Association between physical activity and changes in renal function in patients after acute myocardial infarction: A dual-center prospective study.

BACKGROUND: Acute myocardial infarction (AMI) causes a decline in renal function. This study aimed to elucidate the longitudinal association between physical activity levels and changes in renal function up to 6 months after the onset of AMI. METHODS: In this dual-center prospective observational study, 73 AMI patients (67 men; average age, 65.0±11.7 years) were enrolled from 2017 to 2019. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 and 6 months post-discharge. The renal function was evaluated based on cystatin C-based estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 6 months post-discharge. Generalized estimating equation (GEE) models were used to test the longitudinal association between physical activity levels and within-patient changes in eGFRcys. Both GEE models with a follow-up period of 3 and 6 months were constructed to assess the effects of the passage of time. RESULTS: Patients were stratified into the low (n=36; 2903±1187 steps/day) and high groups (n=37; 7988±3192 steps/day) based on the median number of steps. Both GEE models at the 3- (p=0.027) and 6-month follow-up (p=0.034) showed a significant positive association between the physical activity levels and within-patient changes in eGFRcys. The changes in eGFRcys at 6 months were -0.3 mL/min/1.73 m2 and +4.4 mL/min/1.73 m2 among the low and high group participants, respectively. CONCLUSIONS: There was a significant positive association between physical activity and renal function changes after the onset of AMI, which persisted when the follow-up period was extended from 3 to 6 months. Our findings support the importance of interventions that enable maintaining high physical activity levels as a strategy for preserving renal function in AMI patients.

Association between physical activity and change in renal function in patients after acute myocardial infarction.

BACKGROUND: Combined renal dysfunction worsens the subsequent prognosis in patients after acute myocardial infarction (AMI). Therefore, establishing a therapeutic modality to maintain or improve renal function in AMI patients is necessary. This study aimed to elucidate the association between physical activity level and change in renal function in such patients. DESIGN: Prospective and observational study. METHODS: We enrolled 41 patients (35 men; average age, 67.5 ± 12.6 years) after AMI onset. Blood biochemistry, urinalysis, and physical function tests were conducted at discharge and 3 months after discharge. Renal function was evaluated based on cystatin C based-estimated glomerular filtration rate (eGFRcys). The number of steps was recorded for 3 months post-discharge. Generalized estimating equations (GEE) was used to test the association between physical activity level and within-patient changes in eGFRcys. RESULTS: Patients were stratified into low (n = 21; number of steps, 2335 ± 1219 steps/day) and high groups (n = 20; number of steps, 7102 ± 2365 steps/day). eGFRcys significantly increased from baseline to after 3 months in the high group (76.5 ± 13.8 to 83.2 ± 16.0 mL/min/1.73 m2, q = 0.004), whereas no significant change was observed in the low group (65.1 ± 15.9 to 62.2 ± 20.2 mL/min/1.73 m2, q = 0.125). Result of GEE adjusted for potential confounding variables showed a significant positive association between physical activity level and within-patient changes in eGFRcys (p = 0.003). Changes in eGFRcys was -2.9 mL/min/1.73 m2 among low group versus +6.7 mL/min/1.73 m2 among high group. CONCLUSIONS: Physical activity level was positively associated with changes in renal function, demonstrating that high physical activity may suppress renal function decline in patients after AMI.

Preventive effect of chronic endothelin type A receptor antagonist on coronary microvascular spasm induced by repeated epicardial coronary artery endothelial denudation in pigs.

AIM: We investigated the role of endothelin-1 (ET-1) in coronary microvascular spasm in a porcine model. METHODS: A flowmeter was implanted around the left anterior descending coronary artery (LAD), and epicardial coronary artery endothelial denudation (ED) was performed just distal to the flowmeter every 2 weeks (W) until 6 W in 10 pigs (ED group). Ten pigs were chronically treated with endothelin type A receptor (ET(A)) antagonist (TA-0201, 0.1 mg/kg/day, ED+ET(A) group), while neither ED nor administration of ET(A) antagonist was performed in 12 pigs (Control group). We assessed changes in LAD blood flow and the denuded site diameter induced by acetylcholine (ACh, 0.05 microg/kg i.c.). RESULTS: In the ED group, administration of ACh to LAD induced zero flow without LAD diameter reduction at 8 W. In the ED+ET(A) group, the decrease in LAD blood flow response to ACh was suppressed. Chronic administration of TA-0201 suppressed ROS generation in the myocardium. Decreases of eNOS and intimal thickening were smaller in the TA-0201 administration group than the non-TA-0201 administration group. CONCLUSION: Chronic administration of ET(A) receptor antagonist is effective to prevent coronary microvascular spasm.

Differing effects of metoprolol and propranolol on large vessel and microvessel responsiveness in a porcine model of coronary spasm.

OBJECTIVES: The purpose of this study is to assess the effect of beta1-selective blocker on coronary vasospasm. MATERIALS AND METHODS: Balloon epicardial coronary artery endothelial denudation was performed at the left anterior descending coronary artery every 2 weeks for a total of 4 times in pigs. Changes in denuded site diameter and left anterior descending coronary artery blood flow caused by acetylcholine or serotonin were assessed before each endothelial denudation and at week 8 in untreated pigs (ED group) and in those treated with metoprolol (Meto group) or propranolol (Pro group). RESULTS: In the ED group, decreased blood flow response to acetylcholine enhanced from -20+/-10% before the first ED to -100% (i.e. zero flow) at week 8 without denuded site narrowing, suggesting microvascular spasm, and serotonin-induced left anterior descending coronary artery diameter reduction at week 8 was -92+/-15%. In the Pro group, blood flow reduction by acetylcholine and left anterior descending coronary artery diameter reduction by serotonin did not change compared with those of the ED group. In the Meto group however, blood flow reduction by acetylcholine (week 8, -70+/-16%) and left anterior descending coronary artery diameter reduction by serotonin (week 8, -64+/-15%) were blunted (P<0.01) compared with those of ED and Pro groups. CONCLUSION: The beta1-selective blocker metoprolol was effective to prevent coronary vasospasm.

Specificity of vascular reactivity and remodeling after repeated endothelial injury in a swine model.

We investigated the difference in vascular responses and remodeling between coronary and iliac arteries after repeated endothelial denudation. Endothelial denudation of the left anterior descending coronary artery (LAD) and the right common iliac artery (RIA) was repeated 4 times twice a month using a Fogarty catheter in 21 pigs. Vascular responses to vasoactive drugs were evaluated as % luminal diameter changes on contrast angiography 2 weeks after the last denudation. Corresponding nondenuded sites, ie, the left circumflex coronary artery (LCX) and the left common iliac artery (LIA), were used as references. Acetylcholine (1 microg/kg) did not constrict the LCX (0 +/- 1%) and the LAD (1 +/- 1%, P < 0.05), whereas it constricted the RIA (20 +/- 6%) but not the LIA (-3 +/- 3%, P < 0.01). Alternatively, serotonin (10 microg/kg) constricted the LAD strikingly (88 +/- 5%, P < 0.01 versus LCX and RIA), as well as the RIA (35 +/- 10%, P < 0.05 versus LIA). Vasodilator responses to substance P and isosorbide dinitrate were not different after injury in both arteries. The intima-to-media ratio and adventitia-to-media ratio of the relevant site in cross section of tissue sample from LAD were greater than those from LCX, and were more prominent than those from RIA. The results show that vascular tone regulation after the endothelial injury and vascular remodeling might be altered in a vessel-specific manner.

Effects of antioxidants on coronary microvascular spasm induced by epicardial coronary artery endothelial injury in pigs.

OBJECTIVES: The effect of oxidative stress on coronary microvascular disease is unknown. We investigated whether chronic administration of ascorbic acid (ASC) or glutathione (GSH) prevents microvascular dysfunction and remodeling induced by upstream repeated coronary artery endothelial injury. METHODS: Balloon endothelial injury was repeated at the left anterior descending coronary artery (LAD), just distal to an implanted flow meter, every 2 weeks for 6 weeks in pigs. Changes in LAD blood flow induced by acetylcholine (ACh) and 5-hydroxytryptamine were assessed before each endothelial injury and at 8 weeks after the first endothelial injury in pigs without treatment (endothelial injury group, n = 12) and in pigs treated with oral ASC (3 g/day) (ASC group, n = 12) and ASC (3 g/day) plus GSH (1 g/day) (ASC + GSH group, n = 12). RESULTS: In the endothelial injury group, reduced blood flow in response to ACh was augmented from a decrease of 18 +/- 17% to a decrease of 100% (that is, zero flow, 8 weeks, P < 0.01), accompanied by an increase of ascorbyl free radicals (AFRs) in coronary sinus blood. In contrast, in the ASC + GSH group, blood flow response to ACh was altered to a decrease of 45 +/- 17% (8 weeks, P < 0.01 compared with the endothelial injury group), coronary sinus blood AFRs did not change (8 weeks, 21.4 +/- 12.5 signal intensities, P < 0.01 compared with the endothelial injury group) and the rate of platelet aggregation induced by adenosine diphosphate was small (8 weeks, 56 +/- 17%, P < 0.01 compared with the endothelial injury group). CONCLUSIONS: Chronic administration of antioxidants suppressed microvascular hypercontraction, suggesting that it may be a promising therapeutic strategy for treating coronary microvessel disorders, including microvascular angina.

Repeated epicardial coronary artery endothelial injuries lead to a global spontaneous coronary artery spasm.

OBJECTIVES: This study was conducted to develop a spontaneous coronary spasm model. MATERIALS AND METHODS: Balloon endothelial denudation was carried out in the epicardial left anterior descending coronary artery (LAD) every 2 weeks, for a total of four times, in 12 pigs. Changes in the denuded site diameter and LAD blood flow caused by acetylcholine or serotonin were assessed before each denudation and at week 8. Blood pressure, electrocardiogram (ECG) from the LAD area and LAD blood flow were monitored continuously in conscious and unrestrained pigs. RESULTS: Spontaneous ECG ST depression with a decrease in LAD blood flow appeared at around 2 weeks. In accordance with this, 0.5 microg/kg acetylcholine induced similar ECG and LAD blood flow changes without denuded site narrowing, suggesting microvascular spasm. Thereafter, ECG ST depression or elevation by serotonin via a denuded site spasm was found after 6 weeks and spontaneous ECG ST changes due to epicardial coronary artery spasm were observed. CONCLUSION: Epicardial coronary artery endothelial injury may induce spontaneous vasospasticity in the downstream coronary microvessels as well as in the denuded portion, suggesting functional abnormality through the entire coronary arterial tree.