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Biomedical subjects

G R Martin

Publications and source records attributed to G R Martin.

At least 91 records · Page 5Linked to original sources

Traumatic thoracic aortic rupture in the pediatric patient.

BACKGROUND: Traumatic thoracic aortic rupture is a rare injury in the pediatric patient. Experiences with thoracic aortic rupture in patients less than 17 years of age are needed to help identify factors that can influence injury occurrence, diagnosis, management, and outcome. METHODS: Between July 1989 and December 1995, 6 children were treated operatively for thoracic aortic rupture from blunt trauma at a level I pediatric trauma center. The average age was 13.2 years (range, 8 to 16 years). There were 4 females and 2 males. There were 5 motor vehicle accidents and 1 bicycle accident. Aortic injury was suspected based on the mechanism of injury and abnormal chest roentgenogram results, and was confirmed by aortography (3 cases) or chest computed tomography (2) and transesophageal echocardiography (3). Life-threatening central nervous system or gastrointestinal injuries were evaluated or treated first. Operative repair of the thoracic aorta was performed by cardiopulmonary bypass (2 patients) and clamp and sew technique (4). RESULTS: Aortic ruptures were complete transections at the ligamentum arteriosum in 5 of 6 (83%); the other case was a cervical arch pseudoaneurysm. Associated injuries included pulmonary contusion (100%), pelvic/long bone fractures (50%), visceral laceration/perforation (50%), central nervous system (33%), paraplegia (17%), and myocardial contusion (17%). There were no rib fractures. Four of 5 patients (80%) were not wearing seat belts, and 2 of these were ejected. The average time from injury to the operating room was 17.6 hours (range, 5 to 48 hours); the time from diagnosis to the operating room exceeded 5 hours with aortography and was less than 3 hours with chest computed tomography and transesophageal echocardiography. Each diagnostic modality accurately identified an aortic injury. The average time for cardiopulmonary bypass and for clamp and sew was 52 minutes (range, 49 to 55 minutes) and 34 minutes (range, 16 to 45 minutes), respectively. One patient with preoperative paraplegia regained partial function; there were no other patients with paraplegia. There were no deaths. All patients are alive 2 months to 7 years after repair. CONCLUSIONS: The multiply injured child with severe blunt trauma and an abnormal chest roentgenogram requires a search for aortic injury. We believe the most effective algorithm to follow for the diagnosis of traumatic thoracic aortic rupture in the child involves selective performance of chest computed tomography and transesophageal echocardiography. Our experience suggests that the mechanism of injury, the duration to diagnosis of an aortic injury, and failure to use seat belts may contribute to morbidity. A high index of suspicion and a systematic approach to the diagnosis and to the management strategy for injuries to the thoracic aorta can contribute to a good outcome in those few children who survive the injury.

Adolescent↗

Safety and efficacy of chloral hydrate sedation in children undergoing echocardiography.

The purpose of this prospective study was to determine the safety and efficacy of chloral hydrate sedation in children with known or suspected congenital heart disease. The study population included 405 children with a median age of 13 months (3 weeks to 14 years). Cyanotic heart disease was present in 64 of the children. The median dosage of chloral hydrate given was 77 mg/kg, with a range of 25 to 125 mg/kg. Sedation was achieved in 397 (98%) of the children. The complete study time averaged 2.2 hours (range, 1.6 to 5.2 hours). The time to achieve sedation was 30 minutes or less in 82%, more than 30 but less than 60 minutes in 12%, and more than 60 minutes in 4%; 2% failed to achieve sedation. Children aged 3 years or younger were more likely to be successfully sedated with chloral hydrate (p = 0.003). The type of heart disease did not affect the success of sedation. No child had a clinically significant change in heart rate or blood pressure during sedation; however, oxygen saturation decreased in 24 (6%) of 397 children successfully sedated. Decreases in oxygen saturation occurred more commonly in children with trisomy 21 (7/13) than in children without genetic syndromes (17/384). Vomiting occurred in 23 (6%) of the 405 study subjects, usually immediately after drug administration. Chloral hydrate is a safe and effective agent for sedation of children with known or suspected congenital heart disease who are undergoing echocardiography in the outpatient cardiology clinic.

Adolescent↗

Acoustic quantification: a new tool for diagnostic echocardiography.

Acoustic quantification, a new ultrasound technique, provides a more direct assessment of the health of the myocardium than conventional echocardiography. Through software enhancements, acoustic quantification can characterize the myocardium as viable or nonviable, automatically track the endocardium throughout the cardiac cycle, and show myocardial perfusion defects when used with contrast enhancement. Thus, this technique shows promise in linking perfusion, viability, and global function in adults and perhaps in children.

Animals↗

The effect of forskolin on 5-HT1-like and angiotensin II-induced vasoconstriction and cyclic AMP content of the rabbit isolated femoral artery.

1. A characteristic feature of vasoconstrictor 5-HT1-like receptors in vitro is that responses mediated by these receptors are enhanced by other vasoconstrictor agents. In the present study, we have examined the influence of cellular cyclic AMP on vasoconstrictor responses to activation of 5-HT1-like receptors in isolated ring segments of the rabbit femoral artery (RbFA), and determined whether modulation of this second messenger underlies the ability of angiotensin II, an endogenous vasoconstrictor, to enhance 5-HT1-like responses. 2. In the presence of 0.1 microM ketanserin (to antagonize 5-HT2-receptors) and 0.3 microM prazosin (to antagonize alpha 1-adrenoceptors), 5-HT produced a concentration-related contraction, which was significantly augmented by pre-contraction of the vessel with 0.1-0.45 nM ([A30]) angiotensin II. Responses to 5-HT in the presence of angiotensin II were inhibited by the 5-HT1-like/5-HT2 antagonist, metergoline (1 microM). 3. The directly-acting adenylyl cyclase activator, forskolin (1 microM), abolished responses to angiotensin II and caused a rightward shift and concomitant depression of the 5-HT concentration-effect (E/[A]) curve. Higher concentrations of forskolin (> 10 microM) abolished responses to 5-HT and 1 microM sodium nitroprusside abolished responses to 5-HT and angiotensin II (n = 7). 4. In the presence of angiotensin II (0.1-0.45 nM), however, 1 microM forskolin failed to inhibit 5-HT-induced contractions; the E/A curve for 5-HT (in the presence of forskolin and angiotensin II) was not significantly different from that produced in the presence of angiotensin II alone. Similarly, the presence of angiotensin II (0.1-0.45 nM) was also able to overcome partially the inhibitory effect of 1 microM sodium nitroprusside against 5-HT-induced contractions (n = 7). In marked contrast, 5-HT failed to elicit a contraction in the presence of angiotensin II and 10 microM forskolin (n = 5). 5. 5-HT (1 microM) significantly reduced basal cyclic AMP accumulation by 35%, whereas angiotensin II (0.45 nM) was without effect. The combination of angiotensin II and 5-HT failed to alter significantly the reduction in cyclic AMP produced by 5-HT alone. Forskolin (1 microM) increased cyclic AMP levels 7 fold above basal, but neither 1 microM 5-HT nor a combination of 1 microM 5-HT and 0.45 nM angiotensin II produced a significant decrease in cyclic AMP content. 6. Whilst moderate concentrations of forskolin can inhibit the responses to either agent, simultaneous activation of angiotensin II and 5-HT1-like receptors can overcome the inhibitory effect of elevated levels of cyclic AMP. Since the potentiating effect of angiotensin II, in either the presence or absence of forskolin, occurs without significant alteration of cellular cyclic AMP, it seems likely that a cyclic AMP-independent pathway is implicated in the synergistic interaction between angiotensin II and vasoconstrictor 5-HT1-like receptors.

Angiotensin II↗

Characterization of a 5-HT1B receptor on CHO cells: functional responses in the absence of radioligand binding.

1. Chinese hamster ovary (CHO) cells have been reported to be devoid of 5-HT receptors and have frequently been used as hosts for the expression of cloned 5-HT receptors. Unexpectedly, 5-HT was found to induce profound inhibition of forskolin-stimulated cyclic AMP production in these cells and the aim of this study was to classify the 5-HT receptor involved. 2. In CHO(dhfr-) cells 5-HT was a potent agonist and caused 80-100% inhibition of forskolin stimulated cyclic AMP production. A study using several 5-HT1 receptor agonists revealed the following potencies (p[A50]): RU24969 (9.09 +/- 0.17) > 5-carboxamidotryptamine (8.86 +/- 0.20) > 5-HT (8.07 +/- 0.05) > CP-93,129 (7.74 +/- 0.10) > sumatriptan (5.93 +/- 0.04). All five agonists achieved a similar maximum effect. Irreversible receptor alkylation studies yielded a pKA estimate of 7.04 +/- 0.34 for 5-HT. 3. The 5-HT1A/1B antagonist, (+/-)-cyanopindolol (4-100 nM), caused parallel rightward shifts of the 5-HT concentration-effect curve with no change in asymptote. Schild analysis yielded a pKB estimate of 8.69 +/- 0.09 (Schild slope 1.13 +/- 0.10). (+/-)-Cyanopindolol actually behaved as a partial agonist with an intrinsic activity of 0.2-0.5 and a p[A50] of 8.55. 4. 5-HT (0.01-10 microM) also elicited a concentration-dependent increase in intracellular [Ca2+] in CHO(dhfr-) cells thus demonstrating that dual coupling is not a phenomenon restricted to systems in which there is overexpression of transfected receptors. 5. This agonist and antagonist profile is consistent with the presence of a 5-HT1B receptor. 8-OH-DPAT (1 microM) and renzapride (3 microM) were without effect on forskolin-stimulated cyclic AMP production and ketanserin (0.3 microM) did not antagonize the inhibition produced by 5-HT, thus excluding the involvement of 5-HT1A, 5-HT4, and 5-HT2 receptors. 6. The possibility that expression of a 5-HT1B receptor was associated with the dhfr- mutation was excluded since RU24969, 5-HT and CP-93,129 were also potent agonists in unmutated, CHO-K1 cells: p[A50] 9.03 +/- 0.03, 8.34 +/- 0.05, 7.69 +/- 0.07 respectively, and (+/-)-cyanopindolol (0.1 microM) shifted the 5-HT curve to the right and yielded a pA2 estimate of 8.70 +/- 0.06. 7. Little or no specific binding of [3H]-5-HT (0.1-200 nM) or of the high affinity ligand [125I]-iodocyanopindolol (0.01-3 nM) to CHO(dhfr-) cell membranes could be detected. 5-HT also failed to elicit any increase in the binding of [35S]-GTP gamma S to CHO membranes. 8. In conclusion, cultured CHO cells express 5-HT1B receptors which are negatively coupled to adenylyl cyclase and positively coupled to increases in intracellular calcium. The absence of radioligand binding was unexpected in view of the high potency of 5-HT and the partial agonist activity of the normally 'silent' competitive antagonist, (+/-)-cyanopindolol. This implies very efficient receptor-effector coupling of a low density of 5-HT1B receptors. Clearly, the absence of detectable radioligand binding cannot be assumed to mean the absence of receptors capable of eliciting a significant functional response.

Animals↗

Inhibition of the trigemino-vascular system with 5-HT1D agonist drugs: selectively targeting additional sites of action.

Inappropriate activation of the trigemino-vascular system is thought to be important in the pathogenesis of a migraine attack. The 5-HT1D agonist sumatriptan, which is highly effective in the acute treatment of migraine, inhibits trigemino-vascular activation in animals, although its actions are normally limited to peripheral components of the trigemino-vascular system. 311C90, a novel 5-HT1D agonist drug, which is also highly effective in the acute treatment of migraine, acts not only at these sites, but, additionally within the brainstem, inhibiting trigemino-vascular activation centrally as well as peripherally. This article describes the pre-clinical development of 311C90 and considers, specifically, the approaches taken in the design of a molecule with attributes which facilitate access to brainstem components of the trigeminal pathway and combine this with good oral bioavailability.

Administration, Oral↗

The chick limbless mutation causes abnormalities in limb bud dorsal-ventral patterning: implications for the mechanism of apical ridge formation.

In chick embryos homozygous for the limbless mutation, limb bud outgrowth is initiated, but a morphologically distinct apical ridge does not develop and limbs do not form. Here we report the results of an analysis of gene expression in limbless mutant limb buds. Fgf4, Fgf8, Bmp2 and Msx2, genes that are expressed in the apical ridge of normal limb buds, are not expressed in the mutant limb bud ectoderm, providing molecular support for the hypothesis that limb development fails in the limbless embryo because of the inability of the ectoderm to form a functional ridge. Moreover, Fgf8 expression is not detected in the ectoderm of the prospective limb territory or the early limb bud of limbless embryos. Since the early stages of limb bud outgrowth occur normally in the mutant embryos, this indicates that FGF8 is not required to promote initial limb bud outgrowth. In the absence of FGF8, Shh is also not expressed in the mutant limb buds, although its expression can be induced by application of FGF8-soaked beads. These observations support the hypothesis that Fgf8 is required for the induction of Shh expression during normal limb development. Bmp2 expression was also not detected in mutant limb mesoderm, consistent with the hypothesis that SHH induces its expression. In contrast, SHH is not required for the induction of Hoxd11 or Hoxd13 expression, since expression of both these genes was detected in the mutant limb buds. Thus, some aspects of mesoderm A-P patterning can occur in the absence of SHH and factors normally expressed in the apical ridge. Intriguingly, mutant limbs rescued by local application of FGF displayed a dorsalized feather pattern. Furthermore, the expression of Wnt7a, Lmx1 and En1, genes involved in limb D-V patterning, was found to be abnormal in mutant limb buds. These data suggest that D-V patterning and apical ridge formation are linked, since they show that the limbless mutation affects both processes. We present a model that explains the potential link between D-V positional information and apical ridge formation, and discuss the possible function of the limbless gene in terms of this model.

Animals↗

Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo.

Conversion of a solid primordium to a hollow tube of cells is a morphogenetic process used frequently during vertebrate embryogenesis. In the early mouse embryo, this process of cavitation transforms the solid embryonic ectoderm into a columnar epithelium surrounding a cavity. Using both established cell lines and normal embryos, we provide evidence that cavitation in the early mouse embryo is the result of the interplay of two signals, one from an outer layer of endoderm cells that acts over short distances to create a cavity by inducing apoptosis of the inner ectodermal cells, and the other a rescue signal mediated by contact with the basement membrane that is required for the survival of the columnar cells that line the cavity. This simple model provides a paradigm for investigating tube morphogenesis in diverse developmental settings.

Amnion↗

Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties.

The design and synthesis of a series of novel 5-substituted tryptamines with pharmacological activity at 5-HT1D and other monoamine receptors is described. Structural modifications of N- and C-linked (principally hydantoin) analogues at the 5-position were synthesized and their pharmacological activities were utilized to deduce significant steric and electrostatic requirements of the 5-HT1D and 5-HT2A receptor subtypes. Conformations of the active molecules were computed which, when overlaid, suggested a pharmacophore hypothesis which was consistent with the affinity and selectivity measured at 5-HT1D and 5-HT2A receptors. This pharmacophore is composed of a protonated amine site, an aromatic site, a hydrophobic pocket, and two hydrogen-bonding sites. A "selectivity site" was also identified which, if occupied, induced sensitivity for 5-HT1D over 5-HT2A in this series of molecules. The development and use of the pharmacophore models in compound design is described. In addition, the physicochemical constraints of molecular size and hydrophobicity required for efficient oral absorption are discussed. Utilizing the pharmacophore model in conjunction with the physicochemical constraints of molecular size and log DpH7.4 led to the discovery of 311C90 (6), a new selective 5-HT1D agonist with good oral absorption and potential use in the treatment of migraine.

Animals↗

Autoradiographic mapping of [3H]sumatriptan binding in cat brain stem and spinal cord.

In vitro autoradiography was performed on sections of cat brain stem and spinal cord using [3H]sumatriptan. Localization studies using 20-25 nM [3H]sumatriptan showed specific binding to cells in the trigeminal nucleus caudalis and nucleus tractus solitarius of the brain stem and the dorsal horn of the spinal cord. This binding was unaffected by 8-hydroxy-dipropylaminotetralin (20 nM), but was abolished by 5-carboxamidotryptamine (200 nM). Ketanserin displaced total specific binding in the brain stem with a pIC50 of 6.2 but no apparent regional specificity. These results indicate that [3H]sumatriptan labels predominantly 5-HT1D alpha and/or 5-HT1D beta (but not 5-HT1A or 5-HT1F) receptor subtypes in cat brain stem and spinal cord.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Meso1, a basic-helix-loop-helix protein involved in mammalian presomitic mesoderm development.

To identify genes involved in the regulation of early mammalian development, we have developed a dominant-negative mutant basic-helix-loop-helix (bHLH) protein probe for interaction cloning and have isolated a member of the bHLH family of transcription factors, Meso1. Meso1-E2A heterodimers are capable of binding to oligonucleotide probes that contain a bHLH DNA recognition motif. In mouse embryos, Meso1 is expressed prior to MyoD1 family members. Meso1 expression is first detected at the neural plate stage of development in the paraxial mesoderm of the head and in presomitic mesodermal cells prior to their condensation into somites. Our findings suggest that Meso1 may be a key regulatory gene involved in the early events of vertebrate mesoderm differentiation.

Amino Acid Sequence↗

Indications for echocardiography in the diagnosis of infective endocarditis in children.

The role of transthoracic echocardiography as a diagnostic tool in children suspected of having infective endocarditis (IE) has not been defined. We hypothesized that echocardiography is only useful in children in whom there is high clinical suspicion of IE based on physical examination findings or persistently positive blood cultures. Echocardiographic reports and medical records of all inpatients (n = 133) from 1990 to 1992 who underwent echocardiography for suspected IE were reviewed. Fifty-nine of the 133 patients (44%) identified had either persistently positive blood cultures (n = 48), physical examination findings of IE (n = 20), or both (n = 9). The echocardiogram was positive in 7 of these patients (12%) and negative in all 74 patients without positive physical findings or positive blood cultures (p = 0.003). A new or changing precordial murmur, embolic phenomena, congestive heart failure, mechanical ventilation, and positive blood cultures were predictive of positive echocardiograms for IE by univariate analysis. The presence of fever, immune deficiency, and central lines, alone or in combination, was not predictive of a positive echocardiogram. In the absence of physical findings or persistently positive blood cultures, echocardiography is a low-yield study and is unlikely to aid in the diagnosis of IE in children.

Bacteremia↗

Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports.

OBJECTIVES: We sought to determine the prevalence and natural history of cardiac tumors in patients referred for fetal echocardiography. BACKGROUND: Cardiac tumors are rare; the prevalence, reported from autopsy studies of patients of all ages, varies from 0.0017% to 0.28%. Despite many case reports, the prevalence and natural history of fetal cardiac tumors are unclear. METHODS: Fourteen thousand fetal echocardiograms recorded over an 8-year period in seven centers were available for retrospective review. Medical records and echocardiograms were studied to determine the reason for referral, family history of tuberous sclerosis, prenatal and postnatal course and tumor description and type. RESULTS: Cardiac tumors were present in 19 pregnancies (0.14%). Gestational age at diagnosis ranged from 21 to 38 weeks. The most common indication for referral was a mass on an obstetric ultrasound study. The tumors were singular in 10 patients and multiple in 9. Tumor size ranged from 0.4 x 0.4 to 3.5 x 4 cm, and the majority of tumors were not hemodynamically significant. There were 17 patients with rhabdomyomas, 1 with a fibroma and 1 with an atrial hemangioma. Tuberous sclerosis complex was diagnosed in 10 patients. Partial or complete tumor regression was seen in eight patients; tumors were unchanged in five; and three required operation. CONCLUSIONS: Fetal cardiac tumors, a rare condition, are often benign. The majority of tumors are rhabdomyomas, but not all fetuses with rhabdomyoma have tuberous sclerosis.

Female↗

Visceral endoderm-1 (VE-1): an antigen marker that distinguishes anterior from posterior embryonic visceral endoderm in the early post-implantation mouse embryo.

We describe here an antigen marker, designated VE-1, that is detected early in gastrulation (approximately E6.5 through approximately E7.25) in the anterior visceral endoderm overlying the embryonic ectoderm opposite the primitive streak. The antibody-positive domain extends from the embryonic-extraembryonic junction to the distal tip of the embryo, and laterally around approximately one-third of the circumference of the egg cylinder. Analysis of embryos at earlier stages indicates that VE-1 is first expressed shortly after implantation, at approximately E5.0, in the visceral endoderm on one side of the embryo and thus is the earliest molecular marker of A-P asymmetry in the post-implantation mouse embryo described to date. Although VE-1 was detected with a polyclonal antiserum raised against a 24 amino acid polypeptide sequence of FGF2, we provide evidence that the VE-1 antigen is not FGF2. The data reported here are the first to provide molecular evidence that A-P polarity in the mouse embryo is established by E5.0 and that the visceral endoderm has A-P polarity.

Animals↗

Evidence that 5-HT1D receptors mediate inhibition of sympathetic ganglionic transmission in anaesthetized cats.

In anaesthetized cats, 5-carboxamidotryptamine (5-CT) or 5-hydroxytryptamine (5-HT) (0.3-300 micrograms kg-1,i.v.) inhibited the postganglionic compound action potential evoked by preganglionic electrical stimulation (0.5 Hz) with a similar potency in the stellate and splanchnic ganglia. In the 5-HT experiments transmission thorough the inferior mesenteric ganglia was also recorded. The maximal inhibitory effect of 5-HT was greater on the stellate and splanchnic ganglia (60 +/- 4 and 52 +/- 5%) than on the inferior mesenteric (15 +/- 2%). The effects of 5-HT were unaffected by pretreatment with antagonists (1 mg kg-1;i.v.) for 5-HT2 (BW501C67), 5-HT1A (WAY-100635) and 5-HT3 receptors (ondansetron). However, responses to both 5-HT and 5-CT were attenuated significantly by GR127935 (1 mg kg-1) except the responses to 5-HT at the inferior mesenteric ganglia. These results are consistent with the involvement of 5-HT1D receptors mediating inhibition of sympathetic ganglionic transmission in vivo.

Action Potentials↗

Evidence that activation of 5-HT2 receptors in the forebrain of anaesthetized cats causes sympathoexcitation.

1. The aim of the present experiments was to determine whether the effects of lateral ventricular application of 5-HT on cardiovascular and respiratory variables in anaesthetized cats are mediated by forebrain 5-HT2 receptors. This was carried out by determining whether the effects of 5-HT are blocked by the 5-HT2 antagonist, cinanserin and if they are mimicked by the selective 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). 2. Cats were anaesthetized with a mixture of alpha-chloralose and pentobarbitone sodium, neuromuscularly blocked and artifically ventilated. The following cardiovascular and respiratory variables were recorded: renal, splanchnic and cardiac sympathetic nerve activities, phrenic nerve activity, heart rate, arterial blood pressure, femoral arterial conductance and tracheal pressure. All drugs were administered via the lateral ventricle and the action of these agonists was restricted to forebrain sites by a cannula placed in the Aqueduct of Sylvius. 3. Cumulative doses of 5-HT (10-160 nmol kg-1) and DOI (80-320 nmol kg-1) injected into the lateral ventricle caused significant increases in blood pressure, heart rate, cardiac and splanchnic sympathetic nerve activity and a decrease in femoral arterial conductance. DOI and 5-HT caused a greater increase in cardiac compared with splanchnic nerve activity and failed to change renal nerve activity. 5-HT but not DOI significantly increased the magnitude and the number of phrenic bursts as well as significantly increasing tracheal pressure. The effects of 5-HT also differed from DOI in that 5-HT evoked maximal pressor and near maximal sympathoexcitatory effects after the first dose, whereas the pressor and sympathoexcitatory effects of DOI were graded over the complete dose-range.4 The 5-HT2 antagonist, cinanserin (265 nmol kg-1, i.c.v.) caused significant falls in blood pressure,heart rate and cardiac nerve activity and an increase in femoral arterial conductance. Splanchnic andrenal sympathetic nerve activity, phrenic nerve activity and tracheal pressure were unaffected by cinanserin. After pretreatment with cinanserin all cardiovascular and respiratory effects of 5-HT were significantly attenuated.5 It is concluded that in the cat, as DOI and 5-HT have similar effects on the cardiovascular variables recorded and as the effects of 5-HT are blocked by cinanserin, 5-HT can act on 5-HT2 receptors located in the forebrain to cause differential sympathoexcitation and a rise in arterial blood pressure. Further,the sympathoexcitatory effects mediated by 5-HT2 receptors located in the forebrain differ from those located in the hindbrain in that they mediate increases in cardiac nerve activity and heart rate and also have no effect on renal nerve activity.

Anesthesia↗