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Biomedical subjects

D V Unverferth

Publications and source records attributed to D V Unverferth.

At least 73 records · Page 4Linked to original sources

Combined systolic time intervals and M-mode echocardiography in the evaluation of central hemodynamics in primary pulmonary hypertension.

8 patients with moderate to severe primary pulmonary hypertension underwent systolic time intervals, M-mode echocardiography, and direct hemodynamic studies in order to determine the correlation between noninvasive parameters and hemodynamic variables and to evaluate the utility of these noninvasive studies in primary pulmonary hypertension. The ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) of the systolic time intervals was abnormally increased (greater than 0.42) for each subject; the increase in the PEP/LVET was secondary to a shortening of the left ventricular ejection time in 4 patients, prolongation of the pre-ejection period in 1, or a combination of such, noted in 3. In contrast, echocardiographic parameters of left ventricular function, specifically, percent change in the minor axis of the left ventricle with systole, velocity of circumferential fiber shortening, and ejection fraction, were normal. In addition, a very good correlation was noted between PEP/LVET and total pulmonary resistance (r value = -0.89), while the echocardiographic parameters correlated well with stroke volume and cardiac indices (r values ranged from 0.68 to 0.72). These results indicate that in primary pulmonary hypertension, systolic time intervals provide an estimation of overall cardiac-cardiovascular performance, rather than left ventricular function alone, which in turn, is validly examined by M-mode echocardiography.

Adult↗

The effect of age on central and regional hemodynamics.

16 normal subjects, ranging in age from 24 to 79 years, underwent simultaneous central and regional (renal, hepatic and limb) hemodynamic measurements; the purpose of this investigation was to determine the relationship between these measurements and age. Cardiac index was inversely related to age, with a correlation coefficient of -0.53 (p less than 0.05). Renal blood flow correlated inversely with age at an r value of -0.52 (p less than 0.05). Although the correlation coefficients did not achieve statistical significance, several trends were noted with increasing age: systemic vascular resistance, renal, hepatic and limb vascular resistances, and mean systemic blood pressure increase and hepatic and limb flows decrease. In normal human subjects, certain central and regional hemodynamic parameters change with age; these changes may ultimately influence function and perhaps, drug disposition (liver and kidney) as well.

Adult↗

Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure.

Central and regional (hepatic, renal, and limb) hemodynamic data are presented for a normal population (n = 16) and for a group of patients with congestive heart failure (n = 64). The patient population represented a wide spectrum of severity of congestive heart failure. Various relationships between central and regional hemodynamics were analyzed. The results indicate that in congestive heart failure blood flow to hepatic, renal, and limb regions is significantly decreased, and that this decrease is proportional and linearly related to the reduction in cardiac output. The vascular resistances of these regions correlated directly with systemic vascular resistance. Changes in renal vascular resistance and renal blood flow became attenuated as the severity of the heart failure advanced from moderate to severe and at higher levels of systemic vascular resistance. There was little to no correlation between systemic blood pressure and liver, kidney, and limb blood flow for the range of systemic pressures studied.

Adult↗

Beneficial effects of nifedipine on rest and exercise myocardial energetics in patients with congestive heart failure.

Rest and exercise systemic hemodynamic parameters, coronary blood flow, and myocardial energetics were assessed before and 15 min after the sublingual administration of 20 mg of nifedipine in 10 patients with idiopathic congestive cardiomyopathy. When compared with control, nifedipine increased rest and exercise cardiac index by 37% and 28%, respectively (p less than .001). Peripheral vasodilation was demonstrated with a drop in systemic arterial pressure, exercise pulmonary capillary wedge pressure, and systemic vascular resistance (p less than .05). The calcium-channel blocker did not alter myocardial oxygen consumption; however, coronary blood flow increased by 32% at rest (p less than .01) while coronary vascular resistance diminished both at rest and after exercise compared with control (p less than .05). Nifedipine elicited a decrease in the rest and exercise aortocoronary sinus oxygen difference while the coronary sinus oxygen saturation increased (p less than .01). In this group of patients with idiopathic congestive cardiomyopathy, nifedipine enhanced myocardial performance while increasing coronary blood flow and favorably altering the myocardial oxygen supply-demand balance.

Adult↗

Chronic oral amrinone therapy in congestive heart failure: a double-blind placebo-controlled withdrawal study.

Eighteen patients with congestive heart failure were studied in a double-blind, randomized, placebo-controlled withdrawal trial to evaluate the effectiveness of chronic oral amrinone therapy when added to conventional heart failure therapy. All patients received a four-week lead-in of amrinone 100 mg orally every 8 h, then were randomly assigned to either continued amrinone (nine patients) or placebo (nine patients) groups. Compared to placebo, chronic amrinone therapy did not significantly improve clinical status, left ventricular function as measured by non-invasive testing techniques, or exercise tolerance. Side-effects occurred in every patient receiving amrinone and abated in those patients who received placebo for the last 12 weeks of the study. The limited effectiveness of oral amrinone and the high frequency of side-effects preclude the widespread use of this drug in the chronic therapy of congestive heart failure.

Administration, Oral↗

Reperfusion of the human myocardium by saphenous vein bypass grafts. Biochemical considerations.

The adenine nucleotide content of the human myocardium in the distribution of the left anterior descending coronary artery (LAD) was measured before and after saphenous vein bypass grafting. The purpose of the study were twofold: (1) to relate the level of adenosine triphosphate (ATP) before bypass grafting to the percent stenoses of the LAD and (2) to determine the benefit or lack of benefit of bypass grafting on ATP content. Eighteen patients with angiographically determined LAD lesions of 40% to 100% underwent bypass grafting with standard cardiopulmonary bypass and cardioplegia. Transmural needle biopsy specimens were obtained from the center of the area perfused by the LAD immediately before cross-clamping of the aorta and 30 minutes after reperfusion of the myocardium via the native LAD and the graft. The tissue was divided into thirds: The endocardial and epicardial thirds were analyzed for ATP by high-pressure liquid chromatography and the middle third was viewed by light microscopy. The percent narrowing of the LAD correlated well (r = -0.71) with the ratio of ATP to total adenine nucleotides (TAN) in the endocardium. Epicardial ATP did not correlate with the percent stenoses of the LAD. The endocardial ATP/TAN ratio increased in the group as a whole from 0.51 +/- 0.27 (mean +/- SD) to 0.64 +/- 0.26 (p less than 0.01) after bypass grafting, and this was most impressive in those eight patients with LAD lesions greater than 90% (0.32 +/- 0.20 before grafting to 0.60 +/- 0.29 after grafting, p less than 0.005). However, the epicardial ATP/TAN ratio decreased from 0.75 +/- 0.15 before grafting to 0.64 +/- 0.17 after grafting (p less than 0.05), and this decrease occurred regardless of the percent narrowing of the LAD. There was no difference in vacuolization between the pre-grafting and post-grafting biopsy specimens, and intramyocardial hemorrhage was not observed. This study has demonstrated a close relationship between the degree of LAD stenosis and endocardial ATP content. Also, the endocardium supplied by arteries with greater than 90% lesions had significantly increased ATP while the epicardium had decreased ATP content after bypass grafting.

Adenine Nucleotides↗

Amrinone in severe congestive heart failure: another look at an intriguing new cardioactive drug.

Seven patients with severe congestive heart failure received amrinone i.v. (continuous infusions of 10, 20 and 40 micrograms/kg/min) and orally (1.5, 3.0 and 4.5 mg/kg) in order to determine the comprehensive acute hemodynamic response of this agent. Standard hemodynamic, echocardiographic and systolic time interval measurements were made before and sequentially after amrinone administration. Intravenous amrinone significantly increased cardiac index and stroke volume index, did not alter heart rate and significantly decreased pulmonary capillary wedge pressure, mean systemic blood pressure and systemic and pulmonary vascular resistances. The determinants of left ventricular inotropy, delta P/delta t, pre-ejection period index and velocity of circumferential fiber shortening were not affected by amrinone; dobutamine (5 and 10 micrograms/kg/min), used as an internal standard for inotropy, significantly improved these determinants. Except for a significant reduction in pulmonary capillary wedge pressure, first-dose oral amrinone effected little change in central hemodynamic variables and indices of ventricular inotropy; no additional changes occurred after the fifth dose. In the setting of severe chronic congestive heart failure, short-term iv infusions and oral administration of amrinone elicit only mild to moderate hemodynamic changes. Furthermore, these changes are a result of vasodilation (preload and afterload reduction) rather than positive inotropy.

Adult↗

Early changes in human myocardial nuclei after doxorubicin.

Ten nuclei from the endomyocardial biopsies for each of the following 32 patients were examined by electron microscopy: seven patients before and then four and 24 hours after treatment with first-dose doxorubicin; seven patients before and four and 24 hours after treatment with first-dose doxorubicin plus N-acetyl cysteine; nine patients with doxorubicin induced cardiomyopathy; and nine patients with idiopathic congestive cardiomyopathy. Five criteria were used to semiquantitatively compare nuclei and nucleoli from each group. The most dramatic changes in nuclear and nucleolar morphology were seen four hours after doxorubicin administration. Nucleoli were smaller, contracted or segregated and contained fewer fibrillar centers and a collapsed or fragmented nucleolonema. The addition of N-acetylcysteine to treatment did not alter these results. By 24 hours, nuclei had returned to the pre-treatment status. Long-term doxorubicin therapy produced increased chromatin clumping and slightly contracted nucleoli. The idiopathic congestive cardiomyopathic nuclei differed significantly from these doxorubicin cardiomyopathic nuclei in the decreased amount of chromatin clumping and the increase in fibrillar centers and nucleonema pattern. It is concluded from this study that: (1) doxorubicin markedly alters the morphology of the human myocardial nucleus and nucleolus four hours after treatment, but these changes diminish by 24 hours; (2) N-acetylcysteine treatment fails to prevent these changes; and (3) the nuclei and nucleoli of chronic doxorubicin-induced cardiomyopathy differ significantly from other congestive cardiomyopathies, but do resemble changes seen four hours after the first dose of doxorubicin.

Acetylcysteine↗

Regression of myocardial cellular hypertrophy with vasodilator therapy in chronic congestive heart failure associated with idiopathic dilated cardiomyopathy.

Forty-nine patients with idiopathic dilated cardiomyopathy (IDC) were evaluated to determine the hemodynamic and morphologic effects of vasodilator therapy. Hydralazine (225 mg/day, H), isosorbide dinitrate (160 mg/day, I), and combination H + I therapy were compared with placebo (P) at baseline and after 3 months of continuous therapy. Thirty-three randomly assigned patients completed the study. Hemodynamic parameters included the echocardiographic percent change of left ventricular diameter (% delta D), the systolic time intervals ratio of preejection period to left ventricular ejection time (PEP/LVET), the pulmonary capillary wedge pressure, mean pulmonary artery pressure, cardiac index, systemic vascular resistance, and pulmonary vascular resistance. An endomyocardial biopsy was performed at baseline and after 3 months; the myocardial cell diameter of 50 cells per biopsy was measured. During the 3-month study 5 patients died; there was not a significant difference among the groups in the number of deaths. The % delta D and PEP/LVET did not change in the P or I groups but did improve significantly from baseline in the H and H + I groups. The pulmonary capillary wedge and mean pulmonary artery pressures and the pulmonary vascular resistance did not change in the P or H groups but did decrease significantly in the I and H + I groups. The P and I groups did not have improvement in systemic vascular resistance or cardiac index, whereas the H group had a decrease in systemic vascular resistance and an increase in cardiac index from 2.5 +/- 0.4 to 3.1 +/- 0.4 liters/min/m2 (p less than 0.05). The H + I group also had a decrease in systemic vascular resistance; the cardiac index increased from 2.3 +/- 0.4 to 3.1 +/- 0.4 liters/min/m2 (p less than 0.01). Myocardial cell diameter did not change in the P or I group. Cell diameter of the H group decreased from 25.4 +/- 3.1 microns at baseline to 23.1 +/- 3.8 microns (p less than 0.05) after 3 months of continuous therapy. The H + I group decreased its cell diameter from 23.9 +/- 3.7 to 22.2 +/- 2.2 microns (p less than 0.05). Compared with P and H, patients treated with I alone or H + I had a significant reduction of preload. In contrast to P and I, H alone and H + I elicited improvement in parameters of inotropy and afterload, and this improvement was accompanied by a reduction in cell diameter. Chronic therapy of heart failure with H and H + I effects a persistent augmentation of cardiac function and improvement of myocardial cellular morphology.

Aged↗

Clonidine in congestive heart failure: a vasodilator with negative inotropic effects.

Fourteen patients with moderately severe congestive heart failure (CHF) were given clonidine orally (0.2 and 0.4 mg doses) to determine the hemodynamic effects of a typical centrally acting vasodilator. The 0.2 mg dose significantly reduced mean systemic (15%) and mean pulmonary artery (20%) pressure; the corresponding reductions in vascular resistance were not as great because of a diminished cardiac output. Pulmonary capillary wedge pressure decreased significantly (27%). Heart rate decreased 11% and stroke volume remained unchanged. At a higher dose (0.4 mg), clonidine augmented these reductions but increased stroke volume modestly (15%). Isovolumic developed pressure/duration of isovolumic contraction and the duration of the preejection period were used as indexes of inotropy. After both doses, isovolumic developed pressure/duration of isovolumic contraction decreased dramatically (greater than or equal to 33%) and the preejection period increased substantially (greater than or equal to 18%) (both p less than 0.05). Compared with currently employed vasodilating agents, the centrally acting agent clonidine appears unique in that the drug-induced systemic and pulmonary arterial vasodilation are not accompanied by a commensurate improvement in ventricular systolic function. This lack of improvement appears to be a result of negative inotropic effects.

Adult↗

The hemodynamic and metabolic advantages gained by a three-day infusion of dobutamine in patients with congestive cardiomyopathy.

Most patients with nonischemic congestive cardiomyopathy (COCM) derive subjective benefit from a 3-day intravenous infusion of dobutamine. The mechanism of this improvement was evaluated by the measurement of metabolic factors (serum sodium and blood urea nitrogen [BUN]) during the infusion in 23 group I patients. In addition, six patients (group II) had an endomyocardial biopsy procedure before and after 3 days of bed rest and then after 3 days of dobutamine. The tissue was analyzed for adenosine triphosphate (ATP) and creatine. The eight group III patients had cardiac output, coronary sinus blood flow, and arterial and coronary sinus oxygen saturation measurements before and during two dose increments of dobutamine (5 and 10 micrograms/kg/min). The results demonstrated that the mean sodium of group I patients rose from 135 +/- 3 (means +/- SD) to 137 +/- 4 mEq/L (p less than 0.05) and the BUN fell from 21 +/- 7 to 15 +/- 6 mg/100 ml (p less than 0.001). The ATP/creatine of the endomyocardial biopsies from group II did not change from control with bed rest (0.36 +/- 0.24 to 0.37 +/- 0.24), but rose to 0.62 +/- 0.26 (p less than 0.05) after dobutamine. In group III, the cardiac output and coronary blood flow increased proportionately with increasing doses of dobutamine. These data suggest that there are both metabolic and hemodynamic advantages gained during a 3-day infusion of dobutamine, and that either or both could contribute to the clinical improvement noted in patients with COCM.

Adenosine Triphosphate↗

Amrinone therapy for congestive heart failure in outpatients with idiopathic dilated cardiomyopathy.

Amrinone, 100 mg orally every 8 hours, was administered to 13 patients with moderate-to-severe congestive heart failure (CHF) for 1 month on an outpatient basis to determine the beneficial and undesirable effects of this new cardioactive agent in this clinical setting. These subjects received conventional CHF medications during the course of study. Ten patients who received conventional CHF medications alone served as a control group. Changes in functional classification were not significantly different between the 2 treatment groups. Amrinone augmented exercise capacity 37% above baseline compared with a 12% improvement for the control group. Noninvasive indexes of resting left ventricular function (echocardiography and systolic time intervals) did not change significantly for either group, nor was there a significant change in the exercise ejection fraction. All patients treated with amrinone had greater than or equal to 1 symptom-related or laboratory-detected adverse effect. An increase in the frequency of ventricular ectopic beats was noted at rest in 4 and with exercise in 6 patients (salvos of nonsustained ventricular tachycardia in 2). Six subjects treated with amrinone had gastrointestinal symptoms and 8 developed a viral-like illness. Other adverse effects noted in the amrinone-treated group included near-syncope, headaches, marked anxiety, chest pain, palpitations, maculopapular rash, hypokalemia, and elevation of serum transaminase levels. The control patients had significantly fewer adverse effects. Although individual patients with CHF may benefit from long-term amrinone therapy, the low benefit-to-risk-adverse effect ratio does not warrant widespread application of this drug in the outpatient management of CHF and requires caution when prescribing.

Aminopyridines↗

The effect of left atrial histology and dimension on P wave morphology.

This study correlates left atrial appendage cell size, atrial fibrosis and echocardiographic (echo) measurement of left atrial size with P wave morphology. Twelve patients with known mitral valve disease had echo measurements of left atrial size with P wave morphology. Twelve patients with known mitral valve disease had echo measurements of left atrial size prior to mitral valve surgery; patients had varying degrees of left atrial enlargement. The left atrial appendage, removed at the time of surgery, was stereologically assessed for percent fibrosis and the diameters of 50 cells were measured and averaged. These factors were correlated with P wave amplitude and duration in lead II, greatest length in any led, PR segment (end of P wave to onset of QRS), P to PR segment ratio (in lead II) and the PR interval. There was a good correlation of left atrial cell diameter with P wave amplitude (r = .69, p = 0.01). There was a good inverse correlation of percent fibrosis with the PR segment (r = -.72, p = 0.01) and a direct correlation of fibrosis with the ratio of P wave length to PR segment (r = .67 p = 0.01). There was a trend for percent fibrosis to correlate with PO wave duration but not height. No correlation was noted for any of the P wave characteristics and left atrial size. This study demonstrates that there is a correlation of P wave height with cell diameter and P wave length and PR segment with fibrosis. These data are helpful in understanding the electrocardiographic P wave.

Cardiomegaly↗

Differentiating characteristics of myocardial nuclei in cardiomyopathy.

Myocardial tissue obtained by endomyocardial biopsy was semiquantitatively evaluated for nuclear and nucleolar characteristics in six groups of patients: patients with normal cardiac function (group 1), doxorubicin-induced cardiomyopathy (group 2), idiopathic cardiomyopathy (group 3), alcoholic cardiomyopathy (group 4), post-viral cardiomyopathy (group 5), and chronic valvular heart disease (group 6). From each patient, ten nuclei containing nucleoli were examined and rated on the basis of the following characteristics: chromatin clumping, number of fibrillar centers per nucleolus, nucleolonemal structure, size of nucleolus, number of nucleoli per nucleus, and stage of nucleolar change. Mean values for the nuclear characteristics in each group were compared with normal values using the unpaired t test. In the doxorubicin treated group there were significantly increased chromatin clumping, decreased fibrillar centers, decreased nucleolonemal structure, and increased numbers of contracted nucleoli (indicating later stage). These changes may be linked to lowered nuclear and nucleolar activity. In the idiopathic and post-viral groups, characteristics were consistent with increased nuclear and nucleolar activity. There were no significant changes from normal in the nucleolar features of either the alcoholic or valvular groups. Further comparisons between groups using one-way analysis of variance and multivariate statistical analysis support the conclusion that there are significant differences in the nuclear and nucleolar characteristics of these groups.

Analysis of Variance↗

Dobutamine and hydralazine: comparative influences of positive inotropy and vasodilation on coronary blood flow and myocardial energetics in nonischemic congestive heart failure.

Coronary blood flow and myocardial energetics were assessed after the administration of a parenteral inotrope (dobutamine hydrochloride) and an oral vasodilator agent (hydralazine) in 10 patients with nonischemic congestive heart failure. Dobutamine (5 micrograms/kg per min) and hydralazine (1 mg/kg) when group-matched elicited an identical increase in cardiac index and stroke volume index. Both agents augmented coronary blood flow while reducing coronary vascular resistance. Both forms of therapy elicited a significant increase in myocardial oxygen consumption. Dobutamine, demonstrating a balanced effect on the coronary circulation, induced a proportional increase in coronary blood flow and myocardial oxygen consumption, with the arterial-venous oxygen difference across the coronary vascular bed remaining unchanged. Hydralazine enhanced the myocardial oxygen supply versus demand ratio; despite a significant increase in myocardial oxygen consumption, the arterial-venous oxygen difference and the myocardial extraction ratio diminished. Both forms of therapy enhanced cardiac performance without inducing any electrocardiographic or clinical evidence of ischemia. Dobutamine, a positive inotropic agent, elicited a balanced effect on the coronary circulation while hydralazine, a vasodilator agent, induced a greater increase in coronary flow than in myocardial oxygen demand.

Adult↗

Captopril in primary pulmonary hypertension.

Seven women with primary pulmonary hypertension underwent hemodynamic evaluation, at rest and during exercise, before and after the oral administration of captopril. Dose-response curves were generated for the 25-, 50- and 100-mg doses. Captopril significantly reduced systemic blood pressure and systemic vascular resistance; these effects persisted at submaximal levels of exercise. Captopril did not alter pulmonary artery pressure or resistance, cardiac output or stroke volume at rest or during exercise. Exercise tolerance did not improve. Four of the patients also received captopril chronically for 12 weeks at doses of 75 and 100 mg every 8 hours. Resting and exercise hemodynamic evaluation was repeated at the end of the 12-week period. Except for a persistent reduction in mean systemic blood pressure at rest, chronic captopril administration did not elicit hemodynamic changes. Measured exercise duration did not change during continuous captopril treatment, although one patient reported mild subjective improvement in activity tolerance. In primary pulmonary hypertension, captopril exerts its major effect on systemic vasculature, with little or no effect on the pulmonary circuit. While an occasional patient may experience some clinical improvement with captopril therapy, the majority of adult patients with severe primary pulmonary hypertension will not benefit from its chronic administration.

Adult↗

Improved exercise capacity and differing arterial and venous tolerance during chronic isosorbide dinitrate therapy for congestive heart failure.

We studied 30 patients with moderate-to-severe congestive heart failure in a double-blind, randomized, placebo-controlled trial to determine the acute and long-term effects of isosorbide dinitrate on clinical status and on resting and exercise hemodynamics. Seventeen patients received placebo and 13 isosorbide dinitrate. First-dose isosorbide dinitrate (40 mg orally) decreased resting and exercise pulmonary capillary wedge pressure, pulmonic and systemic arterial pressures and pulmonic and systemic vascular resistances without augmenting exercise capacity. Compared with placebo, chronic therapy with isosorbide dinitrate (40 mg orally every 6 hours for 12 weeks) significantly improved clinical status and exercise capacity. Resting and exercise systemic blood pressure and systemic vascular resistance returned to baseline values during chronic isosorbide dinitrate therapy, but pulmonary capillary wedge pressure, pulmonary artery pressure and pulmonary vascular resistance remained improved. In patients with congestive heart failure, 12 weeks of oral isosorbide dinitrate therapy improves resting and exercise hemodynamics, exercise capacity, and clinical status; tolerance develops to the systemic arterial vascular effects without attenuation of the venous and pulmonary vascular effects.

Blood Pressure↗