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Biomedical subjects

M S Chow

Publications and source records attributed to M S Chow.

At least 19 recordsLinked to original sources
PubMed1992

Effects of different dosages and modes of sodium bicarbonate administration during cardiopulmonary resuscitation.

Systemic acidosis occurs during cardiac arrest and cardiopulmonary resuscitation (CPR). The present study investigated the effect of different modes of sodium bicarbonate administration on blood gas parameters during CPR. Arterial and venous blood gases were obtained during 10 minutes of CPR which was preceded by 3 minutes of unassisted ventricular fibrillation in 36 dogs. Following 1 minute of CPR, the animals received one of four treatments in a randomized and blinded manner: normal saline (NS), sodium bicarbonate bolus dose 1 mEq/kg (B), sodium bicarbonate continuous infusion 0.1 mEq/kg/min (I), and sodium bicarbonate bolus dose (0.5 mEq/kg) plus continuous infusion 0.1 mEq/kg/min (L+I). Eleven dogs completed NS, 8 B, 8 I, and 9 L+I protocol. Following NS infusion, both arterial and venous pH declined consistently over time. Significant differences compared with NS treatment in venous pH were observed at 12 minutes of ventricular fibrillation (L+I, 7.27 +/- 0.05; NS, 7.15 +/- 0.05; B, 7.20 +/- 0.05; I, 7.24 +/- 0.04, each bicarbonate treatment versus NS, and L+I versus B, (P < .05). The B group had an elevated venous PCO2 (mm Hg) concentration following 6 minutes of ventricular fibrillation compared with NS, L+I, and I groups (81 +/- 14 versus 69 +/- 10 versus 68 +/- 10 versus 71 +/- 8, respectively, (P = .07). Arterial pH and PCO2 values showed a similar trend as the venous data with the L+I group demonstrating arterial alkalosis (pH > 7.45) at 12 minutes of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1992

Diltiazem improves resuscitation from experimental ventricular fibrillation in dogs.

OBJECTIVE: To determine the effect of diltiazem on survival immediately after cardiac arrest and cardiopulmonary resuscitation (CPR) in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large, university-affiliated medical center. SUBJECTS: Twenty-eight mongrel dogs, weighing 12 to 16 kg. INTERVENTIONS: After the administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, right ventricle, and great cardiac vein (12 dogs) for sample collection, pressure determinations, and induction of ventricular fibrillation. Dogs were randomized to receive either diltiazem, calcium chloride, or placebo (saline) either before or early during CPR. Dogs underwent 3 mins of unassisted fibrillatory arrest followed by 10 mins of standard CPR using a pneumatic device. After 13 mins of ventricular fibrillation, defibrillation was attempted repeatedly for less than or equal to 10 mins. Successful resuscitation was defined as an organized rhythm with an unassisted systolic BP of greater than 60 mm Hg for greater than or equal to 2 mins. MEASUREMENTS AND MAIN RESULTS: The resuscitation rate was significantly greater in diltiazem-treated animals (100%) than in those dogs receiving calcium (57%) or placebo (29%). Diltiazem-treated animals were resuscitated faster and required fewer defibrillation attempts than did dogs in the other groups. During CPR, coronary artery perfusion pressure and blood gases (arterial, venous, and myocardial) were similar among treatment groups. CONCLUSIONS: Diltiazem improves the resuscitation from experimentally induced ventricular fibrillation when administered before or early during CPR. This response may have important clinical implications in the treatment of patients undergoing cardiac arrest and CPR.

Analysis of Variance↗
PubMed1992

Evaluation and comparison of the adverse effects of streptokinase and alteplase.

The frequency and severity of adverse effects resulting from the administration of streptokinase and alteplase were determined in 126 consecutive patients who received standard dosages of these agents for the treatment of acute myocardial infarction. Evaluation was based on patient assessment by nursing staff, physicians, and the investigators before, during, and after thrombolytic administration. Overall, adverse effects occurred in 15 (41.7%) of 36 patients receiving streptokinase and 12 (13.3%) of 90 receiving alteplase (p = 0.001). No major bleeding or neurologic events were documented. Minor bleeding occurred in 13.9% and 7.8% of streptokinase and alteplase recipients, respectively (p = 0.47), and hypotension in 8 (22.2%) and 5 (5.6%), respectively (p = 0.01). The frequency of hypotension associated with streptokinase was significantly higher than that with alteplase. Thrombolytic-induced hypotension was easily managed and was not associated with sequelae.

Adult↗
PubMed1991

Simple and rapid high-performance liquid chromatographic assay for esmolol.

A procedure for determining esmolol concentrations in blood is described. Dichloromethane was used to extract esmolol from the blood and to inhibit the activity of blood esterases. Blood esmolol concentrations were determined by high-performance liquid chromatography using 3-methoxy-O-demethylencainide as the internal standard. The limit of detection of this assay was 5 ng/ml. The relationship between the peak-height ratio of esmolol and the internal standard was linear in the concentration ranges 10-30,000 ng/ml. The mean absolute and relative recoveries of esmolol from blood were 84 and 89%, with coefficients of variation less than 3%. This method has been used in our laboratory for pharmacokinetic and pharmacodynamic studies.

Adrenergic beta-Antagonists↗
PubMed1991

The effect of CPR on plasma diltiazem concentrations in dogs.

STUDY OBJECTIVE: To determine the effect of cardiac arrest with CPR on diltiazem concentrations in dogs. DESIGN: Prospective, double-blind, randomized trial. SETTING: Laboratory at a large university-affiliated medical center. TYPE OF PARTICIPANTS: Twenty mongrel dogs. INTERVENTIONS: Following administration of anesthesia, catheters were placed in the pulmonary artery, aortic arch, left ventricle, and right ventricle. Dogs were randomized to receive diltiazem (0.5 mg/kg) either 60 minutes before or during cardiac arrest with CPR. After 13 minutes of cardiac arrest, defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: Frequent blood samples for diltiazem concentrations were obtained before, during, and after cardiac arrest. The mean diltiazem concentration rose 70% during CPR in the group that received diltiazem before cardiac arrest. The group that received diltiazem during CPR had concentrations five times greater than expected during sinus rhythm. CONCLUSION: Increased diltiazem concentrations are observed during CPR and are probably related to altered distribution encountered during CPR.

Animals↗
PubMed1991

The effect of haloperidol on ventricular fibrillation threshold in pigs.

Ventricular fibrillation has been observed in association with the administration of haloperidol. This study was designed to determine the effect of intravenous haloperidol on ventricular fibrillation threshold (VFT). VFT's were determined prior to and 15 min. following an intravenous infusion of haloperidol (50 mg administered over 10 min.) in five pigs anaesthetized with alpha-chloralose. VFT's were determined using a single stimulus method. Mean arterial pressure (MAP), heart rate (HR), and electrocardiogram (ECG) were monitored continuously. Mean VFT (mA) at baseline and following haloperidol infusion was 50.2 +/- 4.6 and 65.1 +/- 12.8, respectively (P less than 0.05). Mean MAP (mmHg) at baseline and following haloperidol infusion was 127 +/- 32 and 107 +/- 23, respectively (P less than 0.05). Haloperidol infusion did not significantly influence mean HR, QRS duration or corrected QT interval. Intravenous haloperidol increases VFT and decreases MAP in pigs. In this model, haloperidol may offer protection against ventricular fibrillation. Further study is required to determine the clinical significance of the antifibrillatory effect of haloperidol.

Animals↗
PubMed1991

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance.

The interaction between immunoglobulin G (IgG) and ceftriaxone was studied. Using an ultrafiltration method, we performed dose ranging studies at a ceftriaxone concentration range of 1 to 720 micrograms/ml in the presence of various concentrations of human IgG, human serum albumin (HSA), and combinations of IgG and HSA at pH 7.4 and 37 degrees C. The results showed that ceftriaxone binding to IgG was nonlinear and was consistent with the presence of two binding sites that possess different binding capacities and affinities. Except for increased peak percent binding as the IgG concentration increased, the binding characteristics did not change with IgG concentration. Binding to HSA was consistent, with the presence of only one high-affinity binding site. A mathematical model based on the observed data was constructed; this model was used to predict protein binding at various concentrations of drug, IgG, HSA, or combinations of IgG and HSA in buffer and in plasma medium. Correlations between the observed versus the predicted values were excellent in both media. Simulations with the model indicated that patients with hypergammaglobulinemia have an increased potential of being exposed to prolonged subinhibitory concentrations of ceftriaxone if the drug is given once every 24 h.

Ceftriaxone↗
PubMed1991

The controversy of heparin therapy as an adjunct to thrombolysis in acute myocardial infarction.

Heparin is used routinely in the US as adjunct therapy for prevention of reocclusion after thrombolysis during acute myocardial infarction. A review of the literature shows controversy over the efficacy of heparin following thrombolysis. Both beneficial and a lack of beneficial effects have been reported with heparin. From a pathophysiologic viewpoint, there appears to be a need for full heparinization in the postlytic period because the residual stenosis is highly thrombogenic. However, optimal dose, time, and mode of heparin therapy has not been defined. Despite a lack of definitive data, it seems reasonable to administer intravenous heparin immediately after thrombolytic therapy to achieve a partial thromboplastin time 1.5-2.0 times control that is concurrent with an antiplatelet agent such as aspirin. These recommendations are consistent with the consensus opinion of the American College of Cardiology and the American Heart Association.

Drug Therapy, Combination↗
PubMed1990

The time to reach steady state after the administration of intravenous bolus, constant infusion, and oral immediate-release and sustained-release preparations.

Based on one-compartment pharmacokinetic model, the equations to calculate the specific fractional steady-state of drug level achieved at any time (FSS) after administration of intravenous bolus, constant infusion, and oral immediate-release preparations are reviewed. Also the equation to calculate FSS after administering an oral sustained-release dosage form is derived. From these equations, it can be shown that the drug FSS after these routes of administration is dependent primarily on the elimination rate constant (K). However, for a sustained-release preparation, the FSS is dependent on K, drug release rate constant (Kr), as well as the fraction of sustained release (Fs) of the dosage form. Using the new derived equation for FSS, several simulations were performed to evaluate the effects of Kr K, and Fs. These indicate that the time to achieve a given FSS is prolonged as Kr or K becomes smaller and as Fs becomes large.

Administration, Oral↗
PubMed1989

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.

Anilides↗
PubMed1989

Differences in systemic and myocardial blood acid-base status during cardiopulmonary resuscitation.

Simultaneous arterial (aortic), mixed venous (pulmonary artery), and myocardial venous (great cardiac vein) blood gas and lactate concentrations were obtained in 12 dogs before and during cardiac arrest and CPR. We observed marked mixed venous and myocardial venous acidosis and increased PaCO2 but normal pHa and reduced PaCO2. Furthermore, the pH was significantly lower and the PCO2 significantly higher at the myocardial venous site compared to the mixed venous site, and marked myocardial lactate production occurred during CPR. Calculated bicarbonate and CO2 content (CCO2) did not increase during CPR from any site compared to control values and actually decreased significantly in arterial and myocardial venous samples. Changes in hydrogen ion concentration in both mixed venous and myocardial venous blood correlated with changes in lactate concentration but not total CCO2. Our results during CPR demonstrate a) a significant discrepancy between arterial and mixed venous blood gases but also a large and significant discrepancy between mixed venous and myocardial venous blood gases, b) significant anaerobic systemic and myocardial metabolism, and c) that mixed venous and myocardial venous acidosis is possibly a result of lactic acidosis.

Acid-Base Equilibrium↗
PubMed1989

Epinephrine versus methoxamine in survival postventricular fibrillation and cardiopulmonary resuscitation in dogs.

Previous studies have indicated that methoxamine (an alpha adrenergic receptor agonist) may provide an advantage compared to epinephrine (a mixed alpha and beta adrenergic agonist) during cardiac arrest and CPR. To test this theory, we compared the effects of bolus injections of epinephrine vs. methoxamine on survival, hemodynamic variables, blood gases, and blood lactate concentrations during ventricular fibrillation and CPR in 12 dogs. Each dog underwent a 3-min fibrillatory arrest followed by 10 min of fibrillation and CPR, at which time the animals were defibrillated. Epinephrine (0.05 mg/kg, n = 6) or methoxamine (2 mg/kg, n = 6) was administered at the start of CPR. Both epinephrine and methoxamine produced identical survival rates (5/6) with no differences in coronary perfusion pressure gradients or blood gases (aortic, venous, or great cardiac venous pH, PaO2, or PaCO2) during CPR. Also, there were no differences between the two study groups in myocardial lactate or oxygen extraction ratios during CPR. We conclude that in the dosages tested in our experimental model, epinephrine and methoxamine produce similar results in the variables which we measured.

Animals↗
PubMed1988

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.

Aged↗
PubMed1988

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.

Adult↗
PubMed1988

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.

Adult↗