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Updated: May 31, 2026
Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats
Published on: June 28, 2019
Chronic skeletal muscle ischemia preserves coronary flow in the ischemic rat heart
Varnavas C Varnavas1, Konstantinos Kontaras, Chryssoula Glava
1Department of Cardiology, Red Cross Hospital, Athens, Greece.
Insights
Chronic hindlimb ischemia protects the heart during infarction by increasing coronary blood flow and vessel density, leading to smaller infarct sizes and improved left ventricular function. This cytoprotective effect is mediated by enhanced coronary collateral circulation.
Area of Science:
- Cardiovascular Physiology
- Ischemia-Reperfusion Injury
- Neovascularization
Background:
- Chronic skeletal muscle ischemia is known to confer cytoprotection to the ventricular myocardium during infarction.
- The precise mechanisms underlying this protective effect, particularly the role of neovascularization in the left ventricular myocardium, remain unclear.
- The functional capacity of coronary vessels in the context of chronic limb ischemia has not been adequately studied.
Purpose of the Study:
- To investigate the effects of chronic hindlimb ischemia on myocardial infarct size.
- To evaluate the impact of chronic limb ischemia on coronary blood flow and left ventricular function following ischemia-reperfusion.
- To assess the relationship between neovascularization, coronary blood flow, and cardiac protection.
Main Methods:
- Hindlimb ischemia was induced in Wistar rats via femoral artery excision; control rats underwent sham surgery.
- Myocardial infarction was induced by permanent coronary artery ligation 4 weeks after limb ischemia induction.
- Infarct size, left ventricular function (in isolated hearts), coronary blood flow, and coronary vessel density (via immunohistochemistry) were measured.
Main Results:
- Rats with chronic hindlimb ischemia exhibited significantly smaller infarct sizes compared to controls.
- Left ventricular function, assessed by developed pressure and dP/dt, was significantly improved in limb-ischemic rats post-reperfusion.
- Chronic limb ischemia led to markedly increased coronary vessel density and maintained coronary blood flow after ligation, unlike controls.
Conclusions:
- Chronic hindlimb ischemia significantly decreases myocardial infarct size and attenuates left ventricular dysfunction.
- The protective effects are attributed to increased coronary collateral vessel density and enhanced coronary blood flow.
- This study elucidates a key mechanism of cytoprotection involving improved coronary circulation.
Abstract:
Chronic skeletal muscle ischemia confers cytoprotection to the ventricular myocardium during infarction, but the underlying mechanisms remain unclear. Although neovascularization in the left ventricular myocardium has been proposed as a possible mechanism, the functional capacity of such vessels has not been studied. We examined the effects of chronic limb ischemia on infarct size, coronary blood flow, and left ventricular function after ischemia-reperfusion. Hindlimb ischemia was induced in 65 Wistar rats by excision of the left femoral artery, whereas 65 rats were sham operated. After 4 wk, myocardial infarction was generated by permanent coronary artery ligation. Infarct size was measured 24 h postligation. Left ventricular function was evaluated in isolated hearts after ischemia-reperfusion, 4 wk after limb ischemia. Neovascularization was assessed by immunohistochemistry, and coronary flow was measured under maximum vasodilatation at different perfusion pressures before and after coronary ligation. Infarct size was smaller after limb ischemia compared with controls (24.4 ± 8.1% vs. 46.2 ± 9.5% of the ventricle and 47.6 ± 8.7% vs. 80.1 ± 9.3% of the ischemic area, respectively). Indexes of left ventricular function at the end of reperfusion (divided by baseline values) were improved after limb ischemia (developed pressure: 0.68 ± 0.06 vs. 0.59 ± 0.05, P = 0.008; maximum +dP/dt: 0.70 ± 0.08 vs. 0.59 ± 0.04, P = 0.004; and maximum -dP/dt: 0.86 ± 0.14 vs. 0.72 ± 0.10, P = 0.041). Coronary vessel density was markedly higher (P = 0.00021) in limb ischemic rats. In contrast to controls (F = 5.65, P = 0.00182), where coronary flow decreased, it remained unchanged (F = 1.36, P = 0.28) after ligation in limb ischemic rats. In conclusion, chronic hindlimb ischemia decreases infarct size and attenuates left ventricular dysfunction by increasing coronary collateral vessel density and blood flow.
