J. Martner

The effects of propofol, methohexitone and isoflurane on the baroreceptor reflex in the cat

The effects of propofol (P), methohexitone (M) and isoflurane (I) on the baroreceptor reflex were studied in a cat model in which the blood pressure in a bilateral isolated carotid sinus preparation was artificially varied between 50–200 mmHg. The influence from aortic and cardiopulmonary baroreceptors was excluded by vagotomy. With basal chloralose anaesthesia as control, the investigated anaesthetics were used in doses corresponding to MAC 0.5 and 1.0. The maximum change in systemic mean arterial pressure (MAP) and heart rate (HR) following a defined increase in carotid sinus pressure was used as an index of baroreceptor reflex sensitivity. Compared to control, M and I anaesthesia were associated with significant depression of baroreceptor reflex sensitivity at the high dose (corresponding to MAC 1.0), and during I anaesthesia also at the low dose (MAC 0.5). The baroreceptor reflex sensitivity was maintained during propofol anaesthesia. The carotid sinus pressure interval at which the maximum changes in MAP could be elicited, was significantly higher during M than during P. This indicates resetting of the baroreflex.

Intravenous Infusion of Halothane Dissolved in Fat. Haemodynamic Effects in Dogs

Eight harrier dogs received an i.v. infusion of halothane dissolved 1:9 in a fat emulsion for i.v. nutrition (Intralipidr̀, Vitrum). The rate of infusion was adjusted to maintain end‐tidal halothane concentrations of 0.7% and 1.4%. At 1.4%, mean arterial pressure decreased to 76 ± 8 mmHg (10.1 ± 1.0 kPa) (mean ± s.e.mean) from a pre‐infusion value of 122 ± 6 mmHg (16.2 ± 0.8 kPa) (P<0.01). The concomitant decrease in cardiac output was 39% and left ventricular maximum dp/dt decreased by 50% (P<0.01). Changes in systemic vascular resistance and pulmonary arterial pressure were small. The haemodynamic responses during halothane inhalation, to corresponding end‐tidal concentrations, were similar. Arterial and mixed venous halothane concentration increased in proportion to end‐tidal concentration. There were no changes in arterial Po2 during the halothane‐in‐fat infusion. Triglyceride concentrations in plasma increased 12‐fold. Haemodynamic recovery after the infusion was fast. We conclude that the halothane‐in‐fat infusion caused a dose‐dependent depression of myocardial contractility and arterial pressure, similar to that seen during inhalation, and that end‐tidal concentration could be used for control of the infusion rate.

Does Dopamine Suppress Stress-Induced Intestinal and Renal Vasoconstriction?

Dopamine interference with intestinal and renal sympathetic reflex vasoconstrictor responses was studied in cats anaesthetized with diazepam, fentanyl and nitrous oxide. Vasoconstriction was induced by electric stimulation of the hypothalamic defence‐alarm area and by stimulation of somatic and visceral afferents. In addition, intestinal vasoconstriction was elicited by direct stimulation of postganglionic sympathetic efferent nerves. In the intestine, dopamine administration (7.5 μg ‐ kg‐1 ‐min‐1) was not associated with an attenuation of the investigated sympathetic vasoconstrictor responses, although dopamine per se decreased intestinal vascular resistance by 36 ± 4%. Due to this dopamine‐induced background vasodilation, the intestinal blood flow level during stimulation procedures and concomitant dopamine infusion was higher than during similar stimulations prior to dopamine (for defence‐alarm area stimulation 45 ± 16%, for afferent nerve stimulation 79 ±22% and for efferent postganglionic nerve stimulation 66 ± 16%). In the kidney, dopamine per se had only minor effects on vascular resistance and on changes in vascular tone elicited by the stimulation procedures. The renal blood flow level in response to the stimulation procedures was not significantly affected by dopamine. In conclusion, dopamine may contribute to a sustained intestinal blood flow level when administered during supervening stress‐related sympathetic activation.

Cardiovascular depression by isoflurane and concomitant thoracic epidural anesthesia is reversed by dopamine

Interactive effects between exogenous dopamine (DA) and isoflurane (I) combined with thoracic epidural blockade (TEA) were studied in dogs during chloralose anesthesia. The I–TEA intervention per se decreased heart rate (HR; 28%), mean arterial pressure (MAP; 63%), cardiac output (CO; 54%), left ventricular dP/ dt (LVdP/dt; 75%) and LVdP/dt/systolic arterial pressure (SAP; 42%). Prior to the I–TEA intervention, dopamine increased MAP, CO, LVdP/dt, LVdP/dt/SAP and stroke volume (SV) already at the dose 10 μg–kg‐1. min‐1 and, additionally, increased mean pulmonary artery pressure (MPAP) at the dose 20 μg–kg‐1. min‐1. During the I–TEA intervention, the DA–induced increases in MAP and systemic vascular resistance (SVR) were significantly higher than prior to I–TEA, as indicated by significant ANOVA interactive effects. At the dose 10 μg–kg‐1 min‐1, DA restored MAP, CO, LVdP/dt, LVdP/dt/SAP and SV to levels found before the I–TEA intervention, while HR was restored first at the dose 20 μg–kg‐1 –min‐1. At the dose 20 μg–kg‐1–min‐1, DA also increased MAP (39%), LVdP/dt (119%), LVdP/dt/SAP (73%), SVR (28%) and MPAP (70%) above levels prior to I–TEA. To conclude, exogenous dopamine effectively and dose–dependently counters cardiovascular depression induced by the anesthetic technique of combining I and TEA. The pressor and systemic vasoconstrictor actions of dopamine are potentiated by conjoint administration of I and TEA.

Effects of isoflurane on vascular tone and circulatory autoregulation in the feline small intestine.

The vascular response in autoperfused small intestine was studied in ten cats during basal chloralose anaesthesia and controlled ventilation with either air, nitrous oxide/oxygen (70/30) or 0.7% end‐tidal concentration of isoflurane + nitrous oxide/oxygen (70/30). Intestinal blood flow was measured by the optical drop recording technique, and intestinal perfusion pressure was kept constant at either 100, 75 or 50 mmHg (13.30, 9.98 or 6.65 kPa). At perfusion pressures of 100 and 75 mmHg (13.30 and 9.98 kPa), intestinal blood flow was significantly increased and intestinal vascular resistance decreased during isoflurane + nitrous oxide/oxygen anaesthesia, compared with nitrous oxide/oxygen or air. According to the equation of closed loop gain (Gf), autoregulation was active in the pressure range 100‐75 mmHg (13.30‐9.98 kPa). In the pressure range 75‐50 mmHg (9.98‐6.65 kPa), the autoregulatory capacity was attenuated during air or nitrous oxide/oxygen and absent during isoflurane + nitrous oxide/oxygen. The vasodilator responses and the autoregulatory pattern were not changed by post‐ganglionic intestinal denervation. The intestinal vasodilator effect of isoflurane was further investigated in the denervated intestine, perfused at systemic arterial pressure by local intra‐arterial administration of isoflurane dissolved in a fat emulsion. A dosedependent vasodilator response was hereby observed.

Anaesthesia and cardiovascular regulation.

Cardiovascular homeostasis is dependent on the efficient performance of the effector organs, i.e. the vascular smooth muscle and the heart. Besides inherent activity and local control mechanisms, these effector organs are regulated by circulatory control centres within the central nervous system, which in turn receives information from receptors inside and outside the cardiovascular system. All these components of the circulatory systems, i.e. receptors, afferent and efferent pathways, control centres and effector organs, are possible sites for interactions by anaesthetics. Since different anaesthetics have different potencies and special predilections, there are a large variety of interaction patterns, as is discussed in the paper. Another way of evaluating circulatory effects of drugs used in anaesthesia is to analyse how these drugs may modify circulatory reflexes associated with surgery and trauma. For example, pain, hypoxia and/or hypovolaemia may evoke circulatory adjustments which correspond to and are functionally related to, from experimental physiology, well‐known reflex patterns such as the somatosympathetic reflex, the chemoreceptor reflex and the baroreceptor reflex. These reflex adjustments are liable to modification by anaesthetics, as exemplified in the paper. Due to the complexity of circulatory control and the varying effects of different anaesthetic agents, it is difficult to draw general conclusions. It can, however, be stated that most general anaesthetics depress cardiovascular reflexes in proportion to the depth of anaesthesia, and that suprabulbar centres are more easily depressed than bulbar ones. Opiates seem to have a specific inhibitory effect on circulatory adjustments induced by noxious stimuli. Transmission in efferent and afferent pathways is liable to modification by local anaesthetics, ganglionic blockers or α‐ and β‐receptor antagonists.

Modification by Baroreceptor Feedback of Circulatory Responses to Noxious Stimuli During Anaesthesia in Cats

In eight cats anaesthetized with chloralose, the carotid sinus on one side was either exposed to systemic arterial pressure or perfused with a pump in order to control sinus pressure. Baroreceptor influences from the contralateral carotid sinus and from the aortic arch were interrupted by denervation. Arrangements were made for intermittent electric stimulation of pain fibres in somatic and visceral nerves with stimulation parameters chosen to elicit reproducible increases in arterial blood pressure and in skeletal muscle vascular resistance. The elicited increases in arterial pressure and muscle vascular resistance were both about 40% smaller when the carotid sinus was exposed to systemic arterial pressure in comparison with the experimental condition of a constant carotid sinus pressure. I. v. metoprolol (0.1‐0.3 mg kg‐1) reduced base‐line arterial pressure, but did not attenuate the arterial blood pressure increase in response to pain stimulation. The baroreceptor modulation of the haemodynamic response to the pain stimulation was not affected by metoprolol.

Hemodynamic Consequences of Defence Area Stimulation and Afferent Somatic Nerve Stimulation During Fentanyl‐Nitrous Oxide Anesthesia. Modifying Effects of Droperidol

Stimulation of the hypothalamic defence area and activation of somatic afferents in combination with carotid baroreceptor unloading was performed in cats anesthetized with fentanyl‐nitrous oxide in order to investigate the circulatory consequences in terms of regional blood flow changes. These stimulation procedures, suggested to mimic activation of central neurogenic cardiovascular control mechanisms caused by anesthesia and surgical stress, were found to induce pronounced reductions in intestinal and renal blood flow as well as in diuresis. However, administration of droperidol markedly diminished the renal vasoconstriction as well as the reduction in diuresis in the dose range 0.025–0.10 mg/kg b.w. Doses of 0.15–0.25 mg/kg b.w. virtually abolished any stimulation‐induced increase in renal vascular resistance, whether elicited through activation of the defence area or somatic afferents. This dose also partly blocked the neurogenic increment of intestinal vascular resistance.

Effects of isoflurane on feline intestinal blood flow during hemorrhage‐induced hypovolemia

The influence of isoflurane on intestinal reflex vasoconstriction during hemorrhage was investigated in cats (n= 10) during basal chloralose‐nitrous oxide anesthesia. Intestinal blood flow (IBF) was studied in a model with controllable intestinal perfusion pressures to exclude local myogenic vascular responses related to changes in intraluminal pressure. A jejunal segment, which was dissected free in situ, was perfused via an extracorporeal arterial circuit which included a roller pump and a variable arterio‐venous shunt. Intestinal perfusion pressure wds controlled by adjusting the shunt flow. IBF was measured (optical drop‐recording) before and after hemorrhage (8% of estimated blood volume). The protocol included steady‐state recordings at defined perfusion pressures (50, 75, 100, 125 and 150 mmHg in a randomized order; 6.7, 10.0, 13.3, 16.7 and 20.0 kPa, respectively) with and without the addition of 0.7% (MAC 1.0) isoflurane. IBF levels were consistently higher during isoflurane anesthesia than during basal chloralose anesthesia in the perfusion pressure range 75–150 mmHg (10.0–20.0 kPa). During basal anesthesia, a hemorrhage‐induced decrease in IBF was demonstrated throughout the perfusion pressure range 50 to 150 mmHg (6.7–20.0 kPa). The magnitude of the hemorrhage‐induced decrease in IBF was not significantly influenced by the addition of isoflurane. Thus, IBF, following hemorrhage, was significantly higher during isoflurane anesthesia than during basal chloralose anesthesia at perfusion pressures 50, 100, 125 and 150 mmHg (6.7, 13.3, 16.7 and 20.0 kPa).

Halothane by the I. V. Route in Experimental Animals

In a preliminary investigation, halothane dissolved in a 20% fat emulsion (Intralipid®) was administered intravenously to chloralose‐anaesthetized cats. A dose‐related mixed expiratory concentration of halothane was encountered. The cardiovascular adaptation to i.v. halothane was in agreement with previous reports on haemodynamics during inhalation of halothane. Animal experimental applications for i.v. halothane administration are suggested, while the usefulness of the technique in man remains to be ascertained.