Table 1. Effects of IACI in animal stroke models.

Name year	tMCAO	Infusate/supplements	Infusion rate (mL/min)	Infusion duration (min)	Infusion volume (mL)	Time to target temp (min)	Cortical brain temp (°C)	Striatal brain temp (°C)	Body core temp (°C)	Infarct volume (48 h)	Functional outcome (48 h)	Additional end points
Prereperfusion flushing
Ding et al87	2 h	Saline 23°C	2	3–4	7	3–4	32–33	32–33	NR	−73%	↑	↓ ICAM-1, ↓leukocyte infiltration,↓vascular plugging
		Saline 37°C	2	3–4	7	—	37	37	NR	−63%	↑	↓ ICAM-1, ↓leukocyte infiltration,↓ vascular plugging
Ding et al88	2 h	Saline 23°C+Heparina	3	3–4	8–10	3–4	32.4	33	37.5	−75%	↑ *	—
Ding et al89	2 h	Saline 37°C	2	3	6	NR	NR	NR	NR	NR	NR	↓ IL-1β, TNF-α, ↓ICAM-1
Ding et al90	2 h	Saline 37°C	2	3	6	NR	NR	NR	NR	NR	NR	↓ Edema↓ MMP-2, ↓MMP-9
Prereperfusion IACIs
Ding et al97	3 h	Saline 20°C	0.6	10	6	≤10	33.4	33.9	>36	−93%	↑ *	—
Li et al95	3 h	Saline 20°C	0.6	10	6	NR	NR	NR	NR	−57%*	↑ *	—
Luan et al96	3 h	Saline 20°C	0.6	10	6	≤10	33.4	33.9	>36	NR	NR	↓ ICAM-1, ↓ leukocyte infiltration
Zhao et al91	1.5 h	Saline 20°C	0.6	10	6	≤10	32.8	33.2	37	−44%**	↑**	—
	2 h	Saline 20°C	0.6	10	6	≤10	33.1	33.3	37.1	−33%**	↑**	—
	2.5 h	Saline 20°C	0.6	10	6	≤10	33.2	33.3	37.1	−47%**	↑**	—
	3 h	Saline 20°C	0.6	10	6	≤10	32.9	33.2	37	↔**	↑**	—
Song et al93	3 h	Saline 15°C	0.4	20	8	5–10	33–34	33–34	37	−48%	↑	↔
		Saline15°C+MgSO4b	0.4	20	8	5–10	33–34	33–34	37	−65%	↑	↓ Edema
Chen et al94	2 h	Saline 0°C	NR	NR	2.5	<3	30.5	30.8	NR	−32%	↑	—
		Human Albumin 0°Cc	NR	NR	2.5	<3	30.5	30.8	NR	−67%	↑	—
Postreperfusion Intraarterial Cold Infusions
Ji et al92	3 h	Saline 10°C	0.25	30***	7.5	20–25	34.6	—	NR	−33%	↔	↓ Edema
		Saline 10°C	0.25	3 × 10***	7.5	60–70	34.6	—	NR	−32%	↔	↓ Edema, ↓NSE,↓ MMP-9
Ji et al98	2 h	Saline 10°C	0.17–0.42	20***	NR	NR	33–34	—	NR	−54%	↑	↓ Edema, ↓NSE,↓S100β
	+1 h Rep.	Saline 10°C	0.17–0.42	20***	NR	NR	33–34	—	NR	−42%	↑	↓ Edema, ↓S100β
	+2 h Rep.	Saline 10°C	0.17–0.42	20***	NR	NR	33–34	—	NR	−31%	↑	↓ S100β

IACI, intraarterial cold infusion; ICAM, intracellular adhesion molecule; IL1β, interleukin-1β; MMP-9, matrix metalloproteinase-9; NR, not reported; NSE, neuron-specific enolase; TNF-α, tumor necrosis factor-α; tMCAO, transient middle cerebral artery occlusion.

Effects of intraarterial infusions into the ICA in animal models of stroke in comparison to untreated animals: All experiments were conducted in rats. Prereperfusion flushing uses high infusion rates and relatively high infusion temperatures (23°C to 37°C) to remove vasoactive and inflammatory substances before blood supply to the ischemic tissue is reestablished. Intraarterial cold infusions use lower infusion rates and low infusion temperatures (≤20°C) to induce selective brain hypothermia. Infusions are either started before or after blood flow to the ischemic tissue is reestablished (prereperfusion and postreperfusion infusions).

^a40 IE/mL.

^b120 mg/kg body weight.

^c500 mg/kg body weight, *28 days, ** compared with permanent ischemia, ***active rewarming after infusion.