Tzu-Wang Lang

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

Abstract 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.

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.

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.

Synchronized retroperfusion of coronary veins for circulatory support of jeopardized ischemic myocardium

A retroperfusion system was developed that augments retrograde delivery of arterial blood into an acutely ischemic myocardial region during diastole and facilitates coronary venous drainage in systole. An electrocardiogram-synchronized, gas-actuated bladder pump propels retroperfusate through an autoinflatable balloon catheter whose tip is placed within the regional coronary vein that drains the ischemic myocardium. Experiments were performed in 26 closed chest dogs with 4 hour intracoronary balloon occlusion of the proximal left anterior descending coronary artery. An untreated control series consisted of 13 dogs; the remaining 13 dogs were treated with retroperfusion, which was initiated after the first hour of acute coronary occlusion. Synchronized retroperfusion resulted in a significant 37 +/- 10 per cent (mean +/- standard error of the mean) decrease in left ventricular end-diastolic pressure from 11 +/- 2 to 5 +/- 21 mm Hg, a 20 +/- 4 percent decrease in peak systolic pressure (140 +/- 7 to 110 +/- 6 mm Hg) and a 25 +/- 6 percent reduction in systemic vascular resistance (3,880 +/- 340 to 2,380 +/- 300 dynes sec cm-5). Ischemic region intracoronary S-T segment elevation decreased 40 +/- 15 percent, and potassium loss was reduced 92 +/- 22 percent. Partial pressure of oxygen measured distal to the coronary occlusion decreased 36 +/- 2 percent, suggesting oxygen delivery to and extraction by the jeopardized ischemic myocardium. Ventriculography in four dogs revealed an increase in left ventricular ejection fraction and reversal of ischemic segment dyskinesia by synchronized retroperfusion. A nitro-blue tetrazolium study of 10 excised hearts indicated that 3 hours of synchronized retroperfusion significantly reduced the size of ischemic injury to 3.3 +/- 2 percent of the left ventricle (versus 16.2 +/- 5 percent in the untreated control group). In addition, retroperfusion appeared to correct ischemic arrhythmias. The experimental data suggest that this treatment is capable of improving cardiac function and salvaging jeopardized myocardium. Clinical application is envisioned as a prompt temporary emergency support for acute and profound ischemic dysfunction not readily treatable by other interventions.

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

Abstract 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.

Physiologic principles in the application of circulatory assist for the failing heart: Intraaortic balloon circulatory assist and venoarterial phased partial bypass

Abstract Venoarterial pulsatile partial bypass and intraaortic balloon counterpulse techniques produce (1) diastolic augmentation of aortic pressure which improves perfusion of the myocardium, and (2) a sink in presystolic and systolic pressures which lowers the workload of the left ventricle. Both techniques are effective in reversing the shock state in dogs and in man. Regional hemodynamic studies performed before, during and after counterpulsation explain benefits and drawbacks of each technique.

Significance of S-T segment elevations in acute myocardial ischemia: Evaluation with intracoronary electrode technique

A method is described for measuring intracoronary S-T segment elevations in the closed chest, a technique that appears to provide more reliable measurements of myocardial ischemia. Electrodes were inserted through intracoronary balloon catheters that were placed within a coronary artery and its adjoining vein both proximal and at several points distal to a coronary occlusion. Intracoronary arterial and adjacent venous electrocardiograms produced equivalent tracings. The intracoronary S-T segment elevations after coronary occlusion resembled those recorded from the epicardial surface but were free of artifacts noted in open chest studies. Study of progressive alterations of the intracoronary S-T segment after proximal occlusion of the left anterior descending coronary artery in 18 closed chest dogs revealed a peak segment elevation of 3.2 +/- 0.6 mv within 5 minutes, followed within 2 to 3 hours by spontaneous reduction by more than 40% of the S-T elevation over the occluded zone. In 44% of these animals, the S-T elevation decreased spontaneously to less than 1 mv, and in 22% it decreased to the preocclusion control level within 2 hours of occlusion. This spontaneous decrease in S-T elevation was frequently followed by a secondary increase and then S-T segment fluctuations. Reperfusion of the left anterior descending coronary artery after 30 to 60 minutes of occlusion generally led to a prompt reduction in S-T elevation. In some cases S-T elevations persisted up to 14 hours of occlusion, were reduced after reperfusion and exhibited a renewed pronounced increase after subsequent reocclusion of the left anterior descending coronary artery. During the 1st hour after occlusion, the early S-T segment elevation followed by spontaneous reduction reduction generally corresponded temporally with the derangements in myocardial lactate extraction and potassium loss. However, after 1 hour of occlusion no clear-cut correlation could be established between S-T fluctuations and changes in hemodynamic or myocardial metabolic measurements. We conclude that the new closed chest intracoronary electrocardiographic S-T technique might be of use for monitoring the early ischemic myocardial derangements and to assess benefits or drawbacks of treatment in both the experimental animal and man. Correspondence of S-T segment elevation with lactate and potassium alterations in the coronary-occluded region in the 1st hour after occlusion indicates that S-T segment elevation might represent an index of early myocardial ischemia. The spontaneous S-T changes that follow coronary occlusion must be taken into consideration when investigators utilize S-T segment modification as a sign of effectiveness of treatment.

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

Abstract 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.

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.

Effect of glyceryl trinitrate (nitroglycerin) on the systemic and coronary circulation of the dog

Abstract The effect of glyceryl trinitrate (nitroglycerin) on systemic and coronary hemodynamics was studied in normal dogs by means of electromagnetic flowmeters and integrator computers. When given intravenously, glyceryl trinitrate produced changes in the hemodynamics which can be of benefit to the patient with angina pectoris. The drug first increased the coronary blood flow and cardiac index and reduced peripheral vascular resistance for about 20 seconds. This was followed by normal coronary flow with reduced peripheral and coronary vascular resistance, for about 60 seconds; at the same time cardiac work was markedly reduced. These results confirm that the beneficial effects of nitroglycerine are due to its action on the coronary as well as the systemic circulation.