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Biomedical subjects

J D Horowitz

Publications and source records attributed to J D Horowitz.

At least 127 records · Page 7Linked to original sources
PubMed1985

Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease.

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

Comparison of negative inotropic potency, reversibility, and effects on calcium influx of six calcium channel antagonists in cultured myocardial cells.

The negative inotropic effects of calcium channel antagonists on the myocardium were used as a standard for the definition and determination of potency of this group of drugs. The effects of six calcium channel antagonists (verapamil, methoxyverapamil (D600), nifedipine, lidoflazine, perhexiline and diltiazem) were compared on cultured chick embryo ventricular cells. Drug concentrations producing 50% inhibition of contractile amplitude, derived from linearized concentration-response curves, varied from 2.8 X 10(-8)M for nifedipine to 8.3 X 10(-7)M for perhexiline. Equipotent negative inotropic concentrations of verapamil, D600, perhexiline, diltiazem and lidoflazine produced a similar inhibitory effect on 45Ca uptake into cultured cells. Nifedipine produced no significant inhibition of 45Ca uptake. The time required for recovery of contractility after cessation of drug superfusion varied in the order lidoflazine greater than perhexiline greater than D600 greater than verapamil greater than nifedipine greater than diltiazem. This relative order accords closely with the reported in vivo half-lives of these drugs. It is concluded that while some inhibition of 45Ca2+ uptake into cardiac cells can be demonstrated with five of the six calcium channel blockers studied, the relationship between the degree of inhibition of calcium influx and negative inotropic effects may not be uniform for all calcium channel antagonists.

Animals↗
PubMed1983

Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.

Although beta-adrenergic blocking agents reduce myocardial oxygen consumption and symptoms of myocardial ischemia in patients with coronary artery disease (CAD), propranolol has been reported to exacerbate coronary artery spasm in some patients with variant angina. To determine whether increased coronary vasomotor tone can be induced by beta-adrenergic blockade, we measured the changes in coronary vascular resistance (CVR) during cold pressor testing (CPT) in 15 patients, nine with severe CAD and six with normal left coronary anatomy, before and after i.v. propranolol (0.1 mg/kg). Coronary blood flow was measured by coronary sinus thermodilution. CVR was calculated as mean arterial pressure divided by coronary sinus blood flow. Heart rate was maintained constant at a paced subanginal rate of 95 +/- 5 beats/min. Before propranolol, CPT induced significant increases in coronary vascular resistance in patients with CAD (15.0 +/- 2.2%, p less than 0.02), but no increase in CVR in the normal patients. After propranolol, the CVR change during CPT was augmented for patients with CAD (29 +/- 6%, p less than 0.01) and for the normal population (9 +/- 5%, NS). The potentiated increase in CVR occurred without significant changes in resting CVR or in the magnitude of the hypertensive response to CPT. We conclude that beta-adrenergic blockade with propranolol can potentiate coronary artery vasoconstriction in some patients with CAD, possibly mediated by unopposed alpha-adrenergic vasomotor tone. These changes may be important in patients in whom intense adrenergic stimulation may increase coronary artery tone and adversely influence the balance between myocardial oxygen supply and demand.

Adrenergic beta-Antagonists↗
PubMed1983

Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine.

The biochemical basis of the mechanism of vasodilatation by nitroglycerin (NTG) has not been previously investigated in man. However, evidence from in vitro studies suggests that NTG induces activation of guanylate cyclase via a series of enzymatic reactions that are modulated by the availability of sulfhydryl groups. Cysteine appears to be particularly effective in potentiating guanylate cyclase activation by NTG. To determine whether hemodynamic responsiveness to NTG in man might be modulated by sulfhydryl availability, concentration-response curves for effects of intravenously infused NTG on mean arterial pressure (MAP) and mean pulmonary capillary wedge pressure (PCW) were obtained in 10 patients undergoing cardiac catheterization for investigation of chest pain. NTG infusion was repeated 10 min after the intravenous infusion of 100 mg/kg of the cysteine source N-acetylcysteine (NAC). NAC induced no significant hemodynamic effect, but after NAC infusion there was a significant reduction both in the NTG infusion rate associated with a 10% fall from control values in MAP (25.8 +/- 8.3 to 9.3 +/- 2.7 micrograms/min; p less than .01) and in the infusion rate inducing a 30% reduction in PCW (13.6 +/- 4.6 to 4.2 +/- 1.6 micrograms/min; p less than .02). In a control group of five patients who received no NAC, there was no significant change in responsiveness to NTG between infusions. It is concluded that NAC potentiates the vasodilator effects of NTG in man. This suggests that sulfhydryl availability and/or redox state may be determinants of in vivo responsiveness to NTG.

Acetylcysteine↗
PubMed1982

Lack of interaction between digoxin and quinidine in cultured heart cells.

Previous investigations have raised the possibility that the digoxin-quinidine interaction is associated with a reduction in the positive inotropic effect of digoxin due to displacement of digoxin from cardiac as well as skeletal muscle. To circumvent some of the complexities presented by intact animal models, this interaction was investigated in cultured chick embryo ventricular cells. Quinidine, even at relatively high concentrations (10(-4)--2 x 10(-3) M), did not significantly affect positive inotropic effects of digoxin and did not protect against cellular contracture induced by toxic digoxin concentrations, despite preincubation of cells with quinidine for 60 min. The effects of digoxin on monovalent cation transport, as judged by active uptake of the K analog 86Rb, were also not altered by 10(-4) M to 2 x 10(-3) M quinidine. These data suggest that quinidine does not displace digoxin from Na, K adenosine triphosphatase binding sites in this preparation. Although these data must be extrapolated to the intact animal with caution, our findings suggest that changes digoxin clearance are more likely of primary importance in the digoxin-quinidine interaction, and indicate that the approximately 2-fold increase in serum digoxin concentration observed after addition of quinidine would be expected to have direct effects on myocardial cells comparable with those seen with increased digoxin concentration in the absence of quinidine.

Animals↗
PubMed1981

High-performance liquid chromatographic assay of perhexiline maleate in plasma.

A sensitive assay is described for the calcium antagonist perhexiline maleate. Alkalinized plasma was extracted with nb-hexane, the organic phase was evaporated, and the residue was dansylated prior to analysis by reversed-phase high-performance liquid chromatography using a fluorescence detector. Perhexiline was resolved from its mono- and dihydroxylated metabolites, and the limit of sensitivity was 5 ng of perhexiline/ml. This limit represents approximately 100 times the sensitivity of the previously described GLC assay. Single-dose pharmacokinetic studies were performed with 150- and 300-mg oral doses of perhexiline maleate in five patients with severe angina pectoris and impaired left ventricular function. Peak plasma perhexiline levels occurred 3-6 hr after drug ingestion in four patients and after 12-18 hr in the fifth patient. The mean elimination half-life, measured 24 hr after drug ingestion, varied with plasma perhexiline concentration. It was 11.2 +/- 2.1 hr after the 150-mg dose and 19.1 +/- 2.8 hr after the 300-mg dose. The mean ratio of areas under the concentration-time curve for the 300-versus 150-mg doses ws 5.3:1, suggesting that hepatic metabolism of perhexiline may be saturable and that the bioavailability of perhexiline is dose dependent.

Aged↗
PubMed1981

Effects of captopril (SQ 14,225) in a patient with primary pulmonary hypertension.

In a 33-year-old patient with severe primary pulmonary hypertension, the acute administration of the angiotensin-converting-enzyme inhibitor captopril (SQ 14,225) induced a rise in cardiac output, and a fall in both pulmonary and systemic vascular resistance. Subsequent chronic oral administration of captopril induced only transient clinical improvement, and the patient died. Captopril may nevertheless be useful in the treatment of less advanced cases of this disease.

Adult↗
PubMed1980

Use of dopamine and prazosin combined in the treatment of cardiogenic shock.

Seventeen patients who developed cardiogenic shock after acute myocardial infarction were treated with intravenously infused dopamine. In eight of these patients a stable blood pressure was attained, but oliguria or anuria persisted, and oral treatment with prazosin was instituted. Diuresis occurred in seven of these patients, but was followed by transient hypotension associated with a rapid rise in plasma prazosin levels in three. Four patients left hospital, and there were two long-term survivors. Prazosin may be a useful adjunct to dopamine in the treatment of cardiogenic shock.

Administration, Oral↗
PubMed1980

Hypertensive responses induced by phenylpropanolamine in anorectic and decongestant preparations.

The acute effects of a single capsule of each of two phenylpropanolamine-containing preparations were determined in a group of healthy young adults, by means of a double-blind comparison with matching placebo preparations. Supine diastolic blood-pressure rose to 100 mm Hg or more in 12 out of 37 subjects taking an anorectic preparation ('Trimolets'; 85 mg phenylpropanolamine per capsule) and in 4 out of 34 subjects taking a decongestant preparation ('Contac 500'; 50 mg phenylpropanolamine per capsule). 20 of the subjects taking trimolets reported adverse side effects. The frequency and extent of the hypertensive response to high-dose phenylpropranolamine-containing preparations suggest that clinical use of such preparations should be reviewed and that their availability without prescription may not be appropriate.

Adult↗
PubMed1980

Purification of a peptide with venoconstrictor and vasodepressor activity, from Cohn fraction III-O of human plasma protein.

Cohn fraction III-O of human plasma proteins has previously been shown to contain a peptide which produces vasodilator responses in intact vascular beds. This peptide has bradykinin-like pharmacological actions but it can be distinguished from bradykinin. A process of serial fractionation of Cohn fraction III-O on Sephadex CM-25 and G-25 gels, followed by ion exchange chromatography with gradient elution on a Bio-Rex 70 column and subsequent desalting has permitted purification of this peptide. Amino acid analysis suggested a peptide with 14 amino acyl-residues and a calculated molecular weight of 1,780. The purified material retained the vasodilator properties of impure sources of the peptide, but was highly unstable. There was no interaction with anti-bradykinin antibodies.

Amino Acids↗
PubMed1980

Venoconstrictor activity of some precursor fractions of stable plasma protein solution.

Stable plasma protein solution (SPPS) is a 5% solution of human plasma albumin and some globulins. Rapid infusion of some batches of SPPS and analogous solutions prepared by similar processes induce paradoxical hypotensive reactions. In the current experiments, a number of precursor fractions of a single batch of SPPS were examined for kininogen content and for venoconstrictor activity on the isolated central vein of the rabbit ear. Unheated SPPS contained both venoconstrictor activity and kininogen. Among the various precursor fractions examined, Cohn fraction II + III (a precursor of fraction III-0) contained the greatest venoconstrictor activity. There was no evidence of kininogen depletion during the stages of fractionation examined but some generation of venoconstrictor material. Column chromatography suggested a molecular weight of approximately 1,500 for the major active material in unheated SPPS. It appears possible that the 14-amino acid hypotensive peptide present in fraction III-0 may also be present in SPPS, where it may contribute to the hypotensive effects of this solution.

Animals↗
PubMed1979

Perhexiline maleate in the treatment of severe angina pectoris.

Perhexiline maleate was used as a prophylactic agent in 26 patients suffering from severe angina pectoris. The mean duration of treatment was 8.9 months, with a maximum of 28 months. Fifteen patients experienced a reduction in frequency of attacks to less than one-third of their previous level; six experienced a reduction to two-thirds of their previous level; no patient showed an increase in attack rates. During the period of study, there was one death. Frequently observed side effects included dizziness, gastrointestinal irritation and malaise. One patient developed clinically apparent hepatic dysfunction which resolved on withdrawal of perhexiline maleate, but recurred after rechallenge with a lower dose of the drug; the results of liver function tests in five others showed mild abnormalities. One patient developed peripheral neuropathy after taking perhexiline maleate for 18 months, but this resolved in two months after cessation of therapy. Good responses to perhexiline maleate were observed in patients who were concurrently treated with beta-adrenoreceptor blocking drugs.

Alprenolol↗