Antonio C. Quiroz

Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary pharmacology of enkephalins in the conscious dog

Various enkephalins (ENK) have been reported to alter heart rate, systemic blood pressure, and respiratory function but with variable results. We previously found that pentobarbital anesthesia reversed the increases in heart rate and systemic arterial blood pressure produced by Leu5-ENK in the dog. We have now studied the cardiopulmonary responses to systemically injected enkephalins in the awake, chronically instrumented dog. In these unanesthetized dogs, Leu5-ENK, Met5-ENK, and an ENK dimer increased heart rate, systemic arterial pressure, and respiratory rate in a dose-dependent fashion. D-Phe4, Met5-ENK, an analog with behavioral activity but without analgesic or in vitro opiate effects was inactive. Leu5-ENK was studied in detail; typically, heart rate and systemic pressure increased within 20 sec and returned to baseline in less than 180 sec. Intra-arterial injections produced a smaller increase in heart rate than did intravenous injections, but similar increases in systemic arterial blood pressure were recorded. These cardiovascular responses suggest that systemically injected enkephalins suppress baroreceptor reflexes and may have a role in cardiopulmonary regulation.

Acute and short-term effects of clonidine in heart failure.

The authors performed a randomized, double-blind, placebo-controlled trial to assess the tolerance and effects of chronic oral clonidine administration on the clinical status, exercise tolerance, and ventricular function of 10 male patients with chronic heart failure. Patients were given either oral clonidine (400 μg/day) or matching placebo for twelve weeks and then tapered off medication over a two-week period. Results are summarized as follows: Profiles over time between groups were significantly different for resting heart rate (p = 0.0005), were different for arterial pressure (p=0.04), were different for left ventricular ejection fraction (p < 0.006), and were different for mean accumulated workload (p=0.076). Exercise double product at 25 watts changed little in three patients and showed a decrease in 2 patients following six weeks of oral clonidine; after twelve weeks, it decreased in three patients, increased in 1, and changed little in another. After washout, double product returned toward baseline values. In the placebo groups, double product showed little change. Resting of the heart by decreasing heart rate, systemic arterial blood pressure, and venous tone are thought by the authors to be major contributing factors to the observed beneficial effect of chronic oral clonidine in chronic heart failure.

Comparison of nitrendipine and hydrochlorothiazide for systemic hypertension

Left ventricular (LV) hypertrophy with associated LV systolic and diastolic dysfunction is frequently found in patients with systemic hypertension, and is multifactorial in origin. Although a reduction in blood pressure (BP) often results in regression of hypertrophy, the pharmacologic profiles of the antihypertensive agents used may determine the probability of such regression despite similar levels of BP reduction. Thiazide diuretic drugs may actually result in increased LV hypertrophy; calcium channel antagonists may cause regression or no change. The effects of treatment with nitrendipine (20 mg/day) or hydrochlorothiazide (50 mg/day) were compared in an 8-week, double-blind study of 18 hypertensive subjects aged 50 years or older. BP was significantly reduced (p less than 0.05) by both nitrendipine (from 161 +/- 29/102 +/- 4 to 145 +/- 24/92 +/- 7 mm Hg; mean +/- standard deviation) and hydrochlorothiazide (from 162 +/- 15/105 +/- 6 to 143 +/- 20/95 +/- 7 mm Hg). Plasma norepinephrine increased in the nitrendipine group, from 202 +/- 110 to 332 +/- 220 pg/ml at 8 weeks of therapy and in the hydrochlorothiazide group, from 147 +/- 130 to 313 +/- 277. Plasma renin activity changed from 3.2 +/- 2.4 to 3.5 +/- 2.1 during nitrendipine treatment, but from 2.1 +/- 2.1 to 10.5 +/- 10.8 ng angiotensin l/ml/90 min (p less than 0.05) during treatment with hydrochlorothiazide. Left ventricular mass index did not change significantly with either therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antianginal effects of clonidine.

The effects of clonidine, a central alpha-adrenoceptor agonist, were studied in 12 patients with chronic stable effort angina pectoris in an 18-week randomized, double-blind, two-period (6 weeks each) crossover study with a 3-week inter-period washout phase. Clonidine (200 micrograms as a single dose) produced a decrease in rate-pressure product at rest and during exercise and an increase in exercise tolerance, at 1 and 2 h after administration. Chronic administration of clonidine produced a decrease in rate-pressure product at rest and during exercise and an increase in exercise tolerance after 3 weeks (200 micrograms twice a day) and 6 weeks (400 micrograms twice a day) of treatment.

Hydrogen-platinum electrode system in detection of intravascular shunts

Abstract A modification of the Clark hydrogenplatinum system is described, employing a high-impedance system, platinum-electrode catheters, and stylets for Cournand or Henry needles. Typical curves which illustrate the localization of left-to-right and right-to-left shunts are presented. Valvular regurgitation is readily detected. The advantages of the method are the simplicity and reliability of the detection and localization of small shunts by means of a single intracardiac catheter. The disadvantages of the method are its extreme sensitivity, which complicates evaluation of valvular regurgitation, and the lack of quantitation of the shunt volume.

Circadian variation in blood pressure and heart rate in nonhypertensive congestive heart failure.

This study was designed to determine whether decreases in the circadian variability of arterial blood pressure and heart rate measured in ambulatory patients would correlate with neurohumoral indices of the severity of congestive heart failure not the result of systemic arterial hypertension, and whether treatment with angiotensin-converting enzyme (ACE) inhibitors would restore a more normal pattern. The study also examined the ability of ambulatory blood pressure monitoring to discern pharmacodynamic patterns in patients with congestive heart failure, which is associated with decreased variability in circadian variations in blood pressure and heart rate among hospitalized patients. Increased plasma norepinephrine, renin activity, and atrial natriuretic peptide (ANP) have a positive correlation with worsening clinical status. ACE inhibitors have been found to be beneficial in the treatment of congestive heart failure. Ambulatory 24-h blood pressure and neurohumoral measurements were recorded in 30 patients with congestive heart failure (class II-IV, New York Heart Association) before treatment with lisinopril or captopril and repeated after 6 weeks of treatment. Fourier analysis was used as a curve-smoothing technique to compare the pharmacodynamics of the two ACE inhibitors. The absolute amplitude of systolic blood pressure correlated inversely with plasma norepinephrine and ANP (p = 0.004) but not with renin activity. Mean 24-h systemic arterial blood pressure did not decrease significantly after treatment with ACE inhibitors. An increase in absolute amplitude of systolic blood pressure correlated inversely with baseline amplitude (p < 0.00001). Inspection of the Fourier-smoothed curves demonstrated differences in the circadian effect of lisinopril and captopril on systolic blood pressure and rate-pressure product. Ambulatory 24-h blood pressure monitoring may prove useful in the assessment of the severity and treatment of congestive heart failure.

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Summary: Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 μg/kg, to 22 patients with chronic congestive heart failure (ejection fraction < 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 μg/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 μg/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 μg/kg dose. The cardiac index was reduced by the 158 μg/kg dose, but increased after 251, 398, and 630 μg/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 μg/kg dose level. Thus, nicorandil displays a complex hemodynamic profile over the dose range tested, which most likely reflects variable systemic arterial and venous vasodilation in response to potassium channel activation and nitrate effects at the different doses. Nicorandil improves the hemodynamic abnormalities of heart failure without concomitant tachycardia or increase in plasma catecholamines; this interesting pharmacological profile suggests a possible role for nicorandil in the treatment of congestive heart failure.

The effects of prostaglandin E1 on the systemic and pulmonary circulations of intact dogs. The influence of urethane and pentobarbital anesthesia

Es wird gezeigt, dass Phenobarbital- und Urethan-Anästhesie nach Infusion von PGE1 in den Kreislauf normaler Hunde verschiedene hämodynamische Reaktionen (Herzminutenvolumen, Herzfrequenz, Durchblutung der Peripherie) verursacht. Die Intrakoronarinfusion von PGE1 mit der Narkose ergab einen negativ chronotropen und einen negativ inotropen Effekt.

Prolonged hemodynamic benefits from a high‐dose bolus injection of human atrial natriuretic factor in congestive heart failure

The physiologic and potential pharmacologic roles of atrial natriuretic factor in congestive heart failure have remained confusing. We have evaluated the hemodynamic responses to human atrial natriuretic factor [ANF (102‐126)] given as bolus intravenous doses of 2.0 or 4.5 µg/kg to 12 patients with congestive heart failure. Responses were monitored with pulmonary and systemic arterial catheters in place. By 30 minutes after 4.5 µg/kg ANF (n = 6), heart rate decreased from 97 ± 16 to 91 ± 15 beats/min, right atrial pressure from 14 ± 4 to 12 ± 3 mm Hg, and pulmonary capillary wedge pressure from 33 ± 3 to 23 ± 2 mm Hg (all p < 0.05); responses persisted for 120 minutes. Mean arterial pressure, cardiac index, stroke volume index, and pulmonic and systemic vascular resistances did not change significantly. The 2.0 µg/kg ANF dose produced similar responses, but only heart rate and right atrial pressure decreased significantly. No clinically important side effects were noted. High‐dose ANF bolus doses can be administered simply and safely and improve hemodynamic parameters in chronic heart failure. Therefore ANF does have pharmacologic activity in heart failure and may have therapeutic potential.