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Biomedical subjects

J D Horowitz

Publications and source records attributed to J D Horowitz.

143 records · Page 8Linked to original sources
PubMed1976

A double-blind trial of perhexiline maleate in the prophylaxis of angina pectoris.

Perhexiline maleate, which has no beta adreno-receptor-blocking activity, has been suggested as an effective prophylactic agent for angina pectoris. The effects of perhexilline were compared with those of placebo by a double-blind crossover trial in seven patients with moderate to severe angina pectoris. Attack rates and glyceryl trinitrate consumption were significantly lower during the perhexilline phase than during the placebo phase of treatment. There was also a mild fall in resting heart rate. Three patients who had failed to respond to beta adrenoreceptor-blocking drugs, and one who had suffered reccurrence of symptoms after coronary artery surgery responded favourably to perhexiline. It thus appears that perhexiline maleate is an effective and potentially valuable agent in this condition.

Adult↗
PubMed1969

Cardiovascular responses to partial and total immersion in man.

1. Short-term cardiovascular effects of partial and total immersion of eighteen human subjects in the horizontal plane have been examined. Brachial arterial pressure, heart rate, forearm blood flow and respiratory movements were monitored simultaneously throughout the experiments. Forearm vascular resistance was calculated from the mean blood pressure and mean flow.2. Total immersion, including the face, with breath-holding resulted in a 61 +/- 43% increase in forearm vascular resistance with an associated 29 +/- 15% reduction in forearm blood flow. The concurrent bradycardia was significantly different from the heart rate changes during breath-holding with the torso only immersed, or during total immersion with snorkel-breathing. Neither breath-holding in air or with only the torso immersed, nor total immersion with snorkel-breathing produced such a diving response.3. Breath-holding, after several minutes of total immersion and snorkel-breathing, produced an attenuated diving response. It therefore appears that a full diving response can be obtained only when the apnoea commences at the moment of face immersion.4. The present investigation supports the concept that in man face immersion is an essential predisposing factor for the diving response, and cortical inhibition of the respiratory centre is important for its initiation and maintenance.

Adolescent↗
PubMedDate not supplied

Utility of a weight-based heparin nomogram for patients with acute coronary syndromes.

BACKGROUND: Unfractionated heparin has been pivotal in the management of acute coronary syndromes (ACS), and continues to be used widely despite the emerging role of low molecular weight heparins (LMWH). The apparent superiority of LMWH over unfractionated heparin may, at least partially, reside in its more predictable achievement of therapeutic effect, with high rates of non-therapeutic activated partial thromboplastin time (APTT) results being observed in the intravenous heparin treatment groups. AIM: To evaluate the impact of introduction of a weight-based heparin nomogram developed for use in patients with ACS on frequency of 'therapeutic' APTT results. METHODS: The effectiveness of an existing non-weight-based heparin nomogram in achieving a therapeutic APTT was compared sequentially with that of a weight-based heparin nomogram in 89 and 84 consecutive patients admitted with a diagnosis of ACS. RESULTS: Patients in whom heparin dosage adjustment was weight based rapidly achieved therapeutic APTT. The median time to achieve an APTT within the target range was 8.75 h in the weight-based group versus >24 h in the non-weight-based group. Utilization of a weight-based nomogram was associated with markedly increased proportions of readings within the therapeutic APTT range at 6 h and at 24 h (51%vs. 26% and 72%vs. 36%, respectively). CONCLUSIONS: The current study confirms the marked superiority of the weight-based heparin regimen for treatment of patients with ACS. The nomogram dramatically facilitated the attainment of therapeutic APTT, and may represent the optimal method for titration of heparin dosage to individual heparin requirements in patients with ACS.

Aged↗
PubMedDate not supplied

Can a nurse trained in coronary care expedite emergency department management of patients with acute coronary syndromes?

OBJECTIVE: The goal of this study was to determine the effect of a coronary care-trained nurse (CCTN) on transfer times of patients presenting with acute coronary syndromes (ACS) from the emergency department (ED) to the coronary care unit (CCU) for definitive cardiac treatment (DCT). DESIGN: This was a prospective randomized controlled study. SETTING: The study took place in the ED of a metropolitan public teaching hospital in South Australia. PATIENTS: The study sample was comprised of 893 patients who presented to the ED with a complaint of chest pain. INTERVENTION: An experienced senior CCTN was randomly assigned to work in an ED for 16 randomly selected hours per week; comparable hours over the same period without a CCTN in attendance were used as control data. The major endpoint was time to CCU transfer where DCT was completed for patients with ACS. RESULTS: Out of 893 patients assessed as having possible ACS, 91 (10%) were admitted to the CCU, 47 with a diagnosis of unstable angina pectoris (UAP) and 44 with a diagnosis of acute myocardial infarction. Nineteen patients required thrombolysis and/or percutaneous coronary angioplasty. Mean times (in minutes) to transfer for DCT (95% CI) were 102 (70-134) and 117 (95-139) in the presence and absence of a CCTN, respectively, for all ACS, and 33 (10-55) and 54 (25-82), respectively, for acute myocardial infarction requiring thrombolysis and/or percutaneous coronary angioplasty. CONCLUSIONS: These pilot data show a nonsignificant trend suggesting that DCT is expedited by assignment of senior CCTNs to EDs and provides direction for further study.

Acute Disease↗
PubMedDate not supplied

Comparative trial of mexiletine and lignocaine in the treatment of early ventricular tachyarrhythmias after acute myocardial infarction.

The antiarrhythmic effects of intravenously administered lignocaine and mexiletine were compared over a period of 48 hr in a randomized trial on 24 patients who developed ventricular tachyarrhythmias within 48 hr of the onset of acute myocardial infarction. Mexiletine was given as an initial bolus of 200 mg, followed by an infusion of 1 mg/min reduced to 0.5 mg/min after 1 hr. Lignocaine was given as a bolus of 100 mg, followed by an infusion of 3 mg/min reduced to 2 mg/min after 1 hr. Plasma levels of mexiletine, lignocaine, and monoethylglycinexylidide were monitored. The frequency of "complex" ventricular tachyarrhythmias was significantly lower in the mexiletine-treated group. This group of patients also had significantly fewer ventricular extrasystoles than those receiving lignocaine, the difference being most marked during the second 24 hr of treatment. Too few episodes of ventricular fibrillation occurred for statistical comment. The greater efficacy of mexiletine was not associated with increased drug toxicity.

Adult↗
PubMedDate not supplied

Prevention and reversal of tolerance to nitroglycerine with N-acetylcysteine.

A recent study demonstrated that the sulfhydryl donor N-acetylcysteine (NAC) potentiated hemodynamic responsiveness to nitroglycerine (NTG) in patients with ischaemic heart disease. The interaction between NTG and NAC in rings of bovine coronary artery was examined. Vasodilator responses to NTG were determined after elevation of tone with the thromboxane mimetic U46619 [(15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid]. NAC (1 microM-3 mM) induced no changes in tone of the preparation, but 10 microM NAC significantly potentiated responses to NTG (EC50 reduced from 0.69 +/- 0.19 microM to 0.22 +/- 0.06 microM; p less than 0.01). Increasing degrees of tolerance to NTG were produced at pH 7.4 by preincubating coronary rings with NTG in concentrations of 4.4 and 44 microM, and 0.22 mM. With 0.22 mM NTG, EC50 for subsequently administered NTG was increased to 11.0 +/- 1.8 microM (p less than 0.001 vs. control vessels). The degree of tolerance produced with this concentration of NTG was markedly attenuated by simultaneous (EC50 = 0.50 +/- 0.30 microM; p less than 0.001 vs. tolerant vessels) or subsequent (EC50 = 1.17 +/- 0.59 microM, p less than 0.001 vs. control vessels) incubation with 10 microM NAC. These data confirm that responses to NTG are modulated by sulfhydryl (or specifically cysteine) availability and suggest that in vitro tolerance to NTG is related to sulfhydryl (or cysteine) depletion. It is therefore possible that in vivo potentiation of NTG responses by NAC will be of clinical benefit in preventing or reversing loss of hemodynamic responsiveness to NTG.

Acetylcysteine↗
PubMedDate not supplied

Haemodynamic effects of a single low dose of prazosin in patients with chronic congestive cardiac failure correlations with pharmacokinetics.

The haemodynamic effects and pharmacokinetics of a single orally administered dose of 0.5 mg of prazosin have been compared in six patients with stable severe congestive cardiac failure. Administration of prazosin induced significant decreases in mean pulmonary capillary wedge pressure (from 27.5, s.e.m. = 4.5 to 19.4, s.e.m. = 5.1 mmHg; P less than 0.001), mean arterial blood pressure (from 94.5, s.e.m. = 6.0 to 85.4, s.e.m. = 5.0 mmHg; P less than 0.01), and systemic vascular resistance (from 1690, s.e.m. = 360 to 1420, s.e.m. = 200 dyn. s/cm5; P less than 0.05) and a rise in cardiac index from 1.98 (s.e.m. = 0.07) to 2.28 (s.e.m. = 0.16) litres/min per m2 (P less than 0.05). There was a non-significant fall in heart rate. Pharmacokinetic analysis revealed maximum plasma prazosin concentrations of 4.1 (s.e.m. = 1.4) ng/ml, occurring 2.1 (s.e.m. = 0.4) h after drug ingestion. The mean elimination half-life was 5.1 (s.e.m. = 0.8) h, which is longer than that found in our previous studies in normal subjects. There was considerable interindividual variation in peak plasma prazosin concentrations, elimination half-life and area under the concentration-time curve. While mean maximal haemodynamic effects of prazosin occurred at similar times to the peak plasma concentration of the drug, there was no significant correlation between the extent of haemodynamic response and individual pharmacokinetic parameters. It is concluded that significant and potentially beneficial haemodynamic effects occur with the initial administration of 0.5 mg oral dose of prazosin in patients with stable congestive cardiac failure and it is suggested that in many patients little advantage will be achieved with higher initial doses.

Aged↗
PubMedDate not supplied

Elimination, but not accumulation, of metoprolol by rat isolated perfused heart is selectively impaired by hypoxia.

1. The influence of hypoxia on the time course of regional myocardial accumulation and elimination of the beta 1-adrenoceptor antagonist metoprolol was investigated by a spontaneously beating rat isolated perfused heart preparation. 2. Myocardial metoprolol content was maximal at 2 min in the left and right ventricles and atria. Neither the extent nor the time of maximal myocardial metoprolol content was significantly influenced by the induction of hypoxia. However, maximal myocardial metoprolol content in both atria and right ventricles was significantly higher than that in the left ventricular samples (P < 0.02; one-factor analysis of variance, 17 d.f.). 3. Elimination of metoprolol (as indicated from residual myocardial metoprolol content at 10 min) was impaired in hypoxic left ventricles (P < 0.01 vs normoxia; unpaired t-test, 10 d.f.) but not in right ventricles or atria. This variation in myocardial metoprolol disposition was not apparent from examination of serial metoprolol concentrations in coronary perfusate. 4. Hypoxia selectively impaired the elimination of metoprolol from the left ventricle, but not the process of drug accumulation, by any region of myocardium. It remains to be determined whether this reflects regional variation in the extent of microcirculatory impairment associated with hypoxia.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Myocardial uptake of drugs and clinical effects.

The process of uptake of cardioactive drugs into the myocardium is a major determinant of the efficacy and potential toxicity of such agents. Evaluation of responses to anti-arrhythmic and positive inotropic agents is best performed with reference to their concentration in the myocardium, and the potential toxicity of drugs such as tricyclic antidepressants and anthracycline antineoplastics is likely to be related to peak myocardial drug concentrations. Although it has been appreciated for many years that even during long term drug administration the myocardial drug content may not be readily predictable on the basis of estimation of plasma drug concentrations, methodology for direct assessment of myocardial drug content has remained limited. The results of in vitro experiments, utilising tissue culture preparations of myocardial cells or isolated atria, have shed some light on the role of local factors as determinants of myocardial drug uptake. For many agents, attainment of maximal cardiac drug content in vitro is a very slow process (taking up to 3 hours), although maximal inotropic and electrophysiological effects may occur more rapidly. The prolonged time course of drug washout from these preparations also reflects their extensive and slow intracellular accumulation. Mechanical activity of the myocardium appears to accelerate drug uptake, particularly for otherwise slowly equilibrating agents, but the major determinant of the extent of drug uptake into isolated myocardial preparations is lipophilicity, perhaps reflecting the passage of drugs through the sarcolemma. In intact animals, assessment of myocardial drug content after acute drug administration has been performed utilising serial myocardial biopsy or sacrifice of animals. Studies in open-chested dogs suggest that acute accumulation of agents may be most closely predicted from the second compartment of a 3-compartment pharmacokinetic model, and that there is a variable correlation between changes in plasma and myocardial drug concentrations. For example, bretylium concentrations within the myocardium continue to increase for up to 6 hours after drug administration. Factors which may influence drug uptake into the myocardium in intact animals include ischaemia, which usually results in a delay in both drug uptake and subsequent clearance. This change can also be inferred from the time course of onset of antiarrhythmic drug effects in some models of myocardial ischaemia. Anoxia may also inhibit myocardial drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiovascular Agents↗