Chronic hind limb ischemia reduces myocardial ischemia-reperfusion injury in the rabbit heart by promoting coronary angiogenesis/arteriogenesis.

BACKGROUND/AIM: Application of ischemic injury in a remote organ may provide protection of other tissues against ischemia. We hypothesized that ischemia in the rabbit hind limb protects against myocardial ischemia by increasing angiogenesis/arteriogenesis. MATERIALS AND METHODS: In the first experiment, severe limb ischemia (LI) was induced in 26 New Zealand White rabbits by excision of the femoral artery while another 26 served as controls (no ischemia; sham operation [SHO]). Four weeks later, the blood vessels of the subendocardial and intramyocardial areas of the excised hearts were counted. In the second experiment, 14 LI rabbits and 14 SHO controls were subjected to 30 min of regional heart ischemia and 3 h reperfusion. Infarct size and the areas-at-risk were determined. RESULTS: Compared with controls, LI rabbits showed more subendocardial (103+/-14 vs. 113+/-13 capillaries/mm2, respectively; p=0.01) and intramyocardial blood vessels (102+/-12 vs. 114+/-16 capillaries/mm(2), respectively; p=0.009). LI rabbits had significantly smaller infarct size compared with the SHO animals (infarct areas/areas-at-risk: 14.37+/-11.23% vs. 31.31+/-13.73%, respectively; p=0.003). CONCLUSION: Chronic hind LI reduces myocardial infarct size by promoting coronary angiogenesis/arteriogenesis in an experimental model.

Repeated balloon inflations do not diminish ST segment elevation even though coronary collateral recruitment is promoted in pigs.

OBJECTIVE: Attempts to demonstrate preconditioning during repeated angioplasty balloon inflations (BIs) have not been universally successful. The main obstacle is that the first BI is unreliable, due to the variable degrees of occlusion by the deflated balloon. In the present study, we examined whether ST segment elevation decreases and evaluated its relation to collateral recruitment during repeated angioplasty BIs in the pig. METHODS AND RESULTS: Twenty male pigs, 7 months old, under general anesthesia, underwent 3 repeated BIs of 120 s, with a 5-min interval between them, in the left anterior descending artery or the right coronary artery. A pressure wave wire was used for the measurement of coronary wedge pressure and to obtain the intracoronary ST segment elevation. Intracoronary ST segment elevation was 1.97 +/- 0.76 mV during the 1st BI, 2.09 +/- 0.82 mV during the 2nd BI and 1.84 +/- 0.82 mV during the 3rd BI (p = n.s.). Coronary wedge pressure was 12 +/- 6, 18 +/- 18 and 20 +/- 20 mm Hg (p < 0.05 vs. 1st BI) during the 3 BIs, respectively. CONCLUSION: Repeated BIs do not diminish ST segment elevation in the pig model, even though coronary collateral recruitment is promoted.

Endothelin-A receptor antagonism promotes decreased vasodilation but has no differential effect on coronary artery compliance in hypertensive patients.

The importance of endothelin-1 in the pathophysiology of essential hypertension is unclear. We therefore examined whether there is a differential effect of endothelin-A antagonism on vasodilation and coronary artery compliance in hypertensive compared to normotensive patients. We examined atherosclerotic non-stenotic arteries from 18 non-diabetic, 10 normotensive patients and eight hypertensive patients, before and after intracoronary infusion of BQ-123 (6 mumol), an endothelin-A receptor antagonist. The systolic and diastolic artery lumen area in the proximal segment was measured using an intravascular ultrasound catheter. Systolic blood pressure decreased only in hypertensive patients (F = 5.44, P = 0.03), after BQ-123 administration. The diastolic artery lumen increased from 8.9 +/- 2.9 mm at baseline to 10.8 +/- 3.0 mm after BQ-123 administration (P < 0.05) in normotensive patients and from 10.6 +/- 4.6 mm to 10.8 +/- 4.0 mm (P = NS) in the hypertensive patients (F = 3.98, P = 0.01). The respective values for the systolic artery lumen, in the two groups, before and after BQ-123 were: 10.2 +/- 3.4 mm and 12.7 +/- 3.2 mm (P < 0.01) in the normotensive group and 12.0 +/- 5.5 mm and 12.8 +/- 5.0 mm (P = NS) in the hypertensive group (F = 3.37, P = 0.08). Artery compliance did not have a differential response to BQ-123. In conclusion, endothelin-A antagonism causes decreased vasodilation but does not have a differential effect on coronary artery compliance in hypertensive patients.

Gender does not influence angiogenesis and arteriogenesis in a rabbit model of chronic hind limb ischemia.

OBJECTIVE: Estrogen administration promotes angiogenesis and perfusion in oophorectomized rabbits with chronic limb ischemia. In the present study we tested whether gender affects angiogenesis and arteriogenesis in a rabbit model of chronic hind limb ischemia. METHODS AND RESULTS: Ischemia was induced in one hind limb of five oophorectomized (Ooph), seven non-oophorectomized (NonOoph) female and eight male New Zealand White rabbits by excision of the femoral artery. Ten days after the induction of ischemia (day 0) and at days 15 and 30 systolic calf blood pressure was measured in the ischemic and non-ischemic hind limbs. Revascularization in the ischemic limb was expressed as ischemic/normal limb blood pressure, capillary/muscle fiber density, and non-capillary, non-lymphatic vessels/muscle fiber density after examination of light microscopic sections taken from the abductor muscle of the ischemic limb at the time of death (day 30). Ischemic/normal blood pressure at day 30 in males was 0.62 +/- 0.22, in NonOoph 0.64 +/- 0.09 (P=ns vs. males) and in Ooph 0.39 +/- 0.05 (P<0.05 vs. males and NonOoph), (F=4.69, P=0.02). Ischemic capillary/muscle fiber in males was 0.96 +/- 0.09, in NonOoph 0.95 +/- 0.06 (P=ns vs. males) and in Ooph 0.83 +/- 0.09 (P<0.05 vs. males and NonOoph), (F=5.93, P=0.01). Ischemic non-capillary, non-lymphatic vessels/muscle fiber density in males was 0.11 +/- 0.02, in NonOoph 0.12 +/- 0.03 (P=ns vs. males) and in Ooph 0.08 +/- 0.02 (P<0.05 vs. NonOoph), (F=5.05, P=0.02). CONCLUSION: Gender does not influence angiogenesis and arteriogenesis in the rabbit model of chronic hind limb ischemia. However, estrogen deficiency induced by oophorectomy negatively affects angiogenesis and arteriogenesis.