Hemodynamic trial of sequential treatment with diuretic, vasodilator, and positive inotropic drugs in left ventricular failure following acute myocardial infarction

The circulatory effects induced by two sequential intravenous treatment programs with a diuretic, arteriolar or venodilator , and a positive inotropic drug were studied in a randomized between-group trial in 20 male patients with radiographic and hemodynamic evidence of left ventricular (LV) failure following acute myocardial infarction (AMI). Furosemide induced a substantial diuresis in both groups of patients, in association with reductions in LV filling pressure (p less than 0.01) and cardiac output (p less than 0.05), without significant change in heart rate or systemic arterial pressure. The addition of isosorbide dinitrate was followed by reductions in the systemic arterial (p less than 0.01) and LV filling pressures (p less than 0.01) without significant change in the heart rate or cardiac output. Hydralazine after furosemide reduced systemic vascular resistance (p less than 0.01), but the fall in mean blood pressure (p less than 0.01) was limited by the increase in cardiac output (p less than 0.01); heart rate was also increased (p less than 0.01) and LV filling pressure fell (p less than 0.05). The final addition of the beta-1 adrenoceptor agonist, prenalterol, increased systemic arterial systolic pressure (p less than 0.05), cardiac output (p less than 0.05), and heart rate (p less than 0.01), and reduced systemic vascular resistance (p less than 0.01) in both groups; these changes were greatest in those pretreated with furosemide and isosorbide dinitrate. In both treatment pathways compared with control the reductions in systemic vascular resistance and left heart filling pressure were accompanied by increases in heart rate and cardiac output without substantial changes in systemic blood pressure. Which of these hemodynamic pathways offers the optimum prognosis awaits further study.     

Intravenous amrinone in left ventricular failure complicated by acute myocardial infarction

Hemodynamic dose-response effects of intravenous amrinone were studied in 22 male patients aged 38 to 62 years with left ventricular failure occurring within 18 hours of acute myocardial infarction. After hemodynamic confirmation of a raised left-sided cardiac filling pressure--pulmonary artery occluded pressure greater than 20 mm Hg--patients were randomized to either low-dose infusion of amrinone (200 micrograms/kg/hr for 30 minutes, 400 micrograms/kg/hr for 30 minutes and then 800 micrograms/kg/hr for 30 minutes) or high-dose infusion of the drug (800, 1,600 and 3,200 micrograms/kg/hr sequentially, each for 30 minutes). Hemodynamic measurements were obtained at 1 hour before amrinone and at the end of each infusion step. Low-dose infusion of amrinone resulted in a progressive increase in cardiac output (p less than 0.05) and stroke volume (p less than 0.05) and progressive reductions in pulmonary artery occluded pressure (p less than 0.01) and systemic vascular resistance (p less than 0.05). Systemic blood pressure and heart rate were unchanged. High-dose infusion resulted in a similar increase in cardiac output (p less than 0.05) but no change in stroke volume owing to associated tachycardia (p less than 0.01). There was a significantly greater decrease in pulmonary artery occluded pressure compared with the low-dose infusion (p less than 0.05), and systemic arterial diastolic and mean pressures were also decreased (p less than 0.05). The decrease in systemic vascular resistance was of a similar order to that induced by the low-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of nifedipine during upright exercise in stable angina pectoris and either normal or severely impaired left ventricular function

The immediate effects of sublingual nifedipine (20 mg) were evaluated in 18 men with stable, exercise-related angina pectoris and angiographically confirmed coronary artery obstructions, stratified at the time of left ventricular (LV) angiography according to the degree of LV dysfunction supine at rest (Group 1: n = 9, left ventricular end-diastolic pressure [LVEDP] less than 20 mm Hg; Group 2: n = 9, LVEDP greater than 20 mm Hg). At rest, in the upright posture in both groups, nifedipine reduced the systemic vascular resistance (p less than 0.01). The systemic arterial mean (p less than 0.05) and diastolic (p less than 0.01) pressures were reduced despite an increase in the cardiac output (p less than 0.05). Heart rate was increased only in Group 1 (p less than 0.05). Pulmonary artery occluded pressure was unchanged in both groups. During upright bicycle exercise in all patients, compared to control measurements, systemic arterial pressure (p less than 0.01) and vascular resistance (p less than 0.05) were similarly reduced, while exercise cardiac output response and LV filling pressure did not change after nifedipine. Heart rate was increased in Group 1 (p less than 0.05) and decreased in Group 2 (p less than 0.05). Stroke volume during exercise after nifedipine decreased 1 ml/m2 in Group 1 (p greater than 0.05) and increased 2 ml/m2 in Group 2 (p greater than 0.05) compared to control measurements; the between-group difference in the exercise heart rate and stroke volume responses after nifedipine were significant at the 5% level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intravenous injection of isosorbide dinitrate on the cardiovascular system

An assessment of the acute hemodynamic effect of intravenous isosorbide dinitrate (ISDN) was performed with a Mikro-tip angiocatheter in 10 patients during the diagnostic cardiac catheterization. Both left ventricular (LV) systolic pressure (SP) and end-diastolic pressure (EDP) were decreased by 2 mg of ISDN. Cardiac index, stroke work index and heart rate did not change significantly, and neither systemic vascular resistance nor pulmonary arteriolar resistance was reduced. Isovolumic phase and ejection phase indices of contractility were not altered. End-diastolic stress, an accurate index of preload, was reduced significantly (47.0 +/- 27.6 to 28.7 +/- 24.6 g/cm2, p less than 0.01), and mid-systolic stress, an index of afterload, was also reduced (371 +/- 102 to 332 +/- 85 g/cm2, p less than 0.05). No undesirable side effects were noted during this study. We concluded that bolus intravenous (IV) ISDN safely reduced both preload and afterload. As 2 mg of IV ISDN had no significant change on SVR, a larger dose of ISDN bolus injection might be needed for a significant arterial vasodilating effect. Bolus IV ISDN seems to be very effective in cases in which rapid reduction of LV filling pressure is mandatory.     

Systemic vasoconstrictor effects of oxygen administration in obliterative pulmonary vascular disorders

Although oxygen is frequently administered to patients with obliterative pulmonary vascular disorders (OPVD) for diagnostic and therapeutic purposes, its hemodynamic effects in these patients have not been systematically evaluated. The response to administration of 50 to 70% oxygen was studied in 14 patients with pulmonary hypertension secondary to OPVD. Mean pulmonary artery pressure decreased (from 62 +/- 5 to 57 +/- 5 mm Hg, p less than 0.01) after oxygen inhalation secondary to a decrease in cardiac index (1.9 +/- 0.2 to 1.8 +/- 0.2 liters/min/m2, p less than 0.01), without changes in pulmonary arteriolar resistance. This decline in forward output appeared to result from a systemic vasoconstrictor effect of oxygen (change in systemic vascular resistance from 1,965 +/- 275 to 2,297 +/- 336 dynes s cm-5, p less than 0.01), which decreased heart rate (from 93 +/- 3 to 89 +/- 2 beats/min, p less than 0.01) by stimulation of baroreceptor reflexes and decreased stroke volume (from 22 +/- 3 to 21 +/- 2 ml/beat/m2, p less than 0.05) by increasing impedance to left ventricular ejection. The decrease in left-sided cardiac output likely led to a decline in venous return to the right side of the heart and, consequently, to a decrease in right atrial and pulmonary arterial pressures. Accordingly, the percent decrease in mean pulmonary artery pressure varied linearly and directly with the percent increase in systemic vascular resistance (r = 0.84), but not with changes in pulmonary arteriolar resistance (r = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hydralazine does not inhibit canine hypoxic pulmonary vasoconstriction

Clinical experience with hydralazine has led to conflicting data concerning its effect on the pulmonary vasculature. We studied the effects of hydralazine on the hypoxic pulmonary vasoconstrictor response in 9 dogs challenged with inhalation of 10% oxygen in the presence and absence of hydralazine. Prior to administration of the drug, hypoxia increased cardiac output from 174 +/- 13 to 209 +/- 21 ml/kg/min (p less than 0.05) and pulmonary artery pressure from 9 +/- 1 to 19 +/- 1 mmHg (p less than 0.05). After hydralazine, cardiac output rose during normoxia to 275 +/- 30 and during hypoxia to 305 +/- 34 ml/kg/min (p less than 0.05). Pulmonary artery pressure continued to respond to hypoxia, rising from 11 +/- 1 to 21 +/- 1 mmHg (p less than 0.05) in the presence of hydralazine. Hydralazine reduced pulmonary vascular resistance during normoxia from 173 +/- 14 to 136 +/- 13 dynes X s X cm-5 (p less than 0.05) but even after the drug, pulmonary vascular resistance rose sharply during hypoxia. There was no significant difference in the response to hypoxia of pulmonary artery pressure or pulmonary vascular resistance after hydralazine when compared with that before hydralazine. In a second set of 6 dogs, we repeated these experiments but volume-depleted the dogs after the administration of hydralazine to prevent the passive pulmonary vasodilation that occurs because of the rise in cardiac output with the drug. We again found no inhibition of hypoxic pulmonary vasoconstriction by hydralazine. Finally, we administered sodium nitroprusside to 4 dogs using the same model and found a significant inhibition of hypoxic pulmonary vasoconstriction. Hydralazine, unlike nitroprusside, does not inhibit the pulmonary vascular response to hypoxia.     

Treatment of canine permeability pulmonary edema: short-term effects of dobutamine, furosemide, and hydralazine

The effects of treatment of oleic acid pulmonary edema with dobutamine, furosemide, and hydralazine on cardiopulmonary function in 24 dogs were investigated. Pulmonary capillary wedge pressure (PCWP) was adjusted to approximately 7 mm Hg; 45 min after oleic acid (0.08 ml/kg), dogs were randomly divided into a control group, in which PCWP was maintained at approximately 7 mm Hg, and into treatment groups as described above. Mean time-averaged PCWP was 2.3 mm Hg in dogs treated with dobutamine, 4.1 mm Hg with furosemide, and 4.4 mm Hg with hydralazine. Four hours of treatment with dobutamine and furosemide significantly (p less than .01) reduced accumulation of lung water compared with the control and hydralazine groups. Qs/Qt was lower (p less than .05) with dobutamine and furosemide compared with the other groups. In dogs given hydralazine, cardiac output (CO) and systemic vascular resistance (SVR) remained constant over the 4 hr treatment interval. In contrast, in all other groups, SVR increased and CO decreased (both p less than .05). The short-term pulmonary effects of the above drugs are probably explained by differences in PCWP and/or by regional pulmonary vascular effects.     

A haemodynamic study of the effects of combined slow-calcium channel blockade (nisoldipine) and beta-blockade (metoprolol) in coronary heart disease

The interaction of a new slow-calcium blocker (nisoldipine) and the beta-blocker metoprolol was evaluated in 16 patients with stable angina. Haemodynamic parameters were determined in a control rest and exercise period. Patients were then randomised equally to nisoldipine (4-8 micrograms/kg) or metoprolol (10 mg) and the haemodynamics of monotherapy assessed; finally the second drug was administered and the effects of combination determined. At rest nisoldipine reduced systemic blood pressure and vascular resistance (P less than 0.01); heart rate, cardiac and stroke volume indices increased (P less than 0.01) at an unchanged pulmonary artery occluded pressure. Metoprolol alone reduced heart rate (P less than 0.05) and increased the pulmonary artery occluded pressure (P less than 0.05). Combination therapy reduced systemic blood pressure and vascular resistance (P less than 0.01); cardiac index and pulmonary artery occluded pressure increased (P less than 0.01) at an unchanged heart rate. The effect of combination was influenced by the order of administration; an improvement in cardiac performance was particularly evident when nisoldipine was added to metoprolol. The interaction during dynamic exercise was similar to that at rest. Thus these data indicated the haemodynamic safety of concurrent nisoldipine/metoprolol therapy; the addition of nisoldipine to metoprolol appeared to offset in part the cardiodepressant properties of beta-blockade.     

Treatment of canine low pressure pulmonary edema. Nitroprusside versus hydralazine

In canine oleic acid pulmonary edema, we investigated acute cardiopulmonary effects of different doses of nitroprusside and compared the results with those obtained after intravenously administered hydralazine. Oleic acid increased (p less than 0.05) intrapulmonary shunt (Qs/Qt), increased (p less than 0.01) systemic vascular resistance (SVR), and reduced (p less than 0.05) cardiac output (CO). In the presence of low-pressure pulmonary edema, low-dose nitroprusside (NP1) reduced (p less than 0.01) mean blood pressure (BP) approximately 8%, but with the exception of a small fall in ventricular filling pressure, other parameters remained constant. Compared with control values, a higher dose of nitroprusside (NP2) reduced mean BP 20%, and despite a fall (p less than 0.01) in pulmonary capillary wedge pressure, CO increased (p less than 0.05) 20%. Corresponding to the increase in flow, mean Qs/Qt increased (p less than 0.05) from 26 to 36% with NP2 and arterial O2 tension fell (186 to 166 mmHg, p less than 0.05). Compared with NP2, intravenously administered hydralazine caused a larger (p less than 0.01) change in CO. Despite increased CO and increased (p less than 0.01) mixed venous O2 tension, there was no deterioration in gas exchange with hydralazine. Mean Qs/Qt remained constant and arterial O2 tension, (PaO2) increased (p less than 0.05) from 174 mmHg to 217 mmHg. The increased CO with NP2 and hydralazine is probably explained by the large reduction in systemic vascular resistance. Because Qs/Qt remained constant with hydralazine, the increase in PaO2 is most likely due to the increase in PvO2, which increased because CO increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous, low dose of hydralazine, reduces acute hypoxic pulmonary hypertension without a corresponding fall in systemic arterial pressure

Administration of hydralazine in patients with pulmonary hypertension has been reported to cause excessive systemic vasodilatation, limiting its clinical utility (N Engl J Med 1982; 306: 1326). We studied the effects of hydralazine on hypoxic pulmonary vasoconstriction (HPV) in chronically instrumented sheep and evaluated whether different methods of intravenous administration could prevent severe systemic hypotension. Mean left atrial, pulmonary and systemic arterial pressures (Pla, Ppa and Psa mmHg), cardiac output (CO, l/min, electromagnetic flowmeter) and heart rate were measured continuously. Systemic (SVR) and pulmonary vascular resistances (PVR) were calculated by Psa/CO and (Ppa-Pla)/CO, respectively. Following a 30 min baseline period, we initiated hypoxia with mixture of 10% oxygen in nitrogen. After 20 min of hypoxia we then performed the following two experiments: Group A-Hydralazine (10 micrograms/kg/min) was infused continuously for a further 20 min of hypoxia (n = 6); Group B-Hydralazine (400 micrograms/kg) was administered as a single bolus, followed by an additional 20 min of hypoxia (n = 6). In both Groups A and B, hypoxia produced a prominent pulmonary hypertensive response. Continuous infusion of hydralazine (Group A) significantly decreased the hypoxic values of Ppa and PVR from 25.1 +/- 1.1 to 21.7 +/- 1.6 mmHg (p less than 0.01) and from 4.82 +/- 0.50 to 4.17 +/- 0.40 mmHg/l/min (p less than 0.05), respectively. In Group B, hydralazine as a bolus also significantly decreased HPV, with Ppa dropping from 20.9 +/- 0.9 to 18.3 +/- 1.5 mmHg (p less than 0.05) and PVR falling from 4.98 +/- 0.55 to 4.34 +/- 0.53 mmHg/l/min (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of isosorbide dinitrate on coronary and systemic circulation in children: comparison with dipyridamole]

The effects of isosorbide dinitrate (ISDN) on the coronary and systemic circulation were evaluated in comparison with the effects of dipyridamole (DP) in 8 children with histories of Kawasaki disease and angiographically normal coronary arteries. ISDN (100 micrograms/kg) was administered as an intracoronary injection. DP was administered intravenously at the rate of 0.56 mg/kg for 4 min. In the coronary circulation, DP induced a significant reduction of the afterload, resulting in an increase in cardiac output. However, the pulmonary artery pressure, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure, which are related to the preload, were significantly reduced one min after the ISDN injection. The systolic blood pressure was reduced, while the heart rate was increased. The cardiac output, pressure-rate product or systemic vascular resistance showed no significant change. The systolic work index, however, was significantly reduced. In the coronary circulation, DP significantly increased the coronary sinus blood flow due to dilatation of the resistant vessels. However, ISDN significantly dilated the conductant vessels by 4.0 to 12.9% in diameter. There was, however, no change in the coronary blood flow, coronary perfusion pressure nor coronary vascular resistance. The grade of dilatation of the coronary vessels caused by ISDN was lower in children than in adults.     

Effect of isosorbide dinitrate on cardiac output in severe cardiac failure: relation to initial hemodynamics, ventricular volume, and the preload reserve mechanism

Isosorbide dinitrate (ISDN) improves the clinical and hemodynamic state of patients with heart failure, but may cause dizziness and syncope. To characterize patients in whom cardiac output falls with high-dose nitrate therapy and to examine further the pathophysiology of the fall in cardiac output in these patients, we studies the effect of sublingual ISDN on forward cardiac output in 14 patients with severe cardiac failure (New York Heart Association grades 3-4). We examined systolic and diastolic left ventricular (LV) function from pressure and volume analyses of LV function. After administration of 15 mg ISDN, cardiac output was either unaltered or increased in 7 patients (Group 1) (11 +/- 12%, mean +/- SD), and decreased in 7 (Group 2) (-13 +/- 10%) (Group 1 vs. 2, p less than 0.002). Initial systemic arterial pressure, LV ejection fraction, wedge and LV transmural filling pressures were similar in both groups, but Group 2 patients had a lower systemic vascular resistance (p = 0.07) and tended to have a larger initial LV end-diastolic volume and increased end-diastolic compliance; following ISDN the decrease in LV filling pressure and end-diastolic volume was larger and the product of the changes greater (p less than 0.02). Thus ISDN decreases filling pressure and improves forward cardiac output in some patients with congestive heart failure, but large doses may decrease cardiac output in a subset of patients who have a lower systemic vascular resistance and a larger more compliant ventricle, maintaining forward blood flow predominantly by a preload reserve mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of a new alpha-1 antagonist, AR-C 239 administrated in intravenous bolus, in patients with cardiac insufficiency

A new specific alpha-1 antagonist was studied in 16 patients with left ventricular failure. In Group I (8 patients) the drug was given as a 40 micrograms/kg intravenous bolus, and in Group II (8 patients) at the dose of 80 micrograms/kg. A thermodilution Swan-Ganz catheter, a Millar microtransducer introduced via the femoral artery were relayed to a SYSCOMORAM system to record the systemic artery pressures (SAP), pulmonary artery pressures (PAP), left ventricular pressures, and to calculate cardiac output and systemic and pulmonary arterial resistances (SAR, PAR) over a 30 minute period. In Group I (40 micrograms/kg), administration of AR-C 239 led to a significant decrease in PAP and SAP (-24 +/- 17 p. 100, p less than 0.02) with a fall in time-tension index (-20 +/- 19 p. 100, p less than 0.05) and a significant increase in LV stroke volume (+23 +/- 12 p. 100, p less than 0.01). At 80 micrograms/kg there was also a fall in LV filling pressures (-29 +/- 25 p. 100, p less than 0.05) and PAP (-38 +/- 28 p. 100, p less than 0.02) and an improvement in LV compliance (Gaaschisk -43 +/- 19 p. 100, p less than 0.01). These results show that AR-C 239 is a powerful vasodilator without secondary beta mimetic effects or influence on LV contractility; it may provide an effective means of treating cardiac failure.     

Hemodynamic effect of hydralazine in advanced, stable chronic obstructive pulmonary disease with cor pulmonale. Immediate and short-term evaluation at rest and during exercise

Hydralazine was administered to eight patients (mean age, 69 +/- 2 years) who had stable, advanced chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (mean pulmonary arterial pressure, 31 +/- 3 mm Hg), and cor pulmonale. All of the patients were studied at rest and during exercise. After intravenous administration of hydralazine at rest, there were statistically significant increases in pulmonary arterial pressure (p less than 0.05), cardiac index (p less than 0.005), arterial oxygen saturation (p less than 0.01), and mixed venous saturation (SvO2) (p less than 0.005). Pulmonary vascular resistance did not change, and systemic resistance decreased (p less than 0.005). During exercise, pulmonary arterial pressure increased in all patients, and this increase was not blunted by hydralazine; however, cardiac index (p less than 0.005), arterial oxygen pressure (p less than 0.005), and SvO2 (p less than 0.001) increased further during exercise. The increase in pulmonary vascular resistance was significantly blunted by hydralazine (p less than 0.005). Therapy with the drug was continued orally in seven patients because one patient showed a deleterious response in pulmonary hemodynamics. After seven days of oral hydralazine, pulmonary arterial pressure and pulmonary vascular resistance were not statistically different from control. There were statistically significant increases in cardiac index (p less than 0.005) and SvO2 (p less than 0.05), systemic resistance decreased (p less than 0.01). The same condition was found during exercise; however, only two patients showed pulmonary gas exchange and pulmonary hemodynamic benefit at rest and during exercise with hydralazine therapy. Our results suggest that it is unlikely that vasodilator therapy with hydralazine will be useful in patients with advanced stable COPD and cor pulmonale who seem to have fixed pulmonary vascular disease.     

Unloading effects of vasodilators on peripheral circulation and cardiac hemodynamics in patients with acute myocardial infarction

Effects of three representative vasodilators on peripheral and cardiac hemodynamics were studied in 20 patients with heart failure due to acute myocardial infarction (PCWP greater than 18 mmHg, C1 greater than 2.20 L/min/m2) using venous occlusion plethysmography and a Swan-Ganz catheter. Sublingual isosorbide dinitrate (ISDN) significantly increased calf venous capacitance (CVC) from 5 to 60 min (p less than 0.01) and calf blood flow (CBF) in the initial 15 min (p less than 0.05), while simultaneously lowering PCWP (p less than 0.05) and central venous pressure (p less than 0.05). Calf vascular resistance (CVR), cardiac index, blood pressure, and total systemic peripheral resistance (TSPR) were not affected significantly. Nitroglycerin ointment (NGO) significantly decreased CVR (p less than 0.05) and increased CVC (p less than 0.05) from 60 to 240 min, simultaneously with lowering of PCWP (p less than 0.01), central venous pressure (p less than 0.05), and TSPR (p less than 0.05). Oral prazosin (Pz) increased CBF (p less than 0.01) and CVC (p less than 0.05) from 60 to 240 min, simultaneously with significant lowering of PCWP (p less than 0.01) and TSPR (p less than 0.05), resulting in increased stroke work index (p less than 0.05). These data confirm that ISDN predominantly causes capacitance vessel dilatation and reduce excessive venous return, while Pz and NGO dilate not only capacitance vessels but also resistance vessels, consequently reducing systemic vascular resistance and resulting in increased peripheral blood flow and cardiac performance. It was observed that the higher the base-line calf vascular resistance rose, the better the response to the vasodilator treatment appeared in terms of a decrease in calf vascular resistance.     

Hemodynamic and clinical significance of the pulmonary vascular response to long-term captopril therapy in patients with severe chronic heart failure

Exercise capacity in patients with left heart failure is closely related to the performance of the right ventricle and the pulmonary circulation. To determine the significance of changes in pulmonary resistance during long-term vasodilator therapy, hemodynamic studies were performed before and after 1 to 3 months of treatment with captopril in 75 patients with severe chronic left heart failure. Patients were grouped according to the relative changes in pulmonary and systemic resistances during long-term therapy: patients in Group I (n = 24) showed greater decreases in pulmonary arteriolar resistance (PAR) than in systemic vascular resistance (SVR) (% delta PAR/% delta SVR greater than 1.0), whereas patients in Group II showed predominant systemic vasodilation (% delta PAR/% delta SVR less than 1.0). Despite similar changes in systemic resistance, patients in Group I showed greater increases in cardiac index, stroke volume index and left ventricular stroke work index (p less than 0.01 to 0.001) but less dramatic decreases in mean systemic arterial pressure (p less than 0.02) than did patients in Group II. Despite similar changes in left ventricular filling pressure, patients in Group I showed greater decreases in mean pulmonary artery and mean right atrial pressures (p less than 0.02 to 0.01) than did patients in Group II. Pretreatment variables in Groups I and II were similar, except that plasma renin activity was higher (8.7 +/- 2.1 versus 3.0 +/- 0.6 ng/ml per h) and serum sodium concentration was lower (133.1 +/- 0.9 versus 137.1 +/- 0.6 mEq/liter) in Group II than in Group I (both p less than 0.05). Both groups improved clinically after 1 to 3 months, but symptomatic hypotension occurred more frequently in Group II than in Group I (36 versus 8%) (p less than 0.005). These findings indicate that changes in the pulmonary circulation modulate alterations in both right and left ventricular performance during the treatment of patients with left heart failure. Hyponatremic patients are likely to experience symptomatic hypotension with captopril because they are limited in their ability to increase cardiac output as a result of an inadequate pulmonary vasodilator response to the drug.     

Hemodynamic assessment of intravenous bepridil administration in ischemic heart disease

The hemodynamic effects of intravenous administration of bepridil were evaluated in 17 patients with chronic coronary artery disease who underwent cardiac catheterization. Of the 17 patients, 8 received bepridil, 2 mg/kg of body weight, for 15 minutes followed by 1 mg/kg for 15 minutes (group A), and 9 received 3 mg/kg followed by 1 mg/kg (group B). In group A, the systemic blood pressure (BP) decreased (p less than 0.05) and left ventricular end-diastolic pressure increased minimally (p less than 0.05). Heart rate (HR), pulmonary artery pressure, cardiac output (CO), stroke index, pulmonary vascular resistance and systemic vascular resistance (SVR), stroke work index, "contractility" (+dP/dt) and double product (HR X systolic BP) showed no significant change after bepridil infusion. In contrast, in group B, while +dP/dt decreased (p less than 0.01), SVR also showed a strong downward trend and changed significantly more than in group A; in the context of the latter alteration, CO increased significantly. In addition, the double product (less than 0.025) and systemic BP (p less than 0.05) decreased, though other parameters did not vary significantly. Thus, although a modest dose-related negative inotropic effect (decreased +dP/dt) was seen, dose-related direct systemic vasodilatation (decreased SVR) led to improved cardiac performance (increase in cardiac index) at the larger dose.     

Hemodynamic effects of intravenous isosorbide dinitrate and nitroglycerine in acute myocardial infarction and elevated pulmonary artery wedge pressure

We compared in a randomized fashion the hemodynamic effects of intravenous (IV) isosorbide dinitrate (ISDN) and nitroglycerine (NTG) in 45 patients with acute myocardial infarction and elevated pulmonary artery wedge pressure (Paw). Titration of ISDN dose to lower Paw greater than or equal to 25 percent resulted in a fall of this parameter from 32 +/- 8 to 24 +/- 5 mm Hg and was associated with a fall in mean blood pressure (96 +/- 15 to 90 +/- 14 mm Hg, p less than 0.05), systemic vascular resistance (1715 +/- 572 to 1548 +/- 414 dynes X s X cm-5, (p less than 0.05), pulmonary vascular resistance (182 +/- 106 to 154 +/- 78 dynes X s X cm-5, p less than 0.05) and mean right atrial pressure (11 +/- 4 to 7 +/- 4 mm Hg, p less than 0.05). In addition, ISDN significantly (p less than 0.05) increased cardiac index from 2.37 +/- 0.54 to 2.54 +/- 0.59 L/min/m2, stroke volume index from 28 +/- 8 to 31 +/- 8 ml/m2, and stroke work index from 28 +/- 11 to 31 +/- 12 g X m/m2. The ISDN dose ranged from 50 to 533 micrograms/min (mean +/- SD 326 +/- 176 micrograms/min) and could not be predicted from baseline hemodynamic values. A comparison between the effect of ISDN and NTG in doses producing comparable reduction in Paw showed similar hemodynamic changes. It was concluded that IV ISDN in patients with elevated mean pulmonary artery wedge pressure due to acute myocardial infarction results in a decrease in right and left ventricular preload and afterload and improvement of cardiac output and cardiac work. The effective dose ranges from 50 to 533 micrograms/min and cannot be predicted from baseline hemodynamic values. In doses producing comparable reduction in Paw, ISDN and NTG had similar hemodynamic effects.     

Hemodynamic effects of intravenous diltiazem in patients treated chronically with propranolol

In the search for any deleterious hemodynamic effects of the acute administration of intravenous diltiazem (0.25 mg/kg), in patients on beta blockers, studies were performed in two comparable groups of eight patients with chronic coronary heart disease without clinical signs of heart failure. In the first group, with no previous treatment, the only significant variations observed were a decrease in systemic vascular resistance (p less than 0.01) and an increase in cardiac index (p less than 0.01), which were noted only at 5 minutes. In the second group, receiving long-term oral doses of 120 to 240 mg/day of propranolol, at 5 minutes, despite a slight decrease in peak positive first derivative of left ventricular pressure (p less than 0.05), cardiac index and systolic index increased (p less than 0.05 and p less than 0.01) with decreases in systemic vascular resistance (p less than 0.01) and mean blood pressure (p less than 0.05); at 15 minutes, systemic vascular resistance was still decreased (p less than 0.05) and cardiac index and systolic index were still increased (p less than 0.05). In conclusion, intravenous administration of diltiazem (0.25 mg/kg) to patients with chronic coronary heart disease and no evidence of congestive heart failure, who were receiving propranolol, was safe and prevented, in these patients, the potential deleterious effects of beta blockers, that is, increased peripheral vascular resistance and decreased cardiac output.     

ZK 36-374, a stable analog of prostacyclin, prevents acute hypoxic pulmonary hypertension in the dog

Vasodilator therapy in pulmonary hypertension is limited by the lack of an agent selective for the pulmonary circulation. The effects of intravenous prostacyclin and two stable prostaglandin analogs, ZK 36-374 and CL 115,347, were assessed on the preconstricted pulmonary vasculature of the anesthetized dog. During hypoxic vasoconstriction ZK 36-374 (0.4 micrograms/kg per min) markedly reduced pulmonary artery pressure (26 +/- 3 to 13 +/- 1 mm Hg) (p less than 0.05) and pulmonary vascular resistance (6.2 +/- 1.1 to 2.8 +/- 0.2 mm Hg/liter per min) (p less than 0.01). There was no significant effect on cardiac output, aortic pressure or arterial blood gases. Pulmonary vasoconstriction induced by prostaglandin F2 alpha was similarly affected by ZK 36-374, and in this instance the aortic pressure was also reduced (158 +/- 11 to 129 +/- 11 mm Hg) (p less than 0.01). ZK 36-374 (0.2 micrograms/kg per min) was more effective in lowering hypoxic pulmonary vascular resistance (from 6.5 +/- 0.6 to 3.0 +/- 0.3 mm Hg/liter per min) than was prostacyclin (0.75 micrograms/kg per min) (from 6.3 +/- 0.6 to 4.2 +/- 0.4 mm Hg/liter per min) (p less than 0.05) and resulted in a smaller fall in aortic pressure (p less than 0.05). CL 115,347 (1.0 micrograms/kg per min) had no effect on the pulmonary vasculature during normoxia or when preconstricted by prostaglandin F2 alpha or hypoxia, but reduced aortic pressure and total systemic resistance (p less than 0.05). It appears to be a selective systemic vasodilator with no pulmonary vascular activity.(ABSTRACT TRUNCATED AT 250 WORDS)