Harold S. Marcus

Measurement of Coronary Sinus Blood Flow by Continuous Thermodilution in Man

A technique was developed for measurement of blood flow in the coronary sinus in man by continuous thermodilution. For single determinations, 5% dextrose at room temperature is injected at a constant rate of 35 ml/min for a period of about 20 sec. In 14 subjects with normal coronary arteries the mean coronary sinus blood flow was 122 ± 25 ml/min (range, 83 to 159 ml/min). The blood flow computed per 100 g of left ventricle was 82 ± 16 ml/min, which is in the range of values obtained by nitrous oxide and coincidence counting methods. In 35 patients with arteriographically confirmed coronary artery disease the mean flow was similar (128 ± 20 ml/min; range, 92 to 167 ml/min).A special catheter was used for simultaneous measurement of blood flow in the coronary sinus and great cardiac vein. In eight normal subjects the mean great cardiac vein flow was 68 ± 11 ml/min (range, 51 to 78 ml/min) or 65 ± 10% of the coronary sinus blood flow. The method allowed continuous measurement of flow over a period of several minutes and, for the first time, measurement of rapid changes in myocardial perfusion.

A new technique for measurement of cardiac output by thermodilution in man

Abstract A technique for measurement of cardiac output by thermodilution (COTD) in man has been described. Comparison with cardiac outputs determined simultaneously by the dye-dilution technique (CODYE) in 63 measurements in 20 patients showed close agreement of the 2 methods in a range of values from 2.9 to 8.0 liters/min (COTD = 0.96 CODYE + 0.2, r = 0.96). The reproducibility of measurements was 4.1 percent with the thermodilution and 5.4 percent with the dye-dilution technique. The thermodilution technique does not require withdrawal of blood during measurements and removal of blood for calibration. The calibration is simple and accurate. There is virtually no recirculation, so that a simple integrator can be used for determination of the area beneath the thermodilution curve.

Evaluation of Sino-atrial Node Function in Man by Overdrive Suppression

Sino-atrial node (SAN) function was evaluated in 46 patients, three of whom had the sick sinus syndrome. Patients were paced from the right atrium for 15 to 180 sec at rates of 90, 110, 130, and 150 beats/min. The rapid cessation of pacing was associated with suppression of the SAN at all paced rates and at all durations of pacing. The observed pause was terminated by a sinus beat in all instances. The duration of pacing had little influence on the duration of the observed pause. The pause increased as the pacing rate was increased until, at a rate of 150 beats/min, a marked decrease in the pause was noted. Atropine (1.5-3.0 mg iv) diminished but did not eliminate the SAN suppression. Subthreshold pacing did not suppress SAN function. Three patients with sick sinus syndrome had a greater degree of SAN suppression than normal patients (4732 ± 415 msec [SSS] M ± SEM; 1041 ± 56 msec for normal patients).The determination of the duration of the pause following cessation of atrial pacing provides a technique for recognition of abnormalities of SAN function.

Beneficial Effects of Vasodilator Agents in Severe Mitral Regurgitation Due to Dysfunction of Subvalvar Apparatus

To assess the potential beneficial effects of vasodilator agents in patients with severe mitral regurgitation, sodium nitroprusside was administered intravenously at a rate of 16 to 100 μg/min in eight patients with clinically significant mitral regurgitation presumably due to dysfunction of the subvalvar apparatus. In all patients there was a decrease in the magnitude of the peak ‘V’ wave (from 50 ± 4.5 to 19 ± 2.9 mm Hg) and in left ventricular filling pressure (33 ± 1.8 to 16 ± 1.4 mm Hg), together with a decreased intensity of the apical pansystolic murmur. There was a significant increase in forward cardiac index (2.2 ± 3.5 to 3.3 ± .47 liter/min/M2) and forward stroke volume index (23 ± 4.4 to 36 ± 6.6 ml/M2) along with a reduction in systemic vascular resistance (1802 ± 331 to 1102 ± 241 dynes/sec/cm-5). In the five patients in whom the therapy was continued, relief of symptoms of pulmonary venous congestion occurred. In the four patients in whom left ventricular volumes were determined angiographically, the observed increase in forward stroke volume was due to a reduction in the regurgitant fraction. These findings suggest that the use of vasodilator agents like nitroprusside can achieve the major objectives of treatment of patients with mitral regurgitation: an increase in forward stroke output, a reduction in regurgitant volume and a decrease in pulmonary venous pressure.

Influence of Direct Myocardial Revascularization on Left Ventricular Asynergy and Function in Patients with Coronary Heart Disease With and without Previous Myocardial Infarction

The influence of successful aortocoronary artery bypass surgery on left ventricular asynergy and dysfunction was studied by hemodynamic and angiographic methods in 29 patients with coronary artery disease. Eight patients had the preinfarction syndrome, 10 patients had chronic ischemia without previous infarction, and 11 patients had chronic ischemia with previous infarction. LV asynergy was present preoperatively in 12 of the 18 patients in the first two groups. Marked improvement occurred in all and a normal wall motion was restored in the majority following surgery. More pronounced improvement was noted in the preinfarction syndrome as compared to the group with chronic ischemia and no previous infarct. The ejection fraction was reduced in 12 of the 18 patients in these two groups and significant improvement was observed postoperatively [0.45 ± 0.03 (SEM) to 0.74 ± 0.03]. Increase in ejection fraction was primarily due to a decrease in the end-systolic volume (71 ± 12 to 23 ± 4 ml/m2). The end-diastolic volume was only slightly reduced (114 ± 12 to 97 ± 9 ml/m2). Left ventricular end-diastolic pressure fell from 15 ± 1 to 10 ± 1 mm Hg.In nine of 11 patients who had previous myocardial infarction, abnormal wall motion was present preoperatively. Following surgery, some abnormalities of wall motion persisted in the areas of known infarction, although significant improvement of wall motion occurred in the noninfarcted segments. The ejection fraction was reduced in seven of these 11 patients and improved postoperatively. (0.44 ± 0.05 to 0.59 ± 0.05). The end-systolic volume decreased from 57 ± 5 to 41 ± 6 ml/m2, and the end-diastolic volume was unchanged (106 ± 5 to 108 ml/m2). Left ventricular end-diastolic pressure fell from a mean value of 17 ± 3 to a mean value of 10 ± 2 mmHg following successful surgery. These findings are consistent with improved pump function and were associated with improvement in indices of contractile state. The observations indicate that significant improvement in ventricular wall motion and pump function occurs in patients with obstructive coronary disease following successful aortocoronary artery bypass surgery even in the presence of old myocardial infarction. Since the patients of the present study all had normal initial end-diastolic volumes, however, similar beneficial results might not occur in patients with cardiomegaly and more severe heart failure.

Failure of Intracoronary Nitroglycerin to Alleviate Pacing-Induced Angina

Relief of angina by nitroglycerine has been attributed to two possible mechanisms: (1) Increase in myocardial blood supply by direct action of the drug on the coronary arteries. (2) Reduction in myocardial oxygen demand by action of the drug on the systemic circulation. Sublingual application of nitroglycerin in previous studies did not allow the ruling out of the operation of either or both mechanisms. This study was, therefore, designed in such a way that the effect of the direct action of nitroglycerin on the coronary bed on angina could be studied in the absence of changes in the systemic circulation. In 25 patients undergoing cardiac catheterization and coronary arteriography as possible candidates for revascularization surgery, nitroglycerin, 0.075 mg in 1 ml of 5% dextrose, was injected into the left coronary artery through the angiographic catheter during angina pectoris induced by pacing. Coronary sinus blood flow by the continuous thermodilution method, femoral artery blood pressure, and lead V5 were recorded continuously. In 20 patients the procedure was repeated with injection into the right coronary artery. In none of the 25 patients did the intracoronary injection of nitroglycerin alleviate the angina during the 1-min observation period, whether injected into the obstructed artery or into the artery supplying collaterals to the obstructed artery. The intracoronary injection was ineffective despite a significant increase in coronary sinus blood flow in 14, lasting 26 sec on the average. This suggests that the increase in blood flow did not occur in the ischemic areas where it was needed, but in other areas where the arterioles were not maximally dilated by ischemia. This explanation is further supported by the fact that in five patients with very severe restriction of the left coronary artery system the coronary sinus blood flow failed to increase in response to intracoronary nitroglycerin during angina, but increased significantly in response to nitroglycerin after discontinuation of pacing and disappearance of angina. In six patients, 0.2 mg nitroglycerin injected intravenously 1 min following the intracoronary injection relieved the angina unaffected by the preceding intracoronary injection. The relief was associated with a fall in arterial blood pressure and coronary sinus blood flow. The study indicates that the direct action of nitroglycerin on the coronary bed plays little, if any, role in the antianginal effect of the drug, which appears to be due entirely to the action of the drug on the systemic circulation.

Effects of Isometric Exercise on Cardiac Performance The Grip Test

Twenty-two patients with heart disease performed a standard isometric exercise, sustained handgrip, during the course of diagnostic cardiac catheterization. During handgrip an increase in mean arterial pressure (average 87 to 104 mm Hg) was noted in all patients. Coronary sinus blood flow and myocardial O2 consumption increased (average 45%) in all patients so monitored. Systemic vascular resistance increased in 19 patients, in contrast to the response reported in normal volunteers. The relation between left ventricular stroke-work index and LVEDP (left ventricular function curve) during the control state and during the fourth minute of sustained handgrip provided a simple estimate of left ventricular reserve and correlated well with the New York Heart Association functional classification of the patient studied. Patients with good reserve had a rise in stroke-work with little or no change in LVEDP. Patients with poor reserve had a fall in stroke-work together with a substantial rise in LVEDP. It is concluded that the stress imposed by sustained handgrip provides a simple test for the evaluation of left ventricular reserve.

The effect of intracoronary injection of contrast medium upon coronary blood flow.

The changes in coronary blood flow in response to intracoronary injection of 3 ml of 76% Renografin were studied in 47 patients using the thermodilution technique for continuous measurement of coronary sinus blood flow. Within seconds after left coronary injection, an increase in coronary sinus flow began which peaked at an average of 53% above control in 5-10 seconds. There was a corresponding decrease in coronary resistance. Flow returned to control level in almost all patients within one minute of injection. Twenty-four of 35 patients had no change in coronary sinus flow in response to right coronary injection. This can be explained by the fact that most of the venous flow from the right coronary artery returns in such a way that it cannot be measured by the coronary sinus catheter. Of the eleven patients who did show an increase, seven had angiographically documented right to left collaterals, suggesting that the increase in flow was the result of vasodilatation of the left coronary bed by contrast arriving via the right to left collaterals. The percent changes in flow and resistance in response to left coronary injection were isgnificantly greater in the 13 normals than in the 34 with obstructive disease of the left coronary artery (P lessthan 0.01). Flow rose 70 plus or minus 27% (mean plus or minus standard deviation) in the normals versus 46 plus or minus 25% in the patients with coronary artery disease, while resistance fell 44 plus or minus 9% versus 33 plus or minus 11%. The differences, however, were not sufficient for these changes to be of value in the assessment of the degree of impairment of the coronary arterial bed in the individual patient.

Coronary Hemodynamics and Myocardial Oxygen Metabolism during Oxygen Breathing in Patients with and without Coronary Artery Disease

Oxygen in high concentration (arterial pO2 over 400 mm Hg), administered for 7-10 minutes to six subjects with normal coronary arteries and nine subjects with coronary artery disease caused the following significant changes: The heart rate and cardiac index decreased in both groups. The mean arterial pressure increased in the coronary group. The coronary sinus blood flow fell from 158 ± 11 (mean ± SEM) to 131 ± 13 in the noncoronary and from 151 ± 14 to 138 ± 14 ml/min in the coronary group, due to an increase in coronary resistance. The coronary sinus oxygen tension increased from 19 ± 1 to 22 ± 1 in the noncoronary and from 19 ± 1 to 24 ± 1 mm Hg in the coronary group. The coronary arteriovenous oxygen difference decreased from 13.2 ± 0.6 to 12.5 ± 0.6 ml/100 ml in the coronary group. Left ventricular oxygen consumption fell from 21.5 ± 2.1 to 18.2 ± 2.4 in the noncoronary and from 19.9 ± 2.0 to 16.7 ± 1.7 ml/min in the coronary group. Myocardial lactate extraction increased from 40 ± 9 to 60 ± 4 and from 4 ± 6 to 28 ± 3%, respectively. In four patients with severe coronary artery disease, oxygen breathing reverted myocardial lactate production to extraction. It would appear that oxygen breathing might be beneficial in myocardial ischemia by increasing coronary arterial oxygen tension and reducing myocardial oxygen consumption.

Coronary Hemodynamics during Successive Elevation of Heart Rate by Pacing in Subjects with Angina Pectoris

Coronary sinus blood flow was studied by the continuous thermodilution method in 13 subjects with normal coronary arteries and 14 patients with coronary artery disease during progressive elevation of the heart rate by atrial pacing. In 11 patients of the coronary group angina pectoris developed during pacing. In subjects with normal coronary arteries the coronary sinus blood flow rose proportionately (1.71 ± 0.19 ml/beat) and the coronary resistance decreased proportionately (0.06 ± 0.01 [See Equation in PDF File] beats) to the rise in heart rate. Similar changes in coronary sinus blood flow and coronary resistance were found in the pain-free pacing periods in patients with coronary artery disease (1.79 ± 0.21 ml/beat and 0.07 ± 0.01 [see Equation in pdf file]/10 beats, respectively). However, in the periods in which anginal pain was induced the changes in both flow and resistance were significantly lower than in either the noncoronary group or in the pain-free periods in the coronary group (0.66 ± 0.16 ml/beat and 0.00 ± 0.01[See Equation in PDF File]/10 beats, respectively).The study shows that the coronary blood flow in patients with coronary artery disease not only can be normal at rest, but the coronary bed as a whole can respond to increased metabolic demand by normal increases in flow and normal decreases in resistance up to the point at which coronary insufficiency develops.