Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure.

Atrial natriuretic peptide alters left ventricular performance in patients with heart failure. To assess the direct effects of this hormone on myocardial function, its actions were compared with those of the pure vasodilator nitroprusside in 10 patients with heart failure. Simultaneous left ventricular micromanometer pressure and radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during atrial natriuretic peptide infusion. The baseline end-systolic pressure-volume relation was generated in nine patients from pressure-volume loops obtained during the two baseline periods and during afterload reduction with nitroprusside. Mean arterial pressure decreased with atrial natriuretic peptide (89 +/- 3 to 80 +/- 2 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (90 +/- 4 to 73 +/- 3 mm Hg, p less than 0.05). Left ventricular end-diastolic pressure also decreased with atrial natriuretic peptide (24 +/- 2 to 16 +/- 3 mm Hg, p less than 0.05) and by a greater amount with nitroprusside (24 +/- 2 to 13 +/- 3 mm Hg, p less than 0.05). Cardiac index increased during infusion of each agent from 2.0 +/- 0.2 to 2.4 +/- 0.2 liters/min per m2 (p less than 0.01). Heart rate increased slightly with nitroprusside but did not change with atrial natriuretic peptide. Peak positive first derivative of left ventricular pressure (dP/dt), ejection fraction and stroke work index were unchanged by either agent. The relation between end-systolic pressure and volume during atrial natriuretic peptide infusion was shifted slightly leftward from the baseline value in four patients, slightly rightward in four and not at all in one patient, indicating no consistent inotropic effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of an ultrashort-acting beta-receptor blocker (esmolol) in patients with acute myocardial ischemia and relative contraindications to beta-blockade therapy

The hemodynamic responses to esmolol, an ultrashort-acting (t1/2 = 9 min) beta 1-adrenergic receptor antagonist, were examined in 16 patients with myocardial ischemia and compromised left ventricular function as evidenced by a mean pulmonary capillary wedge pressure of 15 to 25 mm Hg. Esmolol was infused intravenously to a maximal dose of 300 micrograms/kg body weight per min for less than or equal to 48 h in 16 patients: 9 with acute myocardial infarction, 6 with periinfarction angina and 1 with acute unstable angina. The sinus rate and systolic arterial pressure declined rapidly in all patients from baseline values of 99 +/- 12 beats/min and 126 +/- 19 mm Hg to 80 +/- 14 beats/min (p less than 0.05) and 107 +/- 20 mm Hg (p less than or equal to 0.05) during esmolol treatment. Rate-pressure product decreased by 33% and cardiac index by 14% during esmolol treatment, but pulmonary capillary wedge pressure was not significantly altered by drug infusion (19 +/- 3 mm Hg at baseline versus 19 +/- 5 during treatment, p = NS). In all patients there was a rapid return toward baseline hemodynamic measurements within 15 min of stopping administration of esmolol, and virtually complete resolution of drug effect was evident within approximately 30 min. During infusion of esmolol, four of nine patients receiving intravenous nitroglycerin required downward adjustment of nitroglycerin infusion rate to maintain systolic blood pressure greater than 90 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined hemodynamic and scintigraphic assessment of piroximone (MDL 19,205) and comparison with dobutamine and nitroprusside

The acute hemodynamic responses to intravenous infusion of piroximone (MDL 19,205), a nonglycoside, noncatecholamine agent with positive inotropic activity in vitro, were compared with those of intravenous dobutamine and sodium nitroprusside, respectively, in 2 groups of patients with New York Heart Association class III or IV symptoms. Each drug was titrated to optimal dosage (dobutamine, 12.5 +/- 3.9 micrograms/kg/min; nitroprusside, 2.5 +/- 0.6 micrograms/kg/min; piroximone 1.4 +/- 0.6 mg/kg) and simultaneous hemodynamic and scintigraphic values were measured. In group 1, the increase in cardiac index was slightly greater with piroximone than with dobutamine (from 1.6 +/- 0.5 to 2.7 +/- 0.6 vs 2.4 +/- 0.6 liters/min/m2, p less than 0.025) and only piroximone significantly decreased left ventricular (LV) filling pressure (from 29 +/- 7 to 22 +/- 8 mm Hg, p less than 0.05). Both agents increased heart rate and systolic blood pressure. In group 2, cardiac index increased similarly with nitroprusside and piroximone (1.5 +/- 0.6 to 2.6 +/- 0.8 and 1.6 +/- 0.5 to 2.6 +/- 0.5 liters/min/m2, difference not significant), whereas LV filling pressure decreased slightly less with piroximone (29 +/- 7 to 24 +/- 10 vs 30 +/- 7 to 20 +/- 11 mm Hg, difference not significant). Only nitroprusside reduced mean arterial pressure (88 +/- 13 to 72 +/- 12 mm Hg, p less than 0.001 between drugs). In group 1, systolic blood pressure to end-systolic volume ratio increased in 9 of 10 patients taking both piroximone and dobutamine, whereas in group 2, this ratio increased in 7 of 8 patients taking piroximone and declined in 7 of 8 taking nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inotropic effect of nicardipine in patients with heart failure: assessment by left ventricular end-systolic pressure-volume analysis

Nicardipine, a new dihydropyridine calcium channel blocker, has been investigated for the treatment of coronary artery disease and heart failure. To assess the inotropic effect of nicardipine in humans independent of its vasodilator effect, equihypotensive doses of intravenous nitroprusside (mean infusion rate 65 +/- 13 micrograms/min) and nicardipine (mean dose 5.2 +/- 0.4 mg) were administered to 15 patients with heart failure (New York Heart Association functional classes II to IV, radionuclide left ventricular ejection fraction 0.15 +/- 0.02). Left ventricular micromanometer pressure and simultaneous radionuclide left ventricular volume were obtained at baseline, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Heart rate did not change significantly with either nitroprusside or nicardipine. Mean systemic arterial pressure decreased by an average of 21 mm Hg with both drugs. A greater decrease in left ventricular end-diastolic pressure occurred with nitroprusside (27 +/- 2 to 14 +/- 2 mm Hg, p less than 0.01) than with nicardipine (27 +/- 2 to 23 +/- 3 mm Hg, p less than 0.05), and pulmonary capillary wedge pressure decreased significantly only with nitroprusside. Cardiac index increased from 1.8 +/- 0.1 to 2.1 +/- 0.1 liters/min per m2 (p less than 0.05) with nitroprusside and to a greater extent from 1.7 +/- 0.1 to 2.4 +/- 0.1 liters/min per m2 (p less than 0.01) with nicardipine. Left ventricular ejection fraction increased with nicardipine (0.15 +/- 0.01 to 0.19 +/- 0.01, p less than 0.01), but not with nitroprusside. Peak positive first derivative of left ventricular pressure (dP/dt) decreased by 9% with both agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressure dependence of atrial natriuretic peptide during norepinephrine infusion in humans

The relative contribution of increased blood pressure (BP) or norepinephrine (NE), or both, to the stimulatory effect of an NE pressor infusion on circulating immunoreactive atrial natriuretic peptide (ANP) was evaluated in 10 healthy young men. They were studied during an infusion of NE, which was applied initially alone and then in combination with sodium nitroprusside. NE infusion rate was increased in four 30-minute intervals to a final dose of 200 ng/kg body weight per minute, leading to 12-fold higher plasma NE levels than were seen during control conditions. This increased mean BP (from a mean basal value of 94 +/- 3 to 119 +/- 4 [SEM] mm Hg; p less than 0.001) and plasma immunoreactive ANP (from 50 +/- 7 to 112 +/- 17 pg/ml; p less than 0.001), whereas heart rate decreased (p less than 0.001). The NE infusion was continued at the highest dose and an additional infusion of sodium nitroprusside was started to titrate mean BP in 30-minute intervals down to control values; a mean sodium nitroprusside dose of 0.95 micrograms/kg/min restored mean BP to 93 +/- 4 mm Hg (p less than 0.001), decreased plasma immunoreactive ANP to basal values (51 +/- 4 pg/ml; p less than 0.001), increased heart rate (p less than 0.001), and left plasma levels of NE largely unchanged. Plasma protein and hematocrit rose about 5 to 6% (p less than 0.001) during the NE infusion and then decreased about 3 to 4% (p less than 0.001 and p less than 0.01) when sodium nitroprusside was added.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of volume loading, dobutamine, and nitroprusside in patients with predominant right ventricular infarction

To assess the value of volume loading and to determine the relative efficacy of dobutamine compared with nitroprusside therapy in acute right ventricular infarction (RVMI), 13 patients with clinical, hemodynamic, and radionuclide angiographic evidence of RVMI were evaluated. In 10 patients who had an initial pulmonary arterial wedge pressure less than 18 mm Hg, volume loading did not improve cardiac index (1.9 +/- 0.5 [SD] to 2.1 +/- 0.4 liters/min/m2), despite significant increases in mean right atrial pressure (11 +/- 2 to 15 +/- 2 mm Hg, p less than .001) and pulmonary arterial wedge pressure (10 +/- 4 to 15 +/- 2 mm Hg, p less than .001). Nine patients received dobutamine or nitroprusside in random order, while hemodynamic measurements and radionuclide angiograms were obtained simultaneously. Compared with nitroprusside, dobutamine produced a statistically significant increase in cardiac index (2.0 +/- 0.4 to 2.7 +/- 0.5 vs 2.1 +/- 0.4 to 2.3 +/- 0.5 liters/min/m2, p less than .001), stroke volume index (29 +/- 6 to 36 +/- 8 vs 29 +/- 6 to 30 +/- 6 ml/m2, p = .02), and right ventricular ejection fraction (30 +/- 8% to 42 +/- 7% vs 34 +/- 8% to 37 +/- 4%, p less than .01) by two-way analysis of variance. We conclude that volume loading does not improve cardiac index in patients with acute RVMI despite a rise in cardiac filling pressures and that infusion of dobutamine, after appropriate volume loading, produces a significant improvement in cardiac index and right ventricular ejection fraction over those after infusion of nitroprusside.     

Effect of acute hemodynamic decompensation on electrical inducibility of ventricular arrhythmias in patients with dilated cardiomyopathy and complex nonsustained ventricular arrhythmias

In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenosine infusion for the reversal of pulmonary vasoconstriction in biventricular failure. A good test but a poor therapy.

BACKGROUND. Elevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure. METHODS AND RESULTS. Using two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n = 21) and compared it with sodium nitroprusside (n = 18). Patients received 30% oxygen via face mask throughout the study. Adenosine at 100 micrograms/kg min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41 +/- 6% versus 42 +/- 4%) and a greater and more consistent fall in transpulmonary pressure gradient (35 +/- 6% versus 9 +/- 30%, p less than 0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 +/- 0.09 to 1.89 +/- 0.16 l.m-2, p less than 0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7 +/- 2.5 to 33.4 +/- 3.4 mm Hg, p less than 0.05). Renal blood flow was unchanged during adenosine infusion. CONCLUSIONS. Adenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation.     

Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension

The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of tachycardia and hypertension following coronary artery bypass graft surgery: efficacy and haemodynamic effects of esmolol

Hypertension following coronary artery bypass grafting is not uncommon, especially in patients having good left ventricular function. It is often accompanied by tachycardia. The purpose of this study is to determine the efficacy of esmolol in the treatment of tachycardia and hypertension immediately following cardiopulmonary bypass and to study other haemodynamic effects of esmolol. Thirty patients undergoing elective [corrected] coronary artery bypass grafting were included in this prospective study. Morphine-based anaesthetic technique along-with standard bypass techniques were used in all the patients. The study was performed in the operating room about 30-45 minutes after the termination of cardiopulmonary bypass. Patients having a heart rate of more than 90 bpm and systolic blood pressure of more than 130 mm Hg without any inotropic support were included and randomly assigned to esmolol or control group. Esmolol was administered in a bolus dose of 500 micrograms/kg followed by infusion of upto 100 micrograms/kg/min. The patients in the control group were administered comparable volumes of normal saline. Baseline haemodynamic measurements were obtained just before the administration of esmolol or normal saline and were repeated after 5, 10, 15, 30 and 45 min. The baseline measurement in both the groups showed that patients were maintaining a state of hyperdynamic circulation with high systolic blood pressure (esmolol group 148 +/- 15 mm Hg, control group 140 +/- 8 mm Hg; p = NS), heart rate (esmolol group 128 +/- 17 bpm, control group 127 +/- 17 bpm; p = NS) and cardiac index (esmolol group 3.1 +/- 1 L/min/m2, control group 3.3 +/- 0.5 L/min/m2; p = NS). Esmolol decreased systolic blood pressure (p < 0.001), heart rate (p < 0.01) and cardiac index (p < 0.05) at five minutes. These changes persisted throughout the study period. The left ventricular stroke work index decreased at five minutes (p < 0.05) and remained so till 30 minutes. The maximum fall in heart rate (15%) and systolic blood pressure (16%) was observed at 45 minutes. There were no haemodynamic changes in the control group except that cardiac index, stroke volume and left ventricular stroke work index increased at five minutes. We conclude that esmolol lowers the indices of cardiovascular work in patients who demonstrated hyperdynamic circulation. This was achieved by decreasing the heart rate and systolic blood pressure which was accompanied by decrease in cardiac index and left ventricular stroke work index.     

Esmolol: a new ultrashort-acting beta-adrenergic blocking agent for rapid control of heart rate in postoperative supraventricular tachyarrhythmias

Prompt control of heart rate is important for successful treatment of supraventricular tachyarrhythmias early after open heart surgery when sympathetic tone is high and ventricular response rates may be rapid. Esmolol, a new ultrashort-acting (9 minute half-life) beta-receptor blocking agent, was given by continuous intravenous infusion for up to 24 hours in 24 patients (21 with isolated coronary bypass surgery and 3 with valve replacement) 1 to 7 days after surgery. Atrial fibrillation was present in 9 patients, atrial flutter in 2 and sinus tachycardia in 13. Eleven patients had received intravenous digoxin (average dose 0.6 mg, average serum level 1.19 mg/100 ml) before esmolol infusion without adequate control of the supraventricular tachyarrhythmia. After a 1 minute loading infusion of esmolol (500 micrograms/kg per min), maintenance dose, titrated to heart rate and blood pressure response, varied from 25 to 300 micrograms/kg per min. After esmolol administration, at an average dose of 139 +/- 83 micrograms/kg per min, mean heart rate decreased from 130 +/- 15 to 99 +/- 15 beats/min. Within 5 to 18 minutes after initiation of therapy, all patients had achieved a 15% reduction in heart rate at a maintenance dose of 150 micrograms/kg per min or less. A 20% reduction in heart rate was attained in 19 of the 24 patients, and conversion to sinus rhythm occurred during esmolol infusion in 5 of the 11 patients with atrial flutter or fibrillation. Transient asymptomatic hypotension (less than 90/50 mm Hg) was seen in 13 patients, requiring cessation of esmolol therapy in 2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of heart failure on baroreflex control of sympathetic neural activity.

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)     

Inotropic, vascular and neuroendocrine effects of nifedipine in heart failure: comparison with nitroprusside

To evaluate the short-term hemodynamic and neuroendocrine effects of nifedipine in heart failure, it was compared with nitroprusside, a balanced vasodilator without known inotropic effect, in equihypotensive doses during right and left heart catheterization in nine patients with heart failure. Mean arterial pressure decreased from 89 +/- 12 to 76 +/- 14 mm Hg with nitroprusside, and from 90 +/- 12 to 75 +/- 13 mm Hg with sublingual nifedipine. Right atrial, pulmonary artery, pulmonary capillary wedge and left ventricular end-diastolic pressures decreased significantly with nitroprusside, but not with nifedipine. Cardiac index and stroke volume index increased to a similar extent with both drugs; in contrast, stroke work index increased significantly with nitroprusside, but not with nifedipine. Peak rate of left ventricular pressure development (dP/dt) (measured with a micromanometer-tipped catheter in seven patients) was unchanged with nitroprusside, but decreased significantly with nifedipine (747 +/- 292 to 639 +/- 238 mm Hg/s; p less than 0.002). There was no change in heart rate with either medication. Plasma norepinephrine and epinephrine concentrations were not altered significantly by either drug. Plasma renin activity was not changed by nitroprusside infusion, but was increased after the administration of nifedipine. Thus, in contrast to the balanced vasodilator action of nitroprusside, the effect of nifedipine is predominantly on the arterial circulation. In these patients with heart failure, reflex sympathetic stimulation did not occur in response to a decrease in systemic arterial pressure by either vasodilator. A negative inotropic effect occurred after the administration of nifedipine, but not nitroprusside.     

Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs

Atrial natriuretic factor lowers blood pressure in normotensive and hypertensive animal models. The present study examined the mechanism of the blood pressure-lowering effect in 10 normotensive dogs. Four awake dogs previously instrumented with electromagnetic flow probes for measurement of cardiac output and catheters for systemic hemodynamic and cardiac dynamic measurements were studied. After a 30-minute control period, a 3 micrograms/kg bolus followed by 0.3 micrograms/min/kg of a 24-residue synthetic atrial natriuretic factor was infused for 30 minutes, followed by a 1-hour recovery period. Mean arterial pressure fell significantly during infusion (control, 125 +/- 4; infusion, 108 +/- 5; recovery, 125 +/- 9 mm Hg; p less than 0.05) and was accompanied by a slight but significant bradycardia (control, 144 +/- 7; infusion, 134 +/- 5; recovery, 145 +/- 7 beats/min; p less than 0.05). Significant reductions in cardiac output (control, 2.66 +/- 0.60; infusion, 2.18 +/- 0.60; recovery, 2.74 +/- 0.60 L/min; p less than 0.05), stroke volume (control, 18.4 +/- 3.9; infusion, 16.0 +/- 4.2; recovery, 19.0 +/- 3.7 ml/beat; p less than 0.05), and maximum increase in rate of change of left ventricular systolic pressure (control, 2475 +/- 200; infusion, 2088 +/- 216; recovery, 2487 +/- 243 mm Hg/sec; p less than 0.05) were also observed during infusion. No significant changes in total peripheral resistance or central venous pressure were noted, although the latter tended to fall during infusion. A similar pattern was observed in six pentobarbital-anesthetized dogs, except that infusion of atrial natriuretic factor did not induce bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of esmolol in hypertension after cardiac surgery

Systolic hypertension, which is common soon after cardiac surgery, increases cardiac work and may threaten fresh vascular anastomoses. Because postoperative hypertension is often associated with elevated catecholamines and preoperative use of beta-blocking agents, esmolol, an ultrashort-acting beta-blocking agent, was compared with nitroprusside in a crossover study in this setting. Twelve patients, 18 to 28 hours after cardiac surgery (coronary artery bypass graft in 9, aortic valve replacement in 2 and valved aortic conduit with reimplantation of coronary arteries in 1 patient) received controlled infusions of esmolol (mean dosage 142 +/- 100 micrograms/kg/min, range 50 to 300 micrograms/kg/min) and nitroprusside (mean dose 1.6 +/- 1.3 micrograms/kg/min, range 0.5 to 2.75 micrograms/kg/min). In this open-label study, choice of the first drug was randomized, after which patients were then crossed over to the other study drug. Therapeutic response (greater than or equal to 15% systolic blood pressure reduction) was achieved in 11 of 12 esmolol patients and 12 of 12 nitroprusside patients. Both drugs significantly lowered systolic and diastolic blood pressure, as well as left ventricular stroke work index. While the cardiac index was decreased by esmolol and increased by nitroprusside, neither drug significantly changed stroke volume index. Systemic vascular resistance, unchanged by esmolol, was decreased significantly by nitroprusside. Oxygen saturation and Pao2, unchanged with esmolol, were both significantly reduced with nitroprusside. Thus, for hypertension early after cardiac surgery, esmolol is safe, effective and rapid and, compared with nitroprusside, results in less unwanted decrease in diastolic blood pressure and oxygen saturation, but there is more decrease in heart rate and cardiac index.     

Hemodynamic effects of nitroprusside on valvular aortic stenosis.

The effects of acute reduction of left ventricular (LV) loading in valvular aortic stenosis (AS) were examined. Thirty-five consecutive patients with AS (peak-to-peak aortic valve gradient 66 +/- 26 mm Hg, aortic valve area 0.65 +/- 0.22 cm2) were given intravenous sodium nitroprusside (1 to 3 micrograms/kg/min) to reduce systolic aortic pressures by greater than 10 mm Hg (mean aortic pressure 99 +/- 15 to 80 +/- 15 mm Hg; p less than 0.001). Overall, nitroprusside infusion resulted in little change in cardiac index (2.72 +/- 0.61 to 2.67 +/- 0.58 liters/min/m2; p = not significant). Individual patients had a range of responses. Fourteen patients (group 1) had an increase in cardiac index (2.42 +/- 0.59 to 2.74 +/- 0.67 liters/min/m2; p less than 0.001), whereas 21 (group 2) had a decrease or no change (2.93 +/- 0.56 to 2.61 +/- 0.52 liters/min/m2; p less than 0.001). Comparison of these subgroups showed that a cardiac index increase with nitroprusside was significantly predicted by a higher LV end-diastolic pressure (26 +/- 12 vs 15 +/- 6 mm Hg), lower LV ejection fraction (44 +/- 18 vs 62 +/- 12%). smaller aortic valve area (0.52 +/- 0.12 vs 0.74 +/- 0.22 cm2) and lower cardiac index (2.42 +/- 0.59 vs 2.93 +/- 0.56 liters/min/m2) (all values groups 1 and 2, respectively). It is concluded that there is a disparate response to acute vasodilatation in AS. Potentially beneficial effects are seen in a subgroup of patients, especially those with increased filling pressures and impaired LV function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac effects of atrial natriuretic peptide in subjects with normal left ventricular function

The effects of atrial natriuretic peptide (ANP) infusion were determined in 9 subjects undergoing cardiac catheterization that did not disclose heart disease. Data were obtained at rest and during the steady-state phase of alpha-human-(1-28)-atrial natriuretic peptide infusion (0.5 micrograms/kg bolus, 0.05 micrograms/kg/min intravenously for 10 minutes). Mean blood pressure decreased from 105 +/- 3 to 98 +/- 4 mm Hg (p less than 0.05); pressure measurements and left ventricular (LV) angiograms suitable for analysis were available in 7 of 9 subjects at matched heart rate. The ANP infusion reduced LV end-diastolic and end-systolic volume indexes from 93 +/- 6 to 80 +/- 6 ml/m2 (p less than 0.01) and from 25 +/- 3 to 17 +/- 1 ml/m2 (p less than 0.05), respectively. The LV ejection fraction increased insignificantly from 72 +/- 5 to 77 +/- 4%. End-systolic pressure/volume ratio showed a slight but not significant increase (from 3 +/- 0.4 to 4 +/- 0.8). Initial plasma levels of ANP (48 +/- 12 pg/ml) increased to 1,890 +/- 423 pg/ml (p less than 0.001) during the infusion and individual hemodynamic responses were not related to plasma ANP concentrations. These data suggest that the administration of ANP has no negative effects on LV function and the ANP-induced changes on cardiac performance are related to the reduced cardiac load.     

Programmed ventricular stimulation in patients with left ventricular dysfunction and ventricular tachycardia: effects of acute hemodynamic improvement due to nitroprusside

To assess the electrophysiologic effects of acute hemodynamic improvement in patients with left ventricular systolic dysfunction, 12 patients with a left ventricular ejection fraction less than 0.40 and a history of sustained monomorphic ventricular tachycardia were studied. All patients had underlying coronary artery disease. Patients underwent programmed cardiac stimulation in random order during a baseline period and with nitroprusside infusion. Mean pulmonary capillary wedge pressure decreased from 20 +/- 8 mm Hg at baseline study to 8 +/- 3 mm Hg during nitroprusside infusion (p less than 0.0001). Pulmonary artery, right atrial and systemic arterial pressures also decreased with nitroprusside (p less than 0.01). Cardiac output did not change. Left ventricular dimensions, determined by two-dimensional echocardiography, decreased significantly during nitroprusside infusion. The right ventricular effective refractory period, measured during ventricular drive trains at cycle lengths of 400 and 600 ms, were similar during baseline and nitroprusside periods (271 +/- 30 versus 274 +/- 31 ms at 600 ms, and 249 +/- 25 versus 246 +/- 18 ms at 400 ms). In 2 patients no ventricular arrhythmias were induced during either study period; in the other 10, ventricular tachyarrhythmias were induced during both periods. The mean number of extrastimuli required to induce a ventricular tachyarrhythmia was similar during the baseline period (1.8 +/- 0.6) and during nitroprusside infusion (1.9 +/- 0.7). As well, the mean cycle length of ventricular tachycardia induced was similar during the baseline period (347 +/- 61 ms) and during nitroprusside infusion (342 +/- 70 ms).(ABSTRACT TRUNCATED AT 250 WORDS)     

The differential effects of positive inotropic and vasodilator therapy on diastolic properties in patients with congestive cardiomyopathy

Symptoms of congestive heart failure frequently reflect abnormalities in both systolic and diastolic performance. While much work has been reported regarding the mechanisms by which positive inotropic and vasodilator therapy affect systolic performance, little is known about their effect on diastolic function. In 12 patients with diffuse congestive cardiomyopathy micromanometer left ventricular and aortic pressure measurements were recorded simultaneously with two-dimensionally targeted M mode echocardiograms and thermodilution-determined cardiac output. Each patient received dopamine (2, 4, and 6 micrograms/kg/min), and dobutamine (2, 6, and 10 micrograms/kg/min), and 10 received nitroprusside (0.125 to 2.0 micrograms/kg/min). Baseline hemodynamics were characterized by low cardiac index (2.1 +/- 0.7 liter/min/m2, mean +/- SD), high left ventricular end-diastolic pressure (24 +/- 10 mm Hg), and increased end-diastolic (6.8 +/- 1.0 cm) and end-systolic dimensions (6.0 +/- 1.0 cm). All patients had abnormal left ventricular pressure decay with a prolonged time constant (67 +/- 20 msec) and reduced peak diastolic lengthening rates. Dopamine and dobutamine decreased the time constant of relaxation and increased the peak lengthening rate. Dobutamine also reduced the minimum diastolic pressure from 14 +/- 7 to 10 +/- 9 mm Hg (p less than .01); neither drug reduced end-diastolic pressure. In fact, dopamine elevated end-diastolic pressures in seven patients, despite more rapid pressure decay. Diastolic pressure-dimension relations after dopamine and dobutamine showed a leftward shift with a reduced end-systolic chamber size, but no significant changes in passive chamber stiffness. Nitroprusside decreased left ventricular minimum diastolic pressure by 4 +/- 2 mm Hg and end-diastolic pressure by 7 +/- 4 mm Hg (p less than .01). It did not consistently accelerate left ventricular pressure decay at the doses tested. The decreased end-diastolic pressure with nitroprusside was due to a reduced end-diastolic dimension in five patients. In the other patients, all of whom had elevated right atrial pressures, diastolic pressure-dimension relations showed a parallel downward shift after nitroprusside. Thus, positive inotropic therapy with beta 1-adrenoceptor agonists enhances early diastolic distensibility by accelerating relaxation, augmenting filling, and reducing end-systolic chamber size. Vasodilator therapy is much more effective in lowering diastolic pressures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Use of an ultra short-acting beta-blocker in patients with acute myocardial ischemia

Esmolol is a new ultra short-acting (half-life [t1/2] beta 9 min) beta 1-adrenergic-receptor antagonist reported to have no intrinsic sympathomimetic activity. The safety and efficacy of esmolol in lowering the ventricular rate and rate-pressure product in patients with acute myocardial infarction (n = 5), postmyocardial infarction angina (n = 10), or acute unstable angina (n = 4), and without cardiogenic shock were studied. After a 30 min observation period, esmolol was titrated to a maximum dose of 300 micrograms/kg/min and infused for up to 420 min. The ventricular rate fell from 92 +/- 11 (mean +/- SD) to 77 +/- 13 beats/min (p less than .01) and the systolic arterial pressure decreased from 120 +/- 13 to 97 +/- 11 mm Hg (p less than .01) during the initial 30 min titration period. There was no significant change during the maintenance phase, and both the ventricular rate and arterial pressure returned rapidly toward baseline values within 30 min of termination of the infusion. The cardiac index fell from 2.8 +/- 0.6 to 2.2 +/- 0.6 liters/min/m2 (p less than .01) during the same period, and also returned to the baseline level 30 min after termination of the infusion. There was no significant change in the pulmonary capillary wedge pressure, respiratory rate, or PR interval. Five patients required termination of infusion because of hypotension and all recovered uneventfully within 30 min of stopping the esmolol. One patient required a brief infusion of dopamine to restore hemodynamic stability.(ABSTRACT TRUNCATED AT 250 WORDS)