Scavenging dissolved oxygen via acoustic droplet vaporization
Methods and compositions for treating a patient for a condition characterized by an excess blood concentration of dissolved gas in at least one targeted region of the patient are provided. The method comprises administering a composition comprising a perfluorocarbon droplet emulsion into the blood of the patient; insonifying the at least one target region sufficient to achieve formation of microbubbles by droplet vaporization of at least a portion of the perfluorocarbon droplets present in the blood; whereby a concentration gradient favoring movement of gas molecules from the blood into the microbubbles is established for a time frame.
1. A method of treating a patient for a condition characterized by an excess blood concentration of dissolved gas in at least one targeted region of the patient, the method comprising: administering a composition comprising a perfluorocarbon (PFC) droplet emulsion into the blood of the patient; insonifying the at least one target region sufficient to achieve formation of microbubbles by droplet vaporization of at least a portion of the perfluorocarbon droplets present in the blood; whereby a concentration gradient favoring movement of gas molecules from the blood into the microbubbles is established for a time frame.
2. The method according to claim 1 , wherein the condition being treated is decompression sickness and the gas comprises nitrogen.
3. The method according to claim 1 , wherein the condition being treated is a pH-related biological condition and the gas comprises carbon dioxide.
4. The method according to claim 3 , wherein the condition comprises acidosis.
5. The method according to claim 1 , wherein the condition being treated is selected from oxygen toxicity and reperfusion injury and the gas comprises oxygen.
6. The method according to claim 1 , wherein the condition being treated is carbon monoxide poisoning and the gas comprises carbon monoxide.
7. The method according to claim 1 , further comprising preparing the PFC droplet emulsion prior to the step of administration, wherein preparing comprises generating size-isolated PFC droplets.
8. The method according to claim 7 , wherein size-isolated PFC droplets are generated by differential centrifugation.
9. The method according to claim 7 , wherein the size of the generated PFC droplets ranges from 0.3 μm to about 100 μm.
10. The method according to claim 7 , wherein the size of the generated PFC droplets ranges from about 2 μm to about 5 μm diameter.
11. The method according to claim 1 , wherein insonifying comprises administering ultrasound to the target at or above a threshold pressure amplitude, wherein threshold is defined as a minimum pressure amplitude necessary to transition the droplets.
12. The method according to claim 11 , wherein the insonifying comprises administering from between 500 kHz to 10 MHz ultrasound and ultrasound is administered at a pressure amplitude between the threshold pressure and 5 MPa.
13. The method according to claim 12 , wherein the insonifying comprises administering 2 MHz ultrasound and the threshold pressure amplitude is about 1.7 MPa.
14. The method according to claim 1 , wherein the time frame is between 10 milliseconds and 60 seconds.
15. The method according to claim 14 , wherein the time frame is approximately 20 seconds.
16. The method according to claim 1 , wherein the dissolved gas is oxygen and
a percent dissolved oxygen (DO 1 ) in the blood of the patient after insonification is predicted according to an equation:
D
O
l
=
k
n
l
V
l
P
l
0
×
D
O
l
0
wherein
k=Henry's constant for oxygen in water;
n l =number of moles of oxygen in blood surrounding the PFC droplets;
V l =volume of the blood surrounding the PFC droplets;
P l0 =initial partial pressure of oxygen in the blood surrounding the PFC droplets; and
DO l0 =initial dissolved oxygen in the blood surrounding the PFC droplets.
17. The method according to claim 1 , further comprising monitoring the treatment using imaging technology.