Increase In Systemic Arterial Pressure Research Articles

Modeling essential hypertension with a closed-loop mathematical model for the entire human circulation.

Arterial hypertension, defined as an increase in systemic arterial pressure, is a major risk factor for the development of diseases affecting the cardiovascular system. Every year, 9.4 million deaths worldwide are caused by complications arising from hypertension. Despite well-established approaches to diagnosis and treatment, fewer than half of all hypertensive patients have adequately controlled blood pressure. In this scenario, computational models of hypertension can be a practical approach for better quantifying the role played by different components of the cardiovascular system in the determination of this condition. In the present work we adopt a global closed-loop multi-scale mathematical model for the entire human circulation to reproduce a hypertensive scenario. In particular, we modify the model to reproduce alterations in the cardiovascular system that are cause and/or consequence of the hypertensive state. The adaptation does not only affect large systemic arteries and the heart but also the microcirculation, the pulmonary circulation and the venous system. Model outputs for the hypertensive scenario are validated through assessment of computational results against current knowledge on the impact of hypertension on the cardiovascular system.

Hemodynamic response to transseptal transcatheter mitral valve replacement in patients with severe mitral stenosis due to severe mitral annular calcification.

We aimed to investigate the invasive hemodynamic changes with transcatheter mitral valve replacement (TMVR) in patients with severe mitral stenosis due to severe mitral annular calcification. The hemodynamic response to TMVR in patients with mitral stenosis related to degenerative mitral annular calcification has not been fully elucidated. We conducted retrospective review of patients who underwent successful transseptal TMVR with balloon-expandable valves for symptomatic severe mitral stenosis due to mitral annular calcification at our institution between January 2014 and February 2020. Invasive hemodynamic measurements were obtained both before valve implantation (predeployment) and after (postdeployment). Eighteen patients (age 72 ± 10 years, 44% female) were included for the analysis. There was a significant reduction in mean left atrial pressure (23.7 ± 5.6 mmHg versus 20.6 ± 4.8 mmHg; p=.01), left atrial v-wave (mean 39.3 ± 10.2 mmHg versus 32.9 ± 9.9 mmHg; p=.01), and an increase in systemic mean blood pressure (72.6 mmHg ±11.2 versus 79.5 ± 9.9 mmHg; p=.02) postdeployment compared to predeployment. Patients who had symptom improvement at 30-day follow-up tended to have greater reduction in mean left atrial pressure (4.4 ± 4.4 mmHg versus 0.5 ± 5.2 mmHg; p=.16) and v-wave (8.6 ± 9.0 mmHg versus 0.7 ± 8.4 mmHg; p=.10) compared to those who did not experience improvement of symptoms. Transseptal TMVR for severe mitral stenosis due to mitral annular calcification is associated with reductions in mean left atrial pressure and left atrial v-wave, and an increase in systemic arterial pressure.

Scorpion envenomation: state of the art.

Scorpion envenomation is common in the tropical and subtropical regions. It poses a major public health problem with some patients having serious clinical manifestations and severe complications including death. Old World and New World scorpions are usually contrasted because of differences in venom composition, clinical presentation and severity, and, accordingly, different therapeutic approaches. The majority of scorpion stings are either dry or result in low amounts of injected venom, thus explaining why up to 95% of scorpion stings ensue only in local signs. For a clinical envenomation to occur, it has been suggested that the interaction between the quantity of venom introduced in the body of the prey and the distribution volume should ensue in a critical threshold of scorpion toxin plasma concentration. In this case, there is a massive release of neurohormonal mediators (mainly catecholamine), with systemic vasoconstrictor effects eliciting a sharp increase in systemic arterial pressure and LV-filling pressure and decreased cardiac output. This early phase of cardiac dysfunction, also called "vascular phase", is followed by a severe cardiomyopathy, a form of Takotsubo cardiomyopathy, involving both ventricles and reversible in days to weeks. The more comprehensive understanding of the disease pathophysiology has allowed for a well-codified symptomatic treatment, thus contributing to a substantial reduction in the death toll of scorpion envenomation over the past few decades. The standard intensive-care treatment (when available) overcomes envenomation's consequences such as acute pulmonary edema and cardiogenic shock. Even though it continues to inspire many evaluative studies, immunotherapy seems less attractive because of the major role held by mediators in the pathogenesis of envenomation, and unfavorable pharmacokinetic properties to existing sera compared to venom. Meta-analyses of controlled trials of immunotherapy in severe scorpion envenomation reached similar conclusions: there is an acceptable level of evidence in favor of the use of scorpion antivenom (Fab'2) against Centruroides sp. in USA/Mexico, while there is still a need for a higher level of evidence for immunotherapy in the Old World envenomation.

Caffeine and Pressure Flow Autoregulation

The benefits or detriments of caffeine on the human cardiovascular system have not been thoroughly studied and are still poorly understood. In a world where caffeinated beverages are evidently the adult drug of choice (e.g. coffee, energy drinks, soda, tea), investigating its effects on our bodies is of great importance. In this study, we examined the effects of caffeine, taken as a tablet, on pressure-flow autoregulation. Young adults between 18 and 21 years of age were the experimental subjects. They were instrumented to monitor systemic arterial blood pressure, peripheral blood flow, calculated peripheral vascular resistance, and the electrocardiogram during an autoregulatory maneuver in the absence and presence of caffeine. Caffeine-mediated vasoconstriction was observed as early as 15 minutes after its consumption. Sixty minutes post-caffeine, vasoconstriction was so prominent that autoregulation was abolished. This was reflected, in part, as a significant reduction in blood flow that accompanied a 3-fold increase in calculated peripheral resistance and a significant increase in systemic arterial pressure. Heart rate was unaffected by caffeine under our experimental conditions. We conclude that caffeine has the ability to inhibit significant cardiovascular properties including pressure-flow autoregulation. Even though more work is needed, the significant caffeine-mediated changes in flow, pressure and resistance during autoregulation could have serious consequences for the cardiovascular system specifically, and for one’s overall health in general.

Major Clinical Considerations for Secondary Hypertension and Treatment Challenges: Systematic Review

Introduction: In this context, secondary arterial hypertension (SH) is defined as an increase in systemic arterial pressure (SAP) due to an identifiable cause. Only 5 to 10% of patients suffering from hypertension have a secondary form, while the vast majorities have essential hypertension. Objective: This study aimed to describe, through a systematic review, the main considerations on secondary hypertension, presenting its clinical data and main causes, as well as presenting the types of treatments according to the literary results. Methods: Following the criteria of literary search with the use of the Mesh Terms that were cited in the item below on Search strategies, the total of 76 papers that were submitted to the eligibility analysis were collated and, after that, 23 studies were selected, following the rules of systematic review-PRISMA. In general, as an example, the search strategy in MEDLINE / Pubmed, Web of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile (Gale). Major findings: According to epidemiological data, secondary hypertension (SH) presents an incidence of 5.0 to 10.0% of the world population. In this context, since SH cases are difficult to screen and expensive, only patients with clinical suspicion should be examined. In recent years, some new aspects have gained importance in relation to this screening. Thus, increasing evidence suggests that 24-hour ambulatory blood pressure monitoring plays a central role. The prevalence of SH is related to age and clinical characteristics. In addition, some residual hypertension remains after the pathogenic cause of secondary hypertension has been identified and removed because of the existence of essential hypertension. Conclusion:It was concluded with the present study that secondary hypertension effects on average 7.5% of hypertensive patients. Screening in the diagnosis of secondary hypertension is expensive and laborious and should be performed only in patients with high clinical suspicion.

Systemic blood pressure alters cortical blood flow and neurovascular coupling during nociceptive processing in the primary somatosensory cortex of the rat

Inference on nociceptive and pain-related processes from functional magnetic resonance imaging is made with the assumption that the coupling of neuronal activity and cerebral hemodynamic changes is stable. However, since nociceptive stimulation is associated with increases in systemic arterial pressure, it is essential to determine whether this coupling remains the same during different levels of nociception and pain. The main objective of the present study was to compare the amplitude of local field potentials (LFP) and cerebral blood flow (CBF) changes in the primary somatosensory cortex during nociceptive electrical stimulation of the contralateral or ipsilateral forepaw in isoflurane-anesthetized rats, while manipulating mean arterial pressure (MAP). MAP changes induced by nociceptive stimulation were manipulated by transecting the spinal cord at the upper thoracic segments (T1–T2), which interrupts sympathetic pathways and prevents nociception-related MAP increases, while sensory pathways between the forepaws and the brain remain intact. Intensity-dependent increases in MAP and CBF were observed and these effects were abolished or significantly decreased after spinal transection (p<0.001 and p<0.05, respectively). In contrast, the intensity-dependent changes in LFP amplitude were decreased for the contralateral stimulation but increased for the ipsilateral stimulation after spinal transection (p<0.05). Thus, neurovascular coupling was altered differently by stimulus-induced MAP changes, depending on stimulus intensity and location. This demonstrates that CBF changes evoked by nociceptive processing do not always match neuronal activity, which may lead to inaccurate estimation of neuronal activity from hemodynamic changes. These results have important implications for neuroimaging of nociceptive and pain-related processes.

Role of the peripheral chemoreceptor reflex on cardiovascular and sympathetic responses to obstructive sleep apnea in rats

The potential contribution of peripheral chemoreceptors to the responses of systemic arterial pressure, heart rate, and sympathetic nerve activity (SNA) to obstructive sleep apnea was studied. Male Wistar rats had a tracheal balloon inserted to allow induction of apnea, with electrodes for measurement of renal SNA (RSNA) and lumbar SNA (LSNA), and a catheter for measurement of systemic arterial pressure. Electroencephalogram, electromyogram, and electrocardiogram records were also obtained. The tracheal balloon was inflated for 40 seconds during non‐rapid eye movement sleep. Systemic arterial pressure, RSNA, and LSNA increased after onset of tracheal balloon inflation while heart rate decreased. Bilateral carotid body section significantly attenuated the magnitude of the decrease in heart rate observed in intact rats, but had only minor effects on the responses of systemic arterial pressure, RSNA, and LSNA to obstructive sleep apnea. These data suggest that peripheral chemoreceptors may play a critical role in bradycardia in response to obstructive sleep apnea, and a minor role in the increases in systemic arterial pressure, RSNA, and LSNA in conscious rats. JSPS Grant.

Intraosseous Lipid Emulsion

To determine whether intraosseous infusion of a lipid emulsion reverses cardiac pharmacotoxicity in anaesthetized rats. Prospective, randomized animal study. Academic research laboratory. Adult, male Sprague-Dawley rats. We assigned 25 male Sprague-Dawley rats into four groups: intraosseous lipid emulsion, intraosseous saline, IV lipid emulsion, and sham/null. Rats were anesthetized with 1.5% isoflurane and 95% oxygen. The left internal carotid artery and both internal jugular veins were cannulated and a flow probe was placed on the right carotid artery. Subsequently, in animals assigned to the intraosseous groups, the greater trochanter of the left proximal femur was exposed and the intraosseous space was cannulated. After surgical recovery, bupivacaine (10 mg/kg) was injected IV over 20 seconds followed 10 seconds later by treatment with one of the following: intraosseous lipid-emulsion (10 mL/kg over 180 s), intraosseous saline (10 mL/kg over 180 s), IV lipid-emulsion (10 mL/kg over 90 s), or no treatment (sham/null). Electrocardiogram, aortic blood pressure, and carotid blood flow were recorded continuously. Rats treated with intraosseous lipid emulsion experienced a significantly faster recovery of hemodynamic variables (return of 50% flow; median [CI]: 160 s [105-263 s]) than did rats treated with saline (471 s [283-611 s]; p < 0.05) or animals with no treatment (415 s [340-539 s], p < 0.05), but at a similar rate to animals treated with IV lipid emulsion (176 s [152-217 s], p = not significant). All groups experienced persistent negative chronotropic effects. A compensatory increase in systemic arterial pressure was observed in rats treated with lipid emulsion. These proof-of-principle data indicate that intraosseous infusion of lipid emulsion rapidly reverses bupivacaine-induced cardiac toxicity in rats. Further studies are warranted to optimize this novel route of lipid emulsion injection in emergency situations when intravascular access is not secured.

Assessment of Modified Ultrafiltration Hemodynamic Impact by Pressure Recording Analytical Method During Pediatric Cardiac Surgery

Modified ultrafiltration is commonly used in pediatric cardiac surgery. Although its clinical benefits are currently debated, modified ultrafiltration has proved to improve mean arterial pressure in the first postoperative hours. Aim of our study was to measure cardiac index, stroke volume index, and mean arterial pressure modification before and after modified ultrafiltration by means of Pressure Recording Analytical Method. Single-center prospective observational cohort study. Pediatric cardiac surgery operating room. Children below 20 kg that are included in the "pediatric" mode of Pressure Recording Analytical Method. Forty patients were enrolled in this study. Median age, weight, and body surface area at surgery were 3 months (interquartile range, 10 days to 3.5 yr), 5.6 (3.1-15) kg, and 0.31 (0.21-0.56), respectively. During the modified ultrafiltration procedure, a median volume of 17 mL/kg (11-25) was ultrafiltered and a median volume of 11 mL/kg (6-17) was reinfused with a median final modified ultrafiltration balance of -0.15 mL/kg (-4.0 to 0.1). By univariate analyses, there was a 10% increase in postmodified ultrafiltration mean, systolic and diastolic pressures (p = 0.01), stroke volume index (p = 0.02), and cardiac index (p = 0.001) without significant changes in heart rate, central (left and right) venous pressures, stroke volume variation, and inotropic score. By multivariate analysis, when controlling for cardiopulmonary bypass time and age at surgery, cardiac index variation was independently associated with lower preoperative body surface area (beta coefficient -5.5, p = 0.04). According to Pressure Recording Analytical Method assessment, modified ultrafiltration acutely improves myocardial function, as shown by a 10% increase of systemic arterial pressure, stroke volume index, and cardiac index. This effect is more pronounced in smaller sized patients.

Effects of Percutaneous Stimulation of Both Sympathetic and Parasympathetic Cardiac Autonomic Nerves on Cardiac Function in Dogs

Augmentation of left ventricular (LV) contractility and heart rate (HR) by sympathetic nerve stimulation and amelioration of heart failure by vagal nerve stimulation has been reported. However, the effects of concomitant electrical stimulation of both sympathetic and parasympathetic cardiac nerves in tissues such as those of the cardiac plexus remain unclear. This study sought to assess acute changes in cardiac function and hemodynamics in response to endovascular cardiac plexus stimulation (CPS). Twelve dogs received endovascular CPS via a bipolar catheter within the right pulmonary artery. Stimulation frequency (20 Hz) and pulse width (4 milliseconds) were fixed; voltage varied (range, 15-60 V). Results fell into three categories: 1, no response (n = 4); 2, an increase in systemic arterial pressure that was dependent on electrode placement (n = 4); and 3, a very reproducible and stable increase in aortic pressure (n = 4). In the third group, mean systolic aortic pressures, maximum value of the first derivative of LV pressure, and LV stroke work increased with stimulation (P < 0.02 for all parameters) as did cardiac output, end-systolic elastance, and preload recruitable stroke work (P = 0.03). Systemic and pulmonary vascular resistance, central venous pressure, pulmonary arterial pressure, and HR remained unchanged (P > 0.05). In contrast to conventional inotropic agents, endovascular CPS induced significant and selective increases in LV contractility without increasing HR. Efforts to optimize electrode placement and fixation will improve the reproducibility of endovascular CPS treatment.

Exercise Testing and Training in Children With Congenital Heart Disease

The primary function of the cardiopulmonary system is to provide blood flow (and oxygen) in quantities sufficient to support the metabolic needs of the body. The capacity of the cardiopulmonary system to fulfill this function is maximally stressed when an individual's metabolic rate is increased, a condition that occurs most commonly during physical activity/exercise. A number of physiological changes accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise (Figure 1). In normal individuals, these changes (which during upright exercise include a tripling of the resting heart rate, a >60% reduction in systemic and pulmonary vascular resistance, and a >50% increase in stroke volume) can ultimately produce a >5-fold increase in cardiac output. The increase in cardiac output is accompanied by enhanced ventricular preload (as the ventricles move up their Starling curves to accommodate the increased workload), a doubling of systolic and mean pulmonary artery pressures (most of the increase in pulmonary artery pressures is due to the concomitant rise in left-sided filling pressures; the increase in transpulmonary pressure gradient is relatively small), and a more modest increase in systemic arterial pressures.1,–,4 Figure 1. Some of the physiological changes that accompany and facilitate the accommodation of the circulatory system to the hemodynamic demands of exercise. RAp indicates right atrial pressure; LAp, left atrial pressure; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; PAp, pulmonary artery pressure; and AOp, aortic pressure. Congenital heart disease (CHD) may, in a variety of ways and to a variable extent, adversely affect these hemodynamic adaptations. For instance, patients with a Fontan procedure lack a pulmonary ventricle. They therefore cannot increase their pulmonary blood flow and pressures normally (and consequently cannot maintain their ventricular preload and systemic blood flow) during exercise.5 Patients with tetralogy of Fallot and …

Not hearing is believing: novel insight into cardiopulmonary function using agitated contrast and ultrasound

the advancement of science depends heavily on the development and successful application of new techniques. Progress in ultrasound technology has allowed researchers in physiology to examine many important parameters noninvasively, including cerebral blood flow velocity, pulmonary artery systolic

Mouse Hepatic Portal Venoconstrictive Response to Vasoconstrictors Is Much Weaker Than That in Rat

We previously reported that the portal venous pressure (PPV) response of perfused mouse livers to various vasoactive agents was much weaker than that of other mammals such as rat, rabbit, and guinea pigs. The purpose of this study was to determine the responsiveness of PPV in in vivo BALB/c mouse to intraportal injections of the 3 major vasoconstrictors of angiotensin II, norepinephrine, and endothelin-1 in comparison with that in Sprague-Dawley rats. In anesthetized spontaneously breathing animals, PPV, systemic arterial pressure, and central venous pressure were directly and continuously measured. The above-mentioned vasoconstrictors were injected into the portal vein as a bolus repetitively at the doses ranging 0.01-100 nmol/kg. A dose-dependent increase in systemic arterial pressure in response to each vasoconstrictor was observed similarly in both mice and rats. All vasoconstrictors also caused a dose-dependent increase in PPV in both species, but the peak levels in mouse did not reach higher than 7 mm Hg, whereas it reached as high as 15-24 mm Hg in rats. Immunostaining for alpha-smooth muscle actin revealed that smooth muscles were distributed substantially in portal venules of rat but scarcely in that of mouse. In conclusion, PPV response to various vasoconstrictors was limited in anesthetized BALB/c mice, as compared with the anesthetized Sprague-Dawley rats, presumably due to small amount of vascular smooth muscle in mouse portal venules.

Analysis of hemodynamic responses and the proliferative effect of the novel angiotensin peptide Angiotensin A

A novel angiotensin peptide known as angiotensin A (Ang A) has been recently identified in the human plasma. Ang A has been reported to have a higher affinity for AT2 receptors and therefore may modulate the effects of Ang II. The in vivo responses to Ang A as well as the effects of this peptide on proliferation of vascular smooth muscle cells (VSMCs) have not been studied and therefore were investigated. The iv injections of Ang A 0.1, 0.3, and 1.0 μg/kg increased systemic arterial pressure of 30.0 ± 2.0, 46 ± 2, and 60 ± 4 mm Hg, respectively. On the other hand, the iv injections of Ang II at doses of 0.1, 0.3, and 1.0 μg/kg produced increases in systemic arterial pressure of 38.7 ± 3.3, 50 ± 2, and 63 ± 4 mm Hg, respectively. At the doses tested the responses to both Ang A and Ang II were significantly attenuated by the AT1 receptor blocker losartan, but were not altered by the AT2 receptor antagonist PD123,319. The proliferation effect of Ang A when tested in A10 VSMCs cultured in media containing 100 nM or 1 μM showed increases by 75 ± 10% and 99 ± 5% respectively, as determined by BrdU incorporation. In contrast, the proliferation of cells in media containing 100 nM Ang II the increase was only 31 ± 4% over cells grown in control medium. These data demonstrate that both Ang A and Ang II have similar hypertensive activity and Ang A has a greater proliferative effect than Ang II on rat A10 VSMC.

Procena plucne i metabolicke funkcije u toku klasicne i laparoskopske holecistektomije kod pacijenta sa ASA I i ASA II skorom

This is a prospective study of patients treated at the Center for Urgent Surgery, Clinical Center of Serbia. The patients were divided into two groups; i.e., the controls consisted of 30 subjects, who underwent conventional cholecystectomy, and studied group with 30 patients who had laparoscopic cholecystectomy. The patients were homogenized by ASA score (ASA I and ASA II) and on population basis. Hemodynamic parameters and 4 time-point pulmonary function tests were monitored in both groups. Peritoneal insufflation resulted in significant increase of systemic arterial pressure (23%), mean arterial pressure (23.8%), systemic vascular resistance (65%), pulmonary vascular resistance (90%), and significant reduction of cardiac output (24%) and cardiac index (51%). Pneumoperitoneum caused transient restriction of pulmonary function by reducing the thoracic and lung compliance. Fall of pH concentration, increase of PaCO2 and ET CO2 without any changes of PaO2, SO2, base excess and bicarbonate ions concentrations were the sequelae of CO2 absorption from peritoneal cavity. Postoperative "hypothermi", i.e. lowering of body temperature for 0.3 degrees C was the consequence of sudden gas expansion (Joule-Thompson phenomenon), which implies continuous flow of dry gas under pressure over peritoneal surface. Tissue damage factors (D-dimer, C-reactive protein, Protein C) were significantly lower in laparoscopic group, meaning that such mode of treatment resulted in minor postoperative pain and shorter period of recovery. Laparoscopy is a revolution in surgery. Definite success of any laparoscopic intervention depends on anesthesia as its crucial factor, at the same time meeting the patient's wish and expectations to be free from pain and discharged in no time from hospital.

Telemetric signal-driven servocontrol of renal perfusion pressure in acute and chronic rat experiments

The present study was designed to take advantage of telemetry data acquisition and develop an easy and reliable system to servocontrol renal perfusion pressure (RPP). Digitized pressure signals from lower abdominal aorta in rats, reflecting RPP, was obtained by a telemetry device and dynamically exported into an Excel worksheet. A computer program (LabVIEW) compared the RPP data with a preselected pressure range and drove a bidirectional syringe pump to control the inflation of a vascular occluder around the aorta above renal arteries. When RPP was higher than the preselected range, the syringe pump inflated the occluder and decreased RPP, and vice versa. If RPP was within range, there was no action. In this way, RPP was servocontrolled within the desired range. In experiments with norepinephrine- or ANG II-induced acute increases in systemic arterial pressure (120-145 mmHg), the system controlled RPP at a constant range of 100-105 mmHg within 30-50 s and differentiated the pressure-dependent and -independent effects on renal functions. In Dahl S rats with high-salt-induced hypertension, this system maintained RPP at 100-120 mmHg over 10 days, while systemic arterial pressures were 150 +/- 5.9 mmHg in uncontrolled animals. This system also has the ability of simultaneity and multiplexing to control multiple animals. Our results suggest that this is an effective and reliable system to servocontrol RPP, which can be easily established with general computer knowledge. This system provides a powerful tool and may greatly facilitate the studies in pressure-dependent/-independent effects of a variety of cardiovascular factors.

Effects of Low Dose Ketamine on Tourniquet-induced Haemodynamic Responses during General Anaesthesia

This study investigated the effect of a pre-operative low dose of intravenous ketamine on tourniquet-induced haemodynamic changes. Ten minutes after induction of general anaesthesia, 0.1 mg/kg ketamine in 10 ml of saline (ketamine group, n = 14) or 10 ml of normal saline (control group, n = 14) were administered intravenously. Systolic and diastolic blood pressures, and heart rate relative to tourniquet inflation and deflation were recorded and compared within and between groups. Systolic and diastolic blood pressures in the control group significantly increased relative to baseline during the observation period following tourniquet inflation, but generally did not significantly increase in the ketamine group. The control group had a greater percentage of patients with a 30% rise in blood pressure at 60 min after tourniquet inflation compared with the ketamine group (28.6% vs 7.1%), but this was not statistically significant. We conclude that a pre-operative low dose (0.1 mg/kg) of intravenous ketamine can prevent a systemic arterial pressure increase for at least 60 min after tourniquet inflation under general anaesthesia.

Preoperative oral dextromethorphan vs. clonidine to prevent tourniquet-induced cardiovascular responses in orthopaedic patients under general anaesthesia

Preoperative oral dextromethorphan and intravenous clonidine attenuate arterial pressure and heart rate increases during tourniquet inflation under general anaesthesia. The effect of preoperative oral clonidine on these variables has not been investigated. We designed this study to compare the effect of preoperative oral dextromethorphan or clonidine on haemodynamic changes during tourniquet inflation in 75 patients undergoing lower limb surgery under general anaesthesia. Patients were randomly assigned into three groups: dextromethorphan 30 mg (n = 25), clonidine 3 microg kg(-1) (n = 25) and placebo (n = 25). Anaesthesia was maintained with isoflurane 1.2% and N2O 50% in oxygen with endotracheal intubation. Dextromethorphan, clonidine or placebo was given orally in a double-blinded fashion 90 min before induction of anaesthesia. Systolic, diastolic and mean arterial pressure and heart rate were measured at 0, 30, 45, 60 min after the start of tourniquet inflation, before tourniquet release and 20 min after tourniquet deflation. Systolic, diastolic and mean arterial pressure were significantly lower in the clonidine group compared with control after 45, 60 min tourniquet inflation and before tourniquet release (P < 0.05). Twenty minutes after deflation, diastolic and mean arterial pressure in the control group were still increased and significantly higher compared with the clonidine group (P < 0.05). Development of more than a 30% increase in systolic arterial pressure during tourniquet inflation was more frequent in the control group than in the other groups. Preoperative oral clonidine 3 microg kg(-1) significantly prevented tourniquet-induced systemic arterial pressure increase in patients under general anaesthesia better than oral dextromethorphan.

Pressor responses to ephedrine are not impaired in dopamine β‐hydroxylase knockout mice

Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model. Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine beta-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh +/- littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments. In Dbh -/- mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh +/- mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/- and Dbh +/- mice. The present results in Dbh -/- mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh +/- and Dbh -/- mice are useful for the study of direct and indirect mechanisms.

Acute effects of tacrolimus (FK506) on left ventricular mechanics

Tacrolimus (FK506) is a macrolide antibiotic used to minimize transplant rejections. Several macrolides affect ventricular function, but the effects of tacrolimus are unknown. This study evaluated acute effects of escalating doses of tacrolimus on heart rate (HR), left ventricular inotropy, lusitropy, preload (end-diastolic short axis radius on a 2D directed M-mode echocardiogram), and afterload (product of end-diastolic radius and diastolic arterial pressure divided by end-diastolic wall thickness) in anesthetized dogs. Tacrolimus at 0.025 mg kg −1 increased HR and inotropy with continued escalation up to a dose of 0.1 mg kg −1 ( p < 0.01). Conversely, tacrolimus at 0.025 mg kg −1 decreased lusitropy and preload, which never achieved steady states ( p < 0.05). Afterload tended to increase between doses of 0.0125 and 0.025 mg kg −1, and tended to decrease at higher doses, achieving baseline at a dose of 0.1 mg kg −1. Tacrolimus significantly prolonged the QT interval (QTc) between doses of 0.0125 ( p < 0.05) and 0.1 mg kg −1 ( p < 0.001). These effects are consistent with altered calcium kinetics leading to increased cytosolic calcium. Tacrolimus at a clinically relevant dose of 0.1 mg kg −1 possesses profound, acute effects on left ventricular mechanics, suggesting that cardiovascular monitoring may be necessary in tacrolimus-treated patients. Potential adverse effects include myocardial stiffness, transient increase in systemic arterial pressure, and tendency for ventricular arrhythmia.