Joseph C. Greenfield

Regional Myocardial Blood Flow in Awake Dogs

The objectives of this study were to test the hypothesis in awake dogs that during control conditions endocardial vessels are maximally dilated and to determine whether variables introduced by general anesthesia and thoracotomy modify distribution of myocardial blood flow or impair capacity for augmentation of flow in response to a coronary vasodilator stimulus. Myocardial blood flow was measured in relatively small, 2-3 g, left ventricular epicardial and endocardial samples by using 7-10-mum radioisotope-labeled microspheres during control conditions and during infusion of adenosine in dosages which produced maximum increases in coronary blood flow. Measurements were made initially in awake resting animals and were repeated after pentobarbital anesthesia, thoracotomy, and pericardiotomy. Blood flow (mean+/-SEM) in the epicardium and endocardium, respectively, was 0.75+/-0.06 and 0.83+/-0.06 during control conditions and 4.98+/-0.28 and 4.49+/-0.27 cm(3)/min/g during adenosine. These data demonstrate considerable capacity for vasodilation in both myocardial layers and thus refute the hypothesis that endocardial vessels are maximally dilated during control conditions. During control conditions blood flow within epicardial and endocardial layers was essentially homogeneous around the circumference of the left ventricle. In contrast to previous studies in anesthetized animals, however, transmural gradients were present in most regions, i.e., endocardium: epicardium ratio (endo/epi) 1.06-1.16. During adenosine, circumferential epicardial flows were homogeneous; however, circumferential endocardial flows were inhomogeneous and increased less than epicardial flows, endo/epi 0.81-0.99.Anesthesia, thoracotomy, and pericardiotomy increased epicardial and endocardial flow, mean values 1.08+/-0.10 and 1.11+/-0.08 cm(3)/min/g, respectively. Transmural gradients remained in only papillary muscle regions. Adenosine increased epicardial flow comparably before and after anesthesia. Although adenosine increased endocardial flow three- to fourfold after anesthesia, the increase was considerably less than epicardial flow, i.e., endo/epi 0.63-0.78.

Myocardial Blood Flow Distribution in Concentric Left Ventricular Hypertrophy

Regional myocardial blood flow during both control conditions and ischemia-induced vasodilatation was studied in eight chronically instrumented awake dogs. Seven of these animals had coarctation-banding of the ascending aorta performed at 6 wk of age, and the other dog had congenital subvalvular aortic stenosis. The mean left ventricular weight for the group was 157+/-7.6 g, and the left ventricular body weight ratio was 8.76+/-0.47 g/kg. None of the animals exhibited signs of congestive heart failure. During the control state, the mean left ventricular systolic pressure was 249+/-12 mm Hg and the left ventricular end-diastolic pressure was 11.5+/-0.5 mm Hg. The aortic diastolic pressure was 74+/-6 mm Hg. Mean left circumflex coronary artery blood flow was 71+/-6 cm(3)/min. In the animals with coarctation-banding, 52+/-6% of the flow occurred during systole. In the dog with congenital subvalvular aortic stenosis, 5% of the coronary flow was systolic. Mean transmural blood flow during resting conditions was 0.97+/-0.08 cm(3)/min per g, and the ratio of endocardial to epicardial flow (endo/epi) was 0.88+/-0.07. During reactive hyperemia, the mean transmural blood flow increased to 3.5+/-0.30 cm(3)/min per g; however, the endo/epi decreased to 0.52+/-0.06.THESE STUDIES DOCUMENT A DIFFERENCE IN TRANSMURAL BLOOD FLOW DISTRIBUTION BETWEEN THE NORMAL AND THE HYPERTROPHIED LEFT VENTRICLE: during resting conditions, in the normal ventricle, the highest flow occurs in the endocardial layer, whereas in the hypertrophied ventricle, the highest flow is in the middle layers with the endocardial flow less than the epicardial flow. During ischemia-induced vasodilatation, the abnormal endo/epi becomes accentuated markedly. These data demonstrate that, in situations requiring high flow, the endocardial layer of a heart with marked concentric left ventricular hypertrophy may not be perfused adequately.

Pressure-Flow Studies in Man: Effect of Respiration on Left Ventricular Stroke Volume

The pressure gradient technique was used to evaluate effects of respiration on left ventricular stroke volume in 22 patients: 11 normal patients; eight patients with airway obstruction; and three patients with pericardial tamponade. In normals, stroke volume, systolic pressure, and pulse pressure fell an average of 7, 3 and 11% (P < 0.01), respectively, during inspiration. In patients with airway obstruction, these parameters decreased by 25, 12 and 23% (P < 0.001), respectively. After breath-holding, stroke volume also fell immediately with the onset of inspiration in both groups. These results are consistent with a reduction in left ventricular filling during inspiration as the factor primarily responsible for the fall in stroke volume. In patients with pericardial tamponade, variations in left ventricular stroke volume, systolic pressure and pulse pressure were related to: (1) an immediate fall in stroke volume with the onset of inspiration; and (2) a subsequent increase in stroke volume presumably due to an inspiratory increase in right ventricular stroke volume.

Pressure-flow studies in man: effect of atrial systole on left ventricular function

In order to evaluate the effects of atrial contraction on left ventricular function, the pressure gradient technique was used to measure instantaneous aortic blood flow and pressure in nine patients, six having complete heart block and three having normal sinus rhythm. From these data both left ventricular stroke volume and stroke work were calculated. Ventricular rate was controlled by transvenous right ventricular pacing over a range of 50-158 beats/min. At each heart rate, beats which were not preceded by a P wave served as controls. The other beats were divided into six groups according to the duration of the preceding PR interval. The results indicated that stroke volume and stroke work were always affected similarly. In one patient the presence of a P wave did not alter the subsequent stroke volume significantly. In the other patients, beats preceded by P waves had stroke volumes greater than the controls. In general, there was no difference in stroke volume for beats preceded by a P wave having a PR interval within the range of 0.05-0.20 sec. As the PR interval lengthened beyond 0.20 sec stroke volume tended to decrease, especially at more rapid heart rates. The absolute increase in stroke volume after a beat preceded by a P wave (PR interval 0.05-0.20 sec) was quite variable among the patients. For a given patient the absolute increase in stroke volume was essentially independent of heart rate. The percentage change in stroke volume, however, was always greater as the heart rate increased. These data indicate that in most patients atrial systole is important in augmenting ventricular stroke volume and stroke work especially at high heart rates, but the magnitude of these effects are quite variable among patients.

Myocardial Blood Flow Distribution during Ischemia-Induced Coronary Vasodilation in the Unanesthetized Dog

This study was designed to determine whether coronary vasodilation distal to a flow-limiting coronary artery stenosis could result in redistribution of myocardial blood flow to produce subendocardial underperfusion. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flow-meters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was measured using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. A 5(-s) coronary artery occlusion was followed by reactive hyperemia with excess inflow of arterial blood effecting 375+/-20% repayment of the blood flow debt incurred during occlusion. When, after a 5(-s) occlusion, the occluder was only partially released to hold arterial inflow to the preocclusion level for 20 s before complete release, the delayed reactive hyperemia was augmented (mean blood flow repayment = 610+/-45%, P < 0.01). This augmentation of the reactive hyperemia suggested that ischemia was continuing during the interval of coronary vasodilation when coronary inflow was at the preocclusion level. Measurements of regional myocardial blood flow demonstrated that endocardial flow slightly exceeded epicardial flow during control conditions. When arterial inflow was limited to the preocclusion rate during vasodilation after a 5(-s) total coronary artery occlusion, however, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium. Thus, in the presence of a flow-limiting proximal coronary artery stenosis, ischemia-induced coronary vasodilation resulted in redistribution of myocardial blood flow with production of subendocardial ischemia in the presence of a net volume of arterial inflow which, if properly distributed, would have been adequate to prevent myocardial ischemia.

A new computer program for analysis of scalar electrocardiograms.

Abstract A computer program for interpreting the adult 12-lead electrocardiogram has been evaluated. Four thousand electrocardiograms were used in the design of the program which was based on the diagnostic logic used in clinical electrocardiographic interpretation. An evaluation of the program so designed was conducted on 1435 other records, 1008 of which were abnormal. Ninety-seven percent of all records were correctly classified by the computer as either normal or abnormal. Ninety-four percent of all contour abnormality statements made were correct and only 6% of contour abnormality statements were omitted. Ninety-three percent of the normal electrocardiograms were correctly analyzed with most errors consisting of minor ST- and T-wave changes. Of the abnormal tracings, 1.2% were called normal. Eighty-two percent of all 1435 records had a completely acceptable computer interpretation.

Pressure-flow studies in man. An evaluation of the duration of the phases of systole

This study was designed to assess the independent effects of stroke volume and heart rate on the phases of systole and other selected hemodynamic parameters. By means of the pressure gradient technique instantaneous blood pressure and flow were recorded in the ascending aorta at fixed ventricular rates in five patients with complete heart block and in four patients with atrio-ventricular dissociation induced by ventricular pacing. Because of the variable contribution of atrial systole to ventricular filling, a wide range of stroke volumes were observed at each heart rate. The results indicate that the duration of ejection bears a close direct linear relationship to stroke volume while heart rate has only a weak but independent relation. On the other hand, the duration of total systole is related chiefly to the heart rate but stroke volume exerts an important independent effect. In a given patient, both duration of ejection and pulse pressure reflect changes of stroke volume and the product of the duration of ejection and the pulse pressure shows a good correlation with the stroke volume.

Effect of norepinephrine, epinephrine, and angiotensin on blood flow in the internal carotid artery of man

Internal carotid artery blood flow and arterial pressure were measured with a sine-wave electromagnetic flowmeter and a pressure transducer in 22 patients during control period and after the intravenous and intracarotid administration of norepinephrine, epinephrine, and angiotensin. Intravenous infusion of both norepinephrine and angiotensin was accompanied by an increase in cerebral vascular resistance. Administration of norepinephrine, epinephrine, and angiotensin into the internal carotid artery failed to alter blood flow immediately. However, when the systemic blood pressure increased, a concomitant passive rise in blood flow did not occur. Thus, at this time cerebral vascular resistance was significantly increased. It is concluded that these drugs do not have a direct action on the cerebral vessels, but that the increased cerebral vascular resistance after their administration is due to autoregulation or to a combination of autoregulation and reduced arterial carbon dioxide pressure (P(CO2)) secondary to hyperventilation. Similar studies were carried out in the external carotid artery of six patients. Within 10 sec after injection blood flow was markedly reduced, indicating a direct vasoconstricting action on this vascular bed.

Pressure-flow studies in man during atrial fibrillation

In 13 patients who had atrial fibrillation the ascending aortic pressure-flow relationships were measured by the pressure gradient technique. Both the pressure and flow curves were similar in contour to ones previously obtained by this method. From these recordings, relationships between the phases of systole, the ventricular filling time, and various derived parameters of pressure and flow such as the pulse pressure, stroke volume, peak flow, stroke work, and peak power were evaluated. For stroke volumes greater than 15 cm(3) there was little change in the duration of systole in an individual patient. In each patient both the preejection period and the duration of ejection showed a good correlation with stroke volume, peak flow, stroke work, and peak power. When data from all patients were examined, the relationship between stroke volume and duration of ejection was found to be curvilinear and had an overall correlation of r=0.91. There was marked variation from patient to patient in duration of both the preejection period and systole. Similar correlations between the phases of systole were noted with peak flow, peak power, and stroke work. A positive but mediocre correlation was found between the previous RR interval (an index of ventricular filling time) and the subsequent stroke volume. The correlation, in six patients, between two previous RR intervals and stroke volume was considerably better. The relationship between the pulse pressure and stroke volume was reasonably close except in one patient; however, the group correlation was poor due to differences between individuals.

Studies of Blood Flow in Aorta-to-Coronary Venous Bypass Grafts in Man

Pressure-flow measurements were obtained from the vein graft of 57 patients undergoing a single aorta-to-coronary bypass procedure. The flow contour was similar to phasic left coronary artery flow in dogs except for a transient increase during systole possibly related to elongation of the graft. Flow was highest during bypass and decreased to a stable value 30 min after bypass. In 42 patients, flow at this time was 35+/-2 cm(3)/min (mean+/-sem).NO CORRELATIONS WERE DEMONSTRATED BETWEEN FLOW AND THE FOLLOWING: left vs. right grafts, presence or absence of collaterals, total vs. partial block, or the presence or absence of ventricular dyskinesis. In 32 patients, no correlation between these anatomic findings and the presence of reactive hyperemia was demonstrated. In 17 patients, occlusion of the graft for 10 sec resulted in a mean 51.5% flow debt repayment. In nine patients, injection of 0.3 mug of isoproterenol into the graft increased flow from 45+/-6 to 69+/-9 cm(3)/min within 4-7 sec without changes in rate, pressure, time derivative of left ventricular pressure (LV dp/dt), or left ventricular end diastolic pressure (LVEDP). Maximum increases to 87+/-10 cm(3)/min occurred 12-20 sec after injection with concomitant changes in these parameters. Intravenous infusion of norepinephrine did not change vascular resistance, whereas phenylephrine did. In six patients, injection of 0.2 mug of norepinephrine into the graft decreased flow from 49+/-6 to 25+/-5 cm(3)/min within 5-8 sec. Intravenous infusion of 0.15 mg of nitroglycerin decreased coronary vascular resistance from 2.7+/-0.4 to 2.3+/-0.3 mm Hg/cm(3) per min. In five patients, 0.12 mg of nitroglycerin injected into the graft increased flow from 46+/-7 to 71+/-13 cm(3)/min and lasted 20-40 sec.