Hemodynamic and Metabolic Responses to Vasodilator - Circulation

Hemodynamic and Metabolic Responses to Vasodilator - Circulation

to Hemodynamic and Metabolic Responses Vasodilator Therapy in Acute Myocardial Infarction By KANU CHATTERJEE, M.B., M.R.C.P. (LONDON AND EDIN.), WIL...

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Hemodynamic and Metabolic Responses Vasodilator Therapy in Acute Myocardial Infarction

By KANU CHATTERJEE, M.B., M.R.C.P. (LONDON AND EDIN.), WILLIAM W. PARMLEY, M.D., WILLIAM GANZ, M.D., C. Sc., JAMES FORRESTER, M.D., PAUL WALINSKY, M.D., CARLOS CREXELLS, M.D., AND H. J. C. SwAN, M.B., PH.D.

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SUMMARY Hemodynamic effects of vasodilator therapy (phentolamine or nitroprusside) were studied in 38 patients with acute myocardial infarction (AMI). Cardiac metabolism was studied in 19 of the 38 patients. According to the initial level of left ventricular filling pressure (LVFP) and left ventricular stroke work index (SWI), patients were divided into three groups: Group I-nine patients with LVFP 15 mm Hg or less; Group II-14 patients with LVFP> 15 mm Hg and SWI > 20 g-m/m'; Group III-15 patients with LVFP > 15 mm Hg and SWI <20 g-m/m2. In Group I most patients were clinically uncomplicated. In Group IL most patients had clinical left ventricular failure including one patient who had clinical features of cardiogenic shock. Group III patients all had severe left ventricular failure, with eight patients in clinical shock. In all groups LVFP, pulmonary artery pressure, right atrial pressure, and systemic and pulmonary vascular resistance decreased significantly with vasodilator therapy with only a slight to moderate decrease in arterial pressure. In Group I patients SVI decreased (-7%) together with an increase in heart rate. Significant improvement in left ventricular performance, however, was observed in Groups II and III as indicated by increased stroke volume index (SVI) and cardiac index (CI) and decreased LVFP. The increase in SVI and CI was of similar magnitude in both Group LI (SVI +18%, CI +24%) and Group III (SVI +28%, CI +29%) patients, a change suggesting that vasodilation thereby may be applicable and beneficial even in the presence of severe depression of cardiac performance. Improved left ventricular performance in group II and III patients was accompanied by a slight decrease in coronary blood flow, myocardial oxygen consumption, and transmyocardial oxygen extraction. There was no change in myocardial lactate metabolism in any group. In vitro studies in isolated cat papillary muscle preparations showed no direct positive inotropic effect of either phentolamine or nitroprusside. Thus, significant improvement in left ventricular performance occurs during vasodilator therapy in patients with AMI and elevated LVFP, even in the presence of severe depression of cardiac performance. Furthermore, this improvement is not accompanied by increased metabolic cost. Vasodilator therapy, therefore, may have an important role in the treatment of pump failure complicating myocardial infarction.

Additional Indexing W Cardiac metabolism Cardiogenic shock Myocardial infarction Myocardial oxygen consumption Ventricular function curve

Left ventricular filling pressure Phentolamine Nitroprusside

D ESPITE A BETTER UNDERSTANDING of the physiology of acute myocardial infarction, the prognosis of overt pump failure or cardiogenic shock following infarction remains poor with conventional therapy. Traditionally "pump failure"

with reduced cardiac output and pulmonary venous congestion has been treated with diuretic and inotropic agents. Although diuretics may reduce the symptoms of pulmonary venous congestion, they do not improve the cardiac output.' Inotropic agents,

From the Department of Cardiology, Cedars-Sinai Medical Center, 4833 Fountain Avenue, Los Angeles, California. Supported in part by Contract No. NIH-PH-43-68-1333 under Myocardial Infarction Program, National Heart and Lung Institute, NIH Department, Department of Health, Education and Welfare. The work was done while Dr.

Parmley held an Established Investigatorship of the American Heart Association. Address for reprints: Dr. Kanu Chatterjee, Department of Cardiology, Cedars-Sinai Medical Center, 4833 Fountain Avenue, Los Angeles, California 90029.

Circulation, Volume XLVIII, December 1973

Received June 7, 1973; revision accepted for publication July 13, 1973. 1183

CHATTERJEE ET AL.

1184

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like digitalis or norepinephrine, have variable hemodynamic effects in patients with recent myocardial infarction.2 3 Furthermore, the more severe the pump failure, the less effective are these therapeutic agents.4 Recent experimental and clinical investigations suggest that inotropic agents may also enhance ischemia and the magnitude of muscle destruction in the presence of recent infarction.5 Recently, vasodilator drugs like phentolamine and nitroprusside, agents capable of reducing peripheral resistance, have been shown to improve cardiac performance in chronic congestive heart failure as well as in patients with acute infarction."-9 However, the patients with acute infarction who are likely to benefit from such therapy have not been clearly defined. Furthermore, no information is yet available about the metabolic effects of these agents in patients with acute myocardial infarction. The purpose of this study, therefore, was to evaluate hemodynamic and metabolic responses to vasodilator therapy in patients with acute myocardial infarction. Results suggest that significant improvement in cardiac performance occurs during vasodilator therapy even in the presence of severe pump failure. In order to clarify whether improved cardiac performance was due to direct inotropic effects of sodium nitroprusside and phentolamine, in vitro effects of these agents on isolated cat papillary muscles were also studied. Methods Patient Population

Hemodynamic responses to vasodilator therapy were studied in 38 patients (eight females, 30 males, ages 35-78) with historical, ECG, and laboratory evidence of myocardial infarction. Six patients (nos. 3, 4, table 2, nos. 1, 5, 9, table 3, and no. 7, table 4) had past history of hypertension and only two patients (nos. 1 and 5, table 3) were taking methyldopa until approximately 24 hours prior to study. None was receiving any beta blocking or other antihypertensive agents. Cardiac metabolism was studied in 19 of the 38 patients. Thirty-six patients were investigated within 72 hours of the onset of infarction. One patient was studied on the eighth day and another at six weeks following infarction for persistent congestive failure. Twenty patients had anterior, eight inferior, six both anterior and inferior and three subendocardial infarction. In one patient who developed left bundle branch block acutely, the site of infarct could not be determined. Nine patients were in clinical shock at the time of study. Shock was diagnosed when features of diminished organ perfusion (cold, clammy skin, mental obtundation, and oliguria) and hypotension (systolic blood pressure by cuff, 90 mm Hg or less) were present. Twenty-three patients had frank pulmonary edema and seven, mild to

moderate pulmonary congestion at the time of the study. The remaining eight patients did not have any clinical evidence of pulmonary venous congestion. Vasodilator Therapy

Phentolamine was used intravenously by a constant infusion pump (Harvard) in 11 patients. Five mg of phentolamine were administered in the first minute and then at a rate of 0.1 to 2 mg/min. Nitroprusside was infused in the remaining 27 patients at a rate of 16 to 200 ,ug/min with the use of an infusion flow controller.* The infusion rate of phentolamine or nitroprusside was gradually increased until the mean arterial pressure decreased by not more than 20 mm Hg or when there was a significant decrease in the pulmonary capillary wedge pressure. The infusion rate of nitroprusside was then kept constant and hemodynamic and metabolic measurements were repeated. Hemodynamic and Metabolic Measurements Arterial pressure (AP) was monitored continuously through a 20 gauge cannula inserted into the radial

artery. Right atrial (RA), pulmonary artery (PA), and pulmonary capillary wedge (PCW) pressures were recorded through a balloon-tip triple lumen catheter. Cardiac output (CO) was measured by thermodilution techniques with the same catheter.10 11, 12 Coronary sinus flow (CSF) was measured by the constant infusion thermodilution technique.12' 13 For this purpose a special preshaped catheter was inserted into the coronary sinus.13 Blood samples from the coronary sinus and radial artery were analyzed for pH, pC02, and pO.. by a pH/gas analyzer, model 113*. Hemoglobin saturation was determined with a COoximeter model 182.* Samples of arterial and coronary sinus blood were also taken for determination of lactate concentration by an automated modification of the enzymatic method of Hohorst. 14 Derived hemodynamic and metabolic parameters were calculated as follows: Stroke volume index (SVI) = SV/body surface area (BSA) (m1/M2) Stroke work index (SWI) t = SVI x (AP-PCW) x 0.0144 (g-m/m2)) Systemic Vascular Resistance (SVR) = 80 (AP RA/ CO (dynes sec cm-5) Pulmonary Vascular Resistance (PVR) =80 (PA PCW/ CO (dynes sec cm-5) Oxygen content (ml/ 100 m) 1= Hemoglobin saturation x Hemoglobin content (g/ 100 ml) X 1.34. Myocardial 02 consump (ml/min) = (Arterial - CS 0., content [ml/ 100 ml]) x CS blood flow (ml/min) x10-2. *IVAC 200. IVAC Corporation, San Diego, California. *Instrumentation Laboratories

tFor derivation of the constant (0.0144), see Bowie EJW, Thomson JH Jr: Mayo Clinic Laboratory Manual of Hemostasis. Philadelphia, Saunders, 1971, p 31. Circulation, Volume XLVIII, Dlecember 1973

VASODILATOR THERAPY IN AMI Myocardial Lactate Extraction %= Arterial -Coronary Sinus Lactate X 100. Arterial Arterial where consump = consumption; CS = coronary sinus.

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In Vitro Studies In order to evaluate the direct effects of sodium nitroprusside and phentolamine on cardiac muscle contractility, cumulative dose response curves were obtained with these agents added to isolated cat papillary muscles studied in vitro. Following 40 mg/kg pentobarbital intraperitoneally, each cat's heart was rapidly removed, and the right ventricular papillary muscles placed in a muscle bath (Krebs bicarbonate solution, 30°C) aerated with 95% oxygen, 5% CO2. The muscles were stimulated isometrically (12/min) at the peak of the length-active tension curve using mass electrodes parallel to the muscle and a voltage 10% above threshold. Cumulative dose response curves were obtained by adding increasing doses of sodium nitroprusside or phentolamine (10-8 to 10-3M) and observing changes in force development and the maximum rate of force development. Patient Classification

For evaluation of therapy patients were divided into three groups according to the initial level of left ventricular filling pressure (LVFP) and derived stroke work index (SWI). Group I-Patients with normal LVFP (15 mm Hg or less). Ten studies were performed in nine patients in this group. Group II-Patients with LVFP> 15 mm Hg and stroke work index > 20 g-m/m2. There were 14 patients in this group, and 15 studies. Group Ill-Patients with LVFP > 15 mm Hg and a stroke work index of 20 g-m/m2 or less. There were 15 patients in this group and 19 studies.

Clinical data in all three groups of patients are summarized in table 1. The clinical state of the patient correlated well with the initial hemodynamics. Thus, the majority of patients in group I (with a normal LVFP) were free of signs and symptoms of left ventricular failure. In group II patients, on the other hand, 12 of 14 patients had clinical and radiological signs of left ventricular failure and ten of these patients had clinical and/or radiological evidence of frank pulmonary edema. One patient in this group had clinical features of cardiogenic shock. All patients in group III had clinical evidence of left ventricular failure and 14 of 15 patients had frank pulmonary edema at the time of study. The majority of patients in this group were also relatively hypotensive and eight patients had clinical features of cardiogenic shock. Results

The hemodynamic and metabolic responses to phentolamine and nitroprusside were similar, and Circulation, Volume XLVIII, December 1973

1185

therefore, the results for both drugs have been grouped together. The effects of each drug were fully manifest 5 min after reaching the desired infusion rate. The steady state hemodynamic changes observed during vasodilator therapy in all three groups are detailed in tables 2-4. The usual hemodynamic response in each group was decreased systemic and pulmonary vascular resistance; decreased pulmonary artery, right atrial and left ventricular filling pressures; together with a slight to moderate decrease in mean arterial pressure. However, in three patients in group I, three in group II, and five in group III, there was no significant change in AP. During vasodilator therapy in these patients, AP was unchanged, while PCW pressure was reduced and CI usually increased. There was no significant change in heart rate in group II and III patients although it usually increased in group I patients. Cardiac index increased consistently in group II and III patients, but not in group I patients. Hemodynamic responses were similar in both previously hypertensive and normotensive patients. Table 1 Clinical Data

Number of patients Number of studies Age range (years) Male Female Site of Infarct Anterior Inferior Combined Subendocardial Indeterminate Previouts Inifarct S4 gallop

83 gallop

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38 44

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VASODILATOR THERAPY IN AMI

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Figure 1 Individual changes in stroke volume (SV) and left ventricular filling pressure (LVFP) during vasodilator therapy. Each dot represents baseline measurements, while the arrow head represents measurements during phentolamine or nitroprusside infusion. Group 1 patients have a baseline LVFP < 15 mm Hg. Group II patients have a baseline > 15 mm Hg and a SWI > 20 g-m/m2. Group III patients have a baseline LVFP > 15 mm Hg and a SWI < 20 g-m/m2.

Individual changes in SVI and LVFP are illustrated in figure 1. In group I patients with an initial LVFP < 15 mm Hg, the fall in LVFP during vasodilator therapy was usually accompanied by a fall in SVI. In group II patients, stroke volume increased in all but two patients, and in group III patients with the most severe hemodynamic depression, SVI increased in all patients, together with a decrease in LVFP. The importance of initial LVFP in determining the response to vasodilator therapy is illustrated in a representative patient (No. 8 in table 2) in figure 2. During the initial hemodynamic 40r

svI ml/M 2

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response to phentolamine infusion, the LVFP decreased from 22 to 8 mm Hg, and SVI increased from 26 to 34 ml/m2, together with a fall in systemic vascular resistance; with a further increase in the infusion rate, there was a further reduction in LVFP to 5 mm Hg and SVI decreased to 26 ml/m2. It appears, therefore, that improved cardiac performance may not occur in patients with a normal LVFP, but significant improvement may be expected in patients with an elevated LVFP and depressed cardiac performance. Due to a reduction in arterial pressure of variable magnitude, changes in derived SWI were also variable (fig. 3). In group I patients, there was a consistent reduction in SWI, accompanied by a fall in LVFP. In group II patients, changes in SWI were quite variable. In group III patients, however, SWI increased in 16 of 19 studies despite a reduction in arterial pressure. Changes in LVFP and CI are illustrated in each group of patients in figure 4. There was a similar fall in LVFP (-35%) in all three groups of patients. There was a 20-30% increase in CI in group II and III patients, with no significant change in group I patients. Thus, those patients with the greatest hemodynamic derangements (group III) responded most favorably to vasodilator therapy. Metabolic data obtained in 19 patients in the three groups are summarized in table 5. Although there were no statistically significant changes in

CHATTERJEE ET AL.

1190

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Figure 3 stroke work index (SWI) and left ventricular filling pressure during vasodilator

Individual changes in therapy. Format and grouping similar to figure 1.

CSF in any group, it tended to decrease in groups II and III. Myocardial oxygen consumption (MVO2) decreased in all groups, but the change reached a level of statistical significance only in group III. There was no significant change in myocardial lactate extraction in any of the groups. Vasodilator therapy was continued for 24 hours to one week in patients in groups II and III for pump failure. During continued therapy beneficial hemodynamic response, i.e., increased cardiac Cl

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output and decreased filling pressures could be maintained. Periodic adjustment of the infusion rate was, however, often necessary to maintain the hemodynamic response. In surviving patients in groups II and III, vasodilator therapy was gradually tapered off and then discontinued as baseline hemodynamics and clinical status improved. Figure 5 shows the direct effects of sodium nitroprusside and phentolamine on force development of isolated cat papillary muscles studied in vitro. There were no direct positive or negative inotropic effects up to a dose level of 104M. Above that dose level depressant effects were noted. In the therapeutic range, therefore, there were no significant direct positive or negative inotropic effects of either of these two drugs.

V

Figure 4 Changes in left ventricular filling pressure (LVFP) and cardiac index (CI) during vasodilator therapy in all three groups of patients. Results are expressed as the mean + SEM.

The deleterious hemodynamic consequence of loss of previously functioning myocardial segments due to recent myocardial infarction is reduced ejection fraction, i.e., a failure of ventricular emptying.'5' 16 Decreased stroke volume due to impaired ejection will consequently increase endsystolic and therefore end-diastolic volume, and changes in these parameters will, in turn, increase end-diastolic pressure and pulmonary venous pressure, and produce the symptoms and signs of pulmonary venous congestion. Therefore, the major objective of therapy of pump failure complicating myocardi,al infarction is to improve ventricular emptying. Traditional therapy in the early phases of Circulation, Volume XLVIII, December 1973

1191

VASODILATOR THERAPY IN AMI Table 5 Changes in Metabolic Parameters During Impedance Reduction in Aculte Myocardial Infarction I (6)

Control

(No. of patients)

Control

P<

V

II (6)

JIII P<

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the illness with inotropic agents such as diigitalis has not been very successful in improving forward output.2 3' 4In fact, the greater the depxression of baseline cardiac performance, the lowe r the response observed from inotropic drugs iis. Recent experimental and clinical investigations al so suggest that inotropic agents may increase nnyocardial oxygen demand and thereby exaggerate nnyocardial hypoxia.4 5 Increases in preload or end-diastolic volume within limits (volume expansion therapy) may increase forward output.17' 18 IIa clinical practice, however, this mode of therap)y is only applicable to a small number of patiients with reduced cardiac output due to relative otr absolute hypovolemia associated with decreased left ventricular filling pressure. Recently, vasodilator drugs like phento lamine9 19o or nitroprusside6 have been reported t o increase cardiac output in some patients with rnyocardial infarction. The present study not only confirms o

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1O6m. Circulation, Volume XLVIJI, December 1973

these observations but demonstrates that those patients with the highest filling pressure and lowest baseline cardiac output have the most beneficial improvement in hemodynamic performance. This is in contrast to the hemodynamic response observed following inotropic stimulation which causes the least improvement in those patients with the most depression of cardiac function following recent

myocardial infarction. The clinical implication of this observation is of great importance, since recent studies in patients with acute myocardial infarction have demonstrated that the mortality from pump failure is directly proportional to the severity of depression of cardiac performance. Hamosh and Cohn20 reported a mortality rate of 33% in patients with only a moderately decreased SWI, and a much higher mortality (85.7%) in patients with clinical cardiogenie shock, a markedly decreased SWI, and an elevated LVFP. Rackley and Russell21 reported 100% mortality in patients with clinical cardiogenic shock, a cardiac index less than 2.3 liters/min/m2 and a LVFP higher than 15 mm Hg. Prakash et al.22 reported a 94% mortality in patients with a SWI less than 25 g-m/m2 following recent myocardial infarction. In the context of this recent experience, the

present study suggests that vasodilator therapy can not only improve cardiac performance but probably reduce the mortality in patients with severe pump failure following recent myocardial infarction. Thus, of the 15 patients in group III with severe hemodynamic depression, nine (60%) survived. In the present study 19 patients (nine of whom had clinical cardiogenic shock) had a cardiac index of less than 2.3 liters/min/m2 and an elevated LVFP. Of these, 12 patients (63%), including four with car-

diogenic shock, survived. Similarly of 16 patients

with LVSWI less than 25 g_M/M2 and an elevated

1192 LVFP, nine (54%) survived. While the numbers of patients studied are admittedly small and no definite conclusion can be drawn without control

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study, these preliminary results, nevertheless, suggest that this mode of therapy may have an effect on initial moitality. The present study also demonstrates that vasodilator therapy does not improve cardiac performance in patients with a normal or decreased LVFP. Thus in the patients in group I (LVFP < 15 mm Hg), stroke volume index decreased in the majority and left ventricular stroke work index decreased in all but two patients. The mechanism is presumably related to the changes in preload. Thus, although reduction in impedance to aortic ejection will increase forward stroke volume, a concomitant reduction in preload, to substantially less than 10 mm Hg, decreases stroke volume. In this study, changes in end-diastolic volume could not be measured directly and can only be inferred from the measured changes in left ventricular filling pressure, relative to the curvilinear relation between left ventricular diastolic pressure and volume.23 In the presence of a greatly elevated LVFP, a reduction to the range of 14-22 mm Hg (table 4) will cause a minimal decrease in diastolic volume, and the reduction in stroke volume due to decreased preload will be of small magnitude. The concomitant reduction in left ventricular impedance, however, will cause an increase in stroke volume of larger magnitude. In contrast, if left ventricular filling pressure is initially normal, a further reduction of LVFP would likely be associated with a greater decrease in end-diastolic volume. This larger reduction in preload may, thus, cause a reduction in stroke volume greater than the increase resulting from a reduction of left ventricular impedance. The net results in such patients will be a reduction in stroke volume with a compensatory increase in heart rate (table 2). Mechanical deficits, like mitral regurgitation or systolic paradox, which complicate recent myocardial infarction may substantially aggravate depression of cardiac performance.'5 Decreased resistance to left ventricular ejection and reduced left ventricular chamber size during vasodilator therapy in such patients may significantly improve forward output.24 This mechanism might be partly responsible for the marked improvement in cardiac performance observed in some of the patients. The present study also demonstrates that the improved cardiac performance associated with vasodilator therapy apparently was not ac-

CHATTERJEE ET AL. companied by a deleterious effect on over-all myocardial oxygen metabolism. In group II and III patients, in fact, hemodynamic improvement was associated with a decreased myocardial oxygen consumption. There was also no significant reduction in myocardial lactate extraction in any of the groups. This is consistent with the fact the major determinants of myocardial oxygen demand either remained unchanged or fell. The heart rate did not change and the left ventricular systolic and enddiastolic pressures decreased. Since these drugs have no direct effect on myocardial contractility, and since there were no significant changes in heart rate suggestive of reflex effects, it is probable that over-all myocardial contractility was not greatly altered. However, the present study could not evaluate regional, mechanical, and metabolic performance. Without a knowledge of regional metabolism the possibility of increased hypoxia in some areas of the myocardium due to reduction of perfusion pressure during vasodilator therapy cannot be ruled out. Better knowledge of the regional metabolism would be most useful in determining the degree of reduction of arterial pressure that can be tolerated. In clinical practice at the present time, however, this knowledge is not available. Because of the marked improvement in cardiac performance which was observed in the present study, it seems likely that the magnitude of decrease in arterial pressure that occurred did not increase existing ischemia. It should also be emphasized that the benefits of vasodilator therapy were obtained in some patients, without a reduction in mean arterial pressure. With a decrease in systemic vascular resistance, during vasodilator therapy, if there is proportional increase in cardiac output, mean arterial pressure will remain unchanged as the mean arterial pressure (P) is the product of cardiac output (CO) and systemic vascular resistance (SVR) [P = CO x SVR]. Therefore, if changes in cardiac output and systemic vascular resistance can be monitored, beneficial hemodynamic effects of vasodilator therapy can be obtained even in normotensive or hypotensive patients without causing any significant decrease in mean arterial pressure. Thus, the importance of monitoring cardiac output to definite changes in systemic vascular resistance cannot be overemphasized. Although it is clear that marked improvement in cardiac performance may occur with vasodilator therapy, such therapy should not be applied if facilities for hemodynamic monitoring are not Cifrculation, Volume XLVIII, December 1973

VASODILATOR THERAPY IN AMI

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available. Hemodynamic monitoring is not only essential for the selection of patients likely to benefit from such therapy but also for prevention of complications such as an unexpected sudden fall of arterial pressure. Our current practice is 1) to constantly monitor arterial and left ventricular filling pressure (pulmonary artery diastolic or pulmonary capillary wedge pressure) during such therapy, 2) to start an infusion of phentolamine or nitroprusside at a very low dose (nitroprusside: 16 Ag/min) (phentolamine: 0.1 mg/min), 3) to obtain frequent estimations of cardiac output to determine changes in systemic vascular resistance, 4) to adjust the infusion rate of these drugs to maintain a LVFP of 15-18 mm Hg without causing a marked decrease in arterial pressure, and 5) to abandon this mode of therapy if arterial pressure falls markedly before a decrease in LVFP or ivicrease in cardiac output occurs. Acknowledgment The authors would like to acknowledge the technical assistance of Miss Docela Edwards, Mrs. Luciann Robinson, Mr. Jacques Balian, Mr. Roman Kulczycky, Miss Alma Aldredge, Mr. Lance LaForteza, Mr. Stan Wegner and the editorial assistance of Mrs. Sharman Jamison.

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PRAKASH R, SWAN HJC: Renal and extrarenal hemodynamic effects of furosemide in congestive heart failure after acute myocardial infarction. N Engl J Med 288: 1087, 1973 2. HODGES M, FRIESINGER CC, RIGGINs RCK, DAGENAIS

GR: Effects of intravenously administered digoxin on mild left ventricular failure in acute myocardial infarction in man. Am J Cardiol 29: 749, 1972 3. ABRAMS E, FORRESTER J, CHATTERJEE K, DANZIG R,

SWAN HJC: Variability of response to norepinephrine

infusion in acute myocardial infarction. Clin Res 20: 202, 1972 4. BEZDEK W, FoRRESTER J, CHATTERJEE K, GANZ W,

PARMLEY WW, SWAN HJC: Myocardial metabolic effect of ouabain in acute myocardial infarction (AMI). Circulation 46 (suppl II ):II-113, 1972 5. MAROKO PR, KJEKSHUS JK, SOBEL BE, WATANABE T, COVELL JW, Ross J JR, BRAUNWALD E: Factors

influencing infarct size following experimental coronary artery occlusion. Circulation 43: 67, 1971 6. FRANCIOSA JA, GUIHA NH, LIMAS CJ, RODRIGUERA E, COHN JN: Improved left ventricular function during nitroprusside infusion in acute infarction. Lancet 1: 650, 1972 7. MAJID PA, SHARMA B, TAYLOR SH: Phentolamine for vasodilator treatment of severe heart failure. Lancet 2: 719, 1971 Circulation, Volume XLVTII, December 1973

1193 8. GOULD L, ZAHIR M, ErNGER S: Phentolamine and cardiovascular performance. Br Heart J 31: 154, 1969 9. WALINSKY P, CHATTERJEE K, FORRESTER J, PARMLEY WW, SWAN HJC: Improved left ventricular performance with phentolamine in acuite infarction. Circulation 46 (suppl II): II-233, 1972 10. GANZ W, DONOSo R, MARCUS HS, FORRESTE;R J, SWAN HJC: A new technique for measurement of cardiac output by thermodilution in man. Am J Cardiol 27: 392, 1971 11. FORRESTER JS, CANZ W, DIAMOND G, MCHUGH T,

CHONETrE DW, SWAN HJC: Thermodilution cardiac output determination with a single flow-directed catheter. Am Heart J 83: 306, 1972 12. CANZ W, SWAN HJC: Measurement of blood flow by thermodilution. Am J Cardiol 29: 241, 1972 13. CANZ W, TAMURA K, MARCUS HS, DONOSo R, YOSHIDA

S, SWAN HJC: Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation 44: 181, 1971 14. MARBACH EP, WEIL MH: Rapid enzymatic measurement of blood lactate and pyruvate use and significance of metaphosphoric acid as a common precipitant. Clin Chem 13: 314, 1967 15. SWAN HIC, FORRESTER JS, DIAMOND G, CHATT-ERJEE

K, PARMLEY WW: Hemodynamic spectrum of myocardial infarction and cardiogenic shock: A conceptual model. Circulation 45: 1097, 1972 16. HOOD WB JR: Pathophysiology of ischemic heart disease. Progr Cardiovasc Dis 35: 297, 1971 17. CREXELLS C, CHATTrERJEE K, FORRESTER J, SWAN HJC: Optimal level of ventricular filling pressure in acute infarction. Circulation 46 (suppl II): II-74, 1972 18. RUSSELL RO JR, RACKLEY CE, POMBO J, HUNT D,

POTANIN C, DODGE HT: Effects of increasing left ventricular filling pressure in patients with acute myocardial infarction. J Clin Invest 49: 1539, 1970 19. KELLY DT, DELGADO CE, TAYLOR DR, PirT B, Ross RS: Use of phentolamine in acute myocardial infarction associated with hypertension and left ventricular failure. Circulation 47: 729, 1973 20. HAMOSH P, COHN JN: Left ventricular function in acute myocardial infarction. J Clin Invest 50: 523, 1971 21. RACKLEY CE, RUSSELL RO JR: Left ventricular function in acute myocardial infarction and its clinical significance. Circulation 45: 231, 1972 22. PRAKASH R, FORRESTER J, PARMLEY WW, SWAN HJC:

Prognostic implications of left ventricular stroke work index (SWI) in acute myocardial infarction (AMI). Clin Res 20: 391, 1972 23. DIAMOND G, FORRESTER JS: Effect of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation 45: 11, 1972 24. CHATrERJEE K, PARMLEY WW, SWAN HJC, BERMAN G, FORRESTER J, MARCUS HS: Beneficial effects of

vasodilator agents in severe mitral regurgitation due to dysfunction of subvalvar apparatus. Circulation 48: 684, 1973

Hemodynamic and Metabolic Responses to Vasodilator Therapy in Acute Myocardial Infarction KANU CHATTERJEE, WILLIAM W. PARMLEY, WILLIAM GANZ, JAMES FORRESTER, PAUL WALINSKY, CARLOS CREXELLS and H. J. C. SWAN Circulation. 1973;48:1183-1193 doi: 10.1161/01.CIR.48.6.1183 Downloaded from http://circ.ahajournals.org/ by guest on March 11, 2018

Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1973 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539

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