John L. Patterson

GENERAL AND REGIONAL CIRCULATORY ALTERATIONS IN CIRRHOSIS OF THE LIVER.

Abstract The general circulation and the circulation of the upper extremity were studied in sixteen patients with cirrhosis of the liver and in eight healthy control subjects. The cardiac index was increased in ten cirrhotic patients and normal in six. In patients with normal cardiac indices, hand and forearm blood flows and arteriovenous oxygen difference for forearm deep venous blood were not significantly different from corresponding values for the control group. Based on hand and forearm blood flows and arteriovenous oxygen differences for deep and superficial venous blood in the forearm, three types of peripheral circulatory abnormalities were found among the group of patients with high cardiac index: type A was characterized by vasodilatation in skin and skeletal muscle, type B by vasodilatation in skeletal muscle only, and type C by vasodilatation in skin only. The possible causes of these circulatory abnormalities are discussed. It is suggested that multiple causes rather than a single one are probably operative. Hypocapnia could account for the increased cardiac index in patients with vasodilatation in skeletal muscle only (type B).

Effects of respiratory gases on cytochrome a in intact cerebral cortex: is there a critical PO2?

Changes in the redox level of cytochrome a and in the amount of oxygenated hemoglobin were measured by dual wavelength reflectance spectrophotometry in the intact cerebral cortex of cats (cerveau isolé preparation) and in unanesthetized rabbits with chronically implanted cranial windows. Increases in inspired oxygen were accompanied by an increase in the oxidation level of cytochrome a and an increase in the amount of oxygenated hemoglobin in the optical field. These changes were larger in the presence of 5% CO2. Reduction of the inspired oxygen concentration produced a decrease in the oxidation/reduction ratio of cytochrome a and a disoxygenation of hemoglobin. The presence of CO2 at these lower oxygen levels diminished the reduction of cytochrome a and the disoxygenation of hemoglobin. These data indicate that, in the resting subject, the reduction levels of cytochrome a are well above the low values seen in isolated mitochondria. They also indicate that the blood supply to the cerebral cortex is regulated at a level of slight hypoxia.

Dependence of pial arteriolar response to hypercapnia on vessel size

The responses of pial arterioles to changes in PaCO2 were studied in anesthetized cats equipped with cranial windows for the observation of the pial microcirculation. The percentile increase in vessel caliber induced by hypercapnia was size dependent, with the smaller vessels responding more vigorously than the larger ones. In contrast, the vasoconstrictor responses to arterial hypocapnia were size independent. Following topical application of phentolamine (10(-5) M), or after ipsilateral extirpation of the superior cervical ganglion, the increase in arteriolar caliber caused by moderate hypercapnia (5% CO2 inhalation) in the larger arterioles (greater than 100 micron in diameter) increased and became equal to that of the smaller arterioles (less than 100 micron in diameter). The response to hypocapnia was not affected by phentolamine. The results indicate that a major reason for the greater responsiveness of smaller vessels to moderate hypercapnia is the fact that the response of the larger vessels is limited by neurogenic vasoconstriction resulting from increased activity of adrenergic nerves originating from the cervical sympathetic chain. The absence of an influence of the sympathetic nervous system on the responses to hypocapnia is explained by the lack of significant resting neurogenic vasoconstrictor tone in pial arterioles of anesthetized cats.

Observations on dyspnea induced by combinations of respiratory stimuli

Abstract Dyspnea was induced in eleven healthy volunteer subjects by exposure to one or more of the following three respiratory stimuli: (1) 7 per cent carbon dioxide inhalation; (2) exercise; and (3) intravenously administered ethamivan. It was found that stimuli which were ineffective in producing dyspnea individually might become effective in combination. When dyspnea developed as a result of a combination of respiratory stimuli, withdrawal of a sufficiently potent stimulus, while the remaining stimuli were continued, resulted in disappearance of the symptom. These findings suggested a relationship of dyspnea to the net load of respiratory stimuli. In several subjects the onset of dyspnea was accompanied by characteristic changes in the position of the chest at the end of inspiration and in tidal volume consistent with the participation of the proprioceptive mechanism in the production of dyspnea. These changes usually occurred in association with dyspnea developing as a result of the sudden application of a strong respiratory stimulus. An increase in the rate of rise of alveolar ventilation during carbon dioxide inhalation over that observed when carbon dioxide alone was given occurred when carbon dioxide was added to the inspired air of exercising subjects or a subject receiving ethamivan. This increase was even more pronounced when carbon dioxide was inhaled by an exercising subject receiving ethamivan. It is suggested that an increase in the sensitivity of the respiratory center to carbon dioxide inhalation, brought about by ethamivan therapy or by exercise, may account in part for this finding. Certain observations indicated that in addition to the magnitude of a respiratory stimulus, the manner in which it is applied may influence the development of dyspnea. A rapidly increasing stimulus was more effective in producing dyspnea than one which achieved its maximum intensity gradually. Careful questioning of the subjects at the end of the experiment showed that different subjects used varying phraseology to describe dyspnea developing under the same circumstances and that a given subject tended to describe dyspnea developing under widely different circumstances with the same words. These findings suggested that the view that dyspnea developing under different circumstances represents a fundamentally different sensation is erroneous.