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Biomedical subjects

D V Unverferth

Publications and source records attributed to D V Unverferth.

At least 37 records · Page 2Linked to original sources
PubMed1987

Regional myocyte hypertrophy and increased interstitial myocardial fibrosis in hypertrophic cardiomyopathy.

The purpose of this study was to determine if the thickened cardiac walls of patients with hypertrophic cardiomyopathy (HC) are due to increased size or number of myocytes or increased amounts of fibrous tissue. Eight patients, aged 18 to 42 years, who died from complications of HC and 8 age-matched control subjects without heart disease were studied. A 1.5-cm3 block of tissue was removed from the left ventricular free wall, right ventricular free wall and ventricular septum (VS). Each region of each wall was evaluated for fibrous tissue by point counting; cell diameter was measured using an ocular micrometer disc. Cell layers were counted across the walls. The results revealed that increased cell size, cell layers and fibrous tissue are characteristic of HC, but only in the VS are all 3 significantly increased. The fibrous tissue was most extensive in the VS (19 +/- 9%), but it was more extensive than in the control subjects in all 3 walls. Cell diameters were largest in the layers closest to the left ventricular cavity.

Adult↗
PubMed1987

Safety and efficacy of inferior vena caval occlusion to rapidly alter ventricular loading conditions in idiopathic dilated cardiomyopathy.

To investigate the safety and efficacy of inferior vena caval (IVC) balloon occlusion for preload alteration in humans, 13 patients with dilated cardiomyopathy were studied before and during repeated (total of 78) IVC occlusions. Left and right ventricular (LV and RV) micromanometer pressures were simultaneously measured and M-mode and 2-D echocardiograms were recorded at end expiration. Complications were limited to abdominal discomfort in 2 patients. With IVC occlusion, RV collapse fluoroscopically shifted the heart toward midline and ventricular septal motion was frequently disordered. Significant (p = 0.001) changes occurred in RV and LV systolic peak pressures (from 19 +/- 6 to 12 +/- 5 mm Hg and from 129 +/- 34 to 109 +/- 25 mm Hg, respectively). LV and RV end-diastolic pressures also decreased significantly (from 18 +/- 7 to 6 +/- 6 mm Hg and from 5 +/- 3 to 2 +/- 2 mm Hg, respectively) (both p less than or equal to 0.0055). Similarly, LV end-diastolic diameter decreased 13% (from 61 +/- 11 to 53 +/- 12 mm, p = 0.0002). Mean heart rate did not change significantly (from 76 +/- 19 to 78 +/- 21 beats/min). Thus, IVC balloon occlusion provides a safe method of repeatedly altering loading conditions in humans. This approach allows for acquisition of important information regarding cardiac chamber dynamics while minimizing the effects of reflex mechanisms and avoiding use of pharmacologic agents.

Adult↗
PubMed1987

Influence of exercise on coronary sinus blood flow determinations.

Consecutively measured values of coronary sinus blood flow were compared to assess the reproducibility of the coronary sinus thermodilution technique. Values measured at rest and during exercise were evaluated and the influence of the respiratory cycle on reproducibility was studied. Correlation of consecutive values revealed a coefficient of 0.94 at rest and 0.93 during exercise. Differences between mean values of consecutive measurements were nonsignificant. A comparison of the coefficients of variation at rest (8.50 +/- 7.09) and exercise (8.02 +/- 4.75) revealed no significant difference. Variation about mean coronary sinus blood flow due to inspiration and expiration was similar at rest and during exercise (42% and 37%, respectively). Provided that critical variables are closely monitored, the coronary sinus thermodilution technique is a highly reproducible technique in a clinically feasible setting.

Adult↗
PubMed1987

Diastolic time in congestive heart failure.

Diastolic perfusion time is an important determinant of coronary blood flow and subendocardial perfusion. It has been proposed that subendocardial ischemia may exacerbate and perpetuate left ventricular dysfunction in congestive heart failure. Diastolic perfusion time in relation to heart rate was analyzed in 29 digitalized (group 1) and 12 nondigitalized patients (group 2) with heart failure and in 58 normal control subjects. In group 1 there was a strong negative exponential correlation (r = -0.85) and in group 2 a strong negative logarithmic correlation (r = -0.95) between heart rate and diastolic time; both regressions differed significantly from normal control. There was a 9% increase of diastolic time at a heart rate of 60 bpm in group 1 and a 7% increase in group 2 (both p less than 0.05) compared with normal subjects. The curves intersected the regression line of normal subjects at a heart rate of 98 bpm in group 1 and 93 bpm in group 2. At 120 bpm there was a 10% decrease in diastolic time for both groups with heart failure (both p less than 0.05). Changes in diastolic perfusion time relative to heart rate are more pronounced in congestive heart failure such that at faster heart rates this relationship may further impede subendocardial blood flow.

Adult↗
PubMed1987

An analysis of the determinants of exercise performance in congestive heart failure.

Twenty-nine patients with chronic congestive heart failure underwent symptom-limited maximal exercise to define the determinants and predictors of exercise capacity in this condition. Clinically, the combination of age, cardiothoracic ratio, and left ventricular displacement was moderately predictive of exercise capacity (R2 = 0.44, p = 0.004). Noninvasive and angiographic measurements of ventricular performance failed to predict maximal exercise duration. Resting systemic and pulmonary arteriolar resistances correlated modestly with maximal effort tolerance (supine: R2 = 0.25, p = 0.02; upright: R2 = 0.38, p = 0.002). At a predetermined level of submaximal exercise, changes in heart rate and pulmonary arteriolar resistance plus the absolute value of systemic arteriolar resistance correlated moderately with exercise duration (R2 = 0.44, p = 0.003). For all parameters examined, exercise capacity was most reliably determined during the transition from submaximal to maximal exercise through the combination of changes in heart rate and stroke volume and the exercise end point value of systemic arteriolar resistance (R2 = 0.87, p = 0.0001). Exercise capacity in chronic cardiac failure appears to be best explained by the patient's ability to increase heart rate and stroke volume beyond a set submaximal stage of exercise. Excessive vascular resistances may further restrain cardiac performance and the delivery of blood to exercising structures during exhaustive exercise.

Adult↗
PubMed1987

Morphologic and functional characteristics of the heart in Friedreich's ataxia.

The purpose of this study was to characterize the heart in patients with Friedreich's ataxia by two-dimensional echocardiography, systolic time intervals, and heart biopsy. Ten patients with Friedreich's ataxia (seven females and three males, age 15 +/- 7 years) were compared with 10 age-matched normal subjects (five males and five females, age 16 +/- 7 years). The mean systolic blood pressure in the patients with Friedreich's ataxia was lower (114 +/- 9 mm Hg) than that in the control subjects (122 +/- 8 mm Hg; p less than 0.05); diastolic blood pressures were the same. The heart rate in the patients with Friedreich's ataxia (102 +/- 17 beats/minute) was greater than that in the control subjects (76 +/- 12 beats/minute; p less than 0.001). The interventricular septal wall thickness was much greater in Friedreich's ataxia (13 +/- 2 versus 8 +/- 1 mm, p less than 0.001) as was the posterior wall thickness (13 +/- 3 versus 8 +/- 1 mm, p less than 0.001). The left ventricular end-diastolic diameter was smaller in Friedreich's ataxia (35 +/- 6 mm versus 47 +/- 6 mm; p less than 0.01), and the fractional change of the left ventricular minor axis with systole was greater in Friedreich's ataxia (40 +/- 9 percent versus 33 +/- 5 percent; p less than 0.05). An 11th patient with Friedreich's ataxia (age 33) had clinical heart failure, but his course was complicated by alcohol abuse. Heart biopsy in three patients with Friedreich's ataxia demonstrated myocyte hypertrophy (21.5 +/- 2.0 microns diameter; normal, 14 to 17 microns) and increased fibrosis (16 +/- 9 percent; normal, less than 5 percent). Thus, heart disease in Friedreich's ataxia is characterized by myocyte hypertrophy, interstitial fibrosis, increased left ventricular wall thickness, decreased left ventricular cavity size, sinus tachycardia, and normal systolic function. Further biochemical analysis of tissues may lead to the link of the neurologic and cardiac diseases and eventually to more effective therapy of this condition.

Adolescent↗
PubMed1987

Histologic and biochemical correlates of left ventricular chamber dynamics in man.

To investigate the relation between left ventricular chamber dynamics in humans and the quantitative analysis of the histologic and biochemical characteristics of left ventricular endomyocardial biopsy material, 15 patients with a wide range of ventricular function were studied. The pressure-volume relation was determined using simultaneous gated radionuclide angiography, echocardiography and micromanometer pressure. The derived chamber dynamics were then compared with quantitative histologic data (percent fibrosis and cell diameter) and adenosine triphosphate content measurements obtained from the left ventricular biopsy specimen obtained at the time of the pressure-volume studies. The measures of systolic function correlated linearly with high energy phosphate content. The adenosine triphosphate/protein ratio (nanomoles) was shown to parallel ejection fraction (r = 0.81), peak ejection rate (r = -0.73) and peak positive maximal rate of rise in left ventricular pressure (dP/dt) (r = 0.79). No correlation was observed between these variables and the percent fibrosis or cell diameter. Variable results were found in comparing the diastolic properties of the left ventricle with the biopsy data. In general, the high energy phosphate content correlated with measures of active relaxation, but not with the passive filling characteristics of the left ventricle. The adenosine triphosphate/protein ratio was linearly related to peak negative dP/dt (r = -0.74) and the peak filling rate (r = 0.76) but correlated less well with other measures of active and passive diastolic filling. No correlation was found between any diastolic variable and the percent fibrosis or cell diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Long-term indoramin therapy in congestive heart failure: a double-blind, randomized, parallel placebo-controlled trial.

Twenty-one patients with moderately severe congestive heart failure participated in a double-blind, randomized, parallel placebo-controlled trial designed to evaluate the effects of long-term (2 months) indoramin therapy on rest and exercise hemodynamics, exercise capacity and clinical status of patients with this clinical syndrome. The long-term administration of indoramin in patients (mean dose 50 mg every 12 hours) caused a mild reduction from baseline values in supine rest mean systemic blood pressure and, after dosing, elicited a significant reduction in systemic and pulmonary vascular resistances, pulmonary capillary wedge pressure and heart rate as well as a mild increase in stroke volume. Long-term indoramin therapy caused a small decrease, as compared with baseline exercise responses, in systemic and pulmonary vascular resistance and pulmonary capillary wedge pressure at submaximal levels of exercise. It did not alter hemodynamic variables at maximal exercise, exercise capacity or overall clinical status, compared with findings at baseline or with placebo.

Aged↗
PubMed1987

Hemodynamic and metabolic responses of the exercising lower limb of humans.

This study was performed to determine the hemodynamic and metabolic responses of the human lower limb during exercise. Blood flow to the lower extremity was measured and sampled for lactate, catecholamines, and oxygen content in 12 normal men at rest, at all stages of bicycle ergometry, and during the postexercise recovery period. Whole body oxygen consumption and cardiac output were recorded throughout the experiment. Limb blood flow increased in a near-linear manner with both whole body and limb oxygen consumption. Although cardiac output rose with increasing whole body oxygen consumption, the increment in cardiac output diminished between submaximal and maximal levels of exercise resulting in a curvilinear relationship between blood flow to the exercising limb and cardiac output; this indicates that a major redistribution of cardiac output to the exercising lower extremity occurs, particularly at maximal levels of exercise. Covariance analysis suggested that limb oxygen consumption was the primary determinant of limb blood flow and limb vascular resistance during exercise. Arterial and venous lactate and catecholamine concentrations, obtained from the exercising lower extremity, could not be implicated as factors having a major influence on blood flow to that limb. The rate of lactate efflux from the limb during and after exercise, however, was directly related to limb blood flow.

Adult↗
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

Value of endomyocardial biopsy.

The role of endomyocardial biopsy may be restricted to the diagnosis of myocarditis. On the other hand, a broad utilization of the biopsy technique may be championed by those who believe that the light and electron microscopic characteristics of the tissue are important and that the biochemical features of the tissue may hold important clues to the diagnosis and therapy of dilated cardiomyopathy. The popularity of endomyocardial biopsy arises from the ease and safety of the procedure. Light microscopy of the tissue is useful not only to diagnose myocarditis but also to discover infiltrative cardiomyopathies and to characterize the dilated cardiomyopathies by the amount of fibrosis and cellular hypertrophy. Electron microscopy supplies more detailed information on the myofibrils, nuclei, tubular structures, mitochondria, glycogen, and lipofuscin. At present, these data are clinically applicable only to the anthracycline cardiomyopathies. On an investigational basis, subcellular characteristics may help us better understand the etiology and pathogenesis of dilated cardiomyopathy. The greatest promise lies in the biochemical assessment of tissue, which may uncover single or multiple biochemical abnormalities in heart failure. Although the clinical usefulness of endomyocardial biopsy is quite restricted at present, its future looks quite promising.

Amyloid↗
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

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

Evolution of a hereditary cardiac conduction and muscle disorder: a study involving a family with six generations affected.

This study describes six generations of a family with autosomal dominant cardiac conduction system and myocardial disease with recognizable clinical stages. A 20 year follow-up of nine family members, a medical questionnaire of 196, electrocardiographic screening of 91, noninvasive testing of 20, and catheterization with endomyocardial biopsy of six are the basis of this report. The clinical stages are as follows: Stage I occurs in the second and third decades of life and is characterized by an absence of symptoms, normal heart size, sinus bradycardia, and premature atrial contractions. Stage II is marked by first-degree atrioventricular block in the third and fourth decades. Stage III occurs in the fourth and fifth decades and is accompanied by chest pain, fatigue, lightheadedness, and advanced atrioventricular block followed by the development of atrial fibrillation or flutter. Stage IV, in the fifth and sixth decades of life, is characterized by congestive heart failure and recurrent ventricular arrhythmias. Light microscopy of right ventricular endomyocardial biopsy specimens from patients in stage II revealed very mild fibrosis; electron microscopy of the specimens demonstrated mild dilatation of tubules, mitochondrial swelling, and minimal myofibrillar loss. Biopsy specimens from patients with stage III disease were similar to those from patients with stage II disease except for an increase of myofibrillar loss. The stage IV specimens had diffuse fibrosis and more severe tubular dilatation, mitochondrial cristolysis, and myofibrillar loss. At autopsy in the proband, the atrial changes were more severe than the ventricular and were especially marked in the sinoatrial and atrial myocardium. Early recognition of the disease and use of pacemakers and antiarrhythmic agents have proved beneficial for affected family members. Thorough family studies of patients with conduction system disease and/or dilated cardiomyopathy are necessary to better understand the hereditary basis and natural course of this category of disease.

Adolescent↗
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↗