The role of heart rate in myocardial ischemia from restricted coronary perfusion (original) (raw)
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Electrographic response of the heart to myocardial ischemia
2009
Electrocardiographic (ECG) ST segment shifts are often used as markers for detecting myocardial ischemia. Literature suggests that the progression of ischemia, occurs from the endocardium and spreads towards the epicardium, eventually becoming transmural. Our study with animal models has found the progression of ischemia, characterized by ST elevations to be more complex and heterogeneous in its distribution. We used in situ canine preparations, wherein the animals were subjected to demand ischemia by reducing coronary flow and raising the heart rate through atrial pacing. At reduced flow, increasing the heart rate caused pockets of ST elevations to appear variously distributed in the sub-epicardial, mid-myocardial and endocardial regions. Further reduction in coronary flow with simultaneous raising of the heart rate, increased the extent and magnitude of ST elevated regions, that in certain cases became transmural.
Source of Electrocardiographic ST Changes in Subendocardial Ischemia
Circulation Research, 1998
To clarify the source of electrocardiographic ST depression associated with ischemia, a sheep model of subendocardial ischemia was developed in which simultaneous epicardial and endocardial ST potentials were mapped, and a computer model using the bidomain technique was developed to explain the results. To produce ischemia in different territories of the myocardium in the same animal, the left anterior descending coronary artery and left circumflex coronary artery were partially constricted in sequence. Results from 36 sheep and the computer simulation are reported. The distributions of epicardial potentials from either ischemic source were very similar (rϭ0.77Ϯ0.14, PϽ0.0001), with both showing ST depression on the free wall of the left ventricle and no association between the ST depression and the ischemic region. However, endocardial potentials showed that ST elevation was directly associated with the region of reduced blood flow. Insulating the heart from the surrounding tissue with plastic increased the magnitude of epicardial ST potentials, which was consistent with an intramyocardial source. Increasing the percent stenosis of a coronary artery increased epicardial ST depression at the lateral boundary and resulted in ST elevation starting from the ischemic center as ischemia became transmural. Computer simulation using the bidomain model reproduced the epicardial ST patterns and suggested that the ST depression was generated at the lateral boundary between ischemic and normal territories. ST depression on the epicardium reflected the position of this lateral boundary. The boundaries of ischemic territories are shared, and only those appearing on the free wall contribute to external ST potential fields. These effects explain why body surface ST depression does not localize cardiac ischemia in humans. (Circ Res. 1998;82;957-970.) Key Words: ST depression Ⅲ potential mapping Ⅲ bidomain model Ⅲ subendocardial ischemia Ⅲ
Circulation Research, 1979
Regional ischemia was produced in isolated perfused pig hearts and in hearts in situ, by clamping the left descending coronary artery. Intramural and epicardial DC electrograms were recorded from multiple, regularly spaced sites in the central ischemic and border zones and in the normal myocardium. Subepicardial transmembrane potentials were recorded with floating microelectrodes. Transmural tissue biopsies were obtained with a drill from the sites of extracellular potential measurements at various times after coronary occlusion. Tissue levels of adenosine triphosphate (ATP), creatine phosphate (CP), and lactate were determined in this tissue. Glycogen distribution was assessed histochemically. Early ischemic changes are T-Q depression (1.
Ca2+ transient decline and myocardial relaxation are slowed during low flow ischemia in rat hearts
Journal of Clinical Investigation, 1994
The mechanisms that impair myocardial relaxation during ischemia are believed to involve abnormalities of calcium handling. However, there is little direct evidence to support this hypothesis. Therefore, we sought to determine whether the time constant of cytosolic calcium (ICa"2+I) decline (Tc,) was increased during low flow ischemia, and if there was a relationship between the time constant of left ventricular pressure decline (Tp) and Tc. Isolated perfused hearts were studied using indo-1 fluorescence ratio as an index of ICa2 "IcJ. Tp was used as an index of myocardial relaxation. The time constant of decline of the indo-1 ratio increased from 74±5 ms to 95±4, 144±10, and to 204±16 ms when coronary flow was reduced was reduced to 50, 20, and 10% of control, respectively. Indo-1 transients were calibrated to calculate Tc.a-Tc. increased from 67±6 ms to 108±9 and 158±19 ms when coronary flow was reduced to 20 and 10% of control, respectively. There was a linear relationship between rca and Tp (r = 0.82). These data support the hypothesis that during low flow ischemia, impaired myocardial relaxation may be caused by slowing of ICa2"Ic decline. (J.
Circulation, 1987
Previous studies have documented a quantitative relation between alterations in transmural myocardial blood flow and body surface electrocardiographic distributions during rapid atrial pacing after chronic occlusion of the left circumflex coronary artery (LCx). Because other studies have described functional differences between the left anterior descending (LAD) and the LCx perfusion beds, we tested the hypothesis that these two territories exhibit quantitative differences in their responses to demand-dependent myocardial ischemia. To do so, 25 sedated dogs were studied 3 weeks after implantation of an ameroid constrictor around the proximal LCx (15 dogs, group I) or the LAD (group II). Oxygen demand was increased by rapid atrial pacing at rates of 90 to 210 beats/min, myocardial blood flow was measured by serial injections of radiolabeled microspheres, and the electrocardiographic consequences were evaluated by isopotential body surface mapping. Endocardial flows and the endocardial/epicardial flow ratio fell to significantly lower levels during atrial pacing in the ischemic LAD bed than in the LCx perfusion zone. Electrocardiographic patterns indicative of subendocardial ischemia also developed with lesser abnormalities in endocardial/epicardial ratios as determined by logistic regression models, in the LAD than in the LCx bed. Thus the LAD bed is more susceptible to ischemia than the LCx region because of differences in collateral blood flow patterns. In addition, the intensity of the surface electrocardiographic potentials during ischemia was significantly greater, as measured by linear regression, after LAD than after LCx obstruction. These data thus demonstrate significant differences between the two cardiac regions as electrocardiographic potential sources during ischemia.
Circulation, 1983
The spatial distribution of abnormal repolarization potentials caused by regional myocardial ischemia was determined in 45 dogs. Ameroid constrictors were placed around the left circumflex artery in 10, the left anterior descending artery in 10, and the right coronary artery in 10. Ten dogs without constrictors served as controls. Electrocardiographic events were determined from body surface isopotential distributions, which were computed from potentials sensed by 84 torso electrodes. In control dogs, pacing to heart rates of 230 to 250 beats/min increased the intensity of positive and negative surface extrema during the ST segment without altering their spatial features. Two weeks after placement of the ameroid constrictors, tachycardia induced abnormal negative potentials during the ST segment. Localization of these ischemic forces varied with the placement of the constrictor in a manner consistent with the affected perfusion territories. However, much of the torso surface was involved by all lesions, and only small zones of ST segment depression unique to specific lesions could be identified. In five additional dogs a constrictor was placed on the right coronary artery 3 months after implantation of a device on the circumflex vessel. ST segment pattems during pacing in dogs with two lesions were consistent with the sum of the two individual lesions. Thus, the regional nature of myocardial ischemia is detectable in the body surface isopotential distributions, but the degree of spatial overlap may limit the value of such techniques in extending the usesfulness of clinical exercisestress electrocardiography.
Journal of Electrocardiology, 2011
Background: Exacerbation of ST elevation associated with reperfusion has been reported in patients with myocardial infarction. However, the cause of the "reperfusion peak" and relation of its magnitude to the size of myocardial damage has not been explored. The aim of our study was to assess the correlation between the ST-dynamics during reperfusion, the myocardium at risk (MaR), and the infarct size (IS). Methods: Infarction was induced in 15 pigs by a 40-minute-long balloon inflation in the left anterior descending coronary artery. Tetrofosmin Tc 99m was given intravenously after 20 minutes of occlusion, and ex vivo single photon emission computed tomography was performed to assess MaR. Maximal ST elevation in a single lead and maximal sum of ST deviations in 12 leads were measured before, during, and after occlusion from continuous 12-lead electrocardiographic monitoring. A gadolinium-based contrast agent was given intravenously 30 minutes before explantation of the heart. Final IS was estimated using ex vivo cardiac magnetic resonance imaging. Results: All pigs developed an anteroseptal infarct with MaR = 42% ± 9% and IS = 26% ± 7% of left ventricle. In all pigs, reperfusion was accompanied by transitory exacerbation of ST elevation that measured 1300 ± 500 μV as maximum in a single lead compared with 570 ± 220 μV at the end of occlusion (P b .001). The transitory exacerbation of ST elevation exceeded the maximal ST elevation during occlusion (920 ± 420 μV, P b .05). The ST elevation resolved by the end of the reperfusion period (90 ± 30 μV, P b .001). Exacerbation of ST elevation after reperfusion correlated with the final IS (r = 0.64, P = .025 for maximal ST elevation in a single lead and r = 0.80, P = .002 for sum of ST deviations) but not with MaR (r = 0.43, P = .17 for maximal ST elevation in a single lead and r = 0.49, P = .11 for sum of ST deviations). The maximal ST elevation in a single lead and the sum of ST deviations during occlusion did not correlate with either MaR or final IS. Conclusion: In the experiment, exacerbation of ST elevation is common during restoration of blood flow in the occluded coronary artery. The magnitude of the exacerbation of ST elevation after reperfusion in experimentally induced myocardial infarction in pigs is associated with infarct size but not with MaR.
Effect of brief myocardial ischemia on sympathetic coronary vasoconstriction
Circulation Research, 1992
The purpose of the present study was to determine whether sympathetic coronary vasoconstrictor responses are altered after brief ischemia and reperfusion. Adult mongrel dogs were anesthetized and instrumented for measurements of heart rate, arterial pressure, left ventricular pressure, left ventricular dP/dt, anterior myocardial wall thickening, and left circumflex coronary artery (LCX) and left anterior descending coronary artery (LAD) blood flow velocities. Changes in coronary vascular resistance were recorded during intravenous bolus doses of norepinephrine and bilateral electrical stimulation of the stellate ganglia. After f3-adrenergic blockade and bilateral vagotomy, electrical stimulation of the stellate ganglia increased coronary vascular resistance in the LAD and LCX beds by 38±5% and 39±5%, respectively. After a 15-minute LAD occlusion, repeat electrical stimulation produced increases in coronary resistance of 16±3% and 45±8%, respectively (p<0.05 for the LAD before versus after the occlusion). The peak increase in coronary vascular resistance to two doses of norepinephrine was unchanged. After a shorter period of myocardial ischemia (7 minutes), similar increases in coronary resistance to stellate stimulation were observed before (27±4%) and after (26±6%) myocardial ischemia. The mechanism of this impaired sympathetic coronary vasoconstriction was further tested by examining the responses to bretylium and tyramine. Brief ischemia did not alter the coronary constrictor responses to either bretylium or tyramine, suggesting that mechanisms governing prejunctional release of norepinephrine are intact in the postischemic coronary arterial bed. The postischemic myocardium was characterized by mild reductions in left ventricular dP/dt and marked reductions in transmural myocardial wall thickening, characteristic of myocardial stunning. We conclude that after brief myocardial ischemia, coronary vasoconstriction to sympathetic activation is impaired, whereas constriction to direct receptor activation (norepinephrine) and stimulated prejunctional release of a neurotransmitter (bretylium or tyramine) remain intact. These data are consistent with the interpretation that sympathetic efferent neural conduction is impaired in regions of stunned myocardium. (Circulation Research 1992;71:960-969) KEY WoRDS * myocardial ischemia * sympathetic coronary vasoconstriction * left anterior descending coronary artery * left circumflex coronary artery * myocardial stunning P eriods of coronary artery occlusion lasting less than 20 minutes are not associated with myocardial necrosis12 but are accompanied by marked reductions in myocardial function during reperfusion.3-5 This reversible and temporary decrease in ventricular function after brief coronary occlusion has been termed "myocardial stunning" and has been a source of recent intense investigation. Although the hemodynamic and functional myocardial changes associated with myocardial stunning have been well characterized,6'7 little is known regarding the effects of brief periods of ischemia followed by reperfusion on other cardiac structures.