Significant Changes In Cardiac Output Research Articles

Haemodynamic and oxygen transport effects of propofol infusion in critically ill adults

The effects of a sedative infusion of propofol on haemodynamics and oxygen transport were examined in critically ill adult patients. Ten patients receiving mechanical ventilation for treatment of septic shock and respiratory failure were given a decreasing rate propofol infusion designed to achieve and maintain a stable sedation level. Full cardiovascular and oxygen transport variables, arterial blood lactate concentrations and sedation scores were measured before infusion and at 1, 3 and 6 h after starting the infusion. There were significant reductions in mean (SEM) heart rate (97.3 (2.9) to 85.7 (3.9) beat.min-1 p < 0.05), mean arterial pressure (87.6 (3.7) to 76.2 (4.1) mmHg P < 0.05) and systemic vascular resistance index (1461 (137) to 1327 (141) dyne.s.cm-5.m-2 p < 0.05), with no significant change in cardiac filling pressures. There were no significant changes in cardiac output, oxygen delivery, oxygen consumption or arterial blood lactate concentrations. Controlled propofol sedation is well tolerated in appropriately monitored and resuscitated critically ill adult patients, and appears to have no major effects on whole-body oxygen transport.

Effects of phenylephrine and ephedrine on pulmonary arterial pressure in patients with cervical or lumbar epidural anesthesia, or enflurane anesthesia.

The authors studied systemic and pulmonary hemodynamic changes with ephedrine (EP) or phenylephrine (PH) when used to normalize arterial hypotension resulting from acute sympathectomy due to cervical or lumbar epidural anesthesia, or enflurane anesthesia in 52 patients. Both EP (0.2±0.05 mg·kg-1) and PH (0.025±0.008 mg·kg-1) produced a significant increase in pulmonary arterial pressure (PAP) with a concomitant increase in arterial pressure (AP). In the patients anesthetized with cervical epidural block and NO2-O2, systolic PAP increased from 22±5 to 28±8 mmHg with EP and from 23±6 to 32±10 mmHg with PH in response to approximately 30 mmHg increase of AP, and the ratio of the increment of systolic PAP to systolic AP (ΔPAP/ΔAP) was 0.15±0.08 with EP and 0.20±0.13 with PH (P<0.05); these changes did not differ significantly from those observed in the patients having lumbar epidural or enflurane-N2O-O2 anesthesia. The influence on cardiac output (CO) differed significantly between EP and PH; EP increased CO in all three groups (P<0.05), while PH did not elicit any significant changes in CO. A significant relationship between PAP and AP was found in patients given EP; the regression equation was ΔPAP=0.22×ΔAP-2.9 (r=0.77). The relationship in patients given PH was less significant (r=0.38). The results indicated that EP and PH elicit pulmonary hypertensive effect similarly in the patients with a high level of epidural anesthesia and that although both drugs act differently (EP mainly due to increases in the blood flow and PH solely due to its pulmonary vasconstrictive action), the increases in PAP were predictable, to some extent, from the increase of AP in anesthetized humans without predominant cardiopulmonary disorders.

Pressor and endocrine responses to lesions of canine rostral ventrolateral medulla.

To understand the mechanism(s) of reduction in arterial pressure (AP) after kainic acid cytotoxic lesions in the rostral ventrolateral medulla (RVLM), recordings of AP, cardiac output (CO), heart rate (HR), plasma catecholamines, and cortisol were obtained from awake relaxed dogs. Mongrels (n = 12) were instrumented with a solid-state pressure transducer in the descending aorta and a pulse transit-time ultrasonic flowmeter on the aortic arch. After the dogs recovered from thoracotomy, AP, CO, HR, and plasma levels of epinephrine, norepinephrine, and cortisol were recorded periodically or measured at rest over 2-3 wk followed by unilateral, cytotoxic lesion placement in the rostral C1 area of the RVLM. After the dogs recovered from lesion surgery, the measurements were repeated, and, compared with prelesion control values, they showed significantly decreased AP (-23.1 mmHg) and total peripheral resistance (-0.014 peripheral resistance units) but no significant changes in CO or HR. The reduction in AP may be caused partially by significant reductions in plasma epinephrine (-47%), norepinephrine (-34%), and cortisol (-66%) levels. Lesion sites corresponded to the rostral C1 area, immunocytochemically positive for phenylethanolamine-N-methyltransferase (PNMT). These observations support the concept that a discrete site in the RVLM, demarcated by a rostral subgroup of PNMT-immunoreactive cell bodies, contributes to direct sympathoexcitatory support of resting AP. The neurotransmitter responsible for vasomotor tone, however, remains unknown. This study also provides new information suggesting a role for catecholamine and cortisol regulation from this putative vasomotor center.

Effects of low-sodium diet and spironolactone on portal pressure in patients with compensated cirrhosis.

The aim of this study was to investigate the hemodynamic effects of spironolactone associated with a low-sodium diet (n = 14) or a low-sodium diet alone (n = 9) in patients with compensated cirrhosis and portal hypertension. Spironolactone significantly reduced the plasma volume. This effect was associated with a significant reduction in the hepatic venous pressure gradient, from 17.6 +/- 3.6 mm Hg to 15.3 +/- 3.5 mm Hg (-13% +/- 13%; p < 0.01). Azygos blood flow (-20% +/- 20%), cardiac output (-16.2% +/- 10.5%) and mean arterial pressure (-9% +/- 9%) also decreased significantly. However, there were no significant changes in hepatic blood flow. Patients receiving low-sodium diet alone experienced a mild but significant reduction in hepatic venous pressure gradient (-6.3% +/- 6%) and in mean arterial pressure (-4% +/- 5%). There were no significant changes in cardiac output and in hepatic or azygos blood flows. This study indicates that low-sodium diet plus administration of spironolactone reduces portal pressure and azygos blood flow in patients with compensated cirrhosis. Low-sodium diet alone only produces mild effects that are likely to be clinically irrelevant.

Delayed Onset Hypertension with Infrarenal Aortic Cross-Clamping in Dogs

The time course and mechanism of systemic hypertension associated with infrarenal aortic cross-clamping were investigated in 31 chloralose-anesthetized dogs after ligating the tail artery, the paired infrarenal lumbar arteries, and the circumflex iliac arteries bilaterally. Cardiac output, renal blood flow, and suprarenal and infrarenal mean arterial blood pressure were continuously monitored. Infrarenal aortic clamping (90 min) in the standard group ( n = 6) consistently decreased infrarenal blood pressure from 90 ± 6 to 13 ± 1 mm Hg within 1 min, while suprarenal blood pressure gradually increased over 20-30 min from 88 ± 7 to 144 ± 8 mm Hg, where it remained until declamp. The SHAM group (identical operation and instrumentation, without aortic clamping) ( n = 5) showed no statistically significant changes. After 90 min of clamp total peripheral and renal resistance nearly doubled but no statistically significant changes in cardiac output, heart rate, central venous pressure, renal blood flow, renin, or glomerular filtration rate were detected. Upon declamping, pressures returned to control levels within 20 min. Groups with bilateral nephrectomy ( n = 9) or unilateral iliac artery clamping ( n = 7) produced similar time courses and patterns of hemodynamic change. Ablation of afferent nerves from the left hind limb ( n = 4) eliminated the hypertension produced by left iliac artery clamping. The substantial delay (20-30 min) to the onset and full development of suprarenal hypertension, with near immediate infrarenal hypotension, is not consistent with a direct mechanical impedance effect. Hypertension in the presence of a bilateral nephrectomy or unilateral iliac artery clamping combined with its full reversal by nerve section strongly suggests that this is a reflex hypertension. This reflex mechanism of hypertension development has implications for intra- or perioperative events associated with hypertension management.

Nicardipine increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis

The present study investigated the hemodynamic effects of nicardipine, a new calcium channel blocker, and placebo in 14 patients with cirrhosis. Sixty minutes after nicardipine administration (20 mg orally; n = 8), there was a significant increase in hepatic blood flow (25 +/- 21%; p < 0.05) and azygos blood flow (33 +/- 40%; p < 0.05) but no significant change in the hepatic venous pressure gradient. As a result of the increase in hepatic blood flow and the lack of change in the hepatic venous pressure gradient, nicardipine significantly reduced hepatic sinusoidal resistance (-14 +/- 15%; p < 0.05). Enhanced liver perfusion was associated with a significant increase in the hepatic clearance of indocyanine green (from 241 +/- 81 to 265 +/- 92 ml/min, p < 0.05). A mild, well-tolerated decrease in mean arterial pressure (-10 +/- 6%, p < 0.05), without significant changes in cardiac output, systemic vascular resistance and heart rate, was also observed. Placebo administration (n = 6) did not cause significant changes in systemic or hepatic hemodynamics. The results of the present study show that nicardipine, unlike other calcium channel blockers, effectively increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis. The acute beneficial effects of nicardipine should be confirmed in chronic studies.

Clinical and Haemodynamic Effects of Long-Term Treatment with Torasemide in Congestive Heart Failure

The clinical and haemodynamic effects of 12 weeks of treatment with torasemide, 5 mg/day, were measured in 24 men aged 51-60 years with symptoms of mild, chronic, congestive heart failure. Clinical status was assessed by NYHA functional class and haemodynamic effects were measured at rest and during supine bicycle exercise at the beginning and end of the 12-week period of study. Torasemide was well tolerated and there was no significant change in any of the measured safety variables. Clinical status was improved in 16 of the 23 patients assessed after 12 weeks of treatment and none experienced symptomatic deterioration. Compared with pretreatment haemodynamic measurements, right atrial and pulmonary vascular pressures were significantly decreased both at rest and during exercise after torasemide. Systemic arterial pressure was reduced at rest, but there were no significant changes in cardiac output, heart rate, or systemic and pulmonary vascular resistances either at rest or during exercise, neither were there any significant changes in systemic arterial blood oxygen saturation, pulmonary arterial blood pH, gas tensions, or bicarbonate concentration either at rest or during exercise at 12 weeks. The results of these studies indicate that the clinical and haemodynamic benefits of torasemide are not subject to the development of tolerance during sustained treatment.

Arginine vasopressin produces renal vasodilation via V2 receptors in conscious dogs.

In conscious dogs, 36-h water deprivation induced a significant increase in renal blood flow (RBF) with elevation of the plasma arginine vasopressin (AVP) concentration to 9.6 +/- 1.8 pg/ml. To simulate such a condition, a mild elevation of plasma AVP was produced by infusing AVP intravenously at a dose of 0.1 ng.kg-1.min-1 for 20 min. The plasma AVP concentration then increased to 6.8 +/- 0.7 pg/ml. This dose of AVP increased the RBF by 21.7 +/- 2.6% and decreased the renal vascular resistance by 18.1 +/- 2.3% without significant changes in mean arterial pressure, cardiac output, or heart rate. The mechanism of this renal vasodilatory action was examined using newly developed, orally effective, selective AVP antagonists OPC-21268 (a V1-receptor antagonist) and OPC-31260 (a V2-receptor antagonist). In 36-h water-deprived dogs, V2-receptor blockade with OPC-31260 significantly decreased the RBF by 20.5 +/- 2.6% without significant changes in cardiac output. The exogenous AVP-induced renal vasodilatory response tended to be augmented when V1 receptors were blocked by pretreatment with OPC-21268, but the change did not achieve statistical significance. On the other hand, V2-receptor blockade by either pretreatment with OPC-31260 or simultaneous infusion of OPC-31260 inhibited this vasodilatory response. Furthermore, intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP) at a dose of 0.3 ng.kg-1 x min-1 for 20 min significantly increased the RBF by 36.5 +/- 1.7%, and this DDAVP-induced renal vasodilation was inhibited by simultaneous infusion of V2-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Exhaustion of Frank-Starling mechanism in conscious dogs with heart failure.

The goal of this study was to elucidate the ability of the left ventricle to accommodate an increase in preload (Frank-Starling mechanism) in the presence of congestive heart failure (CHF) but in the absence of the complicating effects of hypertrophy and fibrosis. To accomplish this, the effects of volume loading were examined in eight conscious dogs during the control state and after 3 wk of right ventricular pacing (240 beats/min). CHF increased heart rate (by 16 +/- 5 from 92 +/- 5 beats/min), left ventricular (LV) end-diastolic pressure (by 17 +/- 2 from 10 +/- 1 mmHg), and LV end-diastolic volume (EDV; by 23 +/- 4 from 57 +/- 3 ml). Despite reduced LV ejection fraction (from 54 +/- 3 to 31 +/- 3%), there was no significant change in cardiac output (2.5 +/- 0.3 l/min) compared with control (2.7 +/- 0.2 l/min). Stroke volume was preserved (control 19 +/- 2 ml; CHF 18 +/- 2 ml) at a constant heart rate by a shift to the right in the relationship between LV stroke volume and EDV, indicating the importance of chronic ventricular dilatation in maintaining pump performance. In the control state, acute volume load increased LV EDV (by 17 +/- 2 ml) and stroke volume (by 11 +/- 2 ml), whereas in CHF it did not increase LV EDV or stroke volume. Scanning electron microscopy revealed areas of reduced collagen weave pattern surrounding myofibers. Myocyte cross-sectional area by transmission electron microscopy was significantly reduced, and there were multiple electron-dense expansions of the Z lines with disruption of the normal lateral sarcomere alignment. These morphological findings suggest that chronic ventricular dilatation utilized in CHF results from myocyte stretch and morphological intracellular rearrangement. Furthermore, the failing heart cannot further augment stroke volume by acutely increasing EDV in CHF, suggesting that the Frank-Starling reserve is essentially exhausted.

Hemodynamic Effects of Oxygen Therapy in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease

The effects of oxygen therapy in patients with stable COPD have been previously reported; however, the hemodynamic changes induced by oxygen therapy in patients during acute exacerbations of COPD are less well known. To investigate the hemodynamic effects of controlled oxygen therapy in patients with acute exacerbations of COPD shortly after arriving at the hospital, we studied 15 consecutive patients who came to the emergency room with acutely decompensated COPD that did not require mechanical ventilation. Patients were monitored with a pulmonary artery catheter and a radial artery catheter. Oxygen uptake was calculated by the modified Fick equation. Arterial and venous blood gas levels and hemodynamic parameters were measured while breathing room air (baseline) and after 30 min on oxygen therapy via face mask. Measurements were repeated after 24 and 48 h. The fractional concentration of oxygen in the inspired gas (FIO2) administered was adjusted to keep the PaO2 above 55 mm Hg. All patients had a PaO2 below 45 mm Hg at the beginning of the study. After 30 min of oxygen therapy, there was a significant (p < 0.05) increase in arterial oxygen saturation (from 62 +/- 16 to 87 +/- 9 percent), mixed-venous oxygen pressure (from 25 +/- 5 to 43 +/- 11 mm Hg), and oxygen delivery (from 11.1 +/- 3.7 to 19.3 +/- 8.9 ml/kg.min). Oxygen uptake did not change significantly (from 4.1 +/- 1.2 to 4.3 +/- 1.6 ml/kg.min). The oxygen extraction ratio decreased from 37.5 +/- 10.1 to 25.3 +/- 9.6 percent. These changes were maintained during the following 48 h. There were no significant changes in cardiac output and systemic vascular resistance. A trend toward lower values of pulmonary vascular resistance did not reach statistical significance. We conclude that oxygen therapy in patients with acute exacerbations of COPD that do not require mechanical ventilation increases oxygen delivery without changes in cardiac output or oxygen uptake.

Balloon dilation of congenital subaortic stenosis in the dog.

Balloon dilation during cardiac catheterization was evaluated for the treatment of congenital subaortic stenosis (SAS) in nine dogs. Under general anesthesia, bilateral cardiac catheterization was performed through the right jugular vein and carotid artery. Thermodilution cardiac output, and left ventricular and aortic root pressures and angiograms were obtained before and after balloon dilation. Balloons measuring 18-20 mm in diameter and 30-40 mm in length were positioned across the stenosis and three inflations 4-5 minutes apart were performed. There was no significant change in cardiac output, aortic pressure, or degree of aortic regurgitation after balloon dilation. For the entire group balloon dilation resulted in significant decreases in left ventricular systolic pressure (-61.2 +/- 37.2 mm Hg [mean change +/- SD], range -14 to -123), mean systolic pressure gradient (-39.6 +/- 24.4 mm Hg, range -8.4 to -72.2), and peak systolic pressure gradient (-64.3 +/- 46.5 mm Hg, range -17 to -143). Calculated left ventricular outflow cross-sectional area increased significantly (+.4 +/- .5 cm2, range -.06 to + 1.30). Clinical signs improved in the five symptomatic dogs. Individual hemodynamic responses varied widely, but the magnitude of improvement correlated with the severity of obstruction. Three dogs showed a decrease of 60% or greater (> or = 100 mm Hg), and six dogs showed a decrease of 25-50% (17-71 mm Hg) in peak systolic gradient after balloon dilation. Complications were frequent but most were transient and manageable. These preliminary results suggest that balloon dilation can acutely decrease outflow resistance in dogs with SAS and may be effective therapy for some affected dogs.

Safety of low-dose intraoperative bicarbonate therapy

Recent recommendations suggest that sodium bicarbonate may not be useful for the treatment of metabolic acidosis. However, these recommendations are based primarily on both clinical studies and animal models of metabolic acidosis with arterial hypoxemia (PaO2 of < 80 torr [< 10.7 kPa]). This study was designed to determine the safety and physiologic effects of low-dose sodium bicarbonate in humans who developed intraoperative metabolic acidosis in the absence of hypoxemia. Prospective, double-blind, randomized trial. Veterans Affairs Medical Center (a teaching hospital of the University of California, San Francisco). We prospectively studied 40 patients with coronary artery disease who underwent major surgery and developed mild intraoperative metabolic acidosis (decrease of plasma bicarbonate by > 3 mM). Patients were randomly assigned to receive either sodium bicarbonate (n = 20) or sodium chloride (n = 20) by intravenous bolus, up to a maximum dose of 88 mmol of sodium. Bicarbonate treatment significantly increased the mean arterial pH from 7.36 to 7.39; the mean serum bicarbonate concentration from 21 to 25 mmol/L; and PCO2 from 41 to 44 torr (5.5 to 5.9 kPa). Total body oxygen consumption and lactate production did not change. Similarly, no adverse changes occurred in systemic or pulmonary arterial pressures or in cardiac ejection fraction. After bicarbonate administration, both the cardiac output and systemic oxygen consumption decreased by 8% to 11%, while both variables increased by 13% after sodium chloride administration; but, none of the changes was significant. One patient in the bicarbonate group developed myocardial ischemia, compared with three patients in the saline group. Administration of sodium bicarbonate to well-oxygenated patients with mild metabolic acidosis resulted in a correction of the acidosis, without significant changes in cardiac output, total body oxygen use, or PaO2 (oxygen tension). These effects remain to be validated in patients with hypoxemia, more severe acidosis, or less stable circulation.

Early results of intravascular oxygenation

We have used the intravascular oxygenator (IVOX) in eight patients (14-76 years) with acute respiratory failure. At the time of referral for IVOX all patients were on inotropic support, five had pneumothoraces and two were on haemofiltration. Ventilatory data before IVOX were: ventilated for 2-14 days (median 6), PEEP 5-12 cm H2O (12), PIP 34-95 cm H2O (49), FiO2 0.7-1 (1), PaO2 5.4-26 KPa (8.5) and PaCO2 3.7-23 KPa (8). The intravascular oxygenator was used for 6 h-12 days (median 4), the oxygen transfer achieved was 68-140 ml/min (85) and the carbon dioxide removed was 40-106 ml/min (59). It was possible to decrease the ventilator settings with a significant increase in the PaO2 by 48 h (P < 0.05) but the fall in PaCO2 did not reach significance. As the IVOX was turned from "off" to "on" the mean PaO2 increase was 0.35 KPa +/- 0.14 SEM (P = 0.04) and the mean PaCO2 decrease 0.7 KPa +/- 0.2 SEM (P = 0.02) without any significant change in cardiac output. Two patients survived and six died from multisystem failure with three patients being hypoxic at the time of death. Postmortem examinations on five patients did not reveal any IVOX-related complications. We conclude that IVOX is safe but it is not as efficient in gas exchange as extracorporeal membrane oxygenation at present. Further improvement in the gas exchange efficiency of this prototype could render IVOX a very useful device.

Alterations in respiratory function and hemodynamics during laparoscopic cholecystectomy under pneumoperitoneum.

Respiratory function and hemodynamics were studied during laparoscopic cholecystectomy (LC) under a 10 mmHg pneumoperitoneum (PP) by carbon dioxide insufflation. Blood-gas analysis and measurement of cardiac function by using a Swan-Ganz catheter were performed. Creatinine clearance rate was measured preoperatively and intraoperatively. Compared with values obtained before the institution of PP, blood-gas analysis showed a significant increase in PCO2 (P < 0.01), and a significant decrease in pH (P < 0.01) and base excess (P < 0.05) during PP. With respect to cardiac function, there was no significant change in cardiac output, pulmonary arterial pressure, and pulmonary arterial wedge pressure. Intraoperative creatinine clearance rate (Ccr) was decreased in 29 of 48 cases, increased in 18 cases, and unchanged in 1 case, resulting in no significant difference overall between the values measured preoperatively and intraoperatively. However, in eight individual cases, the Ccr was found to have decreased significantly. Although alterations in respiratory function were observed, LC at 10 mmHg PP did not cause any crucial problems in respiratory or cardiac function. It should be kept in mind, however, that renal blood flow may decrease in some cases even at intraabdominal pressures under 10 mmHg.

I.V. BOLUS ADMINISTRATION OF SUBCONVULSIVE DOSES OF LIGNOCAINE TO CONSCIOUS SHEEP: EFFECTS ON CIRCULATORY FUNCTION

We have studied the effects of subconvulsive doses of lignocaine on circulatory function in five conscious, chronically instrumented sheep. In the absence of overt signs of central nervous system toxicity, 50-, 75- or 100-mg i.v. bolus doses of lignocaine induced reductions in myocardial contractility, as assessed by the maximum rate of increase in left ventricular pressure (LV dP/dtmax), of 17 (SD 4)%, 25 (4)% and 33 (4)%, respectively. The durations of these reductions in myocardial contractility were 2-3.5 min. There were no significant changes in cardiac output, coronary artery blood flow, mean arterial pressure, heart rate or left ventricular systolic and diastolic pressures. It is concluded that the initial toxic effects of lignocaine are on the heart rather than the central nervous system, as is generally believed. This negative inotropic effect of lignocaine in vivo may be more deleterious to myocardial function when the heart is compromised by pre-existing disease, or the co-administration of other myocardial depressive drugs.

Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.

Effects of left ventricular pressure unloading during LVAD support on right ventricular contractility.

The effects of left ventricular pressure (LVP) unloading with a left ventricular assist device (LVAD) on right ventricular (RV) end-systolic pressure volume relationships were studied. A Thoratec (Berkeley, CA) LVAD was implanted in open chest anesthetized pigs via apical cannulation, and an electromagnetic flow probe and computer controlled pneumatic occluder were attached to the pulmonary artery. RV and left ventricular (LV) pressures were measured with Millar catheters, and changes in RV volume during ejection were determined by integrating the flow signal. As an index of contractility, RV maximal systolic elastance (Emax) was calculated as the slope of the end systolic, pressure volume relationship between an isovolumic beat and a series of transiently occluded beats at different times in the ejection phase. After an 83 +/- 15% decrease in LV pressure time integral during LVAD pumping, there were no significant changes in cardiac output, mean systemic arterial pressure, or in RV dP/dtmax. Most important, RV Emax during LVAD unloading (0.63 +/- 0.16 mmHg/ml) was unchanged from control (0.62 +/- 0.10 mmHg/ml). Therefore, in the normal intact porcine heart, the effective contractility of the right ventricle is not altered by significant LV pressure unloading produced with a LVAD.

Effect of pentoxifylline on liver plasma flow in normal man

In ten healthy, male subjects the acute effect of pentoxifylline (a methylxanthine derivative) on liver plasma flow was investigated by the extrarenal sorbitol clearance method and on cardiac output by impedance cardiography. On the placebo day liver plasma flow decreased within 4 h from 769 to 683 ml.min-1 (P less than 0.05) and on the pentoxifylline day (300 mg i.v.) it increased from 764 to 801 ml.min-1 (NS). At the end of the experiment the difference between the groups was also significant (P less than 0.05). There was no significant change in cardiac output, blood pressure or heart rate and individual changes in those values were not correlated with liver plasma flow. There was no correlation either between the plasma concentrations of pentoxifylline or its metabolites and the changes in liver plasma flow. It is concluded that, relative to the spontaneous decrease in liver plasma flow at rest on the placebo day, pentoxifylline increased splanchnic perfusion independent of any change in cardiac output.

Effects of alpha 1-blockade on arterial compliance in normotensive and hypertensive rats.

The effects of blockade of alpha 1-adrenergic receptors on the mechanical properties of the arterial wall were studied in 10 spontaneously hypertensive rats (SHR) as compared with 10 matched normotensive Wistar-Kyoto (WKY) rats. Ascending aortic pressure and flow were recorded in open-chest anesthetized rats, and the systemic arterial compliance was calculated. Intravenous injection (1 mg/kg) of Urapidil, a selective alpha 1-adrenergic antagonist, induced a significant decrease in arterial pressure (-26%, p less than 0.01 and -37%, p less than 0.001 in WKY rats and SHR, respectively) without significant changes in cardiac output. In control conditions, systemic arterial compliance was lower in SHR (3.29 +/- 1.52 microliters/mm Hg) than in WKY rats (4.35 +/- 1.35 microliters/mm Hg, p less than 0.01). Urapidil injection induced significant increases in systemic arterial compliance values in both strains (p less than 0.001). In another set of experiments (15 WKY rats and 15 SHR), the carotid compliance (microliters/mm Hg) was determined from the arterial volume-pressure relation under control conditions, after local incubation with Urapidil, and after total abolition of the vascular smooth muscle by KCN. In WKY rats, the carotid compliance increased markedly after incubation with Urapidil at doses corresponding to 1 mg/kg (+31%, p less than 0.01). A further increase in the carotid compliance was observed after KCN poisoning (+11%, p less than 0.05). In SHR, incubation with Urapidil at doses corresponding to 2 mg/kg were necessary to induce a significant increase in compliance (+38%). At this dosage, there was no further increase in compliance after KCN poisoning.(ABSTRACT TRUNCATED AT 250 WORDS)

Diets Enriched with N-3 Fatty Acids Ameliorate Lactic Acidosis by Improving Endotoxin-induced Tissue Hypoperfusion in Guinea Pigs

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.