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Biomedical subjects

S Borzak

Publications and source records attributed to S Borzak.

At least 55 records · Page 3Linked to original sources
PubMed1995

Psychosocial factors related to unrecognized acute myocardial infarction.

Acute myocardial infarction (AMI) often is unrecognized (i.e., a patient fails to notice or report the event to the physician, or the physician fails to diagnose it). Psychosocial differences between patients with recognized and unrecognized AMI have not been examined. We compared 40 patients who sought treatment for a documented AMI with 30 patients who were found on routine electrocardiogram to have had an AMI for which they did not seek medical care. Patients with unrecognized AMI showed greater "alexithymia," or deficient psychologic awareness (p = 0.04; Alexithymia Provoked Response Interview), and a greater belief that chance factors determine their health (p = 0.004; Multidimensional Health Locus of Control Scale). Patients with unrecognized AMI were less likely to have angina, yet did not differ from those with recognized AMI with regard to demographics, smoking, systemic hypertension, diabetes mellitus, AMI location, depression, or hypochondriasis. We hypothesize that deficient psychologic awareness may impede AMI symptom perception or recognition, and that the belief in chance or fate as determining health may inhibit treatment-seeking.

Affective Symptoms↗
PubMed1995

Inhibition of N-acetylation of procainamide and renal clearance of N-acetylprocainamide by para-aminobenzoic acid in humans.

Procainamide administration often results in excessively high serum N-acetylprocainamide (NAPA) concentrations and subtherapeutic serum procainamide concentrations. Inhibition of N-acetylation of procainamide may prevent accumulation of excessive NAPA while maintaining therapeutic serum procainamide concentrations. The purpose of this randomized, two-way crossover study was to determine if para-aminobenzoic acid (PABA) inhibits N-acetylation of procainamide in healthy volunteers. Eleven (7 female, 4 male) fast acetylators of caffeine received, in random order, PABA 1.5 g orally every 6 hours for 5 days, with a single intravenous dose of procainamide 750 mg administered over 30 minutes on the third day, or intravenous procainamide alone. Blood samples were collected during a 48-hour period after initiation of the infusion. Urine was collected over a 72-hour period. Serum procainamide and NAPA concentrations were analyzed using fluorescence polarization immunoassay. Urine procainamide and NAPA concentrations were measured with high performance liquid chromatography. PABA did not significantly influence total or renal procainamide clearance, elimination rate constant, AUC0-00, amount of procainamide excreted unchanged in the urine, or volume of distribution. However, concomitant PABA administration with procainamide resulted in increases in NAPA AUC0-00 and t1/2 and reductions in NAPA Ke, procainamide acetylation (NAPA formation) clearance, and NAPA renal clearance. Although PABA inhibits metabolic conversion of procainamide to NAPA, it also impairs the renal clearance of NAPA (but not procainamide) in healthy subjects. Therefore, PABA may not be useful for optimizing the safety of efficacy of procainamide in patients.

4-Aminobenzoic Acid↗
PubMed1995

Proarrhythmic effects of intravenous vasopressors.

OBJECTIVE: To review the electrophysiologic properties and the in vitro, ex vivo, animal, and human data regarding proarrhythmic effects of intravenous vasopressors. DATA SOURCES: A comprehensive (MEDLINE) search (1960-1994) was conducted for dopamine, epinephrine, norepinephrine, phenylephrine, and methoxamine. STUDY SELECTION: In vitro and ex vivo studies and investigations performed in animals or humans reporting electrophysiologic and/or proarrhythmic effects of the above intravenous vasopressors were selected. A comprehensive search of all human studies involving these agents was conducted to reveal any proarrhythmic effects that may have been reported. In addition, case reports of proarrhythmic effects associated with these agents were reviewed. DATA EXTRACTION: Data regarding electrophysiologic and proarrhythmic effects of these agents were extracted from in vitro, ex vivo, animal, and human studies. Because few studies with the specific purpose of investigating proarrhythmic effects of vasopressors have been performed in humans, all studies involving these drugs for evaluation of hemodynamic effects, clinical efficacy, or other endpoints in humans were reviewed. In addition, data were extracted from case reports of proarrhythmic effects associated with these agents. DATA SYNTHESIS: Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action-potential duration. Dopamine has caused both atrial and ventricular tachyarrhythmias in animals. Human data have revealed dose-related sinus tachycardia, with few reports of clinically significant ventricular arrhythmias. Epinephrine shortens sinus cycle length, increases atrial and ventricular automaticity, promotes atrioventricular nodal conduction, and decreases ventricular effective refractory period (ERP). It is well known to induce ventricular fibrillation and decrease the ventricular fibrillation threshold (VFT) in ex vivo models as well as intact animals. In humans, epinephrine may cause dose-related sinus tachycardia, supraventricular arrhythmias, or, more commonly, ventricular arrhythmias. Norepinephrine increases automaticity of the sinoatrial node, atria, and ventricles; promotes atrioventricular nodal conduction; and decreases ventricular ERP. In vitro/ex vivo and animal data have shown that norepinephrine significantly decreases VFT. Although electrophysiologic studies suggest that norepinephrine may be proarrhythmic, few supporting data exist in humans. Phenylephrine demonstrates differential electrophysiologic effects in atrial and ventricular tissue. Most data suggest that phenylephrine causes prolongation of the ventricular ERP. Rather than being proarrhythmic, phenylephrine may be protective against arrhythmias. The drug elevates VFT in dogs. In humans, phenylephrine effectively terminates supraventricular tachycardias and may be protective against ventricular arrhythmias. Like phenylephrine, methoxamine elevates the repetitive extrasystolic, atrial, and ventricular fibrillatory thresholds. Methoxamine also may have antiarrhythmic effects because of alpha-receptor stimulation and reflex vagal activity. Despite the relatively low risk of arrhythmogenicity associated with intravenous vasopressors, patients should be monitored for potential proarrhythmic effects and appropriate action taken as necessary. Critically ill patients often have concurrent conditions, electrolyte disturbances, and underlying arrhythmias that predispose them to a higher risk of vasopressor proarrhythmic effects. CONCLUSIONS: Controlled data supporting the proarrhythmic potential of intravenous vasopressors in humans are lacking. Sinus tachycardia, asymptomatic ventricular ectopic activity, and other ventricular or supraventricular arrhythmias have been reported in association with dopamine and epinephrine. Phenylephrine and methoxamine have been associated with sinus bradycardia, but otherwise may be antiarrhythmic. Intravenous vasopressors appear relatively safe w

Animals↗
PubMed1994

Magnesium for myocardial infarction?

There are several theoretical mechanisms by which magnesium might be beneficial against ischemic heart disease. Yet numerous studies of its use in acute MI show inconsistent results.

Animals↗
PubMed1993

Thrombolytic therapy for unstable angina.

Thrombolytic therapy for unstable angina has not gained acceptance as a primary treatment for unstable angina (UA) despite the evidence showing a reduction in mortality when these agents are given for myocardial infarction. The purpose of this review is to examine the clinical value of thrombolytic therapy for UA. The multiple lines of evidence supporting intracoronary thrombus formation as a key mechanism in the pathogenesis of UA are reviewed. Studies examining the effect of thrombolytic therapy on angiographic endpoints have shown little effect on the extent of luminal narrowing, but do reveal a decrease in angiographically detected thrombus. Twelve randomized, controlled trials of thrombolytic agents in 611 UA patients with predefined clinical endpoints have been published. These trials varied widely in design and adjunctive therapy both in treated and control grops. Review of these trials show a tendency to fewer clinical events such as death, infarction, and need for revascularization in treated patients, with a corresponding increase in bleeding complications. Clinical efficacy of thrombolytic therapy cannot be excluded by the available data, perhaps in part because of insufficient numbers of patients treated. Determination of the net clinical value of thrombolytic therapy must await larger and more definitive trials.

Angina, Unstable↗
PubMed1993

Discordance between effects of anti-ischemic therapy on ambulatory ischemia, exercise performance and anginal symptoms in patients with stable angina pectoris. The Angina and Silent Ischemia Study Group (ASIS).

OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment.

Aged↗
PubMed1993

Role of cation gradients in hypercontracture of myocytes during simulated ischemia and reperfusion.

We examined the relationship between transsarcolemmal cation gradients and hypercontracture of cardiac myocytes in ischemia and reperfusion using adult rat ventricular myocytes superfused with buffer mimicking normal or ischemic extracellular fluid. Contractile performance of electrically stimulated cells was recorded by an optical video system simultaneously with measurements of intracellular Ca2+ concentration ([Ca2+]i) using fura-2 or intracellular pH (pHi) using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. While cells were exposed to simulated ischemia buffer, the transsarcolemmal H+ gradient was abolished, [Ca2+]i transient stopped, and twitch contraction of myocytes ceased. Upon reperfusion with normal buffer, H+ gradient was quickly restored, Ca2+ transients restarted with transient increase in systolic Ca2+, and twitch contraction restarted with development of hypercontracture, which continued after [Ca2+]i returned to preischemic level even in the presence of near-normal concentrations of high-energy phosphates. When the transsarcolemmal proton, Na+, and Ca2+ gradients were altered so that Na+ entry via Na(+)-H+ exchange and Ca2+ entry via Ca(2+)-Na+ exchange were made less favorable, the transient systolic overshoot of Ca2+ at reperfusion and development of hypercontracture was largely avoided. These results suggest that Na+ and then Ca2+ entry via the Na(+)-H+ and Na(+)-Ca2+ exchangers, respectively, probably contribute to the increase in [Ca2+]i and hypercontracture of myocytes at time of reperfusion in this model.

Acidosis↗
PubMed1992

Na+ efflux mechanisms in ventricular myocytes: measurement of [Na+]i with Na(+)-binding benzofuran isophthalate.

We characterized the Na(+)-sensitive dye benzofuran isophthalate (SBFI) with fluorescence microscopy in isolated, adult rat ventricular myocytes. When cells were loaded with SBFI by incubation with 10 microM of the acetoxymethyl ester, fluorescence excitation spectra were markedly attenuated below 340 nm and the isoemissive point was blue shifted by approximately 25 nm when compared with spectra from SBFI acid in buffered solutions. Fluorescence intensity (49 +/- 3%) was partially released by permeabilization of the sarcolemma with digitonin, suggesting that one-half of the dye molecules are sequestered subcellularly in a compartment shown most likely to be mitochondrial. Intracellular Na+ concentration ([Na+]i) was determined by in situ calibration using cation-selective ionophores and was found to be 14 +/- 2 mM in cells studied at 37 degrees C. The relative importance of Na+ efflux mechanisms in myocytes was investigated. Substitution of Ca2+ and Mg2+ with EGTA in the superfusing medium resulted in a reversible rise of [Na+]i from 13 +/- 2 to 31 +/- 5 mM, which was blocked by 1 microM verapamil. Cellular efflux of Na+ after loading in this manner was found to be insensitive to blockade of Na(+)-Ca2+ exchange but was abolished when Na(+)-K(+)-ATPase was inhibited with zero extracellular K+ concentration. We conclude that SBFI can be used to measure [Na+]i in ventricular cells nondestructively and without impalement. Na+ efflux after loading by Ca2+ and Mg2+ withdrawal is mediated by the Na+ pump with no measurable contribution from Na(+)-Ca2+ exchange.

Animals↗
PubMed1991

Mechanisms of rate staircase in rat ventricular cells.

We studied the steady-state rate staircase in isolated rat ventricular cells stimulated at frequencies ranging up to 6 Hz at 37 degrees C. When contractility was measured as displacement of the cell edge, amplitude of motion decreased while stimulation rates were increased from rest to 1 Hz (negative staircase). With further increases in the rate of stimulation to 6 Hz, amplitude of motion increased for each increment in stimulation rate (positive staircase). Ryanodine at a concentration of 100 nM was a negative inotrope and abolished the rested state contraction and the negative staircase seen between rest and 1 Hz (P less than 0.05) but had no significant effect on twitch amplitude or the staircase at stimulation rates between 1 and 6 Hz. L-type Ca2+ channel inhibition with verapamil (0.2 microM) had little effect on twitch or the negative staircase from rest to 1 Hz, but twitch amplitude was diminished and the staircase was converted from positive to negative at stimulation rates between 1 and 6 Hz (P less than 0.05). We conclude that in rat ventricular cells studied at 37 degrees C, the rate staircase is biphasic: negative from rest to 1 Hz and positive from 1 to 6 Hz. This phenomenon is dominated by Ca2+ release from the sarcoplasmic reticulum at rates less than 1 Hz and by Ca2+ entry through L channels at rates greater than 1 Hz.

Animals↗
PubMed1991

Intravenous nitroglycerin for acute myocardial infarction.

Intravenous nitroglycerin (IV TNG) has been increasingly used in the setting of acute myocardial infarction. The seven randomized trials comparing IV TNG with placebo, and one trial comparing IV isosorbide dinitrate with furosemide, were reviewed for evidence of beneficial clinical effects. IV TNG in low dosage is safe in the setting of acute myocardial infarction and modestly effective in relieving chest pain. Favorable hemodynamic effects are most pronounced in patients with congestive heart failure. Limited evidence suggests that IV TNG, particularly when administered early, reduces both infarct size and mortality when given prophylactically.

Humans↗
PubMed1991

Non-Q wave myocardial infarction.

Non-Q wave myocardial infarction is a distinct and changing clinical entity characterized by lower initial mortality and a higher rate of reinfarction compared to Q wave infarction. Clinical and pathologic data suggest that the syndrome results from transient or incomplete coronary occlusion resulting in an infarct which is smaller than when Q waves are present. High-risk patients can be identified during hospitalization, allowing for aggressive therapy aimed at revascularization. Relatively few clinical trials have examined initial therapy or secondary prevention in this group of patients. These studies are reviewed and management guidelines suggested.

Algorithms↗
PubMed1990

In situ calibration of fura-2 and BCECF fluorescence in adult rat ventricular myocytes.

Quantitation of Ca+ and H+ activities within cells using presently available fluorescent probes is optimal when the fluorescence signal is calibrated in situ after each experiment. Fura-2 and 2',7'-bis(2-carboxy-ethyl)-5,6-carboxyfluoroscein (BCECF) are difficult to calibrate in freshly dissociated adult cardiac myocytes because calibration procedures produce cellular hypercontracture. In situ calibration was accomplished in rat ventricular cells by saturating fura-2 with La3+, an agent known to produce myocardial relaxation. Since fura-2 has different spectral properties when complexed with La3+ than with Ca2+, scaling factors were defined in vitro and then verified by experiments in cultured neonatal myocytes. In adult rat myocytes using the La3+ method, intracellular Ca2+ concentration ([Ca2+]i) was 131 +/- 47 nM (n = 14) in quiescent cells; diastolic [Ca2+]i and systolic [Ca2+]i in myocytes stimulated at 1 Hz were 140 +/- 56 and 1,088 +/- 211 nM (n = 5), respectively. BCECF fluorescence was calibrated in situ by a method that prevented cellular hypercontracture and reported a pH value of 7.10 +/- 0.10 in cells stimulated at 1.5 Hz. An additional advantage of both methods is that the buffers employed prevented large changes in the redox state of intracellular pyridine nucleotides, thus preventing a change in cellular autofluorescence during the calibration procedure.

Aging↗
PubMedDate not supplied

Electrophysiologic and proarrhythmic effects of intravenous inotropic agents.

Intravenous inotropic agents promote increased myocardial contractility via elevation of myocyte calcium concentrations, a mechanism that is also known to promote the development of cardiac arrhythmias. The purpose of this article is to review the electrophysiologic effects and relative potential for proarrhythmia associated with dobutamine, dopamine, and the phosphodiesterase inhibitors amrinone and milrinone. Dobutamine increases sinoatrial node automaticity and decreases atrial and atrioventricular (AV) node refractoriness and AV nodal conduction time. The drug also decreases ventricular refractoriness in both healthy and ischemic myocardium. Dobutamine has been shown to increase heart rate in a dose-related fashion in animals and in humans. In humans, dobutamine has been reported to induce ventricular ectopic activity (VEA) in 3% to 15% of patients, although VEAs are often asymptomatic, requiring no intervention. Ventricular tachycardia (VT) associated with dobutamine appears to occur rarely. Patients with underlying arrhythmias or heart failure or those receiving excessive doses of dobutamine are at greatest risk for proarrhythmia. Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action potential duration. Dopamine has been reported to induce atrial or ventricular arrhythmias in animals. In humans, dopamine may be associated with dose-related sinus tachycardia but has also been reported to cause VEA, which is usually asymptomatic. Dopamine-associated VT appears to occur rarely. Dopamine produces greater elevations in heart rate or frequency of ventricular premature beats at a given value of cardiac index than does dobutamine. The phosphodiesterase inhibitors amrinone and milrinone increase conduction through the AV node and decrease atrial refractoriness. Intravenous administration of these drugs may result in sinus tachycardia in some patients and has been reported to cause VEA, which is often asymptomatic, in up to 17% of patients. VT has also been reported in association with short-term use of intravenous phosphodiesterase inhibitors. In summary, intravenous inotropic agents may be associated with proarrhythmic effects in some patients. The primary arrhythmias reported are sinus tachycardia and VEA, although other supraventricular or ventricular arrhythmias have been reported less commonly. However, clinically significant proarrhythmic effects associated with these agents appear to occur rarely, and, at conventional doses, intravenous inotropic agents are relatively safe with respect to proarrhythmic effects.

Adolescent↗
PubMedDate not supplied

Angiotensin-converting enzyme inhibition after acute myocardial infarction with special reference to the Fourth International Study of Infarct Survival (ISIS-4).

Role of ACE inhibitors in the management of asymptomatic or symptomatic left ventricular (LV) dysfunction after acute myocardial infarction (AMI) is well established. More recently, large clinical trials have evaluated the use of angiotensin-converting enzyme (ACE) inhibitors early after AMI, ie, within 24 hours of symptom onset. This concept has emerged with the understanding of pathophysiological changes occurring after AMI. Neurohormonal activation and ventricular remodelling after AMI form the basis of these changes, whereas the extent of LV dysfunction remains strongly predictive of poor outcome. The large clinical trials with mortality end point have shown modest benefit with early use of ACE inhibitors in an unselected population. However, the generalized use of ACE inhibitors remains controversial because of an overall small benefit. We review the pathophysiological changes occurring after AMI, the rationale for early use of ACE inhibitors, and the data available from the large clinical trials. We recommend consideration of early ACE inhibitor in all but the lowest risk patients. Clinical features of such a low-risk population would include small and nonanterior infarctions in patients less than 65 years of age and with LV ejection fractions greater than 50%. Objective assessment of LV function is warranted during hospitalization for AMI to appropriately select patients for ACE inhibitor therapy. Dosing should be started carefully to avoid hypotension and should be titrated to the goal of doses used in the large trials. Duration of therapy in patients at high risk for death or ventricular enlargement should be indefinite. Further large-scale secondary prevention trials with long-term treatment are underway to assess the effect of ACE inhibition on coronary disease progression and reinfarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Role of antiarrhythmic agents after myocardial infarction with special reference to the EMIAT and CAMIAT trials of amiodarone. European Myocardial Infarct Amiodarone Trial. Canadian Amiodarone Myocardial Infarction Trial.

The role of antiarrhythmic agents in the post-MI patients has been investigated for several years. Recently, clinical trials have assessed the effects of amiodarone in the post-MI population. The Basel Antiarrhythmic Study of Infarct Survival (BASIS) trial showed a reduction in total mortality, sudden death, and life-threatening ventricular arrhythmias with amiodarone therapy. The European Myocardial Infarct Amiodarone Trial (EMIAT) did not show a mortality benefit, but amiodarone was associated with fewer antiarrhythmic deaths. The Canadian Amiodarone Myocardial Infarction Trial (CAMIAT) showed no significant impact on mortality, but arrhythmia deaths and resuscitated cardiac deaths were reduced. Amiodarone therapy after MI should be reserved for the treatment of symptomatic or sustained ventricular arrhythmias. The current data do not support routine use of amiodarone in all patients after MI.

Amiodarone↗
PubMedDate not supplied

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed.

Amiodarone↗