Biomedical subjects

A M Valdes

Publications and source records attributed to A M Valdes.

26 records · Page 2Linked to original sources

PubMed1988

The acute effect of an oral "inotropic" placebo on the exercise capacity of patients with chronic cardiac failure.

Uncontrolled studies have suggested that the newer oral phosphodiesterase inhibitors milrinone and enoximone acutely improve exercise performance in patients with severe chronic cardiac failure. To determine whether an oral placebo presented as an inotropic agent could acutely enhance exercise capacity, two separate groups of stable heart failure patients were studied by serial exercise testing and respiratory gas exchange analysis. Group 1 had nine patients studied four hours after a single oral dose of placebo, and group 2 had ten patients retested after one to two weeks of placebo therapy. No significant change was seen in the mean exercise time, mean peak oxygen consumption, and the mean oxygen consumption at anaerobic threshold after placebo administration in both group 1 and group 2 patients. Improvements in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold occurred in five patients in group 1 and seven patients in group 2. The improvements exceeded the baseline variability of 10 percent in three group 1 patients. Among group 2 patients, the increase in exercise time, peak oxygen consumption, and oxygen consumption at anaerobic threshold exceeded 10 percent in six, four, and four patients, respectively. Thus, stable chronic heart failure patients can achieve a true baseline exercise capacity. Small improvements in exercise performance seen acutely after oral inotropic drug therapy in individual heart failure patients must be interpreted with caution, as they may be due to a placebo effect.

Aged↗

PubMed1987

Acute hemodynamic and hormonal effects of CI-930, a new phosphodiesterase inhibitor, in severe congestive heart failure.

The phosphodiesterase inhibitor CI-930 hydrochloride exerts a positive inotropic and vasodilator effect in experimental animals. The acute hemodynamic and hormonal effects of intravenous CI-930 were studied in 9 patients with severe congestive heart failure. At 60 minutes of drug infusion, there was an increase in cardiac index (2.7 +/- 0.9 vs 2.0 +/- 0.7 liters/min/m2, p less than 0.01) and positive dP/dt (1,390 +/- 470 vs 1,100 +/- 300 mm Hg/s, p less than 0.02). Additionally, there were decreases in mean systemic arterial (78 +/- 16 vs 86 +/- 15 mm Hg, p less than 0.01), mean right atrial (5 +/- 3 vs 9 +/- 4 mm Hg, p less than 0.02), mean pulmonary arterial (27 +/- 11 vs 37 +/- 9 mm Hg, p less than 0.01) and LV end-diastolic (19 +/- 8 vs 28 +/- 6 mm Hg, p less than 0.01) pressures. Heart rate did not change (97 +/- 17 vs 97 +/- 22 beats/min). The inotropic response correlated significantly (r = 0.70, p less than 0.05) with the dose of CI-930. Plasma renin activity did not change significantly (from 16 +/- 9 to 23 +/- 15 ng/ml/hour), nor did plasma norepinephrine or arginine vasopressin levels. The plasma atrial natriuretic peptide level decreased (from 153 +/- 97 to 83 +/- 35 pg/ml, p less than 0.02). These findings suggest that intravenous CI-930 hydrochloride is a useful therapeutic agent in congestive heart failure and that its use does not appear to further activate potentially deleterious hormonal systems.

Heart Failure↗

PubMed1987

Combined therapy with dobutamine and amrinone in severe heart failure. Improved hemodynamics and increased activation of the renin-angiotensin system with combined intravenous therapy.

The hemodynamic and hormonal responses to dobutamine alone and with the addition of amrinone were studied in ten patients with severe heart failure. Dobutamine significantly increased heart rate, cardiac index, and stroke volume index and significantly decreased mean right atrial and systemic arterial pressures and systemic and pulmonary vascular resistance. The addition of amrinone further decreased significantly mean right atrial, pulmonary arterial, and pulmonary arterial wedge pressures and systemic vascular resistance, while heart rate rose. The response of the cardiac index was variable, increasing in seven and decreasing in three patients. Plasma renin activity rose significantly with dobutamine and further increased with amrinone. We conclude that in most patients with severe heart failure, amrinone, when combined with dobutamine, improves hemodynamics. The further increase in heart rate, variable effects on the cardiac index, and marked activation of the renin-angiotensin system suggest caution and potential limitations in the use of this combination.

Adult↗

PubMed1986

Comparative hemodynamic and hormonal response of enoximone and dobutamine in severe congestive heart failure.

The peak hemodynamic effect and hormonal response of the phosphodiesterase inhibitor enoximone (MDL 17,043) were compared with those of dobutamine in 10 patients with severe congestive heart failure. Both agents significantly (p less than 0.05) increased cardiac index, stroke volume index and heart rate. Enoximone tended to decrease mean systemic arterial and pulmonary artery wedge pressures (0.05 less than p less than 0.1), whereas dobutamine did not. Both agents decreased systemic vascular resistance (p less than 0.05). The increase in heart rate was greater with dobutamine than with enoximone (p less than 0.05). Plasma renin activity increased significantly with dobutamine (from 11.3 +/- 13.5 to 17.8 +/- 15.0 ng/ml/hour, p less than 0.01) and with enoximone (from 13.6 +/- 18.3 to 16.6 +/- 18.8 ng/ml/hour, 0.05 less than p less than 0.1). Dobutamine suppressed plasma norepinephrine level (p less than 0.05) and enoximone did not. Neither agent affected the plasma vasopressin level. These data demonstrate a similar acute hemodynamic and hormonal profile for both enoximone and dobutamine. Further, dobutamine, like other beta agonists, provokes renin secretion and may do so to a greater extent than enoximone.

Aged↗

PubMed1986

Positive inotropic therapy for short-term support and long-term management of patients with congestive heart failure: hemodynamic effects and clinical efficacy of MDL 17,043.

The positive inotropic/vasodilator agent MDL 17,043 was evaluated to determine its usefulness for both short-term support of the failing circulation and long-term treatment of patients with congestive heart failure. Both intravenous and oral administration of MDL 17,043 significantly increased cardiac output, stroke volume, stroke work index, and heart rate, and significantly decreased pulmonary arterial wedge, right atrial, and mean arterial pressures as well as systemic and pulmonary arteriolar resistance. Such hemodynamic responsiveness persisted in patients on long-term oral therapy with MDL 17,043. When compared with dobutamine, the peak hemodynamic effects of MDL 17,043 were similar except for somewhat greater increases in heart rate with dobutamine and somewhat greater decreases in mean pulmonary arterial and wedge pressures with MDL 17,043. Both intravenous and oral MDL 17,043 elevated plasma renin activity. Oral doses were rapidly absorbed, and the drug had an elimination half-life of about 20 hr. Although the majority of patients showed clinical improvement at 1 month, this effect tended to wane over time leading to either recurrent heart failure or death. Mortality rates at 1 year are about 46% in class III patients and 97% in class IV patients on long-term oral MDL 17,043. The results of these studies suggest that MDL 17,043 may be useful in the short-term management of the failing circulation; however, its value in the long-term management of patients with chronic heart failure remains unclear and requires further studies for resolution.

Administration, Oral↗

PubMed1985

MDL 17,043 therapy in severe congestive heart failure: characterization of the early and late hemodynamic, pharmacokinetic, hormonal and clinical response.

MDL 17,043, an agent with both inotropic and vasodilator properties, was evaluated in the treatment of chronic severe heart failure. The early and late hemodynamic, hormonal, pharmacokinetic and clinical responses to oral MDL 17,043 were studied in 20 patients. MDL 17,043 acutely increased cardiac output from 3.6 +/- 0.9 to 4.6 +/- 1.0 liters/min (+28%, p less than 0.001) and decreased mean pulmonary artery wedge pressure from 24 +/- 8 to 13 +/- 8 mm Hg (-46%, p less than 0.001), mean right atrial pressure from 10 +/- 5 to 4 +/- 4 mm Hg (-60%, p less than 0.001) and mean arterial pressure from 78 +/- 9 to 70 +/- 11 mm Hg (-10%, p less than 0.001). Hemodynamic improvement was sustained for 8 hours. Plasma renin activity tended to increase (0.10 less than p greater than 0.05), plasma norepinephrine tended to decrease (0.10 less than p greater than 0.05) and arginine vasopressin did not show any directional change. Elimination half-life for MDL 17,043 was approximately 20 hours. Hemodynamic responsiveness was maintained in six patients undergoing restudy at 4 weeks. Initial subjective improvement in the 20 patients occurred in 90%, was present at 4 weeks in 50% and continued longer than 3 months in 25%. Side effects occurred in 75% and required cessation of treatment in 10%. Thirteen (93%) of 14 patients on long-term therapy died (median time after start of MDL 17,043 therapy 39 days). Deaths were sudden in 69%. It is concluded that oral MDL 17,043 produces early and late hemodynamic improvement in patients with severe heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗

PubMed1984

Acute hemodynamic effect of oral MDL 17,043 in severe congestive heart failure.

MDL 17,043, when administered intravenously in humans, produces a significant and salutary hemodynamic response. To determine its acute effect when administered orally (3 mg/kg), 10 patients with severe congestive heart failure were studied by right-sided cardiac catheterization for 8 hours. At 4 hours after drug ingestion, there was significant improvement in several hemodynamic measurements. Cardiac index increased 38% over baseline (from 1.9 +/- 0.4 to 2.6 +/- 0.4 liters/min/m2, p less than 0.01), arteriovenous oxygen difference decreased by 30% (from 8.0 +/- 1.4 to 5.6 +/- 1.2 vol%, p less than 0.01), heart rate increased by 8% (from 85 +/- 16 to 92 +/- 16 beats/min, p less than 0.05), stroke volume index increased by 22% (from 23 +/- 5 to 28 +/- 4 ml/beat/m2, p less than 0.05), left ventricular stroke work increased by 24% (from 18 +/- 5 to 22 +/- 5 g-m/m2, p less than 0.01), mean arterial pressure decreased by 10% (from 79 +/- 6 to 71 +/- 9 mm Hg, p less than 0.01), mean right atrial pressure decreased by 40% (from 10 +/- 5 to 6 +/- 4 mm Hg, p less than 0.01), and mean pulmonary artery wedge pressure decreased by 36% (from 22 +/- 5 to 14 +/- 6 mm Hg, p less than 0.01). Cardiac index, arteriovenous oxygen difference, mean arterial pressure, right atrial pressure, and pulmonary artery wedge pressure remained significantly improved at 8 hours. These findings indicate that MDL 17,043 is active when administered orally and produces beneficial hemodynamic effects for as long as 8 hours.

Aged↗

PubMedDate not supplied

Obesity, cigarette smoking, and telomere length in women.

Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.

Adolescent↗