Mean Pulmonary Artery Wedge Pressure Research Articles

Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent

Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively ( p < 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume ( p < 0.01) and a 42% increase in ejection fraction ( p < 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h ( r = −0.80 and −0.69 for mean pulmonary artery wedge pressure, r = −0.88 and −0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope.

Outcome and complications of prolonged intraaortic balloon counterpulsation in cardiac patients

The risks and benefits of prolonged intraaortic balloon support for the management of refractory congestive heart failure and ischemia were studied in patients with end-stage heart disease who needed support for ≥5 days. Fifty-two insertions were performed by the percutaneous femoral route in 49 patients. The duration of insertion ranged from 5 to 46 days (mean 11.3). Clinical outcome including hemodynamic parameters and complications were recorded. Mean systemic arterial pressure did not change with balloon insertion (74 ± 19 vs 76 ± 11 mm Hg; p = not significant). Both the mean pulmonary artery and pulmonary arterial wedge pressures decreased (33 ± 8 to 26 ± 9 mm Hg [p < 0.01], and 25 ± 8 to 17 ± 6 mm Hg [p < 0.01], respectively). Over time, both parameters tended to increase, but remained significantly less than those before insertion. Cardiac index increased from 1.6 ± 0.4 to 2.2 ± 0.5 liters/min/m 2 on insertion and continued to increase to 2.7 ± 0.5 liters/min/m 2 (p < 0.01) before removal. Definite balloon catheter infection developed in 7 patients, and hemorrhage occurred in an additional 7. Eleven patients had vascular compromise, with loss of pulse in 6, thrombosis of the femoral artery in 1, and pseudoaneurysm in 2. Lacerated femoral artery occurred in 1 patient, and mesenteric artery thrombosis in another. Twenty patients died from progressive heart failure and multiorgan system failure, and 19 survived to receive left ventricular assist device and heart transplantation. Only 10 patients were weaned off the balloon. In conclusion, prolonged intraaortic balloon pump support may be successfully used in end-stage heart disease.

Transient myocardial ischemia stimulates atrial natriuretic factor release

Atrial natriuretic factor release during transient myocardial ischemia was investigated in 29 patients with coronary artery disease and symptoms of angina (Canadian Cardiovascular Association classes II–III). Eleven patients (group I) underwent single-vessel percutaneous transluminal coronary angioplasty. Repeat determinations of mean pulmonary artery wedge pressure and blood sampling from pulmonary artery for atrial natriuretic factor measurements were performed at baseline, and at 2, 5, and 15 minutes after percutaneous transluminal coronary angioplasty was begun. Baseline atrial natriuretic factor levels (34.6 ± 4.5 pg/ml) rose to 56.3 ± 7.3 pg/ml ( p = 0.02) and decreased at 5 minutes (43.7 ± 5.7 pg/ml, not significant) and 15 minutes (35.3 ± 4.4 pg/ml, not significant). Changes in atrial natriuretic factor concentrations were significantly correlated with those in mean pulmonary artery wedge pressure (2 minutes: r = 0.69, p = 0.02; 5 minutes: r = 0.90, p < 0.001). In group II ( n = 10) the increase in atrial natriuretic factor after dye load occurred later (baseline: 25.8 ± 2.1; 60 minutes: 40.6 ± 2.6 pg/ml; p = 0.005) than that observed in group I after percutaneous transluminal coronary angioplasty. In group III, atrial natriuretic factor during angina rose as early (baseline 11.3 ± 1.3; 5 minutes: 20 ± 2.3 pg/ml; p = 0.006) as after percutaneous transluminal coronary angioplasty. Results indicate that transient myocardial ischemia stimulates atrial natriuretic factor release, probably through changes in cardiac function.

Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up

Sixteen patients (12 male and 4 female, age 2–46 years) with endomyocardial biopsy-proven myocarditis were prospectively evaluated with immunosuppressive therapy including azathioprine and prednisolone in addition to other standard measures. Patients were either in NYHA class IV ( n = 12) or class III ( n = 4). Twelve patients showed improvement and the remaining 4 continued to deteriorate: 2 died at 1 and 2 months after therapy and the other 2 were lost to follow-up after 4–6 weeks of therapy. Three of the 12 patients who showed significant improvement, after sudden omission of therapy (at 8 weeks, 6 and 8 months) worsened and died. One patient who showed significant improvement died suddenly after 9 months of therapy while playing football. The remaining patients have shown significant clinical and haemodynamic improvement with normalization of myocardial morphology. Serial haemodynamic studies revealed a significant fall in cardiothoracic ratio (before: 62.3 ± 4.7%; 3 months: 55.1 ± 3.1%, P < 0.0001; 6–12 months: 50.6 ± 1.5%, P < 0.0001), mean pulmonary artery pressure (before: 34.3 ± 13.05 mm; 3 months: 20.4 ± 8.71 mm, P < 0.01; 6–12 months: 20.0 ± 2.75 mm, P < 0.01) and mean pulmonary artery wedge pressure (before: 26.0 ± 9.07 mm; 3 months 14.0 ± 5.63 mm, P < 0.001; 6–12 months: 13.2 ± 4.57 mm, P < 0.001). The left ventricular ejection fraction improved from 24.3 ± 8.36% to 35.8 ± 9.72% ( P < 0.001) at 3 months and 49.8 ± 18.2% ( P < 0.0001) at 6–12 months of therapy. Two patients have been subsequently lost to follow-up whereas the remaining 6 patients are on follow-up for 1–4 years after therapy and are doing fine. Our uncontrolled observations suggest that immunosuppressive therapy may be useful in patients with inflammatory myocarditis.

Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.

Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure.

Early development of nitrate tolerance has been shown in patients with chronic congestive heart failure (CHF) receiving continuous nitroglycerin therapy. The influence of dosing interval of oral isosorbide dinitrate (ISDN), the nitrate preparation most widely used for the treatment of CHF, has not been investigated. We performed a prospective, randomized study to evaluate the effect of various regimens of oral ISDN on the development of early tolerance to its effect on left ventricular filling pressure in patients with moderate to severe CHF. Forty-four responders (20% or greater reduction in mean pulmonary artery wedge pressure lasting 1 hour or longer) were divided into four groups of 11 patients each, and randomized to receive their effective ISDN dose (40-120 mg) Q 4 hours, Q 6 hours, Q 8 hours, or t.i.d. (drug given at 0, 6, 12, and 24 hours allowing 12 hours of ISDN washout interval between the third and fourth doses). All groups demonstrated a significant and comparable reduction in LV filling pressure following administration of the first ISDN dose. Early attenuation of hemodynamic response was demonstrated with frequent dosing (Q 4 hours and Q 6 hours) ISDN. Tolerance was with a Q 8-hour regimen as demonstrated by preserved hemodynamic response to each dose. The effect of each dose, however, was short-term, with return of pulmonary artery wedge pressure to baseline level at 2 to 4 hours, resulting in an intermittent effect totaling no longer than 12 hours of the 30-hour study period. The use of a t.i.d. regimen resulted in marked attenuation of response after the third dose with complete restoration of nitrate effect following a 12-hour washout period between the third and fourth doses. ISDN plasma concentration was measured in five patients in each of the Q 4- and Q 8-hour groups. In the Q 4-hour group, plasma levels were significantly higher after administration of the last dose than after the first dose (area under the curve, 242 +/- 216 versus 123 +/- 130 ng/ml, p less than 0.05), and trough levels before administration of the second and the fifth dose (15 +/- 17 and 27 +/- 27 ng/ml, respectively) were both markedly higher than the baseline value of 2 +/- 4 ng/ml. Our data demonstrate the development of tolerance and early attenuation of effect on left ventricular filling pressure with frequent oral dosing (Q 4 and Q 6 hours) with ISDN in patients with chronic CHF, which may be related to persistently elevated trough blood levels of ISDN. The development of tolerance can be reversed after a washout period of 12 hours and can be prevented with a Q 8-hour administration. These regimens, however, are limited by an inconsistent effect. Although long-term implications of these findings need further evaluation, the present study demonstrates the difficulty of maintaining a persistent ISDN-mediated reduction in left ventricular filling pressure in patients with chronic, moderate to severe CHF. These results suggest the need to use intermittent ISDN therapy allowing a daily nitrate washout interval and the rationale for combined vasodilator therapy in patients with CHF.

Peripartum cardiomyopathy: prognostic variables at initial evaluation

Twenty patients with peripartum cardiomyopathy were followed up for a period ranging from 6–14 months (mean 6±2 months). At initial evaluation, 16 patients were in New York Heart Association Class IV and the remainder in Class III. During follow up, 12 patients improved to Class I, 7 patients either failed to improve or deteriorated and one patient died. Certain variables at initial evaluation were related to prognosis. The patients who deteriorated, as compared to those who improved, were significantly older (30 ± 6.8 vs 24 ± 3 years, P < 0.01), of higher parity (3 ± 1 pregnancies vs 1.5±5 pregnancies, P < 0.001) and had later onset of symptoms after delivery (7.6 ± 4 weeks vs 3 ± 1.3 weeks, P < 0.001). They also had higher echocardiographic left ventricular end diastolic dimensions (7.0 ± 8.4 cm vs 3.0 ± 0.8 cm, P < 0.001) and higher mean pulmonary arterial (38 ± 4 mmHg vs 28 ± 6 mmHg, P < 0.001) and pulmonary arterial wedge pressures (24 ± 2 mmHg vs 20 ± 2 mmHg, P < 0.001) at cardiac catheterization. Conduction defects were present on the surface electrocardiogram in all the patients who deteriorated, as compared to 4 patients who improved. In conclusion, certain variables at initial evaluation can help in identifying high risk subsets with peripartum cardiomyopathy.

Clinical pharmacology of intravenous enoximone: Pharmacodynamics and pharmacokinetics in patients with heart failure

Twenty-one patients with heart failure (New York Heart Association [NYHA] class II to IV) received a 24-hour infusion of enoximone followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I to III received an 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0, or 10.0 μg/kg/min. Group IV patients received a maintenance infusion of 5.0 μg/kg/min without a loading dose. Serial assessment of hemodynamics, plasma levels of enoximone and enoximone sulfoxide, and ventricular ectopy were performed. Enoximone produced a clinically significant increase in cardiac index, and a decrease in mean pulmonary artery wedge pressure and systemic vascular resistance in all groups. Enoximone mildly increased heart rate, and had a minimal effect on mean arterial pressure. There was no statistically significant change in ventricular ectopy during the infusion. Significant hemodynamic improvement was noted at even the lowest infusion rate, and did not increase in linear fashion at higher infusion rates. In patients who did not receive an initial loading bolus of 0.5 mg/kg, the increase in cardiac index was delayed by approximately 1 hour. Plasma concentrations of both enoximone and its major metabolite continued to rise throughout the 24-hour infusion in group III (10.0 μg/kg/min), rather than reaching steady state as predicted by the terminal exponential half-lives of these compounds. This is suggestive of nonlinear pharmacokinetics and indicates a potential for excessive accumulation of enoximone and its metabolite during prolonged infusion. These findings may have important implications in gulding the intravenous administration of enoximone. Intravenous doses of enoximone above 5.0 μg/kg/min may not provide very much additional hemodynamic benefit compared with lower doses and yet may result in significant accumulation of enoximone and its metabolites, leading to an increased potential for toxicity. An initial intravenous bolus of enoximone should be administered prior to continous infusion of enoximone in cases where immediate hemodynamic benefit is desirable.

Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy

Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects or a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3, 100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean ± SD, −17 ± 14%), increases in mean right atrial (31 ± 21%), mean pulmonary artery (14 ± 14%) and mean pulmonary capillary wedge (17 ± 14%) pressures and an increase in cardiac index (18 ± 10%) due to an increased heart rate without any significant change in stroke volume.During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease.It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients.

Comparison of nicardipine and sodium nitroprusside in the treatment of paroxysmal hypertension following aortocoronary bypass surgery

In an open, randomized, multicenter trial, intravenous nicardipine was compared with sodium nitroprusside in 74 patients with hypertension (mean arterial pressure [MAP] ≥ 100 mm Hg) following coronary artery bypass surgery. Nicerdipine was administered as a 2.5- to 12.5-mg bolus followed by a 2 to 4 mg/h infusion, and nitroprusside as a 0.5 to 6.0 μg/kg/min infusion. The aim was to reduce MAP to < 90 mm Hg within 50 minutes and maintain it stable at 85 ± 5 mm Hg. Nicardipine was effective in 35 of 38 patients (92%), and nitroprusside in 29 of 36 (81%) (NS). The decrease in MAP was not statistically different, but time until reaching the therapeutic end-point was shorter with nicardipine( P < 0.01). Significant differences follow: increase in heart rate and decreases in mean pulmonary artery, right atrial, and pulmonary capillary wedge pressures were more marked with nitroprusside ( P < 0.01 and P < 0.05, respectively), whereas elevation of cardiac index and depression of systemic vascular resistance were more marked with nicardipine ( P < 0.01 and P < 0.05, respectively). Postreduction MAP was more stable with nicardipine, 51% ±0 24% of readings falling within the range 85 ± 5 mm Hg versus 41% ± 18% on nitroprusside ( P = 0.058). Dose adjustment during the following 24 hours was less frequent with nicardipine, 1.1 ± 1.6 versus 2.7 ± 2.6 ( P < 0.01). Transfused blood volume was lower with nicardipine (924 ± 644 mL) than nitroprusside (1,306 ± 901 mL) ( P = 0.08), despite similar postoperative blood losses. Rhythm or conduction disturbances occurred in 5 patients with nicardipine and in 6 patients with nitroprusside, and hypotension in 1 and 4 patients, respectively. Postoperative hypertension was rapidly controlled with both drugs. However, the selective arterial effects of nicardipine suggest that it may be the more appropriate choice.

Acid-base status affects gas exchange in canine oleic acid pulmonary edema

The effects of acidosis and alkalosis on pulmonary gas exchange were studied in 32 pentobarbital sodium-anesthetized intact dogs after induction of oleic acid (0.06 ml/kg) pulmonary edema. Gas exchange was assessed at constant ventilation and constant cardiac output, by venous admixture calculations and by intrapulmonary shunt measurements using the sulfur hexafluoride (SF6) method. Metabolic acidosis (pH 7.20) and alkalosis (pH 7.60) were induced with HCl and Carbicarb (isosmolar Na2CO3 and NaHCO3), respectively. Hypercapnia was induced by adding inspiratory CO2, whereas pH was allowed to change (respiratory acidosis, pH 7.20) or maintained constant (isolated hypercapnia). Mean intrapulmonary shunt and pulmonary arterial minus wedge pressure difference, respectively, changed from 44 to 33% (P less than 0.05) and from 9 to 10 mmHg (P greater than 0.05) in metabolic acidosis, from 44 to 62% (P less than 0.001) and from 12 to 8 mmHg (P less than 0.01) in metabolic alkalosis, from 40 to 42% (P greater than 0.05) and from 13 to 16 mmHg (P less than 0.05) in respiratory acidosis, from 42 to 52% (P less than 0.05) and from 8 to 12 mmHg (P less than 0.01) in isolated hypercapnia. These results indicate that acidosis, alkalosis, and hypercapnia markedly influence pulmonary gas exchange and/or pulmonary hemodynamics in dogs with oleic acid pulmonary edema.

A quantitative analysis of hemodynamic effects of the right ventricle included in the circulation of the Fontan procedure.

Right heart hemodynamics were analyzed with a catheter-mounted velocity meter in seven patients after direct atrioventricular anastomosis for Fontan procedure (RV group) and were compared with those obtained in eight patients after direct atriopulmonary anastomosis (RA group). In the RV group, cardiac output was 2.7 +/- 0.6 l/min/m2; mean right atrial and pulmonary artery pressures were both 13 +/- 3 mm Hg; mean pulmonary artery wedge pressure was 7 +/- 5 mm Hg; left ventricular end-diastolic volume, determined angiographically, was 129 +/- 40% of normal; and its ejection fraction was 0.50 +/- 0.09. In the RA group, data were similar to those of the RV group except that right heart pressure were lower in the RV group, which was related to the preoperative condition of the pulmonary circulation. In the RV group, the fraction of ventricular forward flow of the total forward flow in the main pulmonary artery ranged from 0.21 to 0.46 and was not correlated with cardiac output or with any other parameter. The backward flow into the inferior vena cava at ventricular systole was greater than the atrial flow in two patients in whom cardiac output was less than 2.2 l/min/m2, whereas caval backward flow at atrial contraction was greater than ventricular flow in the other five patients, of whom four had a cardiac output greater than 3.1 l/min/m2. We conclude that the inclusion of right ventricle in the circulation of the Fontan procedure does not necessarily improve overall hemodynamics in most patients.

Cardiovascular, Respiratory, and Analgesic Effects of Fentanyl in Unanesthetized Rhesus Monkeys

To determine the suitability of the rhesus monkey as a model for investigation of opioids, we examined the analgesic, respiratory, and cardiovascular effects of fentanyl in six adult male rhesus monkeys. Fentanyl was administered in sequential bolus injections of 2, 4, 16, 64, and 128 micrograms/kg, with 10 min between each dose. Arterial plasma fentanyl concentrations and blood gas tensions were measured 3 and 9 min after each dose and 1, 2, 5, 20, 60, and 120 min after the final dose. At the same time periods, mean systemic arterial, pulmonary arterial, central venous, and pulmonary capillary wedge pressures, cardiac output, heart rate, and respiratory rate were measured. Analgesia was quantified as the time required for tail withdrawal from a standardized noxious stimulus. Tail latency response time increased significantly after the 4-microgram/kg dose (plasma fentanyl concentration = 2.7 +/- 0.9 ng/mL). Maximum tail latency response time was attained after the 64-micrograms/kg dose (43.4 +/- 26.0 ng/mL). Respiratory rate decreased significantly after the 2-microgram/kg dose, and PaCO2 increased significantly after the 4-microgram/kg dose. All animals became apneic, requiring tracheal intubation and controlled ventilation, after the 64-micrograms/kg dose. Also, mean arterial pressure and cardiac output decreased significantly after the 64-micrograms/kg dose. There were no other significant cardiovascular changes. Peak plasma fentanyl concentration after the 128-micrograms/kg dose was 117.0 +/- 49.6 ng/mL. It appears that plasma concentrations of approximately 40 ng/mL are sufficient to reach the full cardiovascular, respiratory, and analgesic effects of fentanyl in the rhesus monkey. Significant respiratory and analgesic effects are evident at concentrations as low as 3 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of released atrial natriuretic peptide after acute myocardial infarction.

The plasma concentration of atrial natriuretic peptide (pANP) was investigated at fixed times during 48 h following the onset of an initial attack of mild acute myocardial infarction (AMI) in 11 patients. Six hours after onset, the mean pANP was elevated, but 6 h later pANP had returned to the baseline level. Forty-eight hours after onset the mean pANP increased again. Thus, the curve of the time course of pANP consisted of 2 peaks separated by a dip. Six hours after onset, systemic hemodynamics and humoral factors were measured in 27 patients. At 48 h they were measured in 14 patients. The late elevation of pANP correlated with mean pulmonary arterial wedge pressure (r = 0.63, n = 14, p less than 0.05), while the early elevation of pANP did not (r = 0.31, n = 27, n.s.). The early elevation of pANP correlated with plasma concentrations of both noradrenaline (r = 0.55, n = 27, p less than 0.01) and creatine phosphokinase (r = 0.54, n = 27, p less than 0.01). In addition, noradrenaline levels positively correlated with mean pulmonary arterial wedge pressure (r = 0.38, n = 27, p less than 0.05). The cause of the early elevation of pANP in AMI is unclear, but it is suggested that injury to myocardium and activated sympathetic nerve activity may be responsible in part.

Relation of mean pulmonary arterial wedge pressure and left ventricular end-diastolic pressure

The flow-directed, balloon-tipped catheter has facilitated the management of critically ill patients by providing a means of measuring right-sided cardiac pressures and output. In addition, it has been used to measure certain left-sided cardiac pressures. Hellems et al 1 reported that a catheter effectively “wedged” in a pulmonary artery (PA) yielded blood that was fully saturated with oxygen and a pressure reflective of that in the left atrium. Subsequently, other investigators substantiated this observation, noting that an oximetrically confirmed PA wedge pressure was similar to left atrial pressure. 2,3 In the absence of mitral valve disease, mean PA wedge pressure is similar to mean left ventricular (LV) diastolic pressure, but there is continuing confusion about the relation between mean PA wedge and LV end-diastolic pressures. 4 In subjects without cardiac disease, mean left atrial pressure (and likewise mean PA wedge pressure) almost always approximates LV end-diastolic pressure 5 and, therefore, can be used to assess LV filling. In contrast, these pressures may be disparate in subjects with cardiac disease. 6 This study was performed to examine the relation of mean PA wedge and LV end-diastolic pressures in patients with and without cardiac disease.

Oral metoprolol therapy in dilated cardiomyopathy: hemodynamic evidence for improved diastolic function accompanying amelioration of symptoms

Twenty patients with dilated cardiomyopathy (11 males and 9 females) aged from 14 to 54 (37.3 ± 10.5) years were treated orally with metoprolol (dose 37.5 mg–100 mg/day, mean 91 ± 18.6 mg/day) after a baseline hemodynamic study. On follow-up, all patients showed improvement in symptomatic status by at least one NYHA class within 2 to 4 weeks of the initiation of therapy. Repeat right heart study and left ventricular angiography (venous digital subtraction angiography) after 3 to 6 months of treatment in 10 patients showed a fall in the mean pulmonary arterial wedge pressure from 24.4 ± 9.6 to 12.8 ± 7.7 mm Hg ( P = 0.025), right ventricular end-diastolic pressure from 8.8 ± 4.7 mm Hg to 4.5 ± 1.9 mm Hg ( P = 0.025) and mean pulmonary arterial pressure from 34.2 ± 12.4 mm Hg to 25.9 ± 10.9 mm Hg ( P < 0.01). There was no significant change in the left ventricular ejection fraction (18.7 ± 1.6% vs. 22 ± 0.48%, P = NS) or cardiac index (2.2 ± 0.48 l/m/m 2 to 2.12 ± 0.68 l/m/m 2, P = NS). These hemodynamic results indicate that the improvement in symptoms and congestive cardiac failure produced by treatment with metoprolol in patients having dilated cardiomyopathy is related to improvement in diastolic function of the myocardium.

The cardiovascular response to digoxin in conscious dogs with left atrial obstruction

In addition to positive inotropic and atrioventricular conduction-blocking properties, digoxin is capable of producing systemic and pulmonary vasoconstriction. However, whether chronic digoxin treatment exacerbates the pulmonary hypertension that results from left atrial (LA) outflow obstruction has not been specifically examined. This study assessed the vascular and inotropic responses to 5 days of digoxin treatment in six conscious dogs before and after filling a permanently implanted LA balloon. Dogs were also instrumented to measure left ventricular (LV) pressure, LV dP/dt, mean systemic arterial (MAP), right atrial (RAP), pulmonary arterial, and pulmonary capillary wedge pressures, as well as cardiac output (CO). Under normal conditions with the balloon empty, digoxin treatment (40 micrograms/kg loading dose and 12 micrograms/kg/d for 5 days) reduced CO (-17%) and increased systemic (SVR) and pulmonary (PVR) vascular resistances 27% and 37%, respectively; heart rate (HR) and LV dP/dt were not changed. Filling the balloon with enough saline to double PVR also increased SVR (52%), HR (42%), and RAP (92%), and reduced CO (-24%). During LA outflow obstruction, 5 days of digoxin reduced HR (-17%), SVR (-29%), and RAP (-23%), but did not alter PVR, CO, or LV dP/dt. This study demonstrates that although systemic and pulmonary vasoconstriction result from chronic digoxin treatment under normal conditions, the drug produces systemic vasodilation and no change in PVR during LA outflow obstruction.

Bronchial Hyperreactivity in Patients with Mitral Valve Disease

To elicit the mechanism of bronchial hyperreactivity (BHR) in chronic heart failure (CHF), a methacholine inhalation test, pulmonary function test, and cardiac catheterization were performed in 19 patients with mitral valve disease (MVD), and the change of severity of BHR before and after mitral valve replacement (MVR) was also examined in seven of 19 patients with MVD. Sixteen of 19 patients with MVD showed significant increase in respiratory resistance in methacholine inhalation test, while all normal subjects did not. The maximal expiratory flow at 25 percent of vital capacity (Vmax25), a parameter of small airway disease, correlated significantly with log cumulative dose producing a 35 percent decrease in respiratory conductance (PD35Grs) (r = 0.536) and the duration of symptoms (r = -0.682). There was a significant correlation between log PD35Grs and mean pulmonary artery wedge pressure (r = -0.466). After MVR, log PD35Grs was significantly improved in all seven operated-on patients, although six patients retained BHR. We conclude that patients with long-term MVD have marked BHR and that BHR in long-term MVD is related to peripheral airway narrowing with organic remodeling, which was not ameliorated with MVR procedure, in addition to pulmonary congestion.

Inhibition of the Metabolism of Atrial Natriuretic Factor Causes Diuresis and Natriuresis in Chronic Heart Failure

Atrial natriuretic factor (ANF) is a peptide hormone secreted by the heart that is degraded in vivo by endopeptidase 24:11 (atriopeptidase). UK 69,578 is a novel atriopeptidase inhibitor that raises plasma levels of ANF in animals and normal volunteers, with associated diuresis and natriuresis. This study examines the effects of UK 69,578 in patients with mild heart failure. UK 69,578 was administered as an intravenous infusion over 20 min in a placebo-controlled, cross-over study to six patients with stable (NYHA Class 2) chronic heart failure. The atriopeptidase inhibitor was well tolerated and no side effects were encountered. Mean baseline plasma ANF was elevated at 88 pg/mL (normal less than 50), and increased 2- to 5-fold after UK 69,578 administration. Plasma ANF did not change significantly following placebo. There was a marked diuresis after UK 69,578 compared to placebo. Urinary sodium excretion doubled for 4 to 6 h, but there was no significant rise in potassium excretion. There was no increase in plasma active renin concentration during the study period. Noninvasive hemodynamic monitoring revealed no significant changes in heart rate, systemic arterial blood pressure, or echocardiographic left ventricular dimensions. However, invasive measurements using a Swan-Ganz catheter demonstrated falls in mean right atrial and pulmonary artery wedge pressures after UK 69,578. There was no change in cardiac output. Thus, inhibition of endopeptidase 24:11 by UK 69,578 results in significant elevation of plasma ANF, with associated diuresis, natriuresis and venodilatation. The compound was well tolerated in these patients with mild chronic heart failure.

Intermittent high frequency ventilation. Clinical evaluation of a new mode of ventilation

In this first clinical study of a new mode of ventilation, called intermittent high frequency ventilation (IHFV), a comparison was made in ten patients after myocardial revascularization, between normal ventilation, high frequency ventilation (HFV) and IHFV at 15, 60, 100 and 160 breaths per min (b.p.m.). During IHFV the ventilation was interrupted for 3 s 7 times per min. The measured mean trapped gas volumes were 219 ml at 60 b.p.m. and 716 ml at 160 b.p.m. At 160 b.p.m. during IHFV, the mean, mean airway pressures, pulmonary artery (PAP) and capillary wedge pressures and the Paco2 were decreased, while the cardiac output increased. When the Paco2 was maintained constant, IHFV also allowed a reduction in the mean peak and mean airway pressures. This new mode of ventilation can prevent sustained increases in the lung volume and provide a reduction in intrapulmonary pressures. It also permits the measurement of the trapped gas volume and end-tidal CO2 gas concentrations several times a minute for the clinical management of patients during high frequency ventilation.