Dopamine or norepinephrine infusion during thoracic epidural anesthesia? Differences in hemodynamic effects and plasma catecholamine levels.

BACKGROUND: During thoracic epidural anesthesia, an intravenous dopamine infusion augments the systemic pressure response and modifies plasma catecholamine levels. If such an altered response occurs when norepinephrine is infused is not clear. Therefore, dopamine and norepinephrine induced circulatory and catecholamine responses were studied before and during thoracic epidural anesthesia. METHODS: Nine chloralose-anesthetized dogs were equipped with thoracic epidural catheters. Dopamine (5, 10, and 20 microg kg(-1) min(-1)), and norepinephrine (0.1, 0.25, and 0.5 microg kg(-1) min(-1)) were infused before and during epidural anesthesia, while cardiovascular performance and plasma catecholamine changes were studied. RESULTS: Thoracic epidural anesthesia decreased arterial pressure, and cardiac contractility. The systemic pressure response induced by dopamine was augmented during epidural anesthesia. Norepinephrine did not increase arterial pressure and myocardial contractility as markedly as dopamine, and cardiac output was not altered. Thoracic epidural anesthesia attenuated the plasma norepinephrine level. Plasma dopamine levels were augmented by the dopamine infusion during epidural anesthesia, while plasma norepinephrine levels were attenuated. In contrast, norepinephrine augmented the plasma norepinephrine levels during epidural anesthesia. In general, plasma norepinephrine levels were three to six times higher during a norepinephrine infusion compared to a dopamine infusion. CONCLUSION: The cardiovascular response to a graded dopamine infusion is augmented during thoracic epidural anesthesia, while norepinephrine-induced effects are unaltered. The modified plasma catecholamine levels may contribute to the hemodynamic differences between dopamine and norepinephrine infusions during thoracic epidural anesthesia.

Effects of fentanyl, nitrous oxide, or both, on baroreceptor reflex regulation in the cat.

We have investigated the effects of fentanyl, nitrous oxide, or both, on carotid sinus baroreceptor reflexes in cats during basal chloralose anaesthesia. The bilaterally isolated carotid sinuses were perfused at prevailing systemic arterial pressure or at predetermined levels of pump-controlled pulsatile pressures of 50-200 mm Hg in steps of 25 mm Hg. Other major baroreceptor sites were denervated by bilateral vagotomy. Fentanyl decreased arterial pressure dose-dependently when the carotid sinuses were perfused at prevailing systemic arterial pressure and when the perfusion pressure was controlled artificially. High-dose fentanyl reduced significantly baroreceptor reflex responses in the sinus perfusion pressure range 50-125 mm Hg. Nitrous oxide increased arterial pressure in the carotid sinus perfusion range 75-125 mm Hg. There was no interaction between nitrous oxide and fentanyl for baroreceptor reflex responses. Our results indicated that baroreceptor reflexes, with and without nitrous oxide, were well preserved by moderate doses of fentanyl while high doses of fentanyl depressed baroreceptor reflexes.

Cardiovascular responses to experimental infra-renal aortic cross-clamping. Modulating effects of isoflurane, sodium nitroprusside and milrinone.

BACKGROUND: Pharmacological control of blood pressure is usually indicated during aortic cross-clamping (AXC). The aim of this study was to analyze the modulation by isoflurane (ISO), sodium nitroprusside (SNP) and milrinone (MIL) of the systemic circulatory responses to a standardized infra-renal AXC. METHODS: Chloralose-anaesthetized pigs were exposed to AXC at control (no vasoactive drugs) and during the administration of each of the drugs. RESULTS: During control, AXC increased mean arterial pressure (MAP, 17 +/- 4%) and systemic vascular resistance (SVR, 27 +/- 7%), but induced no significant changes in cardiac output (CO), heart rate (HR), pulmonary arterial pressures, pulmonary vascular resistance or central venous pressure. Low-dose ISO (0.7%) and investigated doses of SNP and MIL did not significantly alter this response. High-dose ISO (1.4%, attenuated the AXC-induced increase in SVR, but not in MAP. All drugs decreased non-clamp MAP levels. Therefore, with low-dose ISO and with SNP or MIL, peak MAP during AXC was not significantly different from control non-clamp levels (i.e. prior to pharmacological or surgical interventions). High-dose ISO was associated with a MAP during AXC that was below control non-clamp levels. CONCLUSIONS: The objective that during AXC MAP should not exceed control non-clamp levels was achieveable by ISO, SNP or MIL. The modulating actions of the drugs on MAP during AXC were exerted mainly through reductions in non-clamp levels. This systemic hypotension was associated with decreased CO and SVR during ISO, and with decreased SVR and increased HR during SNP and MIL. Attenuation of the AXC-induced increase in SVR was produced only by 1.4% ISO.

Vasodilator effects of desflurane and isoflurane in the feline small intestine.

The influence of desflurane (DES) and isoflurane (ISO) on the intestinal vasculature was investigated in normoventilated cats (n = 10) during basal chloralose anesthesia (control). We measured heart rate, mean arterial pressure (MAP), and intestinal blood flow (optical drop flowmetry). Intestinal vascular resistance (IVR) was derived. To avoid changes in local vascular tone related to alterations in transmural pressure gradients, intestinal arterial pressure was controlled and kept constant by a variable aortic clamp. Measurements were performed during control and during the administration of DES (3.5% and 7.0% end-tidal) or ISO (0.8% and 1.6% end-tidal). Each animal was exposed to both agents, prior to and after intestinal postganglionic denervation. In the innervated intestine, both DES and ISO dose-dependently decreased IVR. At the high dose, DES (50 +/- 10% decrease in IVR) was a significantly more powerful vasodilator than ISO (37 +/- 12% decrease in IVR). In the denervated intestine, less pronounced vasodilations were produced by both DES and ISO, as compared to the innervated state, and there were, in this situation, no significant differences between agents concerning the magnitude of the vasodilation. As indicated by comparisons between the innervated versus the denervated state, both neurogenic and non-neurogenic mechanisms contributed to the vasodilator responses. The vascular relaxation at the high dose was for ISO associated with a significantly more powerful non-neurogenic vasodilation, and for DES associated with a significantly more powerful neurogenic vasodilation. This suggests that withdrawal of sympathetic neurogenic vasoconstrictor tone is more important for the vasodilation produced by DES than it is for ISO.

Are the cardiovascular actions of dopamine altered by isoflurane?

Dopamine seems theoretically to be a rationale choice when adrenergic support is needed to counter undesired cardiovascular depressant effects of isoflurane. Although the cardiovascular effects of isoflurane (ISO) and exogenous dopamine (DA) are well documented, there are no reports on their pharmacological interaction. The effects of ISO 1.4% (MAC 1.0) on the cardiovascular response to exogenous DA were studied in dogs during chloralose anesthesia. Instrumentation included catheterizations of the femoral artery (for aortic pressures and heart rate, HR), the pulmonary artery (for thermodilution cardiac output, CO, and pulmonary arterial pressures) and the left ventricle (for tip-manometer measured left ventricular end-diastolic pressure, LVEDP). ISO per se decreased HR (-16%), mean arterial pressure (MAP; -33%), CO (-29%), left ventricular dP/dt (LV dP/dt; -51%), and increased pulmonary artery occlusion (PAOP; +64%) and LVEDP (+28%). Prior to ISO, DA increased MAP, CO stroke volume (SV), LV dP/dt and LV dP/dt/SAP (systolic arterial pressure) at the dose 10 micrograms.kg-1.min-1. At the dose 20 micrograms.kg-1.min-1 DA, besides these effects, increased PAOP and mean pulmonary artery pressure (MPAP). During ISO, DA at the dose 10 micrograms.kg-1.min-1 restored MAP, CO, and SV to pre-ISO control levels, while LV dP/dt was increased to +96% above the pre-ISO control level. At the dose 20 micrograms.kg-1.min-1, DA increased MAP (+33%), LV dP/dt (+172%), PAOP (+132%) and MPAP (+50%) above pre-ISO control levels. The cardiac effects of DA were similar to when it was given alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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 micrograms.kg-1.min-1 and, additionally, increased mean pulmonary artery pressure (MPAP) at the dose 20 micrograms.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 micrograms.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 micrograms.kg-1.min-1. At the dose 20 micrograms.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.

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.

Local vascular effects of isoflurane during regional intestinal hypothermia in cats.

The influence of isoflurane on intestinal blood flow (IBF) during regional intestinal hypothermia (28 degrees C intraluminal temperature) was investigated in cats (n = 12) during basal chloralose-nitrous oxide anesthesia. A jejunal segment, which was dissected free in situ and intermittently cooled in a saline bath, was perfused via an extracorporeal arterial circuit which included a roller pump and a variable arterio-venous shunt. Intestinal perfusion pressures were controlled by adjusting the shunt flow. IBF was measured (optical drop-recording) during regional normothermia and hypothermia. 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% isoflurane. During normothermia, IBF levels were higher during isoflurane anesthesia than during basal chloralose anesthesia. Regional intestinal hypothermia induced no significant changes in IBF during basal chloralose anesthesia. However, the intestinal vasodilator effects of isoflurane, as shown during normothermia, were efficiently countered by regional cooling of the intestinal segment to 28 degrees C. Accordingly, hypothermia IBF levels were similar, regardless of whether isoflurane was administered or not. This could have an impact on the choice of anesthetic techniques.

Effects of thoracic epidural anesthesia and adrenoceptor blockade on the cardiovascular response to dopamine in the dog.

The cardiovascular effects of dopamine are different before and during thoracic epidural anesthesia (TEA). To evaluate underlying adrenoceptor-mediated mechanisms, dopamine effects were investigated in nine chloralose-anesthetized dogs. The circulatory response to dopamine (0-40 micrograms.kg-1.min-1) was studied before and during TEA, and during TEA after introducing the alpha 1-antagonist prazosin (0.3 mg.kg-1), the alpha 2-antagonist rauwolscine (0.3 mg.kg-1), and the beta 1-antagonist metoprolol (0.5 mg.kg-1). TEA decreased mean arterial pressure (MAP) by 29%, cardiac output (CO) by 36%, heart rate (HR) by 27%, and the maximum rate of change of left ventricular pressure (LVdP/dt) by 52%. Systemic vascular resistance, pulmonary vascular resistance and mean pulmonary artery pressure (MPAP) remained unaltered by TEA. Dopamine-induced increases in MAP and HR were augmented by TEA. Both MAP and LVdP/dt increased above pre-TEA levels at 10 micrograms.kg-1.min-1. Prazosin attenuated the increases in MAP and MPAP by dopamine. Adding rauwolscine almost abolished the dopamine response in MAP and MPAP. Metoprolol almost eliminated the dopamine effects on CO and LVdP/dt. Only minor alterations in cardiac filling pressures were observed during the study. Plasma norepinephrine (NE) concentration was lower during than before TEA at corresponding dopamine infusion rates. NE was reduced by the beta 1-blockade. During TEA, the plasma dopamine levels were generally higher, and they were further increased by adding beta 1-blockade. In conclusion, myocardial contractility and arterial pressure were restored to pre-TEA values by dopamine at 5-10 micrograms.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Interactive effects of isoflurane and amrinone in the feline intestinal and renal circulation.

Interactive effects of the phosphodiesterase-III inhibitor amrinone and isoflurane were investigated in cats. Cardiac output (thermodilution method), and intestinal (IBF) and renal (RBF) blood flows (optical flowmetry) were measured. Intestinal (IVR) and renal (RVR) vascular resistances were derived. To discriminate between pressure-related local myogenic vascular responses and primary vascular drug effects, intestinal and renal perfusion pressures (50 mmHg; 6.7 kPa) were controlled. The protocol included steady-state recordings with and without isoflurane in a randomized order, both before and after the administration of amrinone (2 mg.kg-1 i.v. + 2 mg.kg-1.h-1 i.v.. Amrinone induced no significant changes in IVR or RVR during basal chloralose anesthesia. During administration of 0.8% isoflurane, amrinone produced decreases in IVR and RVR, which were more pronounced than the vasodilator responses induced by this dose of isoflurane alone. On the other hand, with 1.6% isoflurane, amrinone did not add to the vasodilation. The cardiac effects of isoflurane and amrinone were small. Our data indicate that the vascular tone before administration of amrinone could be crucial for the vascular response of the drug and that isoflurane can significantly influence the regional circulatory effects of amrinone.

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 was 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).

Effects of dopamine on intestinal hemodynamics and motility during epidural analgesia in the cat.

The effects of dopamine on intestinal blood flow (IBF) and intestinal contraction rate (ICR), and on mean arterial pressure (MAP) and heart rate (HR) were studied in eight cats before and during epidural analgesia (EDA). Before EDA, dopamine 5 and 10 micrograms.kg-1.min-1 had no effect on IBF, MAP and HR, but the higher infusion rate decreased ICR by 71 +/- 19% (mean +/- 1 s.e.mean) (P less than 0.01). EDA significantly increased IBF when intestinal arterial pressure was maintained at an unchanged level by means of a pump, and transiently increased ICR and intestinal tone, but reduced MAP by 46 +/- 8% (139 +/- 11 to 75 +/- 9 mmHg, P less than 0.01) and HR by 26 +/- 3% (248 +/- 7 to 184 +/- 8 beats.min-1, P less than 0.01). During EDA, dopamine increased IBF further, the response being similar at both infusion rates. 5 micrograms.kg-1.min-1 increased HR by 26 +/- 7 beats.min-1 (P less than 0.01) and MAP by 19 +/- 9 mmHg (ns). The corresponding values at 10 micrograms.kg-1.min-1 were 65 +/- 14 beats.min-1 (P less than 0.01) and 35 +/- 8 mmHg (P less than 0.01), respectively, Vascular autoregulation appeared to be unaffected by dopamine and EDA. The effect of dopamine on ICR was not significantly different to what was seen before EDA. It is concluded that the effects of dopamine on IBF, MAP and HR were markedly different during EDA as compared to before the block and that ICR was reduced by dopamine, while it was transiently increased by EDA.(ABSTRACT TRUNCATED AT 250 WORDS)

SMS 201-995 and provocation tests in preparation of patients with carcinoids for surgery or hepatic arterial embolization.

Patients with midgut carcinoids undergoing surgical resection or ischemic treatment of hepatic metastases by embolization are at risk for development of carcinoid crises due to release of hormonally active tumor products. Eight such patients were treated on nine separate occasions with increasing subcutaneous doses of a synthetic somatostatin analogue (SMS 201-995) 4 days prior to surgery or hepatic arterial embolization. The patients were tested by pentagastrin provocation and simultaneous measurement of serotonin (5-HT) levels in peripheral blood before and after prophylactic treatment, to evaluate the efficacy of SMS 201-995. The provoked release of 5-HT was markedly diminished, and the basal levels of 5-HT were markedly reduced in patients with high initial levels. During surgery or embolization both SMS 201-995, as well as ketanserin, a 5-HT2 receptor blocker, were given. With this combined treatment all patients were hemodynamically stable during surgery or embolization. During embolization the arterial levels of 5-HT increased only moderately, while urinary excretion of 5-hydroxyindoleacetic acid remained unchanged despite a proven adequate embolization. Two patients were operated on without previous treatment with SMS 201-995; both developed severe crises at induction of anesthesia, but IV SMS 201-995 rapidly reversed the bronchoconstriction and facial flush and gradually restored arterial blood pressure, even though cardiac output remained depressed for a prolonged period. The crisis reaction correlated well with high circulating levels of 5-HT, but after treatment with SMS 201-995 these levels were still high.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of halothane, enflurane, and isoflurane on coronary vascular tone, myocardial performance, and oxygen consumption during controlled changes in aortic and left atrial pressure. Studies on isolated working rat hearts in vitro.

The effects of equi-anesthetic concentrations of halothane (HAL, n = 11), enflurane (ENF, n = 11) and isoflurane (ISO, n = 10) on cardiac function were studied and compared with a control group (n = 12) in isolated paced rat hearts by means of an antegrade heart perfusion technique. Left atrial pressure (LAP) and mean aortic pressure (MAP) could be altered independently of each other, and aortic flow, coronary flow (CF), and po2 in venous coronary effluent were continuously recorded. Stroke volume (SV), myocardial oxygen consumption (MVO2), and myocardial oxygen extraction were calculated: 1) MAP was altered from 60 to 120 mmHg at a constant LAP (7.5 mmHg), and 2) LAP was varied from 4 to 12.5 mmHg at a constant MAP (80 mmHg). Left ventricular function curves (LVFC) were constructed and the maximal SV (SVmax) was obtained. The LAP needed to perform 75% of the maximal SV (LAP0.75) was estimated to assess the effect of the anesthetics on diastolic function. HAL ENF and ISO decreased SVmax significantly compared to control. This decrease was more pronounced for HAL (41%) compared to both ENF (26%) and ISO (26%). Accordingly, SV, at various levels of MAP, at a constant LAP, was significantly lower for HAL than for both ENF and ISO, while there was no significant difference between the latter two. None of the anesthetics shifted the LVFC to the right, i.e., did not affect diastolic properties. HAL induced the most pronounced decrease in MVO2, while there was no significant difference between ENF and ISO in this respect. Coronary flow (CF), at controlled perfusion pressures, decreased significantly with HAL but not with ENF or ISO compared to control. CF was significantly higher with ISO compared to both ENF and HAL. HAL and ISO, but not ENF, decreased myocardial oxygen extraction significantly compared to control and, thus, increased the myocardial oxygen supply-to-demand ratio.

Cardiac receptor modulation of blood flow and fluid transport in feline jejunum.

The aim of the study is to determine the effects of selective cardiac receptor unloading on vascular resistance and net fluid transport in the small intestine. In anesthetized cats, cardiac receptors were unloaded by positive pressure ventilation (PPV). Arterial baroreceptor activity was artificially maintained constant. To test if the observed responses were due to a vagal reflex, experiments were performed both in animals with intact vagal nerves (n = 9) and after bilateral cervical vagotomy (n = 8). PPV-induced decreases in central blood volume (CBV) significantly increased intestinal vascular resistance (IVR) and net fluid absorption rate and decreased the transmural potential difference (PD). Cervical vagotomy per se also increased IVR and absorption rate and decreased PD. In vagotomized animals, decreases in CBV had no consistent effects on IVR, net fluid absorption rate, or PD. The results are compatible with cardiac receptor modulation of both blood flow and fluid absorption rate in the feline jejunum. Differences in the response patterns for the vascular and absorptive effects suggest that they may be mediated by separate efferent pathways.

Enhanced protein phosphorylation of carcinogen-initiated 10T1/2 cells accompanies their neoplastic transformation.

Retinyl acetate (RAC) prevents neoplastic transformation of carcinogen-exposed C3H/10T1/2 C18 cells, and has allowed the isolation of cells having the properties expected of initiated cells. After removal of RAC from logarithmically growing initiated cells, cultures first become confluent and growth arrested, as occurs with their normal counterparts. This is followed by an increase in thymidine labelling index and finally by morphological transformation on days 15 and 23, respectively, after seeding and drug removal. The increase in labelling index is the earliest indication yet seen of transformation taking place in these cultures. Phosphorylation of three nonionic detergent-soluble proteins was observed to be correlated with the increase in labelling index. Using two-dimensional gel electrophoresis, a protein of 35 kd (pp35(1)) and one of 38 kd (pp38) were seen to become more heavily phosphorylated in association with the increase in labelling index. A second protein of 35 kd (pp35(2)) was only detected in isolated transformed cells and is phosphorylated in an alkali-resistant manner consistent with phosphorylation of tyrosine residues. Alkali-resistant phosphorylation of pp35(2)) could be eliminated in transformed cells by treatment with RAC. Phosphorylation of pp35(1)) appears to be a permanently acquired characteristic of these cells, and cannot be made to revert. Phosphorylation of pp38, as indicated by isoelectric point, is reduced by RAC treatment. These studies implicate changes in protein phosphorylation in loss of growth control, and suggest that the cancer chemopreventive action of retinoids may also be mediated at this level.

Carotid sinus baroreceptor modulation of fluid transport and blood flow in the feline jejunum.

Carotid sinus baroreceptor control of jejunal fluid transport and vascular resistance was studied in chloralose-anesthetized cats. The carotid sinuses were isolated and perfused with blood from the femoral arteries. The aortic nerves were divided. In an isolated jejunal segment we measured net fluid transport rate, transmural potential difference (PD), and blood flow at a constant perfusion pressure of 75 mmHg. Carotid sinus pressure (CSP) was increased to 200-250 mmHg and was then lowered, in steps of approximately 25 mmHg, down to 50 mmHg. In the pressure interval from 90 to 200 mmHg, decreases in CSP increased jejunal vascular resistance and fluid absorption rate and decreased PD. In the interval from 50 to 90 mmHg, decreases in CSP increased vascular resistance and decreased PD but did not affect net fluid absorption rate. The results indicate that changes in baroreceptor activity may reflexly influence both vascular resistance and fluid transport rate in the feline jejunum, possibly via separate sympathetic mechanisms.

Influence of isoflurane on renal and intestinal vascular responses to stress.

Renal and intestinal vasoconstrictor responses elicited by either hypothalamic defence alarm area activation or stimulation of somatic and visceral afferents were studied in 17 cats. In part I, the circulatory adjustments during 2% (end-tidal) isoflurane plus 70% nitrous oxide in oxygen were compared with a medium-dose fentanyl in 70% nitrous oxide-oxygen sequence which was supplemented by diazepam. In part II, three end-tidal concentrations of isoflurane (1.4%, 2% and 3%) plus nitrous oxide in oxygen were evaluated before and after pre-treatment with droperidol 200 micrograms kg-1. During fentanyl-diazepam anaesthesia, intense vasoconstrictor responses with associated decreases in renal and intestinal blood flows were observed. Isoflurane 2% counteracted this reflex vasoconstriction, particularly in the renal vascular bed. The pressor and vasoconstrictor responses were suppressed by isoflurane in a dose-dependent fashion. After the administration of droperidol, the vascular beds were unaffected by noxious stimulation. It is concluded that isoflurane blunts stress-related vasoconstriction in a dose-dependent fashion, especially in the renal, but also in the intestinal, circulation. Droperidol adds to the vasodilatory effect of isoflurane.

Effects of hyperventilation and hypoventilation on stress-induced intestinal vasoconstriction.

The combined effects of defined changes in ventilation and stress-induced vasoconstriction were studied in the intestinal vascular bed in cats (n = 20) anaesthetized with fentanyl, nitrous oxide and diazepam. Intestinal reflex vasoconstriction was induced by stimulation either of the hypothalamic defence-alarm area or of somatic and visceral pain afferents. The volume-controlled ventilation was changed by altering the tidal volume, and stimulations were performed during either control conditions (Paco2 4.5-5.0 kPa), hyperventilation (Paco2 3.0-3.5 kPa) or hypoventilation (Paco2 6.5-7.5 kPa). The increase in intestinal vascular resistance (IVR) elicited by defence-alarm area stimulation was potentiated during hyperventilation (306 +/- 83% vs 198 +/- 62%; P less than 0.01) and attenuated during hypoventilation (176 +/- 62% vs 240 +/- 44%; P less than 0.05). The increase in IVR elicited by pain fibre stimulation was potentiated during hyperventilation (73 +/- 21% vs 54 +/- 19%; P less than 0.01), but not significantly changed during hypoventilation (47 +/- 19% vs 68 +/- 34% during control ventilation). Our data indicate that the ventilatory pattern can be decisive for the vasoconstrictor response during experimental stress. We suggest that remote neurogenic mechanisms account for the increased responsiveness during hyperventilation. The decreased responsiveness during hypoventilation, on the other hand, seems to correlate with the local vasodilator effects of carbon dioxide.

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 microgram X kg-1 X 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.