Introduction
Materials and methods
In vitro experiments
Preparation of polymorphonuclear leukocytes
Levosimendan incubation
Determination of basal and stimulated oxidative burst activity of PMN
Scavenging of reactive oxygen species
Apoptosis of PMN
Surface expression of CD62L (selectin) and CD18 (integrin) on PMN
Patient study
Patients
Protocol
Statistics
Results
In vitro experiments
Effect of levosimendan on oxidative burst activity of PMN
Effects of levosimendan on apoptosis of PMN
Expression of selectins (CD62L) and integrins (CD18) on the surface of PMN
Patient study
Study population
Acute heart failure (n = 16) | Septic cardiac failure (n = 9) | |
---|---|---|
Mean age | 69 (17) | 74 (16) |
Women | 4 (25%) | 2 (22%) |
SOFA Score | 6 (5-10) | 13 (11-16) |
APACHE II Score | 16 (11-19) | 20 (15-27) |
Patients on catecholamines | 7 (44%) | 9 (100%) |
Patients on mechanical ventilation | 7 (44%) | 9 (100%) |
Patients on CRRT | 4 (25%) | 8 (89%) |
ICU Survival | 12 (75%) | 2 (22%) |
A) Acute heart failure (n = 16) | |||
---|---|---|---|
Hemodynamic parameters | before levosimendan | after levosimendan |
P value
|
EF (%) | 24 (20-29) | 38 (29-59) | 0.003 |
MAP (mmHg) | 80 (70-90) | 75 (70-80) | ns |
CVP (mmHg) | 8 (6-15) | 9 (5-14) | ns |
CI (l/min/m2) | 2.5 (2.3-2.6) | 2.7 (2.6-3.3) | 0.04 |
B) Septic cardiac failure (n = 9)
| |||
Hemodynamic parameters
|
before levosimendan
|
after levosimendan
|
P
value
|
EF (%) | 29 (21-30) | 30 (22-38) | ns |
MAP (mmHg) | 75 (73-80) | 75 (75-85) | ns |
CVP (mmHg) | 9 (5-13) | 12 (9-14) | ns |
CI (l/min/m2) | 2.2 (1.9-3.0) | 3.2 (2.4-3.9) | ns |
A) Acute heart failure (n = 16) | |||
---|---|---|---|
Laboratory parameters | before levosimendan | after levosimendan |
P value
|
Leukocytes (G/L) | 10.5 (8.3-14.8) | 10.5 (7.4-15.7) | ns |
CRP (mg/dL) | 3.2 (0.6-4.1) | 3.1 (1.7-7.4) | ns |
Procalcitonin (μg/L) | 0.3 (0.1-1.4) | 0.4 (0.2-0.8) | ns |
Serum IL - 6 (pg/mL) | 51 (34-327) | 44 (38-136) | ns |
Urea (mg/dL) | 75 (56-125) | 73 (51-150) | ns |
Creatinine (mg/dL) | 1.6 (0.9-2.4) | 1.3 (0.8-2.3) | ns |
Serum cystatin C (mg/L) | 1.6 (1.3-2.4) | 1.7 (1.3-2.6) | ns |
B) Septic cardiac failure (n = 9)
| |||
Laboratory parameters
|
before levosimendan
|
after start levosimendan
|
P
value
|
Leucocytes (G/L) | 10.5 (7.6-16.3) | 11.6 (8.2-14.5) | ns |
CRP (mg/dL) | 14.9 (9.0-21.4) | 14.2 (5.3-21.5) | ns |
Procalcitonin (μg/L) | 4.8 (1.1-26.9) | 2.8 (1.1-21.3) | ns |
Serum IL-6 (pg/mL) | 649 (387-1097) | 787 (477-1033) | ns |
Urea (mg/dL) | 76 (47-128) | 82 (46-159) | ns |
Creatinine (mg/dL) | 1.4 (0.8-2.5) | 1.6 (0.7-2.1) | ns |
Serum cystatin C (mg/L) | 2.3 (2.0-3.1) | 2.4 (2.0-3.0) | ns |
Hemodynamic parameters
Vasopressor support
ICU survival
Respiratory burst activity of patients treated with levosimendan
Patients with acute heart failure (n = 16)
Patients with septic shock (n = 9)
Discussion
Effects of levosimendan on reactive species production of PMN
Effects of levosimendan on apoptosis and cell adhesion molecules
Possible mechanisms of levosimendan responsible for inhibition of respiratory burst activity of PMN
Clinical impact
Limitations
Conclusions
Key messages
-
Levosimendan significantly reduces oxidative burst activity of PMN from healthy volunteers.
-
Immunomodulation (reduced PMN burst activity) by levosimendan can also be observed in critically ill patients suffering from septic shock with septic myocardial depression or acute heart failure.
-
Levosimendan as a substance does not exhibit free radical scavenging properties.