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Background: In the region of South Limburg, the Netherlands, a shared ST-elevation myocardial infarction (STEMI) networking system (SLIM network) was implemented. During out-of-office hours, two percutaneous coronary intervention (PCI) centres—Maastricht University Medical Centre and Zuyderland Medical Centre—are supported by the same interventional cardiologist. The aim of this study was to analyse performance indicators within this network and to compare them with contemporary European Society of Cardiology guidelines. Methods: Key time indicators for an all-comer STEMI population were registered by the emergency medical service and the PCI centres. The time measurements showed a non-Gaussian distribution; they are presented as median with 25th and 75th percentiles. Results: Between 1 February 2018 and 31 March 2019, a total of 570 STEMI patients were admitted to the participating centres. The total system delay (from emergency call to needle time) was 65 min (53–77), with a prehospital system delay of 40 min (34–47) and a door-to-needle time of 22 min (15–34). Compared with in-office hours, out-of-office hours significantly lengthened system delays (55 (47–66) vs 70 min (62–81), p < 0.001), emergency medical service transport times (29 (24–34) vs 35 min (29–40), p < 0.001) and door-to-needle times (17 (14–26) vs 26 min (18–37), p < 0.001). Conclusions: With its effective patient pathway management, the SLIM network was able to meet the quality criteria set by contemporary European revascularisation guidelines. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials for in-stent restenosis (ISR) and de novo lesions in small-diameter vessels have shown promising results, but data on DCB use in real-world practice are still scarce. The aim of the PEARL (Paclitaxel-Eluting Angioplasty Balloon in the Real-World) registry was to evaluate the safety and efficacy of a paclitaxel DCB in real-world percutaneous coronary intervention (PCI) practice., Methods: Between 2014 and 2019, a total of 513 patients treated with the Protégé paclitaxel DCB (Wellinq) were prospectively included at 4 hospitals in the Netherlands. The primary endpoint was 2-year major adverse cardiac event (MACE), defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization (TLR)., Results: DCB was used for ISR in 382 patients and for de novo lesions in 131 patients. Acute coronary syndrome was the reason for presentation in 58.9% of patients. At lesion level, 34.1% of lesions were classified as type B2 and 36.1% as type C. Predilation was performed in 62.2% and noncompliant DCB was used in 40.7% of lesions. DCB-related procedural complications were infrequent (3.3%, mostly coronary dissection [2.3%]). Bailout stenting was required in 3.1%. MACE during 2-year follow-up occurred in 17.1% of patients treated for ISR and 9.7% of patients treated for de novo lesions. The incidence of TLR was 11.7% of ISR patients and 2.9% of de novo patients. History of coronary artery bypass grafting and lesion length were predictors of MACE in patients treated for ISR., Conclusion: The use of Protégé paclitaxel DCB for PCI of ISR and de novo lesions is safe and effective during 2-year follow-up.

Aims: Platelet inhibition induced by P2Y12 receptor antagonists in patients with ST-elevation myocardial infarction (STEMI) can be affected by concomitant use of opioids. The aim of this trial was to examine the effect of intravenous (iv) acetaminophen compared with iv fentanyl on P2Y12 receptor inhibition in patients with STEMI., Methods and Results: The Opioids aNd crushed Ticagrelor In Myocardial infarction Evaluation (ON-TIME 3) trial randomized 195 STEMI patients who were scheduled to undergo primary percutaneous coronary intervention (PCI) and were pre-treated with crushed ticagrelor to iv acetaminophen (N = 98) or iv fentanyl (N = 97) in the ambulance. The primary endpoint, consisting of the level of platelet reactivity units (PRU) measured immediately after primary PCI, was not significantly different between the study arms [median PRU 104 (IQR 37-215) vs. 175 (63-228), P = 0.18]. However, systemic levels of ticagrelor were significantly higher in the acetaminophen arm at the start of primary PCI [151 ng/mL (32-509) vs. 60 ng/mL (13-206), P = 0.007], immediately after primary PCI [326 ng/mL (94-791) vs. 115 ng/mL (38-326), P = 0.002], and at 1 h after primary PCI [488 ng/mL (281-974) vs. 372 ng/mL (95-635), P = 0.002]. Acetaminophen resulted in the same extent of pain relief when compared with fentanyl [reduction of 3 points on 10-step-pain scale before primary PCI (IQR 1-5)] in both study arms (P = 0.67) and immediately after PCI [reduction of 5 points (3-7); P = 0.96]., Conclusion: The iv acetaminophen in comparison with iv fentanyl was not associated with significantly lower platelet reactivity in STEMI patients but resulted in significantly higher ticagrelor plasma levels and was effective in pain relief., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To test the hypothesis that mild hypothermia potentiates the cardioprotection afforded by ischaemic preconditioning so that infarct size limitation can be obtained after coronary artery occlusion (CAO) durations which exceed the cardioprotective range (> 90 min) of either hypothermia or ischaemic preconditioning alone., Methods: Four groups of anaesthetized rats were subjected to different durations of CAO: (i) normothermia (N, 36.5-37.5 degrees C, n = 29), (ii) normothermia + ischaemic preconditioning (N + IP, 15 min CAO followed by 10 min of reperfusion, n = 35), (iii) hypothermia (H, 30-31 degrees C, n = 31) and (iv) hypothermia + ischaemic preconditioning (H + IP, n = 24). Infarct size (IA/AR) was determined after 3 hours of reperfusion using trypan blue to delineate the area at risk (AR) from non-risk region and nitroblue tetrazolium to delineate infarcted area (IA) from viable myocardium., Results: In N the CAO duration versus infarct size relation had a sigmoid shape with virtually no infarction occurring at 15 min CAO and 56 +/- 5% of the area at risk being infarcted at 30 min CAO reaching a plateau of 71 +/- 2% at 60 min CAO. Hypothermia produced a rightward shift of the relation resulting in an approximately 15 min delay in onset of infarction. Ischaemic preconditioning produced a similar reduction in infarct size (23 +/- 4%) at 30 min CAO compared to hypothermia (13 +/- 3%) but also limited infarct size at 45 min to 36 +/- 3% and at 60 min CAO to 50 +/- 3% suggesting a slowing of infarct progression. Neither intervention limited IA/AR produced by 120 min CAO. In H + IP, combined hypothermia and ischaemic preconditioning resulted in synergistic infarct size reduction so that at 45 min and 60 min CAO IA/AR was reduced to 17 +/- 3% and 23 +/- 3%, respectively, and even at 120 min CAO to 58 +/- 5%, which was significantly smaller than during normothermic control conditions (p < 0.05 vs. N)., Conclusion: Mild hypothermia limited IA/AR modestly but markedly enhanced the cardioprotection afforded by ischaemic preconditioning in the in situ rat heart so that irreversible damage produced by even prolonged coronary artery occlusions was limited.

Background: Brief coronary artery occlusions (CAOs) protect both the artery's own perfusion territory ("myocardial preconditioning") and adjacent "virgin" myocardium. Whether ischemia in remote organs protects myocardium is unknown. We examined whether brief occlusion of the anterior mesenteric artery (MAO) or left renal artery (RAO) protects against myocardial infarction., Methods and Results: Area at risk (AR) and infarcted area (IA) were determined in anesthetized rats after 180 minutes of reperfusion following a 60-minute CAO. At normothermia (body temperature, 36.5 degrees C to 37.5 degrees C), IA/AR was 68 +/- 2% (mean +/- SEM, n = 11) in control rats and 50 +/- 3% (n = 9, P < .001) in rats preconditioned by 15-minute CAO 10 minutes before 60-minute CAO. A 15-minute MAO was equally protective (IA/AR = 50 +/- 3%, n = 10, P < .001), whereas 15-minute RAO failed to limit IA/AR (72 +/- 5%, n = 8). Hypothermia (body temperature, 30 degrees C to 31 degrees C) did not affect IA/AR (67 +/- 3%, n = 11) in control animals but enhanced protection by 15-minute CAO (IA/AR = 22 +/- 3%, n = 8), whereas protection by 15-minute MAO (IA/AR = 44 +/- 5%, n = 11, P < .001) was minimally enhanced. Hypothermia unmasked protection by 15-minute RAO (IA/AR = 46 +/- 6%, n = 9, P < .01). Hexamethonium (20 mg/kg IV) did not alter protection by 15-minute CAO, but it abolished protection by 15-minute MAO. When MAO was sustained throughout the study, cardioprotection was absent., Conclusions: Brief ischemia in "remote" organs protects myocardium against infarction as effectively as myocardial preconditioning. The mechanism of protection by MAO differs from that of CAO, because ganglion blockade abolished protection by MAO but not by CAO. The neurogenic pathway is activated during reperfusion after 15-minute MAO, because sustained MAO failed to produce cardioprotection.

Background: Rapid ventricular pacing reduces the incidence of ventricular arrhythmias during a subsequent sustained period of ischemia and reperfusion. We investigated whether rapid ventricular pacing also limits myocardial infarction and determined the role of KATP+ channels in the protection afforded by ventricular pacing., Methods and Results: Myocardial infarction was produced by a 60-minute coronary artery occlusion in open chest pigs. Infarct size of pigs subjected to 10 minutes of ventricular pacing at 200 beats per minute followed by 15 minutes of normal sinus rhythm before the occlusion (79 +/- 3% of the area at risk, mean +/- SEM) was not different from control infarct size (84 +/- 2%). Thirty-minute pacing followed by 15-minute sinus rhythm resulted in modest reductions in infarct size (71 +/- 2%, P<.05 versus control). Thirty minutes of pacing immediately preceding the occlusion without intervening sinus rhythm resulted in considerable limitation of infarct size (63 +/- 4%, P<.05), which was abolished by pretreatment with the KATP+ channel blocker glibenclamide (78 +/- 4%, P=NS). KATP+ channel activation did not appear to involve ischemia: (1) myocardial endocardial/epicardial blood flow ratio was 1.07 +/- 0.08, (2) phosphocreatine and ATP levels and arterial-coronary venous differences in pH and PCO2 were unchanged, (3) end-systolic segment length did not increase and postsystolic shortening was not observed during pacing, and (4) systolic shortening recovered immediately to baseline levels and coronary reactive hyperemia was absent after cessation of pacing. Administration of glibenclamide after 30 minutes of pacing at the onset of 15 minutes of normal sinus rhythm did not attenuate the protection (73 +/- 3%, P<.05 versus control), suggesting the KATP+ channels did not contribute to the moderate degree of protection that was still present 15 minutes after cessation of pacing., Conclusions: Rapid ventricular pacing protects the myocardium against infarction via nonischemic KATP+ channel activation. Continued activation of KATP+ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.

The effect of nifedipine (0.5, 1.0, and 2.0 micrograms/kg/min), metoprolol (0.1, 0.5, and 1.0 mg/kg), the beta 1-selective adrenoceptor partial agonist epanolol (10, 50, and 200 micrograms/kg), or equivalent volumes of isotonic saline (n = 6, in each group), on coronary blood flow capacity were studied in anesthetized swine. Intracoronary bolus injections of adenosine (20 micrograms/kg/0.2 ml) were administered without and during three levels of coronary stenosis, prior to and following each dose of drug, to obtain maximal coronary blood flows at different perfusion pressures in the autoregulatory range. Coronary perfusion pressures were varied by partial inflation of a balloon around the left anterior descending coronary artery. Special care was taken that the stenoses not lead to myocardial ischemia. Three indices of coronary blood flow capacity were used: absolute coronary flow reserve (ACFR, the ratio of maximal to resting coronary blood flow), the slope and the extrapolated pressure at zero flow (Pzf) of the pressure-maximal coronary flow (PMCF) relationship, and relative coronary flow reserve (RCFR, the ratio of maximal coronary blood flow with a stenosis to maximal coronary blood flow without a stenosis) at two of the three levels of stenosis. Nifedipine decreased ACFR from 4.5 +/- 1.9 to 1.9 +/- 0.3 (mean +/- SD; p less than 0.05), reflecting in part the increase in resting coronary blood flow. The nifedipine-induced changes in maximal coronary blood flow were not only due to a drop in perfusion pressure, as the slope of the PMCF relationship decreased from 2.27 +/- 0.49 ml/(min.mm Hg) to 1.54 +/- 0.51 ml/(min.mm Hg) (p less than 0.05), and Pzf decreased from 30 +/- 4 mm Hg to 20 +/- 7 mm Hg (p less than 0.05). Consequently, calculated maximal coronary blood flow was attenuated from 114 +/- 31 ml/min to 93 +/- 37 ml/min at 80 mm Hg, but was enhanced from 23 +/- 13 to 37 +/- 24 ml/min at 40 mm Hg coronary perfusion pressure. In concert with the change in the PMCF relationship, RCFR at equivalent severe stenosis increased from 0.33 +/- 0.06 to 0.47 +/- 0.10 (p less than 0.05). No changes were observed with metoprolol, epanolol, or saline. The effect of nifedipine on the PMCF relationship not only provides a mechanism for the drug's antiischemic action, but should also be considered in the interpretation of coronary flow reserve measurements in patients on nifedipine treatment.

1. The systemic and regional haemodynamic effects of the potassium channel activator EMD 52692 or its solvent were investigated after intravenous and after intracoronary administration in anaesthetized pigs. 2. Consecutive intravenous 10 min infusions of EMD 52692 (0.15, 0.30, 0.60, 1.20 micrograms kg-1 min-1; n = 7) dose-dependently decreased mean arterial blood pressure by up to 50%. This was entirely due to peripheral vasodilatation, since cardiac output did not change. Heart rate increased by up to 50%, while left ventricular end diastolic pressure decreased dose-dependently from 6 +/- 1 mmHg to 3 +/- 1 mmHg (P less than 0.05), and stroke volume decreased from 30 +/- 2 ml to 21 +/- 2 ml (P less than 0.05). Left ventricular dP/dtmax was not affected. 3. Although cardiac output did not change, EMD 52692 caused a redistribution of blood flow from the arteriovenous anastomoses to the capillary channels. Blood flow to the adrenals, small intestine, stomach, bladder, spleen and brain increased, while renal blood flow decreased and blood flow to several muscle groups and skin were not altered. Vascular conductance was increased dose-dependently in all organs, except for the kidneys, where after the initial increase, vascular conductance returned to baseline with the highest dose. Particularly striking were the effects on the vasculature of the brain. With the highest dose of EMD 52692 blood flow more than doubled, while vascular conductance increased four fold. 4. Transmural myocardial blood flow increased slightly, which was entirely due to an increase in subepicardial blood flow. Myocardial O2-consumption and segment length shortening were not significantly affected. 5. After consecutive 10 min intracoronary infusions (0.0095, 0.019, 0.0375 and 0.075 microgram kg-1 min-1; n = 7) into the left anterior descending coronary artery (LADCA), mean arterial blood pressure was maintained with the lowest two doses, but decreased by up to 15% with the higher doses, whereas heart rate increased by up to 24%. Blood flow to the LADCA-perfused myocardium doubled with the highest dose, the subepicardium benefitting the most. Coronary venous O2-saturation increased dose-dependently from 23 +/- 2% to 60 +/- 4%, while myocardial O2-consumption of the LADCA-perfused myocardium was not affected by the drug. 6. It is concluded that EMD 52692 is a potent vasodilator, with particularly pronounced effects on vasculature of the brain. Its selectivity for vascular smooth muscle cells exceeds that for the myocytes, since with doses that are much higher than those of potential clinical interest no negative inotropic effects were observed. The compound primarily dilates arteries but some venodilatation may also occur.