Increasing function of organs having reduced red blood cell flow

Abstract

The present invention relates to a method of therapeutically, or prophylactically, treating a vertebrate to increase tissue oxygenation, or maintain issue oxygenation, in tissue of a vertebrate wherein the tissue has a reduced red blood cell flow, and wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance. The method comprises introducing into the circulatory system of the vertebrate at least one dose of hemoglobin.

What is claimed is:  
     
         1 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to at least one partial obstruction of a blood vessel within the circulatory system of the vertebrate, and wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         2 . The method of  claim 1 , wherein the organ is a muscle.  
     
     
         3 . The method of  claim 1  wherein the organ is a heart.  
     
     
         4 . A method of  claim 3  wherein the heart has a partial stenosis selected from the group consisting of a blood vessel stenosis, a valve stenosis, a stenosis of an opening in the heart and a stenosis of a chamber of the heart.  
     
     
         5 . A method of  claim 1  wherein the polymerized hemoglobin is in a solution of polymerized hemoglobin and a physiologically acceptable carrier.  
     
     
         6 . A method of  claim 1  wherein the polymerized hemoglobin solution has concentration between about 120 grams of hemoglobin per liter and about 140 grams of hemoglobin per liter.  
     
     
         7 . A method of  claim 1  wherein the polymerized hemoglobin is in a physiologically acceptable suspension.  
     
     
         8 . A method of  claim 7  wherein the suspension is an emulsion.  
     
     
         9 . A method of  claim 1  wherein the partial obstruction is a stenosis.  
     
     
         10 . A method of  claim 9  wherein the stenosis is the result of a cause selected from the group consisting of a disease, a vessel wall abnormality, a compression, a chemical effect, vasoconstriction and vasospasms.  
     
     
         11 . A method of  claim 1  wherein the partial obstruction is an intravascular blockage.  
     
     
         12 . A method of  claim 11  wherein the intravascular blockage is a blockage selected from the group consisting of a thrombosis, an embolism, a foreign body and an infection.  
     
     
         13 . A method of  claim 1  wherein the polymerized hemoglobin is administered therapeutically.  
     
     
         14 . A method of  claim 1  wherein the polymerized hemoglobin is administered prophylactically.  
     
     
         15 . A method of  claim 1 , further comprising the step of injecting the polymerized hemoglobin into a vertebrate by an injection method selected from the group consisting of intravascular injection, intracardial injection, intraperitoneal injection, subcutaneous injection, injection into a bone marrow of the vertebrate, and a combination thereof.  
     
     
         16 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance, while the organ has reduced oxygen delivery due to at least one partial obstruction of a blood vessel within the circulatory system of the vertebrate, comprising, introducing into the circulatory system of the vertebrate at least one dose of a polymerized hemoglobin solution wherein said hemoglobin solution has: 
 a) a hemoglobin concentration between about 120 grams/liter and about 140 grams/liter;    b) a methemoglobin content less than 15 percent by weight;    c) an oxyhemoglobin content less than or equal to 10 percent by weight;    d) an endotoxin concentration less than 0.5 endotoxin units per milliliter;    e) less than, or equal to, 15 percent by weight polymerized hemoglobin with a molecular weight greater than 500,000 Daltons; and    f) less than, or equal to, 10 percent by weight polymerized hemoglobin with a molecular weight less than or equal to 65,000 Daltons, thereby increasing function of the organ.    
     
     
         17 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to at least one partial obstruction of a blood vessel within the circulatory system of the vertebrate, and wherein the vertebrate has a major vessel hematocrit of at least about 30% and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         18 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to a decrease in a population of blood vessels associated with the organ, and wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         19 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to a cardiogenic dysfunction of the heart of the vertebrate, and wherein the vertebrate has a normovolemic blood volume and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         20 . A method of  claim 19 , wherein the cardiogenic dysfunction is selected from the group consisting of a myocardial infarction, arrhythmia, cardiomyopathy, cardioneuropathy and pericardial effusion.  
     
     
         21 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to a decrease in a population of blood vessels associated with the organ, and wherein the vertebrate has a major vessel hematocrit of at least about 30% and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         22 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, while the organ has reduced oxygen delivery due to a cardiogenic dysfunction of the heart of the vertebrate, and wherein the vertebrate has a major vessel hematocrit of at least about 30% and at least a normal systemic vascular resistance, comprising introducing into the circulatory system of the vertebrate at least one dose of polymerized hemoglobin, thereby increasing function of the organ.  
     
     
         23 . A method of  claim 22 , wherein the cardiogenic dysfunction is selected from the group consisting of a myocardial infarction, arrhythmia, cardiomyopathy, cardioneuropathy and pericardial effusion.  
     
     
         24 . A method for increasing tissue oxygenation and, consequently, increasing organ function of a vertebrate, wherein the vertebrate has a major vessel hematocrit of at least about 30% and at least a normal systemic vascular resistance, while the organ has reduced oxygen delivery due to at least one partial obstruction of a blood vessel within the circulatory system of the vertebrate, comprising introducing, into the circulatory system of the vertebrate, at least one dose of a polymerized hemoglobin solution wherein said hemoglobin solution has: 
 a) a hemoglobin concentration between about 120 grams/liter and about 140 grams/liter;    b) a methemoglobin content less than 15 percent by weight;    c) an oxyhemoglobin content less than or equal to 10 percent by weight;    d) an endotoxin concentration less than 0.5 endotoxin units per milliliter;    e) less than, or equal to, 15 percent by weight polymerized hemoglobin with a molecular weight greater than 500,000 Daltons; and    f) less than, or equal to, 10 percent by weight polymerized hemoglobin with a molecular weight less than or equal to 65,000 Daltons, thereby increasing function of the organ.