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.     

Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure]

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.     

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.     

Effects of left ventricular preload and afterload on ascending aortic blood velocity and acceleration in coronary artery disease

Doppler measurements of the velocity and acceleration of ascending aortic blood flow have been used as indexes of left ventricular (LV) contractility. Conflicting data exist, however, on the influence of LV loading conditions on these measurements. Therefore, simultaneous LV micromanometer pressure measurements, 2-dimensional echocardiography and continuous-wave Doppler studies were performed before and after preload or afterload manipulation in 16 patients with coronary artery disease. Nitroprusside (n = 9) was administered in combination with saline to maintain preload and achieve a 10 to 20% reduction in mean aortic pressure. Saline (n = 7) was administered (850 +/- 240 ml) to increase LV end-diastolic pressure 25 to 50%. All measurements were obtained during atrial pacing at a heart rate 10 to 15 beats/min above resting sinus rate. The administration of nitroprusside plus saline decreased LV end-systolic wall stress (94 +/- 27 to 67 +/- 14 g/cm2 X 10(3), p = 0.011) without changing LV end-diastolic pressure and end-diastolic dimension. Peak velocity (0.8 +/- 0.2 to 0.9 +/- 0.3, p = 0.044), velocity time integral (11 +/- 4 to 13 +/- 5 cm, p = 0.049) and mean acceleration (12 +/- 4 to 17 +/- 7 m/s2, p = 0.0014) increased significantly. The administration of saline alone significantly increased LV end-diastolic pressure (10 +/- 4 to 22 +/- 4 mm Hg, p = 0.0006), LV end-diastolic dimension (4.8 +/- 0.5 to 5.1 +/- 0.5 cm, p = 0.0001), peak velocity (0.9 +/- 0.3 to 1.0 +/- 0.4 m/s, p = 0.008), velocity-time integral (14 +/- 5 to 18 +/- 7 cm, p = 0.005), and mean acceleration (14 +/- 6 to 17 +/- 7 m/s2, p = 0.041). Thus, even a modest change in either preload or afterload altered peak velocity, the velocity time integral and mean acceleration. These data have important clinical implications regarding the application of Doppler aortic flow indexes in the assessment of LV function.     

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)     

Combined effects of nitrates on the coronary and peripheral circulation in exercise-induced ischemia

We compared the effects of isosorbide dinitrate (ISDN) administered by intracoronary and intravenous routes in 10 patients with severe coronary artery disease, stable effort angina, and very low exercise tolerance. Supine bicycle ergometer exercise was performed under four conditions: 1) control, 2) after intracoronary administration of 0.4 mg ISDN, 3) 1 hour later (control 2), and 4) after administration of intravenous 4 mg ISDN. At rest, intracoronary ISDN caused no significant hemodynamic effects, whereas intravenous infusion of ISDN resulted in a decline in left ventricular (LV) systolic pressure (-20 +/- 5 mm Hg), LV end-diastolic volume (-27 +/- 3%), and LV end-systolic volume (-30 +/- 4%). After intracoronary infusion of ISDN, ST segment depression and the increase in LV end-diastolic pressure and LV end-systolic volume induced by exercise were significantly less abnormal than during control (0.20 +/- 0.09 vs. 0.14 +/- 0.08 mV, 36 +/- 7 vs. 24 +/- 8 mm Hg, and 91 +/- 40% vs. 40 +/- 29%, respectively). When exercise was performed after intravenous infusion of ISDN, the above-mentioned parameters were significantly improved even further: ST segment depression to 0.05 +/- 0.07 mV, end-diastolic pressure to 14 +/- 7 mm Hg, and LV end-systolic volume to 5 +/- 11% (all p less than 0.01 compared with intracoronary ISDN). Thus, in patients with severe coronary artery disease, it is suggested that intracoronary nitrates increase coronary blood supply during effort-induced ischemia, based on significant improvements in the indirect measures of ST segment depression, LV end-diastolic pressure, and LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hydralazine on pressure-volume and stress-volume relations in congestive heart failure secondary to idiopathic dilated cardiomyopathy

The mechanism by which hydralazine improves cardiac function in patients with heart failure is not well characterized. Hydralazine may improve left ventricular (LV) function by decreasing afterloading wall stress or by increasing myocardial contractility. The effect of intravenous hydralazine was assessed in 8 patients with severe idiopathic dilated cardiomyopathy. Hydralazine increased stroke volume index (from 24 +/- 8 to 40 +/- 9 ml/m2, p less than 0.01) and decreased systemic vascular resistance from 1,603 +/- 619 to 810 +/- 317 dynes s cm-5, p less than 0.01) and peak LV wall stress (from 476 +/- 118 to 410 +/- 68 kdynes/cm2, p = 0.02). Two groups were defined by normal or high LV wall stress. Patients with high LV stress had higher LV end-diastolic pressure (38 +/- 12 vs 17 +/- 8 mm Hg, p less than 0.01), LV end-diastolic volume index (184 +/- 24 vs 149 +/- 7 ml/m2, p less than 0.01) and systemic vascular resistance (1,423 +/- 686 vs 846 +/- 293 dynes s cm-5, p = 0.01). Hydralazine decreased stress more in these patients (-101 +/- 57 vs -6 +/- 9 kdynes/cm2, p = 0.02), LV end-diastolic pressure (-12 +/- 7 vs 2 +/- 2 mm Hg, p = 0.02), systolic pressure (-15 +/- 13 vs 3 +/- 4 mm Hg, p = 0.03) and systemic vascular resistance (-1,053 +/- 247 vs -363 +/- 83 dynes s cm-5, p less than 0.01) than in patients with normal LV stress. Decreased LV stress was caused by decreased systolic and diastolic pressures and/or volumes. Late systolic pressure-volume relations in patients with normal LV stress suggested increased myocardial contractility, but this was not confirmed by LV dP/dt. Hydralazine improves LV function in patients with dilated cardiomyopathy by reducing elevated LV wall stress, with little inotropic effect.     

Influence of UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy

The influence of the new inotropic and vasodilating agent UDCG-115 on hemodynamics and myocardial oxygen metabolism was investigated in 11 patients with idiopathic dilated cardiomyopathy (New York Heart Association class II to III). After intravenous administration of UDCG-115, cardiac index increased from 3.03 +/- 0.68 to 3.76 +/- 1.07 L/min/m2 (p less than 0.01), left ventricular ejection fraction increased from 31 +/- 13 to 39 +/- 16% (p less than 0.01), and maximum rate of left ventricular pressure rise increased from 935 +/- 248 to 1056 +/- 284 mm Hg/sec (p less than 0.05). Left ventricular end-diastolic wall stress (index of preload) and left ventricular end-systolic wall stress (index of afterload) decreased by 41% (p less than 0.01) and 34% (p less than 0.001), respectively. Heart rate did not change significantly. With UDCG-115 myocardial oxygen consumption decreased from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 gm (p less than 0.05), and the ratio of myocardial oxygen supply to myocardial oxygen demand increased from 1.40 +/- 0.08 to 1.53 +/- 0.17 (p less than 0.05). Thus intravenous UDCG-115 improves left ventricular function by increasing inotropism and reducing preload and afterload in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.     

Cardiac energetics after intravenous enoximone in idiopathic dilated cardiomyopathy

The acute effects of enoximone on left ventricular (LV) function, myocardial oxygen metabolism and central and systemic hemodynamics were investigated in 12 patients with idiopathic dilated cardiomyopathy. Enoximone was administered intravenously at a rate of 12.5 mg/min; the average dose was 1.42 mg/kg. LV systolic pressure decreased significantly (p less than 0.01) from 128 +/- 18 to 96 +/- 16 mm Hg (mean +/- standard deviation), LV end-diastolic pressure from 16 +/- 3 to 5 +/- 3 mm Hg, LV end-diastolic volume from 288 +/- 43 to 210 +/- 58 ml, LV end-diastolic wall stress from 33 +/- 15 to 11 +/- 5 10(3) dynes/cm2 and LV peak systolic wall stress from 243 +/- 73 to 159 +/- 42 10(3) dynes/cm2. Heart rate increased from 86 +/- 18 to 100 +/- 20 beats/min, ejection fraction from 43 +/- 7 to 52 +/- 14% (p less than 0.05). Cardiac index, stroke volume index and dP/dtmax did not change significantly. Systemic vascular resistance decreased significantly (p less than 0.01) from 1,311 +/- 444 to 1,027 +/- 356 dynes s cm-5, mean pulmonary artery pressure from 13 +/- 6 to 8 +/- 2 mm Hg, mean right atrial pressure from 4 +/- 2 to 2.6 +/- 2 mm Hg and mean arterial pressure from 95 +/- 13 to 74 +/- 13 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of external work of concentric hypertrophied left ventricles in unanesthetized hypertensive dogs

This study aimed to evaluate the change in external work and its control mechanism in the concentric hypertrophied heart induced by systemic hypertension. The calculated stroke work, myocardial contractility, afterload, and preload were examined in the baseline period (Control Stage, CS) and in the eighth week after the induction of perinephritic hypertension (Hypertensive Stage, HS) in unanesthetized dogs. These variables were examined with echocardiograms and high-fidelity left ventricular (LV) and ascending aortic pressures. Mean aortic pressure was significantly (p less than 0.05) elevated from 95 +/- 10 to 134 +/- 27 mmHg in HS. The ratio of end-diastolic wall thickness to radius significantly (p less than 0.05) increased in the HS. The calculated stroke work of the LV chamber was significantly (p less than 0.05) increased from 7022 +/- 1203 to 8860 +/- 1548 X 10(3) erg in HS while the stroke work normalized for wall thickness by calculating the wall stress was not altered (3069 +/- 1086 v.s. 2989 +/- 866 erg; CS v.s. HS) with no significant change in heart rate in HS. In the HS, the end-systolic wall stress (afterload) and the slope of end-systolic wall stress-dimension relationship (myocardial contractility) were unchanged while the end-diastolic wall stress (preload) slightly reduced. These results suggest that, in the concentric hypertrophied left ventricle induced by systemic hypertension, the LV myocardial external work is normal, whereas the LV chamber external work increases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and myocardial energetic changes induced by the new cardiotonic agent,AR-L 115, in patients with coronary artery disease

AR-L 115 has been shown to improve left ventricular (LV) pump function in patients with advanced congestive cardiomyopathy by the intravenous and oral routes. Since AR-L 115 effects on myocardial oxygen consumption (MV?O₂) and coronary blood flow (CSF) are unknown, the hemodynamic, myocardial metabolic, and ECG responses to AR-L 115 (2 mg/kg bolus) were monitored at 9-, 14-, and 9-minute intervals in seven patients with coronary disease, exhibiting ischemia during pacing stress only. Maximal responses occurred at the fourteenth minute after AR-L 115. There were (average) increases in cardiac index by 30%, heart rate by 19%, CSF by 39%, MV?O₂ by 34%, and LV $\text{dp}\text{dt}$ max by 27%. There were (average) decreases in peak LV systolic pressure by 13%, LV end-diastolic pressure by 42%, systemic vascular resistance by 34%, and in coronary vascular resistance by 37%. All changes were significant (p < 0.05). Myocardial lactate extraction, stroke work index, and stroke index remained unchanged (p > 0.05). The modes increase in MV?O₂ is possibly explained by the increase in contractility being partially offset by reductions in LV preload and afterload. AR-L 115-improved LV pump function was accompanied by moderate increases in MV?O₂ and CSF but without evidence of myocardial ischemia.     

Effect of slow-release ISDN on cardiac function in patients with coronary heart disease during bicycle ergometry

In 10 patients with coronary heart disease (CHD), the effect of a single doses of slow-release isosorbide dinitrate (ISDN) on cardiac function was investigated. Haemo-dynamics was examined by right heart catheterization and thermodilution measurement of cardiac output. After placebo and after 2 and 6 hours with 40 mg ISDN, the heart rate (HR), cardiac index (CI), pressure values in the pulmonary artery (PASP, PAMP, PAEDP) and in the aorta (AoSP, AoMP, AoEDP) and systemic vascular resistance (SVR) were measured at rest and during bicycle ergometry. At rest, PASP and PAMP were significantly reduced only 6 hours after ISDN. Under exercise conditions, significantly reduced pressure values in the pulmonary artery were found 2 and 6 hours after ISDN. AoSP was likewise reduced 2 and 6 hours after ISDN. HR, CI and SVR showed no significant differences compared with placebo values. Thus, an effective reduction of left ventricular preload and afterload was seen in patients with CHD during bicycle ergometry.     

Intravenous isosorbide dinitrate during open-heart surgery and its role in the treatment of right-sided congestive heart failure

Recent awareness of the importance of the functional integrity of the right ventricle and the effect of raised pulmonary vascular resistance on cardiac output after cardiopulmonary bypass has focused attention on means of protecting right ventricular myocardium and reducing right ventricular afterload during open-heart surgery. A study of the acute effects of bolus intravenous isosorbide dinitrate (ISDN) has shown that after cardiopulmonary bypass, bolus intravenous ISDN produced highly significant (p less than 0.001) decreases in mean pulmonary arterial pressure (13%), pulmonary vascular resistance (23%) and the ratio of pulmonary to systemic vascular resistance (20%), indicating that active pulmonary vasodilation had occurred in the absence of other hemodynamic changes. The results suggest that possibly the acute effect of low-dose ISDN after cardiopulmonary bypass is predominantly exerted on the right ventricular afterload if systemic arterial pressure is not elevated. Two different clinical situations are described in which intravenous ISDN proved beneficial, one being acute pulmonary hypertension after protamine sulphate and the second being acute right-sided congestive heart failure with systemic hypotension unresponsive to conventional therapeutic measures. Thus, ISDN may prove a useful agent for alleviating right ventricular dysfunction at a time of not infrequent cardiovascular instability, the period after bypass.     

Effect of oral milrinone on end-systolic relations in patients with severe congestive heart failure

The new inotropic agent milrinone has both vasodilator and inotropic cardiovascular effects, but the importance of these effects in patients with severe congestive heart failure (CHF) is controversial. The left ventricular (LV) end-systolic pressure-diameter relation was used to determine the independent inotropic effect of milrinone. Seven patients with New York Heart Association class III CHF were invasively monitored with right-sided heart catheters and radial arterial lines. M-mode echocardiography was used to measure LV dimensions. The effect of a 10-mg oral dose of milrinone on hemodynamic, echocardiographic and end-systolic variables was determined. End-systolic pressure was measured at the dicrotic notch of the arterial pressure tracing and end-systolic LV dimensions at the time of aortic valve closure. Methoxamine (n = 6) or nitroprusside (n = 1) was used to alter afterload so that the end-systolic pressure-diameter relation could be determined. Arterial vasodilation from milrinone was evidenced by a decrease in mean arterial blood pressure (88 +/- 5 to 77 +/- 2 mm Hg, p less than 0.025) and an increase in cardiac index (from 2.7 +/- 0.2 to 3.2 +/- 0.2 liters/min/m2, p less than 0.025), with no change in heart rate (80 +/- 5 beats/min). Milrinone decreased preload as assessed by the pulmonary artery wedge pressure (from 17 +/- 2 to 10 +/- 2 mm Hg, p less than 0.01) and end-diastolic LV diameter (from 7.4 +/- 0.4 to 7.0 +/- 0.4 cm, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of alterations in loading on mitral annular velocity by tissue Doppler echocardiography and its associated ability to predict filling pressures

STUDY OBJECTIVES: Early diastolic mitral annular velocity (E') by tissue Doppler echocardiography (TD) has been reported to be a load-independent index of left ventricular (LV) diastolic function, allowing the early diastolic mitral inflow velocity (E)/E' ratio to be used clinically to predict LV filling pressures. However, preload independence of E' has remained controversial, and E/E' may not consistently be predictive of LV filling pressures. Our objectives were to test the hypotheses that E' is affected by preload, and that alterations of preload, afterload, and contractility also affect E/E'. DESIGN, INTERVENTIONS, AND MEASUREMENTS: An open-chest dog model was used (n = 8). High-fidelity pressure and conductance catheters were used for pressure-volume relations, and E' was obtained by pulsed TD from the apical four-chamber view. Changes in preload and afterload were induced by vena caval and partial aortic occlusions, respectively. Data were collected during control phase and during infusions of dobutamine and esmolol to alter contractility. RESULTS: E' was consistently and significantly associated with acute decreases in LV end-diastolic pressure in each dog (n = 200 beats; r = 0.93 +/- 0.06 [mean +/- SD]). Similar results occurred with dobutamine and esmolol infusions. This preload sensitivity was reflected in E/E', which was inversely (rather than directly) correlated with LV diastolic pressure (r = - 0.67). E/E' was less affected by preload when diastolic dysfunction was induced by sustained partial aortic occlusion (time constant of relaxation increased from 46 +/- 19 to 53 +/- 21 ms, p < 0.001). CONCLUSIONS: E' was significantly influenced by preload with preserved LV function and low filling pressures (< 12 mm Hg); accordingly, E/E' was less predictive of LV filling pressures in this scenario. E/E' was more predictive of LV filling pressures in the presence of diastolic dysfunction.     

Echocardiographic determination of left ventricular stress-velocity relations.

The time course of left ventricular (LV) circumferential stress and fiber shortening velocity (Vcf) were determined at 20 msec intervals in 30 patients from simultaneous recordings of LV pressure (micromanometer) and LV dimensions (echography). In 12 patients with normal LV function, endocardial and midwall maximal (max) Vcf, Vcf at peak stress, and endocardial mean Vcf were significantly greater than in eight patients with myocardial disease. Peak stress was less in the normal subjects (mean equal 241 gl/cm2, range 180 to 310 g/cm2) than in those with myocardial diseases (mean equals 371 g/cm2, range 280 to 513 g/cm2). Vcf was reduced in five out of seven patients with chronic LV volume overload, while peak stress ranged from normal in three to increased in four. Max Vcf, mean Vcf, and peak stress were normal in three patients with chronic LV pressure overload; Vcf at peak stress was normal in two. Good correlation was observed between angiographic determinations of mean Vcf and endocardial max Vcf, Vcf at peak stress and mean Vcf. Induced changes in preload in five patients (dextran infusion at constant heart rate) produced a 12.2 per cent increase in peak stress (P small than 0.05), and insignificant changes in max Vcf (3.7 per cent increase, P = NS), in Vcf at peak stress (5 per cent decrease, P smaller than 0.05), in mean Vcf (0.7 per cent increase, P = NS). Increasing afterload with angiotensin in seven patients (peak stress increased by 45 per cent, P smaller than 0.01) reduced max Vcf, Vcf at peak stress and mean Vcf by 33 per cent, 39 per cent respectively. Lowering afterload in one patient (amyl nitrite) produced an increase in Vcf. Improvement in Vcf was observed in all instances during positive inotropic stimulation (isoproterenol in three normals, digoxin in four with myocardial disease). Thre response of endocardial and midwall Vcf to loading and contractility were similar. In man Vcf is an index of myocardial contractility which is affected minimally by changes in preload but responds inversely to changes in afterload. Its sensitivity to acute afterload changes may, at times, limit its clinical applicability.     

Relative contribution of inotropic and vasodilator effects to amrinone-induced hemodynamic improvement in congestive heart failure

The relative contribution of inotropic and vasodilator effect to amrinone-induced hemodynamic improvement in congestive heart failure (CHF) is unknown. In 9 patients with CHF, the effects of amrinone and nitroprusside on hemodynamic and radionuclide measurements were compared to determine whether reduced afterload accounts for the amrinone-induced decrease in left ventricular end-systolic volume. In each patient, the end-systolic pressure-volume relation was derived using nitroprusside. After terminating nitroprusside treatment, intravenous amrinone (3 mg/kg) caused end-systolic volume to decrease from 148 +/- 32 ml/m2 (mean +/- standard deviation) to 133 +/- 32 ml/m2 (p less than 0.05), causing an increase in cardiac index from 1.9 +/- 0.8 to 2.7 +/- 0.8 liters/min/m2 (p less than 0.001). Arterial end-systolic pressure decreased in all patients during amrinone administration, from 96 +/- 22 to 84 +/- 19 mm Hg (p less than 0.005), as did systemic vascular resistance. Nitroprusside doses needed to match the decrease in LV end-systolic volume induced by amrinone caused significantly greater decreases in arterial end-systolic pressure than did amrinone (p less than 0.01). The amrinone-induced decrease in end-systolic volume exceeded that predicted for a pure vasodilator based on arterial end-systolic pressure and the nitroprusside-derived pressure-volume relation in 6 patients. In 3 patients, the decrease in end-systolic volume did not exceed that expected for a pure vasodilator. In conclusion, after amrinone treatment, afterload reduction occurs in all patients with severe CHF and is the sole effect in some.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

To compare the effects of intravenous dobutamine and milrinone on right ventricular (RV) systolic function, 14 patients with severe congestive heart failure underwent simultaneous radionuclide-hemodynamic study. Patients were randomized to receive intravenous milrinone (50 micrograms/kg bolus then 0.5 microgram/kg/min) or dobutamine (2.5 to 15 micrograms/kg/min) to achieve equal increases in cardiac output. Both drugs significantly improved cardiac performance, with identical 24% increases in mean cardiac index (p less than 0.05 vs baseline; difference not significant for milrinone vs dobutamine) and no change in heart rate. Neither drug substantially altered RV preload, as reflected by mean right atrial pressure and RV end-diastolic volume. Both drugs caused similar increases in RV ejection fraction (mean +/- standard deviation; dobutamine: 0.32 +/- 0.09 to 0.40 +/- 0.11; p less than 0.05; milrinone: 0.35 +/- 0.19 to 0.43 +/- 0.21; p less than 0.05) resulting from reductions in RV end-systolic volume. RV afterload reduction contributed substantially to drug effect on RV systolic performance in patients treated with milrinone but not those treated with dobutamine. With doses effecting equal increases in cardiac index and RV systolic performance, pulmonary artery end-systolic pressure was significantly reduced by milrinone (40 +/- 12 to 33 +/- 12 mm Hg; p less than 0.05), but not by dobutamine. Thus, in patients with congestive heart failure milrinone's effect on RV systolic function is explainable, at least in part, by RV afterload reduction, whereas RV inotropic augmentation contributed more strongly to dobutamine's effect.     

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 intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction

To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.