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Biomedical subjects

M S Chow

Publications and source records attributed to M S Chow.

At least 55 records · Page 3Linked to original sources

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.

Aged↗

A method of determining the in vivo drug release rate constant of sustained-release preparation.

Assuming a one-compartment model and first-order processes for drug release, absorption, and elimination, a new equation to describe the fraction of drug to be absorbed (1-Ft) for a sustained-release product is derived. Based on this equation, when In(1-Ft) vs. time is plotted, the slopes yield the drug release rate constant (Kr), the drug absorption rate constant (Ka), and two intercepts that are a mixed function of Ka, Kr, and the fraction of sustained-release (Fs). The accuracy of this equation to generate pharmacokinetic parameters, such as Ka, Kr, Fs, and the bioavailability-volume of distribution ratio (FD/V) was tested by fitting this equation to multiple simulated plasma concentration-time data (5 sets errorless and 75 sets errant data). The absolute percentage error of Ka and FD/V estimated by this equation is much less than that of traditional polyexponential equation, whereas the absolute percentage error of Kr estimated by this equation is statistically significantly less than that of traditional polyexponential equation. Furthermore, with this equation, it is easier to estimate Fs than with traditional equation. An application of this equation in generating these parameters is illustrated for a quinidine sustained-release dosage form-quinidex.

Delayed-Action Preparations↗

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.

Aged↗

Patency of internal thoracic artery grafts: comparison of right versus left and importance of vessel grafted.

BACKGROUND: The early and late patency of the left internal thoracic artery (LITA) has been studied thoroughly, but less is known about coronary artery bypass grafts constructed from the right internal thoracic artery (RITA). METHODS AND RESULTS: Between January 1984 and March 1991, 413 patients on two surgical services had bilateral arteries or RITAs used as conduits for coronary artery revascularization. Sixty-seven patients (16%; 57 male and 10 female; mean age, 59 years) had graft angiography performed up to 97 months after operation (average, 27 months). In 38 patients, angiography was performed because of angina or other objective evidence of myocardial ischemia. For all 67 patients evaluated, patency of RITA grafts was 86% (58/67), and patency of LITA grafts was 89% (57/64). For grafts to the left anterior descending (LAD) coronary artery, overall patency was 90% (58/64), and there was little difference in patency of the RITA (93%, 28/30) versus the LITA (88%, 30/34). In contrast, the overall patency rate for internal thoracic arteries used to bypass vessels other than the LAD was 76% (45/59, P < .03 versus LAD); for these bypasses to arteries other than the LAD, RITA patency was 74% (26/35), and the patency of LITA grafts was 79% (19/24). Patency of RITA grafts routed through the transverse sinus was similar to patency of other bypasses to non-LAD vessels. Among 12 free grafts that used segments of the RITA, 10 were patent (83%). Of additional saphenous vein grafts, 69% (39/56) were patent at restudy. CONCLUSIONS: This study supports the continued use of the RITA as a conduit for coronary artery revascularization. In our experience, the position of the target vessel is a more important determinant of graft patency than the side of the internal thoracic artery selected for use as a bypass graft.

Coronary Angiography↗

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%.

Adult↗

Evaluation of the need to modify antiarrhythmic therapy because of drug intolerance or inefficacy in patients evaluated by electrophysiology study.

The incidence of recurrent ventricular tachycardia (VT) and drug intolerance after therapy guided by electrophysiology study (EPS) leading to a change in antiarrhythmic therapy is unknown. To explore this issue, we studied 138 patients undergoing EPS with a serial drug-testing protocol. Patients were followed for 24 +/- 21 months (range 1 to 91 months) for recurrent VT, drug intolerance, or both. At baseline EPS, sustained VT (76%), nonsustained VT (20%), and ventricular fibrillation (4%) were induced. On discharge antiarrhythmic therapy, 70 (51%) patients were noninducible (< 16 beats) and 68 (49%) patients remained inducible. Of the 138 patients, 56 (41%) required modification of antiarrhythmic therapy (change in drug or dose) for recurrent VT (n = 20) or drug intolerance (n = 36). These events occurred early during follow-up (8 +/- 12 months). Patients who were rendered noninducible had a greater likelihood of remaining free of antiarrhythmic modification than patients who remained inducible at 1-year (68% and 60%, respectively) and 2-year (63% and 52%, respectively) follow-up examinations (p < 0.05). Likewise, the noninducible patients had a greater likelihood of remaining free of recurrent VT than inducible patients at 1-year (95% and 80%, respectively) and 2-year (92% and 80%, respectively) follow-up testing (p < 0.025). In contrast, the likelihood of remaining free of drug intolerance was similar between inducible and noninducible patients at 1 year (72% and 75%, respectively) and 2 years (69% and 65%, respectively). We conclude that antiarrhythmic therapy guided by EPS requires early modification in more than 40% of patients during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

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.

Adult↗

Antifibrillatory and electrophysiologic actions of moricizine alone and in combination with lidocaine: a prospective, randomized trial.

OBJECTIVE: The Cardiac Arrhythmia Suppression Trial II showed that moricizine acutely increases the occurrence of sudden cardiac death. Thus the objective of this investigation was to evaluate the antifibrillatory properties of moricizine (a new antiarrhythmic agent) alone and in combination with lidocaine (an established antifibrillatory agent). DESIGN: Prospective, double-blind, randomized, placebo-controlled trial. SETTING: Laboratory at a large, university-affiliated medical center. SUBJECTS: Eighteen domestic farm swine with a mean weight of 39 +/- 5 kg. INTERVENTIONS: After pentobarbital anesthesia, the animals were instrumented. A bipolar pacing catheter was placed in the right ventricular apex and a pig-tail catheter was placed in the aortic arch for induction of ventricular fibrillation and aortic blood pressure monitoring. Subsequently, the pigs were randomized to moricizine or control (0.9% saline) groups. Each group underwent three treatment phases: baseline, drug (moricizine 2 mg/kg loading dose, 1.5 mg/kg/hr infusion, or saline bolus and infusion), and drug combined with lidocaine (5 mg/kg loading dose, 4 mg/kg/hr infusion). Ventricular fibrillation threshold was determined every 5 to 10 mins over a 1-hr period during each treatment phase. RESULTS: Ventricular fibrillation threshold values in the animals randomized to control were 16.8 +/- 7.6, 18.1 +/- 8.9, and 23.9 +/- 10.4 mA at baseline during saline infusion, and when saline was combined with lidocaine, respectively. The values during the saline-lidocaine combination treatment phase were significantly greater than the values at baseline and during saline treatment alone (p < .001). Ventricular fibrillation threshold values in the animals randomized to receive moricizine were 15.5 +/- 4.4, 18.1 +/- 5.1, and 21.1 +/- 8.4 mA at baseline, during moricizine infusion, and when moricizine was combined with lidocaine. The values during the lidocaine-moricizine combination treatment phase were significantly greater than values at baseline (p = .005), but not during moricizine treatment alone (p = .16). The increase in ventricular fibrillation threshold from baseline to moricizine (17%) was similar to the increase from baseline to saline (7%), p = .37. The increase in ventricular fibrillation threshold when lidocaine was added to moricizine (13%) was less than the increase with lidocaine alone (32%), p = .05. CONCLUSION: In this experimental model, moricizine, at the dose studied, lacked antifibrillatory properties. Moreover, moricizine did not contribute to the antifibrillatory effects of lidocaine.

Animals↗

Stability of famotidine in an extemporaneously prepared oral liquid.

The stability of famotidine in an extemporaneously prepared oral liquid stored at 4 and 24 degrees C for 30 days was studied. Famotidine liquid was prepared by pulverizing and suspending 12 40-mg tablets in distilled water. This mixture was diluted with cherry syrup to a total volume of 60 mL, resulting in a famotidine concentration of 8 mg/mL. The liquid was divided into two 30-mL amber glass bottles and stored at 4 degrees C and at room temperature (24 degrees C). Samples from each of the two bottles were assayed for famotidine content by high-performance liquid chromatography. Each sample was assayed in duplicate at time 0 and on days 2, 5, 10, 15, 20, 25 and 30. The concentration of famotidine remained above 90% of original concentration for 20 days at 4 degrees C and for 15 days at room temperature. After 30 days, famotidine concentration was reduced by 15% and 24% at 4 degrees C and room temperature respectively. Famotidine liquid 8 mg/mL compounded extemporaneously from tablets was stable for 20 days at 4 degrees C and for 15 days at 24 degrees C.

Chromatography, High Pressure Liquid↗

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↗

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↗

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↗

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↗

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↗

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↗