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Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans
I Vergroesen1, J E Kal, J A Spaan
1Department of Medical Physics, University of Amsterdam, The Netherlands. I.Vergroesen@amc.uva.nl
Insights
This study introduces a method to measure myocardial oxygen supply and demand ratio, crucial for evaluating coronary vasodilating drugs. This ratio helps distinguish genuinely effective drugs from those with apparent effects on coronary blood flow.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Myocardial oxygen consumption significantly influences coronary blood flow.
- Assessing coronary vasodilating drugs solely by blood flow changes can be misleading if oxygen consumption is affected.
Purpose of the Study:
- To establish a reference for quantifying coronary microvascular drug effects.
- To measure the human myocardial oxygen supply:demand ratio.
- To differentiate true coronary vasodilating drugs from apparent ones.
Main Methods:
- A prospective, controlled trial involving 12 patients with coronary artery disease (CAD).
- Cardiac pacing was used to alter myocardial oxygen demand in awake and anesthetized patients.
- Myocardial oxygen supply and demand were calculated, and the ratio was compared to drug-induced changes.
Main Results:
- The myocardial oxygen supply:demand ratio was consistent in awake and anesthetized states (1.50 vs. 1.45).
- Intracoronary nifedipine and felodipine significantly altered the oxygen supply:demand ratio.
- Anesthesia alone did not significantly impact the ratio beyond demand-related increases.
Conclusions:
- The myocardial oxygen supply:demand ratio serves as a vital physiological reference.
- This ratio is a powerful tool for evaluating the efficacy of coronary vasodilating drugs.
- It aids in distinguishing between drugs with true vasodilating properties and those with only apparent effects.
Objective:
Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major determinant of coronary blood flow; therefore, the true vasodilating properties of coronary vasodilating drugs that may have an effect on oxygen consumption cannot be correctly assessed from blood flow changes alone.
Design:
Prospective, controlled trial.
Setting:
Academic hospital.
Patients:
12 patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass grafting.
Interventions:
Cardiac pacing at 30 beats/min above sinus rhythm in awake and anaesthetised patients (fentanyl/pancuronium bromide).
Main Outcome Measures:
Myocardial oxygen supply, defined as coronary sinus blood flow multiplied by arterial oxygen content; myocardial oxygen demand, defined as coronary sinus blood flow multiplied by arteriovenous oxygen content difference. The change in oxygen demand induced by pacing was related to the change in myocardial oxygen supply in awake and anaesthetised patients. This myocardial oxygen supply:demand ratio determined in the reference study was compared with that induced by intravenous and intracoronary drugs (nifedipine, felodipine, urapidil, and sodium nitroprusside) in two pharmacological studies: patients with CAD undergoing cardiac surgery (45 treated with sodium nitroprusside, 27 with nifedipine, and 27 with urapidil to manage arterial blood pressure); and patients with unstable angina (and a similar degree of CAD) undergoing cardiac catheterisation for diagnostic purposes (10 treated with intracoronary nifedipine and 10 with intracoronary felodipine).
Results:
When awake, the ratio of pacing induced oxygen supply:demand changes in the 12 reference study patients was 1.50 (95% confidence intervals (CI), 1.41-1.58), similar to the 1.45 (1.35-1.56) measured in the same patients after induction of anaesthesia. Anaesthesia per se did not increase coronary oxygen supply above the expected increase related to demand changes. The only significant change in the oxygen supply:demand ratio was induced by intracoronary bolus administration of nifedipine and felodipine (10.6 (SE 1.9) and 13.9 (1.9) ml/min, respectively, above the demand related supply).
Conclusions:
Quantification of coronary vasoactive properties in relation to the physiological reference ratio between myocardial oxygen supply and demand may be a powerful tool to differentiate between true and apparent coronary vasoactive drugs.