Heparin in experimental hyperdynamic sepsis
J. MeyerCharles S. CoxDavid N. HerndonHiro NakazawaChristopher W. LentzLillian D. TraberDaniel L. Traber
40
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
Objective To evaluate the hypothesis that heparin administration increases cardiac output and improves oxygenation in experimental hyperdynamic sepsis in sheep. Design Prospective trial. Setting Laboratory at a large university-affiliated medical center. Subjects A total of 14 sheep weighing 28 to 44 kg. Interventions All 14 chronically instrumented sheep received a continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) over 24 hrs. Seven sheep received a fixed bolus of beef lung heparin (5000 units) every 4 hrs intravenously. The other seven sheep served as controls. Measurements and Main Results The heparinized animals showed a triphasic cardiovascular response. Cardiac index increased (p < .05), and systemic vascular resistance index decreased (p < .05) at 2 hrs after the start of the endotoxin infusion (early phase, 0 to 2 hrs). Both variables returned to approximately baseline levels at 4 hrs (second period, 2 to 4 hrs). A hyperdynamic state (in terms of an increased cardiac index), a decreased systemic vascular resistance index, and a decreased mean arterial pressure (MAP) (p <. 05 for all) was observed in the third phase (8 to 24 hrs). In the control group, cardiac index, systemic vascular resistance index, and MAP showed no changes in the first period, but a slight decrease in cardiac index and a slight increase in systemic vascular resistance index in the second period. The onset of the hyperdynamic state was less pronounced in the control group and cardiac index was lower (p < .05); likewise, systemic vascular resistance index was increased (p < .05) when compared with heparinized animals. Both groups developed pulmonary hypertension during the endotoxin infusion. The gas exchange in the heparia group was significantly impaired in the first and second periods, but returned to baseline levels in the hyperdynamic phase, whereas the oxygenation of the nonheparinized animals showed only minor changes in the first and second phases, but deteriorated significantly during the third phase of endotoxemia. Conclusions In this experimental model of hyperdynamic sepsis, heparin significantly in fluenced the cardiopulmonary performanec Heparin preserved gas exchange and increased cardiac output but lowered systemic vascular resistance and MAP in the hyperdynamic states (Crit Care Med 1993; 21:84–89)Keywords:
Cardiac index
Bolus (digestion)
Hyperdynamic circulation
Mean arterial pressure
Cardiac index
Mean arterial pressure
Pulmonary wedge pressure
Cite
Citations (6)
Bispectral index
Cardiac index
Mean arterial pressure
Cite
Citations (11)
The acute haemodynamic effects of i.v. pinacidil 0.2 mg kg‐1 infused over 8 min were studied in 10 normotensive patients undergoing cardiac catheterisation. Mean arterial pressure fell from 94 +/‐ 3 mmHg (mean +/‐ s.e. mean) before infusion to 74 +/‐ 3 mmHg at 10 min after commencing infusion (P less than 0.001) and during this time heart rate increased from 75 +/‐ 4 to 106 +/‐ 7 beats min‐1 (P less than 0.001). Significant changes were recorded until the end of the observation period (70 min after commencing infusion). Cardiac index increased from 3.2 +/‐ 0.2 to 4.0 +/‐ 0.2 l min‐1 m‐2 (P less than 0.001) and systemic vascular resistance fell from 16 +/‐ 1 to 10 +/‐ 1 units (P less than 0.001) at 10 min after commencing infusion. By the end of the observation period, the values had returned to pre‐infusion levels. Only small changes in pulmonary haemodynamics were observed. These results indicate that pinacidil acts as a peripheral arteriolar vasodilator, and as such may have a role in the treatment of arterial hypertension and of cardiac failure.
Cardiac index
Pinacidil
Mean arterial pressure
Cardiac catheterisation
Cite
Citations (13)
Mean arterial pressure
Haemodynamic response
Cite
Citations (2)
We carried out experiments to assess the cardiac and regional haemodynamic effects of single or repeated injections of the novel bradycardic agent, S16257, (7,8‐dimethoxy 3‐{3‐{[(lS)‐(4,5‐dimethoxy‐benzocyclobutan‐l‐yl)methyl]methylamino}propyl}1,3,4,5‐tetrahydro‐2 H ‐benzapin 2‐one), in conscious rats. In the first experiment, male Long Evans rats were chronically instrumented for the measurement of cardiac or regional haemodynamics ( n = 9 in each group), and, on separate experimental days, were randomized to receive i.v. bolus injections of vehicle (5% dextrose) or S16257 at a dose of 1 mg kg −1 . In animals instrumented for the measurement of cardiac haemodynamics ( n = 9), following injection of vehicle, there were no immediate changes, and 7–8 h later there were slight reductions in heart rate and mean arterial blood pressure only. Injection of S16257 caused an immediate, transient, pressor effect but thereafter there were reductions in heart rate, mean arterial blood pressure, cardiac index and total peripheral conductance, together with increases in stroke index and peak aortic flow. The integrated decreases in heart rate, mean arterial blood pressure, cardiac index and total peripheral conductance and increases in stroke index, peak aortic flow, dF/dt max and central venous pressure following S16257 were all significantly greater than the changes after vehicle injection. After injection of S16257, the fall in heart rate and fall in cardiac index were not linearly related. In animals instrumented for the measurement of regional haemodynamics ( n = 9). the bradycardic effect of i.v. S16257 was accompanied by reductions in renal, mesenteric and hindquarters blood flows and vascular conductances that were greater than the changes seen following injection of vehicle, but only for the first 1 h. Considering animals instrumented for the measurement of cardiac and regional haemodynamics together, the bradycardic effect of S16257 was greater the higher the resting heart rate. In the second experiment, animals chronically instrumented for the measurement of cardiac or regional haemodynamics ( n = in each group) were given s.c. injections of S16257 (1 mg kg −1 ) on four consecutive days. The general patterns of change in cardiac and regional haemodynamics following s.c. injection of S16257 were as described above for i.v. injection, although the rates of onset of effects were slower. The bradycardic effect of S16257 was less on the first, than on the subsequent, three days. Overall, these results indicate that the bradycardic action of S16257 is not associated with any signs of negative inotropic action. Only the initial depressor effect of i.v. S16257 is associated with reductions in renal, mesenteric and hindquarters flow and vascular conductance significantly greater than those seen after vehicle injection. With repeated s.c. injection of S16257, there are no signs of desensitization to its bradycardic actions, nor impairment of regional perfusion. If these results extrapolate to the clinical setting, it seems likely that S16257 will have beneficial bradycardic effects, with no concurrent undesirable actions on other aspects of cardiovascular function.
Cardiac index
Mean arterial pressure
Bolus (digestion)
Aortic pressure
Cite
Citations (74)
Hemodynamic indices were determined in 13 anesthetized dogs. In 7 of them,iv injection of endotoxin(E coli 12*10(10)/mL/kg) followed by iv infusion of saline(0.05/ mL/kg/min) increased the vascular resistance, and decreased the mean arterial pressure, the stroke volume, cardiac output and cardiac index. In the other 6 dogs, iv jinfusion of higenamine (dl-demethylcoclaurine) 1 microg/kg/min after iv endotoxin caused no significant changes in blood pressure, decreased the vascular resistance and icreased the stroke volume, cardiac output and cardiac index as compared with those of the control dogs. These results suggest that higenamine improves the circulation of the endotoxin shock dogs.
Cardiac index
Mean arterial pressure
Cite
Citations (1)
Cardiac index
Mean arterial pressure
Cite
Citations (16)
Abstract. The haemodynamic changes during 4 h following maximal upright bicycle exercise were evaluated in six normals in a randomized controlled crossover design. Total peripheral resistance was reduced to 2 h (‐6·7 mmHgmin l ‐1 , P < 0·05); exercising and non‐exercising vascular beds were vasodilated for 2h (‐24·1 and ‐23·8 mmHg min ml ‐1 100ml ‐1 tissue, respectively, P < 0·05), associated with reductions in systolic (‐5·8 mmHg, P < 0·05) and diastolic pressure (‐8·3mmHg, P < 0·05). Rise in cardiac index for 1 h (+0·51min ‐1 m ‐2 , P < 0·05) was accounted for by an elevated heart rate (+14·4 beats min ‐1 , P < 0·01) as stroke volume was unchanged. Body temperature was elevated until 40min (+0·20°C, P < 0·05). The return of all haemodynamic variables to control by 3h suggests a 3 h limit for a hypotensive effect of exercise. Rise in body temperature is not the only factor responsible for the hypotension.
Cardiac index
Crossover study
Cite
Citations (35)
To identify hemodynamic variables that might indicate susceptibility to slowing of heart rate (HR) and to mean arterial pressure (MAP) decrease caused by cold injectate during thermodilution (TD) cardiac output determination, we measured hemodynamic variables in 32 anesthetized patients undergoing major surgery. A total of 608 cardiac output determinations were evaluated for any relationship between the magnitude of HR decreases and basal hemodynamic variables. The magnitude of HR decrease was pronounced in low cardiac index (CI), low mean pulmonary artery pressure (MPAP), and high systemic vascular resistance index (SVRI). Although there was some decrease in MAP associated with cold injectate, neither changes in SVRI nor those in the other hemodynamic variables correlated with the decreases in MAP. These results suggest that decreased CI and MPAP associated with elevated SVRI may be more susceptible to slowing of HR during cardiac output determination by TD in anesthetized patients.
Cardiac index
Mean arterial pressure
Cite
Citations (10)
Objective To test whether systemic vascular resistance and mean arterial pressure increase during the administration of the atrial natriuretic peptide antagonist, HS 142-1, in ovine experimental hyperdynamic sepsis. Design Prospective trial. Setting Research laboratory at a large university medical center. Subjects Chronically instrumented Merino breed ewes (n = 14). Interventions Continuous infusion of Pseudomonas aeruginosa (2.5 x 106 colony-forming units/min) for the experimental period of 48 hrs. One group (HS 142-1) received a continuous infusion of HS 142-1 (3 mg/kg/hr) from 40 to 48 hrs; the remaining sheep ("control") were given the vehicle sodium chloride 0.9%. Measurements and Main Results All sheep developed a hyperdynamic cardiovascular response by 40 hrs that was characterized by low values of systemic vascular resistance index (p < .05) and mean arterial pressure (p < .05), and an increased cardiac index (p < .05). HS 142-1 increased cardiac filling pressures (p < .05) without apparent effects on fluid balance, and was associated with a significantly (p < .05) higher mean arterial pressure than was found in the control group at 44 and 48 hrs. HS 142-1 did not change systemic vascular resistance index. At 44 and 48 hrs, cardiac index values were found to have significantly (p < .05) increased in the animals receiving HS 142-1, when these data were compared with cardiac output values at 40 hrs. Conclusion HS 142-1 increases cardiac filling pressures and maintains mean arterial pressure in hyperdynamic sepsis without reversal of sepsis-induced vasodilation. (Crit Care Med 1997; 25:820-826)
Cardiac index
Mean arterial pressure
Hyperdynamic circulation
Cite
Citations (13)