Thomas W. Moir

Subendocardial Distribution of Coronary Blood Flow and the Effect of Antianginal Drugs

• Histological evidence indicates that the subendocardial layers of the left ventricle are vulnerable to ischemia: areas of necrosis in the subendocardium are greater than they are in the epicardium in transmural infarction (1) and in coronary insufficiency (2), suggesting that antegrade coronary blood flow in the subendocardial layers is less than that in the epicardium because of the proximity of the former to intracavitary left ventricular pressure (3). Initial studies showed a gradient in tissue pressure with systolic pressure in the subendocardium exceeding that in the left ventricular cavity and suggested that systolic extravascular compression could be a significant feature in the transmural distribution of coronary blood flow (3). These findings obtained by indirect methods have been generally confirmed (4-7) by studies using other indirect methods, although the intramyocardial tissue pressure in the inner layers of the left ventricle has not always been found to exceed cavitary pressure (8). Recently, a more direct measurement of myocardial tissue pressure by subminiature pressure transducers (9) has confirmed the presence of a transmural gradient with systolic pressure in the subendocardium of

Effect of Left Ventricular Hypertension, Ischemia and Vasoactive Drugs on the Myocardial Distribution of Coronary Flow

Distribution of coronary flow to the inner and outer layers of the left ventricle of the anesthetized, open chest dog was estimated by the myocardial uptake of 86Rb chloride infused into the cannulated common left coronary artery. With normal relationship of coronary perfusion pressure and left intra-ventricular pressure, there was no significant underperfusion of the endocardium. When left intraventricular pressure was raised and coronary perfusion pressure was held at levels sufficient to provide normal coronary flow, endocardial distribution remained equal to or slightly greater than that to the epicardium. However, when coronary perfusion pressure was lowered, particularly to levels causing obvious signs of myocardial hypoxia, maintenance of a normal left intraventricular pressure resulted in marked underperfusion of the endocardium. The coronary vasoactive drugs, dipyridamole, norepinephrine, vasopressin, and the β-adrenergic receptor blocking agent, propranolol, increased the flow distribution to the endocardium of both the normotensive and hypertensive left ventricle. It is concluded that the systolic tissue pressure which increases from epicardium to endocardium does not cause significant underperfusion of the endocardium in either the normotensive or hypertensive left ventricle as long as normal coronary perfusion pressure and flow are maintained.

The bleeding severity index: Validation and comparison to other methods for classifying bleeding complications of medical therapy

Reports of bleeding complications of medical therapy should be based on valid methods of classification, but the reproducibility of existing methods has not been tested. Therefore, we prospectively studied three methods to classify the severity of bleeding: a purely subjective implicit method, a previously published explicit method using brief criteria, and the bleeding severity index, which is a new explicit method using detailed criteria about the amount, rate, and consequences of bleeding. Three physicians independently reviewed abstracts of 168 patients treated with anticoagulants. The proportion of cases classified as major bleeding varied widely when the implicit method was used (2, 14 and 39%), less when the old explicit method was used (28, 40 and 47%), and not at all when the new bleeding severity index was used (20, 20 and 20%). Intraobserver agreement was excellent for both explicit methods (kappa greater than or equal to 0.95). However, interobserver agreement was better for the bleeding severity index (kappa = 0.87) than for the old explicit method (kappa = 0.69) or the implicit method (kappa = 0.39). We conclude that the classification of bleeding complications of medical therapy depends on the method used. In comparison to older methods, the bleeding severity index is highly reproducible and should be tested more widely to determine whether it can be applied to the burgeoning clinical research in anticoagulation and thrombolysis.

Measurement of Coronary Blood Flow in Dogs with Normal and Abnormal Myocardial Oxygenation and Function

Common left coronary blood flow was measured simultaneously by a recording rotameter and by the Rb86 chloride clearance method in anesthetized, open chest dogs, and compared over a wide range of flow rates and under conditions of both normal and abnormal myocardial oxygenation and function. Although the Rb86 clearance method reflected the same directional changes as metered flow, a systematic underestimate was found which ranged from 27% at ischemic flow rates to 54% at hyperemic rates. Myocardial extraction studies supported the view that coronary flow rate and the resultant time that the isotope was in the capillary bed was the major determinant of the underestimate by the Rb86 method even under conditions of myocardial hypoxia. It was concluded that the Rb86 method gave an accurate estimate of directional change in coronary blood flow but that the magnitude of the underestimate of actual flow limits its use as a quantitative index.

The Determination of Cardiac Output by the Dilution Method without Arterial Sampling II. Validation of Precordial Recording

Technics for determining the cardiac output by recording the dilution curve of injected iodinated I131 human serum albumin from precordial sites have been described. By viewing predominantly either the right or left side of the heart and by rapid delivery of the isotope, quantitation of the dilution curves for cardiac output has been possible without critical requirements for placement of the counter. In a series of 26 determinations in normal patients cardiac output values calculated from simultaneously recorded precordial curves and withdrawn arterial blood showed an average agreement within ± 8 per cent. In a smaller series of 8 determinations on patients in heart failure, an average deviation of ± 9 per cent was found.

Takayasu's arteritis. Report of a case with unusual findings.

Abstract A case of Takayasus arteritis with some unusual findings is presented. The patient was a 35 year old woman with a previous history of ulcerative colitis and rheumatoid arthritis. She presented with a variety of nonspecific systemic symptoms. On physical examination systolic bruits were heard over both carotid and subclavian arteries and the abdominal aorta. On the basis of aortograms, laboratory data and an aortic biopsy the diagnosis of Takayasus arteritis was made. Unusual findings were: (1) the past history of ulcerative colitis and rheumatoid arthritis; (2) involvement of the right pulmonary and right renal arteries; (3) recurrent pericardial effusion; and (4) marked symptomatic improvement after steroid therapy without angiographic evidence of resolution of the arterial lesions.

Autoregulation of Coronary Blood Flow: Effect of Interarterial Pressure Gradients

In the normal heart, transient and adjusted steady state coronary flow rates in response to changes in perfusion pressure are not significantly affected by collateral flow into and from heart muscle surrounding the area perfused by a test artery. An active autoregulatory adjustment tends to counteract flow changes after perfusion pressure is changed. This adjustment is sometimes sufficient to increase vascular resistance above control values. Usually, however, coronary resistance decreases at higher perfusion pressures even though autoregulation is present. The experiments provide no evidence for reflex control of coronary resistance in response to increases in aortic pressure; the initial flow changes can be accounted for by the corresponding increase in perfusion pressure. It is necessary to examine the entire coronary flow pattern after a sudden change in perfusion pressure in order to formulate concepts which include all the important determinants of coronary blood flow.

Thebesian Drainage in the Left Heart of the Dog

Direct left heart drainage from the common left coronary artery has been demonstrated in the normally beating dog heart by an isotope dilution technique. The major portion of this drainage has been shown to be through the left circumflex branch of the common left coronary artery. The left anterior atrial artery, a branch of the left circumflex, has in turn been shown to be the major pathway of drainage from the latter. Left heart drainage could not be demonstrated from isotope injections into the left anterior descendens artery, and in only one preparation could such drainage be documented from the septal branch of the common left artery. The magnitude of left heart Thebesian drainage has been estimated by analysis of time-concentration curves recorded from the aorta. An average of 2% of total common left coronary artery inflow drains directly into the left heart. Although the major drainage is probably into the left atrium, left ventricular drainage has not been excluded.

Thebesian Drainage of the Septal Artery

Direct right ventricular drainage of I131 serum albumin injected into the septal artery of the normally beating dog heart has been demonstrated. By the application of standard dilution equations to the time-concentration curves recorded in the pulmonary artery, estimates of the magnitude of this Thebesian drainage have been made. Approximately 80% of septal artery outflow has been estimated to drain directly into the right ventricle; this amount comprises about 12.8% of total common left coronary flow and, in part, explains the discrepancy found between common left coronary inflow and coronary sinus outflow. The implications of Thebesian drainage of a branch of the common left coronary artery relative to the use of coronary sinus sampling for left ventricular metabolic studies have been discussed.

Phasic and Mean Blood Flow in the Canine Septal Artery and an Estimate of Systolic Resistance in Deep Myocardial Vessels

Phasic flow in the canine septal artery was recorded with an orifice meter supplied by pulsatile aortic pressure. Flow patterns were recorded when right ventricular pressure was normal and contrasted with those following elevation of right ventricular pressure in order to minimize the dynamic effect of the superficial component of the artery. Results indicate that elevation of right ventricular pressure increases the early systolic backflow, largely prevents mid-systolic forward flow, and accentuates early diastolic flow. It is suggested that this pattern does not represent that in arterioles in deep layers of the myocardium. In other experiments the septal artery was perfused through an orifice meter at variable pressures to determine the pressure required to negate mid-systolic flow at high right ventricular pressures. The results indicate that pressures considerably above aortic or right ventricular systolic pressures are required to generate forward mid-systolic septal flow. The mean septal flow was quantitated in terms of total common left inflow. It was found that an average of 16.0% of common left flow enters the septal artery. The significance of this has been discussed in terms of its relationship to the venous drainage of common left coronary arterial inflow.