Henry L. Price

Hemodynamic and Metabolic Effects of Hemorrhage in Man, with Particular Reference to the Splanchnic Circulation

1. Eleven normal subjects were studied before and after removal of 15 to 20% of their blood volume within 35 minutes. 2. This amount of blood loss did not produce conspicuous effects upon any of the usually measured circulatory or metabolic parameters. 3. The results suggest that the splanchnic circulation functions as an important blood reservoir in man, that it can be preferentially depleted of blood by a mechanism which does not automatically increase vascular resistance, and that the ability of our subjects to tolerate blood loss was attributable in large part to this response.

The Effects of Methoxyflurane on Arterial Pressure, Preganglionic Sympathetic Activity and Barostatic Reflexes

The effects of methoxyflurane on arterial pressure and cervical pregangiionic sympathetic activity and the responses of these to stimulation of the aortic depressor nerve were studied in cats. In normal cats end-expired concentrations of methoxyflurane of 0.28, 0.48 and 0.55 per cent produced proportional depressions in arterial pressure. Sympathetic activity was unaffected. The responses of arterial pressure and sympathetic activity to baroreceptor nerve stimulation also were unaffected by methoxyflurane in these concentrations. In baroreceptor-denervated animals methoxyflurane produced a slight reduction in sympathetic activity, believed to be due to a depressant action on the medullary pressor neurons, an action which in normal animals is counteracted by the reflex response to arterial hypotension.

The Effects of Short-acting Barbiturates on Arterial Pressure, Preganglionic Sympathetic Activity and Barostatic Reflexes

The effects of two short-acting barbiturates (thiopental and methohexital) on arterial blood pressure, cervical preganglionic sympathetic activity, and barostatic reflexes have been studied in cats anesthetized with nitrous oxide. Both barbiturates reduced sympathetic nervous activity while failing to extinguish the reflex responses to electrical stimulation of the aortic depressor nerve. In decerebrated animals the same response was seen. Baroreceptor-denervated animals had a similar but exaggerated reaction. Spinal animals developed arterial hypotension without depression of sympathetic activity. It is concluded that the barbiturates inhibit sympathetic nervous activity by inhibiting “pressor” neurons in the medulla oblongata. The medullary “depressor” neurons are relatively unaffected and the barostatic reflexes consequently remain, although they are weakened. The preservation of these reflexes accounts, in part, for the circulatory stability observed during barbiturate anesthesia.

Splanchnic Circulation During Halothane Anesthesia and Hypercapnia in Normal Man

In 9 normal adult men the administration of halothane caused significant alterations in splanchnic hemodynamics which could not be attributed to hypoxia, hypereapnia, hypothermia or surgical stimulation. Halothane caused a reduction of splanchnic perfusion pressure with a parallel fall in splanchnic bood flow. There was no significant change in splanchnic vascular resistance. Intermittent positive pressure respiration was required in only 3 subjects and did not appear to contribute importantly to the results. Administration of carbon dioxide produced striking increases in the splanchnic blood flow associated with a significant fall in the splanchnic vascular resistance. The perfusion pressure was unchanged. The data suggest that halothane interferes with the expected splanchnic vasoconstriction normally seen when hypotension or hypercapnia would be expected to produce sympathetic activation. The degree of vasodilation produced by carbon dioxide and the resulting increase in average blood flow suggest that hepatic ischemia is not an important cause of hepatic dysfunction following halothane anesthesia complicated by hypereapnia.

Control of the splanchnic circulation in man. Role of beta-adrenergic receptors.

Some effects of the β-adrenergic receptor blocker, propranolol, were studied in 20 normal, fasting, conscious men. The measurements made included cardiac output, splanchnic blood flow and oxygen consumption, arterial and hepatic venous blood pressure, and heart rate. The intravenous administration of propranolol (0.13 mg/kg) was followed by significant reductions in splanchnic blood flow and oxygen consumption, in cardiac output and in heart rate. Splanchnic perfusion pressure was unchanged; the splanchnic vascular resistance was significantly elevated. Previous treatment with glucose did not alter these findings. Phenoxybenzamine pretreatment lessened the increase in splanchnic vascular resistance which propranolol ordinarily caused. Ganglion-ic blockade with hexamethonium prevented all of the changes which propranolol produced in untreated individuals. These results may best be explained by assuming that the splanchnic circulation in man is influenced both by α receptors, which cause vasoconstriction when activated, and by β receptors, which when activated caused vasodilatation and increase oxygen consumption.

Can General Anesthetics Produce Splanchnic Visceral Hypoxia by Reducing Regional Blood Flow

Thirty-five normal adult males were studied before and during either cyclopropane or halothane anesthesia in an effort to learn whether these agents cause a critical reduction in the availability of oxygen to the splanchnic viscera. Although hepatic blood flow was markedly reduced during the inhalation of either agent, splanchnic oxygen utilization was not consistently affected, and restoration of blood flow to the initial level gave no clear evidence that an oxygen debt has been incurred during the period of reduced flow. Clearance of indocyanine green dye was reduced in proportion to blood flow when either cyclopropane or halothane was inhaled, but restoration of flow rate to normal did not correct the deficiency in clearance. “Excess” lactate was produced by the splanchnic viscera during cyclopropane but not during halothane anesthesia. This effect could be abolished by a beta adrenergic blocking drug. Therefore, “excess” lactate apparently resulted not from splanehnic ischemia but from metabolic action associated with increased sympathetic nervous activity in these viscera.

Myocardial depression by nitrous oxide and its reversal by Ca

The effects of 50 per cent nitrous oxide on isometric contractile force of electrically stimulated cat papillary muscle suspended in a Tris-buffered solution at five concentrations of Ca++ ranging from 1 to 15 mM were studied. Compared with an equal concentration of nitrogen, or with pure oxygen, nitrous oxide caused a highly significant reduction in contractile force, averaging 22 per cent at 2.5 mM Ca++. This reduction in force, like that caused by halothane, could be antagonized by increasing [Ca++] in the bathing medium. However, the reductions in force caused by equinarcotic concentrations of halothane and nitrous oxide are significantly different in magnitude, suggesting that the mechanisms of anesthetic action in the central nervous system and in the myocardium may not be the same.

Evidence for β-Receptor Activation Produced by Halothane in Normal Man

Normal male volunteers breathed a constant tension of halothane for three hours while arterial blood pressure, right ventricular Pressure and cardiac rate, output and contractile force were monitored. Whole-body oxygen consumption and total peripheral resistance were calcuted Cardiance output and contractile force, initially depressd by halothane, returned to or toward norma1 levels as time passed. Total peripheral resistance, deprased by halothane, was further subreduced with time. Oxygcn consumption was depresed and remained so for the duration of anesthesia. End-expired and arterial Pco2 were maintained within normnl limits and metabolic acidosis did not occur. Tberefore, the progressive increses in cardiac output and conhetile force (and reduction in total peripheral resistance) observed could not be ascribed either to increased tissue oxygen demand or to acidosis. In individual studied during βreceptor blockade the prograssive changes obscrved in the other subjects did not occur. Tbc author conclude that halothane causes activation of adrenergic β receptors in man and that the effect increases with time.

Pulmonary Hemodynamics during General Anesthesia in Man

Pulmonary hemodynamic effects of halothane, halothane–nitrous oxide, and cyclopropane anesthesia were studied in healthy young men. Cardiac output, pulmonary artery and wedge pressures, and arterial and venous oxygen contents were measured. During halothane and halothane–N2O anesthesia there were no significant changes in pulmonary arterial and wedge pressures or in pulmonary vascular resistance. A marked decrease in left ventricular stroke work during halothane anesthesia, with unchanged wedge pressure, suggested myocardial depression. Administration of cyclopropane caused a marked increase in pulmonary arterial and wedge pressures and in pulmonary vascular resistance. The increase in wedge pressure reflected an increase in cardiac work. Increased physiologic shunting occurred with all anesthetic mixtures, but the contribution of maldistribution to the shunt was greater during spontaneous than during controlled respiration. Neither halothane nor cyclopropane prevented changes in pulmonary vascular resistance associated with altered inspired oxygen tension.

Splanchnic Circulation During Nitrous Oxide Anesthesia and Hypocarbia in Normal Man

Circulatory effects of nitrous oxide-d-tubocurarine anesthesia with hyperventilation were studied in healthy, young men. Cardiac output, mean arterial blood pressure, and splanchnic blood flow were measured. During anesthesia and hyperventilation with normal Pco2 (CO2 added to the inspired gases), splanchnic vascular resistance was elevated significantly and the blood flow reduced, but oxygen consumption was unaltered from control values. Cardiac output and total peripheral resistance were unchanged. When Paco2 was not maintained at the normal level, total peripheral resistance and splanchnic vascular resistance were reduced and the respective blood flows augmented compared with the normocarbic period. However, the demand of the splanchnic viscera for oxygen was increased out of proportion to the increase in flow. It is suggested that the nitrous oxide-curarehyperventilation technique may be a poor choice for patients with marginal levels of splanchnic blood flow.