Cardioprotective Effect of the SDF-1α/CXCR4 Axis in Ischemic Postconditioning in Isolated Rat Hearts

BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The SDF-1α, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF-1α/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.

Polyphenol (-)-epigallocatechin gallate-induced cardioprotection may attenuate ischemia-reperfusion injury through adenosine receptor activation: a preliminary study / 대한마취과학회지

BACKGROUND: The activation of guanine nucleotide binding protein-coupled receptors, such as adenosine receptor (ADR) and opioid receptor (OPR), protects the heart against ischemia and reperfusion injury. We hypothesized that ADR or OPR might be involved in polyphenol (-)-epigallocatechin gallate (EGCG)-induced cardioprotection. METHODS: Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 10 microM of EGCG, with or without the ADR or OPR antagonist at early reperfusion. Infarct size measured with 2,3,5-triphenyltetrazolium chloride staining was chosen as end-point. RESULTS: EGCG significantly reduced infarct volume as a percentage of ischemic volume (33.5 +/- 4.1%) compared to control hearts (14.4 +/- 1.1%, P 0.05 vs. EGCG) blocked the anti-infarct effect by EGCG. The infarct reducing effect of EGCG was significantly reversed by 200 nM of the A1 ADR antagonist DPCPX (25.9 +/- 1.1%, P 0.05 vs. EGCG) and 100 nM of the A3 ADR antagonist MRS1334 (24.1 +/- 1.8%, P > 0.05). CONCLUSIONS: The infarct reducing effect of EGCG appears to involve activation of ADR, especially A1 and A2B ADR, but not OPR.

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial K(ATP) Channel Activation in Isolated Rat Hearts

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.

Analysis of the Perioperative Outcomes after Surgical Resection for 145 Patients with Hepatocellular Carcinoma

PURPOSE: Surgical resection for the hepatocellular carcinoma (HCC) is the only proven curative treatment modality. Most of these patients have chronic hepatitis with or without cirrhosis; therefore, curative resection with enough of a safety margin is always challenging for hepatic surgeons. The aim of our retrospective study was to analyze the correlation of the complications with the patient factors, the tumor factors and the surgical factors. MATERIALS & METHOD: A total of 145 patients who had hepatocellular carcinoma were resected surgically during the five year and nine months period between September 2000 and June 2006. We collected the database prospectively and we analyzed the perioperative outcomes from the accumulated database. RESULT: Anatomical resection, standard hemihepatectomy or systematic segmentectomy after injection of methylene blue dye into the portal vein branch was performed in 89 patients, and nonanatomical resection was done in 56 patients. The number of major resections that was more than two sections was 72, and the number of minor resection less than two sections was 73. The mean operative time was 270 minutes, the amount of bleeding was 669ml and the mean time of performing the Pringle maneuver was 31.5 minutes. Perioperative complication were noted in 20.0% of the patients and there were five mortalities (3.4%). The only one significant factor that affected a higher complication rate was the ICG15 and the significant factor that affected the mortality rate was the duration of the Pringle maneuver. CONCLUSION: Type oriented hepatic resection that achieves an adequate surgical resection volume is dependent on the status of the tumor and the hepatic reservoir function with limited bleeding, and these factors will help selected patients obtain a very good outcome with an acceptable complication rate and low mortality.

Effects of Magnesium Sulfate on Supraceliac Aortic Unclamping in Experimental Dogs

Intravascular administration of magnesium (Mg) causes vasodilation and increases renal blood flow. The aim of this study was to investigate the renal effect of Mg following unclamping of the supraceliac aorta. Mongrels were divided into two groups, control (group C, n=7) and Mg group (group Mg, n=7). In group Mg, 30 mg/kg MgSO4 was injected as a bolus immediately prior to unclamping the supraceliac aorta and thereafter as an infusion (10 mg/kg/hr). The group C received an equivalent volume of saline solution. Systemic hemodynamics, renal artery blood flow, renal cortical blood flow (RCBF), renal vascular resistance, and renal function were compared. Following the aortic unclamping, cardiac output and RCBF were less attenuated, and the systemic and renal vascular resistance was elevated to a lesser degree in the group Mg compared to the group C. There was no significant difference in the plasma renin activity, serum creatinine and Cystatin-C between the two groups. The present study shows that Mg infusion improves systemic hemodynamics and RCBF after aortic unclamping. However, we did not observe any improvement in renal function when Mg was administered after supraceliac aortic unclamping.