Dobutamine Administration Research Articles

Dobutamine enhances cardiodepressant effects of receptor-mediated coronary endothelial stimulation.

In humans, intracoronary infusion of substance P reduces left ventricular end-systolic pressure and left ventricular peak systolic pressure because of earlier onset of left ventricular relaxation induced by paracrine myocardial action of mediators released from the coronary endothelium. The present study investigated in humans the effects of beta-adrenergic stimulation, which also induces earlier left ventricular relaxation, on the left ventricular myocardial contractile response to intracoronary infusion of substance P. Data were obtained in 13 patients after cardiac transplantation and in 3 patients with dilated nonischemic cardiomyopathy. Microtip left ventricular pressure recordings were obtained during a 5-minute intracoronary infusion of substance P (20 pmol/min) under control conditions and then repeated during concurrent intravenous administration of dobutamine. In the presence of dobutamine, intracoronary substance P caused a greater fall in left ventricular end-systolic pressure (transplantation control, -9 +/- 11 versus transplantation dobutamine, -20 +/- 18 mm Hg [P < .05]; cardiomyopathy control, -4 +/- 1 versus cardiomyopathy dobutamine, -10 +/- 3 mm Hg [P < .05]) and in left ventricular peak systolic pressure (transplantation control, -14 +/- 10 versus transplantation dobutamine, -30 +/- 22 mm Hg [P < .01]; cardiomyopathy control, -9 +/- 7 versus cardiomyopathy dobutamine, -15 +/- 6 mm Hg [P = .1]). Dobutamine enhances the cardiodepressant effect on myocardial contractile performance of receptor-mediated coronary endothelial stimulation in transplant recipients and in patients with dilated nonischemic cardiomyopathy. This enhancement could result from a potentiating interaction of the relaxation-hastening effect exerted by beta-adrenergic stimulation and by mediators released from the coronary endothelium, such as nitric oxide.

Regional Myocardial Stiffness Measured by a New Tactile Sensor System.

Numerous investigators have attempted to measure regional wall stress directly. However, the measurement systems and devices employed have been too complex for accurate quantification in situ. We have developed a new tactile sensor system for measuring accurately myocardial stiffness in situ and validated its use for estimation of myocardial contractile function. The tactile sensor was placed on the left ventricle of five mongrel dogs, (weighing 12-17 kg) and myocardial stiffness (g/mm2) was measured. Dobutamine (5.0 micrograms/kg/min) and propranolol (0.25 mg/kg) were sequentially administrated intravenously, and the change in myocardial stiffness was monitored. Myocardial stiffness followed a time course similar to that of left ventricular pressure, indicating a close relationship with wall stress. Baseline end-systolic stiffness in 5 dogs was 2.38 +/- 0.19 g/mm2. After administration of dobutamine, end-systolic stiffness increased to 3.26 +/- 0.32 g/mm2 (p < 0.01). After the administration of propranolol, end-systolic stiffness decreased significantly to 1.83 +/- 0.19 g/mm2 (p < 0.01), compared with the baseline values. Regional myocardial stiffness of a beating heart can be measured precisely using our new tactile sensor system. End-systolic stiffness is a useful index for accurate quantification of the regional myocardial contractile state.

Symptomatic and hemodynamic recovery following dobutamine stress echo: benefit of low-dose esmolol administration.

We studied the use of esmolol in patients experiencing minor side effects of palpitations, anxiety, nervousness, and tremors associated with dobutamine stress echocardiography. Dobutamine stress echocardiography is frequently used in the assessment of coronary artery disease. Esmolol administration may enhance patient comfort. Sixty consecutive patients who experienced minor side-effects during dobutamine stress echocardiography were given 0.3 mg/kg esmolol intravenously in the recovery period and compared retrospectively to sixty consecutive controls who underwent dobutamine stress echocardiography, who did not receive esmolol, during the same time period. Both groups were matched for age, ejection fraction, and peak dose of dobutamine. Heart rate and blood pressure were assessed during and after dobutamine administration. Both groups had similar baseline blood pressure (mmHg) (142 +/- 19/72 +/- 14 vs 139 +/- 20/72 +/- 14) and heart rate (beats per minute) (75 +/- 14 vs 75 +/- 17) (esmolol and control respectively, p = ns), but peak heart rate was higher in the esmolol group (126 +/- 14 vs. 116 +/- 14, p < 0.01). In the group who received esmolol, symptomatic relief paralleled the statistically significant decrease in heart rate which occurred within 1 minute of esmolol administration (99.7 +/- 15.3 vs 108.5 +/- 13.1 p < 0.0001); the heart rate in the esmolol group remained significantly lower than the control group for 5 minutes following esmolol administration (92.0 +/- 10.3 vs 96.7 +/- 11.8 p < 0.05). As a percentage of peak heart rate the esmolol group remained significantly lower than the control for 7 minutes (74% vs 80% p < 0.05). Esmolol induced a significant reversal of dobutamine-induced diastolic hypotension (diastolic blood pressure at peak 66 +/- 17 vs 8 min recovery 70 +/- 12, p < 0.03) that was not seen in controls (diastolic blood pressure at peak 64 +/- 18 vs 8 min recovery 65 +/- 14, p = ns). Systolic blood pressure and heart rate remained elevated in both groups 8 min into recovery compared to baseline, suggesting persistent dobutamine effect beyond the expected 2 min pharmacologic half-life of dobutamine. No side-effects from esmolol were seen despite it being used in 9 patients with EF < 35%. Esmolol is effective and well tolerated for the management of dobutamine-related minor side-effects. The mechanism of benefit, in addition to heart rate reduction, may involve a reversal of dobutamine-induced diastolic hypotension. Blood pressure and heart rate recovery are slower than expected from previously published pharmacokinetic data.

Measurement of cardiac output by transoesophageal Doppler echocardiography in anaesthetized horses: comparison with thermodilution

In order to determine if transoesophageal Doppler echocardiography could be used to estimate cardiac output in anaesthetized horses, we have compared the technique with estimations of cardiac output by thermodilution in eight healthy adult thoroughbreds. Measurements of aortic blood flow velocity were made by high pulse repetition frequency (HPRF) and continuous wave (CW) Doppler echocardiography from a 3.5-MHz transoesophageal probe. Cardiac output was increased during the study by administration of dobutamine, providing a range of cardiac output measurements by thermodilution from 15.0 to 64.4 liter min-1. Estimations derived from CW Doppler overestimated cardiac output compared with thermodilution (bias = 4.0 litre min-1). Estimations from HPRF Doppler echocardiography more closely reflected measurements obtained by thermodilution (bias = 0.7 litre min-1). Limits of agreement between the techniques were similar for both modes of insonation (HPRF = -7.7 to 9.1 litre min-1, CW = -4.9 to 12.8 litre min-1). There were significant differences in bias between both Doppler techniques and thermodilution for individual horses. As a result, for any individual horse, limits of agreement between the techniques were closer (HPRF = +/- 6.4 litre min-1, CW = +/- 7.6 litre min-1). We conclude that transoesophageal echocardiography provided an alternative, effective and non-invasive method for measurement of cardiac output in anaesthetized horses.

Interleukin-6 correlates with hemodynamic impairment during dobutamine administration in chronic heart failure

Proinflammatory cytokines have been implicated in the pathophysiology of chronic heart failure. We determined mixed venous levels of interleukin-6 (IL6) in 18 heart transplant candidates before, 1, 4, and 24 h after initiation of dobutamine infusion (3 μg/kg/min) during hemodynamic evaluation. During the first 4 h of dobutamine, systemic vascular resistance decreased (1358 to 1024 dyn × s × cm −5, P = 0.01) while cardiac index (2.3 to 2.9 l/min/m 2, P = 0.008) increased. Both returned to baseline after 24 h. IL6 was elevated at baseline compared to age-matched controls (1.5 ( 0 4.3 ) vs. 0 ( 0 0.5 ), P = 0.003). There was an increase in IL6 from 1.5 ( 0 4.3 ) to 3.6 ( 0.3 5.3 ) pg/ml after 24 h ( P = 0.04). We found higher IL6 levels in the sicker half of patients as defined by pulmonary capillary wedge pressure >24 mmHg ( P = 0.005), mean pulmonary arterial pressure ≥35 mmHg ( P = 0.01), right atrial pressure >13 mmHg ( P = 0.02), and heart rate ≥87/min ( P = 0.02) as well as mean arterial pressure <82 mmHg ( P = 0.005). In conclusion, in this pilot study IL6 correlates with the severity of chronic heart failure during low dose dobutamine infusion.

Effects of dobutamine and enoximone on transmitral and pulmonary venous flow characteristics in patients with left ventricular dysfunction after coronary artery bypass grafting

To assess the effects of dobutamine and enoximone on transmitral (TMF) and pulmonary venous flow (PVF) characteristics. Prospective and randomized. A university hospital intensive care unit. Thirty patients with moderate left ventricular dysfunction after coronary artery bypass grafting (CABG). Patients received either dobutamine, 10 micrograms/kg/min, or enoximone, 20 micrograms/kg/min, for the treatment of a low cardiac index (CI) (< 2.2 L/min/m2). Both drugs significantly (p < 0.05) increased CI from 1.91 +/- 0.17 (dobutamine) and 1.97 +/- 0.17 (enoximone) at baseline to 2.86 +/- 0.70 and 2.84 +/- 0.39 L/min/m2, respectively. Compared with the enoximone (enox)-treated group, the administration of dobutamine (dob) resulted in significantly (p < 0.05) greater increases in mean arterial pressure (dob: 18 +/- 9% v enox: -2 +/- 7%), heart rate (dob: 24 +/- 13% v enox: 3 +/- 5%) and pulmonary artery pressure (dob: 5 +/- 10% v enox: -4 +/- 9%). In contrast, the increase in stroke volume index was significantly less in the dobutamine-treated group (dob: 22 +/- 27% v enox: 41 +/- 21%). The TMF indices, peak E, and peak A wave increased significantly (p < 0.05) after both dobutamine (baseline: 37.3 +/- 6.7 and 41.1 +/- 9.3; max dose: 42.4 +/- 4.3 and 49.0 +/- 10.2 cm/s) and enoximone (baseline: 36.2 +/- 7.5 and 44.2 +/- 10.9; max dose: 40.5 +/- 5.0 and 49.4 +/- 12.1 cm/s) without significantly altering the E/A ratio. Only dobutamine significantly (p < 0.05) decreased isovolumic relaxation time from 109 +/- 24 to 94 +/- 21 ms. There was no significant change in isovolumic relaxation time between the dobutamine (-12% +/- 17%)- and the enoximone (-4% +/- 21%)- treated group. PVF recordings demonstrated a significant increase in time velocity integrals of the S wave with both dobutamine (12.2 +/- 3.1 v 13.7 +/- 3.2 cm) and enoximone (11.0 +/- 3.0 v 12.2 +/- 3.2 cm). No changes in the systolic fraction of the PVF were noted. There were no major differences in parameters reflecting diastolic function between the dobutamine- and the enoximone-treated groups.

Early aneurysm surgery and dehydration therapy in patients with severe subarachnoid haemorrhage without ICH.

We prospectively analysed treatment results in patients with severe subarachnoid haemorrhage (SAH) who underwent early aneurysm surgery, and were managed by dehydration therapy. We studied a total of 31 patients with poor-grade SAH including 18 in grade IV, and 13 in grade V according to the WFNS classification system. Patients who were older than 70 years of age, or those with an intracerebral haemorrhage or absent brainstem response were excluded from this study. At surgery, clot evacuation from the peri-brainstem cisterns with/without external decompression was performed following obliteration of the aneurysmal neck. In the early postoperative period, patients were maintained in negative water balance using osmotic diuretics. When delayed ischaemic deficits had manifested themselves, the pulmonary wedge pressure and/or central venous pressure was immediately increased by the rapid injection of albumin until hypovolaemia reverted to normovolaemia with the continuous administration of dobutamine. The outcome at 3 months was good recovery in 16 (52%) patients, moderate disability in 3 (10%), severe disability in 5 (16%), a vegetative state in 1 (3%), and death in 6 (19%). We though that early aneurysm surgery and postoperative dehydration therapy in the acute stages of brain oedema resulting from primary brain damage are effective in the treatment of patients with severe SAH but reversible primary brain damage.

A novel inotropic vasodilator, OPC-18790, reduces myocardial oxygen consumption and improves mechanical efficiency with congestive heart failure

We analyzed the left ventricular (LV) pressure-volume relation and obtained direct measurements of myocardial oxygen consumption (MVo 2) before and after drug administration in 21 patients with New York Heart Association functional class II to III congestive heart failure to compare the mechanoenergetic effects of OPC-18790, a novel inotropic agent, and dobutamine. Pressure-volume data were obtained by the conductance method, and MVo 2 measurements were obtained with a double-thermistor coronary sinus catheter before and after administration of OPC-18790 and dobutamine. The LV end-diastolic volume index decreased significantly without an increase in the heart rate after administration of OPC-18790, unlike that after administration of dobutamine. Both drugs significantly increased the LV contractility index (E max) and caused similar improvements in ventricular-arterial coupling. OPC-18790 significantly reduced MVo 2, whereas dobutamine increased MVo 2. The ratio of the pressure-volume area to myocardial oxygen consumption (PVA/MVo 2) remained unchanged after administration of OPC-18790 and decreased after administration of dobutamine. The ratio of external work to the pressure-volume area (EW/PVA) was similarly increased by both drugs, resulting in an improvement in mechanical efficiency (EW/MVo 2) with OPC-18790 ( p < 0.05) and in a deterioration with dobutamine ( p < 0.05). OPC-18790 had an energetic advantage over dobutamine in spite of its positive inotropic effect. Our findings suggest that OPC-18790 may be useful for the treatment of patients with congestive heart failure.

Recurrent thrombosis of biventricular-support devices associated with accelerated intravascular coagulation and increased heparin requirements

Recurrent thrombosis of biventricular-support devices associated with accelerated intravascular coagulation and increased heparin requirements

Myocardial signal response to dipyridamole and dobutamine: demonstration of the BOLD effect using a double-echo gradient-echo sequence.

The purpose of this study was to examine the differential myocardial signal responses due to the blood oxygen level dependent (BOLD) effect in magnetic resonance imaging (MRI) under differing conditions of myocardial oxygen supply and demand. The signal response was measured when myocardial blood flow was increased in excess of oxygen demand or when flow was increased in response to increased myocardial oxygen demand. Normal volunteers were studied using a segmented, interleaved, double-echo, gradient-echo sequence at baseline conditions and during pharmacological stress with either dipyridamole (n = 5) or dobutamine (n = 6). Changes in T2* in the myocardium during stress were calculated. Peak coronary flow velocity was measured at rest and during stress using a breath-hold phase contrast technique. Administration of dipyridamole induced a 124 +/- 27% increase in coronary blood flow which resulted in a 46 +/- 22% increase in T2*, consistent with a decrease in myocardial venous deoxyhemoglobin concentration as myocardial oxygen supply exceeds demand. In contrast, the administration of dobutamine resulted in a 41 +/- 25% increase in coronary blood flow but no significant change in T2* (-5 +/- 19%), consistent with a lack of change in myocardial venous deoxyhemoglobin concentration and balanced oxygen supply and demand. Thus, alterations in the relationship between myocardial oxygen supply and demand appear to be detectable using BOLD MRI.

Feasibility of simultaneous Tc99m sestamibi and 2D-echo cardiac imaging during dobutamine pharmacologic stress

Feasibility of simultaneous 2D-Echo and SPECT Tc99m Sestamibi imaging during dobutamine infusion was evaluated in a female population with suspected coronary artery disease and scheduled for diagnostic coronary angiography. A total of 49 consecutive subjects were studied. Patients under continuous ECG and 2D-Echo monitoring underwent standard dobutamine infusion at increasing doses to a diagnostic end-point. Tc99m Sestamibi was administered at the peak of the dobutamine effect. With this approach, 35 patients were identified correctly by 2D-Echo (Sensitivity = 60.1%; Specificity = 83.3%; Agreement = 71.4%; k = 0.43). Perfusion imaging with Tc99m Sestamibi resulted in correctly identifying 41 patients (Sensitivity = 83%; Specificity = 84%; Agreement = 83.6%; k = 0.67). Combining information obtained from the two tests resulted in increased specificity (92%) and decreased sensitivity (64%). Simultaneous assessment of perfusion and function with Tc99m Sestamibi and 2D-Echo imaging during dobutamine administration is easily performed without added risk or discomfort to the patient. Tc99m Sestamibi appeared to be slightly superior to 2D-Echo for the detection of CAD in this population, but the difference does not reach conventional statistical significance. The combined use of the two independent tests did not substantially improve the diagnostic accuracy of each method.

Combined low dose dipyridamole-dobutamine stress echocardiography to identify myocardial viability

Objectives. We sought to evaluate the effects of combined administration of infra-low dose dipyridamole and low dose dobutamine on assessment of myocardial viability.Background. Low dose pharmacologic stress echocardiography with either dobutamine or dipyridamolc infusion has been proposed for the recognition of myocardial viability.Methods. Thirty-four patients with rest wall motion dyssynergy by two-dimensional echocardiography and with angiographically proved coronary artery disease underwent in combination with two-dimensional echocardiographic monitoring: 1) low dose (5 to 10 μg/kg per min over 3 min) dobutamine infusion; 2) infra-low dose (0.28 mg/kg over 4 min) dipyridamole infusion; 3) combination of infra-low dose dipyridamole infusion immediately followed by low dose dobutamine infusion (combined dipyridamole-dobutamine).Results. Follow-up rest echocardiography was available in 30 patients. After revascularization, 82 segments showed a contractile improvement of ≥1 grade, whereas 63 segments remained unchanged. The sensitivity of dobutamine, dipyridamole and combined dipyridamole-dobutamine for predicting recovery was 72% (95% confidence interval [CI] 60.9% to 81.3%), 67% (CI 55.8% to 77%) and 94% (CI 86.3% to 97.9%), respectively. The specificity of dipyridamole, dobutamine and combined dipyridamole-dobutamine was 95% (CI 86.7% to 99%), 92% (CI 82.4% to 97.3%) and 89% (CI 78.4% to 95.4%), respectively. The accuracy of the dobutamine, dipyridamole and combined dipyridamole-dobutamine test was 80%, 79% and 92%, respectively (combined dipyridamole-dobutamine vs. dobutamine, p < 0.05; combined dipyridamole-dobutamine vs. dipyridamole, p < 0.01).Conclusions. Infra-low dose dipyridamole added to low dose dobutamine recruits an inotropic reserve in asynergic segments that were nonresponders after either dobutamine or dipyridamole alone and destined to recover after revascularization.

Reduction of left ventricular hypertrophy with St. Jude Medical 19 mm valve prosthesis.

To determine the permissible range of the St. Jude Medical 19 mm valve (SJM19) as an aortic prosthesis, transvalvular maximal pressure gradient (maxPG) and postoperative reduction of left ventricular (LV) hypertrophy were examined in 21 patients (body surface area [BSA] 1.28-1.56 m2, mean 1.42 m2). Doppler echocardiographically measured maxPG at rest was 31 +/- 16 mmHg, which showed no significant difference from the differences in patients' diseases (aortic regurgitation = AR or stenosis = AS), or BSA. The maxPG, also measured during dobutamine administration when they were less than 40 mmHg at rest, increased significantly from 21 +/- 11 mmHg to 32.1 +/- 15 mmHg, having no differences from the differences in diseases or BSA. Reduction of LV hypertrophy was achieved postoperatively (mean postoperative period of ten months), with the reduction rates of 26 +/- 19% in LV mass and 21 +/- 15% in LV cross-sectional area. No significant differences were found between the reduction rates and the differences in the patients' diseases or BSA. These results indicate that, following the implantation of SJM19, LV hypertrophy was reduced in patients with AR as well as with AS, when their BSA values were less than 1.6 m2. However, limited use is recommended because the increase in pressure gradient during exercise cannot be ignored.

Differing autonomic response to dobutamine in the presence and absence of ischemia: Implications for the autonomic contribution to positive inotropic intervention

Although it is well recognized that dobutamine is a powerful positive inotropic agent mediating increased myocardial contractility through direct β-adrenergic stimulation, the mechanism of its overall circulatory effects appears more complex than that which may be ascribed solely to this direct action on the myocardium. Previous investigations have implied that reflex alterations in autonomic balance may contribute significantly to the response to this agent, but direct evidence describing such a response has not been reported. The objective of this investigation was to assess changes in autonomic tone induced by dobutamine in the presence and absence of ischemia through the measurement of heart rate variability in patients undergoing dobutamine stress echocardiography. Of 25 consecutive patients undergoing dobutamine stress echocardiography, 16 were found to have unequivocal evidence for or against the presence of ischemia during dobutamine infusion. Heart rate data from these 16 patients were submitted for spectral analysis of heart rate variability and quantification of parasympathetically governed high-frequency heart rate variability and sympathetically influenced low-frequency heart rate variability. Of the 16 patients nine were not found to have evidence for ischemia (group 1), and seven were found to have echocardiographic findings consistent with dobutamine-induced ischemia (group 2). The two groups significantly differed ( p = 0.04) in the change in parasympathetic tone associated with dobutamine with a significant ( p = 0.04) increase in parasympathetic tone in group 1 and a numeric decrease in group 2. A significant ( p = 0.04) decrease in sympathetic tone was noted in group 1 as reflected by low-frequency heart rate variability with a numeric increase in this measure in group 2. Patients in group 1 had significantly ( p = 0.0007) increased ejection fraction and were found to have a significantly ( p < 0.05) lower peak heart rate with dobutamine administration as compared with patients in group 2, who were not found to have any change in ejection fraction and who had a greater increase in peak heart rate over baseline. These results indicate that in the absence of myocardial ischemia dobutamine administration is associated with a significant increase in parasympathetic tone and reduction of sympathetic drive, which is not seen in patients in whom ischemia develops with dobutamine stimulation. The autonomic changes in the absence of ischemia may represent a reflex response to myocardial mechanoreceptor or arterial baroreceptor stimulation, which does not occur in the presence of ischemia. Therefore these data provide evidence that alterations in autonomic balance contribute significantly to the circulatory response to dobutamine and suggest that such reflex mechanisms contribute to the response to positive inotropic agents in general.

Beneficial cumulative role of both nitroglycerin and dobutamine on right ventricular systolic function in congestive heart failure patients awaiting heart transplantation

End-stage idiopathic dilated cardiomyopathy or ischemic heart disease usually present with very low cardiac output and severe ventricular dysfunction which may require pharmacological support before heart transplantation. Right ventricular ejection fraction might be an important factor of functional capacity and survival in congestive heart failure. In order to test the immediate response of right ventricular hemodynamic parameters to nitroglycerin and dobutamine usually used to treat severe left ventricular dysfunction, we studied 17 congestive heart failure patients (15 men, two women; mean age 55 ± 13 years) with end-stage idiopathic dilated cardiomyopathy ( n = 10) or end-stage ischemic heart disease ( n = 7), left ventricular ejection fraction <35% (mean 22 ± 8%), and sinus rhythm. A well validated thermodilution technique using a dedicated catheter with a fast catheter-computer response, permitting instantaneous measurements of right ventricular ejection fraction, was used. Right ventricular hemodynamic parameters were recorded at baseline, after an intravenous bolus injection of 3 mg nitroglycerin and after an intravenous infusion of dobutamine administered after nitroglycerin until normalization of cardiac index or a maximal dose of 15 μg/kg/min. Pulmonary artery mean pressure significantly decreased after nitroglycerin (43 ± 9 mmHg at baseline vs. 31 ± 10 mmHg after nitroglycerin, P < 0.0001) and did not subsequently change after dobutamine (32 ± 10 mmHg after dobutamine, ns). Cardiac index was not affected by nitroglycerin (1.7 ± 0.4 l/min/m 2 at baseline vs. 2.0 ± 0.3 l/ min/m 2 after nitroglycerin, ns), but dramatically increased after dobutamine (3.0 ± 1.0 l/min/m 2 after dobutamine, P < 0.0001). Concomitantly to the changes of these two parameters, right ventricular ejection fraction progressively increased (14 ± 8% at baseline vs. 20 ± 10% after nitroglycerin ( P < 0.0006) vs. 28 ± 13% after dobutamine ( P < 0.0001)). Progressive increase of right ventricular ejection fraction after administration of nitroglycerin followed by administration of dobutamine suggests the beneficial cumulative role of both medications on right ventricular systolic function in severe congestive heart failure.

Cardiac Function of an Acute Ischemic Heart Failure Model Produced by Microsphere Injection Into the Left Coronary Artery

The authors produced an acute canine heart failure model by injecting microspheres (ø 15.5 ± 0.1 mm, 5 × 105) into the left coronary artery, and characterized the model in terms of the pressure-volume relationship obtained by the conductance catheter method. Cardiodynamics of the microsphere injection group (M group: n = 10) and control group (C group: n = 12) were studied with 1) heart rate, 2) aortic pressure, 3) cardiac output (CO), 4) maximal ventricular elastance, 5) effective arterial elastance/maximal ventricular elastance, and 6) external work/pressure-volume area efficiency. With microsphere injection, CO and external work/pressure-volume area efficiency significantly decreased. With administration of dobutamine (5 mg/kg/ min), CO and maximal ventricular elastance recovered to normal and aortic pressure became higher than normal. These changes in heart rate, aortic pressure, CO, maximal ventricular elastance, and external work/pressure-volume area efficiency in the M group were comparable in percentage to those in the C groups. Cardiodynamics of this heart failure model generally were stable for 3 hrs after microsphere injection. The authors concluded that this model would be an excellent acute heart failure model for investigating hemodynamic effects of circulatory assist devices.ASAIO Journal1995;41:855-862.

Cardiac Function of an Acute Ischemic Heart Failure Model Produced by Microsphere Injection Into the Left Coronary Artery

The authors produced an acute canine heart failure model by injecting microspheres (phi 15.5 +/- 0.1 mm, 5 x 10(5)) into the left coronary artery, and characterized the model in terms of the pressure-volume relationship obtained by the conductance catheter method. Cardiodynamics of the microsphere injection group (M group: n = 10) and control group (C group: n = 12) were studied with 1) heart rate, 2) aortic pressure, 3) cardiac output (CO), 4) maximal ventricular elastance, 5) effective arterial elastance/maximal ventricular elastance, and 6) external work/pressure-volume area efficiency. With microsphere injection, CO and external work/pressure-volume area efficiency significantly decreased. With administration of dobutamine (5 mg/kg/min), CO and maximal ventricular elastance recovered to normal and aortic pressure became higher than normal. These changes in heart rate, aortic pressure, CO, maximal ventricular elastance, and external work/pressure-volume area efficiency in the M group were comparable in percentage to those in the C groups. Cardiodynamics of this heart failure model generally were stable for 3 hrs after microsphere injection. The authors concluded that this model would be an excellent acute heart failure model for investigating hemodynamic effects of circulatory assist devices.

Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

The purpose of the study was to evaluate whether infusion of a beta-adrenergic agonist, prior to and during exercise, could compensate for reduced sympathetic stimulation and correct deficient acceleration of left ventricular relaxation, so preventing a rise in left ventricular filling pressures during exercise after cardiac transplantation. Abnormal left ventricular relaxation kinetics can contribute to exercise-induced diastolic dysfunction of the cardiac allograft. This was demonstrated in transplant recipients whose acceleration of left ventricular relaxation during exercise was almost negligible recently and whose elevation of left ventricular end-diastolic pressure was high. Decreased adrenergic tone due to denervation could be involved in deficient left ventricular lusitropic response to exercise, because acceleration of left ventricular relaxation during exercise depends on adequate sympathetic stimulation. Serial supine bicycle exercise was performed at an identical workload in eight transplant recipients while in the control state and during continuous infusion of dobutamine, titrated before exercise to achieve a heart rate matching the heart rate at peak exercise in the control state. During control exercise, heart rate rose from 87 +/- 8 to 104 +/- 12 beats.min-1 (P < 0.05), left ventricular end-diastolic pressure from 14 +/- 5 to 20 +/- 4 mmHg (P < 0.05), left ventricular dP/dtmax from 1374 +/- 172 to 1854 +/- 278 mmHg.s-1 (P < 0.05), and cardiac output from 5.8 +/- 0.9 to 8.5 +/- 1.1 l.min-1 P < 0.05). There was a small but significant decrease of the time constant of left ventricular pressure decay (T) from 42 +/- 6 to 38 +/- 6 ms (P < 0.05). During dobutamine infusion, exercise resulted in a further increase in heart rate from 108 +/- 11 to 122 +/- 17 mmHg (P < 0.05), in cardiac output from 7.4 +/- 0.9 to 10.3 +/- 2.5 l.min-1 (P < 0.05), and in left ventricular dP/dtmax from 2181 +/- 220 to 2620 +/- 214 mmHg.s-1 (P < 0.05). These values were higher than the measurements obtained at the end of the control exercise run (P < 0.05). T failed to change (29 +/- 4 vs 27 +/- 5 mmHg, P > 0.05) and left ventricular end-diastolic pressure increased from 5 +/- 3 to 11 +/- 5 mmHg (P < 0.05) but remained lower than at the end of the control exercise run (11 +/- 5 vs 20 +/- 4 mmHg, P < 0.05). Compensation for reduced sympathetic stimulation by administration of dobutamine improves exercise haemodynamics in cardiac transplant recipients, but cannot prevent the exercise-induced rise in left ventricular end-diastolic pressure and correct deficient acceleration of left ventricular relaxation. Abnormal exercise haemodynamics after heart transplantation are therefore only partly related to deficient sympathetic stimulation.

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method.

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.

Stress echocardiography: Comparison of exercise, dipyridamole and dobutamine in detecting and predicting the extent of coronary artery disease

This study was designed to compare exercise, dipyridamole and dobutamine echocardiography in the same patients and to evaluate, by measuring physiologic and echocardiographic variables, the mechanisms by which exercise and dobutamine induce ischemia. The diagnostic value of stress echocardiography has been widely reported, but the specific effects of exercise, dipyridamole and dobutamine have not been directly compared. Furthermore, no echocardiography study has evaluated left ventricular volume changes at ischemic threshold during exercise and dobutamine administration. One hundred patients with suspected (Group A, n = 60) or known (Group B, n = 40) coronary artery disease underwent all three tests in random order. In Group A, the sensitivities of exercise (mean 76%, 95% confidence interval [CI] 58% to 94%) and of dobutamine echocardiography (72%, 95% CI 53% to 91%) were higher than that of dipyridamole (52%, 95% CI 31% to 73%; p = 0.01 and p = 0.02, respectively). Specificity did not differ significantly among tests (94% for exercise [95% CI 86% to 100%] and 97% for dipyridamole and dobutamine [95% CI 91% to 100%]). Accuracy was identical for exercise and dobutamine (87%) and higher than that for dipyridamole (78%, p = 0.06). In Group B, the accuracy in predicting coronary disease extent was 71% for exercise, 33% for dipyridamole and 75% for dobutamine. At ischemic threshold, end-systolic volume index and the ratio of systolic blood pressure to end-systolic volume, a variable related to myocardial contractility, were significantly lower and higher, respectively, with dobutamine than during exercise (p < 0.05). In a clinical setting, exercise echocardiography should represent the first diagnostic approach because it has high diagnostic efficacy and provides additional information on exercise capacity; pharmacologic stress, particularly that of dobutamine, provides a pivotal diagnostic tool when exercise is not feasible or its results are nondiagnostic. Our preliminary data on echocardiographic evaluation at ischemic threshold support the view that myocardial contractility is a major factor in inducing ischemia during dobutamine infusion.