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Quantitative hemodynamic assessment of coronary stenosis has not been previously reported. Resting coronary blood flow and its regional distribution are insensitive indexes for determining critical stenosis, but flow response to a hyperemic stimulus quantifies restrictions on maximal flow due to coronary arterial lesions. Coronary flow responses to temporary occlusion and to selective main coronary arterial injection of sodium diatrizoate (Hypaque-M 75 percent) were studied in 12 consecutive dogs with a surgically implanted electromagnetic flowmeter and separate micrometer constrictor on the left circumflex coronary artery. Selective Hypaque injection adequate for coronary cineangiography increased coronary flow to four times the resting base-line value, peaking at 6 seconds and lasting 3 minutes, a response equivalent to hyperemia after 10 seconds of circumflex arterial occlusion. With progressive micrometer constriction, resting flow measurements did not decrease until there was 85 percent stenosis. Hyperemia after intracoronary injection of Hypaque decreased when there was 30 to 45 percent stenosis and disappeared when there was 88 to 93 percent stenosis. Myocardial images obtained by gamma camera after left atrial injection of 131 iodine-macroaggregated albumin demonstrated uniform regional distribution of resting flow in spite of severe constriction. However, 6 seconds after selective Hypaque injection, left atrial injection of 99m technetium macroaggregates demonstrated distinct perfusion abnormalities in the region of circumflex stenosis. Thus, flow distribution with a severe lesion was normal at rest but showed marked differences due to restricted circumflex versus normal anterior descending hyperemic response after injection of Hypaque. Flow response and regional distribution during coronary hyperemia caused by Hypaque are quantitative measures for physiologically assessing critical coronary stenosis and flow reserve with potential applicability to patients.

A method based on a modified gamma function is developed to define cardiopulmonary parameters (cardiac output, right heart, pulmonary and left heart blood volumes and mean pulmonary time) from radiocardiograms taken with a single detector. The method is well suited to clinical routine and requires only a desk calculator or a mini-computer.

Average left ventricular flow per unit mass (F/W) has been evaluated at rest in 20 normal individuals and 26 patients with arteriographically proven, advanced coronary artery disease, using inert gas techniques modified to take into account methodological problems presented by heterogeneous perfusion within the ventricle. Preliminary studies in a canine model in which corornary flow could be measured directly before and after coronary occlusion indicated (1) that inert gas techniques utilizing venous sampling are suitable for abnormal situations when appropriately long periods of saturation and desaturation, and careful resolution of prolonged venous-arterial differences, are employed; and (2) that traditional inert gas methods are not adequate when F/W is abnormally heterogeneous. Using helium as a tracer, coronary disease patients showed a systematic reduction, in comparison to normal individuals, in average left ventricular F/W at rest (54 ± 11 vs 70 ± 13 ml/min/100 g, P < 0.01). Simultaneous studies with traditional nitrous oxide and krypton techniques did not show this difference because of the methodological limitations of these techniques in the presence of abnormally heterogeneous F/W. We conclude: (1) that useful, accurate measurements of F/W can be obtained in coronary disease if appropriate methodological precautions are taken; and (2) that appreciable portions of the left ventricle have an abnormally low F/W, even at rest, in patients with advanced coronary disease.

Sixteen patients undergoing aortocoronary bypass surgery were evaluated with rest and exercise potassium-43 ( 43 K) myocardial imaging and contrast angiography an average of 5.5 months postoperatively. The results of 43 K imaging allowed the division of these patients into two groups. Group 1 consisted of patients in whom there was either normalization or significant improvement in postoperative images when compared to abnormal preoperative studies (five patients), or patients in whom preoperative imaging was not accomplished but whose postoperative images both at rest and exercise showed a normal homogenous pattern of 43 K distribution (four patients). All patients in this group had at least one patent bypass graft, and 13 of 16 total grafts were patent. Group 2 consisted of seven patients in whom postoperative rest and exercise 43 K studies were either not significantly different from preoperative evaluation, or had worsened. Of these patients, three experienced intraoperative infarction, two demonstrated significant distal native coronary disease, and one had a single occluded graft. In both groups there was good correlation between the anatomic sites of graft patency or occlusion and the location of either increased perfusion or lack thereof on the 43 K image. Perfusion abnormalities occurring in the presence of occluded grafts, or improvement in perfusion occurring in the presence of patent grafts were best appreciated by comparison of exercise images. Abnormalities occurring in the presence of infarction were detected at rest as well. Thus, in this initial group of patients, 43 K rest and exercise myocardial imaging appeared to offer a sensitive noninvasive means of evaluating the results of aortocoronary bypass surgery.

In closed-chest anaesthetized dogs simultaneous measurements of coronary sinus blood flow (CSBF) by thermodilution and myocardial blood flow with 85Krypton (MBF) were compared. Although reproducibility of the two methods was comparable control CSBFs averaged only 60% of total left ventricular flow (obtained by MBF and post-mortem left ventricular weights). Frequent marked discrepancies between percent changes in the two methods followed various interventions. Differences in results obtained by the two methods could be explained on the basis of the anatomy of the canine cardiac venous system and shifts in thermistor position relative to coronary sinus tributaries and right atrium following interventions and catheter softening.

Isovolumetric relaxation and diastolic stiffness of the left ventricle were studied in seven open-chest dogs following serial ligation of coronary arteries. After experimental infarction, diastolic stiffness increased by 221% (p

Hemodynamic predictors of myocardial oxygen consumption (MVO 2 ) during static and dynamic exercise were examined in ten normal subjects. Studies were done under the following circumstances: 1) during upright bicycle exercise at an average heart rate of 147 beats/min, 2) during static exercise with an isometric load in the left hand equal to 17% of the maximal voluntary contraction (MVC), and 3) during combined dynamic exercise (average heart rate 147 beats/min) and static exercise using 17% MVC of the left hand. Mean myocardial blood flow (MBF) was 181 ml/100 gm LV/min during dynamic exercise, 98 ml/100 gm LV/min during static exercise, and 201 ml/100 gm LV/min during combined static and dynamic exercise. Addition of a static load to the dynamic load resulted in a higher blood pressure (average 12 mm Hg), MVO 2 and MBF than during dynamic exercise alone. MVO 2 correlated best with products of heart rate and blood pressure regardless of whether the blood pressure was obtained by a central aortic catheter ( r = 0.88) or by a blood pressure cuff ( r = 0.85). When the current data were combined with previous data, 82 determinations of MVO 2 and MBF in 29 normal subjects during several levels of upright exercise were available for analysis. Forty-four determinations were done during dynamic upright exercise, 18 during exercise after propranolol, ten during combined static and dynamic work, and ten during static work alone. MVO 2 correlated best with the product of heart rate and blood pressure ( r = 0.86). Heart rate alone correlated better with MVO 2 ( r = 0.82) than did the tension time index ( r = 0.65) or the product of systolic blood pressure, heart rate, and ejection time ( r = 0.68). The readily measured variables of heart rate and of heart rate x blood pressure correlated well with MVO 2 in normal young men during exercise under a wide variety of circumstances.

At cardiac catheterization, the effect of isoproterenol on coronary blood flow was compared in six patients with primary myocardial disease and six patients who appeared to have no cardiac disease. Coronary blood flow was measured by selective coronary artery injection of xenon-133 and external monitoring of disappearance curves with a dual probe, digital scintillation counter. In the presence of similar changes in cardiac output and heart rate-systolic pressure product, changes in coronary blood flow and coronary resistance in response to isoproterenol were significantly less ( P < 0.05) in the subjects with primary myocardial disease than in the normal subjects.

The contribution of retrograde coronary flow to total collateral flow was examined transmurally in anesthetized, open-chest dogs subjected to acute obstruction of the left anterior descending coronary artery. Regional coronary flow in normal and ischemic tissue was reflected by the tissue content of radioisotopes of potassium and rubidium and by radioactive microspheres. To measure total collateral flow, one isotope was administered when the retrograde cannula was clamped. The other isotope was administered when the cannula was opened to divert retrograde coronary flow away from acutely ischemic myocardium. Significant quantities of this isotope reached the ischemic region despite diversion of retrograde flow at an average rate of 3.5 ml/min. These results confirm earlier, but disputed, reports that total coronary collateral flow exceeds retrograde flow and are indicative of collateral pathways associated more closely with the microcirculation than with the larger epicardial arteries. Furthermore, the transmural distribution of myocardial blood flow in the ischemic tissue was altered nonuniformly by diversion of retrograde flow: 42 K or 86 Rb uptake was reduced to 25% of control in subepicardial tissue but only to 70% of control in subendocardial tissue. The transmural distribution of radioactive microspheres was similarly affected by diversion of retrograde flow. The results suggest that collateral pathways differ transmurally and may include significant luminal connections. Retrograde coronary flow is not a sensitive index of collateral flow to acutely ischemic subendocardial tissue.

Regional myocardial blood flow was measured using the inert gas washout technique and the Anger scintillation camera following injection of 133Xe into the coronary artery. By applying compartmental analysis to 30-minute washout curves, three compartments were delineated, representing blood flow to fat (IIIF) and myocardium (IM and IIM). Regional heterogeneity of flow was a highly sensitive index of coronary artery disease. Functional images delineated areas of altered perfusion better than quadrantic flow values. Gamma camera images of initial xenon distribution identified patients with severely altered flow.

THE third endogenous catecholamine, dopamine, has been extensively investigated in recent years. Dopamine, the immediate precursor of norepinephrine, is found in high concentrations in sympathetic ...

Twenty-five patients had myocardial blood flow reserve determinations (percentage increase in myocardial blood flow with stress), treadmill exercise tests and coronary and bypass cineangiography pre- and postaortocoronary bypass surgery. Twenty of the patients had the postoperative studies performed three months after operation, three at two months and two at five and six months, respectively. Eleven of the 25 patients had all significant coronary artery obstructions (75% or greater) bypassed and all grafts were open at the time of restudy. Preoperatively, blood flow reserve had been abnormal in nine and all had positive treadmill tests. Postoperatively, all eleven patients had normal myocardial blood flow response to stress and treadmill tests were negative in ten (one patient was not restudied on the treadmill). In six patients, no patent grafts could be demonstrated. These patients continued to show abnormal blood flow reserve and positive treadmill studies. Eight of the 25 patients had partial revascularization in that some grafts were open, some closed, and some significantly occlusive lesions were not bypassed. Four of these eight patients had normal flow and treadmill studies and the remainder continued to have an abnormal response to one or both of the measurements. The relationship between treadmill exercise response, myocardial blood flow reserve, and graft patency was significant at the 0.005 level for patients with all grafts open or closed. No significant correlation was obtained between any of the measurements in those patients with partial revascularization. The data indicate that successful aortocoronary bypass grafting provides myocardial revascularization as reflected in a return to normal of the myocardial blood flow reserve and response to treadmill stress testing.

133 Xenon and 125 I-iodoantipyrine (IAP) solutions were simultaneously injected into the left coronary artery in four normal patients and four patients with coronary artery obstructions. Recirculation was computed by convolution of the fractional decrease of the curve following inlet injection over a second curve obtained following right atrial injection. Uncorrected xenon and IAP curves were not statistically different in spite of the lower myocardium-blood partition coefficient and the recirculation of xenon. Corrected IAP curves could be followed down to 1.7%, whereas xenon curves could be followed only to 7.5%, indicating significant xenon diffusion holdup in fat. Corrected IAP curves deviated from a monoexponential course below 5% of peak in normal patients and at about 10% in patients with coronary artery obstructions. Stochastic analysis gave flow values 22% lower and 45% higher, respectively, than those computed from monoexponential extrapolation of corrected IAP and uncorrected xenon curves. With the double-injection technique, IAP washout can be calculated down to about 1% of peak, accounting for the distribution of 99% of the flow through the tissue to which the indicator is delivered. Monoexponential analysis of corrected IAP curves overestimates flow, because it cannot fit the initial delay component and the final reduction of slope. Xenon washout does not allow quantification of myocardial flow in man.

With electromagnetic flow transducers and pneumatic cuff occluders on the circumflex branch of the left coronary artery in conscious and in anesthetized dogs, we examined the effects of both a temporary reduction in postocclusion hyperemia and one- and two-cardiac cycle occlusions of the artery on the size and the duration of the hyperemic response. After release of 8-second occlusions, flow was prevented from rising to more than 10-20% above the preocclusion value for the expected duration of the hyperemia. Peripheral coronary arterial pressure measurements established that this maneuver produced a pressure gradient. Temporary restriction of arterial inflow markedly reduced the percent repayment of the flow deficit from 618 ± 34± to 213 ± 17% (mean ± SE) and moderately prolonged the duration of the response from 95 ± 4 seconds to 129 ± 5 seconds ( P < 0.0005 for both). In conscious dogs, the mean percent repayment after a one-cycle (0.7-second) occlusion was 227%. Much larger and longer-lasting responses were obtained with one-cycle (0.4-second) occlusions in anesthetized dogs in which heart rate and blood pressure were considerably higher. Since restricting arterial inflow resulted in a large reduction in reactive hyperemia with only a small increase in its duration, local mechanisms acting in the interstitial space and possibly in the vascular smooth muscle may be relatively more important for the hyperemia that occurs after short occlusions than is the myocardial release of freely diffusible metabolites that are removed by the blood stream. The results with one- and two-cycle occlusions suggest that myogenic responses contribute to the hyperemia, since it is unlikely that such brief occlusions produce myocardial hypoxia under resting conditions.

Cardiopep is an acronym for cardioactive polypeptide. It is a newly isolated fraction of bee venom with an estimated molecular weight of 1940. The cardiovascular effects of cardiopep have been studied in a series of 30 isolated perfused Langendorff heart preparations, and in 12 intact animals. When injected into the coronary circulation of the perfused heart, cardiopep produces a 50 ± 10 per cent increase in rate, a 150 ± 50 per cent increase in force of contraction and no change in coronary vascular resistance. These effects lasted for the duration of the experiment. In those hearts in which intrinsic arrhythmias are present, a dose of 0·2 mg of cardiopep produced an immediate restoration of normal cardiac rhythm in addition to the effects on rate and force. In the intact monkey preparation, this same dose of cardiopep produces an increase in heart rate, aortic blood flow and right ventricular force. There are no significant changes in arterial blood pressure, central venous pressure or cortical activity. In addition cardiopep appears to be relatively nontoxic ( LD 50 = 15 mg/kg ) when compared to whole bee venom ( LD 50 = 3·5 mg/kg ). It would appear from these studies that cardiopep is a potent, nontoxic beta-adrenergic-like stimulant not entirely blocked by propranolol and possessing definite anti-arrhythmic properties.

Experience with 184 patients undergoing internal mammary artery bypass grafting has resulted in a reproducible, simplified, and organized surgical technique. Recatheterization study has been performed in 39 asymptomatic and 3 symptomatic patients at two weeks to one year postoperatively. Two distal stenoses and no closures have been found. The advantages of internal mammary arteries as bypass grafts are that the vessels are comparably sized, there is artery-to-artery anastomosis, only a single distal anastomosis per graft is needed, there is no subintimal hyperplasia, and no leg wound problems occur. Disadvantages are that a more tedious dissection of the relatively more friable internal mammary vessel is necessary, only two grafts are available whereas multiple bypasses are sometimes necessary, and the grafts are limited in length. Complications specific to the procedure are injury to the internal mammary artery during preparation (2 patients) and inadequate graft size (5 patients). Flow rates are adequate to relieve angina. Patients with subclavian bruits or differential blood pressure between the right and left arms are not considered candidates for internal mammary artery bypass grafting. The availability of a special 7-0 Prolene suture on a BV-1 needle and the use of optical magnification are especially important adjuncts to the procedure.

To determine a possibility of success in construction of an akinetic septum as a radical correction for single ventricle, seven normal canine hearts were spatially analyzed to obtain ratios which would enable to reconstruct the heart by awaring only the maximum external circumference of the ventricles (the left and right free walls on cross section). Then, those data obtained were employed to construct single ventricle to analyze the possibility of the septal construction in it in Part 11 of this study. On determining the volumes of the right and left ventricles, which was madantory, in Part 11 of this study, in discussion of cardiac function required in the single ventricle corrected with an akinetic septum, two methods were employed, one, being with planimetry on photographs of the hearts cross-sectioned, the other being with planimetry on drawings that were obtained from equations. The equations employed were based on a postulation that both the ventricles were round on cross-section and that they overlapped partly each other. Thereby, one circle was complete and was assumed the left ventricle. The volumes determined by the equations were very close to the volumes measured on the photographed heart. A long axis employed in the analysis of the normal heart was from the apex to the center of the mitral orifice with a reason that this axis would be more beneficial to a surgeon because of easier accessibility to the atrioventricular groove as a landmark on operation. The cross-section in this study was perpendicular to the long axis.

The ability of five prototypic antihistamines (diphenhydramine, promethazine, cyclizine, chlorpheniramine and tripelennamine) to modify the cardiac actions of histamine was studied in order to determine the reactivity of cardiac histamine receptors. Histamine, as a function of dose, increases the rate, the force of contraction, the coronary flow and the time of atrioventricular conduction of the isolated guinea pig heart. Each of the five prototypic antihistamines failed to inhibit histamine-induced stimulation of cardiac rate and contractility. at the same time these antihistamines did inhibit the negative dromotropic effect of histamine. Chlorpheniramine and diphenhydramine antagonized the coronary dilating effect of histamine. These results suggest that two types of histamine receptors may be present in the guinea pig heart: H1-receptors, at the atrioventricular node and coronary vessels; H2-receptors at the sinoatrial node and on the ventricular fibers. The activity of these prototypic antihistamines is consistent with their action exclusively on H1-receptors.

Regional blood flow, determined as the fractional distribution of 137Cs, was measured at rest and during swimming exercise in control rats raised at sea level and in rats altitude-adapted by exposure to a barometric pressure of 440 mmHg for approximately 6 weeks. During both normoxic and hypoxic (11% O2) resting conditions, the altitude-adapted rats exhibited regional distributions of blood flow that differed significantly from those in the control animals. During normoxic and hypoxic swimming, significant redistributions of blood flow were noted in the control animals compared to the resting conditions. Ventricular, diaphragmatic, and working muscle blood flows were increased at the expense of the renal and splanchnic circulations, with a more marked redistribution during the hypoxic swims. Similar redistributions of blood flow were exhibited by the exercising altitude-adapted rats, except that renal and hepatic perfusion was maintained at a significantly higher level during both the normoxic and hypoxic swims. Blood lactate concentrations in control rats during hypoxic exercise were strikingly increased, suggesting that the lactate metabolizing ability of the liver and kidneys was impaired. In the altitude-adapted rats, however, blood lactate levels after exercise were significantly lower than those observed in the control animals. It is suggested that the degree of polycythemia may have determined the magnitude of the blood flow redistribution and the extent of lactate metabolism impairment.

Hearts from infant rats were grafted to the abdominal cavities of infant or adult hosts by end-to-side anastomosis of the graft's aorta to the host dorsal aorta, and of the donor's pulmonary artery to the inferior vena cava of the host. In such transplants, circulation through the heart bypassed the left atrium and ventricle. Four months after operation, the grafts had grown to normal adult sizes and their right ventricles had hypertrophied commensurate with the left side.

The determination of regional blood flow and cardiac output with radioactively labeled microspheres and a reference arterial sample has been assessed in the rabbit. Paired determinations of cardiac output with the microsphere and indocyanine green dye dilution methods correlated well (F=236; p