Subtotal Coronary Artery Occlusion Research Articles

Non-ST elevation myocardial infarction: A new pathophysiological concept could solve the contradiction between accepted cause and clinical observations

Non-ST elevation myocardial infarction (NSTEMI) and ST elevation infarction have many differences in their appearance and prognosis. A comprehensive search made us form a new hypothesis that a further cause also existsin NSTEMI: an acute, critical increase in the already existing high microvascular resistance in addition to the subtotal coronary artery occlusion. Various findings and studies can be interpreted only by our hypothesis: hemodynamic findings, ECG changes, autopsy reports and clinical observations (different long-time prognosis and different result of acute revascularization therapy in NSTEMI, similarities of NSTEMI with other clinical symptoms where increased microvascular resistance can be supposed without coronary artery disease). Despite similarities in the underlying pathologic mechanism non-ST elevation myocardial infarction(NSTEMI) and ST elevation infarction (STEMI) have many differences in their clinical presentation and prognosis. A systematic review of the literature about NSTEMI and the blood supply of the myocardium made us form a hypothesis that a further cause also exists in addition to the accepted cause of NSTEMI (subtotal coronaryartery occlusion): an acute, critical increase in an already existing high intramyocardial microvascular resistance. Knowledge about microcirculation disturbances in ischemic heart disease and development of microcirculation damage can be fitted in our hypothesis. Various findings and studies can be interpreted only by our hypothesis: hemodynamic findings, ECG changes, autopsy reports and clinical observations about NSTEMI. The latest ones involve the different long-time prognosis and different result of acute revascularization therapy in STEMI and NSTEMI. Regarding the repolarization changes on the ECG NSTEMI shows similarities with other clinical symptoms where increased intramyocardial microvascular resistance can be supposed without coronary artery disease: false positive exercise stress test, supraventricular tachycardia, left ventricular strain and conduction disturbances. The acute treatment of NSTEMI should aim to improve the blood inflow to the stiff myocardiumand/or impaired microvascular system and decrease the high microvascular resistance.

Attenuation of coronary flow reserve and myocardial function after temporary subtotal coronary artery occlusion and increased myocardial oxygen demand in dogs

Objectives. We examined whether subtotal coronary artery occlusion and reperfusion alter coronary flow reserve and regional myocardial function.Background. Total coronary artery occlusion followed by reperfusion results in decreased coronary flow reserve and regional myocardial dysfunction.Methods. Thirteen anesthetized dogs were subjected to subtotal occlusion of the left anterior descending coronary artery for 1 h, followed by reperfusion for 1 h. During subtotal left anterior descending occlusion, heart rate was increased by atrial pacing. After reperfusion, coronary flow reserve, indicated by reactive hyperemia, as well as coronary flow responses to acetylcholine and nitroglycerin, regional myocardial function and myocardial leukocyte accumulation were measured.Results. After reperfusion, coronary flow reserve was decreased in the ischemic left anterior descending but not the nonischemic circumflex coronary artery region. Myocardial function was also depressed in the left anterior descending coronary region and did not improve on reperfusion. Histologic study showed no leukocyte infiltration in the ischemic left anterior descending coronary region. Myeloperoxidase, an index of inyocardiai leukocyte accumulation, was similar in the left anterior descending and circumflex coronary regions. Sensitivity of epicardial left anterior descending coronary artery rings to the thromboxane A2analog U46,619 was enhanced, and relaxation of these rings in response to endothelium-dependent relaxants was decreased.Conclusions. Coronary flow reserve is reduced and regional myocardial function depressed after subtotal coronary artery occlusion and increased heart rate. A decreased synthesis or increased breakdown of endothelium-derived relaxing factor may be related to a decrease in coronary flow reserve. However, the reduction in coronary flow reserve appears to be unrelated to leukocyte accumulation in the reperfused region.

Responses of myocardial high energy phosphates and wall thickening to prolonged regional hypoperfusion induced by subtotal coronary stenosis.

The response of the myocardium to prolonged or chronic ischemia may differ from the well documented changes that occur acutely subsequent to the onset of hypoperfusion. Therefore, we have examined in an instrumented canine model and using spatially localized spectroscopy to achieve transmural differentiation, the myocardial HEP and Pi levels as well as wall thickening in situ during prolonged ischemia induced by sustained coronary artery stenosis. The results demonstrate that subtotal coronary artery occlusion causes immediate and transmurally inhomogeneous decreases in the myocardial HEP content and increase in the Pi/CP ratio; however, during prolonged mild hypoperfusion, metabolic changes occur which lead to statistically significant recovery of CP (but not ATP) and disappearance of Pi despite the persistence of reduced blood flow and oxygen supply. Upon release of the occlusion, the previously ischemic muscle recovered blood flow, and some (but not all) of its preischemic contractile function without parallel changes in the HEP levels. It is concluded that normal HEP and Pi levels cannot be equated with either the absence of underperfusion or insensitivity of NMR spectroscopy to ischemia. Rather, it is imperative that both functional and spectroscopic measurements are performed simultaneously to distinguish between ischemic myocardium which is adapted versus unadapted to the hypoperfusion.

Decreased endothelium-dependent vascular relaxation following subtotal coronary artery occlusion in dogs

Total coronary artery occlusion followed by reperfusion leads to neutrophil accumulation in the reperfused myocardium and a reduction in endothelium-dependent coronary artery relaxation. Attenuated coronary artery relaxation in the affected regions is thought to be related to breakdown of endothelium-derived relaxing factor (EDRF) by free oxygen radicals released during reperfusion. To determine if temporary subtotal coronary artery narrowing leads to similar alteration in vascular reactivity, eight open-chest dogs were subjected to 1 h of left anterior descending (LAD) coronary artery narrowing (70% reduction in basal flow) and pacing-induced increase in heart rate (30% above baseline) followed by reperfusion for 1 h. Thereafter reactivity of ischemic-reperfused LAD and nonischemic circumflex (Cx) coronary aftery rings to the thromboxane A 2 analog U46,619 and EDRF-dependent vasorelaxants acetylcholine (ACh), thrombin, and adenosine diphosphate (ADP), as well as to EDRF-independent vasorelaxant nitroglycerin (NTG), was examined. Unlike in the setting of total coronary artery occlusion, reperfused myocardium or LAD did not reveal neutrophil infiltration. However, contraction in response to U46,619 was markedly ( P < 0.001) increased in the LAD rings compared to that in the Cx rings. ACh-induced relaxation was only modestly decreased ( P < .05) in the LAD coronary artery rings, but the relaxation in response to both thrombin and ADP was markedly diminished ( P < .01) as compared to that in the Cx rings. Coronary artery ring relaxation in response to NTG was preserved in the LAD rings. Pretreatment of coronary artery rings with indomethacin did not alter the enhanced contraction or diminished endothelium-dependent relaxation of LAD coronary artery rings. In other experiments, exposure of nonischemic coronary artery rings to the free oxygen radical generating system of xanthine oxidase in vitro resulted in a similar pattern of decrease in EDRF as observed in the ischemic-reperfused LAD segments. Thus EDRF synthesis/activity is diminished following subtotal coronary artery narrowing and increased myocardial oxygey demand, and this phenomenon is not related to neutrophil infiltration. Release of free oxygen radicals from sources other than neutrophils during reperfusion probably accounts for the degradation of EDRF.

Reperfusion of hibernating myocardium: Contractile function, high-energy phosphate content, and myocyte injury after 3 hours of sublethal ischemia and 3 hours of reperfusion in the canine model

Hibernating myocardium has been defined as a persistent impairment of contractile function resulting from reduced coronary blood flow that can be partially or completely resolved once coronary perfusion is restored. In fact, recent clinical reports have documented a dramatic improvement in contractile function after relief of chronic sublethal ischemia. To investigate the phenomenon of sublethal ischemia followed by reperfusion, we assessed myocyte morphology, high-energy phosphate content, and regional contractile function in dogs undergoing (1) 3 hours of subtotal coronary artery occlusion (CO) and 3 hours of reflow or (2) 3 hours of total CO followed by reflow, in which myocyte viability was maintained by extensive collateral perfusion during ischemia (total CO/negligible necrosis). Data were compared with findings in a third group of dogs with total CO and low collateral blood flow during ischemia, in which large confluent infarcts developed. Endocardial blood flow averaged 30 ± 6% ( p < 0.01) and 27 ± 4% ( p < 0.01) of baseline preocclusion values during ischemia in the groups with subtotal CO and total CO/negligible necrosis, versus 3 ± 1% of baseline values in dogs with total CO/confluent necrosis. Both the subtotal CO and total CO/negligible necrosis groups exhibited only mild-to-moderate reversible myocyte injury (assessed by electron microscopy) and had essentially no necrosis: infarct size was 1 ± 1% ( p < 0.01) and 4 ± 2% ( p < 0.01) of the risk region in the subtotal CO and total CO/negligible necrosis groups, versus 55 ± 9% of the risk region in the total CO/confluent necrosis group. Furthermore, myocardial high-energy phosphate stores were in part preserved in all dogs that underwent sublethal ischemia: endocardial adenosine triphosphate (ATP) content was 55 ± 11% ( p < 0.01) and 56 ± 8% ( p < 0.01) versus 11 ± 2% of baseline values in the subtotal CO, total CO/negligible necrosis, and total CO/confluent necrosis groups, respectively. At 3 hours post occlusion, segment shortening averaged +21 ± 10% of baseline values in dogs with subtotal CO, ( p <0.01 versus both total CO groups), −29 ± 9% in dogs with total CO/negligible necrosis, and −36 ± 13% in dogs with total CO/confluent necrosis. Reperfusion after sublethal ischemia produced an acute improvement in contractile function in both the subtotal CO and total CO/negligible necrosis groups. This functional rebound was short lived, however; by 3 hours after reflow, segment shortening had deteriorated to values that did not differ from those measured during ischemia (+20 ± 15% and −24 ± 5% of baseline values in dogs with subtotal CO and total CO/negligible necrosis, respectively). Thus a 3-hour episode of sublethal ischemia in this canine model results in a reduction in contractile function during hypoperfusion associated with preserved myocardial high-energy phosphate stores and prevention of myocyte necrosis. However, in contrast to some clinical reports, reperfusion after sublethal ischemia was not associated with a dramatic improvement in contractile function. Rather the postischemic dysfunction, partial preservation of ATP stores, and creatine phosphate overshoot observed after relief of sublethal ischemia suggest that this previously hypoperfused but viable tissue is stunned during the initial hours after reflow.

Time from onset of symptoms to thrombolytic therapy: A major determinant of myocardial salvage in patients with acute transmural infarction

To determine whether myocardial salvage after successful intracoronary or intravenous thrombolysis is time dependent, the relation between left ventricular wall motion and the time to treatment was studied in 69 patients admitted less than 3 hours after onset of acute transmural myocardial infarction (42 patients with reperfusion by intracoronary streptokinase, 27 by intravenous urokinase). A similar significant relation between the time to treatment and the severity of regional hypokinesia at follow-up was found in the intracoronary and intravenous groups. To better define this relation, particularly during the early phase of infarction, the groups were combined. In patients in whom thrombolytic treatment was initiated within 2 hours after symptom onset, wall motion at follow-up was within 2 standard deviations of the normal mean in 82% (14 of 17 patients). If treatment was started 2 to 5 hours after symptom onset, the probability of improved wall motion decreased to 46% (24 of 52 patients, p less than 0.025). The time/wall motion relation appeared to be independent of infarct location, angiographically visible collateral vessels and the presence of subtotal coronary artery occlusion. The severity of hypokinesia at follow-up study correlated with the magnitude of peak serum creatine kinase (r = -0.71), indicating that thrombolytic therapy initiated within 2 hours after the onset of symptoms improves regional left ventricular function and reduces infarct size more than later therapy does.

Characteristics of coronary blood flow and transmural distribution in miniature pigs.

The relationship between phasic systolic and diastolic coronary blood flow and its transmural distribution has been studied in 29 Yucatan miniature pigs at rest and during heavy exercise, with and without adenosine infusion (1.5 mg . kg-1 . min-1) and with and without a subtotal coronary artery occlusion. Altered factors that affected coronary flow included vascular resistance, perfusion pressure, myocardial oxygen demand, and extra-vascular pressure. The data indicate that, at rest, endomural perfusion is significantly dependent on diastolic blood flow. However, the ability of the myocardial vessels to autoregulate during systole as well as during diastole was clearly shown with the use of adenosine infusion. This ability to regulate flow intrinsically appeared to transcend the endocardial dependency on diastolic perfusion under certain stressful conditions, e.g., during heavy exercise, when the diastolic duration was significantly reduced. Systolic transmural perfusion may then become a significant factor in meeting the blood flow demands of the myocardium. However, due to gradients in vascular resistance, perfusion pressure, and oxygen demand, the coronary reserve of the epicardium appears to be greater than that of the endocardium under any condition.