Intracoronary EnalaPrilat to Reduce MICROvascular Damage During Percutaneous Coronary Intervention (ProMicro) study.

Intracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation. Methods We randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 g) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury. Results Infusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 11 at baseline vs. 19 9 after drug vs. 15 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 15 at baseline vs. 24 15 after drug vs. 33 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p 0.025). Conclusions Intracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedurerelated injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit. (J Am Coll Cardiol 2013;61:615–21) © 2013 by the American College of Cardiology Foundatio

The oxygen consumption paradox of “stunned myocardium” in dogs

The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studied in ancsthetized dogs during 2 h of myocardial reperfusion following either a 15-min (Group I) or 4-h (Group II) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n=8) and Group II (n=5) at 30 min of reperfusion was −33±11% and −34±16% (p=NS) and at 120 min was −23±9% and −40±16% (p=NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during reperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from pre-ischemic levels as measured as a percent of bascline: 104±20% (p=NS) and 111±21% (p=NS). In contrast, regional oxygen consumption in Group II was markedly depressed from bascline at 30 and 120 min of reperfusion: 42±7% (p<.01) and 40±8% (p<.01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitochondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-min coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardium. Therefore, in the post-ischemic myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41748/1/395_2005_Article_BF01906965.pd

Chronotropic incompetence and a higher frequency of myocardial ischemia in exercise echocardiography

Background Exercise echocardiography (EE) is an established method to diagnose coronary artery disease (CAD). Chronotropic incompetence (CI) during the EE may be a marker of myocardial ischemia. The purpose of this investigation was to evaluate the additive value of CI during EE in CAD diagnosis. Methods Between 2000 and 2006, 4042 patients (1900 men with a mean age of 56 ± 11 years) were evaluated by EE. Based on the heart rate (HR) reached during the exercise test, the subjects were divided into two groups: G1 group – 490 patients who failed to achieve 85% of the maximal age-predicted HR, and G2 group – 3552 patients who were able to achieve 85% of the maximal age-predicted HR. Clinical characteristics, left ventricular wall motion abnormalities – wall motion score index (WMSI) – and coronary angiography (CA) were the parameters compared between the two groups. Results The left ventricular wall motion abnormalities were more frequent in G1 group than in G2 group (54% versus 26%; P < 0.00001). WMSI was higher in G1 group than in G2 group, both at rest (1.06 ± 0.17 versus 1.02 ± 0.09; P < 0.0001) and after exercise (1.12 ± 0.23 versus 1.04 ± 0.21; P < 0.0001). In G1 group, 82% of the patients with positive EE for myocardial ischemia presented obstructive coronary, compared to 71% (P = 0.03) in G2 group. Conclusion CI is associated with a higher frequency of myocardial ischemia during EE, reinforcing the concept that CI is a marker of the severity of myocardial ischemia

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance