished the response. The contractility of the atrium was reduced by carotid body hypoxia, and varying degrees of heart block were frequently observed. These responses were abolished by vagotomy and considered to be due to efferent vagal activity. Ventricular function curves showed that carotid body hypoxia usually caused a reduction, never an increase, of ventricular contractility. This indicates a reduction of sympathetic discharge to the heart. The reduction in heart rate after vagotomy and the reduction in ventricular contractility were associated with a concomitant increase of total peripheral resistance. These findings indicate that hypoxic stimulation of the carotid bodies causes a dichotomous sympathetic response, that is, a reduction of sympathetic discharge to the heart and a simultaneous increase of sympathetic discharge to the peripheral vasculature. Systemic hypoxia caused an increase of both ventricular contractility and total peripheral resistance. Consequently, the hemodynamic responses to systemic hypoxia cannot be entirely ascribed to a primary chemoreceptor reflex from the carotid bodies. It is suggested that the cardiac sympathetic responses seen in systemic hypoxia are due, at least in part, to direct hypoxic stimulation of the central nervous system.

Myocardial oxygen availability and cardiac failure in hemorrhagic shock

The relationships between left ventricular function and myocardial O2 availability and metabolism were studied in cats with hemorrhagic shock (AP=30 mm. Hg) with the use of a right heart bypass preparation. Aortic flow and heart rate were held constant. Oxygen-carrying capacity was reduced by diluting donor blood with an equal volume of 5 per cent glucose in saline. Oxygen availability was estimated as the product of arterial O2 content and coronary blood flow. All shock animals showed a progressive metabolic acidemia with time, and a fall in coronary flow concomitantly. Four control animals (AP=75 mm. Hg) as well as two shock animals with high arterial oxygen content and hematocrit showed no significant changes in myocardial O2 metabolism or performance over a period of 90 minutes. Nine shock animals with reduced hematocrit demonstrated a progressive reduction in ventricular function, myocardial O2 metabolism, and O2 availability. As O2 availability fell below 10 ml. per minute per 100 Gm. of heart weight, cardiac failure uniformly appeared and was accompanied by a reduction in O2 extraction and consumption. The correlation between left ventricular dP/dt max and O2 availability was highly significant (r = 0.75, p less than 0.01) in shock animals but not in controls. Thus a close relationship between myocardial O2 metabolism and function during the course of hemorrhagic shock has been demonstrated. Reduced myocardial O2 availability is directly linked with the appearance of cardiac failure.

955 LARYNGEAL INDUCED APNEA IN THE CHEMODENERVATED PIGLET

Laryngeal instillation of certain fluids in the piglet elicits reflex apnea, bradycardia, and hypertension. Chemosensitive receptors at the laryngeal entrance have their afferent pathway in the superior laryngeal nerve. Their stimulation may cause asphyxial death often in the newborn, but rarely in the older piglet. We studied the influence of the peripheral arterial chemoreceptors in modulating laryngeal responses in air-breathing pentobarbital-anesthetized newborn (N=9, age 7.0±0.9d) and older piglets (N=9, age 37.8±4.9d). The change in minute ventilation of exposure to 10% 02 in N2 was 19.3±10.6% (NS) in the newborn and 29.4±11.2% (p<.05) in the older piglets. Pure oxygen transiently depressed ventilation by 53.1±5.1% (p<.001) in the newborn and 51.4±6.3% (p<.001) in the older piglets, indicating that the peripheral chemoreceptors are fully active in the newborn. The duration of the net apnea (water minus saline) was similar in the intact newborn, 9.27±1.48 sec (p<.001) and older piglet,9.73±1.23 sec (p<.001). Carotid chemodenervation abolished the ventilatory response to oxygen but had negligible effect on the duration of laryngeal apnea. We conclude that recovery of spontaneous respiration after laryngeal induced apnea is independent of peripheral chemoreceptor activity. Our findings may have relevance to the clinical problem of sudden infant death, in which pathological abnormalities of the carotid body have recently been described.

166 CARDIOVASCULAR RESPONSES OF NEWBORN PIGLETS IN ENDOTOXIC SHOCK

Circulatory responses to endotoxemia have been well described in adult animal models but not in the newborn. Ten piglets (mean age, 4.6 days) were anesthetized and given E. Coli endotoxin, 5 mg/kg, i.v. Cardiac output (CO), arterial and central venous pressure, pulmonary artery and pulmonary artery wedge pressure (PAWP), arterial blood gas values and serum glucose concentration were measured. Seven piglets survived the three hour protocol. After a slight early elevation in mean arterial pressure there was a decline over the first hour until a plateau was reached at 60% of control. This continued for the duration of the experiment. After an initial drop in CO substantial recovery occurred, followed by a slowly progressive decline. This was accompanied by profound hypoglycemia. Five controls showed no significant circulatory changes. Five pigs older than four weeks were given endotoxin and none survived beyond two hours. Other differences in the older animals included the absence of a plateau phase of hypotension; failure of CO to recover after the early drop; a substantial rise in PAWP; transient hyperglycemia preceding the profound hypoglycemia; and more rapid progression of metabolic acidosis. It is concluded that the newborn piglet is more resistant to the effects of endotoxin than is the older pig. This may be attributable to differences in vasomotor responsiveness.

RECIPROCAL INHIBITION OF CARDIAC RESPONSES TO NORE-PINEPHRINE AND INSULIN

The effects of insulin (IN) and norepinephrine (NE) on left ventricular contractility (LVc) were studied in 20 piglets. Aortic pressure, cardiac output, heart rate and temperature were controlled, and LV dP/dt max was taken to reflect LVc. Hypoglycemia was prevented by giving glucose as necessary. LVc increased 28% (p<.02) 45 min. after IN (20U). Following β-blockade (practolol, 1 mg/kg), in caused a 55% increase in LVc. NE dose-response (DR) curves were obtained before and after IN. Maximal changes in LVc with each dose of NE (0.5-2.0μg) were significantly less in hearts exposed to IN. Duplicate DR curves were identical, indicating that prior exposure to NE did not inhibit subsequent responses. However, in those piglets initially subjected to a NE dose-response curve, IN elicited only an 11% increase of LVc, and this was not significant. Thus, the inotropic response was attenuated (p<.01) in animals previously exposed to NE, Conversely, in animals first subjected to β-blockade, the response to IN was greater (p<.005). These data indicate a reciprocal blocking action by these hormones on piglet myocardium. The cellular mechanisms responsible for these findings remain to be elucidated, but likely involve modulation of Ca++ fluxes.

Cardiac Responses to Sympathetic and Vagal Stimulation in the Newborn Lamb During Acidosis and Hypoxia

Heart rate (HR) and left ventricular co ntractility (VC) responses to sympathetic and vagal nerve stimulation were assessed in 15 lambs from < 1 to 3 days of during lactic acidemia, hypercapnia and hypoxemia. These were compared with responses under control conditions. In all experiments supramaximal electrical stimulation of the left inferior cardiac sympathetic nerve produced large increases of VC as measured by the dP/dt max from a given end-diastolic pressure (LVEDP) when HR, mean aortic pressure and cardiac output (Medicon) were held constant. With a pH of 7.39 the dp/dt max increased from 3,000 (±155 SE) to 4,244 (±147 SE) mm Hg/sec during stimulation, while the LVEDP fell from 7.3 (±0.73 SE) to 5.8 (±0.79). During acidemia the increase (1,310±159 SE) was unchanged. With hypercapnia (PCO2 69 mm Hg) the responses were less (840 mm Hg/sec) than with low PCO2 (1,300 mm Hg/sec, p<0.01). Responses during hypoxemia (PO2 33 mm Hg) were indentical to those with normal PO2. Cardiac slowing in response to stimulation of the right distal vagus N was measured at several frequencies (F) from 1-15/sec, duration 5msec, and 10-15 V. slowing was a function of F, but was unaltered by changes of PO2, PCO2 of pH up to an F of 10/sec. At F 15 the bradycardia was often enhanced by hypercapnia. It is co ncluded that hypoxemia and lactic acidemia do not alter adrenergic (A) or cholinergic (C) transmission, but that hypercapnic acidosis may reduce A, and enhance C during maximal stimulation. This suggests a mechanism whereby autonomic control of the heart may be altered in neonatal asphyxia.