Table 1.

Summary of human studies examining exercise-induced changes in collateral flow, prior to the introduction of the coronary flow index measurement.

Study	Population	Design	Duration	Intervention	Control	Outcomes	Results
Nolewajka et al., 1979 [27]	n = 20 men Mean age 48 years MI previous 3-6 months	RCT	7 months	Exercise = 60-70% max HR, 2x per week for 1 hour (Group session), supervised exercise session x2 per week, unsupervised home exercise x1 per week.	x2 supervised sessions per week (Group) = Light calisthenics & volleyball.	Angiography, Scintigraphy, CPET with stress ECG	The exercise group significantly increased angina threshold and decreased HR at a set workload (p < 0.01). No improvement in collateralization, perfusion or ventricular function.
Fujita et al., 1988 [29]	n =16 (4 men/2 women) Mean age 58 years ≥1 major coronary artery obstruction (16 CTO’s)	RCT	22 days	Exercise (treadmill) 2x daily until angina pain was 60-80% max previously felt. Patients were pre-treated with 5000 IU intravenous heparin.	Exercise (treadmill) 2x daily until angina pain was 60-80% max previously felt.	ECG treadmill test (total exercise time, Rate pressure product (RPP) to time of angina), Radionuclide ventriculography, Angiography	The pre-exercise heparin group demonstrated a significant increase (p < 0.001) in exercise duration and RPP, as well as an increase in RPP at angina onset & ST depression (p < 0.01). None of the above were changed in the exercise-only group. Angiography demonstrated improved collateralization (however this was only evaluated in the exercise & heparin group). No significant increase in ventricular function.
Niebauer et al., 1995 [28]	n = 113 men Mean age 53.5 years Documented coronary stenosis Left ventricular ejection fraction > 35%	RCT	1 year	Initial 3 weeks on a metabolic ward learning to reduce the fat content of their diet (<20% total energy). 30 min exercise daily on a cycle ergometer at a target heart rate close to 75% max (achieved). ≥2 group training sessions per week (60min).	Initial week on metabolic ward receiving identical instructions on diet and the importance of regular physical exercise. Adherence to these instructions was left to their initiative (usual care given by physician).	Angiography, ventriculography, symptom limited exercise test with thallium-201 scintigraphy	Reduction in stenosis severity in the intervention group (p<0.05 versus control). No significant change in collateral formation for either group at 1 year. When both the groups of patients were combined, there was a correlation between stenosis progression and an increase in collaterals (p<0.00001). No significant correlation between collateral formation and exercise performance. No significant difference between collateral formation and stress-induced myocardial ischaemia on thallium-201 scintigraphy.
Belardinelli et al., 1998 [30]	n = 46 (42 men / 4 women) Mean age 57 years Chronic coronary artery disease and impaired left ventricular function (ejection fraction < 40%)	RCT	8 weeks	Supervised exercise (cycle ergometer) at 60% of peak oxygen uptake for 60 min 3x per week for 8 weeks.	Avoid regular exercise and activity with caloric expenditure over 80% peak oxygen consumption. Given a list of acceptable and unacceptable activities.	CPET, Stress Echocardiography, Scintigraphy, Angiography	VO2 peak increased in exercise group versus control (p < 0.001 versus control). Oxygen pulse for a set relative intensity was improved in the exercise group (p < 0.01). Collateral score significantly increased in the exercise group. Ejection fraction significantly improved in the exercise group (p< 0.001 versus control). Thallium activity (scintigraphy) significantly improved in the exercise group (p < 0.001 versus control). The mean collateral score significantly increased only in the exercise group (p < 0.001 versus control).

Abbreviations: RCT: Randomised Control Trial; HR: Heart Rate.