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Biomedical subjects

D V Unverferth

Publications and source records attributed to D V Unverferth.

At least 109 records · Page 6Linked to original sources

Biochemical measurements of endomyocardial biopsies.

The purpose of this study is to investigate the validity of performing biochemical analyses on human endomyocardial biopsies. One problem of such analyses is the decay of metabolites between the time of biopsy and the analyses. This was addressed by varying the time delay from biopsy to submersion in liquid nitrogen (-200 degree C). Neither cyclic AMP or cyclic GMP changed significantly up to 90 seconds after biopsy. The reproducibility of the assays in human heart biopsies was determined by submitting paired samples from each procedure. The ATP content was determined by a fluorescent technique and was related to the protein and creatine content. The average ATP of 25 paired samples was 12.3 nm per mg protein; the average difference between the paired samples was -0.6, and the 95% confidence interval was 5.6 nm/mg protein. The average ATP-to-creatine ratio was 0.25; the 95% confidence interval was 0.12. The cyclic AMP and cyclic GMP were found to average 3.3 and 0.25 femtomoles/mcg protein, respectively. The 95% confidence intervals were 1.8 and 0.12 fmoles/mcg protein. The problems of sampling error and blood and connective tissue contamination decrease the reliability of the biochemical analyses. Reproducibility is adequate, however, to acquire meaningful biochemical information on the human heart.

Adenosine Triphosphate↗

Biochemical and histologic correlates of ventricular end-diastolic pressure.

The associations of elevated left ventricular (LV) and right ventricular (RV) end-diastolic pressure (EDP) were evaluated in 28 patients with non-ischemic congestive cardiomyopathy. Right-sided endomyocardial biopsies from each patient were evaluated for ATP content, percent fibrosis and myocardial fiber diameter. The resting RVEDP and LVEDP and the post-angiographic LVEDP were correlated with the results from the biopsies. There was a correlation of the LVEDP with the RVEDP (r = 0.67, P less than 0.001) by a linear plot. There was no correlation of any EDP measurement with the percent fibrosis. There was, however, a rough correlation of the myocardial fiber diameter with RVEDP (r = 0.40, P less than 0.05). Myocardial ATP content correlated with the RVEDP (r = -0.53, P less than 0.005), the LVEDP (r = -0.65, P less than 0.001) and the post-angiographic LVEDP (r = -0.72, P less than 0.001). These data demonstrate that an elevated ventricular EDP correlates most closely with depressed levels of myocardial ATP. The myocardial cell diameter correlated less well and there was no correlation of EDP with fibrosis. Metabolic factors may be more important than histologic parameters in the elevated ventricular EDP of non-ischemic congestive cardiomyopathy.

Adenosine Triphosphate↗

Hydralazine and isosorbide dinitrate: comparative central and regional hemodynamic effects when administered alone or in combination.

Central and regional hemodynamic studies were performed before and after the oral administration of 75 mg of hydralazine and/or 20 mg of isosorbide dinitrate in 15 patients with low-output congestive heart failure. Hydralazine increased mean cardiac output 17-25%, mean renal blood flow 19%, and limb blood flow 17% (all p < 0.05). Mean hepatic blood flow did not change significantly with hydralazine. Except for a small increase in cardiac output (6%, p < 0.05) at 30 minutes, isosorbide dinitrate did not significantly alter central, renal, hepatic or limb blood flow. Combining isosorbide dinitrate and hydralazine effected similar increases in cardiac output (17-24%, p < 0.05), renal (17%, p < 0.05) and limb (20%, p < 0.05) blood flow as those elicited by hydralazine alone. The combination did not significantly alter mean hepatic blood flow. Hydralazine, alone or combined with isosorbide dinitrate, increases renal and limb blood flow in congestive heart failure in proportion to the augmented cardiac output; isosorbide dinitrate alone does not alter blood flow to these regions. Neither drug (or combination) changes hepatic blood flow in this clinical setting.

Adult↗

Prazosin and hydralazine in congestive heart failure. Regional hemodynamic effects in relation to dose.

Central hemodynamic variables and regional blood flow and vascular resistances were ascertained in patients with severe congestive heart failure before and after the oral administration of prazosin hydrochloride or hydralazine. Prazosin was administered in doses of 2, 5, and 10 mg and hydralazine, 75 and 100 mg. Although both agents significantly increased cardiac output and decreased vascular resistances, their effects on regional blood flow and vascular resistances were considerably different. Prazosin increased hepatic blood flow and reduced hepatic vascular resistance at lower doses; these changes decreased as prazosin was increased. Hydralazine did not significantly alter mean hepatic blood flow or vascular resistance. Prazosin did not affect renal blood flow or renal vascular resistance. In contrast, hydralazine significantly increased renal blood flow and reduced vascular resistance; the changes were dose related. Both drugs augmented limb blood flow and diminished limb vascular resistance; the magnitude of change was dose dependent.

Cardiac Output↗

Positive inotropic effects of hydralazine in human subjects: comparison with prazosin in the setting of congestive heart failure.

Hydralazine possesses positive inotropic properties in animal model preparations. To determine whether this vasodilator elicits a positive inotropic response in the failing human ventricle, hydralazine, 75 or 100 mg, was administered orally to 14 patients with left ventricular dysfunction and congestive heart failure; the results were compared with those of first-dose prazosin at 5 and 10 mg. The duration of the preejection period and the isovolumic developed pressure/duration of isovolumic contraction (delta P/delta t) were used as indexes of inotropy. Prazosin did not effect a significant response in the duration of the preejection period or in the delta P/delta t. Hydralazine significantly shortened the preejection period and increased the delta P/delta t over 8 hours after administration; these data suggest that hydralazine elicits a positive inotropic response in the failing human ventricle.

Dose-Response Relationship, Drug↗

Reproducibility of echocardiography in chronic congestive heart failure.

The purpose of this study was to define the reproducibility of serial echocardiographic measurements of left ventricular size and function. Fourteen patients in stable condition after heart failure (Group I) had five weekly outpatient echocardiograms performed by a single technician with blinded interpretation. The average end-diastolic diameter (EDD) of all patients was 68 mm, with a mean standard deviation of 4 mm and a 95% confidence interval of 8 mm. The average end-systolic diameter (ESD) was 58 mm; the 95% confidence interval was 5.6%. A group of four patients with heart failure (Group II) had daily echocardiograms while undergoing continuous hemodynamic monitoring. Pulmonary capillary blood pressure and thermodilution cardiac outputs were stable throughout the 4-day study period. Daily morning echographic measurements were constant, with 95% confidence interval of the EDD being only 4 mm. The ESD and % delta D had 95% confidence intervals of 2 mm and 3.2%, respectively. The narrow range of measurements (narrow confidence intervals) demonstrates the excellent reproducibility of these echocardiographic parameters.

Echocardiography↗

Long-term benefit of dobutamine in patients with congestive cardiomyopathy.

Dobutamine was given intravenously for three days to 38 patients with congestive cardiomyopathy. The patients were followed by serial determinations of functional class and by non-invasive measurements of left ventricular function-systolic time intervals (PEP/LVET) and echocardiogram (% delta D). The average PEP/LVET declined significantly (p < 0.001) at three days, four and nine weeks, and at 10 months after the discontinuation of dobutamine infusion. Also, 67% (20 of 30) of patients had improvement of the PEP/LVET by greater than -0.04 at seven days. Even two and six months after dobutamine, 58% (15 of 26) and 39% (seven of 18) were improved. Similarly, the % delta D was improved by at least 2% in 60% (18 of 30) at seven days and 55% (16 of 29) at four weeks. At two and six months, 50% (14 of 28) and 42% (10 of 24) were improved. Those patients who did not improve their FC were more likely (five of nine) to have left ventricular free wall thickness (by echocardiogram) less than 0.5 cm./M2. Those who responded usually (22 of 29) had a ventricular wall thickness greater than 0.5 cm./M2. Although the mechanism of the prolonged improvement after a three day infusion of dobutamine is not understood, this study suggests that dobutamine has a role in the therapy of chronic congestive heart failure.

Adolescent↗

Hemodynamic effects of intravenous butopamine in congestive heart failure.

Butopamine is chemically similar to dobutamine but, unlike dobutamine, it is not a catecholamine. Preclinical studies on dogs show that butopamine is inotropic intravenously and orally. We gave butopamine intravenously to eight patients with congestive heart failure using a progressive dose-response protocol ranging from 0.02 to 0.17 mcg/kg/min. The mean cardiac index and stroke volume index increased at doses greater than or equal to 0.06 mcg/kg/min; there was also an increase in heart rate at greater than or equal to 0.06 mcg/kg/min. At greater than or equal to 0.08 mcg/kg/min the augmented stroke volume tended to plateau so that additional increases in the cardiac index were secondary to the elevated heart rate. Improved ventricular performance, measured by systolic time intervals, left ventricular stroke work index, and the calculated mean rate of left ventricular pressure development during isovolumetric contraction (delta P/delta t/PCWP), was noted at greater than or equal to 0.06 mcg/kg/min. Systemic systolic blood pressure increased at greater than or equal to 0.04 mcg/kg/min but diastolic and mean arterial pressures and pulmonary artery and pulmonary capillary wedge pressures did not change. The progressive increase in cardiac output was accompanied by a reduction in pulmonary and systemic vascular resistances. Although mean premature ventricular contractions per minute did not change, two patients experienced a substantial increase in ventricular ectopy at 0.10 and 0.12 mcg/kg/min. Butopamine induces a positive inotropic response in patients with congestive heart failure but for equal increments in cardiac output, butopamine increases heart rate more than dobutamine.

2-Hydroxyphenethylamine↗

Improvement of human myocardial mitochondria after dobutamine: a quantitative ultrastructural study.

Dobutamine is a new inotropic agent that may induce prolonged clinical improvement in patients with congestive cardiomyopathy. Sixteen patients with severe heart failure but without obstructive coronary disease were studied by serial functional class determinations and by noninvasive measurements of left ventricular function before and after bedrest control period and then after a 3-day infusion of dobutamine. An endomyocardial biopsy procedure was performed on 11 patients before and after the bedrest and on all 16 patients before and after dobutamine. Quantitative ultrastructural analysis of the biopsies was performed on electron micrographs (31,200 X) by a grid technique. The number of electron dense particles per 100 mitochondria did not change after bedrest but there was a significant decrease from 84 +/- 14 to 65 +/- 12 (P < .005) in the pre- to postdobutamine biopsies. The cristae to matrix ratio of the mitochondria did not change with bedrest but improved from 0.37 +/- 0.04 to 0.47 +/- 0.05 (P < .02) after dobutamine. The average mitochondrial size did not change significantly in the bedrest control nor in the dobutamine biopsy samples. However, when the 16 patients were divided into those who had a good clinical response (by functional class and noninvasive measurements of left ventricular function) and those who had no or little response, the 10 responders did decrease their average mitochondria size from 0.26 +/- 0.03 mu 2 to 0.23 +/- 0.02 mu 2 (P < .02). The mechanism by which a 3-day infusion of dobutamine induces a prolonged clinical improvement is not well understood. The use of quantitative ultrastructural technique in this study has demonstrated that there is a morphologic basis to the improvement.

Catecholamines↗

The differential diagnosis of paracardiac lesions: pericardial cysts.

The differential diagnosis of paracardiac lesions includes pericardial cysts (PC), which are benign, developmental lesions. Patients with PC are usually asymptomatic, although chest pain or dyspnea may occur. The diagnosis may be established by chest roentgenogram (radiographic contour and location), fluoroscopy (changes in shape with respiration or positioning the patient), and echography (smooth, cystic contour and characteristic location). We present the diagnostic approach to patients with PC, and a review of the case histories of 12 patients with PC. Two symptomatic patients with PC were treated with surgical excision. Cyst aspiration in two patients yielded clear fluid and was initially considered therapeutic, but was followed by gradual reaccumulation of fluid. Six of ten asymptomatic patients followed for three to ten years did not develop symptoms, nor was there radiographic evidence of progressive PC enlargement. Three of ten died from unrelated causes during the follow-up period. Although symptomatic patients with PC may require surgical excision, asymptomatic patients with PC should be managed conservatively.

Adolescent↗

Development of pharmacodynamic tolerance to prozosin in congestive heart failure.

In order to determine and compare the pharmacodynamic responses to single and multiple dose prazosin therapy in cardiac failure, 14 patients with severe low-output heart failure underwent central and regional hemodynamic measurements after random placement in one of two prazosin dosing schedules. A single 5 mg oral dose of prazosin (Group A, no. = 7) significantly increased the cardiac index and stroke volume index while significantly decreasing systemic, pulmonary and pulmonary capillary wedge pressures and vascular resistances. Hepatic plasma flow and limb blood flow increased after the single dose. Striking attenuation of these hemodynamic effects occurred when the same dose was administered after 24 hours of pretreatment with oral prazosin, 2 mg every 8 hours (Group B, no. = 7). The plasma prazosin levels of the two groups, drawn 2 hours after administration, were 24.5 and 30.5 ng/ml, respectively. Repeated administration of prazosin in patients with congestive heart failure results in rapid attenuation of its beneficial central and regional hemodynamic effects. The usefulness of this vasodilator as a preload- and afterload-reducing agent in the clinical setting of chronic congestive heart failure may be limited by the development of pharmacodynamic tolerance.

Administration, Oral↗

The relationship between plasma dobutamine concentrations and cardiovascular responses in cardiac failure.

Plasma dobutamine concentrations and hemodynamic and noninvasive cardiac measurements were made during dobutamine infusions in eight patients with congestive cardiomyopathy and low output heart failure. Plasma concentrations correlated well with infusion rates (2.5, 5.0, 7.5 and 10 microgram/kg/min). Cardiac output and stroke volume increased linearly, whereas pulmonary capillary wedge pressure, and total pulmonary and systemic resistances decreased linearly with increasing dobutamine concentrations. No constant relationship existed between plasma dobutamine levels and changes in heart rate or mean arterial pressure. The noninvasive left ventricular function data (echocardiographic and systolic time intervals) correlated linearly with plasma concentrations and suggest that these noninvasive technics be employed in guiding the administration of this new inotropic agent.

Adult↗

Electrocardiographic voltage in pericardial effusion.

The usefulness of the electrocardiographic sign of "low voltage" in the diagnosis of pericardial effusion was investigated in 122 patients comprising three study groups. Sixty-four patients (group 1) had a pericardial effusion detected and measured by echocardiographic studies. The volume of the effusion showed no correlation with electrocardiographic voltage. A second group of 36 patients was identified as having low voltage on routine electrocardiograms. Only 13 (36 percent) had echocardiographically demonstrable pericardial effusion. Group 3 consisted of 22 patients who required pericardiocentesis. The ECGs obtained immediately after pericardiocentesis showed an increase in average voltage of 0.48 mm in the limb leads and 0.83 mm in the precordial leads for each 100 ml of fluid removed. This study demonstrates that a single ECG with "low voltage" is not useful in the diagnosis of pericardial effusion but that a reduction in the voltage of serial ECGs may suggest the development of pericardial effusion.

Echocardiography↗