Table 1. Animal models of IR injury testing nitrite therapy.

A summary of seven studies that evaluate the potential therapeutic role for nitrite after focal IR injury.

Abbreviations: H&E = hematoxylin & eosin staining, TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, TTC = 2,3,5-triphenyltetrazolium chloride, AST = aspartate transaminase, ALT = alanine transaminase, MPO = myeloperoxidase, ATP = adenosine triphosphate, BUN = blood urea nitrogen, PTIO = 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, L-NAME = N -nitro-L-arginine methyl ester, (−) BOF-4272 = sodium 8-(3-methoxy-4-phenylsulfinylphenyl)pyrazolo[1,5- ]-1,3,5-triazine-4-olate monohydrate, eNOS (−/−) = endothelial nitric oxide synthase knockout mice, HO-1 (−/−) = heme oxygenase-1 knockout mice, ODQ = [1H-[1,2,4]Oxadiazole [4,3-a]quinoxalin-1-one] MRI = magnetic resonance imaging.

First Author Name and Reference	Year of Publication	Animal Model Used	Placebo Used	Dose of Nitrite, Route and Timing of Administration	Timing of Ischemia and Reperfusion	Outcome Measures of Cytoprotection	Inhibitors Used
Web, A[23]	2004	Rat Isolated Heart IR	saline	0.025 - 2.5 uM constant infusion for 15min prior to ischemia onset	60min ischemia and 30min reperfusion	p-nitroblue tetrazolium; left ventricular developed pressure and diastolic blood pressure	PTIO, L-NAME, allopurinol, BOF-4272
Duranski, MR[20]	2005	Mouse Liver and Heart IR	nitrate or saline	2.4 - 1920 nmol intraperitoneal (liver) or intraventricular (heart) midway through the ischemic time	Liver: 45min hepatic artery/portal vein occlusion, 5th reperfusion; Heart: 30min left main coronary artery occlusion, 24h reperfusion	H&E and TUNEL (liver), TTC (heart); AST/ALT (liver)	PTIO, L-NAME, ODQ, ZnDBGG, eNOS(−/−), HO-1(−/−)
Lu, P[22]	2005	Rat Liver IR	none (sham)	All rats given 2 mg/kg (29 nmol/g) nitrite	40min hepatic artery/portal vein occlusion, 3h (labs) or 7d (path) reperfusion	H&E; 7d mortality; ALT MPO and ATP	PTIO, L-NAME, allopurinol
Basireddy, M [61]	2006	Rat Kidney IR	nitrate or saline	1.2 nmol/g intraperitoneal prior to nephrectomy or midway during ischemia; 0.12 - 12 nmol/g intravenous prior to nephrectomy	R nephrectomy and 45min occlusion of L renal pedicle, 24-48h (labs) or 6d (path) reperfusion	H&E; BUN and creatinine	None - No treatment effect observed
Jung, KH [21]	2006	Rat Brain IR	nitrate	48 - 48,000 nmol intravenous at the time of reperfusion	90min occlusion of middle cerebral artery, 3h (LDF) or 24h (TTC) or 7d (neurological testing) reperfusion	TTC; laser doppler flow; neurological testing	PTIO
Tripatra, P [25]	2007	Rat Kidney IR	saline	0.12 nmol/g topically applied to the kidneys or given intravenous 1 min prior to reperfusion	60min bilateral renal ischemia, 6h reperfusion	H&E; BUN, creatinine, creatinine clearance, fractional urinary sodium excretion, AST	PTIO, allopurinol
Gonzalez, FM [24]	2007 (not published)	Canine Heart IR	saline	0.20 µmol/min/kg for 20 min followed by 0.17 µmol/min/kg for 40 min iv OR 0.20 µmol/min/kg for 5 min ending at reperfusion	2h left anterior descending occlusion, 6h reperfusion	TTC, TUNEL; microspheres and MRI	None