Effects of moderate coronary stenosis on myocardial flow reserve in man and in the dog.

The influence of coronary stenosis on resting blood flow (201Tl-uptake) and myocardial flow reserve (bicycle ergometry) is studied in 18 patients with coronary disease. Severe coronary stenosis of 75--90% caused a reduced 201Tl-uptake both at rest and peak exercise. In contrast to this group patients with a 50--60% stenosis have a normal scintigram at rest but focal defects of 201Tl-uptake at peak exercise. Results are compared with experimental data obtained after acute coronary constriction and simultaneous coronary dilatation (myocardial flow reserve, MFR) in 12 dogs. 60% coronary constriction causes a 37% decrease of poststenotic MFR measured with tracer microspheres. Changes of transmural flow distribution (endo/epi ratio) are minor in the left ventricular free wall but significant in the poststenotic septum (endo/epi = .84). It is concluded that even a moderate coronary stenosis of 60% not affecting resting blood flow becomes "critical" under conditions of high flow velocities.

The influence of the size of acute ischaemic myocardial lesions on coronary reserve and left ventricular function in the dog.

Acute ischaemic lesions of 5 and 15% of the left ventricular mass were produced in 10 dogs by ligations of branches of the left anterior descending coronary artery. Under maximal coronary dilatation by Dipyridamole and at constant aortic pressure, an ischaemic lesion of 15% caused reductions of blood flow in the left anterior descending coronary artery of 50% (p less than 0.05), , the R. circumflexus of 36% and of total myocardial blood flow (Argon method) by 44% (p less than 0.02). Parameters of left ventricular function, dp/dtmax and Vmax fell by 26 and 27% respectively (p less than 0.02). Ischaemic lesions of 5% LV mass were detected by 133 Xenon clearance estimations, but had no effect on any of the other variables measured. There was good agreement between estimations of total myocardial blood flow (Argon) and direct measurement of coronary flow with electromagnetic flowmeters (r = 0.957).

[Myocardial blood flow distribution immediately following experimental aortocoronary bypass and 1 year postoperatively]. / Myokardiale Durchblutungsverteilung unmittelbar nach experimentellem aorto-coronarem Bypass und 1 Jahr postoperativ.

A 75--90% stenosis of the left circumflex coronary artery (CCA) was induced over a period of 40 days in 11 mongrel dogs. Coronary blood flow and the distribution of myocardial blood flow (MBF, tracer-microspheres) was measured at rest and after maximal coronary dilatation in 8 dogs before and within 1 hour after coronary bypass. In 3 dogs these measurements are performed 1 year after bypass op. During coronary stenosis distribution of myocardial blood flow in the area supplied by the CCA was unhomogeneous, the subendocardium receiving less. Within 1 hour after opening the graft, MBF to the subendocardium was improved but the unequal distribution not completely abolished. One year after bypass op, however, the quantity and distribution of MBF appear to be normal although revascularized myocardium was perfused in part via coronary collaterals.

[Effects of coronary stenosis and mean aortic pressure on coronary blood flow, poststenotic coronary pressure, and reactive hyperemia]. / Einfluss von Koronarstenose und Aortendruck auf Koronarfluss, Koronardruck und reaktive Hyperämie

Six dogs were subjected to an acute stenosis of the left anterior descending coronary artery. The mean aortic pressure was fixed with a windkessel and an occluder on four different levels. A significant decrease of coronary blood flow and poststenotic coronary pressure was closely related to the level of mean aortic pressure. With lower aortic pressure the decrease occurred earlier than with higher aortic pressure. A 50% stenosis did not significantly influence coronary flow and poststenotic coronary pressure. A 90% stenosis resulted in decrease below 10% of control. In a range of aortic pressure between 60 and 140 mm Hg reactive hyperemia was significantly diminished at a 60% stenosis. Reactive hyperemia was completely abolished when coronary stenosis was 90%.

Experimental coronary artery bypass operation. Myocardial blood flow, ventricular performance and regional myocardial function.

Myocardial blood flow and ventricular function was studied in seven dogs with chronic myocardial ischemia before and after coronary bypass grafting. Restoring blood flow in an area of 25% of the anterior wall of the left ventricle did not significantly improve overall ventricular function. Assessment of intramyocardial pressure as an index of regional myocardial function revealed a consistent enhancement of myocardial contraction at rest, and under pharmacological stress of the heart.

Hemorrhagic shock with fixed hypotension and with spontaneous recovery of blood pressure. A comparison of two shock models.

In 26 dogs anesthetized with a barbiturate peripheral blood flow, O2 consumption and acid-base balance have been studied in two kinds of hemorrhagic shock: 1. Hemorrhagic shock with fixed hypotension (hypotensive shock, n = 12) 2. Hemorrhagic shock with spontaneously recovering arterial blood pressure (normotensive shock, n = 14). In both groups the same amount of blood is withdrawn and stored in a reservoir (31-32 ml/kg) to reduce arterial pressure to 40 mm Hg. In hypotensive shock there is a continuous outflow of blood into the reservoir in order to maintain an arterial pressure of 40 mm Hg. After 1 1/2 hours this shift of blood reverses itself spontaneously. In normotensive shock the arterial pressure is allowed to increase after the initial withdrawal of blood. 1 1/2 hours later it reaches a peak of 93 mm Hg after which it starts declining again. The duration of oligemia which the animals control themselves is nearly identical in both groups (4 hours). Both kinds of hemorrhagic shock have a mortality rate of 80%. The survival time is shorter (p less than 0.01) in hypotensive (3 hours) than in normotensive shock (7 1/2 hours). In both kinds of shock heart rate increases to more than 200 beats/min. However, in hypotensive shock it decreases in the late stage of hypovolemia, whereas the increase is continuous in normotensive shock. Cardiac output is significantly higher in the normotensive animals nearly throughout the entire hypovolemic phase although the initial decrease is the same in both groups (71%). Also a greater increase in total peripheral resistance occurs in these animals. The increased cardiac output and total peripheral resistance. A "centralization" of the circulation is also observed in this kind of shock as is made evident by the changes in the relationship between cardiac output and carotid blood flow. Hyperventilation occurs in both kinds of shock. In hypotensive shock respiratory rate decreases at the end of the oligemic phase possibly due to a smaller cerebral blood flow.

Influence of cinepazide, a vasoactive substance, on canine coronary circulation after acute constriction of the left anterior descending coronary artery.

The left anterior descending coronary artery was variably constricted mechanically in nine dogs. Blood flow in the left anterior descending (LAD) and circumflex coronary arteries (CCA), aortic pressure and peripheral, i.e. post-stenotic coronary pressure were measured. Myocardial perfusion was determined from the clearance of radioactive xenon injected at a depth of 7 mm into the underperfused area supplied by the LAD artery. The vasoactive drug 1-(pyrrolidinyl-1-carbonyl)-methyl-4-(3,4,5-tri-methoxycinnamoyl)piperazine-maleate (cinepazide) was given at doses of 5-10 mg/kg by i.v. route. 1. Blood flow in the LAD was decreased stepwise to 50% of its initial value. There was practically no more coronary reserve. After drug injection, diastolic aortic pressure, that normally falls, was kept constant by clamping. Heart rate, perfusion pressure, post-stenotic pressure, and blood flow and resistance in the LAD showed practically no change. In the CCA, blood flow increased significantly (p less than 0.005) and flow resistance decreased (p less than 0.001). 133Xe clearance showed an increased myocardial perfusion (p less than 0.02) in the territory supplied by the LAD artery. 2. The lumen of the LAD was narrowed by 53%, i.e., coronary reserve was decreased. This constriction was followed by no haemodynamic reaction. After injection of cinepazide, mean and diastolic aortic pressure (p less than 0.02) and post-stenotic coronary pressure (p less than 0.005) decreased. Blood flow increased by 41% in the CCA and by 31% in the LAD. Coronary resistance in these vessels decreased (p less than 0.001 and 0.005, respectively). Here, too, the 133Xe clearance curve showed an increase in myocardial perfusion in the territory supplied by the LAD artery (+78%).

[Myocardial blood flow and ventricular function in dependence on the size of myocardial infarct]. / Myokarddurchblutung und Ventrikelfunktion in Abhängigkeit von der Infarktgrösse.

In eight dogs three branches of the left anterior descending coronary artery were occluded by successive ligations. Each time coronary flow reserve was measured by injecting dipyridamole (0.4 mg.kg-1). After an infarction of 13% of the left ventricle there was a significant decrease of Vmax and dp/dtmax (p less than 0.05). Measurements of regional myocardial blood flow detected an infarction of 5% of the left ventricle, whereas the total myocardial blood flow was reduced significantly when 17% of the left ventricle was infarcted.

[Regional myocardial blood flow and left ventricular function in critical coronary stenosis and after coronary artery bypass grafting in the dog (author's transl)]. / Regionale Myokarddurchblutung und Ventrikelfunktion bei hochgradieger Koronarstenose und nach koronarer Bypass-Operation beim Hund

In 7 mongrel dogs myocardial ischemia is produced by means of an ameroid constrictor placed on the left circumflex coronary artery (CCA). Myocardial blood flow (MBF) is diminished by 56% in an area of 25% of the anterior wall of the left ventricle. A decrease in dp/dtmax suggests a small depression of left ventricular function. After bypass operation the slight changes in EDP, dp/dtmax and Vmax indicate no significant improvement of total ventricular function. MBF increases from 42 +/- 10 ml/100 g/min to 67 +/- 21 ml/100 g/min (p smaller than 0.02) in the area supplied by the bypass. In this region intramyocardial pressure rises significantly suggesting improvement of regional myocardial function.

[Effect of coronary bypass surgery on myocardial pressure and ventricular function in the dog]. / Einfluss der koronaren Bypassoperation auf Myokarddruck und Ventrikelfunktion beim Hund

In 7 dogs a severe stenosis of the left circumflex coronary artery (CCA) is produced in the course of 18 days. The influence of myocardial revascularization on left ventricular function and on intramyocardial pressures in the areas supplied by the CCA and by the left anterior descending coronary artery is studied. Neither under control conditions nor during acute left ventricular pressure load does opening a bypass graft between the carotid artery and CCA induce a significant change in total ventricular function (dp/dtmax, Vmax, left ventricular enddiastolic pressure). However, immediately after opening the graft intramyocardial pressure rises in the CCA area indicating a regional improvement of myocardial function.