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Biomedical subjects

J Kluger

Publications and source records attributed to J Kluger.

At least 73 records · Page 4Linked to original sources
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

Effect of chronic oral moricizine and intravenous epinephrine on ventricular fibrillation and defibrillation thresholds.

The purpose of this study was to determine the effects of chronic oral moricizine therapy and physiological doses of epinephrine on ventricular fibrillation and defibrillation thresholds using an implantable transvenous/subcutaneous defibrillation system in a pig model. Thirteen pigs completed the three phases of the study. After a baseline study on day 1, the animals were randomized to receive moricizine 10-15 mg/kg tid or placebo for seven doses, at which time the protocol was repeated on day 4. The same protocol was again repeated on the same day after infusion of physiological doses of epinephrine. Multiple ventricular fibrillation and defibrillation thresholds were measured during each study. Moricizine did not alter ventricular fibrillation nor defibrillation thresholds, whereas epinephrine increased the ventricular defibrillation threshold from 20.8 J to 23.7 J (P < 0.05). In addition, we observed an increase in both ventricular fibrillation (19.7 J vs 12.6 J; P < 0.05) and defibrillation (20.8 J vs 17.8 J; P 0.05) thresholds over the 4 days of the study. These findings suggest that moricizine may be a safe antiarrhythmic agent to use in patients with implantable cardioverter defibrillators, and that elevated endogenous epinephrine may render defibrillation more difficult.

Administration, Oral↗
PubMed1995

Quantitation of myocardial dysfunction in ischemic heart disease by echocardiographic endocardial surface mapping: correlation with hemodynamic status.

Autopsy studies have suggested that infarction of > 35% of the myocardium is associated with cardiogenic shock. However, the relation between the extent of myocardial dysfunction and hemodynamic status has not been defined in patients in vivo. This study investigated, in patients with short-term and chronic left ventricular dysfunction, the relation between hemodynamic status and the extent of regional dyssynergia measured by two-dimensional echocardiography with quantitative endocardial surface mapping. Sixty patients were classified into hemodynamic groups by pulmonary capillary wedge pressure and cardiac index. Two-dimensional echocardiograms were used to calculate left ventricular endocardial surface area index (ESAi), abnormal wall motion index (AWMi), percentage myocardial dysfunction (%MD), and number of wall motion abnormalities. All patients in class 4 (high pulmonary capillary wedge pressure and low cardiac index had > or = 60% MD. With univariate analysis, hemodynamic class correlated with ESAi, AWMi, %MD, the number of wall motion abnormalities, and two clinical variables (number of infarctions and use of diuretic agents). By stepwise linear regression, only AWMi and the number of infarctions were independently predictive of hemodynamic status.

Aged↗
PubMed1995

Lidocaine prophylaxis for fatal ventricular arrhythmias after acute myocardial infarction.

OBJECTIVE: To compare the efficacy and safety of a 40-hour lidocaine infusion after completion of a 8-hour open-label infusion for prophylaxis of primary ventricular fibrillation in patients with uncomplicated acute myocardial infarction. METHODS: This was a double-blind, randomized placebo-controlled trial held in the coronary care unit of a large nonprofit hospital. We studied 200 patients with uncomplicated acute myocardial infarction in Killip class I or II who came to the hospital within 6 hours of onset of symptoms and 22 patients who had ventricular fibrillation before the start of the study. Intervention consisted of an 8-hour lidocaine infusion followed by placebo or lidocaine for an additional 40 hours. The infusion rate was adjusted in patients > or = 70 years old and in those < 50 kg or > or = 90 kg. Measurements recorded were baseline demographic characteristics, incidence of ventricular arrhythmias, adverse reactions, and death. RESULTS: New congestive heart failure developed during the randomized phase in 9% of patients receiving lidocaine and in 2% of patients receiving placebo (p = 0.03). Ventricular fibrillation did not occur during the treatment period, and sustained ventricular tachycardia developed in one patient receiving placebo. The in-hospital mortality rate was comparable in both groups (4% versus 2%; p = 0.68) but was much higher (13.6%) in patients with initial ventricular fibrillation not included in the randomized study. CONCLUSIONS: A 40-hour age- and weight-adjusted lidocaine infusion administered after an initial 8-hour infusion provoked more congestive heart failure than placebo. In view of the absence of ventricular fibrillation episodes with both infusions, caution should be used when lidocaine is administered for longer than 8 hours in patients with uncomplicated myocardial infarction.

Aged↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
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

Defibrillation energy requirements during moricizine and moricizine-lidocaine therapy.

Defibrillation energy requirements may be altered by antiarrhythmic agents. We investigated the effects of moricizine on the defibrillation threshold (DFT) in 18 pentobarbital-anesthetized pigs. The animals were randomized, in a blinded fashion, to moricizine or control (0.9% saline) treatment groups. Each group underwent three treatment phases: baseline, drug infusion (moricizine or saline), and drug infusion combined with lidocaine. Moricizine (2 mg/kg loading dose, 1.5 mg/kg/h infusion) and lidocaine (5 mg/kg loading dose, 4 mg/kg/h infusion) were dosed to achieve therapeutic concentrations. After 5 s of induced ventricular fibrillation, defibrillation was performed using a cardiac defibrillator interfaced with two epicardial electrode patches. DFTs were determined at baseline, during the drug phase, and during the combination of lidocaine with moricizine or saline. DFT values in the animals randomized to the control group were 15.2 +/- 4.2, 14.0 +/- 3.3, and 17.8 +/- 8.7 J at baseline, saline infusion, and saline combined with lidocaine, respectively. No significant differences were observed among the treatment phases. DFT values in the animals randomized to moricizine group were 12.1 +/- 2.8, 13.8 +/- 5.2, and 22.9 +/- 7.1 J at baseline, moricizine infusion, and moricizine combined with lidocaine, respectively. The DFT values during the lidocaine-moricizine combination treatment phase were significantly greater than baseline and moricizine alone (p < 0.002). The mean change in the DFT from baseline to moricizine (14% increase) was significantly different than the mean change in the DFT from baseline to saline (8% decrease) (p = 0.03). Lidocaine added to moricizine increased the DFT by 84%, which was significantly different from the 27% increase in the DFT when lidocaine was added to saline (p = 0.02). We conclude that moricizine minimally increases the DFT, but the combination of moricizine with lidocaine results in a synergistic rise in the DFT that may have detrimental clinical implications.

Animals↗
PubMed1992

Exacerbation of congestive heart failure secondary to moricizine.

Moricizine, a recently approved phenothiazine antiarrhythmic agent, is reported to be associated with a low frequency of congestive heart failure. A 61-year-old man with a history of congestive heart failure and ischemic heart disease began taking moricizine 250 mg every 8 hours to suppress his monomorphic sustained ventricular tachycardia. After five doses he became progressively short of breath and was in pulmonary edema. Moricizine was discontinued, intravenous diuretics were administered, and the patient's clinical status stabilized. Twelve hours later, however, he developed polymorphic ventricular tachycardia and was not successfully resuscitated. Despite claims as to its safety, limited data strongly suggest that moricizine, like other antiarrhythmics, may be detrimental in patients with preexisting ventricular dysfunction, and should be prescribed with caution.

Connecticut↗
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

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↗
PubMed1990

Preoperative immunostimulation with propionibacterium avidum KP-40 in patients with gastric carcinoma: a prospective randomized study.

Sixty-eight patients admitted for resection of gastric carcinoma entered a prospectively randomized trial. Patients in the therapy group (n = 34) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40. The therapy and control group did not differ with regard to postoperative complications, tumor recurrence rates (therapy group: 41%, control group: 38%), and patient survival rates (survival rate in the therapy group after 25 months: 53%, in the control group after 25 months: 50%).

Adenocarcinoma↗
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↗