Clinical and hemodynamic effects of dobutamine in acute myocardial infarction with left heart failure

We studied the clinical and hemodynamic effects of dobutamine infused for 24 hr into 10 patients with acute myocardial infarction (less than 4 days) complicated by left heart failure (pulmonary wedge pressure greater than 15 mm Hg, cardiac index less than 3.0 liters/min/m2). We measured pulmonary arterial pressures, pulmonary wedge pressure, right atrial pressure, and intravascular systemic blood pressures. The thermodilution method was used for determinations of cardiac output, and the electrocardiogram was followed with a computerized arrhythmia monitoring system. After 1 and 3 hr of infusion with the optimal dose (averaging 8 micron/kg/min), there was a very significant increase of cardiac index (29%) and a decrease of pulmonary wedge pressure (37%) with a moderate increase of heart rate (20%) an without significant changes in blood pressure. After 24 hr of dobutamine infusion, much of the improvement in left ventricular function was lost. This may be attributed either to a decrease of drug action or to an unfavorable evolution of the clinical status. We conclude that infusion of dobutamine is an effective, potent, and well-tolerated short-term procedure in the management of left heart failure during the acute stage of myocardial infarction.     

Haemodynamic effects of salbutamol in patients with acute myocardial infarction and severe left ventricular dysfunction

The haemodynamic effects of salbutamol infusions at rates of 10,20, and 40 micrograms/min were measured in 11 patients with acute myocardial infarction complicated by left ventricular failure. Four patients also had cardiogenic shock. Consistent increases were observed in cardiac outputs at all doses (up to 56% at 40 micrograms/min), while the mean systemic arterial pressure fell slightly (average 5 mm Hg), implying a reduction in peripheral vascular resistance. Changes in right atrial pressure and indirect left atrial pressure (measured as pulmonary artery end-diastolic pressure) were small and not significant. Analysis of data from individual patients showed that the greatest increment in cardiac output was reached at 10 micrograms/min in two cases, 20 microgram/min in three, and 40 micrograms/min in the remaining six. Heart rate at these doses increased by an average of only 10 beats/min. Salbutamol failed to reduce left ventricular filling pressure and cannot be recommended for the treatment of pulmonary oedema in acute myocardial infarction. The increase in cardiac output, however, was considerable, so that the drug may be important in the management of low-output states. This action is probably a result of peripheral arteriolar dilatation (itself a result of beta 2-adrenoreceptor stimulation) and is achieved with little alteration in the principal determinants of myocardial oxygen requirement.     

Use of nitrates in patients with acute myocardial infarction

The use of nitrates in treating acute myocardial infarction is reviewed; proposed mechanisms of action and pertinent pathophysiology are discussed. Oral and sublingual nitrates were first tested in acute myocardial infarction patients with mixed results. Later studies with sublingual nitroglycerin followed by phenylephrine infusion indicated that nitrates were effective in limiting myocardial ischemia and necrosis. I.V. nitroglycerin was then studied; beneficial results were documented by quantifying ECG changes and visualizing the areas of myocardial necrosis with radioisotopes. Mortality was also reduced in nitrate-treated patients. Patients who developed left ventricular failure after acute myocardial infarction benefitted the most from nitrate therapy. The preferred route of nitroglycerin administration is intravenous infusion. The dose is initially 5 micrograms/min and is increased by 5-10 micrograms/min every 5-10 minutes until mean arterial pressure is reduced 10-20% or pulmonary capillary wedge pressure is reduced to 15 mm Hg. Final infusion rates average 40-60 micrograms/min. Nitrates appear to have a role in reducing morbidity and mortality from acute myocardial infarction.     

Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure

The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.     

Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated acute myocardial infarction.

A prospective study evaluated the comparative haemodynamic effects of three Class I antiarrhythmics (lignocaine Class 1B, disopyramide Class 1A and flecainide Class 1C) in 30 patients with uncomplicated acute myocardial infarction. Three groups, each of 10 patients, were allocated to lignocaine (Group I) 1.5 mg kg-1 i.v. loading dose over 10 min followed by infusion at 3 mg kg-1 h-1, disopyramide (Group II) or flecainide (Group III), both administered as a 1.0 mg kg-1 i.v. loading bolus over 10 min followed by a 1.6 mg kg-1 h-1 infusion for 120 min. The plasma levels of each drug were in the described therapeutic range. Lignocaine decreased cardiac index (-0.3 l min-1 m-2 (9%); P less than 0.05) and stroke volume index (-5 ml m-2 (11%); P less than 0.01). Systemic blood pressure, heart rate and systemic vascular resistance index were unchanged. There was a small increase (+3 mm Hg (30%); P less than 0.01) in pulmonary artery occluded pressure (PAOP). Both disopyramide and flecainide increased systemic blood pressure; the maximum increases for mean blood pressure were +10 mm Hg (11%) and +4 mm Hg (4%) respectively. Both drugs reduced cardiac index (-0.5 l min-1 m-2 (16%): -0.4 l min-1 m-2 (11%)) and stroke volume index (-11 ml m-2 (25%): -5 ml m-2 (11%)). There were increases in heart rate (+13: +5 beats min-1) pulmonary artery occluded pressure (+2: +3 mm Hg) and systemic vascular resistance index (+696: +275 dyn s cm-5 m2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prophylaxis against ventricular arrhythmias in suspected acute myocardial infarction: a comparison of tocainide and disopyramide.

Five hundred and seventy one patients admitted to a coronary care unit with suspected acute myocardial infarction were considered for entry into a double-blind study. Two hundred and eighty-three patients were excluded, mainly because of recent treatment with beta-adrenoceptor blocking agents, life threatening arrhythmias requiring specific treatment and left ventricular failure presenting with hypotension or pulmonary oedema. Two hundred and eighty-eight entered the trial of whom 202 were subsequently confirmed to have had myocardial infarction. The effects of tocainide and disopyramide on ventricular arrhythmias were compared with placebo over the first 48 h period. The three treatments were given by a combination of intravenous infusion and oral administration. The doses used were tocainide 500 mg intravenously over 30 min plus 2800 mg orally over 48 h and disopyramide 150 mg intravenously over 30 min plus 1050 mg orally over 48 h. As judged by counts of ventricular premature beats, tocainide and disopyramide exerted a similar and significant antiarrhythmic effect. The median number of ventricular premature beats over the first 24 h of treatment was 58 on placebo compared with 30 on tocainide (P less than 0.05) and 19 on disopyramide (P less than 0.05). The corresponding figures for the second 24 h were 9, 6 and 2, respectively. There were eight deaths and three episodes of ventricular fibrillation with no significant differences between the three treatment groups. Sustained ventricular tachycardia was observed in one patient in the tocainide group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute haemodynamic effects of pinacidil in man.

The acute haemodynamic effects of i.v. pinacidil 0.2 mg kg-1 infused over 8 min were studied in 10 normotensive patients undergoing cardiac catheterisation. Mean arterial pressure fell from 94 +/- 3 mmHg (mean +/- s.e. mean) before infusion to 74 +/- 3 mmHg at 10 min after commencing infusion (P less than 0.001) and during this time heart rate increased from 75 +/- 4 to 106 +/- 7 beats min-1 (P less than 0.001). Significant changes were recorded until the end of the observation period (70 min after commencing infusion). Cardiac index increased from 3.2 +/- 0.2 to 4.0 +/- 0.2 l min-1 m-2 (P less than 0.001) and systemic vascular resistance fell from 16 +/- 1 to 10 +/- 1 units (P less than 0.001) at 10 min after commencing infusion. By the end of the observation period, the values had returned to pre-infusion levels. Only small changes in pulmonary haemodynamics were observed. These results indicate that pinacidil acts as a peripheral arteriolar vasodilator, and as such may have a role in the treatment of arterial hypertension and of cardiac failure.     

Hemodynamic effects of concurrent administration of metoprolol and tocainide in acute myocardial infarction

We evaluated the hemodynamic effects of combined administration of metoprolol and tocainide in nine patients with uncomplicated acute myocardial infarction. After 24 h of treatment with oral metoprolol (50 mg q.8 h), intravenous tocainide was given (750 mg over 15 min), followed by oral administration of both drugs (50 mg metoprolol q.8 h; 800 mg tocainide, then 400 mg q.8 h). Hemodynamic variables were measured before and after 25 h of oral metoprolol treatment, immediately after intravenous tocainide (at 15 and 30 min), and then during continued oral treatment with both drugs (at 2 h 15 min and 25 h 45 min). Following injection of tocainide, cardiac index changed significantly (2.7-2.3 L/min . m2; p less than 0.01), but the increases in pulmonary wedge pressure (9-13 mm Hg) and total systemic resistance (15.9-18.1 IU) were not significant. During the continued oral treatment with both metoprolol and tocainide no significant hemodynamic interaction was observed. We conclude that the injection of tocainide can slightly and transiently depress left ventricular function in patients treated with metoprolol.     

Isosorbide-5-mononitrate in the treatment of acute left ventricular failure following acute myocardial infarction

Summary Eleven patients with acute left ventricular failure following acute myocardial infarction (mean pulmonary capillary wedge pressure [PCW]>20 20 mmHg) were entered into an open, haemodynamic study of oral isosorbide-5-mononitrate (ISMN). Left ventricular failure was resistant to intravenous diuretic therapy. No patient received concurrent cardioactive drugs nor further diuretic therapy during the study period. Haemodynamic data were acquired via a flow-directed thermodilution catheter placed in the pulmonary artery. Baseline data were acquired prior to the intravenous administration of an ISMN challenge. Thereafter, oral ISMN (20 mg, 8 hourly) was administered over 48 h.Following intravenous ISMN challenge, mean PCW fell from 26.2 to 17.5 mmHg. Cardiac index fell from 2.4 to 2.3 l/min/m² due to a fall in heart rate (103 to 96.8 beats/min) as stroke volume and blood pressure were unchanged. At 8 h following ISMN, two patients were withdrawn due to hypotension (systolic pressure <85 mmHg). In the remainder, PCW remained acceptable throughout 48 h (13.1 mmHg at 48 h), cardiac output, systemic blood pressure and heart rate showed no further significant change.These data suggest that ISMN is effective in the treatment of acute left ventricular failure following acute myocardial infarction.     

重组人脑钠肽对慢性心衰犬血流动力学和肾功能的影响

目的研究国产重组人脑钠肽(rhBNP)对慢性心衰犬血流动力学及肾功能的影响。方法用右心室快速起搏(RVP)或狭窄下腔静脉(TIVCC)形成犬的心衰模型。结果RVP心衰犬iv rhBNP后,平均动脉压(MAP)、左室内压(LVSP)、LVdp/dt、肺动脉压(PAP)、左室舒张末期压(LVEDP)、总外周阻力(TPR)及肾血管阻力(RVR)呈剂量依赖性下降,LVdp/dt/P、左室做功(LVW)、心输出量(CO)和心率(HR)无明显改变;TIVCC心衰犬在iv同剂量rhBNP后,MAP,LVEDP和CO下降,其他心功能指标无明显改变。两种心衰犬给药后尿量和尿钠排出量均增加。结论rhBNP有舒张血管和利尿作用,能明显降低心衰犬的心脏前后负荷,不影响心脏收缩功能。     

Haemodynamic dose-response effects of a transdermal nitrate delivery system in acute myocardial infarction with and without left heart failure

The haemodynamic effects of a transdermal nitroglycerin delivery system (NTG-TTS) were investigated in 67 patients with a recent myocardial infarction. The study objectives were to define the dose-response effects of NTG-TTS and to examine the influence of baseline haemodynamic status on subsequent response. Therefore, patients with normal cardiac function [pulmonary artery occluded pressure (PAOP) less than 18 mm Hg, n = 40] and those with acute heart failure (PAOP greater than 18 mm Hg, n = 27) were studied after one of three regimens (TTS-10, TTS-20, or TTS-40) with the intention of securing 10 evaluable patients in each group. In patients with acute heart failure, all three doses reduced the left ventricular filling pressure with a modest decrease in systemic arterial pressure; cardiac index and heart rate were unaltered. The systemic vascular resistance was significantly reduced from 120 min. In patients with normal left ventricular function, there were small but significant reductions in systemic arterial pressure and vascular resistance with limited increases in heart rate; the cardiac stroke work index was reduced. These results are compatible with actions of NTG-TTS mainly on capacitance vessels; PAOP fell with limited impact on systemic arterial pressure and vascular resistance index. This mode of nitrate delivery resulted in a low incidence of hypotension and side-effects; comparison with other delivery methods in myocardial infarction seems indicated.     

Effects of histamine H1-receptor blockade on respiratory and cardiac manifestation of systemic anaphylaxis.

In vivo anaphylaxis is associated with respiratory distress and cardiovascular failure. The present investigation was designed to further characterize respiratory and cardiac anaphylactic events. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin together with Freund's adjuvant. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed application of the antigen induced an initial increase of left ventricular pressure which was followed by a rapid decrease 5 min after antigenic challenge. Enddiastolic left ventricular pressure increased within 3 min, thus indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, heart rate steadily decreased. All animals died within 15 min. Simultaneously with cardiac anaphylactic malfunction, severe arterial hypoxia and carbon dioxide retention occurred, revealing respiratory distress. Histamine is known as a potent bronchoconstrictor via histamine H1-receptor stimulation. Administration of H1-receptor antagonists to improve respiration may therefore provide further information on the contribution of pulmonary malfunction to anaphylactic cardiovascular shock. Therefore, additional experiments were performed with sensitized guinea pigs pretreated with the histamine H1-receptor blocker mepyramine. In these experiments the antigenic challenge induced a dissociation of cardiac and respiratory manifestation of anaphylaxis. Despite inhibition of hypoxia and carbon dioxide retention, left ventricular pump failure and occurrence of myocardial ischemia were delayed but not suppressed. It is concluded that histamine is an important mediator of anaphylactic respiratory distress. However, vasoactive anaphylactic mediators other than histamine are primarily involved in anaphylactic cardiac malfunction occurring during the later phase of systemic anaphylaxis.     

Haemodynamic dose-response effects of intravenous amrinone in left ventricular failure complicating acute myocardial infarction

The haemodynamic dose-response effects of intravenous amrinone were measured in 16 male patients, aged 40-65 years, with radiographic and haemodynamic evidence of left ventricular failure 4-18 h after acute myocardial infarction. After a l-h control period to confirm stable haemodynamic baseline variables, patients were randomised to either low-dose (200-400-800 micrograms/kg/h) or high-dose (800-1600-3200 micrograms/kg/h) intravenous amrinone. Each of the three infusions was given consecutively over 30 min (total infusion time 90 min) in each group, and haemodynamic measurements were made at the end of each infusion step. No arrhythmias or other untoward side effects, including haematological changes, were observed during the infusions. In both groups, intravenous amrinone reduced the pulmonary artery-occluded pressure (PAOP) (p less than 0.01), increased the cardiac output (p less than 0.05), and reduced the systemic vascular resistance (p less than 0.05). The reductions in PAOP and systemic arterial diastolic pressure and the increase in heart rate were directly dose-related, but the changes in cardiac output and systemic vascular resistance were not. These results suggest that peripheral vasodilation, particularly of venous capacitance vessels, as well as positive inotropic stimulation, may play a role in the haemodynamic changes induced by intravenous amrinone in acute ischaemic left ventricular failure.     

Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or without impaired left ventricular function.

1. The haemodynamic effects of a new cardioselective postsynaptic alpha 1-adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable coronary disease, with or without impaired left ventricular function. At rest the haemodynamic effects to two dose-response regimens were determined. In an initial eight patients 0.125, 0.125 and 0.25 micrograms kg-1 were administered peripherally at 15 min intervals; the haemodynamic measurements were determined between 10 to 15 min after each dose. In a further 17 patients, the dose regimen was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 micrograms kg-1. The exercise effects were determined by comparison of measurements during 4 min of supine sub-maximal bicycle exercise at a fixed workload before and after drug treatment. 2. At rest, the lower dose regimen of UK-52,046 significantly reduced systemic mean arterial blood pressure (-5 mm Hg; P less than 0.05) and increased cardiac index (+0.2 l min-1 m-2, P less than 0.01). The higher dose regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P less than 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P less than 0.01) and vascular resistance index (-314 dyn s cm-5 m2; P less than 0.05) with an increase in heart rate (+7%, P less than 0.05) and cardiac index (+0.2 l min-1 m-2, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitrate therapy for left ventricular failure complicating acute myocardial infarction: a haemodynamic comparison of intravenous, buccal, and transdermal delivery systems

The haemodynamic effects of three different methods of nitrate administration [intravenous (i.v.) isosorbide dinitrate (ISDN) and buccal and transdermal nitroglycerin (NTG)] were evaluated in 36 patients with acute left ventricular failure due to a recent myocardial infarction. Similar reductions in pulmonary artery occluded pressure (p less than 0.01) followed all three regimens without change in heart rate and cardiac and stroke volume indices. Significant reductions in systemic arterial pressure and vascular resistance followed both ISDN and buccal NTG but not transdermal NTG. A disadvantage of the buccal NTG delivery was an abrupt and, on occasion, inappropriate reduction in blood pressure. The more gradual and controlled reduction of systemic blood pressure with substantial falls in pulmonary artery occluded pressure following ISDN infusion suggest that in the context of myocardial infarction this method of nitrate delivery may have safety advantages; however, when invasive haemodynamic monitoring facilities are not available, transdermal delivery may offer a practical alternative.     

Vasodilators in myocardial infarction: rationale and current status.

While digitalis and diuretics constitute conventional therapy of congestive heart failure due to acute myocardial infarction, systemic vasodilator drugs offer an innovative approach of decreasing left ventricular systolic wall tension (afterload) by reducing aortic impedance and/or by reducing cardic venous return. Thus, vasodilators increase lowered cardiac output by diminishing peripheral vascular resistance and/or decreasing increased left ventricular end-diastolic pressure (ventricular preload) by reducing venous tone. Concomitantly, there is a reduction of myocardial oxygen demand thereby potentially limiting infarct size and ischaemia. The vasodilators produce disparate modifications of cardiac function depending on their differing alterations of preload versus impedance: nitrates principally cause venodilatation (decrease left ventricular end-diastolic pressure); sodium nitroprusside, phentolamine and prazosin produced relatively balanced arterial and venous dilatation (decrease left ventricular end-diastolic pressure while increasing cardiac output, provided upper limits of normal left ventricular end-diastolic pressure are maintained); and hydrallazine solely effects arteriolar dilatation (increases cardiac output). Combined sodium nitroprusside and dopamine therapy synergistically enhances cardiac output and decreases left ventricular end diastolic pressure. In addition, sodium nitroprusside is aided by mechanical counterpulsation which sustains myocardial perfusion pressure in acute myocardial infarction.     

Modulation of inotropic therapy by venodilation in acute heart failure: a randomised comparison of four inotropic agents, alone and combined with isosorbide dinitrate.

The effects of four inotropic agents with differing ancillary properties [a cardiac glycoside (digoxin), a combined alpha- and beta-adrenergic agonist (dobutamine), a beta-adrenergic agonist (prenalterol), and a phosphodiesterase inhibitor (amrinone)] alone and with subsequent addition of isosorbide dinitrate were compared in 48 consecutive acute myocardial infarction patients with radiographic and haemodynamic (pulmonary artery occluded pressure greater than 18 mm Hg) left ventricular failure. All agents with the exception of dobutamine reduced the elevated left heart filling pressure; only digoxin and dobutamine augmented the cardiac stroke volume index. All drugs except digoxin reduced the SVRI; an arteriolar constrictor response was evident 60 min after digoxin and a tachycardia resulted after combined alpha- and beta- and beta-adrenergic stimulations (dobutamine and prenalterol, respectively). The addition of isosorbide dinitrate reversed the inotrope-induced elevations of systemic arterial pressure and resulted in additional reductions in left heart filling pressure. These data suggest that, in the absence of substantial venodilator properties in an inotropic compound, reduction in elevated left heart filling pressure is not achieved with inotropic therapy alone in acute left ventricular failure and combining a venodilator may be haemodynamically advantageous.     

Nifedipine following acute myocardial infarction--dependence of response on baseline haemodynamic status

The haemodynamic effects of nifedipine (20 mg sublingually) were studied in 40 patients with acute myocardial infarction within 18 h of the onset of symptoms. To determine the influence of preload and afterload on the haemodynamic response to nifedipine, patients were prospectively stratified equally into four groups of 10 patients based on systemic blood pressure level (less than or greater than 160/100 mm Hg) and level of left ventricular filling pressure [pulmonary artery-occluded pressure (PAOP) less than or greater than 18 mm Hg]. In all groups, nifedipine reduced systemic arterial pressure (p less than 0.01) and vascular resistance index (p less than 0.01); heart rate (p less than 0.01) and cardiac index (p less than 0.01) were increased. PAOP was reduced by nifedipine only in those hypertensive patients in whom it was initially raised; in these patients cardiac stroke volume index also increased (p less than 0.01). In hypertensive patients with normal PAOP the cardiac stroke work index was reduced. In patients with normal systemic and pulmonary arterial pressures, nifedipine had no beneficial effects on cardiac function. These data suggested that haemodynamic criteria may allow selection of patients for nifedipine therapy following myocardial infarction; clear advantages were evident only in hypertensive patients in both the presence and the absence of left ventricular failure.     

The haemodynamic and metabolic effects of tolmesoxide with special reference to impaired myocardial function.

The haemodynamic, metabolic and regional blood flow effects of the vasodilator, tolmesoxide (1 mg kg-1 min-1 for 20 min by intravenous infusion) were examined in two groups of greyhound dogs anaesthetized with alpha-chloralose and mechanically ventilated. One group of dogs was thoracotomized and subjected to acute coronary artery occlusion. In these dogs tolmesoxide was infused 2.5 h after occlusion when there was evidence of impaired myocardial function. Tolmesoxide administration resulted in marked systemic hypotension which was associated with myocardial stimulation (increase in heart rate and LVdP/dtmax). These effects were less marked in thoracotomized dogs subjected to coronary artery occlusion. Cardiac stimulation was attenuated by pretreatment with the beta-adrenoceptor antagonist, atenolol. Peripheral resistance and left ventricular end-diastolic pressure (LVEDP) were reduced by tolmesoxide. In spite of the systemic hypotension, the marked reduction in LVEDP resulted in an enhanced subendocardial driving pressure and an increased blood flow to ischaemic regions of the left ventricular wall as measured with Xe133 clearance. Blood flow to normal regions of the left ventricular wall was also increased by tolmesoxide. A metabolic and respiratory acidosis may have contributed to the haemodynamic effects of tolmesoxide. Plasma renin levels were significantly elevated by the drug. Tolmesoxide administration thus resulted in cardiac stimulation, reduced both pre-load and after-load, yet maintained coronary and pulmonary perfusion. This haemodynamic profile of tolmesoxide would explain the beneficial effects obtained with this drug in the treatment of cardiac failure.     

Effect of infused adenosine on cardiac output and systemic resistance in normal subjects.

1. The purine nucleoside adenosine relaxes smooth muscle in vitro and is a vasodilator in animals, but its effects on cardiac output and systemic vascular resistance have not been measured in normal conscious human subjects. 2. We have studied the effects of infused adenosine in doses of 0.005, 0.03 and 0.07 mg kg-1 min-1 on pulmonary blood flow and systemic vascular resistance in eight healthy volunteers, using a non-invasive, inert gas method and mass spectrometry. 3. At a dose of 0.07 mg kg-1 min-1, there was a rise in effective pulmonary blood flow (which is approximately equivalent to cardiac output) of 0.52 +/- 0.08 l min-1 m-2 (mean +/- s.e. mean) and a fall in estimated systemic vascular resistance of 357 +/- 44 dyn s cm-5. Despite this marked systemic vasodilation, there was no significant change in mean heart rate. 4. The effects of this dose of adenosine were maximal 2 min after starting the infusion, and had disappeared within 5 min of stopping it. 5. Adenosine may be therapeutically useful in the reduction of left ventricular afterload, where the absence of reflex tachycardia may be advantageous. We suggest that adenosine in doses of 0.03 mg kg-1 min-1 should be evaluated as a selective pulmonary vasodilator.