Induction of rapid ventricular tachycardia or fibrillation during therapy with amiodarone is associated with an increased risk of sudden death. To determine whether the addition of a type IA antiarrhythmic agent to therapy would improve outcome, 37 patients in whom ventricular tachyarrhythmia of a cycle length less than 350 msec was induced after 14 +/- 2 days of amiodarone were randomly assigned to therapy with amiodarone alone (group 1, 20 patients) or amiodarone plus type IA agent (group 2, 17 patients). Type IA therapy consisted of procainamide in 13 patients and quinidine in four procainamide-intolerant patients. To assess the short-term effects of a type IA agent on inducibility of ventricular tachyarrhythmia, cycle length, and hemodynamic tolerance, 16 of 20 patients in group 1 and all patients in group 2 underwent repeat programmed stimulation after the intravenous administration of procainamide during amiodarone therapy (mean procainamide serum concentration 7.2 +/- 2.0 micrograms/ml). Procainamide prevented induction of sustained arrhythmia in only two of 33 patients. Procainamide increased the cycle length of induced ventricular tachycardia from 283 +/- 30 to 352 +/- 46 msec (p less than .001). After the addition of procainamide, 16 of 31 patients vs 10 of 37 patients on amiodarone alone had an induced arrhythmia that was tolerated hemodynamically (p less than .05). There were no differences between groups 1 and 2 with respect to patient or arrhythmia characteristics, response to short-term procainamide, or duration of follow-up. The mean follow-up for all patients was 14 +/- 10 months.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been postulated that platelet function plays an important role in the initiation of atherosclerosis. Currently there are no definitive data on the longer-term effects of regular physical exercise on platelet function in humans. We assessed the influence of regular moderate-intensity physical exercise (brisk walking to slow jogging) on platelet aggregation in a population-based sample of middle-aged, overweight, mildly hypertensive men in eastern Finland. In this controlled study, we evaluated the net effect of exercise on platelet aggregation by studying changes in optical density and ATP release in platelet-rich plasma. A significant inhibition of secondary platelet aggregation from 27% to 36% was observed in the men taking regular exercise. These findings give new insight into the possible protective effects of exercise against the risk of ischemic heart disease.

Although blood cardioplegia preserves perioperative ventricular function better than crystalloid cardioplegia, late results are uncertain. Nuclear ventriculograms were used to assess ventricular function in 47 patients undergoing coronary bypass surgery who were randomly assigned to receive blood (23 patients) or crystalloid cardioplegia (24 patients). Data were acquired at rest and during maximal exercise (bicycle ergometer) 1 month before surgery (PRE), 5 months after surgery (POST), and perioperatively at rest 3 to 5 hr after operation (PERI). Perioperatively, blood cardioplegia decreased ischemic injury (less elevation in creatine kinase-MB fraction and aspartate aminotransferase; p less than .05), preserved ventricular performance (lower stroke work index at higher left ventricular end-diastolic volume index after crystalloid than blood cardioplegia; p = .02 by analysis of covariance [ANOCOVA]) and preserved systolic function (higher left ventricular end-systolic volume index [LVESVI] at similar systolic blood pressure after crystalloid than blood cardioplegia; p = .02 by ANOCOVA). Postoperatively, resting ventricular performance and systolic function were not different with blood and crystalloid cardioplegia and were similar to preoperative measurements. Postoperatively, the response to exercise was similar between the two groups and was improved compared with that at PRE. Postoperative systolic function at exercise was similar between the two groups but was better than that at PRE (higher systolic blood pressure at similar LVESVI; p = .01 by ANOCOVA). The type of cardioplegic solution influenced perioperative but not late postoperative function after elective coronary artery bypass surgery.

Combined proximal left anterior descending and proximal left circumflex, or "left main equivalent" (LMEQ), disease defines a prognostic angiographic high-risk patient population. We assessed the effect of coronary bypass surgery compared with medical therapy in 903 patients with LMEQ disease by stratified life table and Cox regression analysis. The 5 year survival rates of the 639 and 264 patients who received surgical vs medical therapy was 85% vs 55%, respectively (p less than .001). Analysis of patient subsets stratified by age, angina class, right coronary disease, and ejection fraction revealed a significant survival benefit for surgically treated patients in most strata. Cox regression analysis revealed improved survival for surgically treated patients after adjustment for important baseline variables known to influence prognosis. Surgically treated patients had significantly less angina and need for antianginal drugs compared with the medically treated group. When the Coronary Artery Surgery Study randomized and randomizable LMEQ patients were analyzed, coronary bypass surgery improved 5 year survival when preoperative ejection fraction was under 0.50 but not when ejection fraction was 0.50 or higher. Thus coronary bypass surgery prolongs and improves quality of life (as defined by angina status and need for antianginal drugs) in most patients with LMEQ disease but does not appear to improve 5 year survival in a small subset of LMEQ patients who are asymptomatic after myocardial infarction or who have mild chronic stable angina and are under age 65 with well-preserved left ventricular function.

Exercise conditioning involves adaptations in the heart, peripheral circulation, and trained skeletal muscle that result in improved exercise capacity. Since the specific influence of beta-adrenergic stimulation on these various adaptations has not been clear, we studied the effect of beta 1-selective and nonselective beta-adrenergic blockade on the exercise conditioning response of 24 healthy, sedentary men after an intensive 6 week aerobic training program. Subjects randomly assigned to receive placebo, 50 mg bid atenolol, or 40 mg bid nadolol were tested before and after training both on and off drugs. Comparable reductions in maximal exercise heart rate occurred with atenolol and nadolol, indicating equivalent beta 1-adrenergic blockade. Vascular beta 2-adrenergic selectivity was maintained with atenolol as determined by calf plethysmography during intravenous infusion of epinephrine. All subjects trained at greater than 85% of maximal heart rate and 80% of VO2 max determined on drug. VO2 max increased after training 16 +/- 2% (p less than .05) in the placebo group and 6 +/- 2% (p less than .05) in the atenolol group, while there was no change in the nadolol group. At maximal exercise, subjects receiving placebo increased their exercise duration and oxygen pulse significantly greater than those receiving atenolol or nadolol. During submaximal exercise there were reductions in heart rate and heart rate-blood pressure product in all three groups, but these reductions were greater with placebo than with either drug. Leg blood flow during submaximal exercise decreased 24 +/- 2% (p less than .01) in the placebo group but was unchanged in the atenolol and nadolol groups. Lactates in arterialized blood during submaximal exercise were reduced equivalently in all three groups after training. Capillary/fiber ratio in vastus lateralis muscle biopsy specimens increased 31 +/- 6% in the placebo group and 21 +/- 6% in the atenolol group (both p less than .05) and tended to increase in the nadolol group. Succinic dehydrogenase and cytochrome oxidase activities in muscle biopsy specimens increased equivalently in all three groups, especially during submaximal exercise, these changes were less marked than that with placebo. While beta-adrenergic blockade attenuated the exercise conditioning response, skeletal muscle adaptations including increases in oxidative enzymes, capillary supply, and decreases in exercise blood lactates were unaffected. Cardiac and peripheral vascular adaptations do appear to be affected by beta-adrenergic blockade during training. Cardioselectivity does not seem to be important in modifying these effects.

To examine the effects of propranolol and nifedipine on exercise-induced attack in patients with variant angina, exercise 201Tl myocardial scintigraphy with quantitative analysis by emission-computed tomography was performed in 20 patients with variant angina after oral propranolol (80 mg), nifedipine (20 mg), and placebo. Exercise-induced attack occurred in 11 patients on placebo, in 14 on propranolol, and in none on nifedipine. The exercise duration was significantly shorter in those on propranolol (p less than .05), but significantly longer in patients on nifedipine (p less than .05) than in those on placebo. The peak rate-pressure product was significantly lower in patients on propranolol (p less than .01), but did not change in those on nifedipine, as compared with that in patients on placebo. The size of the perfusion defect as measured by 201Tl tomography was significantly greater in patients on propranolol (p less than .05), but significantly less in those on nifedipine (p less than .01) than in those on placebo. In conclusion, propranolol does not suppress but rather may aggravate exercise-induced attack in patients with variant angina, while nifedipine suppresses it. This unfavorable effect of propranolol on exercise-induced attack in patients with variant angina is likely to be due to a reduction of regional myocardial blood flow.

To determine whether alteration of intrinsic myocardial stiffness is responsible for the reduction of left ventricular filling pressure and volume by nifedipine in patients with impaired baseline ventricular function, we evaluated the hemodynamic responses in 32 patients undergoing diagnostic cardiac catheterization. Micromanometric pressure and ventriculographic dimensional data were acquired before and 30 min after randomly assigned administration of nifedipine (20 mg sublingual) or placebo. A mathematical model requiring no assumptions about the stress-radius relationship or direct measurement of strain was used. No hemodynamic variables were changed after placebo. Left ventricular end-diastolic volume and pressure declined and cardiac output increased after nifedipine, particularly in subjects with impaired ventricular performance. Despite these salutary effects, intrinsic myocardial stiffness, elastic stiffness at a common level of stress, chamber stiffness, and rate of isovolumic relaxation were unchanged after nifedipine, even in patients with abnormal baseline ventricular function. The potent peripheral arteriodilator effect of nifedipine, rather than any direct myocardial or ventricular effects, appears to be responsible for the improved systolic and diastolic performance.

From 1975 to 1979, 540 patients undergoing valve replacement were entered into a randomized trial and received either a Björk-Shiley (273 patients) or a porcine heterograft prosthesis (initially a Hancock valve [107 patients] and later a Carpentier-Edwards prosthesis [160 patients]). Two hundred and sixty-two patients required mitral valve replacement, 210 required aortic valve replacement, 60 required mitral and aortic valve replacement, and eight also required associated tricuspid valve replacement (six mitral valve replacement; two mitral plus aortic valve replacement). Analysis of 34 preoperative and operative variables showed the treatment groups to be well randomized. In-hospital mortality was not significantly different among patients receiving the three prostheses for aortic valve replacement (7.6% overall) and mitral plus aortic valve replacement (10% overall), but there was a higher in-hospital mortality for patients undergoing mitral valve replacement with the Carpentier-Edwards prosthesis (15.5% compared with 8.8% overall; p = .03). This difference could not be explained on the basis of any preoperative or operative variable. Median follow-up was 5.6 (range 2.8 to 8.3) years. Actuarial survival after mitral valve replacement was 56.7 +/- 7.0% at 7 years, that after aortic valve replacement was 69.6 +/- 9.6% at 7 years, and that after mitral plus aortic valve replacement was 62.5 +/- 20.0% at 7 years. There was no significant difference in actuarial survival of patients receiving the three prostheses within the mitral, aortic, and mitral plus aortic valve replacement groups, nor was there a difference when these groups were amalgamated. Thirty-seven patients required reoperation for valve failure (15 with Björk-Shiley, 12 with Hancock, and 10 with Carpentier-Edwards valves; p = NS) and 11 died at reoperation (four with Björk-Shiley, four with Hancock, and three with Carpentier-Edwards valves; overall operative mortality 29.7%). Up to 7 years after surgery, there was no significant difference in the incidence of thromboembolism in patients with different prostheses undergoing mitral or aortic valve replacement. There were too few patients undergoing mitral plus aortic valve replacement for meaningful comparison. There was no significant beneficial effect of anticoagulants in patients undergoing mitral or aortic valve replacement with porcine prostheses, but patients were not randomly allocated to anticoagulant treatment. All patients with Björk-Shiley prostheses received anticoagulants.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of abrupt withdrawal or continuation of beta-blockade therapy during acute myocardial infarction were evaluated in 326 patients participating in the Multicenter Investigation of the Limitation of Infarct Size (MILIS). Thirty-nine patients previously receiving a beta-blocker and randomly selected for withdrawal of beta-blockers and placebo treatment during infarction (group 1) were compared with 272 patients previously untreated with beta-blockers who were also randomly assigned to placebo therapy (group 2). There were no significant differences between the two groups in MB creatine kinase isoenzyme (15.8 +/- 10.9 vs 18.2 +/- 14.4 g-eq/m2, respectively) estimates of infarct size, radionuclide-determined left ventricular ejection fractions within 18 hr of infarction (0.44 +/- 0.15 vs 0.47 +/- 0.16) or 10 days later (0.42 +/- 0.14 vs 0.47 +/- 0.16), creatine kinase-determined incidence of infarct extension (13% vs 6%), congestive heart failure (43% vs 37%), nonfatal ventricular fibrillation (5% vs 7%), or in-hospital mortality (13% vs 9%). Patients in group 1 had more recurrent ischemic chest pain (p = .002) within the first 24 hr after infarction, but not thereafter. However, this did not appear to be related to a rebound increase in systolic blood pressure, heart rate, or double product. In a separate analysis, 20 propranolol-eligible group 1 patients randomly selected for withdrawal of beta-blockade (group 3) were compared with 15 patients randomly selected for continuation of prior beta-blockade therapy (group 4). This comparison yielded similar results. These data indicate that the beta-blockade withdrawal phenomenon is not a major clinical problem in patients with acute myocardial infarction. beta-Blockade therapy can be discontinued abruptly during acute myocardial infarction if clinically indicated.

Although thromboxane A2 is a potent platelet agonist and vasoconstrictor in vitro, our knowledge of its pathophysiologic importance in human disease is limited. To facilitate the elucidation of its role in vivo, we sought to define a human syndrome in which pharmacologic interventions designed to inhibit the biosynthesis or biologic actions of thromboxane A2 might be appropriately assessed. Patients with severe peripheral vascular disease were selected on the basis of elevated plasma beta-thromboglobulin and circulating platelet aggregates and compared with healthy, age-matched control subjects. In addition to the platelet indexes, their bleeding time was shorter and excretion of 2,3-dinor-thromboxane B2, a noninvasive index of thromboxane formation in vivo, and 2,3-dinor-6-keto-prostaglandin F 1 alpha, the major urinary metabolite of prostacyclin, was markedly increased. A selective inhibitor of thromboxane synthase, imidazo (1,5-2) pyridine-5-hexanoic acid, was administered to these patients under randomized, double-blind, controlled conditions. Platelet aggregation ex vivo, the circulating platelet aggregate ratio, and the bleeding time were all unaltered, despite almost maximal inhibition of platelet thromboxane formation 1 hr after dosing. By contrast, pronounced inhibition of aggregation was observed when platelet cyclooxygenase was inhibited by aspirin. During long-term dosing with the synthetic inhibitor, inhibition of thromboxane biosynthesis was incomplete, which would permit continued thromboxane-dependent platelet aggregation to occur. However, the failure of enzyme blockade to influence platelet function at the time of maximal drug action, despite efficient inhibition of serum thromboxane B2, suggests that accumulation of proaggregatory endoperoxides is also likely to have contributed to the persistence of platelet activation. We have characterized a human preparation in which platelet activation coexists with increased thromboxane biosynthesis. In this setting, platelet activation persists despite long-term administration of a thromboxane synthase inhibitor in a dosing regimen representative of that employed in clinical trials. Prolongation of drug action and combination with antagonists of the shared endoperoxide/thromboxane A2 receptor may be necessary to assess the potential of selective inhibition of thromboxane synthase as a therapeutic strategy in man.

This was a prospective, placebo-controlled, single-blind trial of moricizine (ethmozine) in a dose averaging 10 mg/kg/day in 50 patients, the single entrance criterion being the presence of 10 or more runs of nonsustained ventricular tachycardia (VT) on a screening 24 hr ambulatory electrocardiographic (ECG) recording. Electrophysiologic study was not included as part of this trial design. The placebo frequency of VT (average 3 days of recording) was 1036 +/- 479 runs of VT per day. Most patients (31/50) had coronary artery disease. The study population had a mean left ventricular ejection fraction (LVEF) of 36 +/- 16%; 20 patients also had a history of sustained VT. Protocol failure was defined as failure to achieve a 75% or greater reduction in runs of VT (as judged by ambulatory ECG recording) and/or recurrence of sustained VT while on moricizine. Among the 48 patients treated with moricizine, the drug was initially efficacious in 35 (73%), with two-thirds having total abolition of nonsustained VT. Although it was effective in reducing runs of nonsustained VT, moricizine was ineffective in preventing the recurrence of sustained VT (63% failure rate). Side effects were uncommon and the drug was well tolerated in most patients with LVEFs of 30% or less.

The goal of this study was to verify whether myocardial protection could be achieved via the intracoronary administration of propranolol in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Accordingly, 21 patients undergoing PTCA were randomly assigned to receive either intracoronary placebo (group A, n = 10) or intracoronary propranolol (group B, n = 11). Three balloon inflations (i.e., coronary artery occlusions) were performed in each patient. Inflations I and II (maximum duration 60 sec) served as control occlusions. Inflation III (maximum duration 120 sec) was performed either after intracoronary administration of saline (2 ml) or propranolol (1.1 +/- 0.2 mg). The following electrocardiographic index of myocardial ischemic injury were measured: (1) time to development of ST segment elevation equal to 0.1 mV and (2) magnitude of ST segment elevation after 60 sec of coronary artery occlusion. Both indexes did not differ significantly between the groups during inflations I and II. In group A the time to development of ST segment elevation of 0.1 mV remained unchanged between the second and third occlusions (25 +/- 5 and 26 +/- 4 sec during inflations II and III, respectively). In group B subselective injection of propranolol into the affected coronary artery significantly prolonged the time to ST segment elevation of 0.1 mV from 19 +/- 4 sec (inflation II) to 53 +/- 9 sec (inflation III; p less than .001). Administration of placebo did not change the magnitude of ST segment elevation 60 sec after coronary artery occlusion between the second and third occlusion in group A (0.16 +/- 0.02 and 0.18 +/- 0.03 mV, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of congestive heart failure was studied in the Beta Blocker Heart Attack Trial in which postmyocardial infarction patients between the ages of 30 and 69 years, with no contraindication to propranolol, were randomly assigned to receive placebo (n = 1921) or propranolol 180 or 240 mg daily (n = 1916) 5 to 21 days after admission to the hospital for the event. Survivors of acute myocardial infarction with compensated or mild congestive heart failure, including those on digitalis and diuretics, were included in the study. A history of congestive heart failure before randomization characterized 710 (18.5%) patients: 345 (18.0%) in the propranolol group and 365 (19.0%) in the placebo group. The incidence of definite congestive heart failure after randomization and during the study was 6.7% in both groups. In patients with a history of congestive heart failure before randomization, 51 of 345 (14.8%) in the propranolol group and 46 of 365 (12.6%) in the placebo group developed congestive heart failure during an average 25 month follow-up. In the patients with no history of congestive heart failure, 5% in the propranolol group developed congestive heart failure and 5.3% in the placebo group developed congestive heart failure. Baseline characteristics predictive of the occurrence of congestive heart failure by multivariate analyses included an increased cardiothoracic ratio, diabetes, increased heart rate, low baseline weight, prior myocardial infarction, age, and more than 10 ventricular premature beats per hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

Piroximone (MDL 19,205), a new phosphodiesterase inhibitor with positive inotropic and vasodilating properties, was administered orally to 12 patients with severe congestive heart failure (NYHA class III to IV). After a mean dose of 1.7 +/- 0.4 (SD) mg/kg, cardiac index increased from 2.0 +/- 0.5 to 3.0 +/- 0.6 liters/min/m2 while pulmonary wedge pressure decreased from 23 +/- 6 to 15.6 +/- 7 mm Hg and systemic vascular resistance from 1520 +/- 370 to 1000 +/- 320 dyne-sec-cm-5. Mean arterial pressure was slightly reduced from 80 +/- 13 to 75 +/- 11 mm Hg and forearm blood flow increased by 79% (all p less than .01). Eleven patients were selected for long-term treatment. Two patients received a heart transplant soon after the treatment was started. The remaining nine patients were followed for a mean of 5.6 months (range 2 to 10). Severe congestive heart failure recurred in eight of these nine patients, resulting in the death of three patients within 4 months. The remaining six patients underwent repeat hemodynamic evaluation 2 months after the initiation of the treatment. A short-term hemodynamic response to the drug in this group demonstrated that piroximone retains its circulatory effect during continuous therapy. Nevertheless, three more patients of this group died within 8 months and two required heart transplants. Of the nine patients receiving long-term treatment, only one had sustained subjective improvement and increased exercise capacity. Therefore long-term therapy with piroximone did not appear to benefit patients with severe congestive heart failure. A drug-related deterioration of their clinical status cannot be excluded.

Thirty-seven patients with severe chronic heart failure were entered into an open-ended trial with milrinone at an initial daily dose ranging form 20 to 30 mg. Mean duration of treatment was 48 weeks and ranged from 1 to 134 weeks. Twenty-five patients (67%) reported a substantial improvement in well-being with less dyspnea or fatigue, but this was not associated with a significant increase in maximal oxygen uptake: 10.2 +/- 2.9 vs 10.7 +/- 2.4 ml/kg/min (NS). At intervals ranging from 6 to 54 weeks, they experienced a recurrence of symptoms that was partially reversed by increasing the dose of milrinone to a maximum of 50 mg/day. In 15 patients whose symptoms could not be controlled by milrinone alone, captopril was added. The combination of captopril and milrinone was well tolerated and produced a symptomatic improvement in 10 of the 15 patients (67%). Maximal oxygen uptake, however, was not significantly increased by addition of captopril to milrinone: 10.6 +/- 2.7 vs 11.6 +/- 3.3 ml/kg/min. Twenty-four patients died: 12 of sudden death and 12 of gradual worsening of heart failure. During prolonged administration of milrinone, no patient experienced overt clinical adverse reactions directly attributable to the drug. Left ventricular end-diastolic dimension increased from 3.6 +/- 0.7 to 4.1 +/- 0.9 cm/m2 (p less than .05) after a mean duration of 50 weeks of milrinone therapy. Accordingly, long-term therapy with milrinone appears to improve functional status without eliciting overt clinical adverse reactions. However, the possibility that milrinone might have contributed to the high mortality noted during this therapeutic trial cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

To assess the long-term efficacy of milrinone in patients with severe congestive heart failure, we obtained hemodynamic measurements (systemic arterial and right heart catheterization) in 13 patients at baseline and after intravenous administration of milrinone. After continuous oral milrinone therapy of 8 +/- 4 months duration, repeat hemodynamic study was performed in patients on oral milrinone therapy, after withdrawal of milrinone, and after readministration of milrinone intravenously. Comparison of initial baseline and withdrawal hemodynamic measurements for the group as a whole showed no interval progression of heart failure, as reflected by the pulmonary capillary wedge pressure (27 +/- 8 to 24 +/- 12 mm Hg, NS) or the cardiac index (2.0 +/- 0.4 to 2.1 +/- 0.8 liters/min/m2, NS). Individual comparisons of milrinone-free hemodynamics revealed that five patients had improved hemodynamically, three patients were unchanged, and five patients had deteriorated, four of whom manifested dependence on milrinone with a progressive hemodynamic decline after milrinone withdrawal which required readministration of milrinone on an emergency basis. Continued efficacy of milrinone was observed on readmission after withdrawal: pulmonary capillary wedge pressure fell from 27 +/- 8 to 16 +/- 10 mm Hg (p = .001) initially and from 24 +/- 12 to 13 +/- 11 mm Hg (p = .001) at readministration, while cardiac index rose from 2.0 +/- 0.4 to 2.8 +/- 0.5 liters/min/m2 (p = .001) initially and from 2.1 +/- 0.8 to 2.7 +/- 0.5 liters/min/m2 (p = .005) upon readministration.(ABSTRACT TRUNCATED AT 250 WORDS)

Milrinone and dobutamine were compared in 15 patients with New York Heart Association functional class III and IV congestive heart failure. Dobutamine and milrinone were administered intravenously according a graded titration schedule up to maximum doses (14 micrograms/kg/min and 75 micrograms/kg, respectively) or until increased ventricular ectopy or a reduction in left ventricular end-diastolic pressure to 10 mm Hg or less occurred. Although both agents markedly increased cardiac index, milrinone caused a significantly greater reduction in left and right heart filling pressures and mean arterial pressure than did dobutamine, and for any given increase in dP/dt, milrinone caused a greater reduction in systemic vascular resistance than did dobutamine. Thus, the hemodynamic effects of milrinone are best represented by a combination of the actions of dobutamine, a positive inotropic agent, and a vasodilator such as nitroprusside, which causes both arterial and venous dilation. The positive inotropic responses of individual patients to dobutamine (5 micrograms/kg/min) and milrinone (25 micrograms/kg) were compared. The increases in dP/dt with both agents were variable, and correlated poorly (r = .50; p = .059). Patients were divided into two groups: Group I consisted of eight patients in whom the ratio of the increase in dP/dt with dobutamine vs milrinone was greater than 1.0 (good dobutamine responders); group II consisted of seven patients in whom this ratio was less than 1.0 (poor dobutamine responders).(ABSTRACT TRUNCATED AT 250 WORDS)

To assess their comparative effects on hemodynamics and myocardial energetics, we administered nitroprusside (1.5 +/- 0.6 microgram/kg-min), dobutamine (10 +/- 3 micrograms/kg-min), and milrinone (67 +/- 13 micrograms/kg-min) sequentially to 10 patients with severe (NYHA class III or IV) congestive heart failure. Each agent led to a significant (p = .001) increase in cardiac index (1.9 +/- 0.5 to 2.7 +/- 0.6 liters/min/m2; 1.7 +/- 0.4 to 2.6 +/- 0.6 liters/min/m2; and 1.8 +/- 0.5 to 2.7 +/- 0.5 liters/min/m2, for nitroprusside, dobutamine, and milrinone, respectively). Dobutamine did not produce a significant change in the pulmonary capillary wedge pressure (27 +/- 5 to 24 +/- 6 mm Hg, NS) nor in mean arterial pressure (83 +/- 9 to 86 +/- 10 mm Hg, NS), but caused a significant rise in heart rate (85 +/- 16 to 99 +/- 17 beats/min, p = .001) and in myocardial oxygen consumption (8.7 +/- 2.1 to 11.1 +/- 3.8 ml O2/min, p = .03). In contrast, nitroprusside and milrinone each caused a significant (p = .001) fall in the pulmonary capillary wedge pressure (27 +/- 6 to 19 +/- 7 mm Hg and 26 +/- 6 to 19 +/- 9 mm Hg, respectively), without significantly increasing either the heart rate (87 +/- 18 to 85 +/- 17 beats/min and 86 +/- 17 to 89 +/- 17 beats/min, respectively) or myocardial oxygen consumption (8.8 +/- 2.3 to 7.6 +/- 2.1 ml O2/min and 8.8 +/- 2.1 to 8.4 +/- 2.1 ml O2/min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The potent vasodilating properties of the bipyridine derivatives confounds the assessment of changes in contractility as measured by peak positive left ventricular dP/dt and explains why the positive inotropic action of these agents has not been consistently demonstrated in patients with ventricular dysfunction. Therefore we studied the individual dose-response effects of intravenous milrinone on myocardial contractility as measured by peak positive left ventricular dP/dt in the context of concurrent changes in ventricular filling pressure. Incremental doses of milrinone caused a dose-related increase in peak positive left ventricular dP/dt in six of 11 patients. Peak positive left ventricular dP/dt was unchanged in four patients and reduced in one patient, all of whom experienced a substantial fall in left ventricular filling pressure. Thus milrinone has a definite inotropic effect in addition to its potent vasodilating properties.