TY - JOUR
T1 - Cardioprotection and myocardial reperfusion
T2 - Pitfalls to clinical application
AU - Heide, Richard S.Vander
AU - Steenbergen, Charles
PY - 2013/8/2
Y1 - 2013/8/2
N2 - With the advent of thrombolytic therapy and angioplasty, it has become possible to reduce myocardial infarct size through early reperfusion. Enormous effort has been expended to find therapies that can further reduce infarct size after early intervention. Animal studies have identified many cardioprotective pathways that have the potential to reduce infarct size if activated before the onset of ischemia. More recently, interventions effective at the onset of reperfusion have been described. Although basic research has identified many targets, most has been conducted in rodent models which may not be directly applicable to human disease and even promising agents have been disappointing in large-scale clinical trials. There are many potential explanations for this failure which is the subject of this review. Potential factors include (1) the variability inherent in the patient population, whereas animal studies usually use single sex homogeneous groups maintained on standard diets in carefully controlled environments; (2) the duration of ischemia is generally shorter in animal studies, resulting in potentially more salvageable myocardium than is often the case in patients; (3) that the animals are usually young without comorbidities, whereas the patient population is generally older and has significant comorbidities; (4) animals are not treated with medications a priori, whereas the patient population is often taking medications that may affect ischemic injury; and (5) animal studies may not involve thorough assessment of effects on organs other than the heart, whereas patients can experience adverse effects of treatment in other organs that can preclude clinical use.
AB - With the advent of thrombolytic therapy and angioplasty, it has become possible to reduce myocardial infarct size through early reperfusion. Enormous effort has been expended to find therapies that can further reduce infarct size after early intervention. Animal studies have identified many cardioprotective pathways that have the potential to reduce infarct size if activated before the onset of ischemia. More recently, interventions effective at the onset of reperfusion have been described. Although basic research has identified many targets, most has been conducted in rodent models which may not be directly applicable to human disease and even promising agents have been disappointing in large-scale clinical trials. There are many potential explanations for this failure which is the subject of this review. Potential factors include (1) the variability inherent in the patient population, whereas animal studies usually use single sex homogeneous groups maintained on standard diets in carefully controlled environments; (2) the duration of ischemia is generally shorter in animal studies, resulting in potentially more salvageable myocardium than is often the case in patients; (3) that the animals are usually young without comorbidities, whereas the patient population is generally older and has significant comorbidities; (4) animals are not treated with medications a priori, whereas the patient population is often taking medications that may affect ischemic injury; and (5) animal studies may not involve thorough assessment of effects on organs other than the heart, whereas patients can experience adverse effects of treatment in other organs that can preclude clinical use.
KW - clinical trial
KW - myocardial infarction
KW - reperfusion injury
UR - http://www.scopus.com/inward/record.url?scp=84881630526&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84881630526&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.113.300765
DO - 10.1161/CIRCRESAHA.113.300765
M3 - Review article
C2 - 23908333
AN - SCOPUS:84881630526
SN - 0009-7330
VL - 113
SP - 464
EP - 477
JO - Circulation research
JF - Circulation research
IS - 4
ER -