A comparison of prostacyclin and sodium nitroprusside for the treatment of heart failure after cardiac surgery

OBJECTIVE: To study the effects of the two vasodilators, prostacyclin and sodium nitroprusside, on central hemodynamics in heart failure after cardiac surgery. DESIGN: Randomized cross-over study. SETTING: Multi-institutional university hospital. PARTICIPANTS: Ten patients. Inclusion criteria: cardiac index less than 2.5 L/min/m2; pulmonary capillary wedge pressure greater than 15 mmHg, systemic vascular resistance index greater than 2,500 dynes.s.cm-5/m2, and treatment with inotropic support. Five patients were treated with intra-aortic balloon counterpulsation. INTERVENTIONS: After control measurements, mean arterial pressure was decreased by 10% to 20% with each vasodilator in each patient. MEASUREMENTS AND RESULTS: Sodium nitroprusside induced decreases in mean pulmonary arterial pressure (-21%), pulmonary capillary wedge pressure (-29%), central venous pressure (-17%), and systemic vascular resistance (-25%), and increases in cardiac output (+7%) and stroke volume (+6%) compared with control. Prostacyclin decreased mean pulmonary arterial pressure (-14%), pulmonary capillary wedge pressure (-19%), central venous pressure (-7%), and systemic (-40%) and pulmonary (-25%) vascular resistances, whereas cardiac output (+25%) and stroke volume (+22%) increased compared with control. Prostacyclin, compared with sodium nitroprusside, induced a more pronounced increase in cardiac output and stroke volume, associated with less pronounced decreases in cardiac filling pressures and more profound decreases in systemic and pulmonary vascular resistances. CONCLUSION: Prostacyclin appears to be a useful agent, superior to sodium nitroprusside, in the treatment of postoperative heart failure in patients with normal or mildly elevated cardiac filling pressures, where vasodilator treatment is indicated.     

Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium

Haemodynamic variables were measured following administration of rocuronium 0.6 mg.kg-1 or vecuronium 0.08 mg.kg-1 (approximately equivalent to 2 x ED95 doses) in patients anaesthetized with fentanyl 50 micrograms.kg-1 and scheduled to undergo elective coronary artery bypass grafting. There were increases in stroke volume index (+15%) and cardiac index (+11%), and a decrease in pulmonary capillary wedge pressure (-25%) following administration of rocuronium (P < 0.05). The changes in heart rate (+7%), mean arterial pressure (-5%), systemic vascular resistance (-12%) and other measured or derived indices were insignificant. In comparison the administration of vecuronium was associated with decreases in heart rate (-7%), mean pulmonary artery pressure (-17%), central venous pressure (-15%) and the rate-pressure product (-9%) (P < 0.05). The changes in mean arterial pressure (-7%), cardiac index (-6%) and systemic vascular resistance (-8%) following vecuronium were insignificant. There were no differences in any of the variables between rocuronium and vecuronium. The absolute values of all variables were, however, within acceptable clinical limits. There was no evidence of histamine release in any patient. The present study shows that rocuronium 0.6 mg.kg-1 is associated with changes of only small magnitude in haemodynamic variables.     

Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension

BACKGROUND: Monitoring left ventricular preload is critical to achieve adequate fluid resuscitation in patients with hypotension and sepsis. This prospective study tested the correlation of the pulmonary artery occlusion pressure, the left ventricular end-diastolic area index measured by transesophageal echocardiography, the arterial systolic pressure variation (the difference between maximal and minimal systolic blood pressure values during one mechanical breath), and its delta down (dDown) component (= apneic - minimum systolic blood pressure) with the response of cardiac output to volume expansion during sepsis. METHODS: Preload parameters were measured at baseline and during graded volume expansion (increments of 500 ml) in 15 patients with sepsis-induced hypotension who required mechanical ventilation. Each volume-loading step (VLS) was classified as a responder (increase in stroke volume index > or = 15%) or a nonresponder. Successive VLSs were performed until a nonresponder VLS was obtained. RESULTS: Thirty-five VLSs (21 responders) were performed. Fluid loading caused an overall significant increase in pulmonary artery occlusion pressure and end-diastolic area index, and a significant decrease in systolic pressure variation and delta down (P < 0.01). There was a significant difference between responder and nonresponder VLSs in end-diastolic area index, systolic pressure variation, and dDown, but not in pulmonary artery occlusion pressure. Receiver-operator curve analysis showed that dDown was a more accurate indicator of the response of stroke volume index to volume loading than end-diastolic area index and pulmonary artery occlusion pressure. A dDown component of more than 5 mmHg indicated that the stroke volume index would increase in response to a subsequent fluid challenge (positive and negative predictive values: 95% and 93%, respectively). CONCLUSION: The dDown component of the systolic pressure variation is a sensitive indicator of the response of cardiac output to volume infusion in patient with sepsis-induced hypotension who require mechanical ventilation.     

Acute cardiovascular effects of insulin-like growth factor I in patients with chronic heart failure

Insulin-like growth factor I (IGF-I) enhances myofibrillar development in cardiomyocytes of rats in culture and in vivo. In addition, IGF-I has vasodilatory effects and improves cardiac function in healthy volunteers. This study was conducted to evaluate the acute hemodynamic effects of IGF-I in patients with chronic heart failure Eight patients with chronic heart failure were randomized to receive recombinant human IGF-I (60 micrograms/kg) or placebo, i.v., over 4 h in a cross-over, double blind study on 2 consecutive days. Electrocardiogram as well as systemic hemodynamics were continuously monitored over 7 h by flow-guided thermodilution and radial artery catheters. IGF-I was well tolerated by all patients, and no pathological changes on electrocardiogram were recorded. Compared with placebo, IGF-I increased the cardiac index by 27 +/- 3.7% (+/- SE; P < 0.0005) and the stroke volume index by 21 +/- 5.6% (P < 0.05), and decreased systemic vascular resistance by 28 +/- 4.4% (P < 0.0002), right atrial pressure by 33 +/- 9.0% (P < 0.003), and pulmonary artery wedge pressure by 25 +/- 6.1% (P < 0.03). Mean systemic and pulmonary artery pressure as well as heart rate and pulmonary vascular resistance were not significantly influenced by IGF-I treatment. Insulin and C peptide levels were decreased by IGF-I, whereas glucose and electrolyte levels remained unchanged. Urinary levels of norepinephrine decreased significantly (P < 0.05) during IGF-I infusion. Thus, acute administration of IGF-I in patients with chronic heart failure is safe and improves cardiac performance by afterload reduction and possibly by positive inotropic effects. Further investigations to establish whether the observed acute effects of IGF-I are maintained during chronic therapy appear to be warranted.     

Afterload reduction therapy with nitroprusside in severe aortic regurgitation: improved cardiac performance and reduced regurgitant volume

To assess the hemodynamic effects of afterload reduction in severe aortic regurgitation, nitroprusside was infused at cardiac catheterization in 12 patients with aortic regurgitation. Cardiac hemodynamics, angiographic variables and regurgitant volumes were quantified during control periods, and nitroprusside was infused to reduce systemic systolic pressure to 110 to 125 mm Hg. The following were reduced by the drug: systolic arterial pressure (from 154 +/- 6.4 to 115 +/- 2.3 mm Hg, P less than 0.001); left ventricular end-diastolic pressure (from 23 +/- 2.2 to 11 +/- 1.0 mm Hg, P less than 0.001); systemic vascular resistance (from 1,782 +/- 133 to 1,148 +/- 94 dynes sec cm-5, P less than 0.001); left ventricular end-diastolic volume (from 242 +/- 25 to 196 +/- 19 ml, P less than 0.001); aortic regurgitant fraction (from 0.53 +/- 0.05 to 0.44 +/- 0.06, P less than 0.01); and aortic regurgitant minute volume (from 5.5 +/- 0.10 to 4.3 +/- 0.09 liters/min, P less than 0.01). Effective cardiac index increased (from 2.49 +/- 0.19 to 3.10 +/- 0.24 liters/min per m2, P less than 0.01), and left ventricular ejection fraction rose (from 0.55 +/- 0.03 to 0.61 +/- 0.03, P less than 0.005). These data indicate that afterload reduction with nitroprusside in severe aortic regurgitation improves cardiac performance, greatly decreases left ventricular preload and reduces aortic regurgitant volume. Thus, nitroprusside therapy has special value in severe aortic regurgitation that is of particular benefit in critical clinical conditions.     

Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism

The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min-1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and autonomic effects of intravenous saterinone in patients with chronic heart failure

In this study, the hemodynamic and neurohumoral/autonomic effects of intravenous saterinone (a selective phosphodiesterase type III inhibitor, with additional alpha 1-blocking properties) were evaluated. In a double-blind, placebo-controlled design, 36 patients with moderate to severe heart failure were studied (saterinone, n = 24; placebo, n = 12). Invasive hemodynamic measurements, by using right-heart catheterization, were performed, as well as measurement of plasma neurohormones and analysis of heart rate variability (HRV), to study drug influences on neurohumoral activation and autonomic tone. Systemic vascular resistance significantly decreased during saterinone infusion, accompanied by a decrease in systemic blood pressure (both p values < 0.05) and an increase in heart rate (p = 0.05). Filling pressures also decreased during saterinone, but this was statistically significant only for pulmonary capillary wedge pressure, whereas the cardiac index remained unaffected. Plasma neurohormones (norepinephrine, epinephrine, and renin activity) were not significantly influenced by saterinone. HRV analysis revealed no significant effect of saterinone on autonomic tone. These results suggest that intravenous saterinone has a significant vasodilating effect in patients with moderate to severe chronic heart failure (CHF), without exerting an adverse effect on the autonomic nervous system, as demonstrated by assessment of plasma neurohormones and HRV analysis.     

Use of 201Thallium brain SPECT, image registration, and semi-quantitative analysis in the follow-up of brain tumors

BACKGROUND: Vasodilator drugs are increasingly being discussed as possible antiglaucomatous substances. Aim of the present study is to evaluate, from a hemodynamic point of view, the vasodilator drug isosorbide dinitrate (ISDN) regarding its suitability for glaucoma therapy. METHODS: 20 healthy subjects (mean age: 28 yrs) volunteered to participate in the study. In randomized order, each subject received one tablet containing 40 mg ISDN (sequels) or--in a second trial--one tablet placebo (+500 mg of the analgetic metamizol, respectively, for prophylaxis of nitrate headache). 1 h before as well as 1, 3, 5, and 7 hrs after medication, the following variables were determined using oculo-oscillo-dynamography: systolic ophthalmic artery pressure (SOAP), systolic ocular perfusion pressure (SOPP), ocular pulsation amplitude (OPA) and the product OPA x heart rate (HR). Intraocular pressure (IOP) as well as systolic and diastolic brachial artery pressures (SBAP, DBAP) were also measured. RESULTS: After administration of ISDN (+analgetic), the variables SBAP, SOAP and SOPP were significantly (p = 0.01) lowered compared to placebo (+analgetic), and also the IOP tended to be lower (p = 0.08). The maximum reduction was found 3-5 hrs after medication: SBAP 10.9 mm Hg (9%), SOAP 12.5 mm Hg (14%), SOPP 11.3 mm Hg (14.5%), and IOP 1.5 mm Hg (12%). The relation SOAP vs. SBAP was significantly (p = 0.0004) linear, the correlation coefficient amounted to 0.39. DBAP remained unchanged, HR was increased by 4-7 beats/min (p = 0.08). OPA and the product OPA x HR showed highly significant decreases by maximum values of 44% and 40%, respectively. CONCLUSION: ISDN (+analgetic) caused a reduction of SOAP and SOPP, which can be accounted for by the reduced systolic systemic blood pressure. In addition, there was a decrease of OPA and of the product OPA x HR (a measure of pulsatile ocular blood flow), which finding may be explained by a cardiac stroke volume reduction that is typical for nitrates. Due to these hemodynamic effects and due to the only weak IOP reduction, ISDN does not appear to be suitable for glaucoma therapy.     

Mechanism of adenosine-induced elevation of pulmonary capillary wedge pressure in humans

BACKGROUND: Continuous intravenous administration of adenosine to humans often results in a paradoxical rise in pulmonary capillary wedge pressure (PCWP), whereas arterial resistance is lowered and cardiac output and heart rate increase. This is believed to be due to diastolic stiffening of the ventricle or to a negative inotropic effect. In the present study, we tested these and other mechanisms by using pressure-volume (PV) analysis and echocardiography. METHODS AND RESULTS: Fifteen patients with normal rest left ventricular function underwent cardiac catheterization and received adenosine at a rate of 140 micrograms/kg per minute IV for 6 to 10 minutes. PV relations were measured in 9 patients (without coronary artery disease) using the conductance catheter method. In 6 additional patients with coronary artery disease, echocardiograms were used to assess wall thickness and function, and aortic and coronary sinus blood, lactate, oxygen, and adenosine levels were measured. Adenosine increased PCWP by 19% (+2.6 mm Hg) in both patient groups while lowering arterial load by 30% and increasing cardiac output by 45% (all P < .001). There was no significant effect of adenosine on mean linear chamber compliance or monoexponential elastic stiffness, as the diastolic PV relation was unchanged in most patients. Diastolic wall thickness also was unaltered. Thus, the PCWP rise did not appear to be due to diastolic stiffening. Adenosine induced a rightward shift of the end-systolic PV relation (ESPVR) (+12.7 +/- 3.7 mL) without a slope change. This shift likely reflected effects of afterload reduction, as other indexes (stroke work-end-diastolic volume relation and dP/dtmax at matched preload) were either unchanged or increased. Furthermore, this modest shift in ESPVR was more than compensated for by vasodilation and tachycardia, so reduced systolic function could not explain the increase in PCWP. There also was no net lactate production to suggest ischemia. Rather than arising from direct myocardial effects, PCWP elevation was most easily explained by a change in vascular loading, as both left ventricular end-diastolic volume and right atrial pressure increased (P < .05). This suggests that adenosine induced a redistribution of blood volume toward the central thorax. CONCLUSIONS: PCWP elevation in response to adenosine primarily results from changes in vascular loading rather than from direct effects on cardiac diastolic or systolic function.     

Enhancement of latent inhibition in the rat by the atypical antipsychotic agent remoxipride

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.     

Determinants of the pulmonary artery pressure rise in left ventricular dysfunction

Pulmonary artery hypertension in patients with left ventricular dysfunction is related to poor outcome but the role of cardiac functional abnormalities in the genesis of pulmonary hypertension remains unknown. The aim of this prospective study was to identify the determinants of pulmonary hypertension in 102 consecutive patients with primary left ventricular dysfunction (ejection fraction < 50%). Systolic pulmonary artery pressure was measured by continuous wave Doppler. Left ventricular systolic and diastolic function, severity of functional mitral regurgitation, cardiac output, and left atrial volume were assessed using Doppler echocardiography. In patients with left ventricular dysfunction, systolic pulmonary artery pressure was increased (51 +/- 14 mmHg, range 23 to 87 mmHg). Mitral deceleration time (r = -0.61; p = 0.0001) and mitral effective regurgitant orifice (r = 0.50; p = 0.0001) were the strongest parameters related to systolic pulmonary artery pressure. Multivariate analysis identified these two variables as the strongest predictors of systolic pulmonary artery pressure in association with the mitral E/A ratio (p = 0.006) and age (p = 0.005). In conclusion, pulmonary hypertension is common and variable in patients with left ventricular dysfunction. It is closely related to diastolic dysfunction and severity of functional mitral regurgitation but not independently to the degree of left ventricular systolic dysfunction. These findings underline the importance of assessing diastolic function and quantifying mitral regurgitation in patients with left ventricular dysfunction.     

Central venous pressure, pulmonary capillary wedge pressure and intrathoracic blood volumes as preload indicators in cardiac surgery patients

OBJECTIVE: Monitoring of cardiac preload is mainly performed by measurement of central venous and pulmonary capillary wedge pressure in combination with assessment of cardiac output, applying the pulmonary arterial thermal dilution technique. However, the filling pressures are negatively influenced by mechanical ventilation and the pulmonary artery catheter is criticized because of its inherent risks. Measurement of right atria, right ventricular, global end diastolic and intrathoracic blood volume index by arterial thermal dye dilution utilizing the COLD-system may represent an alternative. METHODS: In 30 CABG patients with an uncomplicated postoperative course the mentioned parameters were measured 1, 3, 6, 12 and 24 h postoperatively to prove their qualification as preload indicators: As patients received no inotropic support, changes of cardiac index and stroke volume index must correlate to changes of presumably preload indicating parameters. RESULTS: When arterial and pulmonary arterial thermal dilution were compared, no differences were found; the correlation coefficient being 0.96, the bias 0.16 l/min per m2 (2.4%) and coefficients of variation did not exceed 7%. Changes of central venous pressure, capillary wedge pressure, right atrial end diastolic volume index and right ventricular end diastolic volume index did not correlate at all to changes of cardiac and stroke volume index (coefficients ranged from -0.01 to 0.28). In contrast, intrathoracic and global end diastolic blood volume indices with coefficients from 0.76 to 0.87, did show a good correlation to cardiac and stroke volume index. CONCLUSION: Central venous pressure, capillary wedge pressure, right atrial and right ventricular end diastolic volumes are no suitable preload parameters in cardiac surgery intensive care, compared to intrathoracic and global end diastolic blood volumes. The latter show a higher clinical value and can be obtained by less invasive methods, as no pulmonary artery catheter is required.     

Haemodynamic changes in neurogenic pulmonary oedema: effect of dobutamine

The haemodynamic and gas exchange abnormalities occurring in neurogenic pulmonary oedema (NPO) were examined retrospectively in 20 patients admitted to the Intensive Therapy Unit (ITU) over a 45-month period (February 1992 to November 1995). In 12 patients, where vasoactive therapy with dobutamine was employed, its effect on haemodynamics was examined. Cardiac index (CI median 2.2 l min-1 m-2) and left ventricular stroke work index (LVSWI 20 g.m.m-2) were markedly depressed, while pulmonary artery wedge pressure (PAWP 17 mmHg), mean pulmonary artery pressure (MPAP 30.5 mmHg), systemic vascular resistance index (SVRI 2852 dyne.s.cm-5.m2) and pulmonary vascular resistance index (PVRI 393 dyne.s.cm-5.m2) were substantially elevated above normal values. Mean arterial pressure (MAP 82.5 mmHg) and heart rate (HR 102 bpm) were within normal limits. The poor oxygenation is indicated by a median PaO2/fiO2 ratio of 18.0 kPa. Patients treated with dobutamine showed significant increases in CI and LVSWI and significant falls in SVRI and PAWP at 2 and 6 h after institution of therapy, and there was a significant rise in PaO2/fiO2 ratio to 27.8 kPa at 6 h. NPO was generally associated with severe depression of myocardial function and elevation of pulmonary vascular pressures. This dysfunction was readily reversed by dobutamine.     

Right ventricular size is acutely decreased by inhaled nitric oxide in newborns with pulmonary hypertension

The pressure and volume demands of the right and left ventricles may dramatically change following selective pulmonary vasodilation in newborns with pulmonary hypertension. Thus, ventricular planimetry was performed by two-dimensional echocardiography in 35 newborns with lung disease and increased pulmonary vascular resistance who were treated with inhaled nitric oxide to determine the influence of therapy on right and left ventricular size and function. The end-diastolic and end-systolic areas of each ventricle were measured from apical 4-chamber images before, and 30 to 60 minutes after, the onset of 20 parts per million inhaled nitric oxide. Estimates of ventricular function were determined by the systolic decrease in ventricular area, (diastolic area - systolic area) x 100/diastolic area. Heart rate, systemic blood pressure, and left ventricular areas did not change. However, the oxygenation index, the proportion of right-to-left ductal shunt (nonrestrictive ductus arteriosus, n = 22), the systolic pulmonary arterial pressure (closed or restrictive ductus arteriosus, n = 13), and the right ventricular diastolic and systolic areas were decreased after nitric oxide inhalation. The baseline systolic decrease in left ventricular area was lower in a subgroup of patients who developed an increase in left ventricular diastolic area following nitric oxide inhalation. Thus, nitric oxide improves pulmonary hemodynamics and decreases right ventricular size in newborns with lung disease and pulmonary hypertension. However, newborns may develop an increase in left ventricular size if left ventricular function is decreased prior to therapy.     

Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease

Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 microg/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 microg/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5+/-13% vs +1+/-13%, p=0.386) and flow (+179+/-90% vs +169+/-96%, p=0.756), or in the systolic wall thickening responses (+134+/-65% vs +118+/-57%, p=0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121+/-73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129+/-48%, p=0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia.     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart failure

BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective pulmonary vasodilator. Reports of increases in left ventricular end-diastolic pressure and episodes of pulmonary edema during the clinical use of inhaled nitric oxide in patients with preexisting left ventricular dysfunction have raised concerns that this agent may have myocardial depressant effects. We therefore undertook a study of the effects of inhaled nitric oxide on myocardial contractility in a porcine model of ventricular failure and pulmonary hypertension. METHODS: After inducing heart failure in 10 pigs by rapid ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the conductance method) were obtained in six animals at baseline and during administration of inhaled nitric oxide at concentrations of 20 and 40 ppm. Myocardial contractile state was assessed by the end-systolic pressure-volume relationship and preload-recruitable stroke work, whereas diastolic function was measured in terms of the end-diastolic pressure-volume relationship and the pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart failure and pulmonary hypertension, and inhaled nitric oxide induced significant reductions in mean pulmonary artery pressure and pulmonary vascular resistance. Although left ventricular end-diastolic pressure increased during administration of inhaled nitric oxide, no changes were observed in measures of systolic or diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular resistance but did not alter myocardial contractility or diastolic function. Increases in left ventricular end-diastolic pressure during inhaled nitric oxide therapy are therefore not due to myocardial depression and may be related to increases in volume delivery to the left side of the heart resulting from reduced pulmonary vascular resistance.     

Early hemodynamic effects of olprinone hydrochloride after coronary artery bypass grafting

Our purpose was to evaluate the hemodynamic effects of olprinone hydrochloride early after coronary artery bypass grafting (CABG). Fifteen patients undergoing CABG were administered a constant infusion of 0.1 microgram/kg/min of olprinone and continued for 4 hours. No bolus infusion of olprinone was administered before continuous infusion. Systolic systemic arterial pressure, systolic pulmonary arterial pressure, systemic vascular resistance and pulmonary vascular resistance were significantly decreased. There were no significant changes in heart rate, mean central venous pressure, mean left atrial pressure and left ventricular stroke work index. Cardiac index was significantly increased, but a correlation between cardiac index and mixed venous blood oxygen saturation was not found. Double product was significantly decreased, which described above suggest that olprinone achieved improvement of left cardiac function without more myocardial oxygen consumption. Severe transient hypotension (systolic arterial pressure < 80 mmHg) after infusion of olprinone was observed in three patients. Olprinone administered soon after CABG surgery had beneficial effects in terms of improvement of hemodynamic status without more oxygen consumption and reduction of pulmonary vascular resistance. However transient hypotension was a serious clinical problem in patients after open heart surgery, especially in CABG patients who need suitable systolic arterial pressure to keep enough blood perfusion of arterial bypass grafts.     

Temporal effects of prolonged hypoxaemia and reoxygenation on systemic, pulmonary and mesenteric perfusions in newborn piglets

OBJECTIVE: Temporal effects of prolonged hypoxaemia and reoxygenation, on the systemic pulmonary and mesenteric circulations in newborn piglets, were investigated. METHODS: Two groups [control (n = 5), hypoxaemic (n = 7)] of 1-3 day old anaesthetised piglets were instrumented with ultrasound flow probes placed to measure cardiac, hepatic arterial flow and portal venous flow indices, and catheters inserted for measurements of systemic and pulmonary arterial pressures. Hypoxaemia with arterial oxygen saturation 40-50% was maintained for 3 h, followed by reoxygenation with 100% inspired oxygen. RESULTS: Cardiac index was transiently elevated at 30-60 min of hypoxaemia (23% increase from baseline 158 +/- 39 ml/kg/min), along with increases in stroke volume but not heart rate. A significant decrease in systemic vascular resistance after 30 min of hypoxaemia was followed by hypotension at 180 min of hypoxaemia. Progressive pulmonary hypertension with significant vasoconstriction was found after 30 min of hypoxaemia. The hypoxaemic mesenteric vasoconstriction was transient with a 37% decrease in portal venous flow index at 15 min of hypoxaemia (29 +/- 12 vs. 46 +/- 18 ml/kg/min of baseline, p < 0.05). The hepatic arterial to total hepatic oxygen delivery ratio increased significantly during hypoxaemia. In contrast to the significant increase in systemic oxygen extraction throughout hypoxaemia, elevation in mesenteric oxygen extraction decreased after 30 min of hypoxaemia associated with modest decreases in oxygen consumption. Following reoxygenation, the pulmonary hypertension was partially reversed. Cardiac index decreased further (130 +/- 39 ml/kg/min) with reduced stroke volume, persistent systemic hypotension and decreased systemic oxygen delivery. CONCLUSIONS: We demonstrated differential temporal changes in systemic, pulmonary and mesenteric circulatory responses during prolonged hypoxaemia. Cautions need to be taken upon reoxygenation because the neonates are at risk of developing myocardial stunning, persistent pulmonary hypertension and necrotising enterocolitis.     

Right ventricular function in patients with dilated cardiomyopathy: assessment using krypton-81 m blood pool scintigraphy

The characteristics and pathogenesis of right ventricular dysfunction in 14 patients with dilated cardiomyopathy (DCM) were investigated by equilibrium right ventricular blood pool scintigraphy using ultrashort-lifetime 81mKr. Thirteen patients with severe left ventricular dysfunction due to old anterior myocardial infarction (OMI) and nine normal subjects were used as controls. The right ventricular end-diastolic pressure and volume index, mean pulmonary arterial pressure, and total pulmonary vascular resistance index were almost the same in the DCM and OMI patients. The right ventricular ejection fraction was 44.2 +/- 6.0% (mean +/- SD) in DCM patients and 47.1 +/- 7.9% in OMI patients, both significantly lower than those in the normal subjects (54.5 +/- 5.3%), but with no difference between the two case groups. The right ventricular peak filling rate was significantly reduced in both case groups as compared with the normal subjects (2.46 +/- 0.81 EDV/sec). The reduction was significantly greater (p < 0.05) in the DCM group (0.97 +/- 0.47 EDV/sec) than in the OMI group (1.61 +/- 0.46 EDV/sec). Cineangiography showed that the wall motion abnormality of the interventricular septum was remarkable in OMI patients, but was relatively mild in DCM patients. Lesions of the interventricular septum may be of major importance in right ventricular dysfunction in OMI, while extensive severe damage to the right ventricular free wall may be important in DCM. 81mKr blood pool scintigraphy is useful in the study of the right ventricular systolic and diastolic function. The diastolic parameters are more sensitive indicators for evaluation of right ventricular function in DCM than the systolic parameters.