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US 5,181,518 AGranted
Method of evaluating cardioprotective agents
OwnerPaul F. McDonaghinventor
Life of this patent
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Abstract
A bioassay and model is disclosed for screening experimental cardioprotective drugs and techniques, which employs small laboratory animal hearts in a model which mimics the pathophysiologic process.
Claims21
A bioassay model adapted for use with an isolated mammalian heart which mimics the human pathophysiologic process in order to screen experimental drugs and techniques for protection from ischemia-reperfusion injury comprising an extracorpeal coronary circuit comprising
- (1) means for associating the mammalian heart with the model;
- (2) a source of a first perfusate;
- (3) a source of a second perfusate comprising whole blood;
- (4) conduit means adapted for perfusing the first and second perfusates to the associated heart;
- (5) means for determining and evaluating cardiac pump function comprising an inflatable balloon adapted for insertion within the left ventricle of the associated heart through the mitral valve and first transducer means communicating with the balloon by a first lead for monitoring cardiac pump action as a function of pressure within the balloon;
- and
- (6) means for determining and evaluating coronary perfusion pressure comprising second transducer means communicating by a second lead with the conduit means for perfusing the first and second perfusate.
4 more elements
A bioassay method for determining reperfusion/ischemia injury comprising the steps of:
- (1) perfusing a first perfusate containing red blood cells through a coronary perfusion circuit to an isolated mammalian heart;
- (2) obtaining cardiac pump function and coronary perfusion pressure data while perfusing the first perfusate;
- (3) stopping perfusion for a predetermined period of time to cause ischemia;
- (4) perfusing a second perfusate containing whole blood through the coronary perfusion circuit for a predetermined period of time either prior to or immediately after ischemia;
- (5) immediately after the predetermined period of time of ischemia commencing reperfusion of the first perfusate;
- (6) monitoring cardiac pump function during reperfusion obtaining cardiac pump function and coronary perfusion data during reperfusion;
- and
- (7) comparing the preischemia and the reperfusion data, whereby to determine the extent of reperfusion injury.
5 more elements
A bioassay method for determining reperfusion injury comprising the steps of:
- (1) providing a bioassay model comprising an extracorpeal coronary circuit including an animal heart which mimics the human pathophysiologic process in order to screen experimental drugs and techniques for protection from ischemia-reperfusion injury;
- (2) circulating through the circuit to the animal heart in the model a first perfusate maintaining normal cardiac pump function;
- (3) determining the ventricular function of the heart while the perfusate is circulating through the bioassay model;
- (4) stopping circulation of the perfusate whereby to cause ischemia;
- (5) replacing the first perfusate with a second perfusate comprising a solution containing whole blood either just prior to or after the period of ischemia;
- (6) after a predetermined period of ischemia, reperfusing the perfusate to the heart;
- and
- (7) during reperfusion determining the ventricular function of the heart, whereby to obtain a comparison of postischemic to preischemic ventricular function.
5 more elements
Dependencies are inferred from the claim text.