Comparison of haemodynamic responses to dopamine and salbutamol in severe cardiogenic shock complicating acute myocardial infarction.

Twelve patients with severe persistent cardiogenic shock complicating acute myocardial infarction underwent single crossover treatment with intravenous dopamine and salbutamol to determine the more beneficial therapy. Salbutamol (10 to 40 microgram/min) reduced systemic vascular resistance and progressively increased both cardiac index and stroke index. Heart rate increased from 95 to 104 beats/min. Changes in mean arterial pressure and pulmonary artery end-diastolic pressure were small and insignificant. Dopamine infusion at rates of 200 and 400 micrograms/min also increased cardiac index and stroke index. Systemic vascular resistance fell slightly but mean arterial pressure rose from 57 to 65 mm Hg. Heart rate increased from 95 to 105 beats/min. Changes in pulmonary artery end-diastolic pressure were again small and insignificant. Dopamine infusion at 800 micrograms/min caused an appreciable increase in systemic vascular resistance; a further increment in mean arterial pressure was observed, though cardiac index fell slightly. Heart rate and pulmonary artery end-diastolic pressure rose steeply. Salbutamol, a vasodilator, increased cardiac output in patients with cardiogenic shock complicating acute myocardial infarction but did not influence blood pressure. If correction of hypotension is essential dopamine in low doses may be the preferred agent. Doses of 800 microgram/min, which is within the therapeutic range, worsen other manifestations of left ventricular dysfunction.     

Synergistic effects of a combined salbutamol-nitroprusside regimen in acute myocardial infarction and severe left ventricular failure.

The haemodynamic effects of a simultaneous infusion of salbutamol and nitroprusside were measured in 20 patients with acute myocardial infarction and severe left ventricular failure. Six patients also had clinical manifestations of cardiogenic shock. Ten patients received salbutamol first with the subsequent addition of nitroprusside; in the other 10 patients nitroprusside was infused first. Salbutamol was infused at a constant rate of 20 micrograms/min in all patients, while the dose of nitroprusside, which averaged 51.25 micrograms/min, was adjusted to reduce left ventricular filling pressure (measured as pulmonary artery end-diastolic pressure) to approximately 15 mm Hg with reference to sternal angle. Cardiac index increased in all patients from a mean of 1.8 to 2.6 l/min/m2 while pulmonary artery end-diastolic pressure fell significantly from 24 to 16 mm Hg. The adverse effects were small in most patients: heart rate did not increase significantly and systolic arterial pressure fell on average from 112 to 96 mm Hg. Ten of the 20 patients survived to leave hospital. Nitroprusside accounted for most of the fall in filling pressure irrespective of treatment sequence, whereas both drugs contributed to the augmented cardiac output. The haemodynamic benefits of this combined regimen were considerably greater than those achieved by either drug alone. Thus salbutamol and nitroprusside have synergistic effects which influence favourably the two principal manifestations of left ventricular dysfunction after extensive myocardial infarction.     

Haemodynamic effects of salbutamol in patients with acute myocardial infarction and severe left ventricular dysfunction.

The haemodynamic effects of salbutamol infusions at rates of 10,20, and 40 micrograms/min were measured in 11 patients with acute myocardial infarction complicated by left ventricular failure. Four patients also had cardiogenic shock. Consistent increases were observed in cardiac outputs at all doses (up to 56% at 40 micrograms/min), while the mean systemic arterial pressure fell slightly (average 5 mm Hg), implying a reduction in peripheral vascular resistance. Changes in right atrial pressure and indirect left atrial pressure (measured as pulmonary artery end-diastolic pressure) were small and not significant. Analysis of data from individual patients showed that the greatest increment in cardiac output was reached at 10 micrograms/min in two cases, 20 microgram/min in three, and 40 micrograms/min in the remaining six. Heart rate at these doses increased by an average of only 10 beats/min. Salbutamol failed to reduce left ventricular filling pressure and cannot be recommended for the treatment of pulmonary oedema in acute myocardial infarction. The increase in cardiac output, however, was considerable, so that the drug may be important in the management of low-output states. This action is probably a result of peripheral arteriolar dilatation (itself a result of beta 2-adrenoreceptor stimulation) and is achieved with little alteration in the principal determinants of myocardial oxygen requirement.     

Haemodynamic effects of intravenous morphine in patients with acute myocardial infarction complicated by severe left ventricular failure.

The haemodynamic effects of intravenous morphine sulphate (0.2 mg/kg body weight) were measured in 10 patients with acute myocardial infarction complicated by severe left ventricular failure. Fifteen minutes after morphine injection there was a significant fall in mean heart rate (from 109 to 101 beats/min) and mean systemic arterial pressure (from 80 to 65 mm HG), and a small fall in mean cardiac index (from 2.4 to 2.21/min/m2). Haemodynamic changes at 45 minutes were similar. Neither stroke index nor indirect left ventricular filling pressure (measured as pulmonary artery end-diastolic pressure) were consistently improved 15 or 45 minutes after injection. The useful action of morphine in relieving distressing cardiac dyspnoea is not adequately explained by systemic venous blood pooling. These results suggest that the effects of morphine on the central nervous system are more important.     

Pulmonary oedema without critical increase in left atrial pressure in acute myocardial infarction.

Twelve patients with acute myocardial infarction and radiological evidence of pulmonary oedema were observed in whom the left atrial pressure, measured indirectly as pulmonary artery end-diastolic pressure, was not critically increased (range 5-12 mm Hg with reference to sternal angle). Eight of the patients had been treated with frusemide, but only six had responded: hence in at least half of the series diuresis could not account for the anomalous finding. Six patients with low cardiac output were given infusions to expand plasma volume. Appreciable increments in mean values for cardiac index (1.6 to 2.0 1/min/m2), stroke index (18 to 23 ml/beat/m2), mean arterial pressure (65 to 86 mm Hg), and pulmonary artery end-diastolic pressure (8 to 15 mm Hg) were recorded. This group, and the remaining six patients with higher cardiac output, survived to leave hospital. Delay in radiographic clearing after a fall of left atrial pressure was a possible explanation for the relatively low pulmonary artery end-diastolic pressures, especially in the patients treated successfully with diuretics. Other mechanisms, such as alterations in pulmonary vascular permeability, might also have contributed to the syndrome. Pulmonary oedema without a critical increase in the left atrial pressure is unusual in acute myocardial infarction but the therapeutic implications are important. Withdrawal;of diuretics may be indicated, and in some cases expansion of plasma volume may lead to striking clinical improvement.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Seasonal variation of cardiovascular function in the marmot, Marmota flaviventris

Monthly measurements of heart rate, mean arterial pressure, and cardiac output were made on active and hibernating marmots from the time of emergence from hibernation through the next hibernation period. From these measurements cardiac index, stroke index, and total peripheral resistance were calculated on the basis of estimated lean body mass. Heart rate was low after emergence (132 +/- 9.5 beats (B)/min), peaked in August (160 +/- 9.3 B/min), and then fell slightly in September and October. During hibernation heart rate fell to 9 +/- 1.1 B/min. Mean arterial pressure, which was low in early spring (101 +/- 6.9 mm Hg), rose to a peak value in June (131 +/- 7.7 mm Hg) and remained essentially unchanged until hibernation when it fell to 52 +/- 4.0 mm Hg. Cardiac index (61 +/- 4.9 ml/kg min) in March rose to a peak in May (83 +/- 8.5 ml/kg min) and fell linearly until October. There was an additional drop in cardiac index during hibernation (7.6 +/- 0.9 ml/kg min). Total peripheral resistance increased linearly from the time of emergence until October. Most of this change was due to the decrease in cardiac index. Stroke index showed no significant changes in the prehibernation period, but increased by 55% during hibernation. Maintenance of arterial pressure in the months preceding hibernation in the face of diminishing cardiac index indicate that alterations in vasomotor tone or shifts in patterns of blood flow occurred prior to the hibernation period.     

Hemodynamic Response to Exercise After Beta-Adrenergic Blockade with Propranolol in Patients with Mitral Valve Obstruction

Propranolol (P) .13 mg./kg. was given to seven patients with mitral valve obstruction the changes in resting and exercise hemodynamics were followed by means of combined right and left heart catheterization. Changes were variable. At rest there was a decrease in heart rate of 10 beats/min. with no consistent change in stroke volume, cardiac output, left ventricular systolic (LVS) or left atrial (LA) pressure after P. Mean left ventricular end-diastolic (LVED) pressure was increased 3 mm., mean pulmonary artery (PA) pressure was increased 4 mm., and mean mitral valve gradient was reduced 3 mm. Hg by P. During exercise, mean LVS pressure was decreased 31 mm., mean LVED pressure increased 3 mm., mean LA pressure decreased 3 mm., and mean mitral valve gradient was reduced 5 mm. Hg after P. Mean exercise PA pressure was unchanged, cardiac output was reduced 0.9 1./min., and mean heart rate was reduced 37 beats/min., while stroke volume increased 3 ml./beat after P. Exercise pulmonary vascular resistance was increased from 6.1 to 8.2 units by P. Despite a slower heart rate, the diastolic filling period was not increased. P has no place in the treatment of the majority of patients with mitral stenosis because it further reduces cardiac performance below normal.     

Dobutamine enhances both contractile function and energy reserves in hypoperfused canine right ventricle

Although the beta(1)-adrenergic agent dobutamine is used clinically to provide inotropic support to the failing myocardium, it could jeopardize the myocardium by depleting energy reserves. This investigation delineated the contractile and energetic effects of low versus high dobutamine doses in the hypoperfused right ventricular (RV) myocardium. The right coronary artery (RCA) of anesthetized dogs was cannulated for controlled perfusion with arterial blood, and regional RV contractile function was measured. RCA perfusion pressure was lowered from 100 mmHg baseline to 40 mmHg, and flow fell by 54%. At 15-min hypoperfusion, dobutamine was infused into the RCA at either 0.01 (low-dose dobutamine) or 0.06 microgram. kg(-1). min(-1) (high-dose dobutamine) for 15 min. Regional power (systolic segment shortening x isometric developed force x heart rate) stabilized at 63% of baseline during hypoperfusion. Low-dose dobutamine restored power to baseline but did not increase RV myocardial O(2) consumption (MVO(2)) and thus increased myocardial O(2) utilization efficiency (O(2)UE:power/MVO(2)). At 5 min, high-dose dobutamine enhancement of power was similar to that of low-dose dobutamine, but by 15 min, power and O(2)UE fell to untreated levels. Remarkably, low-dose dobutamine tripled cytosolic phosphorylation potential; in contrast, high-dose dobutamine lowered phosphorylation potential to 45% of the untreated value. Analyses of glucose uptake and glycolytic intermediates revealed sustained enhancement of glycolysis by low-dose dobutamine, but glycolysis became limited at glyceraldehyde 3-phosphate dehydrogenase during high-dose dobutamine treatment. In summary, low-dose dobutamine improved mechanical performance and efficiency of the hypoperfused RV myocardium while increasing myocardial energy reserves, but high-dose dobutamine failed to sustain improved function and depleted energy reserves. Dobutamine is capable of improving both contractile function and cellular energetics in the hypoperfused RV myocardium, but dosage should be carefully selected.     

Evaluation of digitalis in cardiac failure.

Ten patients in sinus rhythm with symptomatic cardiac failure participated in a study investigating the value of digitalis at rest and during dynamic exercise. A haemodynamic profile and left ventricular ejection fraction were measured before treatment, after intravenous ouabain, and after six weeks of maintenance treatment with digoxin. There was no significant change in the haemodynamic profile or in the left ventricular ejection fraction at rest after either glycoside. During exercise there was a significant reduction in left ventricular filling pressure from 39 +/- 3 mm Hg to 34 +/- 3 mm Hg (p less than 0.05) after ouabain and to 33 +/- 3 mm Hg (p less than 0.02) after digoxin. Cardiac index improved from 33 +/- 0.3 1/min/m2 to 4.0 +/- 0.4 l/min/m2 (p less than 0.01) after ouabain and to 3.8 +/- 0.4 l/min/m2 (p less than 0.01) after digoxin. During exercise stroke volume index and stroke work index also improved significantly with both glycosides. This was accompanied by an increase in left ventricular ejection fraction from 29 +/- 2% to 36 +/- 3% (p less than 0.05) after ouabain and digoxin. In this study both intravenous ouabain and maintenance treatment with oral digoxin exerted a modest positive inotropic effect in patients with cardiac failure in sinus rhythm. The haemodynamic benefit, however, was manifest only during exertion.     

Pericardium modulates left and right ventricular stroke volumes to compensate for sudden changes in atrial volume

The pericardium may modulate acute compensatory changes in stroke volumes seen with sudden changes in cardiac volume, but such a mechanism has never been clearly demonstrated. In eight open-chest dogs, we measured left and right ventricular pressures, diameters, stroke volumes, and pericardial pressures during rapid (approximately 300 ms) systolic infusions or withdrawals of approximately 25 ml blood into and out of the left atrium and right atrium. Control beats, the infusion/withdrawal beat, and 4-10 subsequent beats were studied. With infusions, ipsilateral ventricular end-diastolic transmural pressure, diameter, and stroke volume increased. With the pericardium closed, there was a compensatory decrease in contralateral transmural pressure, diameter, and stroke volume, mediated by opposite changes in transmural end-diastolic pressures. The sum of the ipsilateral increase and contralateral decrease in stroke volume approximated the infused volume. Corresponding changes were seen with blood withdrawals. This direct ventricular interaction was diminished when pericardial pressure was <5 mmHg and absent when the pericardium was opened. Pericardial constraint appears essential for immediate biventricular compensatory responses to acute atrial volume changes.     

Cardiac Stress Test Induced by Dobutamine and Monitored by Cardiac Catheterization in Mice

Dobutamine is a β-adrenergic agonist with an affinity higher for receptor expressed in the heart (β₁) than for receptors expressed in the arteries (β₂). When systemically administered, it increases cardiac demand. Thus, dobutamine unmasks abnormal rhythm or ischemic areas potentially at risk of infarction. Monitoring of heart function during a cardiac stress test can be performed by either ecocardiography or cardiac catheterization. The latter is an invasive but more accurate and informative technique that the former.Cardiac stress test induced by dobutamine and monitored by cardiac catheterization accomplished as described here allows, in a single experiment, the measurement of the following hemodynamic parameters: heart rate (HR), systolic pressure, diastolic pressure, end-diastolic pressure, maximal positive pressure development (dP/dtmax) and maximal negative pressure development (dP/dt_min), at baseline conditions and under increasing doses of dobutamine.As expected, in normal mice we observed a dobutamine dose-related increase in HR, dP/dt_max and dP/dt_min. Moreover, at the highest dose tested (12 ng/g/min) the cardiac decompensation of high fat diet-induced obese mice was unmasked.     

Reference cardiopulmonary values in normal dogs

The purpose of this project was to collate canine cardiopulmonary measurements from published and unpublished studies in our laboratory in 97 instrumented, unsedated, normovolemic dogs. Body weight; arterial and mixed-venous pH and blood gases; mean arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressures; cardiac output; heart rate; hemoglobin; and core temperature were measured. Body surface area; bicarbonate concentration; base deficit; cardiac index; stroke volume index, systemic and pulmonary vascular resistance indices; left and right cardiac work indices; alveolar partial pressure of oxygen (pO2) ; alveolar-arterial pO2 gradient (A-apO2); arterial, mixed-venous, and pulmonary capillary oxygen content; oxygen delivery; oxygen consumption; oxygen extraction; venous admixture; arterial and mixed-venous blood CO2 contents; and CO2 production were calculated. In the 97 normal, resting dogs, mean arterial and mixed-venous pH were 7.38 and 7.36, respectively; partial pressure of carbon dioxide (pCO2), 40.2 and 44.1 mm Hg, respectively; base-deficit, -2.1 and -1.9 mEq/liter, respectively; pO2, 99.5 and 49.3 mm Hg, respectively; oxygen content, 17.8 and 14.2 ml/dl, respectively; A-a pO2 was 6.3 mm Hg; and venous admixture was 3.6%. The mean arterial blood pressure (ABPm), mean pulmonary arterial blood pressure (PAPm), pulmonary artery occlusion pressure (PAOP) were 103, 14, and 5.5 mm Hg, respectively; heart rate was 87 beats/min; cardiac index (CI) was 4.42 liters/min/m2; systemic and pulmonary vascular resistances were 1931 and 194 dynes.sec.cm-5, respectively; oxygen delivery, consumption and extraction were 790 and 164 ml/min/m2 and 20.5%, respectively. This study represents a collation of cardiopulmonary values obtained from a large number of dogs (97) from a single laboratory using the same measurement techniques.     

Cardiovascular responses to lower body negative pressure in trained and untrained older men.

To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2 max) = 52.4 +/- 1.7 ml.kg-1 x min-1] and nine age-matched control subjects (C) (VO2 max = 31.0 +/- 2.9 ml.kg-1 x min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of 99mTc-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2 max among older men is associated with improved orthostatic responses.     

Haemodynamic effects of buprenorphine after heart surgery.

The effect of buprenorphine on the cardiovascular system was examined in 11 patients during the period of reduced cardiac reserve after open-heart surgery. Within 10 minutes of giving the full analgesic dose (5 microgram/kg) intravenously the mean heart rate had fallen significantly by six beats/min. Although in two patients the mean arterial pressure fell by 24 mm Hg, there was no overall change in mean arterial pressure, cardiac output, or peripheral resistance. In a further six patients buprenorphine was used successfully as the sole analgesic after open-heart surgery. Buprenorphine appears to be safer than morphine for use in patients with reduced cardiac reserve and is of similar analgesic efficacy.     

Echocardiographic evaluation of space shuttle crewmembers

Echocardiographic measurements were obtained before and after space flight from 17 members of four shuttle crews. Measurements obtained 1 h after landing (L+0) compared with preflight values (n = 7) demonstrated an increase in heart rate (HR) (16 beats/min, 30.5%, P less than 0.05), mean arterial pressure (12%, P less than 0.05), and systemic vascular resistance (34%, P less than 0.05). End-diastolic volume index (EDVI) fell 17 ml/m2 (-23%, P less than 0.005) and stroke volume index (SVI) fell 15 ml/m2 (-28%, P less than 0.05). Repeat measurements taken 1-2 wk later (n = 17) demonstrated that HR had returned to normal (4 beats/min, P less than 0.05); however, EDVI remained significantly below preflight levels (-11%, P less than 0.005). End-systolic volume index (ESVI) was also still significantly lower (-23%, P less than 0.01). This delayed recovery occurred despite ability of the subjects to fully ambulate and exercise during the postflight period. These results indicate that spaceflight induces significant changes in heart volume affecting left ventricular function. The exact reasons for these specific changes remain unknown and will require additional measurements before, during, and after flight. The prolonged recovery period for the present subject group probably relates to their high level of aerobic conditioning.     

Acute plasma expansion: left ventricular hemodynamics and endocrine function during exercise.

In 11 healthy subjects (8 males and 3 females, age 21-59 yr) left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volumes were measured in the supine position by isotope cardiography at rest and during two submaximal one-legged exercise loads before and 1 h after acute plasma expansion (PE) by use of a 6% dextran solution (500-750 ml). After PE, blood volume increased from 5.22 +/- 0.92 to 5.71 +/- 1.02 (SD) liters (P < 0.01). At rest, cardiac output increased 30% (5.3 +/- 1.0 to 6.9 +/- 1.6 l/min; P < 0.01), stroke volume increased from 90 +/- 20 to 100 +/- 28 ml (P < 0.05), and LVEDV increased from 134 +/- 29 to 142 +/- 40 ml (NS). LVESV was unchanged (44 +/- 11 and 42 +/- 14 ml). Heart rate rose from 60 +/- 7 to 71 +/- 10 beats/min (P < 0.01). The cardiac preload [central venous pressure (CVP)] was insignificantly elevated (4.9 +/- 2.1 and 5.3 +/- 3.0 mmHg); systemic vascular resistance and arterial pressures were significantly reduced (mean pressure fell from 91 +/- 11 to 85 +/- 11 mmHg, P < 0.01). Left ventricular peak filling and peak ejection rates both increased (19 and 14%, respectively; P < 0.05). During exercise, cardiac output remained elevated after PE compared with the control situation, predominantly due to a 10- to 14-ml rise in stroke volume caused by an increased LVEDV, whereas LVESV was unchanged. CVP increased after PE by 2.1 and 3.0 mmHg, respectively (P < 0.05).2+ remained unchanged during exercise compared with rest after PE in     

Hemodynamic effects of anti-G suit inflation in a 1-G environment

This study evaluated effects of various anti-G inflation pressures on cardiac volumes and the relationship of these volume changes to mean arterial pressure changes. Ventricular volumes were calculated using two-dimensional echocardiography. An anti-G suit was inflated to 2, 4, and 6 psi in the standing and supine positions for 10 male subjects. In the supine position, mean arterial pressure increased from base line for all three inflation pressures (P = 0.05). The end-diastolic volume increased after 2-psi inflation (P = 0.03). Cardiac output or stroke volume did not change. After standing, mean arterial pressure (P = 0.002), end-diastolic volume (P = 0.002), and stroke volume (P = 0.05) fell after suit deflation. Peripheral vascular resistance fell in the 2- and 4-psi inflation profiles. In the standing protocol, mean arterial pressure, end-diastolic volume, stroke volume, and cardiac output rose with all three inflation pressures (P less than 0.05). After reclining, heart rate increased (P = 0.02) and mean arterial pressure fell (P less than 0.05) in the 4- and 6-psi inflation profiles after suit deflation. Increases in mean arterial pressure are caused by increases in cardiac preload and cardiac output after inflation of the anti-G suit while subjects were standing. Increased cardiac preload was not consistently seen after inflation while subjects were supine. Changes in end-diastolic volume and mean arterial pressure were dependent on the pressure used to inflate the anti-G suit.     

Effects of dihydroergotamine on hemodynamic molsidomine actions in anesthetized dogs

In pentobarbital-anesthetized mongrel dogs the intravenous actions of 0.50 mg/kg molsidomine on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimensions (preload), left ventricular systolic and peripheral blood pressures, and total peripheral resistance (afterload), as well as on heart rate, dP/dt, stroke volume, and cardiac output (heart performance) were studied for 2 h. Hemodynamic molsidomine effects were influenced by increasing amounts of intravenously infused dihydroergotamine solution (DHE, 1-64 micrograms X kg-1 X min-1). Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h but decreased ventricular and peripheral pressures for 45 min. Systemic vascular resistance showed a tendency to decrease while heart rate and LV dP/dtmax were not altered. DHE infusion reversed molsidomine effects on the preload and afterload of the heart. The diminished stroke volume was elevated so that cardiac output also increased. Total peripheral resistance increased while heart rate fell in a dose-dependent fashion. The LV dP/dtmax remained unchanged until the highest dose of 64 micrograms X kg-1 X min-1 DHE elevated the isovolumic myocardial contractility. These experiments indicate that DHE can reverse the intravenous molsidomine effects on hemodynamics. Most likely, this is mediated through peripheral vasoconstriction of venous capacitance vessels, thereby affecting molsidomine's action on postcapillary beds of the circulation.     

The effect of selective umbilical embolization on the common umbilical artery pulsatility index and umbilical vascular resistance in fetal sheep.

In eight anaesthesized fetal sheep (gestational age 112-127 days; term 147 days), embolization of the umbilical placental circulation was performed in order to evaluate the response of the umbilical artery pulsatility index to an exclusive increase in umbilical vascular resistance. Measurements were performed using a 20 MHz pulsed Doppler transducer and an electromagnetic flow meter mounted on the common umbilical artery and catheters at the aortic trifurcation and in one of the umbilical veins. Umbilical vascular resistance was calculated according the Poiseuille equation as the ratio of aortic to umbilical venous pressure gradient and umbilical blood flow. Microspheres were administered at 15-min intervals through a catheter in one of the cotyledonary arteries, until fetal heart rate had decreased beneath 100 beats/min or had become arrhythmic. The period of examination per fetus varied between 60 and 120 min, after which cardiac decompensation occurred. During this period, umbilical perfusion pressure increased from 20.3 +/- 4.9 to 28.1 +/- 4.7 mmHg (SD; P less than 0.01), umbilical blood flow (ml/min) decreased from 342 +/- 127 to 115 +/- 99 mmHg (SD; P less than 0.01), umbilical vascular resistance increased from 0.065 +/- 0.022 to 0.342 +/- 0.150 mmHg.min/ml (P less than 0.01) and common umbilical artery pulsatility index increased from 0.97 +/- 0.23 to 4.03 +/- 1.69 (P less than 0.01). Fetal heart rate did not change significantly (168 +/- 33 prior to cardiac decompensation versus 178 +/- 19 beats/min at baseline condition). The linear correlation between common umbilical artery pulsatility index and umbilical vascular resistance varied between 0.83 and 0.99 and the average correlation was 0.93 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)