Relation between myocardial injury and postextrasystolic potentiation of regional function measured by two-dimensional echocardiography.

An experimental study was designed to validate postextrasystolic potentiation assessment of myocardial viability or functional reserve of cardiac segments after acute coronary occlusion. Segmental systolic fractional area changes and wall thickening in pacing-induced postextrasystolic beats were mapped in 12 closed chest dogs by two-dimensional echocardiography during a control period and from 20 minutes to 3 hours after occlusion of the left anterior descending coronary artery. The extent of myocardial ischemic and necrotic zones was evaluated in left ventricular slices and subsegements corresponding to echographic cross sections. During two-dimensional echocardiography, left ventricular segments that were found to be neither ischemic nor necrotic always exhibited a significant augmentation of both fractional area change and wall thickening during the postextrasystolic beat that followed an induced premature contraction with a 42.4% coupling interval. In segments without necrosis but with varying degrees of ischemia, significant postextrasystolic potentiation was also demonstrated, even after 3 hours of occlusion. In contrast, segments that developed more than 80% necrosis failed to potentiate systolic fractional area change after 2 hours, and systolic wall thickening, even after 20 minutes of coronary occlusion. Statistical evaluation revealed a characteristic threshold at 41 to 60% necrosis, beyond which no potentiation of function could be elicited 3 hours after occlusion. Extrapolation from the experimental data suggests that when two-dimensional echographic studies in myocardial ischemia indicate postextrasystolic augmentation of segmental left ventricular function, the latter segments may be assumed to contain only small infarcts or to consist of reversibly ischemic and normal myocardium. Conversely, segments that fail to exhibit postextrasystolic potentiation can be assumed to be more than 60% necrotic.

Verification of myocardial contrast two-dimensional echocardiographic assessment of perfusion defects in ischemic myocardium.

Myocardial contrast two-dimensional echocardiography was used in 21 closed chest dogs to assess its ability to delineate the extent of underperfused acutely ischemic myocardium. An agitated saline-Renografin echocardiographic contrast agent was injected into the left main coronary artery after left anterior descending coronary artery occlusion, and the size of the contrast echo-free area characterizing the perfusion defect was outlined in short-axis cross sections of the left ventricle. In 13 dogs, monastral blue dye was injected after 45 minutes of coronary artery occlusion and before sacrifice to provide anatomic delineation of underperfused zones in equivalent sections. Perfusion defects assessed by contrast two-dimensional echocardiography correlated well with those delineated by monastral blue dye (r = 0.91). Contrast echocardiographic study was also performed in eight other dogs at 5 hours of occlusion, after which infarct size was measured with triphenyl-tetrazolium-chloride. Contrast echocardiographic outline of the perfusion deficiency correlated but slightly overestimated the extent of necrosis (r = 0.88). It is concluded that contrast two-dimensional echocardiography can detect and outline the underperfused "risk area" during acute coronary artery occlusion, and may also permit assessment of the extent of myocardial infarction.

Relation between functional response to nitroglycerin and extent of myocardial necrosis in dogs: mapping of the left ventricle by 2-dimensional echocardiography.

The relation between functional response to brief nitroglycerin infusions and extent of myocardial damage was studied sequentially in closed-chest dogs with acute occlusion of the left anterior descending coronary artery. Two-dimensional echocardiography was used to derive segmental left ventricular (LV) function (systolic fractional area change and systolic wall thickening), and this function was compared with the extent of necrosis measured 5 hours after occlusion in equivalent segments of corresponding pathologic slabs. Two-dimensional echocardiographic study before the dogs were killed indicated that remote nonnecrotic segments always responded to nitroglycerin by significant augmentation of segmental LV function. Segments in which necrosis was less than 40% showed a significant nitroglycerin-induced potentiation in segmental LV function. In contrast, segments in which necrosis was greater than 60% had no potentiation with nitroglycerin. In those segments in which eventual necrosis was 60 to 80%, significant nitroglycerin-induced augmentation in segmental LV function was observed only before and 30 minutes after the coronary occlusion. When the degree of necrosis was greater than 80%, no significant potentiation of segmental LV function was observed even as early as 30 minutes after occlusion. Thus, the degree of nitroglycerin-induced potentiation of segmental cardiac function is closely associated with the extent of myocardial necrosis in the particular ventricular segment. Two-dimensional echocardiography coupled with a nitroglycerin potentiation test might be useful for assessment of the viability of ischemic myocardium.

The relationship of vascular injury and myocardial hemorrhage to necrosis after reperfusion.

Early reperfusion may salvage ischemic myocardium; late reperfusion often intensifies morphologic changes of necrosis and causes hemorrhage. To determine whether hemorrhage after reperfusion increases the extent of myocardial infarction, six closed-chest, anesthetized dogs underwent balloon occlusion of the left anterior descending coronary artery for 5.5 hours, followed by 30 minutes of reflow. Colloidal carbon was injected distal to the balloon before reperfusion to label injured vessels. After sacrifice, the area of myocardial necrosis was measured by planimetry of 1-cm-thick serial slices of left ventricle stained with triphenyl tetrazolium chloride. Areas of hemorrhage and vascular injury were also measured. In all hearts, the extent of hemorrhage and vascular injury was less than the extent of necrosis (10.2 +/- 4.6% vs 19.8 +/- 8.6% [mean +/- SD], p < 0.01). Further, hemorrhage was always within the area of necrosis, primarily in the subendocardial portion. Hemorrhage after reperfusion occurred only in necrotic tissue where carbon labeling indicated severe vascular injury before reperfusion, suggesting that the hemorrhage was the consequence of preexisting microvascular injury, not its cause.

Hypothermic coronary venous phased retroperfusion: a closed-chest treatment of acute regional myocardial ischemia.

Hypothermic synchronized retroperfusion (HSRP) was applied in closed-chest dogs after acute coronary occlusion to determine whether this intervention can significantly retard the otherwise rapidly developing irreversible ischemic injury. The left anterior descending coronary artery (LAD) was occluded for 3 hours in 22 dogs and for 6 hours in 16 dogs. Starting 30 minutes after occlusion, HSRP was applied during maintained coronary occlusion in 21 dogs. The remaining dogs served as untreated controls. Arterial blood was cooled to 20 degrees C and retroperfused in diastole into the regional coronary veins. Hemodynamics, contrast cineangiography and two-dimensional echocardiography were measured sequentially. Glycogen-depleted ischemic areas and necrotic zones were delineated in transverse slices of the left ventricle. Untreated controls dogs further deteriorated; in contrast, HSRP between 30 minutes and 3- and 6-hour LAD occlusion significantly reduced the rate-pressure product (21.3 +/- 4.0% or 26.8 +/- 8.2%) and left ventricular end-diastolic pressure (39.5 +/- 9.5% or 51.4 +/- 7.7%) and increased ejection fraction (28 +/- 17% and 33 +/- 2.0%). HSRP caused no arrhythmias and led to much less necrosis of ischemic myocardium in the treated 3- or 6-hour occlusion series (7.4 +/- 2.7% or 28.9 +/- 12.6%) than in respective untreated controls (47.1 +/- 8.9% and 72.3 +/- 5.9%). Moderately hypothermic closed-chest phased retroperfusion appears to protect reversibly injured ischemic myocardium and improve cardiac function. Such treatment may be particularly suitable in the earliest stages of evolving myocardial infarction, when maintenance of myocardial viability is essential for preservation of jeopardized myocardium while awaiting coronary bypass revascularization or nonsurgical thrombolytic reperfusion.

Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis.

We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischemia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent reperfusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.

Effects of late coronary artery reperfusion after myocardial necrosis is complete.

Early reperfusion salvages reversibly injured ischemic myocardium. Late reperfusion, after necrosis is complete, could be beneficial by accelerating healing, or the hemorrhage and contraction-band necrosis associated with reperfusion could impair healing. In closed-chest anesthetized dogs the left anterior descending coronary artery was occluded with a balloon-tipped catheter for either 1 day followed by reperfusion for 6 days (n = 9) or for 7 days without reperfusion (n = 9). All dogs were killed after 7 days. Pathologic changes were studied in transverse whole-mount ventricular histologic sections. When the two groups were compared, no differences were found in: (1) infarct size, 15.7 +/- 9.9% vs 10.2 +/- 8.6 (mean +/- SD); (2) number of transmural infarcts, 5 of 9 vs 6 of 9; (3) ratio of infarcted/normal wall thickness, 0.93 +/- 0.09 vs 0.95 +/- 0.13; (4) thickness of zone of collagen deposition at periphery of infarct, 1.69 +/- 1.16 mm vs 1.67 +/- 0.56; and (5) amount of hemorrhage, calcification, and inflammation. Thus, in this model, reperfusion after necrosis is complete did not improve or impair healing.