Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction.

A decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p less than 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A.M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A.M. seem to be closely related.

[Definition and significance of the area at risk in myocardial infarct and the ischemic border zone in acute myocardial infarct]. / Definition und Bedeutung des Infarktrisikogebietes und der ischämischen Randzone bei akutem experimentellem Myokardinfarkt.

Early localisation of infarction, estimation of infarct size and visualisation of metabolic and structural changes is of great importance for the management of acute myocardial infarction. This paper is based on an experimental model using a combination of in-vivo and in-vitro methods that allow the evaluation of the area at risk of infarction, the border zone and its changes over time. The purpose of the study was to characterize the topography and the time course of the border zone. The border zone forms an approximately 2 mm wide margin at the lateral edges of the infarct, with increasing width of the border zone along the subepicardium. Increasing duration of ischemia is associated with a dynamic sequence of events, not only within the area at risk of infarction but also in the peri-ischemic border zone, leading to an expansion of the subepicardial margin due to improved collateral blood flow over time. The area at risk of infarction is characterized by early distinct metabolic changes that were visualized as soon as 90 to 120 seconds following coronary artery occlusion. After 6 hours of occlusion almost the entire area at risk shows signs of irreversible injury due to severe hypoperfusion. The border zone, in contrast, is characterized by only moderate metabolic changes due to greater collateral perfusion (45 to 80% of the regional blood flow in the non-ischemic vascular bed). Several interventions were chosen and evaluated for their effects on the dynamic course of events within the area at risk of infarction and in the border zone. Interventions that have strong myocardial protective effects such as the combination of alpha- and beta-blockade, the application of specific O2-carriers (Perfluorocarbons) and pressure controlled retrograde perfusion via the coronary sinus ("PICSO"), not only reduce infarct size by 20 to 40% of the myocardium at risk of infarction, but also induce substantial topographic, functional and metabolic changes within the border zone.

[Hemofiltration and the neurohumoral system in patients with severe heart failure]. / Hämofiltration und neurohumorale Systeme bei Patienten mit schwerer Herzinsuffizienz.

6 fluid overloaded patients with congestive heart failure, NYHA classification IV, resistant to drug therapy, were treated by pump driven venovenous hemofiltration. The sympathetic nervous system measured by plasma norepinephrine concentration was stimulated in all patients. 4 of 6 patients had a markedly enhanced plasma renin activity. Between 7 and 20 l of fluid were removed by hemofiltration. The expected increase of plasma norepinephrine did not occur in 4 out of 6 patients. The improvement of cardiac pump function by hemofiltration could be an explanation for this apparent paradoxical regulation. Patients who had almost a normal plasma renin activity prior to hemofiltration showed a marked increase after the procedure. In patients with extremely high levels of plasma renin activity we noted a decrease after hemofiltration. Almost in every patient with a serum sodium concentration lower or equal 132 mmol/l the plasma renin activity was markedly elevated. Patients with normal serum sodium concentrations exhibited only slightly elevated plasma renin activity. Therefore, a hyponatremia in patients with heart failure can be used as a marker for high plasma renin activity. All patients had a significant improvement of the clinical state after hemofiltration. 3 patients, however, showed deterioration within a few weeks, due to the severity of the disease. Their plasma norepinephrine levels remained high or had a tendency to increase.

[Methods of hemofiltration]. / Methoden der Hämofiltration.

The methods of continuous hemofiltration therapy are described. The various forms of blood access are discussed, especially the pumpdriven venovenous form of hemofiltration utilizing a double lumen catheter in the superior caval vein is demonstrated as an alternative to the spontaneous arteriovenous method. The own experiences in over 140 patients with renal, cardial and pulmonal indications are summarized.

[Hemofiltration in chronic heart failure]. / Hämofiltration bei chronischer Herzinsuffizienz.

30 patients with severe congestive heart failure (NYHA IV) unresponsive to medical management were treated by continuous hemofiltration (CHF). 57% of patients received arteriovenous CHF and 43% of patients venovenous, machine assisted CHF over 95 +/- 31 hours. A reduction of body edemas was achieved. The removal of body fluid by CHF between 2 and 40 kg led to a reduction of body edemas and short-term clinical improvement. Furthermore CHF treatment induced hemodynamic improvement with a reduction of central venous pressure (18 +/- 6 cm H2O pre CHF vs 8 +/- 4 cm H2O post CHF p less than 0.01) and a reduction of left ventricular filling pressure (22 +/- 6 mm Hg vs 14 +/- 5 mm Hg, p less than 0.01), while the left ventricular ejection fraction remained unchanged. Patients with low serum sodium levels (less than 132 mval/l) benefited most. While 28/30 of patients has short-term clinical improvement between 2 and 8 weeks, 38% of patients had long-term benefits.

Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion.

The effect of pressure-controlled intermittent coronary sinus (CS) occlusion on myocardial infarction (MI) size was evaluated. A device for this purpose was developed that consisted of a balloon catheter and pump system that produced controlled, intermittent occlusion of the CS and used CS pressure as a feedback to determine the duration of occlusion. It was hypothesized that proper selection of occlusion and non-occlusion times would both facilitate improved retrograde flow to ischemic areas and allow for more complete venous washout of metabolites. In 13 treated dogs and 12 control dogs before treatment, myocardium at risk of MI was estimated by injection of technetium-labeled microspheres. Intermittent CS occlusion was then begun, 15 minutes after coronary artery occlusion, and continued until termination of the experiment 6 hours later. Postmortem determination of infarct size was performed using the triphenyltetrazolium chloride staining technique. Intermittent CS occlusion begun 15 minutes after coronary artery occlusion and continued for 6 hours resulted in a 45% average reduction in MI size (p less than 0.001). During CS occlusion, the sinus systolic mean pressure increased from 10 to 44 mm Hg, while the distal coronary artery mean pressure increased by an average of 36% (from 22 to 30 mm Hg, p less than 0.05). These results suggest intermittent occlusion may be an effective treatment for evolving MI. This therapy, used alone or combined with other therapies (e.g., administration of pharmacologic agents), appears to have great clinical potential.

[Ergometry and long-term ECG for assessing bradycardiac and tachycardiac heart rhythm disorders in symptomatic patients over 70]. / Ergometrie und Langzeit-EKG zur Abklärung von bradykarden und tachykarden Herzrhythmustörungen bei symptomatischen Patienten über 70 Jahre.

The usefulness of exercise testing and long term-ECG recording in old age was evaluated in a retrospective study. During a period of 24 months 317 long-term-ECGs in 195 patients greater than 70 years and 208 exercise tests in patients greater than 70 years were performed. The mean age of the patients was 73 +/- 3 years. Long-term ECG revealed a high incidence of supraventricular arrhythmias, while PVCs were found in only 28.7% of patients and PVCs greater than 30/h in only 7.3% of patients. Complex ventricular arrhythmias occurred in 25% of patients. Long-term ECG recording appeared to be of particular value in detecting abnormal regulation of heart rate and bradycardia, although symptom correlation with arrhythmias recorded was rare. Exercise testing revealed a higher incidence of PVCs with PVCs recorded in 67% of patients and PVCs greater than 2/min in 42% of patients. The incidence of complex ventricular arrhythmias was slightly greater compared to long-term recording with 29% of all patients. Exercise testing was particularly useful in detecting complex arrhythmias in patients with additional signs of myocardial ischemia (ST-segment depression and/or angina pectoris during increasing levels of exercise). Thus comparing both exercise testing and long-term ECG both appeared to be useful methods to uncover arrhythmias in symptomic patients older than 70 years and have to be considered as complementary tools. Exercise testing is particularly useful in recovering complex ventricular arrhythmias in patients with signs of myocardial ischemia during exercise. Long-term ECG on the other hand allows better recognition of bradycardias and conduction defects that may also be present and may contribute to the patients symptoms.

Fluorocarbons reduce myocardial ischemic damage after coronary occlusion.

Open-chest, anesthetized dogs with occlusions of the left anterior descending coronary artery breathed 100 percent oxygen while they were bled to a hematocrit of 25 percent and infused with an approximately equal volume (40 milliliters per kilogram) of fluorocarbon preparation or Ringer solution. Dogs breathing room air and receiving no treatment served as controls. After undergoing 6 hours of coronary occlusion, animals bled and treated with fluorocarbons developed smaller infarctions than those receiving Ringer solution or no treatment.