Reflex Sympathetic Stimulation Research Articles

A Comparative Study of the Effect of Propofol and Etomidate as an Induction Agent on Haemodynamic Changes during Induction and Endotracheal Intubation

Aims: Presently Propofol and Etomidate are popular as rapid acting inducing agents. Due to reflex sympathetic stimulation, direct laryngoscopy and endotracheal intubation typically cause a cardiovascular stress response characterized by hypertension and tachycardia. This study is conducted to compare the effects of these two drugs on hemodynamic responses during induction and endotracheal intubation, to compare time of induction to choose the better induction agent and to study adverse effects of the two drugs, if any.
 Study Design: Prospective double blind study
 Place and Duration of Study: Department of anaesthesiology Dr D.Y Patil medical college hospital and research centre Pimpri Pune Duration -Sept.2018 -sept 2021.
 Methodology: This is prospective randomized double-blind study. 60 ASA I and II patients randomly divided into two groups group P and group E of 30 each of either sex in age group of 18-65 years posted for elective surgery under general anesthesia. Group P: (n-30) received 2.5mg/kg Propofol and Group E:(n-30) received 0.3mg/kg Etomidate for induction. vital parameters such as HR, SBP, DBP, MAP, and SPO2 recorded at baseline (T0), before induction (T1), after induction (T2), during laryngoscopy (T3 ) ,after intubation at 1min, 2min, 3min, 5min and at 10 min. Time of induction was taken as period between time of start of study drug till loss of eyelash reflex
 Conclusion: Induction time between the two study groups was statistically insignificant. (p>0.05) The fall in heart rate at post induction (T2), at 1 min, 2 min after intubation in Group P as compared to Group E was statistically significant, fall in SBP, DBP and MAP at post induction (T2), at 1 min, 2 min, 3 min and 5 min after intubation in Group P as compared to Group E was statistically significant. Pain on injection was more with propofol. However, myoclonus was more with etomidate.

A comparative study of haemodynamic response during LMA supreme insertion versus endotracheal intubation in paralysed patients during general anaesthesia

Introduction: LMA Supreme is a device which has recently been gaining popularly as an aid to airway management. During ETT intubation induces reflex sympathetic adrenal stimulation which is associated with raised levels of plasma catecholamines. This raised catecholamines induce hypertension and tachycardia. These effects should be avoided in patients with hypertension, ischemic heart disease, stenotic valvular heart disease, and raised intracranial tension, LMA Supreme can be used to over come the sympathetic response.Materials and Methods: 80 patients of either sex, aged 18 to 50 yrs posted for elective surgeries. Randomized to 2 groups N=40 each. We recorded HR, SBP, DBP, MAP, ETCO2, SPO2 at 0, 1, 5, 10 min and post extubation after LMA Supreme insertion, ET tube intubation and ease of insertion, no of attempts and post operative complications.Results: LMA Supreme airway is a safe and effective mean of maintaining airway. Ease and the simplicity makes the device well tolerated and the pressure response is less than endotracheal intubation. In our study we have observed the ETT intubation had increased haemodynamic responses when compared with LMA-S insertion.Conclusion: LMA Supreme can be suitable alternative to ETT intubation in elective adult surgeries. LMA-S with its unique design will help to expand Anaesthesiologist efficiency in the management of patients.

Comparison Of Fentanyl And Clonidine In Attenuation Of Haemodynamic Response To Laryngoscopy And Endotracheal Intubation

Background: Laryngoscopy and endotracheal intubation has led to provision of safer anaesthesia due to better control of airway and ventilation. It is associated with reflex sympathetic stimulation resulting in an increase in heart-rate and blood-pressure, which is known as pressor response to laryngoscopy and intubation.Various drugs have been used to avoid this pressor response. This study was aimed to assess the effects of IV Fentanyl and IV Clonidine on pressor responses occurring due to laryngoscopy and intubation in normotensive patients posted for a planned surgical procedure under general anaesthesia.Methods: Approval from the institutional ethical committee was taken for the study. We conducted this study in 60 patients belonging to ASA grade I and II, of 18 to 65 years of age, of either sex, scheduled for planned surgical procedures under general anaesthesia.Patients were randomly allocated into 2 groups; the study drug was injected IV slowly 10 mins before induction.Group-F: received Inj Fentanyl 2mcg/kgGroup-C: received Inj. Clonidine 2mcg/kgObservations were noted in terms of heart-rate, systolic-BP, diastolic-BP, mean-BP and spO2.Results: We observed that Clonidine pre-treatment provided better blunting of stress response duringlaryngoscopy and intubation without causing clinically significant sedation, respiratory depression, bradycardiaor hypotension compare to Fentanyl.Conclusion:We came to a conclusion that Clonidine provided better response compare to Fenatanyl in obliterating the rise in heart-rate and blood pressure on laryngoscopy and intubation.

Comparison of efficacy of Lignocaine 1.5 mg/kg & Dexmedetomidine 1 μg/kg in attenuating the hemodynamic pressure response to laryngoscopy & intubation

Background: Dexmedetomidine attenuates the hemodynamic stress response tolaryngoscopy and intubation more effectively compared with Lignocaine without any deleterious effects. To study the efficacy of Lignocaine 1.5 mg/kg & Dexmedetomidine 1 μg/kg in attenuating the hemodynamic pressure response to laryngoscopy & intubation. Material and Methods: A total of 100 American Society of Anesthesiologists (ASA) physical status I and II patients aged between 18 and 50 years undergoing elective surgery were enrolled in the study. Patients posted for elective surgery were randomly selected and divided into two groups. Group L = 50 Patients had given 1.5mg/kg Lignocaine; Group D = 50 Patients had given 1µg / kg Dexmedetomidin. Results: In Dexmedetomidine group, HR, SBP, DBP and MAP showed significant decrease throughout the study period, as compared to Lignocaine group. The statistical analysis shows that, in Dexmedetomidine group, HR, SBP, DBP and MAP showed significant decrease throughout the study period, as compared to Lignocaine group. Conclusion: Newer agents like Dexmedetomidine, a centrally acting alpha-2 agonist suppresses reflex sympathetic stimulation caused by laryngoscopy & intubation more effectively than Lignocaine. Thus, it is concluded that Dexmeditoedine is a better drug compared to Lignocaine in attenuating pressure response to laryngoscopy & intubation.

A Comparative Study of Clonidine and Lignocaine for Attenuating Pressor Responses to Laryngoscopy and Endotracheal Intubation in Neurosurgical Cases.

Background and Aims:Laryngoscopy and endotracheal intubation are associated with reflex sympathetic stimulation, known as pressor response and can cause major complications. We compared the attenuating effect of time-tested lignocaine versus clonidine on the hemodynamic response to laryngoscopy and intubation in neurosurgical cases.Design:A prospective, randomized, comparative, double-blind study with a sample size of sixty patients.Methods:Sixty patients undergoing elective neurosurgery were randomly allocated into one of the two groups: Group L (n = 30) received lignocaine 1.5 mg/kg intravenous (i.v.) before induction and Group C (n = 30) received clonidine 2 μg/kg i.v. before induction. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were recorded at baseline, after drug, after induction and 1, 2, 3,5,10, and 15 min after intubation.Statistical Analysis:Statistical software, namely, SPSS, version 15.0 by SPSS Inc., Chicago, USA was used for the analysis of data with Chi-square test to compare intergroup hemodynamic parameters.Results:Mean HR remained above baseline at all times after intubation in lignocaine group but decreased at 2 min after intubation and remained below baseline at all times in the clonidine group. SBP, DBP, and MAP all increased above baseline at 1 min after intubation in lignocaine group, and decreased below baseline at 2 min after intubation, whereas in the clonidine group they all decreased below baseline after drug administration and remained below baseline at all times. Therefore, clonidine is very effective in attenuating pressor responses and this difference between the groups is statistically very significant with P < 0.001.Conclusion:Clonidine is more effective than lignocaine for attenuating the pressor responses to laryngoscopy and endotracheal intubation in neurosurgical cases.

Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.

COUNTERPOINT: ACTIVE VENOCONSTRICTION IS NOT IMPORTANT IN MAINTAINING OR RAISING END-DIASTOLIC VOLUME AND STROKE VOLUME DURING EXERCISE AND ORTHOSTASIS

Veins were considered merely as passive conduits of blood until Mellander ([13][1]) reported that stimulation of sympathetic nerves supplying the cat's hindquarters resulted in a decrease in regional blood volume. This and other work led Folkow and Mellander ([4][2]) to assert that veins were “at

Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects

OBJECTIVESWe sought to assess the effects of brain natriuretic peptide (BNP) on systemic and regional sympathetic nervous activity (SNA) in both patients with congestive heart failure (CHF) and healthy control subjects.BACKGROUNDAlthough the response of SNA to atrial natriuretic peptide (ANP) has been well documented, the response of SNA to BNP is largely unknown.METHODSWe assessed cardiac and whole-body SNA using the norepinephrine (NE) tracer dilution method before and after infusion of two doses of BNP (3 and 15 ng/kg body weight per min) in 11 patients with stable CHF (ejection fraction 24 ± 2%) and 12 age-matched healthy control subjects. In addition, renal SNA and hemodynamic variables were assessed at baseline and after the higher BNP dose.RESULTSLow dose BNP did not change blood pressure or whole-body NE spillover, but reduced cardiac NE spillover in both groups by 32 ± 13 pmol/min (p < 0.05). In both groups, high dose BNP reduced pulmonary capillary pressure by 5 ± 1 mm Hg (p < 0.001) and mean arterial pressure by 6 ± 3 mm Hg (p < 0.05), without a concomitant increase in whole-body NE spillover; however, cardiac NE spillover returned to baseline levels. Renal NE spillover remained virtually unchanged in healthy control subjects (501 ± 120 to 564 ± 115 pmol/min), but was reduced in patients with CHF (976 ± 133 to 656 ± 127 pmol/min, p < 0.01).CONCLUSIONSOur results demonstrate a sympathoinhibitory effect of BNP. Cardiac sympathetic inhibition was observed at BNP concentrations within the physiologic range, whereas high dose BNP, when arterial and filling pressures fell and reflex sympathetic stimulation was expected, systemic and cardiac SNA equated to baseline values. There was inhibition of renal SNA in patients with CHF, but not in healthy control subjects. Whether this effect is specific to BNP or related to reduced filling pressure remains to be determined.

Inhibitory Effects of Nitric Oxide and Nitrosative Stress on Dopamine-β-Hydroxylase

Dopamine-beta-hydroxylase (DbetaH) is a copper-containing enzyme that uses molecular oxygen and ascorbate to catalyze the addition of a hydroxyl group on the beta-carbon of dopamine to form norepinephrine. While norepinephrine causes vasoconstriction following reflex sympathetic stimulation, nitric oxide (NO) formation results in vasodilatation via a guanylyl cyclase-dependent mechanism. In this report, we investigated the relationship between NO and DbetaH enzymatic activity. In the initial in vitro experiments, the activity of purified DbetaH was inhibited by the NO donor, diethylamine/NO (DEA/NO), with an IC(50) of 1 mm. The inclusion of either azide or GSH partially restored DbetaH activity, suggesting the involvement of the reactive nitrogen oxide species, N(2)O(3). Treatment of human neuroblastoma cells (SK-N-MC) with diethylamine/NO decreased cellular DbetaH activity without affecting their growth rate and was augmented by the depletion of intracellular GSH. Co-culture of the SK-N-MC cells with interferon-gamma and lipopolysaccharide-activated macrophages, which release NO, also reduced the DbetaH activity in the neuroblastoma cells. Our results are consistent with the hypothesis that nitrosative stress, mediated by N(2)O(3), can result in the inhibition of norepinephrine biosynthesis and may contribute to the regulation of neurotransmission and vasodilatation.

Impairment of the myocardial vasomotor response to cold pressor stress in collateral dependent myocardium.

OBJECTIVE: To study the vasomotor response (cold pressor/basal flow) in myocardium perfused entirely by collaterals, using the reflex sympathetic stimulation of cold pressor stress. DESIGN: Regional myocardial blood flow was...

Use of Calcium Antagonists in Patients with Ischemic Heart Disease and Systemic Hypertension

Ischemic heart disease (IHD) and systemic hypertension commonly coexist in a large number of patients, and the presence of hypertension is a risk factor for worsening IHD. A monotherapy that would effectively treat both is thus an attractive idea, and calcium antagonists have been evaluated in this role. Calcium antagonists exert therapeutic effects through a combination of actions, including systemic and peripheral vasodilation, negative inotropy, and reduced nodal conduction. In randomized, double-blind clinical trials, verapamil compares favorably with propranolol in the alleviation of angina and hypertension. Both diltiazem and nifedipine, as well as long-acting diltiazem, are also effective in treating the combined condition. In addition, each of these drugs enhances exercise tolerance and favors compliance with calcium antagonist therapy. Recent questions regarding the safety of this class of drug have tempered the enthusiasm for their use as first-line therapy in cardiovascular disease. In particular, short-acting dihydropyridine derivatives, including nifedipine and isradipine, may increase cardiovascular morbidity and mortality because of reflex sympathetic stimulation. The results of appropriately controlled, prospective clinical trials will provide more definitive conclusions. For now, we must be cautious in the use of calcium antagonist monotherapy for combined IHD and hypertension.

Calcium antagonists during and after myocardial infarction.

Calcium antagonists, or calcium channel entry blockers, have been advocated as cardioprotective agents in acute myocardial infarction (AMI) on the basis of animal experiments, which show that they will reduce the harmful effects of the calcium overload which follows ischaemia, particularly during reperfusion, and also that they will reduce coronary artery spasm. Unfortunately, these promising actions have not translated into clear mortality data. An overview of the large amount of data from properly randomised controlled clinical trials shows clear differences between the dihydropyridine class of calcium antagonists such as nifedipine, and the non-dihydropyridines verapamil and diltiazem. Most of the data with the former group derive from trials with short-acting formulations of nifedipine (TRENT, HINT, SPRINT-I and -II). Overall, none of these trials showed significant benefit in either AMI or post-MI prophylaxis. There was a trend for harm, with HINT stopped early because of excess reinfarction with nifedipine, compared with metoprolol. In contrast, and when taken together, the DAVIT-I and DAVIT-II studies with verapamil show significant reductions in sudden death, reinfarction and total mortality. The greatest benefit occurred in those patients with relatively good left ventricular function. Similar but less significant trends were seen in studies with diltiazem. It is clear that calcium antagonists, unlike beta-blockers, cannot be treated as a similar class. It seems likely that the adverse effects of nifedipine are related to reflex sympathetic cardiac stimulation as a result of the predominantly vasodilator action of these dihydropyridine compounds. Data on newer dihydropyridines with fewer reflex effects are awaited. In the meantime it seems sensible to use proven agents such as beta-blockers or verapamil. These data on AMI and the months following have recently been paralleled by case control studies in hypertension, which similarly have suggested harm from the use of predominantly short acting formulations of nifedipine compared with beta-blockers and which led to a warning statement by the US National Heart, Lung, and Blood Institute on 1 September 1995.

Regional origins of 3-methoxy-4-hydroxyphenylglycol in plasma: effects of chronic sympathetic nervous activation and denervation, and acute reflex sympathetic stimulation

The plasma level and urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal metabolite of noradrenaline in the brain, are often used as indicators of central nervous system noradrenergic activity. Using percutaneously placed catheters, we studied the regional inputs into the plasma MHPG pool in 62 healthy volunteers. Veno-arterial plasma concentration differences and regional organ blood flows were used to quantify the relative amounts of MHPG contributed by various sites into plasma. Positive veno-arterial concentration gradients were found across the forearm, cardiac and jugular vessels in the healthy subjects. By far the majority of MHPG in plasma was derived from skeletal muscle, 5.3 ± 1.8 nmol/min, with only minimal contribution (0.9 ± 0.2 nmol/min) from the brain. Thus, to obtain an accurate indication of central nervous system noradrenergic activity the confounding influences of regional MHPG production must be excluded. 34 patients with chronic congestive heart failure, 6 patients with pure autonomic failure and 9 recent heart transplant recipients were used to investigate the possible effects of chronic sympathetic nervous system overactivity and sympathetic underactivity and denervation on peripheral MHPG production and plasma MHPG concentration. To examine the utility of plasma MHPG determinations as an indicator of acute alterations in sympathetic nervous activity we examined the influence of a variety of laboratory stressors on the arterial level and cardiac production of MHPG. The resting arterial plasma MHPG concentration mirrored sympathetic function in the patients with cardiac failure (sympathetic activation) and pure autonomic failure (sympathetic denervation), with mean MHPG plasma concentrations being 180 and 40% of those in healthy subjects. Cardiac MHPG production was increased in heart failure patients, and near zero with the cardiac sympathetic denervation accompanying transplantation and pure autonomic failure. In contrast, acute reflex stimulation of sympathetic nervous activity was not associated with parallel changes in the arterial level or cardiac production of MHPG. Measurements of peripheral plasma MHPG levels provide an index of prevailing sympathetic nervous function in clinical models of sympathetic overactivity and denervation, but are insensitive to acute sympathetic nervous system responses.

Efficacy and safety of nisoldipine coat core in the management of angina pectoris, systemic hypertension, and ischemic ventricular dysfunction

The effects of the long-acting dihydropyridine calcium antagonist nisoldipine coat core (CC) have been investigated in > 3,500 patients with angina pectoris, hypertension, arid ischemic ventricular dysfunction. In patients with angina pectoris, nisoldipine CC improved total treadmill exercise duration (p = 0.027), delayed the onset of angina pectoris (p = 0.009), and increased time to exercise-induced ST-segment depression (p = 0.061). In general, nisoldipine 20–40 mg was effective, and the dose-response curve flattened thereafter. In patients with hypertension, 10–40 mg once daily as monotherapy reduced blood pressure (p < 0.05), with a fall in diastolic pressure of ≥ 10 mm Hg or a final diastolic pressure of <90 mm Hg in 35–63% of patients. In most patients followed for a year, nisoldipine CC was continued as monotherapy. Efficacy was similar in patients <65 and >65 years of age. In the Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy (DEFIANT-I) study of patients recovering from myocardial infarction, nisoldipine CC had a salutary effect on diastolic ventricular function, with a higher transmitral early filling velocity and shorter isovolumic relaxation time than in patients receiving placebo. Bicycle exercise capacity was greater (by 12 W; 95% confidence interval, 0.8–23.3) and exercise-induced ischemia occurred less frequently. The nisoldipine CC data pool (3,679 patients) showed that the drug was well tolerated with a low incidence of side effects. Angina pectoris, chest pain, and dyspnea, occurred less frequently with nisoldipine CC, and mortality was slightly lower in patients taking the drug (0.28% vs 0.37%). The absence or very low incidence of acute vasodilatory effects may indicate that complications associated with sharp peak and trough effects of drug (reflex sympathetic stimulation, catecholamine release, activation of the renin—angiotensin system) may be less frequent with long-acting calcium antagonists.

Systemic hemodynamic, forearm vascular, renal, and humoral responses to sustained cardiopulmonary baroreceptor deactivation in well-compensated cirrhosis

The aim of this study was to assess baroreceptor function in well-compensated cirrhosis by determining the forearm vascular, renal, and humoral responses to sustained baroreceptor deactivation. The effect of sodium status on baroreceptor function was also assessed. Eight cirrhotic patients and 10 age- and sex-matched controls were studied twice after a 20 mmol and 200 mmol of sodium/d diet for 7 days. Systemic and renal hemodynamics, renal sodium handling, forearm blood flow, and neurohurioral factors were assessed before, during, and after the application of lower body negative pressure (LBNP) for 1 hour. Controls and cirrhotic patients had similar baseline mean arterial pressure, heart rate, forearm and renal hemodynamics. High-sodium intake resulted in suppression of sympathetic nervous activity in the controls (plasma norepinephrine, 1.06 ± 0.11 mmol/L on low vs. 0.76 ± 0.08 nmol/L on high sodium; P = 0.01) but not in the cirrhotic patients (1.35 ± 0.22 mmol/L on low vs. 1.26 ± 0.11 mmol/L on high sodium; P > 0.05). Both groups responded to LBNP with significant further increases in plasma norepinephrine, resulting in significant decreases in forearm blood flow on both sodium diets. Controls also responded with a significant worsening of renal hemodynamics on low-sodium diet only, but this was not observed in the cirrhotic patients on either diet. Therefore, in well-compensated cirrhotic patients: (1) sympathetic activation occurs despite an adequate, effective arterial filling, and this may contribute to sodium retention; and (2) baroreceptor function is normal. Apparent end organ unresponsiveness within the renal circulation may account for the lack of renal hemodynamic changes to reflex sympathetic stimulation.

Systemic hemodynamic, forearm vascular, renal, and humoral responses to sustained cardiopulmonary baroreceptor deactivation in well-compensated cirrhosis

The aim of this study was to assess baroreceptor function in well-compensated cirrhosis by determining the forearm vascular, renal, and humoral responses to sustained baroreceptor deactivation. The effect of sodium status on baroreceptor function was also assessed. Eight cirrhotic patients and 10 age- and sex-matched controls were studied twice after a 20 mmol and 200 mmol of sodium/d diet for 7 days. Systemic and renal hemodynamics, renal sodium handling, forearm blood flow, and neurohumoral factors were assessed before, during, and after the application of lower body negative pressure (LBNP) for 1 hour. Controls and cirrhotic patients had similar baseline mean arterial pressure, heart rate, forearm and renal hemodynamics. High-sodium intake resulted in suppression of sympathetic nervous activity in the controls (plasma norepinephrine, 1.06 +/- 0.11 nmol/L on low vs. 0.76 +/- 0.08 nmol/L on high sodium; P = 0.01) but not in the cirrhotic patients (1.35 +/- 0.22 nmol/L on low vs. 1.26 +/- 0.11 nmol/L on high sodium; P > 0.05). Both groups responded to LBNP with significant further increases in plasma norepinephrine, resulting in significant decreases in forearm blood flow on both sodium diets. Controls also responded with a significant worsening of renal hemodynamics on low-sodium diet only, but this was not observed in the cirrhotic patients on either diet. Therefore, in well-compensated cirrhotic patients: (1) sympathetic activation occurs despite an adequate, effective arterial filling, and this may contribute to sodium retention; and (2) baroreceptor function is normal. Apparent end organ unresponsiveness within the renal circulation may account for the lack of renal hemodynamic changes to reflex sympathetic stimulation.

Acute Effects of Nifedipine on Systolic and Diastolic Ventricular Function in Patients With Chronic Obstructive Pulmonary Disease

To evaluate how nifedipine influences systolic and diastolic ventricular function, the effects of 20 mg sublingual nifedipine were studied in 13 stable COPD patients. Nifedipine induced no change in mean pulmonary arterial pressure, decreased mean arterial pressure, pulmonary and systemic vascular resistance index, and increased heart rate and cardiac index. It also caused an increase in right and left ventricular ejection fractions. The end-diastolic volume index of both ventricles remained unchanged, whereas the end-systolic volume index tended to decrease without reaching a significant level, and the right ventricular contractility increased. After nifedipine administration, right and left ventricular compliance increased. This study suggests that short-term administration of nifedipine improves the systolic function by a decrease in ventricular afterload and an increase in ventricular contractility and increases the ventricular compliance by a reflex sympathetic stimulation and an afterload reduction.

Effect of Verapamil on Ventricular Function

Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.

Does alpha sympathetic blockade prevent urinary retention following anorectal surgery?

Urinary retention is the most common complication after anorectal surgery, with rates as high as 52 percent reported. With the trend toward early discharge, avoidance of this complication is particularly important. Perioperative fluid restriction and the use of short-acting anesthetics have been shown to be effective in decreasing postoperative urinary retention rates but are not applicable in all cases. Reflex sympathetic stimulation, possibly as a result of perianal pain, may lead to increased muscular tone of the internal sphincter at the bladder neck. This theory had led to the effective use of alpha-adrenergic blockade in the treatment of established cases of urinary retention after anorectal surgery, herniorrhaphy, and major pelvic surgery. However, the prophylactic role of alpha blockade after anorectal surgery has not been studied. In a double-blind, prospective, randomized study, 51 patients were treated with either prazosin and alpha-adrenergic blocker or placebo prior to and immediately after elective anorectal surgery. Urinary retention rates were similar in the two groups. At this time, prophylactic alpha-adrenergic blockade is not recommended for the prevention of urinary retention after anorectal surgery.

Interaction of neuropeptide Y and the sympathetic nervous system in vascular control in man.

There is increasing evidence that neuropeptide Y (NPY) contributes to the autonomic control of the circulation. NPY coexists with noradrenaline in perivascular nerve terminals, may be released during sympathetic stimulation, and is a potent constrictor of the human coronary circulation and other vascular beds. In vitro studies show that NPY can act either directly on vascular smooth muscle or indirectly by modulation of the presynaptic release or the postsynaptic actions of noradrenaline. It is unclear to what extent these mechanisms operate in vivo. The effect on forearm blood flow of intra-arterial NPY was studied in six volunteers during coinfusion of noradrenaline and during reflex sympathetic stimulation induced by lower-body negative pressure. NPY alone induced a dose-dependent reduction of forearm blood flow in all subjects studied, to a maximum of 49 +/- 6.1%. The reduction of flow during infusion of noradrenaline alone was 42 +/- 8%. The response to noradrenaline was unaffected by coinfusion of a threshold constrictor dose of NPY (50 pmol/min). Furthermore, the reflex sympathetic vasoconstrictor response to 20 cm H2O of lower-body negative pressure was similar in both the infused and control arms during the infusion of 50 pmol/min NPY. The response to noradrenaline was abolished by alpha-blockade with phentolamine, but the flow reduction induced by NPY was unaffected by alpha-blockade. NPY is a potent constrictor of human forearm resistance vessels and has a direct effect independent of alpha-receptors. NPY has no detectable modulating effect in vivo on the action of endogenous or infused noradrenaline.