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.

Regional atrial blood flow in dogs. Effect of hypertrophy on coronary flow reserve.

Little is known regarding regional atrial blood flow responses during varying hemodynamic states in both the normal and hypertrophied atria. This study was undertaken to develop a canine model of chronic atrial hypertrophy and to define in both this group and in normal dogs the regional blood flow response to acute atrial fibrillation and to measure coronary flow reserve. In the 12 dogs with atrial but not ventricular hypertrophy the mean left and right atrial weights were 75 and 47% respectively greater than in the normal group. Blood flow in the normal dogs was less in the appendage than in the non-appendage region for both atria and increased significantly during atrial fibrillation. Similar findings were noted in the hypertrophy group except that during control conditions the left atrial appendage flow was similar to the nonappendage flow. Minimal vascular resistance for the hypertrophy group, 39 +/- 3 was significantly (P less than 0.05) greater when compared to the normal group 28 +/- 2 mmHg/cm3 per min per g. Thus, significant regional blood flow differences occur in both the normal and hypertrophied atria. In addition, atrial hypertrophy does not alter the autoregulatory capacity to the hemodynamic stress of atrial fibrillation but does reduce coronary flow reserve.

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.

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.

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.

Effects of nitroglycerin and propranolol on the distribution of transmural myocardial blood flow during ischemia in the absence of hemodynamic changes in the unanesthetized dog.

Chronically instrumented awake dogs were used to study the effects of nitroglycerin and propranolol on the transmural distribution of myocardial blood flow during transient ischemia. Studies were carried out 7-14 d after implantation of an electromagnetic flowmeter probe and balloon occluder on the left circumflex coronary artery, placement of epicardial minor axis sonar crystals, and implantation of left atrial, left ventricular, and aortic catheters. The occluder was inflated to completely interrupt flow for 10 s followed by partial release to reestablish flow at 60% of the preocclusion level. During this partial release, which served as the control for the study, regional myocardial blood flow was measured with 7- to 10-mum radioactive microspheres. After control measurements, seven dogs were given nitroglycerin (0.4 mg i.v.) and eight dogs propranolol (0.2 mg/kg i.v.). 5 min later the occlusion and partial release sequence was repeated, and regional myocardial blood flow was measured when heart rate, aortic and left ventricular end-diastolic pressure, and minor axis diameter were unchanged from control values.The data values were selected so that total flow to the ischemic region during partial release after nitroglycerin or propranolol administration was not significantly different from flow during the control partial release. After nitroglycerin administration, endocardial flow (endo) in the ischemic region increased from 0.46+/-0.07 to 0.59+/-0.06 ml/min per g (P < 0.006); epicardial flow (epi) decreased from 0.78+/-0.09 to 0.70+/-0.08 ml/min per g (P < 0.04). The endo:epi ratio increased from 0.65+/-0.07 to 0.92+/-0.10 (P < 0.05). In contrast, administration of propranolol produced no significant change in transmural flow (endo, 0.42+/-0.02 and 0.46+/-0.03 ml/min per g; epi, 0.71+/-0.06 and 0.70+/-0.07 ml/min per g) or in the endo:epi ratio (0.60+/-0.03, 0.66+/-0.06) in the ischemic region. Nitroglycerin and propranolol produce different effects on the transmural distribution of blood flow to ischemic myocardium. Nitroglycerin can increase blood flow to the underperfused endocardium in the absence of alterations in heart size, hemodynamic parameters, and total transmural flow to the ischemic region. Under similar conditions, propranolol has no significant effect on the transmural distribution of blood flow to an ischemic region.

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.

Regional myocardial blood flow during graded treadmill exercise in the dog.

Regional myocardial blood flow was measured in nine dogs at rest and during three levels of treadmill exercise by using left atrial injections of 7-10-mum radioactive microspheres. At rest, heart rate was 76 plus or minus 3 beats/min (mean plus or minus SEM), mean left ventricular myocardial flow was 0.94 plus or minus 0.09 ml/min/g and endocardial flow (endo) exceeded epicardial flow (epi) in all regions (endo/epi equals 1.12-1.33). When treadmill exercise was regulated to increase heart rates from 152 plus or minus 3 to 190 plus or minus 3 to 240 plus or minus 6 beats/min, myocardial blood flow (MBF) to all regions of the left ventricle increased linearly with heart rate (HR) from 1.83 plus or minus 0.11 to 2.75 plus or minus 0.22 to 3.90 plus or minus 0.26 ml/min/g (MBF EQUALs 0.0175 HR - 0.523 PLUS OR MINUS 0.614, R EQUALS 0.87). Exercise abolished the gradient of blood flow favoring the left ventricular endocardium at rest, so that the endo/epi flow ratios were not significantly different from 1.00. Right ventricular flows were consistently less than corresponding left ventricular flows, but showed a similar linear increase with heart rate. Right ventricular endo/epi ratios were not different from 1.00 either at rest or during exercise. Thus, exercise resulted in increased myocardial blood flow to all regions of the left and right ventricles with maintenance of subendocardial flow equal to subepicardial flow.

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.

Pressure-flow studies in man: effect of atrial systole on ventricular function in mitral stenosis.

The effect of atrial contraction on left ventricular function in six patients with varying degrees of mitral stenosis was determined by utilizing the pressure gradient technique to measure instantaneous aortic blood flow and pressure. Aortic flow was measured as ventricular rate was controlled by right ventricular pacing to create A-V (atrioventricular) dissociation at varying rates (90-150 beats/min). At each heart rate, beats with preceding P waves, effective atrial systole, were grouped according to the duration of the P-R interval. Beats without P waves served as controls. There was always a significant increase in stroke volume, created by effective atrial systole, but the P-R interval at which it took place was different for each patient. There was no difference in the stroke volume for beats preceded by P waves having a P-R interval within the range of 0.05-0.20 sec. These beats were grouped for each patient, subjected to regression analysis, and compared to control beats. The absolute and percent change created by effective atrial systole was inversely proportional to the severity of the disease as determined by mitral valve orifice size. Effective atrial systole plays less of a role in augmenting left ventricular function in patients with mitral stenosis than in patients with normal valves.

Local effects of acute cellular injury on regional myocardial blood flow.

This study was designed to examine local effects of acute cellular injury on regional myocardial blood flow. Studies were carried out in awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and an occluder on the left circumflex coronary artery. Regional myocardial blood flow was measured by using 7-10-mum radioisotope-labeled microspheres after reestablishing inflow to a region subjected to a 2-h complete coronary occlusion. Microspheres were injected 15 s, 15 min, 4 h, and 3 days after reperfusion to assess effects of cell injury at varying intervals after reperfusion. Effects of acute cellular injury on blood flow were assessed by determining the relationship between regional blood flow and the extent of subsequent cellular necrosis measured in multiple tissue samples, weight 1-2 g, from the entire ischemic zone. The extent of cellular necrosis was determined from histological sections of each tissue sample. Prolonged ischemia effected local tissue responses which altered perfusion as a function of the interval after reperfusion and the subsequent extent of myocardial necrosis. Although the net response in each region immediately after reperfusion was vasodilation, the hyperemia in regions which subsequently suffered cellular necrosis was attenuated in direct proportion to the extent of subsequent infarction. Blood flow to acutely injured regions remained equal to, or in excess of, flow to nonischemic regions 15 min after reperfusion, but at 4 h and 3 days after reperfusion, flow was significantly decreased in regions with greater than 50% infarction. Thus, these data indicate that prolonged ischemia initiates tissue responses which progressively reduce myocardial perfusion after reperfusion. These effects on tissue perfusion may result from normal responses to irreversible injury and (or) abnormal responses to reversible and thus, potentially alterable, ischemic injury.

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.

Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog.

This study was designed to determin the effect of nitroglycerin upon transmural distribution of myocardial blood flow in the awake dog during normal conditions and in the presence of ischemia-induced coronary vasodilation. Studies were performed in chronically prepared dogs with electromagnetic flowmeters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was estimated by using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. During control conditions endocardial flow (0.86 plus or minus SEM 0.05 ml/min per g) slightly exceeded epicardial flow (0.72 plus or minus 0.03 ml/min per g, P smaller than 0.05), and this distribution of flow was not significantly altered by nitroglycerin. After a 5-s coronary artery occlusion, reactive hyperemia occurred with excess inflow of arterial blood effecting 360 plus or minus 15% repayment of the blood flow debt incurred during occlusion. When arterial inflow was limited to the preocclusion rate during coronary vasodilation after a 5-s total coronary artery occlusion, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium, and the delayed reactive hyperemia was markedly augmented (mean blood flow debt repayment =775plus or minus 105%, P smaller than 0.01). Tese data suggested that subendocardial underperfusion during the interval of coronary vasodilation in the presence of a flow-limiting proximal coronary artery stenosis caused continuing subendocardial ischemia which resulted in augmentation of the reactive hyperemic response. In this experimental model both the redistribution of myocardial blood flow which occurred during an interval of restricted arterial inflow after a 5-s coronary artery occlusion and augmentation of the subsequent reactive hyperemic response were returned toward normal by nitroglycerin. This effect of nitroglycerin may have resulted, at least in part, from its ability to vasodilate the penetrating arteries which deliver blood from the epicardial surface to the subendocardium.

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.

Functional improvement of jeopardized myocardium following intracoronary streptokinase infusion in acute myocardial infarction.

The effect of reperfusion on regional left ventricular performance following acute myocardial infarction in man was determined. Intracoronary streptokinase was administered in 24 patients within 6 h of the onset of symptoms. 15 patients (62%) were successfully recanalized during the initial study. Mean percent radial shortening (%RS) in both the jeopardized and compensatory regions were determined using 23 radii from the centroid of diastolic and systolic angiographic silhouettes. Sequential measurements were obtained during repeat cardiac catheterization studies at 24 h in 19 patients and before discharge from the hospital (16 +/- 11 d) in 15 patients. At the time of the predischarge study, each acutely reperfused patient showed improvement in %RS in the jeopardized region (P = 0.01) with 56% returning to the normal range. Despite the uniform improvement in the contractile function of the jeopardized region in each reperfused patient, the global ejection fraction showed no improvement or a decrease at the time of the chronic study in 44%. This was due to a decrease in the compensatory wall motion in the uninvolved segments between the acute and chronic study in each case. Neither the %RS nor the ejection fraction changed significantly at the time of the chronic study in the patients who could not be acutely recanalized. These data indicate (a) significant salvage of jeopardized myocardium associated with recovery of contractile function in patients reperfused during the first 6 h of chest pain following acute myocardial infarction; (b) no improvement in regional or global left ventricular performance in patients who could not be reperfused acutely; and (c) the ejection fraction is strongly influenced by changes in the compensatory wall motion of the uninvolved segments and does not accurately reflect changes in the contractile function of the jeopardized myocardium.

The effect of cardiac tamponade on coronary haemodynamics in the awake dog.

Phasic left circumflex coronary artery and aortic blood flow were monitored in six awake dogs during a control period and at several degrees of cardiac tamponade. A mean pericardial pressure of 24 plus or minus 3 mm Hg (mean plus or minus SEM) was attained at the maximum tamponade level. Total left circumflex coronary blood flow decreased 51% while the systolic portion of this flow became negative or retrograde. Following acute relief of the tamponade, a coronary hyperaemic response was noted. It it suggested that myocardial ischaemia may be partially responsible for the depressed cardiac function seen in this condition and that extravascular compression of the epicardial vessels may limit the coronary blood flow during systole.

Effect of aminophylline on coronary reactive and functional hyperaemic response in conscious dogs.

This study was undertaken to determine whether adenosine release from myocardial cells plays a role in coronary reactive and functional vasomotion. Reactive hyperaemic blood flow responses to 10 s complete occlusions and 400 ms diastolic occlusions of the left circumflex coronary artery and to the vasomotor responses to the increased cardiac demand following ventricular extra-activation were examined in a chronic, heart-blocked dog preparation during a control period and following intravenous bolus administration of aminophylline (5 mg X kg-1). Aminophylline administration resulted in a 19% decrease in the blood flow debt repayment ratio of 10 s reactive hyperaemic responses compared with the control period. However, administration of aminophylline had no effect on the coronary vascular response to 400 ms diastolic occlusions or to ventricular extra-activations. These observations indicate that adenosine may play a role in the coronary vascular response to prolonged interventions but that other factors, as yet unidentified, may be implicated in the beat-to-beat regulation of coronary vascular resistance.

Repetitive episodes of brief ischaemia (12 min) do not produce a cumulative depletion of high energy phosphate compounds.

During myocardial ischaemia the purine (ATP, GTP) and pyrimidine (CTP, UTP) nucleotide content of the myocyte falls. When the ischaemic episode resolves, many hours or even days are required for restoration of nucleotide pools. These observations suggest that repetitive episodes of ischaemia might produce progressive depletion of nucleotide pools. In order to determine the effect of repetitive episodes of brief ischaemia on nucleotide pools, open-chest dogs underwent three 12 min periods of occlusion of the left anterior descending coronary artery, with each occlusion followed by 10 min of reperfusion. During the first occlusion nucleotide pools decreased by 30% (ATP); 36% (GTP), 52% (CTP), and 48% (UTP). The subsequent two occlusions produced no further decrease in nucleotide pools. The myocardial content of adenine nucleotide catabolites (adenosine + inosine + hypoxanthine) tended to be greater during the first occlusion than during the subsequent occlusions, and substrate delivery (ie regional myocardial blood flow) was similar during each of the periods of ischaemia. These results indicate that a decrease in the rate of nucleotide degradation, rather than an increase in nucleotide synthesis, accounts for the maintenance of nucleotide content during subsequent ischaemic episodes after the initial ischaemic period. Thus repetitive episodes of regional ischaemia do not produce a cumulative decrease in the high energy phosphate content of the myocardium.

Relation of left ventricular mass to geometry of the proximal coronary arteries in the dog.

Proximal epicardial coronary artery luminal diameters were measured from silicone casts formed in situ in freshly excised hearts under a constant pressure of 100 mm Hg. Twenty-five coronary arteries from 15 normal dogs and 22 coronary arteries in 13 dogs with either chronic pressure or volume overload hypertrophy were studied. Mean left ventricular (LV) body weight ratios were 4.75 +/- 1.01 g/kg in the normal dogs, 8.4 +/- 1.7 g/kg in the pressure-overload dogs, and 6.2 +/- 0.6 g/kg in the volume-overload dogs. The cross-sectional area of the left circumflex (LC) coronary artery was determined at 11 branch sites. The ratio of the area of the branches to the area of the parent vessel was 1.095 +/- 0.105, indicating that the cross-sectional area after a branch point increased. A poor correlation existed between LV mass and coronary artery diameter in both normal and hypertrophy groups for the LC (r = 0.44), the left anterior descending (LAD) (r = 0.63), and the combined LC and LAD (r = 0.52). The mean cross-sectional area of the combined LC and LAD was 0.12 cm2 in the normal group and 0.15 cm2 in the hypertrophy group; this increase was not statistically significant (p = 0.13). When the mean cross-sectional area of the combined vessels was adjusted for heart weight, there was a decrease in the cross-sectional area/100 g of myocardium in the hypertrophy group compared with the control group. These data demonstrate that coronary artery luminal diameter in the dog does not increase commensurately with the increase in mass associated with myocardial hypertrophy.

Effect of atrial fibrillation on atrial blood flow in conscious dogs.

This study was undertaken to examine the independent effects of atrial tachycardia, ventricular tachycardia, and atrial fibrillation (AF) on atrial and ventricular blood flow in conscious, heart-blocked dogs using radioactive microspheres. Atrial blood flow averaged 0.54 +/- 0.08 ml/min/g during the control period at an atrial rate of 124 beats/min and a ventricular rate of 90 beats/min. Atrial flow increased to 0.72 +/- 0.12 ml/min/g during atrial pacing at 236 beats/min, but was not significantly altered by ventricular pacing at 200 beats/min. AF at a ventricular rate of 90 beats/min resulted in atrial flow values of 0.91 +/- 0.08 ml/min/g. The ratio of atrial flow to left ventricular flow during AF averaged 1.18 +/- 0.08. Administration of a maximal vasodilating dose of adenosine during AF further increased atrial flow to 2.18 +/- 0.16 ml/min/g. Atrial tachycardia or AF did not significantly affect ventricular blood flow. These data indicate (1) that atrial blood flow increases significantly during AF, reaching flow values per gram of tissue comparable to those of the left ventricle, and (2) that this flow is regulated by the metabolic needs of the atrial tissue and does not represent maximal vasodilation.