Page 17 - Coronary hemodynamics in acute myocardial infarction - Matthijs Bax

General introduction and outline of the thesis
advocated to be administered at the time of PPCI to ameliorate myocardial 1 reperfusion where it can significantly improve myocardial microcirculation.
However, a recent meta-analysis failed to demonstrate clinically significant
benefits in this form of therapy.43 A meta-analysis showed adenosine therapy
to be promising in some subgroups in patients undergoing PPCI as it was associated with a lower incidence of no-reflow, improved left ventricular ejection fraction and less heart failure. However, it failed to show reduction of hard endpoints such as mortality or re-infarction.44 Beside adenosine and nicorandil, other agents such as diltiazem, verapamil, urapidil, nitroprusside and anisodamine were evaluated for the purpose of optimization of reperfusion therapy. In a meta-analysis evaluating these seven pharmacological agents, administered in the setting of PPCI, demonstrated improved coronary flow but no corresponding benefits regarding cardiac function and clinical outcomes for adenosine, nicorandil and verapamil compared to standard care.45 Only intracoronary administered anisodamine appeared to improve reperfusion, cardiac function and clinical outcomes in small sized studies. Given the complexity of the cardioprotective signal transduction,46 combined treatment of several targets maybe needed.47
In summary, many experimental studies have been performed in which both pharmacological interventions and mechanical interventions, such as pre- and post-conditioning, remote or not, demonstrated a significant reduction in the infarct size. However, as we know now from studies performed in de last two decades, none of these agents have shown a relevant effect in larger sized clinical studies.48, 49
Coronary blood flow regulation and microvascular function
The control of coronary blood flow is determined by the metabolic demand of the heart muscle and has both long-term adaptation as well as acute regulation mechanisms. The acute regulation aims to meet the metabolic need. The intrinsic tendency of an organ to maintain blood flow despite changes in arterial perfusion pressure is named autoregulation.50 Coronary pressure-flow autoregulation maintains the relatively constant coronary blood flow through adaptive changes in microvascular resistance.51 The coronary blood flow can mathematically be described as a correlate to Ohm’s Law (Flow = Δ Pressure / Resistance). Bayliss described in 1902 that the vascular myogenic response is
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