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Published on: June 7, 2011
Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion
J R Kersten1, P S Pagel, D C Warltier
1Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Insights
Protamine was found to inhibit the development of new blood vessels in the heart. This study shows protamine blocks coronary collateral growth in dogs with chronic myocardial ischemia.
Area of Science:
- Cardiovascular Research
- Angiogenesis Studies
- Ischemic Heart Disease Models
Background:
- Protamine is known to inhibit angiogenesis in laboratory and animal studies.
- Its specific impact on the development of coronary collateral circulation in response to ischemia remains unexamined.
Purpose of the Study:
- To investigate the effect of subcutaneously administered protamine on coronary collateral development.
- To test the hypothesis that protamine inhibits collateral growth in a canine model of chronic myocardial ischemia.
Main Methods:
- Canine model with daily, repetitive left anterior descending coronary artery occlusions for 22 days.
- Measurement of regional myocardial blood flow, LAD segment shortening, and coronary flow debt repayment.
- Comparison between saline-treated and protamine-treated groups.
Main Results:
- Saline-treated dogs showed significant increases in collateral blood flow and improved cardiac function over 22 days.
- Protamine treatment significantly attenuated collateral perfusion increases and sustained contractile dysfunction.
- Protamine inhibited the development of coronary collateral circulation in response to chronic ischemia.
Conclusions:
- Subcutaneous administration of protamine inhibits the development of coronary collateral circulation.
- Protamine's anti-angiogenic properties extend to the coronary vasculature in a setting of chronic ischemia.
Abstract:
Protamine has been demonstrated to inhibit angiogenesis in vitro and in vivo; however, its effect on coronary collateral development has not been examined. The present investigation tested the hypothesis that subcutaneously administered protamine inhibits canine coronary collateral development in response to chronic myocardial ischemia. Dogs underwent daily, repetitive, 2-min, left anterior descending coronary artery (LAD) occlusions for 22 consecutive days. Regional myocardial blood flow (radioactive microspheres), LAD segment shortening, and coronary flow debt repayment were measured in saline-treated (n = 7) and protamine-treated (n = 6) dogs on days 1, 8, 15, and 22. Coronary collateral development in saline-treated dogs was demonstrated by time-dependent significant (P < 0.05) increases in collateral blood flow to ischemic myocardium [day 1 0.10 +/- 0.01 vs. day 22 0.88 +/- 0.05 (SE) ml.min-1.g-1], progressive normalization of myocardial contractile function during LAD occlusion, and successive reduction in flow debt repayment. In contrast, protamine treatment significantly attenuated, increases in collateral perfusion (day 1 0.13 +/- 0.02 vs. day 22 0.36 +/- 0.03 ml.min-1.g-1). Regional contractile dysfunction and postocclusive reactive hyperemic responses were sustained over time in protamine-treated compared with saline-treated dogs. The results demonstrate that protamine inhibits coronary collateral development in response to chronic myocardial ischemia.
