Alcohol Consumption and Depression Among University Students and Their Perception of Alcohol Use.

OBJECTIVES: To investigate the association between alcohol use and depression among university students in Hong Kong, their stress-coping methods, and their knowledge and perception of the effects of alcohol on health. METHODS: 345 full-time undergraduate students from The University of Hong Kong were invited to complete a questionnaire to assess their alcohol consumption (Alcohol Use Disorders Identification Test, CAGE questionnaire), depressive symptoms (Patient Health Questionnaire-9), and stress-coping methods (Coping Orientation to Problems Experienced Inventory), as well as knowledge and perception of alcohol consumption on health. Multiple linear regression was used to determine significant variables associated with depressive symptoms. Multinominal logistic regression was used to determine the effect of such variables on depressive symptom caseness and AUDIT drinking risk groups. RESULTS: 43.2% of respondents were moderate- to high-risk drinkers, but only 23.2% were self-reported as moderate- to high-level drinkers. 57.9% of respondents had mild to severe depressive symptoms. Probable depression was more likely to occur in female students, those with higher general stress, those who do not use social support for stress-coping, and those who smoke. High-risk drinkers were more likely to occur in older students, smokers, those with higher household income, and those with higher general stress levels. Students with higher levels of depressive symptoms and higher risk of alcohol consumption were more likely to use avoidance for stress-coping. 89.5% of students considered alcohol consumption moderately to very harmful to health, but students demonstrated only moderate knowledge levels of alcohol consumption on health. CONCLUSION: Alcohol consumption and depressive symptoms are prevalent among university students in Hong Kong. The use of avoidance for stress-coping is common in those with higher levels of depressive symptoms and higher-risk drinkers. Students tend to avoid seeking help for depressive symptoms and potentially take up drinking as a coping strategy. Context-specific approaches should be used when providing counselling services for student wellbeing in university settings. Further education of university students on knowledge and perception of alcohol consumption on health should be provided.

Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold.

OBJECTIVES: We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone's active metabolite desethylamiodarone (DEA). BACKGROUND: Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT. METHODS: We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks. RESULTS: Amiodarone caused a dose-response increase in DFT (mean +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at baseline to 23.1 +/- 7.4 (dose 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p = 0.18. CONCLUSIONS: DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent.

Rimantadine pharmacokinetics in healthy subjects and patients with end-stage renal failure.

The single-dose (two 100 mg doses) pharmacokinetics of rimantadine hydrochloride were compared in eight patients with end-stage renal disease who were on hemodialysis and seven age-matched healthy subjects. Plasma and urine rimantadine concentrations were determined by a GC/MS method. The plasma half-life (43.6 vs 27.5 hours) and AUC (9.9 +/- 2.1 vs 6.0 +/- 1.6 micrograms.hr/ml) were significantly (p less than 0.05) increased in the patient population. No significant differences were noted in the maximum rimantadine concentration, time of maximum concentration, or apparent volume of distribution. Urinary excretion of unchanged rimantadine accounted for 16% of the dose in the healthy subjects. Hemodialysis did not appreciably remove rimantadine. These findings suggest that rimantadine dosage may need to be reduced in patients with end-stage renal disease but supplemental doses on dialysis days are not required.

The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine.

Although propafenone is a known substrate and inhibitor of the cytochrome P450 4-hydroxylation pathway of debrisoquin (CYP2D6 isozyme), its effects on other hepatic mixed- function oxidative isozymes have not been extensively evaluated. We studied the influence of propafenone on the disposition of continuously infused lidocaine in 12 healthy male volunteers. Placebo or propafenone (225 mg every 8 hours) was orally administered for 4 days before and during lidocaine administration (2 mg/kg/hr for 22 hours). In the 11 (92%) subjects phenotyped as extensive metabolizers, propafenone significantly increased the lidocaine area under the plasma concentration time curve (81.7 +/- 16.2 versus 76.3 +/- 15.6 micrograms.hr/ml; p < or = 0.05) and reduced systemic lidocaine clearance (9.53 +/- 1.77 versus 10.27 +/- 2.24 ml/min/kg; p < or = 0.05), but did not significantly affect volume of distribution at steady state (2.48 +/- 0.33 versus 2.64 +/- 0.45 L/kg; p = 0.10) or mean residence time (4.37 +/- 0.92 versus 4.47 +/- 0.87 hours; difference not significant) compared with placebo, respectively. Adverse central nervous system effects were significantly worse in severity and duration during the propafenone phase (p < or = 0.05). Propafenone minimally inhibits the metabolism of lidocaine. This suggests that the ability of propafenone to inhibit metabolic pathways exclusive of the CYP2D6 isozyme may be limited. In addition, potentiation of disturbing central nervous system adverse effects may occur during combination therapy of propafenone and lidocaine.

Effect of renal impairment on the pharmacokinetics of cibenzoline.

Sixteen subjects completed an open-label study designed to assess the effect of renal impairment on the disposition of cibenzoline. The study included 10 patients with mild or moderate renal impairment creatinine clearance less than 60 ml/min/70 kg) and six healthy subjects in the same age range, each of whom received a single 130 mg oral dose of cibenzoline. The pharmacokinetic parameters observed in the healthy volunteers were similar to those reported previously. Maximum plasma concentration, time of maximum concentration, and apparent volume of distribution after single doses in patients with renal impairment were in the same range as those observed in healthy volunteers. The elimination half-life increased with decreasing renal function from a mean value of approximately 8 hours in healthy volunteers to more than 20 hours in patients with moderate renal impairment. Renal clearance and the fraction of the dose excreted unchanged in the urine decreased with decreasing creatinine clearance. The results of this study suggest that the dosage of cibenzoline should be reduced or the dosage interval increased in patients with reduced renal function to avoid excessive drug accumulation.

Disopyramide hemodialysis and kinetics in patients requiring long-term hemodialysis.

Disopyramide hemodialysis and kinetics after 200 mg orally in six patients receiving long-term hemodialysis were examined. Mean volume of distribution (area) was 66.5 +/- 13 l. Mean times of the peak serum concentration and mean peak serum concentration were 2.3 +/- 0.9 hr and 3.1 +/- 0.9 microgram/ml. Mean absorption half-life (t 1/2) was 21.6 +/- 12.5 min. Mean disopyramide elimination t 1/2 during dialysis was 16.8 +/- 11.9 hr, not significantly different from mean elimination t 1/2 without dialysis of 16.1 +/- 5.2 hr. End-dialysis bath concentrations of disopyramide showed that not more than 2.4% of the dose was dialyzed during a 2-hr dialysis period. Our data indicate that at therapeutic concentrations disopyramide was not appreciably dialyzed.

Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine.

The frequent recurrence of paroxysmal atrial fibrillation (PAF) despite the use of standard antiarrhythmic agents prompted the use of new therapeutic approaches. There are few data on systematic assessment of PAF control with stepwise dose escalation and the use of a drug combination. Low-dose quinidine may promote the efficacy of propafenone by inhibiting its degradation through the cytochrome P450 pathway (CYP2D6). We prescribed propafenone 300 to 450 mg/day to 60 patients with PAF for 8 weeks, and 62% were symptomatically controlled. The 19 refractory patients were randomized in a double-blinded fashion to receive either a higher dose of propafenone (450 to 675 mg/day) or the standard dose of propafenone with low-dose quinidine 150 mg/day, each for an 8-week study period, and subsequently crossed over to the alternative treatment. The resulting serum propafenone concentrations were 259 +/- 208 and 336 +/- 237 mg/day (p >0.5), respectively. Both treatment arms prolonged the time to the first symptomatic atrial fibrillation (AF) recurrence and the interval between attacks, and AF was controlled in 37% of patients. However, the higher dose of propafenone was associated with gastrointestinal side effects not present with the low-dose quinidine combination. Of the 10 refractory patients, 7 were further controlled with a standard dose of propafenone plus quinidine (600 mg/day). Overall, control of PAF was achieved in 85% of patients at the end of 8 months; adverse effects necessitating withdrawal were observed in 6%, and uncontrolled AF in 5% of patients. There was no difference in the mean AF rate during recurrences in all phases, and ventricular proarrhythmia was not seen. This study documents the role of stepwise antiarrhythmic treatment of PAF. The use of a standard dose of propafenone, followed by low-dose quinidine combination to reduce propafenone degradation, and the combined standard dose of propafenone and quinidine may be used to maximize efficacy and tolerability.

Usefulness of intravenous metoprolol to prevent syncope induced by head-up tilt.

Intravenous metoprolol was found to be significantly more effective than placebo in preventing head-up tilt-table induced neurally mediated syncope. The reproducibility of acute tilt-table testing is only 63% and suggests caution in the interpretation of acute drug testing during tilt-table studies.

Benefit/risk of estrogen therapy in cardiovascular disease: current knowledge and future challenges.

In the United States, cardiovascular disease represents the leading cause of death among women. A majority of the deaths are due to coronary disease. In addition, the incidence of heart attacks increases with age. Among those who are 65 years of age or older, the estimated heart attack rate is 374,000 per year for women, compared with 440,000 per year for men. In the past three decades, a number of observational studies have suggested that estrogen therapy can reduce the risk of coronary disease in postmenopausal women. This protective effect appears to be much greater in women who have existing coronary disease. These observational data point to the potential usefulness of estrogen therapy in preventing cardiovascular death among women. Although large, well-controlled, clinical trials are needed to confirm the benefit of estrogen therapy, several important findings strongly support the cardioprotective effect of estrogen therapy. For example, in monkeys estrogen prevents the accumulation of low-density lipoprotein (LDL) cholesterol (a known risk factor for heart disease) in coronary arteries, and estrogen has also been shown to increase high-density lipoprotein (HDL) cholesterol (a known cardioprotective factor). Estrogen also possesses a vasodilating property, which can improve cardiac performance in ischemic heart disease. In addition, recent studies have demonstrated that estrogens (especially equilin) exhibit a high antioxidant effect, which may also be related to cardioprotectivity. Although estrogen therapy has been observed to decrease the risk of coronary disease, long-term estrogen therapy has also been found to increase the risk of uterine carcinoma; the addition of progesterone to estrogen therapy may lessen this undesirable risk, however. On the other hand the addition of progesterone to estrogen therapy may decrease estrogen's beneficial effect on HDL cholesterol. What should be the present position on estrogen therapy in postmenopausal women? What is the best dosage regimen? Should it be used alone or in combination with a progesterone? These important issues are discussed, as are several current clinical trials addressing the issue of estrogen therapy in postmenopausal women.

Lorcainide for the treatment of refractory ventricular tachycardia: clinical and electrophysiologic results.

The electrophysiologic effects and antiarrhythmic efficacy of lorcainide were evaluated using programmed electrical stimulation (PES) in 14 patients with ventricular tachycardia (VT) refractory to conventional drug therapy. Lorcainide was administered orally (200-400 mg/d, eight patients), intravenously (150 mg/d, one patient), or by both routes (250-380 mg/d, five patients) prior to PES. In 13 patients undergoing both control and lorcainide PES, lorcainide increased the QRS duration (102 +/- 28 to 125 +/- 28 ms, P less than .001) and the QTc interval (430 +/- 39 to 471 +/- 32 ms, P less than .01) but had no effect on the RR interval (786 +/- 156 to 780 +/- 172 ms, P greater than .2). The right ventricular effective refractory period increased from 258 +/- 8 to 285 +/- 22 ms (P less than .001). Lorcainide prevented VT induction or resulted in induction of only well-tolerated, nonsustained VT in six of 14 patients (43%). The cycle length of induced VT increased from 264 +/- 32 to 306 +/- 34 ms (P less than .01). Of six patients started on chronic therapy, four still receive lorcainide after 18 +/- 7 months. Adverse effects have consisted mainly of sleep disturbances. Thus, it can be stated that lorcainide is effective in certain patients with VT refractory to conventional therapy.

An evaluation of the pharmacokinetics, pharmacodynamics, and dialyzability of verapamil in chronic hemodialysis patients.

The pharmacokinetics and pharmacodynamics of verapamil were investigated in six chronic hemodialysis patients. A single oral 120-mg dose was administered both on a non-hemodialysis day and a hemodialysis day separated by greater than or equal to 7 days. Blood pressure and PR interval were measured simultaneously with each blood sample. Plasma verapamil and norverapamil concentrations were analyzed by high pressure liquid chromatography. The mean Cmax, tmax, AUC, apparent plasma clearance, and terminal t 1/2 were 190 +/- 108 ng/mL, 0.6 +/- 0.2 hour, 676 +/- 443 ng.hr/mL, 3926 +/- 1933 mL/min, and 11.4 +/- 4.0 hr, respectively, on the nonhemodialysis day. The dialysis clearance of verapamil and norverapamil was negligible. The t 1/2 during hemodialysis was 3.6 +/- 1.1 hr, compared with 3.4 +/- 0.7 hr during the same period of time postdose on the nonhemodialysis day (NS, P greater than .05). Systolic and diastolic blood pressure decreased for up to 4 hours postdose, whereas the PR interval tended to increase. Conclusions include: (1) the single oral-dose pharmacokinetics and pharmacodynamics of verapamil in chronic hemodialysis patients are similar to published data in normal subjects and cardiac patients and (2) verapamil and norverapamil are not significantly removed by hemodialysis, so that supplemental doses are not necessary.

Clinical and electrophysiologic effects of flecainide in patients with refractory ventricular tachycardia.

The electrophysiologic effects and antiarrhythmic efficacy of flecainide were evaluated by electrophysiologic study (EPS) in 20 patients with ventricular tachycardia (VT) refractory to an average 2.9 drugs. In 19 patients EPSs were performed with patients not receiving antiarrhythmic medications and receiving oral flecainide therapy at steady state (mean dose, 235 +/- 67 mg/day). Flecainide significantly increased the QRS complex duration (27%, P less than .001), PR interval (17%, P less than .001), and right ventricular effective refractory periods 8.5% and 21.1% (P less than .01) for the first and second extrastimuli, respectively. During baseline EPS, 17 patients were induced into VT and two were noninducible. Flecainide prevented EPS-induced VT in five patients and the induced VT became slow and hemodynamically stable in three. Two patients who failed flecainide monotherapy were induced into slow hemodynamically stable VT with flecainide in combination with amiodarone. The two noninducible patients, during baseline EPS, had suppression of spontaneous VT with flecainide. Overall, 13 of 20 patients received flecainide either alone or in combination with amiodarone for chronic therapy. Side effects encountered during the study consisted of blurred vision, dizziness, weakness, lethargy, nausea, worsened heart failure and bradyarrhythmias. After a mean 9-month follow-up (3 to 16 months) nine patients remain on flecainide therapy. There were three recurrences of slow, hemodynamically stable VT and no episodes of sudden death. Low-dose flecainide, either alone or in combination with other agents, is effective therapy for certain patients with refractory VT but heart failure remains a significant concern in patients with depressed left ventricular function.

Acute effects of combination of IB and IC antiarrhythmics for the treatment of ventricular tachycardia.

There are limited data on the effects of Class IB and IC antiarrhythmic drug combination for the treatment of ventricular tachycardia. The present study evaluated this combination in 12 patients who had sustained ventricular tachycardia (SuVT) during programmed electrical stimulation (PES) and failed IC antiarrhythmic therapy. Following combination of lidocaine and a IC agent (7 with encainide and 5 with flecainide), two had no inducible ventricular tachycardia (VT) and one had nonsustained VT (NSVT). In seven of nine patients who still had SuVT, the mean VT cycle length increased 40 +/- 25 msec post combination compared to IC antiarrhythmic therapy. Seven patients who had a favorable response to the initial combination (less than 10 beats of NSVT, or greater than or equal to 10 beats of VT with a greater than 100 msec increase in cycle length compared to baseline and no hemodynamic compromise) were then placed on IC + oral IB agent (5 with mexiletine, 2 with tocainide). Similar effects on VT inducibility and cycle length were observed following the oral combination. In conclusion, the addition of lidocaine to IC therapy produced favorable effects on induced ventricular tachycardia in 58% of patients compared to IC agent alone. Also, a positive PES response to lidocaine and IC therapy corresponded to a similar positive response when either mexiletine or tocainide was substituted for lidocaine.

Efficacy of class 1C antiarrhythmic agents in patients with inducible ventricular tachycardia refractory to therapy with class 1A antiarrhythmic drugs.

The efficacy of class 1C antiarrhythmic agents was determined in 36 patients with inducible sustained monomorphic ventricular tachycardia during baseline electrophysiology study (EPS), who continued to have inducible monomorphic ventricular tachycardia during EPS on class 1A antiarrhythmic therapy. Of 12 patients who partially responded to class 1A drugs, 11 (91.7%) continued to have a partial response during EPS on class 1C therapy, whereas one patient did not respond. Of 24 nonresponders to class 1A therapy, 2 (8.3%) responded during EPS on class 1C therapy, 7 (29.2%) partially responded, and 15 (62.5%) did not respond. In the 24 nonresponders to class 1A therapy, 9 of 17 patients (53%) with left ventricular ejection fraction (EF) > or = 30% responded or partially responded to class 1C therapy, compared with none of 7 patients with EF < 30% (P < .05). The EPS on class 1C agents in patients who fail to respond to class 1A therapy may be warranted only in those with EF > or = 30%.

Clinical pharmacokinetics of controlled-release disopyramide in patients with cardiac arrhythmias.

UNLABELLED: The pharmacokinetics of the controlled-release preparation of disopyramide phosphate (Norpace CR, Searle Laboratories, Chicago, IL) were studied in ten patients with cardiac arrhythmias. Multiple-serum disopyramide concentrations were obtained after a 300-mg oral dose. Each patient then received chronic oral therapy with the controlled-release preparation (400 to 1000 mg/day) on an every-12-hour schedule. At steady state, disopyramide trough concentrations were obtained. Serum disopyramide concentrations were determined by high performance liquid chromatography. The regimen was well tolerated by all patients. The mean (+/- SD) time to maximum concentration, maximum concentration, and concentrations 11 and 24 hours after the initial dose were 5.5 +/- 1.3 hours and 2.8 +/- 0.8, 2.0 +/- 0.9, and 1.2 +/- 0.5 micrograms/mL, respectively. A low Cmax to trough concentration ratio of 1.35 +/- 0.26 was observed after the initial dose. Linear regression analysis of the serum disopyramide concentrations 11 hours after initial dose (trough) versus trough concentrations at steady state (dose adjusted) showed a strong correlation (r = 0.87, intercept = 0.03, and slope = 1.9). Regression analysis also showed a strong relationship between the area under the curve (AUC) from time 0 to 11 hours after the initial dose and the trough at steady state (r = 0.86). CONCLUSIONS: The controlled-release preparation of disopyramide, when administered every 12 hours in patients with cardiac arrhythmias, should produce low peaks to trough fluctuations. Because disopyramide concentrations after the initial dose correlate well with trough concentrations at steady state, these concentrations may provide a simple and convenient method for prospective monitoring of disopyramide therapy in patients receiving the controlled-release preparation.

Terbutaline infusion in cardiogenic shock: acute hemodynamic effects and clinical response.

The effect of terbutaline infusion was studied in six patients with cardiogenic shock due to acute myocardial infarction. Terbutaline was initiated at 3 micrograms/kg/min, and the subsequent infusion rate was adjusted according to heart rate and blood pressure. At 3 hours after infusion arterial pressure increased from 62 +/- 13 mm Hg (mean +/- S.D.) to 89 +/- 13 mm Hg (P less than 0.001), cardiac index increased from 1.38 +/- 0.29 liter/min/m2 to 2.68 +/- 0.47 liter/min/m2 (P less than 0.001), and heart rate increased from 92 +/- 32 beats/min to 112 +/- 29 beats/min (P less than 0.005). Pulmonary artery wedge pressure fell from 24 +/- 7 mm Hg to 17 +/- 3 mm Hg (P less than 0.01), right atrial pressure fell from 12 +/- 4 mm Hg to 6 +/- 3 mm Hg (P less than 0.005), and systemic vascular resistance fell from 1880 +/- 641 dyn-sec/cm5 to 1515 +/- 418 dyn-sec/cm5 (P less than 0.05). In addition, urine flow increased from 4 +/- 6 ml/hr to 314 +/- 237 ml/hr (P less than 0.05), and subjective improvement was noted in all subjects. Undesirable effects observed were hypokalemia (all subjects), supraventricular tachycardia (one subject), and ventricular ectopic beats (three subjects), which responded to potassium replacement and other treatments. All patients required prolonged maintenance infusion to maintain adequate hemodynamic and clinical response. Four patients were weaned off from maintenance therapy after a mean duration of 4.8 days and eventually were discharged from the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial metabolic effects of intravenous terbutaline in patients with severe heart failure due to coronary artery disease.

Intravenous terbutaline, 0.3 mg/kg/min for 30 minutes followed by 0.15 mg/min for 60 minutes, was studied in nine patients with severe heart failure due to documented coronary artery disease. Hemodynamic and myocardial metabolic effects were measured during terbutaline infusion. Cardiac index and stroke index increased, whereas mean pulmonary artery wedge pressure and pulmonary vascular resistance decreased significantly. No significant alterations in aortic oxygen content, coronary sinus oxygen content, myocardial oxygen extraction, and myocardial lactate extraction were observed during terbutaline infusion. No patient developed angina or electrocardiographic changes suggestive of ischemia. These results indicate that intravenous terbutaline infusion, at the dosage employed, produces beneficial hemodynamic effects without a deterioration of myocardial metabolism in patients with heart failure due to coronary artery disease.

Mexiletine in the treatment of recurrent ventricular tachycardia. Prediction of long-term arrhythmia suppression from acute and short-term response.

Acute intravenous and short-term oral mexiletine therapy was effective in suppressing the arrhythmia in six of eight patients with recurrent ventricular tachycardia. Five of the six patients who were placed on maintenance therapy remained asymptomatic during a mean follow-up of 15 months. The study shows that the acute and short-term suppression of ventricular tachycardia by mexiletine can be a useful predictor of its long-term efficacy.

A comparison of 10% pentastarch and 5% albumin in patients undergoing open-heart surgery.

Colloids are useful in cardiac surgery to increase preload and improve cardiac output without the risks associated with blood transfusions. Pentastarch is a new low-molecular weight hydroxyethyl starch compound under investigation for this purpose. The authors compared, in a randomized fashion, 12 patients who received pentastarch and 17 patients who received albumin for volume expansion after open-heart surgery. During the 24-hour study period there was no significant difference between the two groups with respect to systemic blood pressure, mean arterial pressure, cardiac index, right atrial pressure, and pulmonary capillary wedge pressure, with the exception of a higher mean arterial pressure and systolic blood pressure at 4 hours in the albumin group and higher heart rate at 12 hours in the pentastarch group. In addition, postoperative prothrombin time, partial thromboplastin time, fibrinogen, platelets, and factor VIII levels were not significantly different between the two groups. There were no complications attributed to colloid administration. The hemodynamic parameters were further evaluated in a subset of 6 pentastarch and 9 albumin patients who received the first 500 mL of colloid in a similar time frame and under similar clinical conditions. The patients who received pentastarch showed a significantly greater increase in cardiac index than did the patients who received albumin. No significant change in other parameters were noted between the two groups. The authors conclude that pentastarch is as safe as albumin and may be a more effective volume expander than albumin when used in open-heart surgery patients.

Efficacy of intravenous granisetron in suppressing the bradycardia and hypotension associated with a rabbit model of the Bezold-Jarisch reflex.

This study investigated whether granisetron, a 5-HT3 receptor antagonist, can alter the Bezold-Jarisch reflex (i.e., hypotension and inappropriate heart rate slowing). A hemorrhagic rabbit model that has been shown to induce the Bezold-Jarisch reflex was used. In 11 rabbits (3.8 kg), catheters were placed in the carotid arteries one day before experimental hemorrhage. On the day of the study, the rabbits were given intravenous granisetron (50 micrograms/kg) or an equal volume of saline. Five minutes after administration of granisetron or saline, hemorrhage was induced by continuous blood withdrawal at 5 mL/min and blood pressure (BP) and heart rates were obtained at frequent intervals until systolic BP declined to 80 mmHg. Six rabbits received saline and five granisetron. An average of 77.6 mL +/- 16.4 mL of blood was removed in the group receiving granisetron (compared with 56.5 mL +/- 13.1 mL for the saline group) before achieving the target systolic BP of 80 mmHg. The group receiving granisetron demonstrated the same ability to increase their heart rate from baseline as the saline group. However, the granisetron group had a final heart rate that was closer to their maximal heart rate than the saline group. In this animal model, granisetron was significantly more effective at preventing inappropriate heart rate slowing and allowed significantly more blood to be removed before reaching the target blood pressure. This implies that granisetron may be effective in preventing vasovagal syncope, although further study should be carried out to verify these potentially interesting findings.