OBJECTIVES

Clinical pathways (CPs) ensure adherence to heart failure (HF) management guidelines. To optimize quality care in a low resource setting, an evidence-based care pathway for the management of acute HF was implemented at the emergency department (ED) of the Philippine General Hospital (PGH), the designated national tertiary hospital and referral center. This study aimed to describe the characteristics of adults with acute HF admitted at the ED and evaluate the quality of care they received, measured using physician adherence to the hospital’s acute heart failure CP.

METHODS

This was a retrospective, descriptive cohort study. We reviewed the inpatient charts of all adult patients with acute HF admitted to the ED of the PGH and referred to the Division of Cardiovascular Medicine between December 1, 2022 and May 31, 2023. Quality of care was assessed based on adherence to quality indicators adapted from routine and conditional order sets detailed in the pathway. Descriptive statistics was utilized to describe patient characteristics, quality of care, and outcomes.

RESULTS

Two hundred thirty-six (236) patients were included, with a mean age of 51.8 years. Majority were male (53.4%); hypertension (61.4%) and ischemic heart disease (53.8%) were the most common comorbidities, and infection the most common precipitant of decompensation (60.6%). There were optimal adherence rates to routine orders, which included referrals to Internal Medicine and Cardiology, baseline vital signs monitoring, fluid intake and output monitoring, chest radiograph, complete blood count, blood urea nitrogen, sodium, potassium, prothrombin time, partial thromboplastin time, arterial blood gas, urinalysis, and N-terminal pro b-type natriuretic peptide. Conditional orders, such as oxygen support, focused echocardiography, thyroid - stimulating hormone, and the use of vasopressors, diuretics, and venous thromboembolism prophylactic agents, were optimally performed when warranted. However, we noted suboptimal adherence to certain resource-intensive conditional orders, such as hourly monitoring of urine output (61.4%), hooking to cardiac monitor (53.8%), and performance of 12-lead ECG within 10 minutes (56.8%). Further, only 43.9% of patients were referred to the intensive care unit. Troponin I, calcium, magnesium, and albumin were ordered in excess.

CONCLUSION

Overall adherence rate of physicians to the hospital’s Acute Heart Failure Pathway was satisfactory. Work is needed to improve adherence to hourly urine output monitoring, consistent hooking to cardiac monitor, and timely performance of 12-lead ECG – an effort that begins with expanding in-hospital diagnostic equipment and human resource supply. We recommend continuous pathway implementation with periodic evaluation and stakeholder feedback to further improve quality of care.

Human ; Male ; Female ; Middle Aged: 45-64 Yrs Old ; Adult ; Albumins ; Blood ; Blood Urea Nitrogen ; Calcium ; Cardiology ; Chart ; Charts ; Cohort Studies ; Critical Care ; Critical Pathways ; Diagnostic Equipment ; Disease ; Diuretics ; Echocardiography ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Equipment And Supplies ; Evaluation Studies As Topic ; Feedback ; Heart ; Heart Diseases ; Heart Failure ; Hormones ; Hospitals ; Hospitals, General ; Humans ; Hypertension ; Indicators And Reagents ; Infection ; Infections ; Inpatients ; Intensive Care Units ; Internal Medicine ; Lead ; Magnesium ; Male ; Medicine ; Myocardial Ischemia ; Natriuretic Peptide, Brain ; Natriuretic Peptides ; Nitrogen ; Overall ; Oxygen ; Partial Thromboplastin Time ; Patients ; Peptides ; Philippines ; Physicians ; Potassium ; Prothrombin ; Prothrombin Time ; Quality Of Health Care ; Referral And Consultation ; Sodium ; Statistics ; Tertiary Care Centers ; Thorax ; Thromboembolism ; Thromboplastin ; Thyroid Gland ; Time ; Troponin ; Troponin I ; Universities ; Urea ; Urinalysis ; Urine ; Venous Thromboembolism ; Vital Signs ; Work ; Workforce

BACKGROUND

Ischemic heart disease is the leading cause of mortality in the Philippines. Despite strong recommendations from clinical practice guidelines for reperfusion for acute myocardial infarction (AMI), local data reveal low rates of primary percutaneous coronary intervention (PCI) and early invasive strategies due to financial constraints and system inefficiencies. The recent expansion of the Philippine Health Insurance Corporation (PHIC) AMI benefits package presents an opportunity to improve access to appropriate care. A standardized, evidence-based national clinical pathway is needed to guide healthcare providers and ensure consistent, high-quality care of AMI across various healthcare settings.

OBJECTIVE

To develop a standardized, evidence-based national clinical pathway for the management of AMI patients eligible under the PHIC IHD-AMI benefits package.

METHODOLOGY

Existing AMI clinical pathways from nine public and private hospitals in the Philippines were collected and reviewed. A multidisciplinary Technical Working Group (TWG) appraised current guidelines using the AGREE II tool and evaluated the collected pathways to identify strengths, gaps and variations in practice. A draft pathway was created and refined through consensus-building with cardiology experts and stakeholders to develop the final pathway.

RESULTS

The final national AMI clinical pathway integrates evidence-based best practices and accounts for differences in institutional resources. It standardizes the use of ECG and cardiac biomarkers for diagnosis, provides clear criteria and timelines for reperfusion therapy, defines indications for coronary angiography and PCI, and recommends optimal medical therapy and cardiac rehabilitation.

CONCLUSION

The national AMI clinical pathway is a critical step toward improving the quality, equity and efficiency of AMI care in the Philippines. Developed through a collaborative, evidence-based process, it aligns clinical management with international standards while addressing local healthcare system realities. Adoption by PHIC as a quality standard is expected to enhance guideline adherence, inform health policy and financing, and drive improvements in health outcomes. Continued implementation support, monitoring and evaluation are necessary to ensure its impact, particularly in under-resourced or geographically isolated settings.

Myocardial Infarction ; Myocardial Ischemia ; Infarction

BACKGROUND

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality among Filipinos. The guideline-recommended treatment for AMI includes emergency care, early electrocardiogram, emergent coronary angiogram and angioplasty, intensive care, medical management and cardiac rehabilitation. However, the cost of treatment is very high and not affordable for most Filipinos. To address this, the Philippine Health Insurance Corporation (PHIC) released the ischemic heart disease – acute myocardial infarction (IHD-AMI) Benefits Package under Circular No. 2024-0032 on December 21, 2024. This package significantly increased the insurance coverage for AMI to include invasive procedures and cardiac rehabilitation. The UP-Philippine General Hospital (UP-PGH) was the first to implement this package. This paper documents the initial planning, system changes and innovations undertaken by UP-PGH to support implementation.

METHODOLOGY

This qualitative descriptive study used retrospective document review to detail revision of the existing acute coronary syndrome (ACS) pathway and development of the AMl pathway, restructuring of patient flow and upgrades in infrastructure and hospital capabilities. Meeting minutes from the Division of Cardiovascular Medicine and UP-PGH were reviewed to describe the hospital's preparation and implementation process.

RESULTS

UP-PGH established an efficient, evidence-based ACS and AMI pathway. Hospital protocols, staffing, infrastructure and equipment were aligned to implement the PHIC IHD-AMI Benefit Package. Key steps included resources upgrade, stakeholder consultations, pathway redesign, workflow development, process alignment and monitoring systems.

CONCLUSION

The PHIC IHD-AMI Benefit Package can be successfully implemented in a tertiary hospital with catheterization laboratory. The documented process at UP-PGH can serve as a model for other institutions planning to utilize the package.

Myocardial Infarction ; Myocardial Ischemia ; Acute Coronary Syndrome ; Insurance, Health ; Philippines

Ischemic heart disease (IHD) remains the most common cause of death while cerebrovascular disease (CVD) is the third most common in the Philippines. IHD and CVD represent complications resulting from prevalent non-communicable diseases (NCDs) and risk factors which present important opportunities for primary and secondary prevention.

This study aimed to pilot a sustainable multisectoral approach for community-based screening and management of cardiovascular (CV) risk factors and determine the effects of a multisectoral collaboration approach on the rate of screening, prevalence and control rates for selected risk factors.

This is a quality improvement project that determines the baseline prevalence and control rates of CV risk factors followed by intense screening efforts with support from private partnerships. The project's core components are: (a) capacity building (b) information dissemination; (c) service provision; and (d) health monitoring. Rates of screening, prevalence and control were monitored over a two-year period.

A total of 94,125 patients were screened through the ONE Cavite Project over two years (January 2021 to December 2022). A total of 61,271 were newly identified as having hypertension (65.1%), 24,069 diagnosed with diabetes mellitus type 2 (25.6%), 29,257 diagnosed to have dyslipidemia (31.1%) and 13,204 smokers (14.0%) were identified.

Intensification of screening was successful in improving identification of individuals with NCDs. The impact of continued educational support for both providers and patients in this study reaffirmed its role as a central component of NCD diagnosis, management and prevention.

Hypertension ; Diabetes Mellitus ; Dyslipidemias ; Myocardial Ischemia ; Primary Prevention

BACKGROUND

Ischemic heart disease is the leading cause of mortality in the Philippines. Despite strong recommendations from clinical practice guidelines for reperfusion for acute myocardial infarction (AMI), local data reveal low rates of primary percutaneous coronary intervention (PCI) and early invasive strategies due to financial constraints and system inefficiencies. The recent expansion of the Philippine Health Insurance Corporation (PHIC) AMI benefits package presents an opportunity to improve access to appropriate care. A standardized, evidence-based national clinical pathway is needed to guide healthcare providers and ensure consistent, high-quality care of AMI across various healthcare settings.

OBJECTIVE

To develop a standardized, evidence-based national clinical pathway for the management of AMI patients eligible under the PHIC IHD-AMI benefits package.

METHODOLOGY

Existing AMI clinical pathways from nine public and private hospitals in the Philippines were collected and reviewed. A multidisciplinary Technical Working Group (TWG) appraised current guidelines using the AGREE II tool and evaluated the collected pathways to identify strengths, gaps and variations in practice. A draft pathway was created and refined through consensus-building with cardiology experts and stakeholders to develop the final pathway.

RESULTS

The final national AMI clinical pathway integrates evidence-based best practices and accounts for differences in institutional resources. It standardizes the use of ECG and cardiac biomarkers for diagnosis, provides clear criteria and timelines for reperfusion therapy, defines indications for coronary angiography and PCI, and recommends optimal medical therapy and cardiac rehabilitation.

CONCLUSION

The national AMI clinical pathway is a critical step toward improving the quality, equity and efficiency of AMI care in the Philippines. Developed through a collaborative, evidence-based process, it aligns clinical management with international standards while addressing local healthcare system realities. Adoption by PHIC as a quality standard is expected to enhance guideline adherence, inform health policy and financing, and drive improvements in health outcomes. Continued implementation support, monitoring and evaluation are necessary to ensure its impact, particularly in under-resourced or geographically isolated settings.

Myocardial Infarction ; Myocardial Ischemia ; Infarction

BACKGROUND

Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality among Filipinos. The guideline-recommended treatment for AMI includes emergency care, early electrocardiogram, emergent coronary angiogram and angioplasty, intensive care, medical management and cardiac rehabilitation. However, the cost of treatment is very high and not affordable for most Filipinos. To address this, the Philippine Health Insurance Corporation (PHIC) released the ischemic heart disease – acute myocardial infarction (IHD-AMI) Benefits Package under Circular No. 2024-0032 on December 21, 2024. This package significantly increased the insurance coverage for AMI to include invasive procedures and cardiac rehabilitation. The UP-Philippine General Hospital (UP-PGH) was the first to implement this package. This paper documents the initial planning, system changes and innovations undertaken by UP-PGH to support implementation.

METHODOLOGY

This qualitative descriptive study used retrospective document review to detail revision of the existing acute coronary syndrome (ACS) pathway and development of the AMl pathway, restructuring of patient flow and upgrades in infrastructure and hospital capabilities. Meeting minutes from the Division of Cardiovascular Medicine and UP-PGH were reviewed to describe the hospital's preparation and implementation process.

RESULTS

UP-PGH established an efficient, evidence-based ACS and AMI pathway. Hospital protocols, staffing, infrastructure and equipment were aligned to implement the PHIC IHD-AMI Benefit Package. Key steps included resources upgrade, stakeholder consultations, pathway redesign, workflow development, process alignment and monitoring systems.

CONCLUSION

The PHIC IHD-AMI Benefit Package can be successfully implemented in a tertiary hospital with catheterization laboratory. The documented process at UP-PGH can serve as a model for other institutions planning to utilize the package.

Myocardial Infarction ; Myocardial Ischemia ; Acute Coronary Syndrome ; Insurance, Health ; Philippines

Ischemic heart disease (IHD) remains the most common cause of death while cerebrovascular disease (CVD) is the third most common in the Philippines. IHD and CVD represent complications resulting from prevalent non-communicable diseases (NCDs) and risk factors which present important opportunities for primary and secondary prevention.

This study aimed to pilot a sustainable multisectoral approach for community-based screening and management of cardiovascular (CV) risk factors and determine the effects of a multisectoral collaboration approach on the rate of screening, prevalence and control rates for selected risk factors.

This is a quality improvement project that determines the baseline prevalence and control rates of CV risk factors followed by intense screening efforts with support from private partnerships. The project's core components are: (a) capacity building (b) information dissemination; (c) service provision; and (d) health monitoring. Rates of screening, prevalence and control were monitored over a two-year period.

A total of 94,125 patients were screened through the ONE Cavite Project over two years (January 2021 to December 2022). A total of 61,271 were newly identified as having hypertension (65.1%), 24,069 diagnosed with diabetes mellitus type 2 (25.6%), 29,257 diagnosed to have dyslipidemia (31.1%) and 13,204 smokers (14.0%) were identified.

Intensification of screening was successful in improving identification of individuals with NCDs. The impact of continued educational support for both providers and patients in this study reaffirmed its role as a central component of NCD diagnosis, management and prevention.

Hypertension ; Diabetes Mellitus ; Dyslipidemias ; Myocardial Ischemia ; Primary Prevention

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

OBJECTIVE: To explore the neuroprotective effect and underlying mechanism of Xingnao Kaiqiao acupuncture (acupuncture for regaining consciousness and opening orifices) in the rat models of cerebral ischemia-reperfusion injury (CIRI) based on the p53 protein (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway. METHODS: Of 102 male Wistar rats, 20 rats were randomly collected as a sham-operation group. Using a modified external carotid artery filament insertion method, CIRI models were prepared by occluding the middle cerebral artery in the rest rats. After modeling and excluding 1 non-successfully modeled rat and 1 dead one, the other modeled rats were randomized into a model group, an agonist group, an acupuncture group, and an acupuncture + agonist group, 20 rats in each one. Xingnao Kaiqiao acupuncture therapy was delivered in the rats of the acupuncture group and the acupuncture + agonist group. The acupoints included "Shuigou" (GV26), bilateral "Neiguan" (PC6), and "Sanyinjiao" (SP6) on the affected side. Electroacupuncture was attached to "Neiguan" (PC6) and "Sanyinjiao" (SP6) on the affected side, with dense-disperse wave, a frequency of 2 Hz/15 Hz and intensity of 1 mA. The intervention was delivered twice daily, 20 min each time and for 7 consecutive days. In the agonist group and acupuncture+agonist group, p53 agonist, COTI-2 was intraperitoneally injected (15 mg/kg), once daily for 7 consecutive days. Neurological deficit was evaluated using Zausinger's six-point scale. Cerebral infarction volume was quantified by triphenyl tetrazolium chloride (TTC) staining. Histopathological changes were observed using hematoxylin-eosin (HE) staining. Iron deposition was assessed by Prussian blue staining. Mitochondrial ultrastructure in the ischemic cortex was examined under transmission electron microscopy (TEM). Serum iron (Fe²⁺) was measured with chromometry. Malondialdehyde (MDA) and glutathione (GSH) levels in the ischemic hippocampus were determined using thiobarbituric acid and microplate assays, respectively. The mean fluorescence intensity of reactive oxygen species (ROS) in the ischemic cortex was analyzed by flow cytometry. The mRNA and protein expression of GPX4, SLC7A11, and p53 in the ischemic hippocampus were evaluated using quantitative real-time PCR (qRT-PCR) and Western blotting, respectively. RESULTS: Compared with the sham-operated group, the model group exhibited the decrease in neurological deficit score (P<0.01), and the increase in cerebral infarction volume percentage (P<0.01). The changes of brain tissue were presented in extensive cellular necrosis, pyknotic and deeply-stained nuclei, and vacuolar degeneration. The iron deposition was elevated in cortex and hippocampus (P<0.01), mitochondrial membrane density increased, the cristae was broken or reduced, and the outer membrane ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were elevated (P<0.01) and the level of GSH was reduced (P<0.01). The mRNA and protein expression of GPX4 and SLC7A11 was reduced (P<0.01), while that of p53 rose (P<0.01). When compared with the model group, in the agonist group, the neurological deficit score was reduced (P<0.05), the percentage of infarction volume was higher (P<0.01), the histopathological damage was further exacerbated, and the percentage of iron deposition increased in the cortex and hippocampus (P<0.01). The mitochondrial quantity decreased, the membrane density increased, the mitochondrial cristae were broken or reduced, and the outer membrane was ruptured. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were higher (P<0.01, P<0.05) and the level of GSH was reduced (P<0.05). The mRNA and protein expression of GPX4 and SLC7A11 decreased (P<0.01, P<0.05), while that of p53 was elevated (P<0.01). Besides, in comparison with the model group, the neurological deficit score was higher in the acupuncture group and the acupuncture + agonist group (P<0.01, P<0.05), the percentage of cerebral infarction volume was lower in the acupuncture group (P<0.01), the pathological damage of brain tissue was alleviated in the acupuncture group and the acupuncture + agonist group, and the percentage of iron depositiondecreased in the cortex and hippocampus (P<0.01). The mitochondrial structure was relatively clear, the mitochondrial cristae were fractured or reduced mildly in the acupuncture group and the acupuncture + agonist group. The levels of Fe²⁺ and MDA, as well as the mean flourscence intensity of ROS were lower (P<0.01) and the level of GSH was higher (P<0.01) in the acupuncture group. The mean fluorescence intensity of ROS were dropped (P<0.01) in the acupuncture + agonist group. The mRNA expression of GPX4 and SLC7A11 was elevated (P<0.01) and that of p53 was reduced (P<0.01, P<0.05) in either the acupuncture group or the acupuncture + agonist group; the protein expression of GPX4 and SLC7A11 rose (P<0.05, P<0.01) and that of p53 was dropped (P<0.01) in the acupuncture group; and the protein expression of p53 was also lower in the acupuncture + agonist group (P<0.05). When compared with the agonist group, in the acupuncture + agonist group, neurological deficit score increased (P<0.01), the percentage of cerebral infarction volume decreased (P<0.01), the pathological brain tissue damage was reduced, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was relatively clear and the cristae broken or reduced slightly; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were dropped (P<0.01), while the level of GSH increased (P<0.05); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01). In comparison with the acupuncture + agonist group, in the acupuncture group, the neurological deficit score increased (P<0.05), the percentage of cerebral infarction volume decreased (P<0.05), the pathological brain tissue damage was alleviated, the percentage of iron deposition in cortex and hippocampus decreased (P<0.01), the mitochondrial structure was normal in tendency; the levels of Fe²⁺ and MDA, as well as the mean fluorescence intensity of ROS were reduced (P<0.05), while the level of GSH rose (P<0.01); the mRNA and protein expression of GPX4 and SLC7411 was elevated (P<0.01, P<0.05), and that of p53 reduced (P<0.01, P<0.05). CONCLUSION Xingnao Kaiqiao acupuncture can alleviate neurological damage in CIRI rats, which is obtained probably by inhibiting ferroptosis through p53/SLC7A11/GPX4 pathway.
Animals ; Reperfusion Injury/metabolism* ; Male ; Acupuncture Therapy ; Rats ; Tumor Suppressor Protein p53/genetics* ; Brain Ischemia/metabolism* ; Rats, Wistar ; Signal Transduction ; Humans ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Disease Models, Animal ; Acupuncture Points ; Amino Acid Transport System y+/genetics*