Table 3.
Functional effects of targeting granules released by neutrophil degranulation in ischemic heart disease
| Intervention | Research object | Age | Models | Drug dosage | Administration method | experimental period | Major outcome | Reference |
|---|---|---|---|---|---|---|---|---|
| PF-1355 (an oral MPO inhibitor) | Female C57BL/6J mice | 8–12 weeks | MI | 50 mg/kg of PF-1355 dissolved in vehicle excipient containing 40 mM Tris, 0.5% hydroxypropylmethylcellulose acetate succinate (HPMCAS) and 10% hydroxypropyl methylcellulose (HPMC), pH 10, | Twice daily by oral gavage | 7 days | Decreased inflammation cells infiltration and attenuated left ventricular dilation | 20 |
| PF-1355 (an oral MPO inhibitor) | Female C57BL/6J mice | 8–12 weeks | MI | 50 mg/kg of PF-1355 dissolved in vehicle excipient containing 40 mM Tris, 0.5% hydroxypropylmethylcellulose acetate succinate (HPMCAS) and 10% hydroxypropyl methylcellulose (HPMC), pH 10 | Twice daily by oral gavage | 21 days of constant treatment | Both the cardiac function and remodeling were significantly improved | 20 |
| Pharmacological blockade of NE | Male C57BL/6 wild-type animal | Unknown | I/R | Unknown | Unknown | Unknown | Does not impact neutrophil transendothelial migration; Suppressed the increase in size of matrix protein low expression regions in the cremaster muscle I/R injury model | 61 |
| Sivelestat (an NE inhibitor) | C57BL/6J mice | Male approximately 10–12 weeks weighed at least 25 g | MI | 100 mg/kg/day | Once daily by intraperitoneally injected | 7 day | Improved survival and preserved cardiac function post-MI | 62 |
| Recombinant elafin (an endogenous neutrophil elastase inhibitor) | Patients | Perioperatively in patient | Patient undergoing coronary artery bypass surgery | 200 mg intravenous bolus administered | EMPIRE Eudra CT 2010-019527-58 | Unknown | Promising results (protective) | 63 |
| Sivelestat sodium hydrate (a selective NE inhibitor) | Swine | 20–35 kg | Ligation of the left anterior descending coronary artery for 12-min, followed by 90-min reperfusion | 6 and 60 mg/ml | Infused intracoronally | Starting just after reperfusion until the end of experiment | Attenuates myocardial contractile dysfunction due to myocardial stunning, thereby suppressing the production of interleukin-6 in activated neutrophils | 64 |
| Sivelestat (a NE inhibitor) | Adult male Wistar rats | Adult (240–300 g body weight) | I/R | Sivelestat was dissolved in KHB (10 μg/mL) to obtain a final concentration of 19 μmol/L | Infusion | 10 min before ischemia and for the first 10 min of reperfusion | Attenuates myocardial injury after cardioplegic arrest | 65 |
| SSR69071 (an elastase inhibitor) | Male New Zealand white rabbits | Weighing 2–3 kg | Coronary artery occlusion for 30 min followed by reperfusion for 120 min | 1 and 3 mg/kg | Intravenous intravenously | 15 min before coronary ligation or 25 min after coronary ligation (5 min before reperfusion) | Reduces myocardial infarct size | 66 |
| The mCRAMP peptide | Male C57BL/6 mice | 8–10 weeks | Ligation of the left anterior descending artery for 30 min followed by cardiac reperfusion for 24 h | 4 mg/kg/day | Intraperitoneally injected | Three consecutive days | Inhibited cardiomyocyte apoptosis | 97 |
| The cathelicidin related antimicrobial peptide (CRAMP) | C57 BL/6 mice | Unknown | MI | 10 μg/10 μL | Inject | 5 weeks after treatment | Enhanced functional recovery, smaller scar size and higher capillary density | 101 |
| Neuregulin-1 | Male Sprague Dawley rats | 7–8 weeks old with average body weight 298.56 ± 38.73 g | AMI | 10 μg/kg | Inject via the tail vein 2 h after the operation | Continued once daily for 7 days | Attenuates MI-induced dysfunctional cardiac electrical conduction | 124 |
| Apigenin | Male Wistar rats, | Weighing 220–250 g | AMI | 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively | Inject | Once a day | Ameliorates acute myocardial infarction of rats via inhibiting MMP-9 and inflammatory reactions | 125 |
| Trimetazidine | Male C57Bl/6 mice | Aged 8–12 weeks, weighing 22–25 g | MI | 20 mg/kg/day | Intraperitoneal injection | 7 days | Suppressed oxidative stress, inhibited MMP-2 and MMP-9, prevents cardiac rupture in mice with MI | 126 |
| Icariin | Male Sprague–Dawley rats |
Age, 7–8 weeks Weight, 220–250 g |
MI | At dosages of 3, 6, 12, and 20 mg/kg per day dissolved in the same amount of saline | Inject | 28 days after surgery | Attenuated myocardial apoptosis following MI by inhibiting apoptosis and CD147/MMP-9 pathway | 127 |
| Arginase inhibitor N-omega-hydroxy-nor-L-arginine (nor-NOHA) | Male Sprague – Dawley rats | 270– 400 g | 30 min of coronary artery ligation, followed by 2 h of reperfusion | 100 mg/kg | Intravenous as bolus injections | 15 min before the onset of ischemia | Protects from MI. Increase tenfold of the citrulline/ornithine ratio and decrease the infarct size | 133 |
| Arginase inhibitor N(ω) -hydroxy-nor-l-arginine (nor-NOHA; | Male Wistar rats (Charles River, Germany) | Weight 300–350 g | 30-min coronary artery ligation and reperfusion up to 8 days, | 100 mg/kg | Intravenously | 15 min before ischemia | Prevent the development of microvascular dysfunction and myocardial injury following I/R | 134 |
| Nrginase inhibitor (nor-NOHA | Female farm pigs | 27–38 kg | Coronary artery occlusion for 40 min followed by 4 h reperfusion | 2 mg/min | Systemic intravenous infusion | Started at 30 min of ischemia and continued up to 5 min after start of reperfusion | Local arginase inhibition during early reperfusion reduces infarct size | 135 |
MPO: Myeloperoxidase; MI: myocardial infarction; NGAL: neutrophil gelatinase-associated lipocalin; IR: Ischemia–reperfusion; MMP: matrix metalloproteinases proteins; CRAMP: Cathelicidin; NE: neutrophil elastase. Nor-NOHA: N-hydroxy-nor-L-arginine