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Biomedical subjects

J Kluger

Publications and source records attributed to J Kluger.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1989

Cifenline in the short-term treatment of patients with ventricular premature complexes: a double-blind placebo-controlled study.

To study the efficacy and safety of cifenline (cibenzoline), a new antiarrhythmic agent, we enrolled 46 patients with greater than 700 premature ventricular complexes (VPCs)/24 h in an ambulatory electrocardiography study. During an open-label titration phase, 25 patients showed greater than 75% VPC suppression while receiving 130 mg (15 patients) or 160 mg (10 patients) cifenline twice daily. During a double-blind placebo-controlled phase in 23 of these patients, cifenline was more effective than placebo in controlling VPCs (p less than 0.0001) and VPC pairs (p less than 0.025). A small (0.01 s) increase in QRS duration was observed (p less than 0.05) during cifenline treatment. Adverse experiences included gastrointestinal complaints and dizziness as well as two instances of hypotension and one instance of symptomatic ventricular tachycardia. Cifenline appears to be effective and well tolerated in the treatment of VPCs.

Adult↗
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↗
PubMed1988

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.

Administration, Oral↗
PubMed1988

Antifibrillatory effects of high dose bretylium and a lidocaine-bretylium combination during cardiopulmonary resuscitation.

Previous CPR studies from our laboratory have shown that a standard iv dose of lidocaine (2 mg/kg) has a rapid antifibrillatory effect, while a standard dose of bretylium (5 mg/kg) produces a delayed but more pronounced effect. In order to determine the optimal doses, we investigated the antifibrillatory effects of a) high dose bretylium (10 mg/kg) and b) a combination of lidocaine (2 mg/kg) and bretylium (5 mg/kg) during CPR in two groups of anesthetized dogs. Ventricular fibrillation threshold (VFT) was determined using a train method and CPR was performed by a pneumatic device. During both a control and drug phase, the VFT was determined in each dog before CPR, and after each of three consecutive 3-min CPR periods. The combination of lidocaine and bretylium (11 dogs) caused a significant increase in VFT compared to the control phase after each of the 3-min CPR periods and maintained this effect for greater than 2 h. Bretylium 10 mg/kg (eight dogs) significantly elevated the VFT only after the third 3-min CPR period. We conclude that the combination of standard doses of lidocaine and bretylium produces a rapid and prolonged antifibrillatory effect and may be the optimal regimen in the CPR setting. High dose bretylium has a delayed onset of effect and appears to produce no greater effect than standard doses of the drug.

Animals↗
PubMed1988

A nonradioactive iothalamate method for measuring glomerular filtration rate and its use to study the renal handling of cibenzoline.

A high-pressure liquid chromatographic method was developed to measure nonradioactive iothalamate in serum and urine for use in estimating glomerular filtration rate (GFR). This method was used to study the renal handling of cibenzoline, an experimental antiarrhythmic drug. The mean cibenzoline clearance was 3.5 +/- 2.5 (SD) times the glomerular filtration rate. The clearance of non-protein-bound cibenzoline was seven times GFR, indicating excretion by the renal tubular secretory pathway for organic bases. This drug, at the doses used, did not lower creatinine clearance, indicating that the effect of basic drugs competing with creatinine for the base secretory pathway appears to be dose and drug dependent.

Adult↗
PubMed1988

Combination high dose amrinone and dopamine in the management of moribund cardiogenic shock after open heart surgery.

Two patients who suffered severe cardiogenic shock after open-heart surgery were successfully resuscitated with high doses of amrinone and dopamine. Both patients had required cardiopulmonary resuscitation and neither was responsive to more conventional mechanical and pharmacologic intervention. Neither patient suffered any serious side effects and both were eventually discharged from the hospital in good condition. These two case reports suggest the potential for using higher than previously reported doses of amrinone in combination with dopamine for the successful treatment of moribund cardiogenic shock in the post open-heart surgical patient. Further studies are needed to assess whether this high-dose drug combination will be successful in patients who present with severe cardiogenic shock unrelated to the post open-heart surgical setting.

Aged↗
PubMed1988

[Preoperative nonspecific immunostimulation with Propionibacterium granulosum KP-45 in patients with colorectal cancer. A prospective randomized study].

The effect of preoperative unspecific immunomodulation with Propionibacterium granulosum KP-45 (P.g.) on postoperative complications and patient survival was evaluated in a prospectively randomized trial in patients with colorectal tumor resection. Patients of the therapy group (n = 51) received at least 3 days before operation an infusion of 10 mg P.g., patients of the control group (n = 49) were not treated at all. The wound infection rate and the number of re-explorations were significantly lower in the therapy group, however, patient survival and tumor recurrence rates were not positively affected by this P.g. pre-treatment.

Clinical Trials as Topic↗
PubMed1987

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.

Adult↗
PubMed1986

Prediction of steady-state trough serum procainamide concentrations after administration of a sustained-release procainamide preparation.

Four methods of predicting steady-state trough serum procainamide concentrations (SPC) were compared in 15 patients receiving sustained-release procainamide (Procan-SR) therapy. All methods were based on a one-compartment pharmacokinetic model. Method 1 utilized nine initial measured SPC and individualized pharmacokinetic parameters for prediction of the steady-state SPC. Method 2 utilized three SPC and individualized pharmacokinetic parameters. Method 3 utilized two SPC and an individualized apparent elimination rate constant plus other average pharmacokinetic parameters. Method 4 utilized all averaged pharmacokinetic parameters (required no initial SPC). The predicted and measured SPCs for each method were analyzed by linear regression. Regression equations and correlation coefficients (r) for Methods 1, 2, 3, and 4 were as follows: predicted SPC = 0.72 measured SPC + 1.60 (r = 0.86), predicted SPC = 0.67 measured SPC + 1.74 (r = 0.82), predicted SPC = 0.13 measured SPC + 2.57 (r = 0.58), and predicted SPC = 0.15 measured SPC + 2.47 (r = 0.52), respectively. The precision, as measured by the mean squared prediction error (95% confidence interval) for Methods 1, 2, 3, and 4 was 1.44 (0.61, 2.27), 1.75 (0.93, 2.57), 2.81 (1.3, 4.49), and 3.68 (1.12, 6.26), respectively. (Eighty-five percent of the predictions were within +/- 1.5 micrograms/ml of the measured SPC by Methods 1 and 2, as compared with 69% by Methods 3 and 4.) Bias, as measured by the mean prediction error (95% confidence interval) for Methods 1, 2, 3, and 4 were -0.44 (-0.90, 0.03), -0.34 (-0.87, 0.18), -0.43 (-1.09, 0.24), and -0.98 (-1.66, -0.31).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Epoprostenol sodium (prostacyclin) infusion in acute myocardial infarction.

Epoprostenol (prostacyclin) is a potent inhibitor of platelet aggregation and causes relaxation of vascular smooth muscle. These effects may be beneficial in patients with acute myocardial infarction. The effect of epoprostenol infusion in patients with acute myocardial infarction was evaluated in a randomised double blind study of 45 patients with evidence of myocardial infarction of less than 16 hours' duration. The patients were given a 72 hour infusion of epoprostenol (23) or placebo (22). The maximum dose was 5 ng/kg/min. The mean time to treatment was 8.3 hours (range 3.8-15.9 hours). The mean dose was 4.9 ng/kg/min. The patients were followed until day 30. No significant differences were found between the groups in mortality, development of congestive heart failure, cardiogenic shock, arrhythmias, recurrent chest pain, reinfarction, peak creatine kinase concentration, or the time taken to attain peak creatine kinase concentration. No significant difference in baseline ejection fraction was noted between groups, and no significant change in ejection fraction occurred within each group or between groups. The only significant side effect was the development of facial flushing in the epoprostenol group. In this pilot study epoprostenol was well tolerated by patients with acute myocardial infarction. No benefit from epoprostenol could be demonstrated at the dose range used when the drug was administered within 16 hours of the onset of symptoms.

Adolescent↗
PubMed1986

The effect of lidocaine and bretylium on the defibrillation threshold during cardiac arrest and cardiopulmonary resuscitation.

The effect of intravenous lidocaine, 2 mg/kg, and bretylium, 5 mg/kg, on defibrillation threshold (DFT) was investigated in alpha-chloralose anesthetized dogs undergoing conventional closed chest cardiopulmonary resuscitation (CPR) following induced ventricular fibrillation. Ventricular fibrillation was induced electrically and CPR was performed by a pneumatic device set to compress the chest 60 times and inflate the lung 12 times a minute. Defibrillation was achieved using underdamped sinusoidal current shocks from a special defibrillator which allowed determination of delivered energy. The DFT was defined as the peak current which defibrillated, but no more than 20% higher than a current which did not defibrillate. All DFTs were obtained within 5 min of CPR. The mean +/- SD current and energy thresholds required for defibrillation during lidocaine-CPR (seven dogs) were 17.0 +/- 8.9 A and 53.0 +/- 40.7 J as compared to 12.5 +/- 6.2 A and 34.3 +/- 30.7 J, respectively during control-CPR (P less than 0.05). The mean +/- SD current and energy thresholds during bretylium-CPR were 11.0 +/- 3.4 A and 24.1 +/- 1.3 J as compared to 11.8 +/- 1.7 A and 29.4 +/- 9.6 J, respectively, during control-CPR (NS). These results show that lidocaine acutely elevated defibrillation threshold whereas bretylium did not produce such an effect. The effect on DFT along with other pharmacologic properties should be considered when lidocaine or bretylium is used in the setting of cardiac arrest and CPR.

Animals↗
PubMed1985

Antifibrillatory effects of lidocaine and bretylium immediately postcardiopulmonary resuscitation.

The antifibrillatory effects of lidocaine and bretylium in the postcardiopulmonary resuscitation (CPR) setting were examined using ventricular fibrillation threshold (VFT) determinations in anesthetized dogs. The dogs were fibrillated and CPR was carried out with a pneumatic device. Lidocaine and bretylium were administered intravenously at the onset of CPR, and VFT was serially determined after defibrillation following three consecutive 3-minute CPR periods. A dose of 2 mg/kg of lidocaine caused a significant increase in VFT determinations after the first but not subsequent 3-minute CPR periods; a dose of 1 mg/kg of lidocaine was ineffective at any time point. A dose of 5 mg/kg of bretylium elevated the VFT after the second and third but not the first 3-minute period. In dogs who received lidocaine, a significant elevation of VFT determinations were found to be associated with a high blood lidocaine concentration (mean 13.8 +/- 8.3 micrograms/ml). The present study demonstrates that a 2 mg/kg dose of lidocaine administered during CPR rapidly increases VFT determinations after CPR (within 5 minutes), whereas, a 5 mg/kg dose of bretylium significantly elevates VFT determinations but at a later time (within 10 minutes). The observed significant effect of lidocaine appears to be associated with high lidocaine blood concentrations (greater than 6 micrograms/ml).

Animals↗