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The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis.

Zhang Q, Yuan W, Wang G, Wu J, Wang M, Li C - Crit Care (2014)

Bottom Line: Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05).Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05).Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively).

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. zqian604@163.com.

ABSTRACT

Introduction: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.

Methods: Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation.

Results: After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).

Conclusions: Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

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Schematic representation of a microdialysis probe implanted into the piglet myocardium.
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Fig2: Schematic representation of a microdialysis probe implanted into the piglet myocardium.

Mentions: The chest was opened by median strenotomy, and the heart was suspended in a pericardial cradle. Two pairs of 2-mm piezoelectric transducers were placed on the endocardial surface of the left ventricle (LV) on the major and minor axes. A tourniquet was placed around the inferior vena cava. Heparin sodium (200 U/kg) was administered intravenously before probe implantation to prevent blood coagulation [14]. Two microdialysis catheters (CMA70; CMA Microdialysis AB, Kista, Sweden) were implanted separately into the lateral wall of the LV myocardium midway between the apex and base of the heart. The CMA70 catheters were perfused with Ringer’s solution in situ for 45 minutes before baseline measurements were taken, and a constant flow was maintained (2.5 μl/min) using a microdialysis pump (CMA106; Microdialysis AB) [14] (Figure 2). The dialysate was collected by using a dialysate collector (CMA142; Microdialysis AB) every 30 minutes. The ISF from the LV wall was collected through the microdialysis tubes for 10 minutes (baseline). VF was then electrically induced and continued for 8 minutes. VF was defined as an electrocardiogram showing waveforms corresponding to VF and a rapid decline in mean aortic pressure (MAP) toward zero. Ventilation was stopped during VF induction, and ventilation was withheld for the entire 8-minute duration of VF. ISF was collected continuously at 0 to 2, 2 to 4, 4 to 6, and 6 to 8 minutes of VF.Figure 2


The protective effects of a phosphodiesterase 5 inhibitor, sildenafil, on postresuscitation cardiac dysfunction of cardiac arrest: metabolic evidence from microdialysis.

Zhang Q, Yuan W, Wang G, Wu J, Wang M, Li C - Crit Care (2014)

Schematic representation of a microdialysis probe implanted into the piglet myocardium.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4262990&req=5

Fig2: Schematic representation of a microdialysis probe implanted into the piglet myocardium.
Mentions: The chest was opened by median strenotomy, and the heart was suspended in a pericardial cradle. Two pairs of 2-mm piezoelectric transducers were placed on the endocardial surface of the left ventricle (LV) on the major and minor axes. A tourniquet was placed around the inferior vena cava. Heparin sodium (200 U/kg) was administered intravenously before probe implantation to prevent blood coagulation [14]. Two microdialysis catheters (CMA70; CMA Microdialysis AB, Kista, Sweden) were implanted separately into the lateral wall of the LV myocardium midway between the apex and base of the heart. The CMA70 catheters were perfused with Ringer’s solution in situ for 45 minutes before baseline measurements were taken, and a constant flow was maintained (2.5 μl/min) using a microdialysis pump (CMA106; Microdialysis AB) [14] (Figure 2). The dialysate was collected by using a dialysate collector (CMA142; Microdialysis AB) every 30 minutes. The ISF from the LV wall was collected through the microdialysis tubes for 10 minutes (baseline). VF was then electrically induced and continued for 8 minutes. VF was defined as an electrocardiogram showing waveforms corresponding to VF and a rapid decline in mean aortic pressure (MAP) toward zero. Ventilation was stopped during VF induction, and ventilation was withheld for the entire 8-minute duration of VF. ISF was collected continuously at 0 to 2, 2 to 4, 4 to 6, and 6 to 8 minutes of VF.Figure 2

Bottom Line: Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05).Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05).Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively).

View Article: PubMed Central - PubMed

Affiliation: Department of Emergency Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8# Worker's Stadium South Road, Chao-yang District, Beijing, 100020, China. zqian604@163.com.

ABSTRACT

Introduction: Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion injury. The aim of this study was to determine, by obtaining metabolic evidence from microdialysis, if sildenafil could reduce the severity of postresuscitation myocardial dysfunction and lead to cardioprotection through beneficial effects on energy metabolism.

Methods: Twenty-four male piglets were randomly divided into three groups: sildenafil (n = 8), saline (SA; n = 8) and sham operation (n = 8). Sildenafil pretreatment consisted of 0.5 mg/kg sildenafil administered once intraperitoneally 30 minutes prior to ventricular fibrillation (VF). The myocardial interstitial fluid (ISF) concentrations of glucose, lactate, pyruvate, glutamate and glycerol were determined by microdialysis before VF. Afterward, the piglets were subjected to 8 minutes of untreated VF followed by 15 minutes of open-chest cardiopulmonary resuscitation. ISF was collected continuously, and the experiment was terminated 24 hours after resuscitation.

Results: After 8 minutes of untreated VF, the sildenafil group exhibited higher glucose and pyruvate concentrations of ISF and lower lactate and glutamate levels in comparison with the SA group, and these data reached statistical significance (P < 0.05). Advanced cardiac life support was delivered to both groups, with a 24-hour survival rate showing a promising trend in the sildenafil group (7 of 8 versus 3 of 8 survivors, P < 0.05). Compared with the SA group, the sildenafil group had a better outcome in terms of hemodynamic and oxygen metabolism parameters (P < 0.05). Myocardial tissue analysis revealed a dramatic increase in the contents of ATP, ADP and phosphocreatine in the sildenafil group versus the SA group at 24 hours after return of spontaneous circulation (ROSC; P = 0.03, P = 0.02 and P = 0.02, respectively). Furthermore, 24 hours after ROSC, the sildenafil group had marked elevations in activity of left ventricular Na(+)-K(+)-ATPase and Ca(2+)-ATPase compared with the SA group (P = 0.03, P = 0.04, respectively).

Conclusions: Sildenafil could reduce the severity of postresuscitation myocardial dysfunction, and it produced better clearance of metabolic waste in the ISF. This work might provide insights into the development of a novel strategy to treat postresuscitation myocardial dysfunction.

Show MeSH
Related in: MedlinePlus