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Biomedical subjects

C V Leier

Publications and source records attributed to C V Leier.

At least 91 records · Page 5Linked to original sources
PubMed1986

Determination of pindolol in human plasma and urine by high-performance liquid chromatography with ultraviolet detection.

This paper presents a rapid, simple and economical method for assaying pindolol concentrations in plasma and urine by high-performance liquid chromatography using ultraviolet detection. It is sensitive enough for use in single-dose pharmacokinetic studies and may also be used to determine pindolol concentrations in the plasma from patients taking the drug, provided that the patient is not taking any of the drugs which interfere with the method. Drugs which were found to interfere with the pindolol peak are quinidine, n-acetylprocainamide and lidocaine. Disopyramide, oxprenolol and levobunolol interfered with the internal standard peak.

Alprenolol↗
PubMed1986

Extent of myocardial fibrosis and cellular hypertrophy in dilated cardiomyopathy.

The distribution of fibrosis and cellular hypertrophy was studied in the hearts of patients with dilated cardiomyopathy (DC). Transmural sections were removed from the left and right ventricular free walls and the ventricular septum of 9 patients with heart failure and 6 control subjects. These sections were stained with hematoxylin-eosin (to determine cell size) and trichrome (to determine percent fibrosis). The sections were separated into equal areas from epicardium to endocardium in the free walls and right to left across the septum. Percent fibrosis was greater in patients with DC (20 +/- 4%) than control subjects (4 +/- 1%, p = 0.0001). A pattern of increasing fibrosis in the left ventricular free wall from epicardium (14 +/- 6%) to endocardium (22 +/- 9%, p less than 0.05) was documented. Fibrosis was greater on the left (21 +/- 12%) than the right (15 +/- 6%, p less than 0.05) side of the septum. No pattern was evident in the right ventricular free wall or in the control group. Myocardial cell diameter was greater in the heart failure group (22 +/- 5 micron) than the control group (17 +/- 2 micron, p less than 0.05), but no pattern of hypertrophy across the walls was seen. The increased fibrosis, the pattern of fibrosis and the increased cell diameter in patients with DC help to characterize DC.

Adult↗
PubMed1986

Hemodynamic changes after meals and placebo treatment in chronic congestive heart failure.

To determine whether significant spontaneous hemodynamic changes occur without therapeutic intervention, 15 patients with stable heart failure underwent right-sided cardiac catheterization and were observed without active treatment during an 8-hour period. Significant changes that mimic those seen during treatment with vasodilating medications were found. Increases were seen in heart rate (minimum 82 +/- 19 beats/min, maximum 88 +/- 18 beats/min, p less than 0.05) and cardiac index (minimum 2.14 +/- 0.45 liters/min/m2, maximum 2.42 +/- 0.79 liters/min/m2, p less than 0.05). Decreases were observed in pulmonary artery wedge pressure (maximum 24 +/- 7 mm Hg, minimum 21 +/- 7 mm Hg, p less than 0.05) and systemic vascular resistance (maximum 1,600 +/- 280 dynes-s-cm5, minimum 1,390 +/- 310 dynes-s-cm-5, p less than 0.05). Except for the decrease in pulmonary artery wedge pressure, all hemodynamic changes appeared to be related to eating. In addition, a statistically significant postprandial decrease in mean blood pressure (before meal 85 +/- 12 mm Hg, after meal 78 +/- 11 mm Hg, p less than 0.05) was seen. These data reinforce the need for caution in interpreting small hemodynamic changes, even if statistically significant, and they indicate the desirability of including placebo groups or phases in drug studies and of performing hemodynamic measurements the postabsorptive state.

Adult↗
PubMed1986

Dose- and time-dependent binding and kinetics of pindolol in patients with congestive heart failure.

Dose- and time-dependent pharmacokinetics and plasma protein binding of pindolol were studied in patients with idiopathic cardiomyopathy who had mild to moderate congestive heart failure. The binding and plasma concentrations of pindolol at various times following the oral administration of single 5- and 10-mg doses and multiple 10-mg doses were determined. The binding of pindolol to plasma protein was time-dependent, increasing from 26% on the first day to 31% during the third day of treatment (P less than .05); this was probably due to increased alpha-1-acid glycoprotein concentration. Analysis of the plasma concentration-time data indicated dose-independent pharmacokinetics. Pindolol pharmacokinetics were time-dependent in one patient. Absorption and elimination half-lives ranged between 0.05 to 0.6 and 1.6 to 7.2 hours, respectively.

Adult↗
PubMed1986

In vivo validation of the origin of the esophageal electrocardiogram.

Esophageal electrocardiography is a clinical and investigational technique that is useful for determining atrial conduction intervals, analyzing atrial rhythms and mapping conduction pathways. Although the left atrial origin of the esophageal electrocardiogram has long been implied, recently that origin has been questioned. In the present study, the origin of the esophageal deflection is defined by direct right and left atrial mapping studies performed with simultaneous esophageal electrograms obtained from three positions (high, mid and low). Seven patients with normal left atrial dimensions (group I) and five patients with left atrial enlargement (group II) underwent transseptal catheterization during the course of electrophysiologic study. In group I (normal left atrial dimensions), conduction time from the high right atrium to each of the three esophageal positions corresponded to conduction times to left atrial sites ranging from 1 to 3 cm lateral to the left interatrial septum. The mid- and low esophageal conduction times were all significantly longer than conduction time to the left side of the septum (p less than 0.05). In group II (enlarged left atrium), conduction times to each of the esophageal sites corresponded to conduction times to left atrial sites lying between the mid-left atrium and a point 1 cm lateral to the left side of the septum. A significant trend toward longer conduction time to the mid-esophageal position than to the left septum was noted (p less than 0.1). In both groups, conduction times measured with the esophageal catheter were significantly longer than conduction time to the right interatrial septum (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

The hemodynamic and clinical responses to terazosin, a new alpha blocking agent, in congestive heart failure.

To determine the hemodynamic effects of a new alpha 1 blocker, terazosin, in congestive heart failure, six patients with this condition underwent hemodynamic testing (at rest and during exercise) before and after dosing. Doses of 2, 5, and 10 mg were examined in sequence over 3 days to define dose-response characteristics. Terazosin, in these doses, decreased pulmonary and systemic vascular resistances and right atrial and pulmonary capillary wedge pressures. Terazosin increased stroke volume and cardiac output, presumably through afterload-reduction, without altering heart rate. These aforementioned responses were apparent both at rest and during exercise. While a direct relationship existed between dose and plasma concentration, a similar relationship was not observed for dose (or plasma concentration) and hemodynamic response; no differences were noted between the hemodynamic responses to the three doses. Improvement in hemodynamics persisted and the clinical status and exercise capacity improved in the four patients chronically treated (over 2 months) with terazosin. Treating the heightened tone of the sympathetic nervous system in congestive heart failure with the alpha 1 blocker, terazosin, may be of benefit to some patients afflicted with this disorder.

Adrenergic alpha-Antagonists↗
PubMed1986

Preliminary observations of chronic indoramin therapy in congestive heart failure.

Twenty-one patients with congestive heart failure (New York Heart Association functional class III) underwent a double-blind, parallel, placebo-controlled, randomized trial of indoramin (average dose of 50 mg every 12 h in 11 patients) versus placebo (n = 10). The study lasted 2 months and was initiated and terminated with the measurement of resting and exercise hemodynamics. Compared with baseline values, chronic administration of indoramin caused a mild reduction in resting mean systemic blood pressure (mean change of -10 mm Hg), and postdosing results included a drop in systemic and pulmonary vascular resistances and pulmonary capillary wedge pressure and a mild increase in stroke volume. Compared with baseline responses, chronic indoramin administration (postdosing) elicited a mild reduction in systemic and pulmonary vascular resistances and pulmonary capillary wedge pressure during submaximal exercise. At this dose, chronic indoramin administration did not alter hemodynamics at maximal exercise or exercise duration to maximal exercise. While certain individual patients experienced clinical improvement on chronic indoramin therapy, the overall clinical status (symptoms, signs, diuretic requirements) of the indoramin-treated group did not change significantly when compared with that of the placebo control group.

Blood Pressure↗
PubMed1986

Aging of the human myocardium: a histologic study based upon endomyocardial biopsy.

This study assesses the effect of aging on human myocardial morphology. Fifteen patients, ranging in age from 28 to 75 with normal cardiac history, physical examination and noninvasive tests of left ventricular function, underwent right ventricular endomyocardial biopsy prior to cancer chemotherapy. Cell diameter, nuclear area and fibrosis were quantified by light microscopy. Semiquantitative methods of electron microscopy were used to grade lipofuscin deposition, tubular dilation, myofibrillar loss, folding of discs and lipid deposition. The results demonstrated that myocardial cell diameter correlated directly with age (r = 0.73, p less than 0.01) and systolic blood pressure (r = 0.51, p less than 0.05). Nuclear area (r = 0.76, p less than 0.01) and folded discs (r = 0.53, p less than 0.05), two signs of increased protein production also correlated with age. Lipid deposition (r = 0.40), tubular dilation (r = 0.31) and lipofuscin deposition (r = 0.20) increased with, but did not correlate significantly with age. Lipid deposition (r = 0.56, p less than 0.05) and tubular dilation (r = 0.43, p less than 0.05) did correlate with cell diameter. Thus, the aging myocardium is characterized by increased cell size and some degenerative changes.

Adult↗
PubMed1986

Hemodynamic-inotropic response to beta-blocker with intrinsic sympathomimetic activity in patients with congestive cardiomyopathy.

The rest and exercise hemodynamic-inotropic response to administration of the beta-blocker pindolol was evaluated in 10 patients with congestive cardiomyopathy to determine whether the intrinsic sympathomimetic activity (ISA) of this agent may preserve ventricular function in the setting of beta-blockade. A significant (p less than .05) rise in systemic and pulmonary vascular resistance and a decline in stroke volume and cardiac index was observed after a single 10 mg dose. The change in cardiac index was negatively correlated with free drug concentration (r = -.59, p less than .01); the change in pulmonary and systemic vascular resistance showed a positive correlation with plasma concentration (r = .67, r = .57, respectively; all p less than .05). The response to exercise reflected a predominant beta-blocking effect, with a significant decrease in peak heart rate and cardiac index and an increase in pulmonary vascular resistance. There were no significant changes in variables of right or left ventricular inotropy after administration of the drug. The mean baseline plasma norepinephrine concentration for the population was 609 +/- 172 pg/ml (normal = 196 +/- 7 pg/ml) and was markedly elevated in two patients (931 and 2053 pg/ml) who developed severe pindolol-induced hypotension. Renin increased markedly in these two patients, but decreased in each of the remaining eight patients. These data indicate that although inotropy is not adversely affected by pindolol, increased afterload, which appears to be mediated by peripheral beta-blockade, results in a reduction in ventricular performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cardiovascular effects of ophthalmic timolol.

We studied cardiovascular effects related to ophthalmic timolol maleate, a beta-adrenergic blocker commonly used to treat chronic glaucoma. Twenty normal subjects were randomly assigned to two double-blind treatment groups each with ten subjects. One group received two drops of ophthalmic timolol (0.5%) twice daily for 4 weeks, and the other received two drops of placebo (artificial tears) twice daily for 4 weeks. Ophthalmic timolol significantly decreased resting and maximal exercise heart rate after the first dose and maximal exercise heart rate during chronic dosing. Chronic timolol administration reduced oxygen consumption at maximal exercise and blunted the augmentation in exercise capacity seen during chronic placebo therapy. Cardiac sympathetic tone and inotropy were reduced after ophthalmic timolol treatment. Despite the presence of drug-induced cardiovascular effects, the plasma levels of timolol were often undetectable and never exceeded 2.8 ng/mL.

Adult↗
PubMed1986

Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure.

Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Electrophysiologic mechanisms of provoked atrial flutter in mitral valve prolapse syndrome.

To examine the electrophysiologic determinants of provoked atrial flutter (AF) in patients with mitral valve prolapse (MVP), studies were performed in 4 groups of patients: group 1 (n = 5), patients with MVP and AF; group 2 (n = 6), patients without MVP but with AF; group 3 (n = 6), patients with MVP but without AF; and group 4 (n = 5), patients without MVP and without AF. P-wave duration, intraatrial conduction, interatrial conduction and effective refractory periods for both the high right atrium and the low right atrium were longer in group 2 than in group 1. The effective refractory period of the low right atrium was longer in group 3 than in group 1. The interatrial conduction interval was longer in group 2 than in group 4. Thus, in patients without MVP, atrial conduction delay is the predominant determinant of AF, whereas differences in right atrial refractoriness appear to be most important to the provocation of AF in the patient with MVP. These differences in atrial refractoriness may be a result of abnormal autonomic influences in patients with MVP.

Adolescent↗
PubMed1985

Usefulness of a free radical scavenger in preventing doxorubicin-induced heart failure in dogs.

This study was designed to investigate whether either of 2 dosage schedules of N-acetylcysteine (NAC) was effective in preventing chronic doxorubicin-induced heart failure in dogs. Thirty-eight dogs were randomly assigned to 1 of 4 groups: controls, 10 dogs; doxorubicin only, 12 dogs; doxorubicin + low dose NAC, 8 dogs; and doxorubicin + high dose NAC, 8 dogs. All dogs except the controls received 1 mg/kg of doxorubicin weekly for 8 weeks and then every other week for 8 weeks. The doxorubicin + low-dose NAC group received 140 mg/kg of NAC 30 minutes before each dose of doxorubicin. The doxorubicin + high-dose NAC group received NAC before and then twice a day for 5 days. Systolic time intervals and echocardiograms were obtained weekly; cardiac catheterization was performed at the conclusion of the study. Of the 38 dogs in the study, 9 died; all deaths were in the doxorubicin treatment groups. The incidence of death was not different between the doxorubicin-only, the doxorubicin + low-dose and the doxorubicin + high-dose NAC groups. The noninvasive and the invasive and the catheterization data generally revealed poorer cardiac function of the doxorubicin treatment groups than in controls. However, no significant differences existed between the doxorubicin-only and doxorubicin + low-dose and doxorubicin + high-dose NAC groups. In conclusion, NAC in a low- or high-dose regimen did not significantly ameliorate doxorubicin cardiac toxicity. Because NAC is a free radical scavenger, perhaps doxorubicin cardiac toxicity is not a result of free radical generation.

Acetylcysteine↗
PubMed1985

Prolonged electrical systole and QT greater than QS2 secondary to coronary artery disease.

Dyssynchronous depolarization-repolarization in the left ventricular (LV) myocardium may produce QT greater than QS2 or long QT. In 41 patients with coronary artery disease (CAD) and LV aneurysm, 46 patients with CAD and a history of acute myocardial infarction (AMI) but no LV aneurysm, and 52 patients with CAD without previous AMI, QT and QS2 were measured simultaneously at a speed of 100 mm/s within 48 hours of cardiac catheterization. Patients receiving class I antiarrhythmic drugs were excluded. The incidence of QT greater than QS2 was significantly greater in patients with LV aneurysm (71%) than in those with previous AMI (22%) and those with CAD but no previous AMI (20%) (p less than 0.001). Likewise, the incidence of long QT corrected for heart rate was significantly greater in patients with LV aneurysm (54%) than in those with previous AMI (7%) and those with CAD and no previous AMI (6%) (p less than 0.0001). The incidence of QT greater than QS2 in another 19 patients with previous AMI who were receiving digitalis therapy was significantly greater (65%) than in those with previous AMI but not receiving digitalis therapy (22%) (p less than 0.001). The incidence of long QT corrected for heart rate and QT greater than QS2 was not statistically different between patients with previous AMI and those with CAD but no previous AMI. The QT greater than QS2 or long QT in patients with aneurysm is probably a result of dyssynchronous depolarization or repolarization within or in the border zone of the LV aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Failure of percutaneous transluminal coronary angioplasty to stimulate platelet and prostaglandin activity.

Platelet function and prostaglandin activity were evaluated in nine patients with coronary artery disease undergoing percutaneous left anterior descending coronary artery angioplasty (PTCA) and compared to nine normal controls. Transcoronary measurements (arterial-coronary sinus) of platelet counts, mean platelet volume, platelet factor 4 (PF4), beta thromboglobulin, thromboxane (B2), and 6-keto-PGF 1 alpha were made. When compared to normal controls, the patients with coronary artery disease had higher circulating baseline levels of PF4 in the coronary sinus. There was no transcardiac production of any factor at baseline or immediately after infusion of nitroglycerin or performance of PTCA. These results suggest that PTCA does not grossly alter arachidonic acid metabolism or platelet activity.

6-Ketoprostaglandin F1 alpha↗