Nitroprusside-induced Hypotension Research Articles

Anaphylaxis stimulates afferent vagal nerve activity and efferent sympathetic nerve activity in the stomach of anesthetized rats.

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15-55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (ef-GSNA), but not the efferent vagal nerve activity, increased only at the early phase (1-10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis.

Isolated bilateral globus pallidus infarcts in a patient with aortic dissection and Nitroprusside-induced hypotension: A case report (P5.043)

Isolated bilateral globus pallidus infarcts in a patient with aortic dissection and Nitroprusside-induced hypotension: A case report (P5.043)

Effect of glutamate on the vestibulo-solitary projection after sodium nitroprusside-induced hypotension in conscious rats.

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

Impaired Baroreflex Function in Mice Overexpressing Alpha-Synuclein

Cardiovascular autonomic dysfunction, such as orthostatic hypotension consequent to baroreflex failure and cardiac sympathetic denervation, is frequently observed in the synucleinopathy Parkinson’s disease (PD). In the present study, the baroreceptor reflex was assessed in mice overexpressing human wildtype alpha-synuclein (Thy1-aSyn), a genetic mouse model of synucleinopathy. The beat-to-beat change in heart rate (HR), computed from R–R interval, in relation to blood pressure was measured in anesthetized and conscious mice equipped with arterial blood pressure telemetry transducers during transient bouts of hypertension and hypotension. Compared to wildtype, tachycardia following nitroprusside-induced hypotension was significantly reduced in Thy1-aSyn mice. Thy1-aSyn mice also showed an abnormal cardiovascular response (i.e., diminished tachycardia) to muscarinic blockade with atropine. We conclude that Thy1-aSyn mice have impaired basal and dynamic range of sympathetic and parasympathetic-mediated changes in HR and will be a useful model for long-term study of cardiovascular autonomic dysfunction associated with PD.

Effects of sodium nitroprusside-induced controlled hypotension on pancreatic function assessed by pancreatitis-associated protein in patients undergoing radical prostatectomy: Retraction

Effects of sodium nitroprusside-induced controlled hypotension on pancreatic function assessed by pancreatitis-associated protein in patients undergoing radical prostatectomy: Retraction

The Effects of Sodium Nitroprusside-Induced Hypotension on Splanchnic Perfusion and Hepatocellular Integrity

The Effects of Sodium Nitroprusside-Induced Hypotension on Splanchnic Perfusion and Hepatocellular Integrity

Antecedent Hypoglycemia Impairs Autonomic Cardiovascular Function

OBJECTIVE— Glycemic control decreases the incidence and progression of diabetic complications but increases the incidence of hypoglycemia. Hypoglycemia can impair hormonal and autonomic responses to subsequent hypoglycemia. Intensive glycemic control may increase mortality in individuals with type 2 diabetes at high risk for cardiovascular complications. We tested the hypothesis that prior exposure to hypoglycemia leads to impaired cardiovascular autonomic function.RESEARCH DESIGN AND METHODS— Twenty healthy subjects (age 28 ± 2 years; 10 men) participated in two 3-day inpatient visits, separated by 1–3 months. Autonomic testing was performed on days 1 and 3 to measure sympathetic, parasympathetic, and baroreflex function. A 2-h hyperinsulinemic [hypoglycemic (2.8 mmol/l) or euglycemic (5.0 mmol/l)] clamp was performed in the morning and in the afternoon of day 2.RESULTS— Comparison of the day 3 autonomic measurements demonstrated that antecedent hypoglycemia leads to 1) reduced baroreflex sensitivity (16.7 ± 1.8 vs. 13.8 ± 1.4 ms/mmHg, P = 0.03); 2) decreased muscle sympathetic nerve activity response to transient nitroprusside-induced hypotension (53.3 ± 3.7 vs. 40.1 ± 2.7 bursts/min, P < 0.01); and 3) reduced (P < 0.001) plasma norepinephrine response to lower body negative pressure (3.0 ± 0.3 vs. 2.0 ± 0.2 nmol/l at −40 mmHg).CONCLUSIONS— Baroreflex sensitivity and the sympathetic response to hypotensive stress are attenuated after antecedent hypoglycemia. Because impaired autonomic function, including decreased cardiac vagal baroreflex sensitivity, may contribute directly to mortality in diabetes and cardiovascular disease, our findings raise new concerns regarding the consequences of hypoglycemia.

Overexpression of eNOS prevents the development of renovascular hypertension in mice

Gene therapy has become an important tool for understanding several cardiovascular diseases. In the present study we investigated the effects of endothelial nitric oxide synthase (eNOS) overexpression on renovascular hypertension. Experiments were carried out in C57BL/6 mice randomly assigned to either a two-kidney one-clip (2K1C) hypertension group or a sham-operated group. At the same time surgery was carried out, both 2K1C and sham mice received an intravenous injection of recombinant adenovirus expressing the functional gene eNOS or the reporter gene beta-galactosidase (beta-gal). Fourteen days later, arterial pressure, baroreflex sensitivity, and cardiac sympathetic and parasympathetic tone were evaluated in conscious mice. Measurement of mean arterial pressure showed arterial hypertension in 2K1C-betagal mice compared with sham-betagal mice (121 +/- 3 vs. 96 +/- 2 mm Hg, p < 0.01), which was prevented by eNOS overexpression (2K1C-eNOS 100 +/- 4 vs. sham-eNOS 99 +/- 3 mm Hg). Linear regression analysis of the reflex tachycardia response to sodium nitroprusside-induced hypotension showed that baroreflex sensitivity was significantly attenuated in 2K1C-betagal mice (5.8 +/- 0.5 vs. sham-betagal 8.0 +/- 0.8 beats.min-1 x mm Hg-1, p < 0.05), but this decrease was not prevented by eNOS overexpression (2K1C-eNOS 7.2 +/- 0.5 vs. sham-eNOS 8.8 +/- 0.7 beats x min-1 x mm Hg-1, p < 0.05). The cardiac sympathetic tone was augmented and the vagal tone was reduced in 2K1C-betagal (152 +/- 17 and 45 +/- 12 beats.min-1, respectively) compared with sham-betagal mice (112 +/- 6 and 89 +/- 7 beats.min-1, respectively), and similar results were observed in 2K1C-eNOS mice compared with sham-eNOS. The data indicate that eNOS overexpression was able to prevent the development of 2K1C renovascular hypertension in mice, without affecting other characteristic cardiovascular dysfunctions.

Impairment of sympathetic baroreceptor reflexes in obese Zucker rats

Adult obese Zucker rats (OZRs) have elevated sympathetic vasomotor tone and arterial pressure (AP) with blunted baroreflex-mediated changes in heart rate (HR) compared with adult lean Zucker rats (LZRs). The present study examined whether compromised cardiac baroreflexes are indicative of attenuated sympathetic responses. In addition, because juvenile OZRs have a normal mean AP, we determined whether baroreflexes are fully functional prior to hypertension. At 13 wk, adult OZRs had an elevated baseline mean AP compared with LZRs (137 +/- 3 vs. 123 +/- 5 mmHg, P < 0.05) under urethane anesthesia. Phenylephrine-induced increases in AP evoked smaller inhibitions of splanchnic sympathetic nerve activity (SNA) and HR in OZRs compared with LZRs. In addition, sympathoexcitatory responses to nitroprusside-induced hypotension were also blunted in OZRs. Sigmoid analysis revealed a decreased gain, a higher mean AP at the midpoint of the curve (AP(50)), and a reduced range of changes in SNA in OZRs. In contrast, at 7 wk of age, although juvenile OZRs weighed more than LZRs (313 +/- 13 vs. 204 +/- 4 g, P < 0.05), mean AP was comparable in both groups (122 +/- 5 vs. 121 +/- 4 mmHg, not significant). In these rats, rapid changes in AP evoked comparable changes in SNA and HR in OZRs and LZRs. Sigmoid analysis revealed that, although the gain of the reflex was blunted in OZRs (P < 0.05), the mean AP(50) and range of changes in SNA were comparable in OZRs and LZRs. Together, these data indicate that in adult OZRs, sympathetic responses to acute changes in AP are smaller than those observed in adult LZRs and that impairment of baroreceptor reflexes in OZR is not limited to the regulation of HR but extends to sympathetic vasomotor control. In addition, most of these deficits in baroreflex control of SNA develop in adulthood long after the onset of obesity and when other deficits in cardiovascular regulation are present.

Urocortin 1 modulates the neurohumoral response to acute nitroprusside-induced hypotension in sheep

In addition to haemodynamic actions, Ucn1 (urocortin 1) has been reported to affect a number of hormonal systems; however, it remains unclear whether Ucn1 modulates circulating hormones under physiological conditions. Accordingly, in the present study, we have examined the effects of Ucn1 on haemodynamics, hormones and renal indices in normal conscious sheep subjected to a nitroprusside-induced hypotensive stimulus designed to alter hormonal levels within the physiological range. Ucn1 administration did not alter the haemodynamic response to nitroprusside-induced hypotension. However, compared with the rise observed on the control day, plasma ANP (atrial natriuretic peptide; P=0.043), BNP (brain natriuretic peptide; P=0.038) and endothelin-1 (P=0.011) levels were reduced following Ucn1 administration. Associated with this significant reduction in natriuretic peptides, the increase in urinary sodium output associated with rising pressures post-nitroprusside was abolished following Ucn1 administration (P=0.048). Ucn1 had no significant effect on the response of hormones of the renin-angiotensin-aldosterone system or the hypothalamo-pituitary-adrenal axis. In conclusion, Ucn1, administered at physiologically relevant levels during nitroprusside-induced hypotension, attenuates the secretion/release of endothelin-1 and the cardiac natriuretic peptides ANP and BNP. Suppression of ANP and BNP probably led to an attenuated natriuretic response to recovery from acute hypotension. The threshold for the action of Ucn1 on the natriuretic peptides and endothelin-1 appears to be below that of other actions of Ucn1.

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Influence of sympathetic tone on heart rate during vagal stimulation and nitroprusside induced hypotension in ovine fetus

Objective To characterize effects of sympathetic tone on fetal heart rate (FHR) reflex responses and FHR variability in late gestation. Design/Methods Changes in FHR and autonomic tones were studied (i) after electrical vagal stimulation and (ii) during nitroprusside-induced hypotension, in seven late gestation ovine fetus in control condition (ctrl), after dobutamine (β1-activation) and atenolol (β1-blockade). Results are expressed as mean ± SEM. Results (i) Minimal FHR after vagal stimulation was not influenced by atenolol or dobutamine but dobutamine accelerated FHR normalization. (ii) During nitroprusside induced hypotension atenolol inhibited the initial increases in FHR and FHR variability (measured by SD and LFnu) but not the bradycardia occurring below a mean arterial pressure of 38 ± 2 mmHg. Dobutamine did not abolish the depressor reflex. During hypotension the positive chronotropic effect of sympathetic tone increased from 15 ± 2 to 42 ± 7 bpm then decreased at a rate of − 7.6 ± 1.5 bpm mmHg − 1 , vagal negative chronotropic influence steadily increased at a rate of 1.9 ± 0.4 bpm mmHg − 1 . Changes in FHR variability were not correlated with vagal or sympathetic chronotropic effects. Conclusions β1-stimulation does not affect sinus-node response to vagal stimulation but improves the speed of FHR normalization. FHR response to hypotension depends on an initial increase in both sympathetic and parasympathetic chronotropic effects that is associated with a sympathetic dependent increase in FHR variability and is followed by a withdrawal of sympathetic tone.

Novel therapeutic option in hypertensive crisis: sildenafil augments nitroprusside-induced hypotension

Sodium nitroprusside (SNP) produces hypotension by increasing nitric oxide-mediated generation of cyclic guanosine monophosphate (cGMP), which causes vasodilatation. On the other hand, sildenafil, a phosphodiesterase type 5 inhibitor (PDE5), increases cGMP by inhibiting its degradation by PDE5. Hence, theoretically, the two should be complementary. We present a case where the two agents were used together to manage a hypertensive crisis. This, to the best of our knowledge, is the first such case report worldwide.

Esmolol attenuates hepatic blood flow responses during sodium nitroprusside-induced hypotension in dogs.

The hemodynamic responses secondary to sympathetic suppression by esmolol may alter blood flow to splanchnic organs. We investigated whether esmolol might modify splanchnic organ blood flow responses during sodium nitroprusside (SNP)-induced hypotension in dogs anesthetized with sevoflurane. The control group (n = 10) received SNP (SNP group). The ES25 and ES100 groups (n = 10, each) received SNP combined with esmolol infused at a constant rate of 25 and 100 micro g*kg(-1)*min(-1) during the hypotensive period after a mean arterial pressure (MAP) of 60 mmHg was attained by the infusion of a 0.03% SNP solution, respectively. The renal, hepatic, and pancreatic blood flows (RBF, HBF, and PBF) were measured by using the hydrogen clearance method. Cardiac index in the SNP group increased (P < 0.01), but in the ES groups it decreased (P < 0.01). Left ventricular dP/dtmax in the SNP group remained unchanged, but in the ES groups it decreased (P < 0.01, each) during the hypotensive period. Except for HBF in the SNP group, the splanchnic blood flow in all groups decreased (P < 0.01, each). The HBF in the ES groups was lower than that in the SNP group (SNP vs ES25, ES100; 70 +/- 1 vs 64 +/- 5, 6 3 +/- 3 mL*min(-1)*100 g(-1)). This study shows that the differences in HBF between SNP-induced hypotension with or without esmolol may be due to the changes in cardiac output caused by alterations of cardiac contractility. These findings suggest that a small dose of esmolol may impair the maintenance of HBF during SNP-induced hypotension.

Internal thoracic artery flow competition: studies in a canine H-graft model.

Internal thoracic artery (ITA) flow competition is a diversion of graft flow through intact ITA branches with a net decrease in perfusion to the grafted coronary. Although a widely acknowledged phenomenon, the conditions under which flow competition occurs have not been established. This is examined in a canine H-graft model. Eight dogs had a right ITA segment interposed (H-graft) between their in situ left ITA (LITA) and the snared left anterior descending (LAD) coronary artery. Proximal LITA and H-graft flows were measured at baseline and during pacing-induced tachycardia, phenylephrine-induced hypertension, and nitroprusside-induced hypotension. Flows were measured with the distal LITA open and occluded. Two additional animals were subjected to eight separate 2-min periods of LAD ischemia, after which post-ischemic H-graft flow measurements were obtained with and without distal LIMA occlusion. During baseline conditions, proximal LITA flow was greater when the distal LITA was open rather than occluded (46+/-15 versus 35+/-12 ml/min, respectively; P=0.002), but H-graft flow did not change significantly (32+/-18 versus 35+/-18 ml/min, respectively; P=0.21). Similarly, occlusion of the distal LITA had no impact on H-graft flow during tachycardia, hypertension, or hypotension. Only in animals subjected to transient LAD ischemia did H-graft flow increase with distal LITA occlusion, albeit marginally (65+/-7-70+/-9 ml/min, occluded versus open, respectively; P=0.04). Mild diversion of flow from the LAD was demonstrated during immediate post-ischemic coronary reperfusion only, and could not be elicited under any other physiologic condition. These data suggest that flow competition is unlikely to constitute a clinically significant limitation to the use of H-grafts or other modalities that leave ITA branches patent.

Postnatal cardiovascular function after manipulation of fetal growth by embryo transfer in the horse.

This study used between-breed embryo transfer in the horse to investigate the effects of maternal size and uterine capacity on fetal growth and postnatal cardiovascular and neuroendocrine functions. Equine embryos were transferred to establish eight Thoroughbred-in-Thoroughbred (TinT), seven Pony-in-Pony (PinP), five Thoroughbred-in-Pony (TinP) and eight Pony-in-Thoroughbred (PinT), pregnancies. Maternal and foal weights and placental microscopic area were measured at birth. At 6 days of postnatal life, arterial blood pressure and heart rate were monitored and blood samples were taken for hormone analysis before, during and after a 10 min period of nitroprusside-induced hypotension. Values for maternal and foal weights and placental area at birth were larger in TinT than in PinP pregnancies (P < 0.05). PinT pregnancies resulted in larger placentae and heavier foals relative to PinP (P < 0.05). TinP had smaller placentae and lighter foals relative to TinT (P < 0.05). Growth-enhanced (PinT) foals showed elevated basal arterial blood pressure and baroreflex threshold, reduced baroreflex sensitivity, diminished plasma catecholamine responses to acute stress, and increased cortisol responsiveness to ACTH. Conversely, growth-restricted (TinP) foals showed no change in basal arterial blood pressure, baroreflex threshold or adrenocortical responsiveness to ACTH, but had enhanced baroreflex sensitivity and augmented plasma catecholamine responses to acute stress. The data show that fetal growth acceleration as well as fetal growth restriction, resulting from between-breed embryo transfer in the horse, leads to altered postnatal regulation of blood pressure and the circulating concentrations of cortisol. These findings suggest that deviations in the pattern and rate of fetal growth both above and below the normal trajectory may influence cardiovascular function in postnatal life.

Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats.

Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng x kg(-1) x min(-1) iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes.

Neurochemistry of nerve fibers apposing sympathetic preganglionic neurons activated by sustained hypotension.

Sympathetic preganglionic neurons (SPN) in rat spinal cord were activated by the reflex stimulation of bulbospinal sympathetic neuronal pathways after a nitroprusside-induced hypotension. Hypotension-sensitive SPN, identified by immunoreactivity (IR) to the product of the immediate early gene c-fos and to choline acetyltransferase, were localized in the intermediolateral cell column of thoracic and upper lumbar cord, particularly middle to lower thoracic cord. Putative neurotransmitters, or their markers, in varicose fiber networks around SPN were identified. Nearly all hypotension-sensitive (Fos-IR) SPN were apposed by varicose fibers immunoreactive for tyrosine hydroxylase, serotonin, substance P, or enkephalin. Neuropeptide Y (NPY)- or phenylethanolamine-N-methyl transferase (PNMT)-IR varicose fibers apposed Fos-IR SPN in the upper and middle thoracic spinal cord, but in lower thoracic segments some Fos-IR SPN lacked these appositions. In thoracic segment 12, 51% +/- 5% of Fos-IR SPN (n = 9 rats) lacked PNMT contacts and 25% +/- 3% of Fos-IR SPN (n = 8 rats) lacked NPY contacts. In contrast to other chemically defined afferents, galanin-IR varicose fibers apposed fewer than half of the Fos-IR SPN in the middle to lower thoracic cord. Neurotransmitters/neuromodulators that might influence the activity of SPN acting in the baroreflex-mediated control of blood pressure have been identified. Uniformity in the neurochemistry of some fibers making connections with Fos-IR SPN, regardless of their segmental origin, suggests that common sets of neurons provide convergent inputs to all hypotension-sensitive SPN. Other fibers show topographic differences in their contacts with Fos-IR SPN, suggesting that subgroups of hypotension-sensitive SPN are targeted by particular neuron groups.

Hypotension-induced dopamine release in prefrontal cortex is mediated by local glutamatergic projections at the level of nerve terminals.

In a previous study it was shown that nitroprusside-induced hypotension strongly enhances the release of dopamine (DA) in the prefrontal cortex (PFC). In the present study we have further investigated the mechanism involved in this effect. Glutamate receptor antagonists were infused into the ventral tegmental area (VTA) or PFC, while DA release was measured in the ipsilateral PFC and hypotension was applied by intravenous infusion of nitroprusside. Infusion into the VTA of neither a NMDA receptor antagonist (CPP), nor a non-NMDA antagonist (DNQX) affected the hypotension-induced increase of DA in the PFC. Intracortical infusion of CPP also failed to affect significantly, whereas local infusion of DNQX inhibited the hypotension-enhanced release of DA dose-dependently. The stimulation of DA release was relatively small in the VTA as well as in the nucleus accumbens when compared with the response in the PFC. It is concluded that DA released from mesocortical neurons can be modulated by two different mechanisms: first, by glutamate afferents to the VTA that modify the nerve-impulse flow of DA neurons; and, second, by glutamate afferents to the PFC that act at the level of the DA nerve terminals. The behaviour context (arousal or stress versus hypotension) determines which type of interaction predominates.

Retracted: Cerebral effects and blood sparing efficiency of sodium nitroprusside-induced hypotension alone and in combination with acute normovolaemic haemodilution

The combined reduction of oxygen-carrying capacity and perfusion pressure during the combination of acute normovolaemic haemodilution (ANH) and controlled hypotension (CH) raises concerns of hypoperfusion and ischaemic injury to the brain. Forty-two patients undergoing radical prostatectomy were prospectively allocated to receive CH induced by sodium nitroprusside (mean arterial pressure (MAP) 50 mm Hg), a combination of CH+ANH (post-ANH haematocrit 29%; intraoperative MAP 50 mm Hg), or standard anaesthesia (control). Serum levels of the brain-originated proteins neuron-specific enolase (NSE) and protein S-100, blood loss, transfusion requirements, adverse effects, and postoperative recovery profile were compared among the three groups. Intraoperative blood loss in the CH group (mean (SD)) (788 (193) ml) and CH+ANH group (861 (184) ml) was significantly less than in the control group (1335 (460) ml). Significantly fewer total units of allogeneic packed red blood cells (PRBC) were transfused in the patients receiving hypotensive anaesthesia (CH, 3 units; CH+ANH, 2 units; control, 17 units). There was no difference in immediate postoperative recovery profile among the three groups as determined by the emergence from anaesthesia and time to discharge from the postanaesthesia care unit. Serum S-100 protein concentrations increased significantly in all groups from baseline to peak concentrations 2 h postoperatively (CH 0.25 (0.11) microg litre(-1); CH+ANH 0.31 (0.12) microg litre(-1); control 0.31 (0.10) microg litre(-1)). A return to baseline values was seen within 24 h postoperatively in all patients. No changes in NSE concentrations were seen. Our observations suggest that CH and CH+ANH were effective in reducing blood loss and transfusion requirements in patients undergoing radical prostatectomy. Increased serum S-100 protein concentrations imply a disturbance in astroglial cell membrane integrity and an increased endothelial permeability of the blood-brain barrier. There were no associations between serum S-100 protein or NSE and adverse cognitive effects. Further work needs to be done to determine the prognostic importance of S-100 protein and NSE as surrogate variables of postoperative cerebral complications.