Large Resistance Vessels Research Articles

Segmental vascular responses to acute hypertension in cerebrum and brain stem.

The goal of this study was to examine hemodynamic mechanisms that contribute to regional differences in autoregulation during acute hypertension. We measured blood flow (microspheres) and pressure in pial arteries (approximately 160 microns) of anesthetized cats and calculated resistance of large and small vessels in cerebrum and brain stem. Moderate elevation of aortic pressure increased resistance of both large and small vessels in cerebrum but only small vessels in brain stem. During severe hypertension, resistance of both large and small vessels in cerebrum decreased and blood flow increased markedly. In contrast, in the brain stem large artery resistance did not change, small vessel resistance increased, and blood flow increased only modestly during severe hypertension. Pial artery pressure was 20 mmHg higher in brain stem than cerebrum during control conditions and 30-50 mmHg higher during moderate and severe hypertension. We conclude that resistance of large arteries is less and thus pial artery pressure is higher in brain stem than cerebrum under control conditions. More effective autoregulation in the brain stem than cerebrum during severe hypertension is due to greater resistance of small, not large, cerebral vessels.

Effects of vasodilator stimuli on resistance of large and small cerebral vessels.

We have examined effects of vasodilator stimuli on segmental resistance in the cerebral circulation. Our hypothesis was that resistance of large arteries, as well as small vessels, contributes to cerebral vascular responses to vasodilator stimuli. We measured cerebral blood flow with microspheres in anesthetized rabbits and measured pressure in pial arteries approximately 100 microns diameter using a servo-null method. These values were used to calculate resistance of large arteries (greater than 100 microns diameter) and small vessels (less than 100 microns diameter). Under control conditions, resistance of large arteries accounted for one-third to one-half of total cerebral vascular resistance. Intracarotid infusion of acetylcholine (1 microgram/min) reduced large arterial resistance by 69% and small vessel resistance by 58%. Adenosine also produced marked reductions in resistance of both large and small cerebral vessels. In contrast, seizures reduced large arterial resistance by 50% and small vessel resistance by 85%. Pial arterial pressure, which depends on the ratio of large and small vessel resistance, increased during infusion of acetylcholine and adenosine, but decreased during seizures. We conclude that both large and small cerebral vessels are responsive to acetylcholine and adenosine, and seizures produce preferential reduction in resistance of small vessels.

Response of cerebral arteries to sympathetic stimulation during acute hypertension.

Our goal was to determine whether sympathetic stimulation during acute hypertension constricts large cerebral arteries and attenuates increases in cerebral microvascular pressure. We measured cerebral blood flow with microspheres and pressure in small pial arteries with a servonull device in anesthetized cats. During moderate hypertension, sympathetic stimulation had little effect on resistance of large or small cerebral vessels. During severe hypertension, sympathetic stimulation prevented passive decreases in resistance of large cerebral arteries and allowed pronounced constriction of small vessels. During hypertension, there was a large increase in pressure in small pial arteries. Although sympathetic stimulation prevented decreases in resistance of large arteries during severe hypertension, it did not attenuate increases in pressure in pial arteries approximately 200 micron in diameter and only modestly attenuated increases in pressure in pial arteries approximately 100 micron in diameter. These findings indicate that sympathetic stimulation has important effects on resistance of both large and small cerebral vessels during severe hypertension. Thus, although stimulation produces dilation of small cerebral vessels during normotension, sympathetic stimulation allowed constriction of small vessels during severe hypertension. These results also indicate that sympathetic stimulation does not prevent increases in pressure in small pial arteries. Thus, protection of the blood-brain barrier by stimulation of sympathetic nerves during hypertension is not the result of attenuation of increases in pial artery pressure.

Functional consequences and intracoronary localization of alpha-adrenergic stimulation of the canine coronary circulation

Although alpha-adrenergic stimulation can increase coronary vascular resistance, it remains unknown whether the vasoconstriction can override intrinsic coronary regulatory influences to produce ischemia. Methoxamine, 2 to 4 mg, was infused into the circumflex coronary artery of 23 chloralose-anesthetized open chest dogs, and resulted in a 68% increase in coronary vascular resistance. The functional consequence of this increased coronary vascular resistance was assessed by gated radionuclide ventriculography and ST-T wave changes on the electrocardiogram. In six dogs (Group I), aortic pressure changed trivially (less than 5 mm Hg) to allow distinction between direct effects of the flow reduction and indirect effects of increased aortic pressure. In this group, coronary blood flow decreased 33% from a control value of 44 +/- 10 ml/min (p less than 0.001) and left ventricular ejection fraction decreased from 0.54 +/- 0.12 to 0.46 +/- 0.10 (p less than 0.025). In eight dogs (Group II) in which aortic pressure increased by more than 5 mm Hg, left ventricular ejection fraction decreased from 0.46 +/- 0.07 to 0.39 +/- 0.09 (p less than 0.002). Pressure gradients were measured between the aorta and a distal coronary artery branch to calculate small and large vessel resistances separately in four other dogs (Group III). The resistance of small coronary arteries accounted for 92% of the total increase in coronary vascular resistance produced by methoxamine. In five other dogs (Group IV), intracoronary methoxamine, 2 mg, produced ST-T wave changes suggestive of ischemia as it increased coronary vascular resistance by 33%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 8-bromo-cyclic guanosine monophosphate (cGMP) on coronary artery constriction in isolated rabbit hearts

The vasodilator 8-bromo-guanosine 3':5'-monophosphate (8-bromo-cGMP) effectively counteracts vasopressin-induced coronary artery constriction in a supported perfused working rabbit heart. In this preparation, the coronary arteries remain in contact with the beating heart. The obtuse marginal artery and portions of the left anterior descending coronary artery were deprived of endothelium. Perfusion was carried out with Krebs-Henseleit solution, oxygenated with a disposable infant oxygenator. The internal diameter of large coronary arteries was determined by color arteriography (injection of patent blue dye and gated photography). The effect of vasopressin with and without the addition of 8-bromo-cGMP on cardiac performance (cardiac output, left ventricular systolic pressure, left ventricular end-diastolic pressure, maximal rate of rise in left ventricular pressure [dP/dtmax], mean aortic pressure) and large coronary vessel and total coronary vascular resistance was determined in nine experiments. In addition, changes in coronary sinus partial pressure of carbon dioxide (PCO2) and pH were observed. Vasopressin alone caused a significant decline in coronary flow, myocardial oxygen consumption and coronary sinus pH. Cardiac performance declined, probably because of myocardial ischemia. Large coronary vessel and total coronary vascular resistance rose. The vasodilator 8-bromo-cGMP strongly inhibited the vasoconstrictor action of vasopressin, counteracted the increase in large and total coronary vascular resistance, prevented the fall in myocardial oxygen consumption and eliminated changes in pH or PCO2 of coronary sinus effluent. Because of the elimination of myocardial ischemia by 8-bromo-cGMP, cardiac performance was normalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of nipradilol, a beta-adrenoceptor blocker with vasodilating properties.

In anesthetized dogs, an intravenous injection of nipradilol produced a long lasting fall in mean arterial blood pressure which was accompanied by transient decreases in peripheral vascular resistance and sustained decreases in heart rate, cardiac output and left ventricular (LV) dP/dt. LV end-diastolic pressure (LVEDP) was not changed while LV diameters and central venous pressure were slightly increased. Under propranolol pretreatment conditions, nipradilol no longer affected the heart rate, but the drug still induced a transient reduction in peripheral vascular resistance, and sustained decreases in arterial blood pressure and cardiac output. Furthermore, indicators of LV preload (LVEDP, LV end-diastolic diameter and central venous pressure) were significantly reduced, suggesting a direct dilating action of nipradilol on capacitance vessels. In intact conscious dogs, nipradilol caused a sustained reduction in LVEDP, while propranolol increased LVEDP. After administration of nipradilol, coronary blood flow in anesthetized dogs decreased in association with diminished myocardial oxygen consumption, and large coronary vessel resistance also decreased. Nipradilol competitively antagonized the isoproterenol-induced positive chronotropic response (DR10: 0.04 mg/Kg, i.v.) and the phenylephrine-induced vasopressor response (DR10: 3.95 mg/Kg, i.v.). In conclusion, nipradilol, in contrast to propranolol, possesses the properties to decrease arterial blood pressure, LV preload and large coronary vessel resistance through its dilating action on arterial and venous vessels. It is proposed that nipradilol may be beneficial for the treatment of hypertension and coronary heart disease.

A model for the study of coronary spasm induced changes in cardiac metabolism

A model is described which permits the study of localized and generalized arterial spasm in the intact working perfused rabbit heart with a perfluorochemical (FC-43) as perfusate. Coronary arteries were visualized by intraatrial injection of Patent Blue Dye with gated photography. Localized spasm resulted from topical spray of histamine (40 mumols) on the epicardial surface overlying an obtuse marginal artery. Before and following topical administration of histamine, regional coronary flow was determined using radioisotope-labeled microspheres. Generalized arterial spasm was initiated by intraatrial injection of histamine (10 mumols). After topical administration, abtuse marginal artery diameter decreased by 57%; large vessel resistance rose 32 fold; 20% rise of total coronary resistance resulted in a slight reduction of total coronary flow (16%). Heart rate, cardiac output, dP/dtmax and myocardial oxygen consumption did not change. However, regional coronary flow in the myocardium supplied by the affected artery diminished 21% resulting in ischemic changes in redox pairs. After intraatrial injection of histamine, changes were more pronounced. Obtuse marginal artery diameter declined by 88% resulting in 3300-fold rise of large vessel resistance. Total coronary resistance increased 150%, coronary flow and cardiac output diminished (56% and 24%). Both heart rate and dP/dtmax increased (16% and 17%). Generalized coronary spasm after intraatrial histamine injection resulted in severe metabolic effects: Myocardial oxygen consumption (-48%); ATP (-29%); creatine phosphate (-34%); redox ratios, alpha-glycerophosphate/dihydroxyacetone phosphate and lactate/pyruvate, increased by 449% and 114%, respectively. The findings illustrate that localized and generalized coronary spasm can be produced and quantitated in a working heart model.

A new method for the visualization of subepicardial coronary arteries in small isolated mammalian hearts.

A model is described which permits direct visualization of large coronary arteries in a supported modified perfused heart preparation, using a perfluorochemical (FC-43) as perfusate. Filling of a large coronary artery with Patent Blue Dye is recorded by gated photography (color arteriography). The technique is applicable to the study of reactivity (spasm) of coronary arteries in hearts of small and large animals (rats, rabbits, dogs). The technique has the following advantages: preservation of vascular endothelium, adequate oxygenation, avoidance of major surgical intervention to implant sensors for the detection of changes in coronary diameter, quantitative evaluation of time dependent changes in geometry of large coronary arteries and simultaneous measurement of large coronary vessel and total coronary vascular resistance.

Cerebrovascular aspects of converting-enzyme inhibition I: Effects of intravenous captopril in spontaneously hypertensive and normotensive rats.

The cerebrovascular effects of converting enzyme inhibition were examined in normotensive and hypertensive rats. Cerebral blood flow was measured using the intracarotid 133xenon injection method in halothane/nitrous oxide anaesthetized animals. The main finding was that following intravenous administration of captopril (10 mg/kg), cerebral blood flow autoregulation was markedly altered. Although cerebral blood flow was unchanged from baseline levels, both the lower and upper limits of autoregulation were reset to lower mean arterial pressure and the autoregulatory plateau shortened. The lower limit was shifted 20-30 mmHg, the upper limit 50-60 mmHg, and the plateau shortened by 20-40 mmHg. The effect was interpreted as being a consequence of compensatory autoregulatory constriction of small resistance vessels in the brain following captopril-induced dilatation of large resistance vessels. It was inferred that locally produced angiotensin II might play a role in the resistance of large cerebral arteries.

Alpha 1- and alpha 2-adrenoceptor-mediated vasoconstriction of large and small canine coronary arteries in vivo.

The role of alpha-adrenoceptor subtypes mediating vasoconstriction of large epicardial and small resistive coronary arteries was investigated in 26 open-chest dogs. The left circumflex coronary artery was perfused at a constant pressure. Large vessel vasomotion was determined by measurement of circumflex coronary arterial diameter (ultrasonic transit-time technique); the vasomotion of the small resistive coronary arteries was determined from calculated end-diastolic circumflex artery resistance. beta-Receptors were blocked by propranolol (2 mg/kg i.v.) and both vagal nerves were cut. In eight dogs, the intracoronary administration of the alpha 1-adrenoceptor agonist methoxamine (500 micrograms) increased calculated large vessel resistance by 18.8 +/- 5.7% and end-diastolic resistance by 9.5 +/- 0.3%. Intracoronary administration of the alpha 2-adrenoceptor agonist BHT 920 (500 micrograms) did not affect large vessel resistance, but increased end-diastolic resistance by 37.5 +/- 5.6%. In an additional 18 dogs, left cardiac sympathetic nerve stimulation induced an increase in large vessel resistance by 11.1 +/- 0.9% and in end-diastolic resistance by 31.8 +/- 3.0%. The increase in large vessel resistance was prevented by the alpha 1-adrenoceptor antagonist prazosin (1.2 mg/kg i.v.), which still permitted an increase in end-diastolic resistance by 23.0 +/- 3.2%. The increase in end-diastolic resistance was prevented by the alpha 2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.), which still permitted an increase in large vessel resistance by 11.9 +/- 2.4%. The calcium antagonist nifedipine (20 micrograms/kg i.v.) prevented both the increase in large vessel resistance and end-diastolic resistance during sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of vanadate in the dog

We have investigated the cardiovascular actions of vanadate, a naturally occurring Na+-K+-ATPase inhibitor, in six series of pentobarbitalized dogs. In three of the series, isomotic sodium vanadate was infused intravenously at progressively faster rates while arterial pressure and other parameters were measured. In two other series, the solution was infused directly into the coronary artery with coronary flow held constant during measurement of perfusion pressure, left ventricular contractile force (LVCF), and dP/dt. In one series, the agent was infused into the brachial artery with brachial artery flow held constant, and small and large vessel resistances in skin and muscle were calculated. Intravenous infusion increased arterial pressure and reduced cardiac output, the latter resulting from both decreased heart rate and stroke volume. LVCF fell. Total peripheral, pulmonary, coronary, and renal resistances rose. Coronary and renal flows fell, and the latter was associated with reduced urine flow. Intracoronary infusion raised coronary resistance, but had little effect on heart rate, LVCF, and dP/dt. Intrabrachial infusion raisedthe resistance to flow through all components of the forelimb vascular bed. Thus, in the dog, vanadate activates vascular smooth muscle, but has little effect on cardiac muscle. In the latter respect, its action differs from that of ouabain.

Femoral artery input impedance and circulatory reserve in experimental stenosis

Graded degrees of experimental stenosis were studied in the femoral arteries of anesthetized mongrel dogs in terms of resistance and impedance to blood flow and diminished circulatory reserve. Progressive increases in the level of stenosis resulted in progressive increases in (a) the large vessel resistance ( R L), computed from mean blood pressure drop across and mean blood flow through the stenosis, and in (b) the large vessel impedance ( Z L), computed as the average input impedance modulus in the frequency range of 3 to 19 Hz, determined from pulsatile pressure and flow measured simultaneously 2 cm proximal to the stenosis. Linear relationships between Z L and R L were found over all levels of stenosis with nearly identical slopes and intercepts under both resting ( r = 0.92) and vasodilated ( r = 0.85) conditions. Thus Z L, determined from measurements at the input of a stenotic vascular bed, provides an index of the resistance to flow of the large vessel over wide ranges of stenosis severity and distal peripheral resistance. Flow reserve (the arithmetic difference between maximum mean flow and steady-state mean flow at any given level of stenosis) decreased significantly with a stepwise increase in either R L or Z L, compared to a slight concomitant change in steady-state flow. Arterial input impedance therefore has been found to be useful in providing physiological information about the resistance to blood flow of a distal stenosis and about the resulting impairment of circulatory function.

Alpha adrenergic vasoconstriction and nitroglycerin vasodilation of large coronary arteries in the conscious dog.

The effects of methoxamine and nitroglycerin on measurements of large vessel (left circumflex) coronary dimensions were examined in eight conscious dogs using an ultrasonic dimension gauge, and total coronary resistance was calculated from measurements of arterial pressure and coronary blood flow. Methoxamine (50 mug/kg per min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex diameter (9+/-2%) and external (18+/-4%) and internal (27+/-5%) cross-sectional areas, at a time when mean arterial pressure rose by 65+/-5%, left ventricular dP/dt had decreased only slightly, and heart rate and mean coronary blood flow remained at control levels. Calculated large vessel and total coronary resistances rose similarly, i.e., by 108+/-29 and 92+/-14%, respectively. Methoxamine reduced coronary arterial wall stiffness from control at comparable stress levels, although at any common radius, wall stiffness was augmented substantially. Nitroglycerin (25 mug/kg) induced an initial decrease in coronary dimensions along with the fall in arterial pressure. However, left circumflex coronary dimensions then rose, reaching a maximum 5 min later at a time when left circumflex coronary blood flow was reduced and heart rate and left ventricular dP/dt were at control levels. At this time, significantly different effects were observed on large vessel coronary resistance, which fell by 18+/-2%, and on total coronary resistance, which rose by 11+/-4%. Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce cross-sectional area, despite the opposing elevation of distending pressure.

Effect of dilation of the distal coronary bed on flow and resistance in severely stenotic coronary arteries in the dog

Studies were performed to evaluate the hemodynamic response of severely stenotic coronary arteries to dilation of the distal coronary bed. A critical stenosis was produced with an adjustable wire snare on the left anterior descending or circumflex arteries of open chest dogs. Coronary flow, distal coronary pressure and aortic pressure were measured. In one group of experiments, coronary arteriolar dilatation was induced by transient occlusion of the artery distal to the stenosis. After the release of a transient occlusion in vessels without a critical stenosis, flow increased (from 33 +/- 4 to 85 +/- 8 ml/min, P less than 0.01), distal pressure decreased slightly (from 86 +/- 4 to 80 +/- 4 mm Hg, P less than 0.01), and large vessel resistance did not change significantly (from 0.06 +/- 0.02 to 0.08 +/- 0.03 units). After the release of a transient occlusion in vessels with a critical stenosis, flow decreased (from 23 +/- 3 to 12 +/- 2 ml/min, P less than 0.01), distal pressure decreased to persistently low levels (from 63 +/- 2 to 29 +/- 2 mm Hg, P less than 0.01), and large vessel resistance increased (from 1.4 +/- 0.3 to 6.7 +/- 1.8 units, P less than 0.01). In a separate group of experiments, radio-opaque contrast medium was used to dilate the distal coronary bed. In these studies dilation of the distal coronary of arteries with a critical stenosis again resulted in a decrease in coronary blood flow (from 35 +/- 4 to 19 +/- 3 ml/min, P less than 0.01), a decrease in distal coronary pressure (from 84 +/- 6 to 35 +/- 6 mm Hg, P less than 0.01) and an increase in large arterial resistance (from 1.0 +/- 0.2 to 5.5 +/- 1.2 units, P less than 0.02). Therefore, in coronary vessels with severe stenosis, dilation of the distal coronary bed may result in a paradoxical decrease in coronary blood flow.

Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.

Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.

The pressure-resistance relationships of regional resistances within the coronary circulation and the steal phenomenon

On narcotized dogs the descending branch of the left coronary artery was ligated and the peripheral vascular bed embolized with microspheres. A maximal pharmacological dilatation was induced with carbochromen and dipyridamol and the pressure flow relation of the regional resistances within the coronary circulation investigated. An increase in the aortic pressure from 100 to 120 mm Hg decreased the total resistance of the circumflex branch by 6%. The precollateral resistance, however, which represents chiefly the resistance of large coronary vessels, at the same time increased by 8%.

Differential response of large and small coronary arteries to nitroglycerin and angiotensin. Autoregulation and tachyphylaxis.

Large proximal and smaller distal coronary arteries respond differently to pharmacologic agents, but the role of autoregulation is not known. We examined this role in dogs by cannulating the main left coronary artery and a distal left anterior descending artery branch. With coronary flow held constant, the distal coronary artery pressure and the gradient from proximal to distal artery were proportional to the small and the large vessel resistance, respectively. At normal perfusion pressure, nitroglycerin injected directly into the coronary artery caused a transient fall in small vessel resistance and a prolonged decrease in large vessel resistance. During ischemia, when small vessels autoregulated and small vessel resistance was minimal, nitroglycerin lowered only large vessel resistance. Angiotensin injected directly into the coronary artery increased small and large vessel resistance; the slower response of large vessel resistance followed a passive dilation caused by increased perfusion pressure. Continuous infusions of nitroglycerin and angiotensin maintained dilation and constriction of large vessels, respectively, but small vessels demonstrated tachyphylaxis. Only adenosine infusion maintained dilation in both large and small vessels. In response to varying perfusion, small vessels autoregulated and large vessels responded passively to changes in perfusion pressure. We concluded that small coronary arteries respond to cardiac metabolism and demonstrate escape from prolonged dilation and constriction. Conversely, large vessels respond continuously to sustained mechanical and pharmacologic stimuli independently of the nutritional state of the myocardium.

A comparison of the pharmacology of the isolated rabbit ear and its central artery.

SummaryThe vascoconstrictor potency of angiotensin on the rabbit ear was greatly reduced by sectioning the ear so that only the proximal portion remained, or by removal of the entire vasculature other than a small segment of the central artery immediately distal to the site of cannulation.The above procedure had much less effect on the vasoconstrictor potencies of noradrenaline and histamine.The findings indicate that angiotensin's action on the ear vessels is mediated largely beyond the larger resistance vessels such as the central artery, whereas noradrenaline and histamine constrict both large and small resistance vessels.It is concluded that comparison of drug effects on the whole ear and on the central artery alone provides a useful guide to their sites of action on the ear vasculature.

Effect of nitroglycerin and dipyridamole on regional coronary resistance.

We studied the changes caused by intravenous injection of nitroglycerin (0.3 to 0.6 mg) and dipyridamole (5 to 10 mg) on the resistance of large and small coronary arteries of dogs. The direction of change in resistance of large conductive vessels (R c ) was estimated by dividing the pressure drop from aorta to a superficial branch by the flow in that vessel. The total resistance (R t ) in the same vessel was estimated by relating aortic pressure to the same flow. The effects of both drugs on aortic pressure were comparable 3 to 7 minutes after injection. Nitroglycerin during this period caused a reduction in R c , whereas dipyridamole caused a significant reduction in R t for 12 minutes but no consistent changes in R c . In the same preparation, small intracoronary doses of the drugs, which hardly affected the aortic pressure, caused comparable changes in resistance. This was also evident in a preparation in which the flow in the coronary vessel was held constant. These two drugs therefore differ in their site of action on the coronary vascular bed, a difference which may explain their contrasting therapeutic effects in chronic coronary disease in man.

Physiologic Evaluation of Angina Pectoris

Electrocardiographic and ballistocardiographic observations have been the only objective methods easily available for assessment of the state of the coronary circulation. As has been pointed out, however, these methods give only indirect information concerning the hemodynamic status and functional adequacy of the coronary circulation. The extensive pathologic studies of the coronary arteries in angina pectoris”2 have demonstrated that these vessels seldom show a single vascular disturbance, but more often, demonstrate diffuse involvement of the entire coronary vascular tree leading to increased large vessel resistance to blood flow. Physiological principles have been applied to the understanding of other cardiac problems, particularly valvular, congenital and constrictive heart disease and congestive heart failure. They have led to the development of objective hemodynamic methods of evaluation which would appear to be of value for the coronary circulation as well. We have attempted such an approach. Our findings are based on a correlative clinical, electrocardiographic and cardiac catheterization study of 43 patients. Coronary sinus catheterization was performed and coronary blood flow measured by the nitrous oxide technique’ as modified by Goodale and Hackel.4 Diastolic coronary vascular resistance was calculated.5 The group of 43 patients was subdivided as follows: Group 1 was the normal group, composed of 10 patients with negative histories, physical examinations and resting and post-exercise electrocardiograms. Group 2 was the abnormal group, composed of 23 patIents with typical angina pectoris and positive electrocardiographic examinations. Group 3 was designated the unknown group, composed of 10 patients, all of whom complained of atypical chest pain, and In whom the resting and exercise electrocardiograms were negative or equivocal. Three of these patients had left ventricular hypertrophy secondary to aortlc valve disease. The open columns in Figure 1 summarize the results of resting studies performed in normals, in patients with coronary artery disease and in those with increased left ventricular work. Coronary flow was essentially the same in all three groups; in the coronary group it was actually 19 per cent above normal. Diastolic coronary vascular resistance, which encompasses coronary inflow time as well as perfusion pressure, is perhaps the most useful index of the cross-sectional area of the coronary vascular bed. Again, no difference was found among these groups. In a recent report evaluating internal mammary ligation for angina pectoris, nitrous oxide flows were performed at rest. The authors found no difference in values before and after ligation, and therefore, concluded