Systemic and coronary hemodynamic effects of pinacidil in awake normotensive and hypertensive dogs

We studied the systemic and coronary hemodynamic effects of a new antihypertensive agent, pinacidil, in nine morphine-sedated chronically instrumented dogs with one-kidney renal hypertension and eight similarly treated sham-operated normotensive dogs. The renal hypertensive dogs exhibited higher mean aortic blood pressure, total peripheral vascular resistance, and plasma renin activity before pinacidil administration than the sham-operated animals. The renal hypertensive dogs also had a lower left ventricular norepinephrine content, but the two groups did not differ significantly in plasma norepinephrine levels, cardiac output, or heart rate. Pinacidil decreased mean aortic pressure and total peripheral vascular resistance and increased cardiac output and heart rate in both groups. The changes in aortic pressure, total peripheral vascular resistance, and cardiac output were similar between the two groups, but the increase in heart rate was attenuated in renal hypertension. The peak rate of rise of left ventricular pressure (dP/dt), the ratio of left ventricular dP/dt and the developed pressure during isovolumic contraction (dP/dt/P), myocardial oxygen consumption, and plasma norepinephrine levels increased after pinacidil administration in the sham-operated dogs, but did not change in the renal hypertension group. The two groups did not differ in their responses of left ventricular dP/dt to intravenous isoproterenol. Pinacidil also caused coronary vasodilation in both groups, as evidenced by an increase in coronary blood flow and decreases in coronary vascular resistance and myocardial oxygen extraction. The decrease in myocardial oxygen extraction was similar in the two groups, but the increase in coronary blood flow was significantly less (p less than 0.05), probably because of the absence of an increase in myocardial oxygen consumption in the renal hypertensive dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure

The effects of amrinone, dobutamine, and a combination of the two drugs on peak positive left ventricular dP/dt and left ventricular performance were evaluated in 11 patients with chronic congestive heart failure. When administered alone, both dobutamine (10.9 micrograms/kg/min) and intravenous amrinone (1.9 mg/kg/min) significantly increased left ventricular dP/dt and performance. When compared with dobutamine alone, the addition of amrinone resulted in further increases in left ventricular dP/dt and cardiac index (to 1319 +/- 419 from 1202 +/- 376 mm Hg/sec, p less than .002, and to 3.56 +/- 0.78 from 3.04 +/- 0.67 liters/min/m2, p less than .01, respectively). The combination also induced a further reduction in left ventricular end-diastolic pressure (to 15.3 +/- 11.3 from 18.2 +/- 10.3 mm Hg, p less than .05) when compared with amrinone alone. The combination of dobutamine and amrinone increased heart rate slightly when compared with either drug alone, but did not further reduce systemic arterial pressure when compared with amrinone alone. The dose-response curve of left ventricular dP/dt and performance during titration of dobutamine with and without the addition of intravenous amrinone was evaluated in seven patients. The addition of amrinone to any dose of dobutamine produced higher cardiac index and lower systemic vascular resistance than dobutamine or amrinone alone. Thus, when compared with dobutamine alone in patients with chronic congestive heart failure, the addition of intravenous amrinone to dobutamine results in an additive improvement in left ventricular performance throughout the dose range.     

Potential mechanisms of improved left ventricular function with enoximone in severe congestive heart failure

Enoximone, a phosphodiesterase inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in systemic hemodynamics in patients with severe chronic congestive heart failure. Cardiac index, stroke volume index and stroke work index increase, and there is a significant decrease in pulmonary capillary wedge pressure. Left ventricular dP/dt increases, despite a decrease in arterial pressure and systemic vascular resistance and without any significant change in heart rate, indicating a positive inotropic effect. A marked decrease in systemic vascular resistance indicates that decreased left ventricular outflow resistance resulting from peripheral vasodilation also contributes to improvement in left ventricular function. In some patients, left ventricular end-diastolic volume increases despite a marked decrease in pulmonary capillary wedge pressure, suggesting an improvement in apparent left ventricular compliance, which may also be contributory to improved left ventricular function.     

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.     

Hemodynamic and coronary effects of intravenous verapamil in coronary insufficiency

Verapamil inhibits calcium influx through the slow calcium canals. The coronary an haemodynamic effects of intravenous Verapamil were studied in 8 patients with chronic coronary insufficiency documented by coronary arteriography. The following measurements were made in spontaneous rhythm and during atrial pacing under basal conditions and 10 minutes after intravenous Verapamil (0.10 to 0.17 mg/kg) relayed with a continuous infusion of 5 x 10(-3) mg/Kg/mn: heart rate, cardiac output, left ventricularr pressure (Millar 5 F micromanometer), femoral artery pressure, coronary sinus flow by continuous thermodilution, oxygen and lactate concentrations in arterial and arterio-venous oxygen difference, and index of myocardial oxygen consumption and the coefficient of lactate extraction were then calculated. The coronary and haemodynamic effects of atrial pacing were similar before and after Verapamil at a given rate. Left ventricula end diastolic pressure decreased, cardiac output and total systemic resistance were unchanged, dP/dt max increased but to a lesser degree after Verapamil (P less than 0.05). Coronary arterio-venous oxygen difference decreased after Verapamil. The coronary and haemodynamic effects of Verapamil were similar in spontaneous rhythm and during atrial pacing. In spontaneous rhythm, the heart rate and left ventricular end diastolic pressure increased. In spontaneous and paced rhythm, femoral artery pressure, total systemic resistance and dP/dt max decreased. Cardiac output remained the same. Myocardial oxygen consumption decreased mainly because of a reduced coronary arterio-venous oxygen difference and because of unchanged coronary flow in spontaneous rhythm oxygen consumption seems to have a favourable effect on the myocardial energy equilibrium as shown by the increased coefficient of lactate extraction during atrial pacing after Verapamil. This study shows the negative inotropic and arterial vasodilator effects of Verapamil to be responsible for the reduced myocardial oxygen consumption. It also caused coronary artery vasodilation.     

Chronic beta-adrenoceptor blockade prevents the development of beta-adrenergic subsensitivity in experimental right-sided congestive heart failure in dogs.

BACKGROUND. The reductions of myocardial beta-adrenergic receptor density and responsiveness to catecholamines in congestive heart failure are associated with excessive sympathetic stimulation. The purpose of this study was to determine whether the myocardial changes could be prevented by beta-receptor blockade. METHODS AND RESULTS. We administered the oral beta-receptor blocking agent nadolol (40 mg/day) to dogs during an early stage of experimental right heart failure and to sham-operated dogs for 5 weeks. Animals receiving no nadolol were studied concurrently. Nadolol treatment did not prevent right ventricular hypertrophy or elevated concentrations of plasma norepinephrine that occurred in right heart failure, nor did it affect the decrease in myocardial norepinephrine content and norepinephrine uptake activity, suggesting that the hemodynamic stress imposed on the right ventricle of dogs with right heart failure was similar regardless of the presence or absence of beta-receptor blockade. Resting heart rate, right atrial pressure, aortic pressure, cardiac output, right ventricular dP/dt, and left ventricular dP/dt and dP/dt/P measured 5 days after discontinuation of nadolol did not differ significantly from those without nadolol treatment in either right heart failure or sham-operated animals. Sham-operated dogs also showed no changes in myocardial beta-receptor or adenylate cyclase activity after nadolol treatment. However, nadolol treatment prevented the reduction of myocardial beta-receptor density and attenuated the decrease in the cardiac beta-adrenergic sensitivity that occurred in right heart failure. CONCLUSIONS. Excessive sympathetic stimulation may play an important role in the development of beta-receptor downregulation and beta-adrenergic subsensitivity in right heart failure.     

Experimental myocardial infarction: XI. Circulatory effects of hypoxia in intact conscious dogs with coronary occlussion

This study was designed to detect possible deleterious effects of systemic hypoxia upon the ischemic canine heart. Myocardial infarction was produced in intact conscious dogs by occluding either the left anterior descending or the circumflex coronary artery, using a balloon cuff implanted around the vessel. Periods of 12, 8 and 6 percent oxygen breathing were imposed on the animals before and after acute myocardial infarction. Cardiac output, systemic arterial and pulmonary arterial pressures and the maximal rate of rise of left ventricular pressure (dP/dt) increased with hypoxia produced by breathing of 6 percent oxygen both before and after coronary occlusion. Left ventricular end-diastolic pressure did not increase during hypoxia after myocardial infarction. Thus, despite the presence of ischemic heart failure (sinus tachycardia, increased left ventricular end-diastolic pressure), the response to hypoxia was quantitatively similar to the response observed before coronary occlusion. Hypoxia after coronary occlusion did not further depress overall left ventricular function.     

Evaluation of the alpha and beta blocking effects of intravenous labetalol on left ventricular function in coronary artery disease

Intravenous labetalol was evaluated in 10 patients with stable angina without heart failure. Mean dose was 1.75 mg/kg (range 1.5-2 mg/kg). Measurements were taken within one minute after the injection, and at 1, 5 and 15 minutes thereafter. Labetalol significantly decreased blood pressure and increased heart rate. Peak aortic flow velocity increased only significantly at 1 minute; dP/dt+ max. was significantly decreased during all the measurements. Left ventricular end diastolic pressure did not change. Thus in patients without failure left ventricular function remained stable despite the negative inotropic effects of labetalol.     

Effects of growth hormone in rats with postinfarction left ventricular dysfunction

Summary Growth hormone may affect cardiac function. In rats, chronic hypersecretion of growth hormone leads to increased maximum isometric contractile force of the left ventricular papillary muscle in vitro. In humans, administration of growth hormone can increase myocardial contractility. However, cardiac effects of growth hormone in heart failure or cardiac dysfunction have not been studied to date. The current study was to evaluate the cardiac effects of growth hormone in conscious rats with postinfarction left ventricular dysfunction and sham controls. Ligation of the left coronary artery or sham operation was performed, then 4 weeks after surgery, recombinant human growth hormone (2 mg/kg/day, SC) or vehicle was administered for 15 days. Catheters were implanted 13 days after treatment with growth hormone or vehicle. Hemodynamic parameters were measured in conscious rats 2 days after catheterization. In vehicle-treated rats, left ventricular systolic pressure, maximum dP/dt, and arterial pressure were significantly decreased and left ventricular end-diastolic pressure was significantly increased in the ligation group compared with sham controls. Growth hormone treatment increased left ventricular systolic pressure (p<0.05) and dP/dt (p<0.05) and reduced left ventricular end-diastolic pressure (p<0.05), significantly in the ligated rats. In sham rats, growth hormone tended to decrease arterial pressure but did not alter ventricular contractility. Neither ligation nor growth hormone significantly altered heart rate and right atrial pressure. These results suggest that growth hormone treatment may improve cardiac function by increasing myocardial contractility in cardiac dysfunction or heart failure.     

Experimental right ventricular hypertrophy and failure in swine.

Following pulmonary arterial constriction, 22 pigs developed right ventricular failure and 10 right ventricular hypertrophy. Comparing results with those obtained in 21 normal pigs (no pulmonary artery constriction), it was found the right ventricular peak systolic and end-diastolic pressures, cardiac output, and right ventricular weight distinguished hypertrophied and failing hearts from normal ones. Cardiac output was lower in failing hearts than in hypertrophied hearts and was the only variable which significantly differentiated between these two groups. Left ventricular pressures and left ventricular and right ventricular dP/dtmax, and maximum [(dP/dt)/P] did not distinguish failing from hypertrophied hearts. Left ventricular pressure, maximum [(dP/dt)/P] and left ventricular and right ventricular dP/dtmax were not significantly different in the three groups.     

Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure.

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.     

Cellular basis of ventricular remodeling after myocardial infarction.

To determine whether acute left ventricular failure associated with myocardial infarction leads to architectural changes in the spared nonischemic portion of the ventricular wall, large infarcts were produced in rats, and the animals were sacrificed 2 days after surgery. Left ventricular end-diastolic pressure was increased, whereas left ventricular dP/dt and systolic pressure were decreased, indicating the presence of severe ventricular dysfunction. Absolute infarct size, determined by measuring the fraction of myocyte nuclei lost from the left ventricular free wall, averaged 63%. Transverse midchamber diameter increased by 20%, and wall thickness diminished by 33%. The number of mural myocytes in this spared region of the left ventricular free wall decreased by 36% and the capillary profiles by 40%. Thus, side-to-side slippage of myocytes in the myocardium occurs acutely in association with ventricular dilation after a large myocardial infarction. In order to analyze the chronic consequences of myocardial infarction on ventricular remodeling, a second group of experiments was performed in which the left coronary artery was ligated and the functional and structural properties of the heart were examined 1 month later. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), a 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased 9-fold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Thus, decompensated eccentric ventricular hypertrophy develops chronically after infarction and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistence of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.     

Effects of changes in airway pressure on the left ventricle and left atrium of dogs

The effects of negative and positive airway pressure were examined in eight closed chest, chronically instrumented dogs to determine beat to beat changes in left ventricular pressure, left ventricular dP/dt, left ventricular dimensions, and oesophageal pressure. As an index of afterload, systolic transmural pressure was calculated by subtracting oesophageal pressure from left ventricular pressure. With each change in airway pressure left ventricular end systolic minor axis diameter and left ventricular end diastolic minor axis diameter increased significantly. Left atrial end diastolic dimension increased significantly with negative airway pressure and did not change with positive airway pressure. Left ventricular dP/dt and left ventricular fractional shortening did not change. With the Mueller manoeuvre left ventricular systolic pressure decreased significantly from 106(4.2) mm Hg to 100.9(4.2) mm Hg and systolic transmural pressure increased significantly from 105.1(4.6) mm Hg to 110.4(4.3) mm Hg. With a transient increase in positive airway pressure of 30 mm Hg (4.0 kPa), left ventricular pressure increased significantly from 106.9(4.8) mm Hg to 113.9(5.9) mm Hg and systolic transmural pressure decreased significantly from 106.6(4.9) mm Hg to 99.8(4.6) mm Hg. The addition of positive end expiratory pressure of 10 cm H2O (0.98 kPa) or autonomic blockade with atropine and propranolol did not alter these results. Thus manoeuvres which cause opposite effects on systolic transmural pressure produce similar increases in left heart dimensions, suggesting that increases in pulmonary venous return and not changes in afterload may be the important determinants of left ventricular dimensional changes during changes in airway pressure.     

Improved systolic and diastolic myocardial function with intracoronary pyruvate in patients with congestive heart failure

BACKGROUND: Pyruvate increases myocardial performance in isolated myocardium and improves hemodynamics in patients with congestive heart failure. AIMS: To investigate the influence of pyruvate on detailed parameters of systolic and diastolic left ventricular (LV) function. METHODS AND RESULTS: In patients with heart failure due to dilated cardiomyopathy (LVEF 30+/-4%, n=9) pyruvate was infused intracoronarily. LV function was analysed before, during and after application of different pyruvate concentrations using a LV-micromanometer catheter. LV volumes were determined using cine ventriculography. Pyruvate increased maximum rate of LV isovolumic pressure rise (Peak +dP/dt) from 802+/-106 to 1125+/-103 mmHg/s (P<0.05). Left ventricular end-diastolic pressure declined in parallel from 17+/-2 to 12+/-2 mmHg (P<0.05) and heart rate decreased from 79+/-4 to 72+/-5 min(-1) (P<0.05). Stroke volume index increased from 34+/-4 to 43+/-6 ml/m(2) (P<0.05), end-diastolic LV volume remained unchanged, thus left ventricular ejection fraction increased with pyruvate from 30+/-4 to 39+/-4% (P<0.05). Maximum rate of LV isovolumic pressure decline (Peak -dP/dt) was significantly increased with pyruvate (from 794+/-94 to 980+/-108 mmHg/s; P<0.05) and mean arterial pressure increased from 80+/-5 to 88+/-4 mmHg (P<0.05). Discontinuation of pyruvate resulted in immediate reversibility of its effects. CONCLUSION: Intracoronary pyruvate improves systolic and diastolic myocardial function and increases ejection fraction without increasing heart rate. Pyruvate thus exhibits the profile of a favourable inotropic agent, however, further investigation for the treatment of patients with acute heart failure is mandatory.     

Nitroprusside infusion in experimental acute myocardial infarction with systemic hypertension: effects on systemic hemodynamics and regional myocardial blood flows

The effects of graded doses of nitroprusside on regional myocardial blood flow were studied in awake, acutely hypertensive dogs with acute myocardial infarction. Acute systemic hypertension was produced by infusing a mixture of norepinephrine and epinephrine for 80 minutes after coronary artery occlusion. The increase in aortic pressure produced by catecholamine infusion was accompanied by increases in heart rate, left ventricular (LV) end-diastolic pressure, first derivative of LV pressure (dP/dt), dP/dt at an LV developed pressure of 50 mm Hg (dP/dt/P) and pressure-rate product, but total peripheral vascular resistance did not change significantly. Two graded doses of nitroprusside were then infused, each for 25 minutes, beginning 30 minutes after the onset of coronary artery occlusion. The smaller dose of nitroprusside returned aortic pressure to control levels and significantly reduced total peripheral vascular resistance and LV end-diastolic pressure, but did not affect cardiac output, heart rate, LV dP/dt, dP/dt/P and pressure-rate product. Regional blood flow increased to both the ischemic and normal myocardium. The larger dose of nitroprusside further reduced aortic pressure and total peripheral vascular resistance and LV end-diastolic pressure and significantly increased heart rate and cardiac output. However, LV dP/dt, dP/dt/P and pressure-rate product remained unchanged. Regional blood flow to normal myocardium increased, but the increase in ischemic endocardial blood flow produced by the smaller dose of nitroprusside was no longer significant when the larger dose was administered. These changes were not produced by administration of normal saline solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between ionized calcium concentration and ventricular pump performance in the dog under hemodynamically controlled conditions

The effect of plasma ionized calcium concentration on left ventricular function was studied in the canine heart on right heart bypass. Stroke volume, mean arterial pressure and heart rate were controlled. Plasma ionized calcium was lowered to 0.58 ± 0.01 mM by citrate infusion and raised to 1.70 ± 0.01 mM by calcium chloride infusion in random order in each dog. Left ventricular function at each of these ionized calcium levels was compared with that in an immediately preceding normocalcemic period. At a constant stroke work (16.9 ± 0.2 g-m), sustained hypercalcemia was associated with a small decrease in left ventricular end-diastolic pressure (1.7 ± 0.7 cm H₂O, p <0.05) despite a marked increase in peak left ventricular dP/dt (first derivative of ventricular pressure) averaging 34 percent (p <0.001). Coronary blood flow, tension-time index and myocardial oxygen consumption were not significantly altered. Stroke work determined at a left ventricular end-diastolic pressure of 14 cm H₂O, by interpolation in left ventricular function curves, was 11 ± 4.4 percent above that at control normocalcemia (p <0.05).At a constant stroke work (16.9 ± 0.2 g-m), sustained hypocalcemia was associated with a marked depression of left ventricular function as demonstrated by a substantial increase (from 4.9 ± 0.3 to 12.7 ± 1.1 cm H₂O, p <0.0001) in left ventricular end-diastolic pressure (p <0.0001), decreased mean systolic ejection rate (p <0.01) and decreased peak left ventricular dP/dt (p <0.0001). Coronary blood flow increased (p <0.05) whereas myocardial oxygen consumption did not change significantly. A marked displacement of left ventricular function curves to the right (compared with curves obtained during normocalcemia) was observed, and stroke work determined at a left ventricular end-diastolic pressure of 14 cm H₂O was 52 ± 5.4 percent below control level (p <0.001).It appears that hypercalcemia, when initiated from a normal control level, provides only a small enhancement of ventricular pump performance (as indexed by the stroke work-left ventricular end-diastolic pressure relation) despite a marked increase in peak left ventricular dP/dt, whereas marked improvement of left ventricular performance may be expected when calcium infusion is initiated from an ionized calcium level that is below normal.     

Haemodynamic effects of ICI 118,587 in cardiomyopathy.

The haemodynamic effects of a new beta 1-adrenoceptor partial agonist, ICI 118,587, were studied in 10 patients with dilated cardiomyopathy and moderate to severe cardiac failure. Simultaneous right and left heart catheterisations were performed. Resting central haemodynamic indices were measured before and 15 min after an intravenous dose of 0.05 mg/kg and then 15 min after an additional intravenous dose of 0.15 mg/kg of ICI 118,587. Left ventricular performance was improved--as shown by significant increases in systolic left ventricular pressure, maximum rate of rise in left ventricular pressure (dP/dt max), and cardiac output and a decrease in left ventricular end diastolic pressure--without an undesirable increase in heart rate. The top of the dose response curve was reached after the lower dose. An important unwanted effect was seen in the most severely diseased patient, whose left ventricular systolic pressure, dP/dt max, and cardiac output decreased. This was probably due to the drug's antagonistic property supervening in this patient, who probably had high concentrations of circulating catecholamines. It is concluded that ICI 118,587 has a positive inotropic action and improves cardiac performance in patients with dilated cardiomyopathy and moderate cardiac failure, although care should be exercised when the drug is given intravenously in severe failure.     

Haemodynamic effects of ICI 118,587 in cardiomyopathy

The haemodynamic effects of a new beta 1-adrenoceptor partial agonist, ICI 118,587, were studied in 10 patients with dilated cardiomyopathy and moderate to severe cardiac failure. Simultaneous right and left heart catheterisations were performed. Resting central haemodynamic indices were measured before and 15 min after an intravenous dose of 0.05 mg/kg and then 15 min after an additional intravenous dose of 0.15 mg/kg of ICI 118,587. Left ventricular performance was improved--as shown by significant increases in systolic left ventricular pressure, maximum rate of rise in left ventricular pressure (dP/dt max), and cardiac output and a decrease in left ventricular end diastolic pressure--without an undesirable increase in heart rate. The top of the dose response curve was reached after the lower dose. An important unwanted effect was seen in the most severely diseased patient, whose left ventricular systolic pressure, dP/dt max, and cardiac output decreased. This was probably due to the drug's antagonistic property supervening in this patient, who probably had high concentrations of circulating catecholamines. It is concluded that ICI 118,587 has a positive inotropic action and improves cardiac performance in patients with dilated cardiomyopathy and moderate cardiac failure, although care should be exercised when the drug is given intravenously in severe failure.     

快速右心室起搏心力衰竭犬模型的建立

目的应用改进的快速右心室起搏的方法制备慢性心力衰竭犬模型,分析模型相应的临床和血流动力学及病理变化。方法选择比格犬12只,随机分为起搏组(7只)和对照组(5只),起搏组采用230 ppm的频率快速右心室起搏4周,之后改用180 ppm的频率维持右心室起搏4周。对照组正常喂养不处理,4周后测量相应指标。起搏组起搏前、起搏1、8周后,分别行心脏超声、血流动力学检测,之后处死取心脏做病理切片检查。结果与对照组和同组起搏前比较,起搏组犬起搏4、8周后,出现慢性心力衰竭的相应临床表现;超声心动图示各心腔内径均变大,左心室射血分数明显下降,左心导管示左心室舒张末压力增加,左心室收缩末压力及左心室内压最大上升及下降速率降低,差异有统计学意义(P<0.05,P<0.01)。结论经过改进的快速右心室起搏方法,可以产生相对稳定的慢性心力衰竭犬模型。