N. S. Faithfull

Cardiovascular changes during whole body hyperthermia treatment of advanced malignancy

SummaryCardiovascular studies were carried out on patients subjected to whole body hyperthermia treatment for advanced malignancy in order to assess the magnitude of the changes occurring and the degree of strain imposed on the system. The subjects, who were anaesthetised with a nitrous oxide/oxygen and relaxant sequence, were heated in a modified Siemens hyperthermia cabin and maintained at a body temperature of 41.8‡ C for 2 h. The results of 30 treatments are presented. Large increases in cardiac output and heart rate were accompanied by large decreases in peripheral resistance in both the systemic and pulmonary vascular beds. The pulmonary arterial pressure rose whereas that in the systemic circulation fell. This caused right ventricular work to increase proportionately more than left ventricular work. Care should be exercised when subjecting patients with limited right ventricular function to this treatment.

TISSUE OXYGEN TENSION IN THE CEREBRAL CORTEX OF THE RABBIT

Polarographic techniques were employed to measure oxygen partial pressure using 10 micron glass-protected gold microelectrodes. When inserting the electrode into the cortex, a PO2-profile is produced. The average PO2 was about 9 mm Hg. Nearly all measurements were below 25 mm Hg and measurements above 50 mm Hg were rare. When the FiO2 was increased from 0.3 to 1.0, tissue PO2 increased, then gradually decreased. This is probably due to vasoconstriction of pre-capillary sphincters. Acute hypoxia showed the opposite effect, but the autoregulation does not seem to be so effective. When CO2 was added to the inspiratory gas mixture the PO2 increased and showed little tendency to return to normal values. This increase in PO2 is due to the direct effect of CO2 and H+ on the blood vessels, causing vasodilation, and therefore an increase in blood flow and tissue oxygenation.

Gas Exchange during Peritoneal Perfusion with Perfluorocarbon Emulsions

The fact that fluorocarbons have a very high solubility for oxygen was very dramatically demonstrated by Clark and Gollan (1966), when they were able to show survival of mice completely immersed in these liquids for extended periods of time. The animals were able to obtain sufficient oxygen by respiring the liquid. After removal from the fluorocarbons the animals showed no apparent ill effects from the experience.

Oxygen Supply to the Myocardium

This paper concerns aspects of oxygenation of the myocardium in relation to coronary artery flow and in relation to areas of ischaemic hypoxia. These results were obtained during the course of experiments designed to set up a myocardial ischaemia model and to investigate the effects of haemodilution on myocardial oxygenation. These studies involved the use of various inspired oxygen concentrations (FIO2’s) and cross-clamping of a terminal branch of the left anterior descending coronary artery, (Faithfull et al 1983a). The paper is inevitably somewhat ‘anecdotal’ in nature, but nevertheless does throw some light on the complicated nature of the oxygenation of myocardial tissue.

Tissue Oxygenation by Fluorocarbons

Fluorocarbons have a very high solubility for oxygen and this was very dramatically shown by Clark and Gollan (1966), when they were able to demonstrate survival of mice completely immersed in these liquids for extended periods of time. The animals were able to obtain sufficient oxygen by respiring the liquid and after removal showed no apparent ill effects from the experience.

Liver damage and extraction of indocyanine green under whole body hyperthermia

SummaryThe role of hepatic oxygenation in causing liver damage during treatment with whole body hyperthermia (WBHT) was investigated, following observations that this toxicity was not related to the maximum core temperature or the heat dose administered. Measurement of hepatic blood flow during WBHT was attempted in four patients, using continuous infusion of indocyanine green (ICG). The flow values obtained were unrealistically large, in two cases more than half the cardiac output, due to considerable decreases in ICG extraction during treatment. The two patients with the greatest liver function changes were also those in whom the most hepatic damage was seen following treatment. Plasma disappearance of ICG following treatment was also abnormal in all patients.These findings indicate that WBHT affects liver function in all patients treated to some extent, an effect that may last up to several days following treatment. Possible mechanisms are changes in hepatic metabolism, selective heating of the liver and in some patients hepatic hypoxia rather than a direct effect of heat alone.

Whole Body Hyperthermia as a Treatment Modality

Currently, one of the most effective methods for heating deep seated tumours is by warming up the entire patient. In this way temperatures to a maximum level of 42°C can be obtained. Over 35 papers have been published on the various aspects of whole body hyperthermia. Some only deal with description of the various methods, others the required anaesthesia, a large number of papers deal with physiological effects and toxicity and, finally, some 14 different publications have reported the results obtained. Historically the method of whole body hyperthermia dates back to the late 1890’s, when Coley treated patients with injections of bacterial toxins. Unfortunately, there is still some confusion as to whether the reported beneficial effects were achieved by the elevated temperatures or by undefined immunological reactions. To confuse the issue even more, no detailed report remains on how the exact mixture of bacterial toxins was composed, and therefore it is not possible to reproduce the results today. In view of the fact that immunological factors in tumour therapy do not play a significant role (Mastrangelo et al., 1984), despite all the claims that have been made, it is likely that the elevated temperatures have been instrumental. After these initial successes, there has not been much activity in this field of whole body hyperthermia for more than half a century.

Cardiovascular and Oxygenation Changes During Whole Body Hyperthermia

In the last few years, many reports of whole body hyperthermia treatment have appeared in literature. In most centres this is conducted under general anaesthesia, (1–6) others use a generalised sedation technique. (7–9) In depth studies of cardiovascular changes have been very few and far between and only two centres appear to have measured the cardiac output and pulmonary artery pressures. (4, 7) To date we have only found one group of investigators who have reported measurements of oxygen consumption. (13)

Alterations in Oxyhemoglobin Dissociation Curve During Normoxic Acute Normovolemic Hemodilution

Shifts in the oxygen dissociation curve (O.D.C.) have been taken into account when studying oxygen delivery to tissue as a dependent factor of oxygen availability. It can be assumed that changes in the oxyhemoglobin dissociation characteristics of the blood will have a certain effect on the amount of oxygen available (1,2).

Myocardial oxygen supply under critical conditions, the effects of hemodilution and fluorocarbons.

This article reviews the factors influencing myocardial oxygen supply and demand. The regulative mechanisms in coronary blood flow, especially in critical conditions, are explained. Myocardial oxygenation in coronary artery disease is discussed with special reference to pharmacological intervention. An extensive evaluation of the effects of hemodilution on both the healthy and diseased heart is presented. Effects of hemodilution with fluorocarbons for the treatment or prevention of myocardial ischemia are shown with the aid of intramyocardial oxygen partial pressure measurements.