Hemodynamic effects of noninvasive systolic unloading (nitroprusside) and diastolic augmentation (external counterpulsation) in patients with acute myocardial infarction

The two major beneficial hemodynamic effects of invasive circulatory assistance (intraaortic balloon pumping) are (1) left ventricular systolic unloading, and (2) diastolic augmentation of aortic pressure. In this study, these effects were produced noninvasively in 17 patients (13 with acute myocardial infarction, 5 of whom had cardiogenic shock). Systolic unloading produced by the constant intravenous infusion of sodium nitroprusside (16 to 200 μg/min) caused a reduction in pulmonary capillary wedge pressure (27 to 19 mm Hg), a rise in cardiac index (1.71 to 2.25 liters/min per m²), and a reduction in mean arterial pressure (81 to 73 mm Hg). Diastolic augmentation with external counterpulsation produced a 20 mm Hg increase in peak, and a 7 mm Hg increase in mean diastolic arterial pressure. Cardiac index rose 14 percent after external counterpulsation in the patients with acute myocardial infarction. The results of combined use of these two modes of therapy (nitroprusside plus external counterpulsation) were better than those of either alone, in that external counterpulsation reversed the decrease in diastolic arterial pressure produced by nitroprusside, and also increased cardiac index further in six of nine patients. Thus it is feasible to utilize the principles of invasive circulatory assistance in a noninvasive way to produce hemodynamic improvement in patients with acute myocardial infarction.     

Transvalvular left ventricular assistance in cardiogenic shock secondary to acute myocardial infarction: Evidence for recovery from near fatal myocardial stunning

Objectives. The purpose of this study was to test the hypothesis that transvalvular left ventricular assistance would support the circulation in patients with cardiogenic shock secondary to acute myocardial infarction and allow recovery of function in patients with a reversibly (stunned) left ventricle.Background. Cardiogenic shock occurs in 7.5% of patients presenting with acute myocardial infarction, resulting in survival of only 20%. Despite the use of aggressive intervesntional therapy in patients with shock secondary to anterior myocardial infarction, survival remains as low as 33%.Methods. We studied 11 patients with acute myocardial infarction and cardiogenic shock, as defined by a cardiac index <2 liters/min per m², pulmonary capillary wedge pressure >18 mm Hg and systolic blood pressure <90 mm Hg during positive inotropic therapy. Patients were 57 ± 13 years old (mean ± SD) and had a mean left ventricular ejection fraction of 25 ± 11%, mean arterial pressure of 69 ± 13 mm Hg and mean cardiac index of 1.6 ± 0.4 liters/min per m²of admission to the study.Results. During the 1st 24 h of left ventricular assistance, pulmonary capillary wedge pressure decreased from 26 ± 4 to 16 ± 4 mm Hg (p = 0.01), cardiac index increased from 1.6 ± 0.4 to 2.4 ± 0.4 liters/min per m², and the dopamine hydrochloride dose decreased from 51 ± 92 to 18 ± 12 μg/kg body weight per min. In survivors, cardiac index improved to 3.2 ± 0.5 liters/min per m²(p = 0.01), and left ventricular ejection fraction improved to 34 ± 5% (p < 0.05). The overall survival in the study group was 4 (36%) of 11 patients (95% confidence interval [CI]8% to 65%), and 4 (66%) of 6 patients (95% CI 29% to 100%) with a Q wave anterior myocardial infarction survived.Conclusions. Transvalvular left ventricular support during cardiogenic shock complicating acute myocardial infarction is feasible and results in significant hemodynamic and functional improvement.     

Effects of intraaortic balloon pumping on acute myocardial infarction in 64 cases of cardiogenic shock, severe heart failure and mechanical heart failure

Of the patients treated in the CCU of Nippon Medical School for acute myocardial infarction in the past 5 years and 8 months, 44 with cardiogenic shock, 11 with severe heart failure, 7 with ventricular septal perforation and 2 with mitral regurgitation were treated by IABP. The peak effect of IABP on the hemodynamics of patients with cardiogenic shock was noted 24 hours after starting on IABP. When hemodynamics were compared between surviving and dead groups, there was a significant difference in stroke volume index between the two groups. When left ventricular function was compared between them, it was suggested that patients whose left ventricular function does not respond to IABP for 48 hours or longer are more likely to die than responders. Twenty-four of 44 patients became independent of IABP, but no more than 13 patients (30%) survived for 6 months or longer. Isosorbide dinitrate (ISDN) was combined with IABP in 7 patients who had a persistence of heart failure in spite of IABP. Combination therapy with IABP and ISDN elicited a significant increase in cardiac index, a significant decrease in pulmonary capillary wedge pressure, mean pulmonary arterial pressure and total peripheral resistance and a pronounced improvement in left ventricular function, and all 7 patients became independent of IABP. In the patients with acute myocardial infarction complicated with ventricular septal perforation, the mean systolic arterial pressure was 87.7 +/- 8.3 mmHg, mean pulmonary capillary wedge pressure, 20.3 +/- 7.4 mmHg and pulmonary-to-systemic flow ratio, 3.12 +/- 0.95 before starting on IABP. When the hemodynamics at 3 hours of IABP were compared to the pre-IABP values, the right atrial pressure, pulmonary capillary wedge pressure and pulmonary-to-systemic flow ratio had a tendency to decline, but the changes were not statistically significant, except for the peak arterial pressure which showed a significant elevation at 3 hours of IABP. Three of the 7 patients became dependent on IABP, and 2 of the 3 patients were saved by emergency operation.     

Therapie des akuten Herzversagens, medikament?se Strategie

The leading pathophysiology of acute heart failure and cardiogenic shock is acute or subacute myocardial infarction. Reperfusion of the occluded coronary vessel accompanied by adequate support of cardiac function via assist systems, preferentially the intraaortic balloon counterpulsation, is the therapy of choice. Adjustment of preload (high pulmonary capillary pressure in-acute myocardial infarction with small heart, low pulmonary capillary wedge pressure in patients with large ventricles and chronic heart failure, high central venous pressure in patients with right heart failure, and right ventricle myocardial infarction) and afterload (peripheral arterial vasodilatation, recommended systolic arterial pressure 80-90 mm Hg) but not maximization of cardiac output play an important role. Positive inotropic drugs should be considered when these strategies fail. In acute right heart failure in pulmonary hypertension, a preferential pulmonary vasodilatation with intravenous or inhalative prostaglandins or inhalative NO are of utmost importance. Systemic hypotension is not a contraindication in this pathophysiology.     

Natural evolution of left ventricular haemodynamics following uncomplicated acute myocardial infarction

In an attempt to investigate the changes in left ventricular haemodynamics following uncomplicated myocardial infarction 95 patients with definite electrocardiographic signs of infarction, without clinical signs of cardiac failure, were monitored with a Swan Ganz catheter for the first 24 hours after admission to hospital. The median delay from onset of symptoms was 6.8 hours. Mean heart rate increased (83-86 beats/min; P less than 0.05) while stroke volume index fell (38.4-36.6 ml/m2; P less than 0.05); cardiac index therefore remained unchanged during the observation period. As a result of a fall in arterial pressure both systemic vascular resistance and left ventricular stroke work index fell significantly (P less than 0.01). Pulmonary wedge pressure also fell (13.6-10.5 mm Hg; P less than 0.001), but this fall was confined to patients whose initial reading was above the median of 13 mm Hg. Pulmonary wedge pressure fell both among the 41 patients who required some medical therapy (15.6-10.8 mm Hg; P less than 0.001) and the 54 who received no medication throughout the 24 hours (12.0-9.8 mm Hg; P less than 0.05). The 39 patients with anterior wall infarction had higher baseline pulmonary wedge pressure and systemic vascular resistance than the 42 with inferior wall infarction. Later the stroke volume and stroke work index were persistently lower reflecting the greater degree of impairment of left ventricular function in anterior wall infarction. In conclusion, following an uncomplicated myocardial infarction, cardiac index was maintained, despite a fall in stroke volume, by an increase in heart rate. Pulmonary wedge pressure showed both a spontaneous fall and a fall in those patients given additional medical therapy during the study period.     

Percutaneous transluminal coronary angioplasty improves survival in acute myocardial infarction complicated by cardiogenic shock

Modest survival benefits have been reported in patients with acute myocardial infarction complicated by cardiogenic shock who were treated with early surgical revascularization or thrombolytic therapy. To determine whether coronary angioplasty improves survival, 87 patients with cardiogenic shock complicating acute myocardial infarction at the University of Michigan, Ann Arbor, Michigan, from 1975 to 1985 were retrospectively analyzed. Patients in group 1 (n = 59) were treated with conventional therapy; patients in group 2 (n = 24) were treated with conventional therapy and angioplasty. Extent of coronary artery disease, infarct location, and incidence of multivessel disease were similar between groups. Hemodynamic variables including cardiac index, mean arterial pressure, and pulmonary capillary wedge pressure were also similar. The 30-day survival was significantly improved for group 2 patients (50% vs. 17%, p = 0.006). Survival in group 2 patients with successful angioplasty was 77% (10 of 13 patients) versus 18% (two of 11 patients) in patients with unsuccessful angioplasty, (p = 0.006). The findings suggest that angioplasty improves survival in cardiogenic shock compared with conventional therapy with survival contingent upon successful reperfusion of the infarct-related artery.     

Hemodynamic spectrum of “dominant” right ventricular infarction in 19 patients

In 19 patients right ventricular infarction was diagnosed on the basis of electrocardiographic features of acute inferior infarction and clinical evidence of elevation of systemic venous pressure and an absence of pulmonary congestion. Right heart catheterization documented elevated right ventricular end-diastolic pressure (mean 15.5 mm Hg) and commensurate right atrial pressure (mean 14.9 mm Hg). In all patients the pulmonary capillary wedge pressure (mean 13.2 mm Hg) was exceeded or equaled by the right ventricular end-diastolic pressure, suggesting a disproportionate reduction in right ventricular compliance or contractile function, or both. Thirteen patients were hypotensive (systolic blood pressure less than 100 mm Hg on admission), including six patients with cardiogenic shock.

Right ventricular infarction is an uncommon and potentially reversible cause of cardiogenic shock;yet, in the experimental model, isolated right ventricular damage is relatively well tolerated. To identify the factors associated with systemic hypotension, data from patients with and without compromised systemic hemodynamic function were compared. In hypotensive patients, the right ventricular end-diastolic pressure was significantly higher (16.8 versus 12.8 mm Hg;p < 0.01) and reflected more extensive right ventricular damage. A pulmonary wedge pressure of 15 mm Hg or more was noted only among the hypotensive patients, and their wedge pressure (mean 14.8 mm Hg) was significantly greater than that of normotensive patients (mean 9.7 mm Hg, p < 0.05). Therefore, in patients with right ventricular infarction, an additional impairment of left ventricular function due to associated infarction of the inferior left ventricle is a significant factor causing hypotension. The elevated wedge pressure may influence right ventricular output by affecting pulmonary arterial diastolic pressure and right ventricular afterload. Right ventricular peak systolic pressure as an index of right ventricular afterload was significantly higher in hypotensive than in normotensive patients (30.5 versus 23.8 mm Hg, p < 0.03), and there was a linear correlation between this pressure and the pulmonary capillary wedge pressure (r = 0.895, p < 0.001).

There was one hospital death (mortality rate 5.3 percent). Clinical management generally consisted of administration of fluids and digitalis and implantation of a temporary pacemaker. This study emphasizes the relatively favorable prognosis of this condition and suggests that aggressive diagnosis and management are appropriate.     

Acute hemodynamic effect of a vascular antagonist of vasopressin in patients with congestive heart failure

To assess the role of arginine vasopressin (AVP) in congestive heart failure (CHF), 10 patients with CHF refractory to conventional treatment were studied before and 60 minutes after intravenous administration of 5 micrograms/kg of d(CH2)5Tyr(Me)AVP, a specific antagonist of AVP at the vascular receptor level. Heart rate, systemic arterial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index by thermodilution and cutaneous blood flow by laser-Doppler technique were measured. In 9 patients with no significant hemodynamic and cutaneous blood flow response to the AVP antagonist, baseline values (mean +/- standard deviation) were: heart rate, 77 +/- 14 beats/min; systemic arterial pressure, 120/79 +/- 18/8 mm Hg; pulmonary arterial pressure, 42/21 +/- 12/8 mm Hg; pulmonary capillary wedge pressure, 19 +/- 7 mm Hg; cardiac index, 2.2 +/- 0.6 liters/min/m2; plasma AVP, 2.3 +/- 0.8 pg/ml; and plasma osmolality, 284 +/- 14 mosm/kg H2O. The tenth patient had the most severe CHF. His plasma AVP level was 55 pg/ml and plasma osmolality was 290 mosm/kg. He responded to the AVP antagonist with a decrease in systemic arterial pressure from 115/61 to 79/41 mm Hg, in pulmonary arterial pressure from 58/31 to 33/13 mm Hg and in pulmonary capillary wedge pressure from 28 to 15 mm Hg. Simultaneously, cardiac index increased from 1.1 to 2.2 liters/min/m2 and heart rate from 113 to 120 beats/min; cutaneous blood flow increased 5-fold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic evaluation of cardiac insufficiency in the acute stage of myocardial infarct]

In 70 patients hemodynamic controls were preformed during the first 4 days after acute myocardial infarction. A sufficient regulation of heart function and the circulation at rest was accepted with the following conditions: pulmonary artery wedge pressure less than or equal to 13mm Hg, mean right atrial pressure less than or equal to 6 mm Hg, mean systemic arterial pressure greater than 70 mm Hg, cardiac index greater than 2.51/min/m2 and stroke index greater than 25 ml/m2. In 88% of the patients with acute myocardial infarction a cardiac failure was present at rest. The pressures in the right atrium and left atrium (from wedge pressures) were elevated and cardiac output was reduced. The ratio of stroke work index/mean pulmonary artery wedge pressure allowed a more precise differentiation between a compensated and failing heart (X +/- S = 3.6 +/- 0.7 resp. 1.7 +/- 0.6 g m/m2 mm Hg). In the average, a significant improvement of the hemodynamic alterations, due or not due to therapy, occurred only at the 3rd day or later. In the individual case, this improvement points to a favorable prognosis.     

The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells

STUDY OBJECTIVE: To determine the hemodynamic alterations occurring during therapy with the maximally tolerated doses of interleukin-2 and lymphokine-activated killer cells. DESIGN: Case series. SETTING: Referal-based inpatient oncology service at a university medical center. PATIENTS: A sequential sample of 13 patients with metastatic colon carcinoma, malignant melanoma, or hypernephroma who were receiving treatment with interleukin-2 and lymphokine-activated killer cells in the maximally tolerated doses. MEASUREMENTS and MAIN RESULTS: Pretreatment variables of mean arterial pressure, systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, and cardiac index were compared with the same variables measured either immediately before the eighth dose of interleukin-2 or immediately before the initiation of pressor support with dopamine hydrochloride. When these values were compared with the pretreatment values, patients showed a significant decrease in mean arterial pressure (92 mm Hg compared with 75 mm Hg; P less than 0.0001), and systemic vascular resistance (15.1 compared with 8.5 mm Hg/L . min; P less than 0.0001), but an increase in heart rate (73 compared with 110 beats/min; P less than 0.0001) and cardiac index (3.1 compared with 4.7 L/min . m2 body surface area; P less than 0.0001). No significant change was noted in pulmonary capillary wedge pressure. Low systemic vascular resistance persisted throughout interleukin-2 therapy. Although blood pressure normalized in 24 hours, the systemic vascular resistance remained below baseline levels 6 days after interluekin therapy had been stopped. INTERVENTIONS: Blood pressure was successfully supported at greater than 90 mm Hg with dopamine hydrochloride or phenylephrine hydrochloride, or both. CONCLUSIONS: Therapy with high doses of interleukin-2 induces hemodynamic changes consistent with a high-output and low-resistance state similar to changes noted during the early phase of septic shock.     

Emergency percutaneous cardiopulmonary bypass support in cardiogenic shock from acute myocardial infarction

Emergency percutaneous cardiopulmonary bypass support was instituted in 8 consecutive patients, ages 42 to 80 years, in cardiogenic shock for 30 to 180 minutes (mean 106) due to acute myocardial infarction. The location of the infarction was inferior in 4, anterior in 3 and lateral in 1. Four patients had a history of prior myocardial infarction. Two patients were in cardiac arrest; the remaining 6 had a mean blood pressure of 43 to 55 mm Hg before the bypass. Five had pulmonary capillary Wedge pressure greater than or equal to 20 mm Hg. One patient, with a right ventricular infarction, had a pulmonary wedge pressure of 10 mm Hg. Percutaneous insertion of 20Fr cannulas was carried out. Flow rates of 3.2 to 5.2 liters/min were achieved. Two patients in cardiac arrest regained consciousness while still in ventricular fibrillation or asystole. Left ventricular ejection fraction ranged from 17 to 40% (mean 32). One patient had left main, 4 had multivessel, and 4 had 1-vessel coronary disease. Seven patients had successful angioplasty of 15 of 16 lesions attempted, with all infarct-related vessels successfully dilated. One patient had lesions unsuitable for either bypass or angioplasty and died. Need for blood transfusion was the most frequent complication. One patient required surgical repair of the femoral artery. All 7 patients are alive at a mean follow-up of 8.2 months. It is concluded that cardiopulmonary bypass can be safely instituted percutaneously, hemodynamically stabilize patients in cardiogenic shock and facilitate emergency complex coronary angioplasty, which may be life-saving.     

Combined therapy with digoxin and nitroprusside in heart failure complicating acute myocardial infarction.

The hemodynamic effects of digoxin plus nitroprusside were compared with those of nitroprusside alone in 11 patients with congestive heart failure complicating acute myocardlal infarction. Hemodynamic measurements were made using a Swan-Ganz thermodilution catheter and a bedside thermodilution cardiac output computer. Patients received increasing doses of nitroprusside until mean arterial pressure decreased to 70 mm Hg or pulmonary arterial wedge pressure decreased to 16 mm Hg. The infusion rate of nitroprusside was then held constant for 120 minutes. After 30 minutes of constant nitroprusside infusion, 0.5 mg of digoxin was given intravenously. Hemodynamic measurements were obtained before treatment with nitroprusside and immediately before and 30, 60 and 90 minutes after the administration of digoxin.Nitroprusside produced a significant decrease in pulmonary arterial wedge pressure (24 to 16 mm Hg), mean arterial pressure (92 to 85 mm Hg and systemic vascular resistance (1,816 to 1,480 dynes sec cm^?5) and a significant increase in cardiac index (2.19 to 2.51 liters/min per m²). Ninety minutes after the administration of digoxin, cardiac index was further increased (2.51 to 28.2 liters/min per m², P = 0.03) and systemic vascular resistance was tower (1,480 to 1,320 dynes sec cm^?5, P = 0.03). Pulmonary arterial wedge pressure was not further decreased by the addition of digoxin. Thus, the addition of digoxin further increases cardiac output in patients with congestive heart failure complicating myocardial infarction who are receiving nitroprusside but does not produce any further decrease in pulmonary arterial wedge pressure.     

The effect of flosequinan in patients with heart failure of acute onset complicating acute myocardial infarction

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in 18 patients with severe heart failure of acute onset complicating acute myocardial infarction, which was resistant to high doses of diuretics, nitrates and dobutamine given intravenously. Flosequinan was added to conventional therapy at 3.5 +/- 0.8 days from the infarction, in the form of a single oral dose of 100 mg. Hemodynamic measurements were performed every hour for 4 hours after the administration, without any other drug being added. The infusion rate of nitrates was kept constant. Flosequinan produced hemodynamic improvement in this group. The effect peaked at 2 hours and remained at this level at 4 hours. Pulmonary capillary wedge pressure decreased from 27.6 +/- 4.3 to 16.8 +/- 2.8 mm Hg and cardiac output increased from 3.5 +/- 0.3 to 4.1 +/- 0.4 l/min (P less than 0.001). Pulmonary arterial and right atrial pressures and systemic and pulmonary vascular resistances were also significantly reduced. Heart rate and mean systemic arterial pressure were not significantly altered. Administration of flosequinan was not associated with symptomatic hypotension, cardiac arrhythmias or other adverse events. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure, complicating acute myocardial infarction, which is resistant to conventional therapy. Flosequinan is safe and well tolerated. Studies for longer time periods are indicated.     

Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock

BACKGROUND: Thyroid hormone level abnormalities commonly exist in severe heart failure and may be of prognostic value. The therapeutic potential of using thyroid hormone for cardiogenic shock resulting from progressive heart failure has not been previously delineated. We sought to evaluate the role of an intravenous infusion of thyroxine as an adjunct to conventional inotropic agents and intra-aortic balloon counterpulsation in patients with severe heart failure with cardiogenic shock. METHODS AND RESULTS: We studied 10 consecutive patients with severe systolic heart failure that progressed to a cardiogenic shock state unresponsive to conventional pharmacological inotropic measures. Intravenous thyroxine (20 micrograms/h) was used as an adjunctive salvage measure after the failure of conventional pharmacological and mechanical support by intra-aortic balloon pump. The invasive hemodynamic profile (right atrial pressure, pulmonary capillary wedge pressure, cardiac index, mean arterial pressure), overall clinical status, core temperature, renal function, and tachyarrhythmias were compared before and sequentially at 6, 24, and 36 hours after the initiation of thyroxine administration. Long-term outcome was also defined. All patients had statistically significant improvements in cardiac index, pulmonary capillary wedge pressure, and mean arterial pressure at 24 and 36 hours post-initiation of thyroxine. No sustained tachyarrhythmias were seen during the thyroxine infusion. In 9 of 10 patients who underwent left ventricular assist device placement and/or heart transplantation, the use of thyroxine served as an effective adjunctive measure to allow transitioning to definitive surgical therapy. The 6-month and 1-year cohort survival rates, achieved by the transition to surgical therapy, were 90% and 80%, respectively. CONCLUSION: The beneficial hemodynamic properties of intravenous thyroid hormone can be effectively used in otherwise terminal situations of cardiogenic shock, and in such situations, the use of thyroid hormone can serve as a pharmacological adjunct to a definite surgical intervention. Further studies in larger numbers of patients might be warranted to confirm these findings.     

Variability of hemodynamic responses to acute digitalization in chronic cardiac failure due to cardiomyopathy and coronary artery disease

Eight patients with chronic congestive heart failure (four with cardiomyopathy and four with ischemic heart disease) underwent hemodynamic studies during acute administration of digoxin, given intravenously in two 0.5 mg doses 2 hours apart. Observations were made before administration of digitalis (control period) and serially thereafter for 4 hours after the first dose. Resting mean cardiac index and pulmonary arterial wedge pressure were as follows: 2.0 liters/min per m² and 23 mm Hg (control period); 2.1 and 24 (at 1 hour); 2.0 and 23 (at 2 hours); 2.7 and 19 (at 3 hours); and 2.3 and 20 (at 4 hours). Exercise responses of mean cardiac index and pulmonary arterial wedge pressure in five patients were: 3.1 liters/min per m² and 36 mm Hg (control period); 3.2 and 33 (at 1 hour); 3.2 and 28 (at 2 hours); 3.1 and 27 (at 3 hours); and 3.4 and 31 (at 4 hours). The pulmonary arterial wedge pressure remained elevated during exercise in all cases. Arrhythmias were seen in five patients after administration of 0.5 mg of digoxin. Hemodynamic improvement at 4 hours involving both reduced filling pressure and increased blood flow was observed in only two patients at rest and in one additional patient during exercise. Acute deterioration of cardiac function (elevated pulmonary arterial wedge pressure or decreased cardiac index) occurred 30 minutes after administration of digoxin in four patients, concomitantly with increased systemic resistance. In six patients, a peak hemodynamic effect appeared 1 to 1 $\text{1}\text{2}$ hours after administration of digoxin, with partial or total loss of initial benefit by 2 and 4 hours.In previously performed studies observations have seldom exceeded 1 hour; the results of this 4 hour study suggest that, in patients with cardiomyopathy or coronary artery disease and chronic congestive heart failure, acute digitalization does not necessarily lead to consistent, marked or lasting hemodynamic improvement. Thus, current concepts of the use of digitalis in such patients may require revision.     

Coronary angioplasty for acute mitral regurgitation due to myocardial infarction. A nonsurgical treatment preserving mitral valve integrity

Three patients presented to the cardiac catheterization laboratory with myocardial infarction, severe mitral regurgitation, and pulmonary edema. Two patients were in cardiogenic shock at the time of cardiac catheterization. Percutaneous transluminal coronary angioplasty was done on the occluded artery in all three patients with resolution of the pulmonary edema as well as auscultative evidence of mitral regurgitation. The mean pulmonary wedge pressure dropped from 34 to 10 mm Hg in these patients. Mean follow-up of 11.7 months showed no evidence of clinical heart failure, angina pectoris, or auscultative evidence of mitral regurgitation.     

Hemodynamic effects of sulmazol (ARL-115 BS), a new vasodilator and positive inotropic agent, in patients with cardiogenic shock

The imidazol-pyridine ARL-115 BS (sulmazol) has both positive inotropic and vasodilatory effects. Its hemodynamic effects were studied in 13 patients with shock after myocardial infarction. All patients required dobutamine or dopamine, while nine were treated with intra-aortic balloon counterpulsation. After a loading dose of 50 mg, sulmazol was administered at 50 mg/h followed by 100 mg/h during 30 or 60 minutes. At the highest dose of sulmazol, cardiac output increased from 4.3 +/- 1.1 to 4.9 +/- 1.5 1/min; systemic vascular resistance decreased from 1405 +/- 473 to 1228 +/- 439 dynes . s . cm-5, while pulmonary capillary wedge pressure decreased from 22 +/- 6 to 17 +/- 7 mm Hg. No changes occurred in heart rate or mean arterial pressure. The effect of sulmazol was greater than the effect of an increased dosage of dobutamine in five patients in whom this was studied. Episodes of supraventricular tachycardia occurred in two patients. No other side effects were observed. The hemodynamic changes caused by sulmazol favour its use in the treatment of acute cardiac failure, and cardiogenic shock.     

Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol.

OBJECTIVE: To compare the efficacy of milrinone and dobutamine in patients chronically treated with carvedilol. BACKGROUND: Milrinone and dobutamine are used to manage decompensated heart failure, but their efficacy in patients on beta-blocker therapy was unknown. METHODS: Twenty patients with decompensated heart failure were prospectively enrolled. Inotropic responses to milrinone (12.5, 25 or 50 microg/kg bolus infusions) or dobutamine (5, 10, 15 or 20 microg/kg/min infusions) were evaluated by right-heart catheterization. RESULTS: Milrinone increased cardiac index (2.0-2.6 l/min/m2, P=0.0001) without significantly altering heart rate (70-75 bpm, P=0.19). Milrinone decreased mean pulmonary artery pressure (36-29 mm Hg, P=0.0001), pulmonary capillary wedge pressure (24-18 mm Hg, P=0.0001) and mean arterial blood pressure (78-75 mm Hg, P=0.0002). Left ventricular stroke volume index increased in the milrinone group (31-35 ml/beat/m2, P=0.0001). Dobutamine produced an increase in cardiac index (2.4-3.3 l/min/m2, P=0.0001) only at doses that are not typically used to treat heart failure (15-20 microg/kg/min). At these doses, dobutamine increased heart rate (68-82 bpm, P=0.008), mean systemic pressure (90-117 mm Hg, P=0.0001) and mean pulmonary artery pressure (21-30 mm Hg, P=0.001). Dobutamine did not alter left ventricular stroke volume index or pulmonary capillary wedge pressure. Conclusions: Dobutamine and milrinone have different hemodynamic effects in patients treated chronically with carvedilol. These differences should be considered when selecting inotropic therapy for decompensated heart failure.     

Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone

A 24-hour infusion of levosimendan was added to dobutamine in 18 patients (aged 63 +/- 9 years) hospitalized for management of decompensated New York Heart Association functional class IV heart failure refractory to a continuous 24-hour infusion of dobutamine (10 microg/kg/min) and furosemide (10 mg/hour); the primary study end point was a >or=40% increase in cardiac index and a >or=25% decrease in pulmonary capillary wedge pressure compared with pretreatment measurements.The primary end point was reached in one of the patients treated with dobutamine alone versus 7 patients (39%) treated with levosimendan and dobutamine combined (p = 0.008), whereas at 24 hours, the combined treatment was associated with a 0.76 +/- 0.78 L/min/m(2) (p = 0.001) mean increase in cardiac index and a 6.4 +/- 7.3 mm Hg (p = 0.002) mean decrease in pulmonary capillary wedge pressure compared with measurements obtained after 24 hours of dobutamine infusion alone. Symptoms were alleviated in all patients, and all but 3 were discharged from the hospital.     

The acute hemodynamic effects of a new agent, MDL 17,043, in the treatment of congestive heart failure

MDL 17,043 administered intravenously or orally exerts positive inotropic and vasodilator actions in experimental animal preparations. We studied its acute hemodynamic effects in 15 patients with severe congestive heart failure by right-heart catheterization. Intravenous MDL 17,043 at 10 minutes increased cardiac index (3.4 +/- 0.8 vs 1.9 +/- 0.4 l/min/m2), narrowed arteriovenous oxygen content difference (4.6 +/- 0.8 vs 7.8 +/- 2.0 vol%), increased heart rate (98 +/- 14 vs 89 +/- 18 beats/min), and decreased systemic arterial (67 +/- 10 vs 83 +/- 11 mm Hg), pulmonary capillary wedge (12 +/- 5 vs 24 +/- 5 mm Hg) and right atrial (6 +/- 5 vs 12 +/- 7 mm Hg) mean pressures significantly (p less than 0.001). In 11 patients, hemodynamics were monitored hourly for 6 hours. Compared with baseline, the cardiac index and heart rate were higher and mean systemic arterial pressure was lower for 6 hours; pulmonary capillary and right atrial mean pressures were significantly lower for 5 hours. No serious arrhythmias or side effects occurred. These data suggest that MDL 17,043 may be useful for treating congestive heart failure.