Combination therapy for maximal myocardial infarct size reduction.
The aim of this study was to test whether myocardial infarct size reduction would be optimized by combining three known effective therapies: cariporide, regional hypothermia, and ischemic preconditioning (CHIP). Before coronary artery occlusion (CAO), treated rabbits (CHIP, n = 7) received cariporide (0.3 mg/kg), ischemic preconditioning (7 minutes ischemia and 5 minutes reperfusion), then 20 minutes of mild regional hypothermia (34 degrees C). Control rabbits (n = 7) received saline and a 34-minute waiting period. All received 30 minutes of CAO and reperfusion. In another study, rabbits (n = 8 in each group) received 90 minutes of CAO. In the 30-minute protocol, the authors found that hearts in both groups were equally ischemic during CAO. Mean ischemic risk zones were similar in both groups; however, in CHIP hearts, infarct size was 4 +/- 1% of risk zone, a reduction of 91% compared with control rabbits (44 +/- 7% of the risk zone, P = 0.001). In the 90-minute protocol, risk zone size was similar in both groups, but infarct size in control hearts was 76 +/- 3% of the risk zone compared with 34 +/- 7% in CHIP treated hearts (P = 0.0003). In summary, the combined treatment provided extraordinary protection. Infarct comprised only 4% of the risk region after 30-minute ischemia-a far greater reduction than was previously observed in the same laboratory using any single intervention. After 90 minutes of ischemia, infarct was 55% lower in CHIP hearts, suggesting that this therapeutic approach dramatically reduces ischemia/reperfusion cell death, even during long occlusions.
Hale
S L
SL
Heart Institute of Good Samaritan Hospital, Los Angeles, CA 90017, USA. sharon.hale@attglobal.net
Kloner
R A
RA
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006146:Guanidines / Q000627:therapeutic use*; D007036:Hypothermia, Induced; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control / Q000628:therapy*; D011817:Rabbits; D013450:Sulfones / Q000627:therapeutic use*; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D006146:Guanidines; D013450:Sulfones; C093373:cariporide