Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function.

The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.     

Closed chest model of intracoronary occlusion for study of regional cardiac function

A new closed chest animal technique permits selective intracoronary balloon occlusion and measurement of hemodynamic and regional metabolic function before and during occlusion and reperfusion. The distal end of the double lumen balloon catheter provides information about the nature and extent of flow distal to the occlusion and permits blood sampling or administration of pharmacologic agents directly into the ischemic zone. Independent blood sampling from the great cardiac vein by means of a specially designed balloon catheter and from the coronary sinus by cannula allows simultaneous biochemical and regional blood flow measurements from the occluded and nonoccluded segments of the heart. Simultaneous intracoronary epicardial electrocardiograms permit electrophysiologic correlation with regional hemodynamic and metabolic events. The administration of oxygen by tracheal airway can increase partial oxygen tension in the circulation distal to coronary occlusion. When intracoronary pressures distal to occlusion are markedly reduced, the frequency of ventricular fibrillation is much greater.     

Regional and global myocardial effects of intravenous and sublingual nitroglycerin treatment after experimental acute coronary occlusion

The consequences of sublingual and intravenous nitroglycerin treatment after acute coronary occlusion were studied in 18 closed chest dogs. Intravenous (0.1 mg/min) or sublingual (0.4 mg/15 min) nitroglycerin therapy was instituted 1 hour after occlusion and the effects were observed over a period of 2 hours. Hemodynamics and global and regional cardiac function were measured in both the coronary occluded and nonoccluded segments of the left ventricle before and during coronary occlusion, and after administration of nitroglycerin. A similar nine dog control series was used to establish the significance of the measured effects of nitroglycerin.Intravenous nitroglycerin therapy after 1 hour of occlusion resulted in a marked increase in heart rate (37 ± 12 [mean ± standard error of the mean] percent), reduction of systolic blood pressure (9 ± 3 percent), decrease in left ventricular end-diastolic and end-systolic volumes (32 ± 5 percent and 34 ± 5 percent), increase in coronary sinus flow (64 ± 24 percent) and decrease in left ventricular stroke work (29 ± 8 percent). Sublingually administered nitroglycerin produced similar trends but much less pronounced effects. However, intravenous or sublingual administration of nitroglycerin provided no improvement or caused further deterioration in ischemic region lactate extraction and potassium loss. The left ventricular ejection fraction, which was severely depressed after 1 hour of occlusion, changed minimally after administration of nitroglycerin, and there was no evidence of any correction of regional left ventricular akinesia or dyskinesia. Whereas mean systemic vascular resistance changed minimally as a result of nitroglycerin therapy, it increased 19 ± 8 percent during a corresponding period of an untreated coronary occlusion series suggesting that nitroglycerin prevented an anticipated increase. Postocclusion S-T segment elevation in the electrocardiogram persisted after treatment.Our data corroborated that nitroglycerin reduced left ventricular volumes and increased coronary sinus flow; however, these improvements were accompanied by persisting metabolic and mechanical derangements in the ischemic region.     

Consequences of reperfusion after coronary occlusion. Effects on hemodynamic and regional myocardial metabolic function

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion.These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.     

Diastolic retroperfusion of acutely ischemic myocardium.

The effectiveness of coronary venous retroperfusion treatment of an ischemic myocardial segment was assessed by measurements of regional and global myocardial function in 16 dogs. The left anterior descending coronary artery was acutely occluded for 75 minutes. After the first 30 minutes of occlusion, diastolic retroperfusion was instituted for 45 minutes by synchronized pumping of arterial blood from the brachial artery into the anterior interventricular coronary vein. Data collected in the preocclusion control period, during occlusion and the subsequent retroperfusion period included simultaneous measurement os ischemic and border zone myocardial forces, epicardial electrocardiographic S-T segments, intracoronary pressure, coronary blood flow and oxygen pressure (PO2) sampled distal to the site of occlusion. Retroperfusion resulted in significant improvement from the level of regional dysfunction observed after 30 minutes of occlusion: Ischemic zone myocardial force increased 106%, epicardial S-T elevation decreased 46%, normalized peripheral left anterior descending coronary arterial flow increased 50% and distal left anterior descending PO2 decreased 44%. These regional improvements were significant when compared with findings in an untreated series of 12 dogs with 75 minutes occlusion of the left anterior descending coronary artery. Diastolic-augmented coronary venous retroperfusion with arterial blood provided significant but not complete restoration of function in the ischemic segment. Therefore, in the earliest phase of acute myocardial infarction, retroperfusion might represent a useful temporary support to an otherwise inaccessible jeopardized zone of the heart. Regional retroperfusion may constitute an effective emergency procedure, particularly when the occlusive lesions are diffuse and other medical or surgical emergency procedures are inadvisable, unavailable or ineffective.     

Progressive alterations of cardiac hemodynamic and regional metabolic function after acute coronary occlusion

Hemodynamic and regional metabolic function was assessed simultaneously in 34 closed chest dogs during a preocclusion control period and 3 hours of intracoronary balloon occlusion of the proximal left anterior descending artery. The data indicate immediate alteration in hemodynamic measurements with many fluctuations in the 3 hour occlusion period. No specific hemodynamic pattern was evident. When the mean data were analyzed, occlusion was found to cause early increases in left ventricular end-diastolic pressure (43 percent) and systemic vascular resistance (21 percent), and decreases in peak systolic pressure (5 percent), maximal rate of rise of left ventricular pressure (dP/dt) (20 percent), cardiac output (19 percent), stroke work (26 percent) and coronary sinus blood flow (19 percent).Regional metabolic measurements showed significantly different metabolic function in the occluded and nonoccluded zones of the left ventricle. Lactate balance decreased to near production levels, and a substantial potassium loss occurred in the occluded zone shortly after occlusion; lactate and potassium balances later fluctuated, but usually remained depressed. Abnormal lactate metabolism and potassium efflux were often observed in the nonoccluded zone. A 6 to 8 percent increase in oxygen extraction was noted in both segments.Progressive alterations in hemodynamic and metabolic function of the heart after coronary occlusion are not uniform and exhibit dynamic fluctuations. Although a direct relation was noted between the degree of metabolic dysfunction and hemodynamic change, individual experiments often revealed a distinct metabolic-mechanical dissociation.     

Consequences of coronary arterial occlusion on remote myocardium: effects of occlusion and reperfusion.

Focal necrosis (microinfarcts) and regional lactate derangements were observed in closed chest dogs in the nonoccluded (remote) posterior segments of the left and right ventricles after acute occlusion of the proximal left anterior descending coronary artery. Focal infarcts in the remote areas were observed in five of the six dogs with 7 days of occlusion of the left anterior descending artery and in six of seven dogs with 7 days of reperfusion after 3 hours of occlusion. There was a good correlation between the finding of microinfarcts and myocardial lactate derangements in the corresponding remote myocardium. No significant lactate derangements or microinfarcts were found in sham experiments. These findings suggest that ischemia of the remote myocardium frequently accompanies an acute coronary occlusion and may result in irreversible focal lesions.     

Revascularization after 3 hours of coronary arterial occlusion: effects on regional cardiac metabolic function and infarct size.

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.     

Enhanced left ventricular performance with phentolamine in acute myocardial infarction

The hemodynamic effects of phentolamine (Regitine) were evaluated in nine patients with increased left ventricular filling pressure and clinical left ventricular failure (Group A) and five patients with normal left ventricular filling pressure and an uncomplicated course (Group B) within 48 hours of an acute myocardial infarction. Decreased afterload was noted in both groups after administration of phentolamine. Improved left ventricular performance was noted only in Group A and was manifested by a decrease in left ventricular filling pressure (from 23.9 to 13.6 mm Hg), increase in cardiac index (from 2.1 to 2.9 liters/min per m²), increase in stroke volume index (from 22.5 to 29.3 cc/beat per m²), and little change in heart rate (from 94.2 to 99.8 beats/min). In contrast, a decrease in stroke volume index (32 to 26 cc/beat per m²) and a greater increase in heart rate (77 to 94 beats/min) were noted in Group B. Reduction of preload, which accompanies a reduction in afterload with administration of phentolamine, may have caused a greater decrease in end-diastolic volume in Group B, resulting in the reduced stroke volume index and compensatory increase in heart rate. Our findings suggest that afterload reduction induced by administration of phentolamine enhances depressed left ventricular function in patients with increased left ventricular filling pressure after myocardial infarction. Careful monitoring to prevent complications is required.     

Advances in clinical management of acute myocardial infarction in the past 25 years

The management of acute myocardial infarction in the past 25 years has emerged from a state of masterful inactivity to one of intensive care based on a new discipline of aggressive management. This has increased the chances of survival of the victim of infarction and cquld well be one of the major reasons for the decline in mortality due to coronary heart disease in the United States since 1968. Because resuscitative techniques must be instituted within 4 minutes after the onset of cardiac arrest, the attendant nurse had to learn (he new emergency lifesaving techniques and assume a crucial role as a physician's assistant. The various stages in the evolution of coronary care discipline began with cardiopulmonary resuscitation and were followed by pacemaker application, arrhythmia prophylaxis and insertion of pulmonary venous flow-directed catheters and arterial lines that permit monitoring and control of ventricular filling pressures. Other developments in better management of the failing heart have included methods to salvage jeopardized myocardium, strategies for the prevention of sudden death, the application of revascularization techniques after acute coronary occlusion and new noninvasive computerized technology to provide enhanced contrast images of cardiac perfusion that can be directly integrated with measurement of function.     

Derangements of myocardial metabolism preceding onset of ventricular fibrillation after coronary occlusion

To determine alterations in myocardial metabolism and and hemodynamics that occur within the first 30 minutes after coronary arterial occlusion, before the onset of ventricular fibrillation, measurements were compared in two series of dogs. Series A, 90 dogs that did not manifest ventricular fibrillation after coronary occlusion, were considered a control group. Series B consisted of 28 dogs that had ventricular fibrillation within 30 minutes after occlusion. All had similar comprehensive measurements completed preceding the onset of ventricular fibrillation. The animals in series B (subseuqnt fibrillation) had significantly higher heart rates before and after coronary occlusion. In this series cardiac metabolism of the occluded segment judged by transmyocardial lactate extraction, potassium balance, sodium/potassium ratio and blood pH because grossly more abnormal after coronary occlusion than in series A. In 5 animals whose measurements were obtained within 5 minutes of the onset of ventricular fibrillation, a sudden massive lactate production, potassium loss and increased acidosis of the occluded portion supervened minutes before the onset of the fatal arrhythmia. Animals with ventricular fibrillation had higher intracoronary S-T segment elevation that persisted until the onset of ventricular fibrillation. Measurements of abnormal hemodynamic function (left ventricular end-diastolic pressure, peak systolic pressure and first derivative of left ventricular pressure [DP/dt]) were not associated with an increased incidence of ventricular fibrillation. The study indicates that animals that manifest ventricular fibrillation within 30 minutes after coronary occlusion have higher preocclusion heart rates, a more severe metabolic disorder of the coronary occluded segment and more persistent intracoronary S-T segment elevation compared with animals that do not manifest ventricular fibrillation.     

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.