Grayson G. Geary

Prognosis after recovery from first acute myocardial infarction: Determinants of reinfarction and sudden death

Factors associated with total cardiac mortality, sudden cardiac death and reinfarction were studied in 325 male survivors aged younger than 60 years of age (mean 50) of a first myocardial infarction (MI). All patients had undergone exercise testing and cineangiocardiography 4 weeks after MI, 24% underwent coronary artery surgery and 30% received beta-blocking therapy. Patients were followed 1 to 6 years (mean 3.5). Total cardiac mortality was best predicted by the left ventricular (LV) ejection fraction (EF) and by a coronary prognostic index. In contrast, neither the severity of coronary arterial lesions measured with a scoring system nor the results of the exercise test gave significant prediction of mortality. Of the 2 major late sequelae of MI, reinfarction could not be predicted by any clinical or cineangiocardiographic variable. However, sudden death not associated with reinfarction was significantly more common (p less than 0.001) when EF was less than or equal to 40% than when it was greater than 40%. Comparison of patients with an EF less than or equal to 40% who did or did not die suddenly showed that LV dilation (high volumes at ventriculography) was an added risk factor, but the extent of coronary occlusions and stenoses was not. It is concluded that, at least for groups of patients treated with standard modern methods after MI, the main determinant of medium-term survival is the extent of LV damage. The state of the coronary arteries and the presence of ischemic myocardium during exercise are only of secondary importance for survival.

Defining the anatomic perfusion bed of an occluded coronary artery and the region at risk to infarction. A comparative study in the baboon, pig and dog.

Abstract To assess selectively the effectiveness of therapeutic interventions to reduce infarct size, it is important to assess both ultimate infarct size as well as the size of the region of myocardium at risk to infarction. The anatomically defined perfusion bed of an occluded artery has generally been assumed to be synonymous with the region at risk of infarction. This assumption was tested by delineating the anatomic perfusion bed of an occluded artery with microvascular dyes and by examining the relation of the anatomic perfusion bed to the region of acute ischemic injury. In 8 baboons, 12 pigs and 15 dogs a major branch of the left anterior descending or left circumflex coronary artery was occluded. At 2 and 30 minutes after occlusion the eplcardial area of ischemic injury was determined by epicardial S-T segment mapping. The boundary of epicardial S-T segment elevation was resolved to within 1 mm and marked directly on the ventricular surface. The heart was then excised and the perfusion bed of the occluded artery was delineated by either (1) injecting different colored silicone rubber microvascular dyes into the previously occluded artery as well as the adjacent perfusion beds (direct method), or (2) injecting dye only into the adjacent perfusion beds (defect method). Serial cross-sections of the left ventricle from the direct and defect dye-perfused hearts in all three species showed the perfusion bed of the occluded artery to be readily demarcated. Microscopic examination demonstrated no evidence of capillary anastomoses and minimal inter-digitation of capillaries at the perfusion bed boundaries. In dye-perfused hearts, the baboon and the pig showed no evidence of precapillary anastomoses between perfusion beds; however, the dog demonstrated numerous epicardial collateral channels. The epicardial area of the anatomic perfusion bed correlated closely with the epicardial area of S-T segment elevation at 2 minutes after occlusion in the baboon (r = 0.97), pig (r = 0.99) and dog (r = 0.96). The epicardial area of S-T segment elevation did not change through the 30 minute period of occlusion in the baboon and the pig, but in the dog it showed a progressive and variable reduction reflecting the gradual recruitment of existing collateral channels from adjacent perfusion beds. It is concluded that the techniques of direct and defect dye delineation accurately define the anatomic perfusion bed of an occluded coronary artery. This anatomic perfusion bed corresponds to the region of myocardium undergoing acute ischemic injury and hence the region at risk to infarction immediately after coronary occlusion in the three species studied.

Failure of nifedipine therapy to reduce myocardial infarct size in the baboon.

The value of nifedipine in reducing the ultimate size of an infarct associated with a period of coronary occlusion followed by reperfusion was assessed. Eight baboons were administered a bolus dose of nifedipine, 5 micrograms/kg intravenously, and then a maintenance dose of 30 micrograms/kg per hour was begun 1 hour before occlusion. This regimen resulted in an 8.5 +/- 1.2 percent (mean +/- standard error) decrease in mean arterial pressure. The left anterior descending coronary artery was occluded for 2 hours and then perfusion restored. At 2 hours after reperfusion the nifedipine infusion was discontinued. Eight control baboons underwent an identical protocol without nifedipine therapy. At 24 hours after occlusion, microvascular dyes were injected into the left anterior descending coronary artery and adjacent arteries to delineate the perfusion bed of the previously occluded artery. The volume of infarction was determined with planimetry and compared with the volume of the perfusion bed of the occluded artery. The area of infarction was always contained within the perfusion bed of the occluded artery. The mean percent of the perfusion bed with infarction was 50.1 +/- 5.8 in the control group and 41.7 +/- 9.5 in the treated group (difference not significant; p greater than 0.05). In both control and treated groups of baboons hemorrhage occurred only within the region of infarction. In both groups electron microscopy revealed large electron-dense granules within the mitochondria. In conclusion nifedipine therapy during a 2 hour period of coronary occlusion followed by reperfusion did not result in any significant reduction in ultimate infarct size in the baboon.

Experimental studyDefining the anatomic perfusion bed of an occluded coronary artery and the region at risk to infarction: A comparative study in the baboon, pig and dog☆

Abstract To assess selectively the effectiveness of therapeutic interventions to reduce infarct size, it is important to assess both ultimate infarct size as well as the size of the region of myocardium at risk to infarction. The anatomically defined perfusion bed of an occluded artery has generally been assumed to be synonymous with the region at risk of infarction. This assumption was tested by delineating the anatomic perfusion bed of an occluded artery with microvascular dyes and by examining the relation of the anatomic perfusion bed to the region of acute ischemic injury. In 8 baboons, 12 pigs and 15 dogs a major branch of the left anterior descending or left circumflex coronary artery was occluded. At 2 and 30 minutes after occlusion the eplcardial area of ischemic injury was determined by epicardial S-T segment mapping. The boundary of epicardial S-T segment elevation was resolved to within 1 mm and marked directly on the ventricular surface. The heart was then excised and the perfusion bed of the occluded artery was delineated by either (1) injecting different colored silicone rubber microvascular dyes into the previously occluded artery as well as the adjacent perfusion beds (direct method), or (2) injecting dye only into the adjacent perfusion beds (defect method). Serial cross-sections of the left ventricle from the direct and defect dye-perfused hearts in all three species showed the perfusion bed of the occluded artery to be readily demarcated. Microscopic examination demonstrated no evidence of capillary anastomoses and minimal inter-digitation of capillaries at the perfusion bed boundaries. In dye-perfused hearts, the baboon and the pig showed no evidence of precapillary anastomoses between perfusion beds; however, the dog demonstrated numerous epicardial collateral channels. The epicardial area of the anatomic perfusion bed correlated closely with the epicardial area of S-T segment elevation at 2 minutes after occlusion in the baboon (r = 0.97), pig (r = 0.99) and dog (r = 0.96). The epicardial area of S-T segment elevation did not change through the 30 minute period of occlusion in the baboon and the pig, but in the dog it showed a progressive and variable reduction reflecting the gradual recruitment of existing collateral channels from adjacent perfusion beds. It is concluded that the techniques of direct and defect dye delineation accurately define the anatomic perfusion bed of an occluded coronary artery. This anatomic perfusion bed corresponds to the region of myocardium undergoing acute ischemic injury and hence the region at risk to infarction immediately after coronary occlusion in the three species studied.

Reduction in infarct size by synchronized selective coronary venous retroperfusion of arterialized blood

The effectiveness of selective synchronized pulsatile coronary venous retroperfusion for the temporary metabolic support of a region of acutely ischemic myocardium has previously been demonstrated. This study was designed to determine the degree of reduction in ultimate infarct size that may be achieved when coronary venous retroperfusion initiated early after coronary occlusion is combined with later anterograde reperfusion. In 10 baboons, the proximal left anterior descending coronary artery was occluded for 4 hours at which time anterograde reperfusion was restored. In five baboons (Group A), coronary venous retroperfusion was initiated 15 minutes after occlusion. Five baboons (Group B) underwent an identical procedure without coronary venous retroperfusion. Epicardial electrograms were recorded from 24 sites overlying the ischemic region. At 24 hours, hearts were excised and serial transverse sections of the left ventricle were stained with nitroblue tetrazolium for stereometric determination of infarct size. In Group A 12 +/- 5.4 percent (mean +/- standard error of the mean) of epicardial sites with S-T segment elevation at 15 minutes after occlusion showed subsequent Q waves, compared with 96 +/- 2.3 percent in Group B (p less than 0.01). In Group A 4.8 +/- 1.7 percent of the left ventricular mass was infarcted, compared with 30.6 +/- 4.2 percent in Group B (p less than 0.01). The results demonstrated the effectiveness of coronary venous retroperfusion in preserving ischemic myocardium such that anterograde reperfusion resulted in a mean reduction of 84 percent in ultimate infarct size.

Quantitative assessment of infarct size reduction by coronary venous retroperfusion in baboons

Initial favorable reports in which coronary venous retroperfusion was begun after acute coronary artery occlusion have demonstrated a reversal of ischemic injury and improved left ventricular function. However, little information has been generated to document the extent to which retroperfusion may decrease ultimate histologically determined infarct size. The objective of the present study was to evaluate the effectiveness of retroperfusion in reducing infarct size by using an accurate quantitative method in which infarct size was related to the size of the anatomic perfusion bed of the occluded artery (region at risk for infarction). In an experimental group of 5 baboons, the left anterior descending coronary artery was occluded and coronary venous retroperfusion started 1 hour after occlusion. After a 4-hour period of occlusion, retroperfusion was discontinued and anterograde perfusion was simultaneously restored. A control group of 5 baboons underwent an identical procedure without retroperfusion. Twenty-four hours after occlusion, hearts were excised and the previously occluded left anterior descending coronary artery as well as the adjacent arteries were infected with microvascular dye to delineate the perfusion bed of the occluded artery. Planimetry of serial corss-sections of the left ventricle enabled the size of the perfusion bed of the occluded artery and size of the infarct to be determined. The mean percentage of the perfusion bed infarcted in the control group was 94.1 +/- 0.9 (mean +/- standard error) and in the retroperfused group was 57.4 +/- 3.5 (p less than 0.001). Hence, the results demonstrated that when retroperfusion was initiated after 1 hour of coronary occlusion, the mean percentage of the perfusion bed salvaged was increased by 36.7%.

Quantitative effect of early coronary artery reperfusion in baboons. Extent of salvage of the perfusion bed of an occluded artery.

We the examined extent to which ischemic myocardium was salvaged by reperfusion using a method that allowed expression of the volume of infarction as a percentage of the volume of the perfusion bed of the occluded artery (region at risk of infarction). In eight baboons, the left anterior descending coronary artery (LAD) was occluded for 2 hours, after which perfusion was restored. A control group of eight baboons underwent an identical protocol, but perfusion was not restored. Twenty‐four hours after occlusion, microvascular dyes were injected into the LAD and adjacent arteries to delineate the perfusion bed of the occluded artery. The volume of infarction and volume of the perfusion bed were determined planimetrically. The mean percentage of the perfusion bed infarcted in the control baboons was 94.2 ± 3.5% and 50.1 ± 5.8% in the reperfused baboons. Hence, the mean percentage of the perfusion bed infarcted was reduced by 44.1% in the reperfused group compared with the control group (p < 0.001). In reperfused baboons, hemorrhage occurred in the region of infarction but did not result in infarct extension. We conclude that reperfusion after 2 hours of coronary occlusion results in substantial salvage of ischemic myocardium in the baboon.

Epicardial mapping and electrocardiographic models of myocardial ischemic injury.

The amplitude and distribution of epicardial ST-segment elevation (STP) were examined for an 8-hour period after coronary occlusion in eight baboons and five pigs. STt was determined from unipolar epicardial electrograms obtained from a high-resolution matrix of fixed electrodes overlying a transmural region of ischemia. A relatively uniform degree of STt was observed overlying the ischemic region for 20 minutes after coronary occlusion. A gradient in STt from the periphery to the center of the ischemic region was documented after 20 minutes of ischemia. In 10 other pigs, change in the degree of STt was examined contingent on either an increase (five pigs) or decrease (five pigs) in the size of the ischemic region after 1 hour of preexisting ischemia. An abrupt increase in the number of electrodes that showed STt (NST) from 7.8 i 1.24 (SEM) to 14.8 ± 1.35 (90%) was associated with an increase in mean STt of 58% from 4.28 ± 0.61 mV to 6.78 ± 0.84 (p < 0.05). An abrupt decrease in NST from 25.2 ± 2.63 to 14.6 ± 2.22 (42%) was associated with a decrease in mean STt of 24%, from 8.2 ± 0.36 mV to 6.3 ± 0.30 mV (p < 0.01). The results during early ischemia (less than 20 minutes of ischemia) are accurately represented by a model of ischemia in which injury current arises only at the ischemic boundary. The results during later ischemia (after 20 minutes of ischemia) may be represented by a model in which STR is considered dependent on injury currents generated throughout the ischemic region.

An electrocardiographic model of myocardial ischemic injury

Previous electrocardiographic models of myocardial ischemic injury have assumed that transmembrane potential changes are uniform throughout a region of ischemia such that injury currents arise exclusively at the boundary between normal and ischemic myocardium. In such models, the distribution and amplitude of ST segment deflections are considered to arise from a polarized surface interfacing normal and ischemic myocardium. This concept in modeling ischemic injury was derived from the application of principles of electric field theory which had been successfully applied previously to ventricular activation in which QRS potentials are considered to arise from polarized surfaces representing the relatively narrow interfaces between depolarized and nondepolarized myocardium. The present paper outlines the limitations of modeling ischemic injury as a polarized surface in terms of the failure of the predictions of such a model to be supported by the experimentally observed: 1) distribution and relative amplitude of epicardial ST segment elevation overlying a region of ischemia; 2) directional changes in epicardial ST segment elevation that occur with changes in the size of an ischemic region; and 3) nonuniform distribution of transmembrane potential changes which occur within a region of ischemia. A new electrocardiographic model of ischemic injury is formulated which accounts for the nonuniform distribution of transmembrane potential changes which occur throughout a region of ischemia. The model accurately describes experimental observations regarding ST segment deflections which had remained inconsistent with previous models.

Failure of pretreatment with propranolol to reduce the zone of myocardial infarction after 2 hours of coronary occlusion in the primate heart

Abstract The present study assessed the value of pretreatment with propranolol to reduce ultimate myocardial infarct size after acute coronary artery occlusion in the primate heart. An experimental group of 8 baboons was administered a 2-mg/kg loading dose of propranolol intravenously over a 20-minute period before coronary occlusion. This regimen resulted in (1) a decrease in heart rate from 104 ± 19 to 73 ± 8 beats/min (mean ± standard deviation) (p