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Biomedical subjects

M S Chow

Publications and source records attributed to M S Chow.

At least 37 records · Page 2Linked to original sources
PubMed1998

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.

Animals↗
PubMed1998

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.

Amiodarone↗
PubMed1998

Factors affecting the outcome of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility.

OBJECTIVE: To describe and analyse the factors affecting the pregnancy rate of laparoscopic ovarian drilling for polycystic ovarian syndrome in women with anovulatory infertility. DESIGN: A retrospective study. SETTING: A specialist infertility clinic based at a teaching hospital in England. POPULATION: One hundred and eighteen women, for whom hospital records and follow up data were available, with polycystic ovarian syndrome who underwent laparoscopic ovarian surgery for anovulatory infertility over a five year period, between January 1991 and December 1995. MAIN OUTCOME MEASURES: Ovulation and pregnancy rate. RESULTS: The cumulative conception rate 12 months after the treatment was 54%. Women who conceived following the surgery had a shorter duration of infertility, were treated with diathermy (rather than laser), had higher pre-operative luteinising hormone levels, were younger and were more likely to have ultrasonographic evidence of polycystic ovarian disease. Logistic multiple regression analysis showed that the duration of infertility, modality used in treatment (laser or diathermy) and the pre-operative levels were the main determinants of the outcome. CONCLUSION: Women with polycystic ovarian syndrome respond favourably to laparoscopic ovarian drilling. The success rate in women with infertility duration of less than three years, treated with diathermy, in whom the pre-operative level was more than 10 IU/L reached 79%.

Adult↗
PubMed1998

The pharmacokinetics of intravenous testosterone in elderly men with coronary artery disease.

Intracoronary testosterone injections have recently been shown to possess coronary vasodilating effects. The same may be true for intravenous testosterone, but the pharmacokinetic and hemodynamic aspects need exploration before pharmacologic studies can begin. This trial determined the pharmacokinetic and hemodynamic properties of 300 microg of testosterone given intravenously. Degree of testosterone aromatization to 17-beta estradiol after exogenous administration and overall patient tolerability also were evaluated. Eleven elderly men with coronary artery disease participated in the study and were given 300 microg of testosterone intravenously over 10 minutes. Serum blood concentrations of testosterone and 17-beta estradiol were measured at baseline and then periodically. Testosterone serum concentrations were stripped and fit to a two-compartment model for all patients. The volume of distribution (Vdarea) was 80.36 +/- 24.51 L, and the elimination half-life was 55.93 +/- 23.06 minutes. No hemodynamic differences or side effects were noted. The serum concentrations of 17-beta estradiol were significantly increased from baseline beginning 5 minutes after infusion to the end of the study (180 minutes after infusion).

Aged↗
PubMed1997

Stability of omeprazole in an extemporaneously prepared oral liquid.

The stability of omeprazole 2 mg/mL. in an extemporaneously prepared oral liquid was studied. The contents of five 20-mg omeprazole capsules were mixed with 50 mL of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this liquid were prepared for storage at 24, 5, and -20 degrees C. A 3-mL. sample of each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26, and 30 and assayed by high-performance liquid chromatography. The liquids stored at 5 degrees C and at -20 degrees C did not change color during the study period, but the color of the liquid stored at 24 degrees C changed from white to brown. There were no significant changes in the omeprazole concentrations of the liquids stored at 5 and -20 degrees C during the study period, but the omeprazole concentration of the liquid stored at 24 degrees C was < 90% of the initial concentration on day 18. Omeprazole 2 mg/mL in an oral liquid compounded extemporaneously from capsules and sodium bicarbonate injection was stable for up to 14 days at 24 degrees C and for up to 30 days at 5 and -20 degrees C.

Anti-Ulcer Agents↗
PubMed1997

Stability of granisetron hydrochloride in an extemporaneously prepared oral liquid.

The stability of granisetron 0.2 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral liquid was studied. Twelve 1-mg granisetron tablets were pulverized and suspended in 30 mL of distilled water. This mixture was then diluted with cherry syrup to produce a 60-mL oral liquid with a granisetron concentration of 0.2 mg/mL. Half of the preparation was stored at 5 degrees C, and half was stored at 24 degrees C. Samples were taken on days 0, 1, 2, 3, 4, 6, 8, 10, 12, and 14 and assayed by high-performance liquid chromatography. There was no change in the liquid's color, consistency, or pH, and the concentrations of granisetron ranged from 97% to 104% of initial concentration during the 14 days at 5 and 24 degrees C. Granisetron 0.2 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral liquid was stable for up to 14 days.

Chromatography, High Pressure Liquid↗
PubMed1997

Local delivery of heparin to balloon angioplasty sites with a new angiotherapy catheter: pharmacokinetics and effect on platelet deposition in the porcine model.

The purpose of this study was to assess the efficacy of local heparin delivery to balloon angioplasty sites in an in vivo porcine model by using a newly designed angiotherapy catheter that allows for prolonged drug infusion while maintaining distal arterial perfusion. Protocols were designed to assess the safety of intracoronary drug delivery, the effect of infusion time and drug concentration on intramural heparin deposition, the distribution of heparin within the arterial wall, the histologic effects of local heparin delivery, the wash-out of intramurally deposited heparin, and the effect of heparin delivery on early platelet deposition following balloon injury in peripheral and coronary vessels. Local intracoronary delivery of heparin was well tolerated in all animals. Between 0.04 and 0.08% of infused heparin was intramurally deposited at the time of drug delivery, with longer infusion durations and higher concentrations of heparin resulting in greater intramural deposition. Autoradiography demonstrated homogenous distribution of heparin throughout the intima, media, and adventitia, with localization in the nuclei, cytoplasm, and extracellular space. Histologic analysis demonstrated no additional vessel trauma from local drug delivery beyond that seen with conventional angioplasty. Wash-out studies demonstrated a biexponential disappearance of intramurally deposited drug, with rapid release of heparin over the first 60 min and persistence of small amounts of drug for at least 7 d. Locally delivered heparin significantly attenuated the deposition of platelets in peripheral vessels, although a similar decrease in platelet deposition in the coronary arteries was not statistically significant. Local delivery of heparin directly to coronary angioplasty sites is possible with the use of a new angiotherapy catheter. Wash-out of heparin from the arterial wall is initially rapid, although drug is detectable for up to 1 wk following delivery. In porcine peripheral arteries, use of this technique significantly decreases early platelet deposition following balloon injury.

Angioplasty, Balloon, Coronary↗
PubMed1997

Amiodarone induced torsades de pointes with excessive QT dispersion following quinidine induced polymorphic ventricular tachycardia.

We report a case of amiodarone induced torsades de pointes (TdP) associated with increase QT dispersion in a patient with a history of quinidine induced TdP. An increase in QT dispersion of > 100% was noted on the 12 lead surface ECG postamiodarone therapy. In summary, amiodarone has a potential to induce TdP in patients with a previous history of quinidine induced TdP. QT dispersion could be a potential marker of TdP in these patients.

Adult↗
PubMed1996

Disposition of intravenous amiodarone in subjects with normal and impaired renal function.

In a study designed to determine the influence of renal dysfunction on the disposition of amiodarone and its metabolite, desethylamiodarone (DEA), 30 subjects received a single 5 mg/kg intravenous dose of amiodarone over 15 minutes. Of the 30, 11 had normal renal function (group I; mean +/- SD glomerular filtration rate [GFR] = 118 +/- 20 mL/min/1.73 m2), 9 had renal impairment (group II; GFR = 23 +/- 10 mL/min/1.73 m2), and 10 were long-term hemodialysis patients (group III; 4 of these patients were studied during dialysis). Total and free concentrations of amiodarone and DEA were measured by high-performance liquid chromatography. There were no significant differences between the three groups in mean systemic clearance, steady state volume of distribution, or mean residence time of amiodarone. However, the area under the concentration-time curve (AUC) for amiodarone was significantly higher in group I than in group II, and this finding was related to total body weight. Free fraction was similar in groups I and III. The disposition of amiodarone and its metabolite DEA was similar in patients with normal renal function, moderate renal dysfunction, and end-stage renal disease. Thus, dosage adjustment in patients with renal impairment is not necessary based on this pharmacokinetic analysis.

Adult↗
PubMed1996

Pharmacokinetics of intravenous amiodarone in patients with impaired left ventricular function.

To evaluate the potential need for modification of dose regimens of intravenous amiodarone in patients with left ventricular dysfunction, the pharmacokinetics of amiodarone and its active metabolite, desethylamiodarone (DEA), were examined after a single 15-minute intravenous infusion of amiodarone 5 mg/kg. Three parallel groups of otherwise healthy volunteers with normal (n = 12), moderately impaired (ejection fraction > 30 but < or = 45%; n = 6), or severely impaired (ejection fraction < or = 30%; n = 6) left ventricular function were enrolled in the study. Serial blood samples were obtained over a 76-day period for estimation of pharmacokinetic parameters. With the exception of the half-life (t1/2) of DEA, statistical comparisons revealed no significant between-group differences in pharmacokinetic parameters or correlations between pharmacokinetic parameters and ejection fractions. The t1/2 of DEA was increased by approximately 60% in patients with severe left ventricular dysfunction compared with that in patients with moderately impaired and normal left ventricular function. The rate of DEA formation is slow, however, and its concentration relative to amiodarone is low. Therefore, it is unlikely that concentrations of DEA in serum would reach levels that contribute significantly to the pharmacologic activity of amiodarone during short-term (up to 2 weeks) intravenous amiodarone therapy. Single doses of amiodarone were well tolerated. The results of this study suggest that intravenous amiodarone can be used with appropriate observation to control arrhythmias, regardless of the degree of left ventricular dysfunction.

Adult↗
PubMed1996

Aortic reconstruction in kidney transplant recipients.

Renal transplantation has increased the longevity of patients with uremia. An increasing number undergo aortic reconstruction, which exposes the transplanted kidney to ischemic injury. To evaluate the risk for renal failure, loss of the transplant, and methods of renal protection, we reviewed our experience. Clinical data were reviewed for 10 consecutive patients (7 men, 3 women; mean age 52.7 years [range 32 to 75 years]) with a transplanted kidney who underwent aortic reconstruction between 1977 and 1994 at our institution. Mean interval between renal transplantation and aortic reconstruction was 5.9 years (range 1 month to 12.7 years). Seven patients required emergency repair because of dissection (2 patients), aneurysm rupture (4 patients), or symptomatic aneurysm (1 patient); three underwent elective repair. Reasons for reconstruction included aortic dissection (2 patients), aneurysm of the descending thoracic (2 patients), thoracoabdominal (1 patient), or abdominal aorta (3 patients), and aortoiliac occlusive disease (2 patients). Patients with thoracic or thoracoabdominal reconstructions underwent repair with atriofemoral, aortofemoral, or femorofemoral shunt placement or bypass. Of the five abdominal aortic reconstructions, the kidney was protected with aortofemoral shunt placement in one patient and cold renal perfusion in three. In two of them, topical cooling of the kidney also was used. One patient with acute aortic dissection died at 39 days as a result of respiratory failure. Loss of the recently transplanted kidney was caused by acute rejection. One patient had a transient increase in serum creatinine concentration. Eight no worsening of renal function, and none of the nine survivors lost the transplanted kidney. We concluded that aortic reconstruction can be safely performed in kidney transplant recipients. Patients in whom thoracic or thoracoabdominal aortic reconstruction was required were protected with an atriofemoral or aortofemoral bypass or shunt. Patients undergoing abdominal aortic reconstruction did well when cold renal perfusion with or without local cooling of the transplant was used for renal protection. Transplanted kidneys appeared to tolerate ischemic injury similarly to native kidneys.

Adult↗
PubMed1996

Antifibrillatory effect of esmolol alone and in combination with lidocaine.

The primary objective of this study was to determine the effect of esmolol, administered alone and in combination with lidocaine, on ventricular fibrillation threshold (VFT) in pigs. A secondary objective was to determine the relationship between blood esmolol concentrations and VFT. We determined VFT using a train of electrical stimuli delivered to the right ventricle after eight paced beats at a basic cycle length of 285 ms. Current was increased in 2-mA increments until VF occurred. VFT determinations were performed during administration of esmolol 1,000 mu g/kg/min, during a continuous infusion of lidocaine, and during infusion of esmolol and lidocaine in combination. Mean increases in VFT from baseline during infusion of esmolol and lidocaine alone were 32.3 +/- 12.9 and 8.5 +/- 7.2 mA, respectively (p < 0.05, each drug compared with baseline; p < 0.05, esmolol vs. lidocaine). Mean increase in VFT from baseline during infusion of the combination was 52.0 +/- 22.0 mA (p < 0.05 as compared with baseline and with esmolol or lidocaine alone). The relationship between blood esmolol concentrations and VFT was described by a counterclockwise hysteresis curve, suggesting delay in equilibration of esmolol between blood and site of effect. The antifibrillatory efficacy of esmolol is significantly greater than that of lidocaine in this model. Administration of the two agents in combination resulted in significantly greater antifibrillatory efficacy than that associated with either drug administered alone.

Adrenergic beta-Antagonists↗
PubMed1996

Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic drug monitoring.

Recently, much interest has focused on the use of once-daily aminoglycosides (ODA) in the medical literature. In late 1992, we implemented a hospital-wide ODA program for adult patients at our 850-bed community-teaching hospital. In the first phase of implementation, therapeutic drug monitoring (TDM) was accomplished with the use of a random serum concentration and a nomogram that had been developed at our institution. In the second phase, serum drug concentrations were eliminated on patients with normal renal function. The fully implemented program resulted in a 40% decrease in the request for gentamicin and tobramycin serum concentrations as compared with historic ordering patterns for conventional aminoglycoside dosing regimens. In addition, the incidence of nephrotoxicity was also reduced from 3 to 5% with conventional aminoglycoside dosing, to 1.2 and 1.3% for phases 1 and 2, respectively. Furthermore, the elimination of TDM requests totaling 300 for gentamicin and 50 for tobramycin per month is expected to result in an annual institutional savings of > $100,000.

Adult↗
PubMed1996

Intravenous amiodarone: pharmacology, pharmacokinetics, and clinical use.

OBJECTIVE: To review the clinical pharmacology, pharmacokinetics, and clinical efficacy and safety of intravenous amiodarone. DATA IDENTIFICATION: Articles were identified through a computer search of the English-language literature using MEDLINE (KR Information OnDisc) and the search term amiodarone. Additional articles were identified through examination of the bibliographies of the articles initially retrieved. STUDY SELECTION: Relevant or representative animal studies, clinical trials, and case reports were selected for evaluation. Particular emphasis was placed on studies pertaining to the use of intravenous amiodarone in treatment-refractory ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). DATA EXTRACTION: The literature was assessed for adequate description of patients, study methodologies (e.g., study design, number of patients), and outcomes. DATA SYNTHESIS: Amiodarone is an unusual class III antiarrhythmic that produces each of the four main types of antiarrhythmic action in addition to other effects, such as vasodilatory, selective antithyroid, and other activities that may be therapeutically relevant. Amiodarone pharmacokinetics demonstrate extensive interpatient variability and are characterized by wide tissue distribution (steady-state volume of distribution 40-84 L/kg), slow total body clearance (90-158 mL/h/kg), long terminal elimination half-life (20-47 d), and extensive hepatic metabolism. The onset of maximal antiarrhythmic effect is a function of both amiodarone dosage and time. The high plasma concentrations achieved with intravenous dosing do not fully replicate the electrophysiologic effects observed following long-term oral administration, particularly with respect to class III activity. Available data suggest that intravenous amiodarone is associated with an efficacy rate of 50% or more in treatment-refractory VT/VF, and has a relatively rapid (2-24 h) onset of action. The drug is relatively well tolerated, but close hemodynamic, electrocardiographic, and hepatic function monitoring are required. The value of using amiodarone serum concentrations to guide therapy remains uncertain. CONCLUSIONS: Intravenous amiodarone is an effective, relatively safe antiarrhythmic for the treatment of recurrent, hemodynamically unstable VT/VF refractory to other drug therapy in the acute care setting.

Amiodarone↗