Ziyin Bushen Decoction Alleviates Perimenopausal Syndrome in Rats by Enhancing Estradiol Production.

Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups (n = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ERα), GnRHR, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ERα, CYP17, CYP11A1, CYP19, 17ßHSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.

Analysis of internal spermatic vein embolization through catheter versus laparoscopic high ligation in treatment of left varicocele.

OBJECTIVE: Varicocele is a common disease in young and middle-aged men. This study aims to compare the efficacy of internal spermatic vein embolization of left varicocele versus laparoscopic high ligation. METHODS: From January 2017 to September 2018, a total of 69 varicocele patients were admitted and given the opportunity to choose the treatment option. Among these, 26 patients were treated with sclerosing agent injection, while 43 patients underwent laparoscopic surgery. They were followed up for 12 months after surgery, and the technical success rate, recurrence rate, complication rate, cost, operative time, and hospitalization time with regard to these two methods were analyzed. RESULTS: All patients completed the medical procedures. There was no recurrence in patients in the sclerotherapy group during the follow-up period; however, the complication rate was 19.2%. Furthermore, the operative time, hospitalization time, and cost of treatment were 31.1 ± 11.1 min, 1.2 ± 0.49 days, and 9613.11 ± 895.97 Yuan, respectively. In the laparoscopic group, 9 patients underwent laparoscopic bilateral high ligation, while 34 patients received treatment on the left side alone. The recurrence rate of left varicocele was 4.7% and the complication rate was 44.2%. Furthermore, the operative time, hospitalization time, and treatment cost were 50.4 ± 14.48 min, 4.0 ± 2.02 days, and 10,948.29 ± 2547.00 Yuan, respectively. Moreover, there were statistically significant differences (P < 0.05) in operative time, hospitalization time, and treatment cost. Patients in the sclerotherapy group had an advantage with respect to the overall complication rate when compared with patients from the laparoscopic group (X2 = 4.448, P < 0.05), and there was a statistically significant difference in hydrocele (X2 = 4.555, P < 0.05). However, there was no significant difference in the recurrence rate between these two groups (X2 = 1.245, P > 0.05). CONCLUSION: Patients who underwent sclerotherapy showed a higher technical success rate, a lower recurrence rate, fewer complications, and shorter hospitalization time compared to those treated with laparoscopic ligation. Transcatheter sclerosing agent injection may be a preferable treatment option for patients with unilateral varicocele.

Efficacy of Endovenous Laser Treatment Combined with Sclerosing Foam in Treating Varicose Veins of the Lower Extremities.

INTRODUCTION: This study aims to investigate the efficacy of incision-free endovenous laser treatment (EVLT) combined with sclerosing foam in treating varicose veins of the lower extremities. METHODS: A total of 140 patients (186 limbs) who underwent laser closure of the great saphenous vein + injection sclerotherapy were included in the present study. Preoperative information, intraoperative conditions, duration of the operation, and length of hospital stay were recorded in detail. During the 6-month follow-up, the closure of the trunk and branches of the great saphenous vein, postoperative pain, the recovery of ulcer and dermatitis, and postoperative complications were traced. RESULTS: All patients were treated with laser closure of the great saphenous vein and lauromacrogol injection. Twenty-six stage C6 limbs (lower extremity with ulcer) healed within 6 months, and the postoperative subjective pain disappeared after 1 month. In six patients, pigmentation in the surgical site did not completely disappear at 6 months after the operation. Saphenous nerve injury was found in five patients within 3 months after the operation, and all healed at 6 months after the operation. CONCLUSION: EVLT combined with sclerosing foam is effective for treating varicose great saphenous veins. TRIAL REGISTRATION: This study was registered at http://www.chictr.org.cn (registration number: ChiCTR1900021409).

Nanoparticle-mediated arresten gene inhibits neointimal formation of vein grafts: an experimental research.

BACKGROUND: Recently, we established a new rat model of venous arterialization by grafting the jugular vein into carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft diseases. Using this model, we studied nanoparticles that mediated the arresten gene to inhibit the neointimal formation of vein grafts. METHODS: Thirty healthy Wistar female rats were randomly divided into three groups. Rat models of grafting the jugular vein into carotid arteries were established. Before and after surgery, all rats were subjected to anticoagulant drugs; and these were subcutaneously injected through different reagents after surgery. Group A: subcutaneous injection of nanoparticles to mediate the arresten gene (0.2 mL); group B: subcutaneous injection of blank nanoparticles (0.2 mL); group C: subcutaneous injection of saline (0.2 mL). At two weeks after the operation, veins of the objective blood vessel were obtained. Pathological changes of local vascular tissues and the new intima hyperplasia of experimental vascular segments were observed. Immunohistochemistry was used to observe the expression of MMPs. RESULTS: (I) After two weeks, pathological intimal hyperplasia reactions were more obvious in groups B and C than in group A (P<0.05). The difference between groups B and C was not statistically significant (P>0.05); (II) the expression of MMP-2 could be observed in different degrees among the three groups. The expression of MMP-2 markedly increased in groups B and C compared to group A (P<0.05), but the difference between these two groups was not statistically significant (P>0.05). CONCLUSIONS: (I) Nanoparticle-mediated arresten genes can reduce intimal hyperplasia in grafts; (II) we have recently shown that this gene reduced intimal hyperplasia, and this reduction is related to the reduced expression of MMP-2. This shows that the arresten gene can inhibit the degradation of the extracellular matrix (ECM).

Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: in vitro and in vivo evaluation.

OBJECTIVE: To investigate the therapeutic effects of cationic nanoliposome-mediated gene therapy combined with immunotherapy for colon cancer treatment. METHODS: Recombinant plasmids containing green and red fluorescent protein reporter genes were constructed using gene cloning methods. Gene-carrying cationic nanoliposomes were prepared based on the electrostatic adherence principle and then transfected into dendritic cells (DC), which were transplanted into colon cancer cells. RESULTS: Recombinant plasmids containing green or red fluorescent protein reporter genes were successfully constructed by gene cloning and confirmed by restriction enzyme digestion and sequencing. Gene-carrying cationic nanoliposomes were transfected into colon cancer cells, and good gene expression was detected. A better level of apoptosis was observed in the combined group of tyrosine kinase receptor 3 ligand (FL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), while the lowest level was detected in the control group. The parameters in the FL and TRAIL groups were between the above-mentioned combined group. CONCLUSION: Cationic nanoliposomes have the advantage of being gene carriers. The joint therapeutic effects of the two genes are superior to those of a single gene. Gene therapy combined with immunotherapy has significant implications for cancer treatment.

Endovascular treatment of Budd-Chiari syndrome.

BACKGROUND: Budd-Chiari syndrome (BCS) is a posthepatic portal hypertension caused by the obstruction of the lumen of the hepatic veins or the proximal inferior vena cava (IVC). This study aimed to evaluate the clinical experience of interventional therapy for Budd-Chiari syndrome. METHODS: IVC venography was carried out first, the obliteration or stenosis in the IVC was opened or dilated with the hard guided wire or Rups100 puncture needle and balloon, then a stent was routinely implanted for the type of obliteration or stenosis. RESULTS: The procedure was successful in 821 out of 903 cases including IVC intervention in 760 cases, and hepatic vein intervention in 61 cases. An IVC stent was used in 517 cases and hepatic vein stent in 19 cases. There were no pulmonary embolisms, but acute renal failure occurred in eight cases, hepatic coma in two cases and acute heart failure in 43 cases. Two patients died in this group and five cases were complicated with acute IVC thrombosis. Follow up of 7 to 124 months was made in 679 cases with recurrence found in 59 cases. CONCLUSIONS: Interventional therapy is safe and effective with a fast recovery for most types of BCS. It is gradually becoming the first therapeutic choice.

[Studying the therapeutic effects of hemoperfusion with continuous venovenous hemofiltration on the patients with acute paraquat poisoning].

OBJECTIVE: To explore the therapeutic effects of hemoperfusion (HP) with continuous venovenous hemofiltration (CVVH) on the patients with acute paraquat poisoning. METHODS: Ninety-one patients with acute paraquat poisoning were randomly divided into HP group (49 cases) and HP-CVVH group (42 cases). The mortality, survival duration and the death causes between the two groups were compared and analyzed. RESULTS: There were no significant differences in mortality (59.2% versus 61.9%) between the two groups. The mean time between poisoning and death in HP-CVVH group was (4.9 +/- 3.1) days, which was significantly longer than that (3.5 +/- 2.0) days in HP group (P < 0.05). The death proportion on 4th day after poisoning in HP group was 62.1% (18/29), which was significantly higher than that (30.8%, 8/26) in HP-CVVH group (P < 0.05). The hypoxia appeared in 4.3 +/- 2.5 days after poisoning in HP-CVVH group, which was significantly longer than that (3.2 +/- 1.9) days in HP group (P < 0.05). The mortality due to respiratory failure in HP group was 20.4% (10/49), which was significantly lower than that (40.5%, 17/42) in HP-CVVH group (P < 0.05). The incidence of acute renal failure in HP group was 63.3% (31/49), which was significantly higher than that (40.5%, 17/42) in HP-CVVH group (P < 0.05). CONCLUSION: The combined therapy of HP and CVVH can prevent the patients with acute paraquat poisoning from early death and prolong the survival duration, but can not reduce mortality for the patients with acute paraquat poisoning.

Correlation between the expression of the BAG-1 gene and clinicopathologic factors in colorectal cancer.

OBJECTIVE: The present study aims to investigate the expression and significance of the anti-apoptotic gene Bag-1 in colorectal cancer and to evaluate the relationship between the gene and the disease. METHODS: Bag-1 expression was examined in 320 colorectal cancer and 30 normal colorectal tissue samples using reverse transcriptase polymerase chain reaction (RT-PCR) and the immunohistochemical staining (streptavidin-biotin-peroxidase complex method. RESULTS: Using RT-PCR, Bag-1 was observed to be expressed in colorectal cancer tissues, but not in normal colorectal tissues. The expression of Bag-1 in colorectal cancer was closely correlated with pathologic grade, distant metastasis, Dukes stage, and prognosis, but it was not correlated with the pathologic type, tumor diameter, depth of invasion, and lymph node metastasis. CONCLUSION: Bag-1 protein was found to be overexpressed in colorectal cancer. They might be regarded as a biomarker for the diagnosis of the early stages of colorectal cancer. In addition, they have particular significance for the prognosis of colorectal cancer.

[Study on the prognosis of patients with acute paraquat intoxication].

OBJECTIVE: To study the correlation factors of acute paraquat intoxication prognosis. METHODS: The early paraquat concentration in plasma and urine, leukocyte count, hepatic and renal function, amylase, electrolyte and the parameters of arterial blood gas were analyzed retrospectively in 111 patients with acute paraquat intoxication. RESULTS: 43 cases (38.7%) of all the 111 patients survived and the other 68 cases (61.3%) died. The patient, whose paraquat concentration was not more than 8.0 µg/ml in plasma and 276.0 µg/ml in urine, could survive. But some patients could die, only if there was no paraquat found in plasma. The paraquat levels in plasma and urine were significantly lower in survivors [(0.82 ± 1.70), (28.12 ± 51.17) µg/ml] than in nonsurvivors [(9.32 ± 12.04), (384.53 ± 597.93) µg/ml, respectively] (P < 0.01). The levels of leukocyte count, serum creatinine, aspartate aminotransferase (AST), and amylase were significantly higher in nonsurvivors than in survivors (P < 0.05, P < 0.01). In addition, metabolic acidosis was easier to appear in nonsurvivors. The multiple logistic regression analysis indicated that the paraquat concentration in plasma and urine, leukocyte count, creatinine and base excess were all related to survival. CONCLUSION: The higher paraquat concentration in plasma and urine, leucocytosis, renal dysfunction and metabolic acidosis are all important factors for the prognosis of paraquat intoxication.

[Analysis of the occurrence of pulmonary embolism in 20 years in single medical center].

OBJECTIVE: To evaluate the correlation of pulmonary embolism (PE) and original diseases by retrospectively analysis of the patients for 20 years in single medical center. METHODS: Five hundred and five patients with PE were admitted and treated in General Hospital of Chinese PLA from January 1989 to January 2009, and their clinical data were retrospectively reviewed to analyze the risk factors of PE and the correlations of PE with the original diseases. RESULTS: Of the 505 patients with PE in the past 20 years, the incidence of PE was increased year by year, especially it increased spectacularly after the year of 2004 [61.2% (309) vs. 38.8% (196)]. It was found to be most prevalent in patients of 4160 years old. Its incidence in males was 1.52 folds higher than that of the females [60.4% (305) vs. 39.6% (200)]. Dyspnea, chest pain and hemoptysis were the initial symptoms in the PE patients. Among the 505 patients, 40.0% of them complained dyspnea with chest pain and hemoptysis. Among them, dyspnea occurred in 100.0% of patients, hemoptysis in 52.1%, and chest pain in 40.0%. In 31.1% of the patients if was complicated with deep venous thrombosis (DVT), 19.8% of them suffering from varicosity, 9.5% of them had the history of surgery less than 30 days before, 22.0% of them suffering from neoplasm, 3.6% of them were accompanied with cerebrovascular disease within 4 days, 17.4% of them were accompanied with infection, 10.1% of them were accompanied with primary pulmonary hypertension, and 16.8% of them were accompanied with heart diseases. Multivariate analysis showed that the history of surgery, DVT and neoplasm had significant correlation with the occurrence of PE [odds ratio (95% confidence interval), OR (95%CI) was 4.540 (2.186-9.443), 0.325 (0.155-0.682), 2.610 (1.020-6.708), P<0.05 or P<0.01], while oral contraception, primary pulmonary hypertension and cerebrovascular disease showed a less significant correlation with the occurrence of PE [OR (95%CI) was 0.297 (0.078-1.126), 3.210 (0.855-12.110), 2.939 (0.862-10.020), all P>0.05]. The age and infection did not show significant correlation with the occurrence of PE [OR (95%CI) was 1.041 (0.674-1.607) and 0.820 (0.410-1.665), both P>0.05]. CONCLUSION: The PE is difficult in diagnosis, but with increasing cognizance, the diagnostic rate of PE has been increased. Patients with history of surgical operation, DVT or neoplasm, who complain dyspnea without known cause, chest pain or hemoptysis, should be subjected to further examinations, as to confirm the diagnosis of PE, then the survival rate of the patients with PE may be elevated.

Pharmacokinetics and safety of a new bioengineered thrombolytic agent, human tissue urokinase type plasminogen activator in Chinese healthy volunteers.

The aim of our study was to investigate the pharmacokinetics and safety of human tissue urokinase type plasminogen activator (HTUPA) in healthy Chinese subjects after intravenous administration. Thirty-two subjects were given intravenous injection doses of 5-35 mg of HTUPA for safety evaluation. Twenty-four subjects were given 10, 20 or 30 mg HTUPA for pharmacokinetic assessment. Safety and tolerance were evaluated by monitoring adverse events, laboratory parameters, electrocardiography and vital signs. HTUPA concentration in human serum samples was determined by an enzyme-linked immunosorbent assay (ELISA) method. The main pharmacokinetic parameters were calculated by DAS software. HTUPA was generally well tolerated and in the whole study course no serious adverse events occurred. The main pharmacokinetic parameters were as follows: geometric mean [95% confidence interval, CI] for t1/2 were 1.5 (1.4, 1.6), 1.3 (1.2, 1.4), and 1.2 (1.2, 1.3) h, AUC0-t were 1.0 (0.7, 1.3), 2.1 (1.5, 2.7), and 5.6 (4.7, 6.6) mg h L(-1), AUC0-∞ were 1.1 (0.8, 1.3), 2.1 (1.5, 2.7), and 5.8 (4.7, 6.7) mg h L(-1) for 10, 20, and 30 mg group, respectively. The main pharmacokinetic parameters were not significantly different between males and females (P>0.05). No serious adverse events were reported by the subjects or revealed by clinical or laboratory examinations, suggesting the given doses were safe and well tolerated.

Etiology and clinical features of fever of unknown origin / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the etiology and clinical features of fever of unknown origin (FUO).</p><p><b>METHODS</b>The clinical data including etiology, diagnostic approaches, and clinical features were retrospectively analyzed in 816 patients with FUO who were presented in our department from January 2000 to January 2009.</p><p><b>RESULTS</b>Of these 816 FUO cases, 766 (93.9%) were confirmed to be with infective diseases(40.4%, n=330), connective tissue diseases (34.4%, n=281), malignant tumors (10.9%, n=89), other known diseases (8.1%, n=66), and unknown diseases (6.1%, n=50). The most common infective disease was tuberculosis (49.7%, 164/330), the most common connective tissue disease was adult-onset Stills disease (AOSD)(55.2%, 155/281), the most common malignant tumor was lymphoma(56.2%, 50/89), and the most common "other known disease" was Crohns disease(22.7%, 15/66). All lung cancer cases had obstructive pneumonia. Significantly more elderly patients suffered from infective diseases (49.4% vs.32.0%) and malignant tumor (15.6% vs. 6.4%) compared with the non-elderly (both P=0.0000), while the proportion of connective tissue diseases was significantly less than that of the non-elderly (17.9% vs. 50.1%, P=0.0000).</p><p><b>CONCLUSIONS</b>Most FUO can be confirmed after careful examinations and analysis. The main cause of FUO is infective diseases, especially tuberculosis in the elderly. The connective tissue diseases and malignant tumors are also important causes.</p>

[Study on the expression of uncoupling protein 2 in the kidney of the rats with hypothyroidism].

OBJECTIVE: To observe the change in the expression of uncoupling protein 2 (UCP2) in kidney mitochondria in rats with hypothyroidism, and study the mechanism of renal injury due to hypothyroidism. METHODS: The Wistar rats were randomly divided into control group (n=10) and hypothyroidism group (n=10). The hypothyroidism rat model was reproduced by low-iodine diet. The intake of iodine in control group and hypothyroidism group were 10.00 µg/d and 1.24 µg/d, respectively. The rats were raised under these conditions respectively for 3 months after they adapted to the feeding for 1 week. Then the thyroid function parameters were measured in blood, and the expressions of UCP2 protein and mRNA in renal tissue were measured by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) methods. RESULTS: The thyrotropic-stimulating hormone (TSH, mU/L) in hypothyroidism group was significantly higher than that in control group (4.88±1.37 vs. 1.65±0.33, P<0.05). The levels of total triiodothyronine (TT(3)), total thyroxine (TT(4)), free triiodothyronine (FT(3)) and free thyroxine (FT(4)) in serum in hypothyroidism group were significantly lower than those in control group [TT(3) (nmol/L) : 0.54±0.07 vs. 0.98±0.17, TT(4) (nmol/L): 7.82±2.18 vs. 48.78±3.65, FT(3) (pmol/L): 2.28±0.22 vs. 2.99±0.10, FT(4) (pmol/L): 11.38±1.74 vs. 29.27±0.95, all P<0.01]. The immunohistochemistry study revealed that the UCP2 protein expression in both renal glomeruli and tubule tissues in the hypothyroidism group was significantly lower than that of control group (renal glomeruli: 0.17±0.02 vs. 0.24±0.04, renal tubule: 0.19±0.02 vs. 0.25±0.02, both P<0.01). The RT-PCR showed that the UCP2 mRNA expression in the hypothyroidism group was significantly lower than that of control group (0.70±0.19 vs. 1.30±0.09, P<0.01). CONCLUSION: Hypothyroidism may produce damage to kidney, which is related to the down-regulation of UCP2 expression in the mitochondria of renal cells.

[Vicissitude of antibiotic sensitivity of Gram negative bacilli in patients with infection in emergency departments in Beijing during 2005 to 2007].

OBJECTIVE: To investigate changes in antibiotic sensitivity of Gram negative bacilli infections among emergency patients in large hospitals in Beijing during 2005 to 2007. METHODS: Retrospective analysis of all the identified strains of Gram negative bacilli, and their sensitivity to antibiotic obtained in the emergency departments of 5 top first-class hospitals in Beijing for recent 3 years. RESULTS: Two thousand two hundred and eighty-five strains of Gram negative bacilli had taken 64.62% of all, the priority 5 of which were Pseudomonas aeruginosa (23.89%), Escherichia coli (19.91%), Acinetobacter baumanii (17.59%), Klebsiella pneumoniae (8.05%) and Staphylococcus maltophilia (3.94%). The sensitivity of commonly used antibiotics plummeted greatly in recent 3 years, especially carbapenems, cephalosporins and quinolones. The resistance of imipenem-resistant Pseudomonas aeruginosa was 17.30%, 22.53%, 31.92% respectively. The resistance of imipenem-resistant Acinetobacter baumanii was 13.87%, 12.09%, 23.56% respectively. CONCLUSION: Infectious bacteria in emergency departments in Beijing top first-class hospitals tend to show the characteristics of hospital infection. In recent years, the sensitivity of bacilli to antibiotic has dropped greatly. The situation of antibiotics resistance might be depressed.

[Experimental study of the effects of mild hypothermia on the acute myocardial infarction size in the rabbits with coronary artery reperfusion].

OBJECTIVE: To study the effect of mild hypothermia on the acute myocardial infarction size in the rabbits with coronary artery reperfusion. METHODS: fourteen rabbits were randomly divided into two groups: mild hypothermia group and control group. Each group underwent 45 minutes of left anterior descending coronary artery occlusion and 2 hours of reperfusion. Core temperatures were measured with thermistor. The mild hypothermia group received ice cooling around the body and the core temperature was dropped to 32-35 centigrade after occluded for 30 minutes, while the control group's body temperature were kept above 38 centigrade. The myocardial area at risk and the infarct area were determined with Evan's blue dye and triphenyl tetrazolium chloride (TTC). RESULTS: The total elevated amplitude of ST segment in chest leads V1, V3 and V5 in the mild hypothermia group was (25.8+/-8.5) mV, it was lower than that in the control group (37.7+/-6.5) Mv (P=0.021). The changes of serum MB isoenzyme of creatine kinase (CK-MB) activities in mild hypothermia group was (2646.9+/-1227.3) U/L, it was significantly lower than that in the control group (4787.8+/-1934.2) U/L(P=0.045). The weight of infarct myocardium of the mild hypothermia group was (0.23+/-0.05)g, it was lower than that in the control group (0.42+/-0.16)g (P=0.020). Myocardial infarct size as a percentage of the risk zone (0.214+/-0.044 vs. 0.357+/-0.066, P=0.001) and of the left ventricle weight (0.041+/-0.010 vs. 0.071+/-0.027, P=0.029) were smaller than those in the control group. The ratio of the survived myocardial area over the risk zone in the mild hypothermia group was significantly higher than that in the control group (0.786+/-0.044 vs. 0.643+/-0.066, P<0.001). CONCLUSION: Mild hypothermia may reduce infarct size in the rabbits with transient acute myocardial infarction, and increase survived myocardium in the risk zone.