Alterations in regional myocardial blood flow after nitroprusside and nitroglycerin in patients with and without significant coronary artery disease

To evaluate vasodilator-induced redistribution of regional myocardial blood flow, intravenous sodium nitroprusside and nitroglycerin were administered in doses producing matched reductions (15%) in mean arterial pressure at constant heart rate. Anterior left ventricular great cardiac vein blood flow (thermodilution) was measured in 14 patients without angiographic anterior collateral supply. Global coronary sinus blood flow remained constant with both nitroprusside and nitroglycerin administration, despite significant reductions in mean arterial pressure. However, nitroglycerin reduced great vein flow by 25 +/- 17% and nitroprusside by 10 +/- 16% (p less than 0.01). Subgroup analysis indicated that the nitroglycerin-nitroprusside regional blood flow differences were more pronounced in patients without significant left anterior descending coronary artery narrowing. Neither vasodilator produced significant differences in arterial-coronary sinus oxygen or lactate contents, calculated myocardial oxygen consumption, left ventricular dP/dt, or electrocardiographic or clinical signs of myocardial ischemia. Despite qualitatively similar hemodynamic effects, comparisons of vasodilator-induced relative reductions in normally supplied anterior left ventricular regional coronary blood flow suggest a mechanism of the reported beneficial effects of nitroglycerin on potentially ischemic myocardial regions.     

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.     

Effect of nitroglycerin and arterial hypertension on myocardial blood flow following acute coronary artery occlusion in the dog.

This study was designed to evaluate the effects of nitroglycerin and phenylephrine-induced arterial hypertension on regional myocardial blood flow in awake dogs with acute occlusion of the left circumflex coronary artery. Myocardial blood flow to four transmural layers from epicardium to endocardium was estimated with 7-9 micron radionuclide labeled microspheres in 1) the non-ischemic myocardium, 2) the central ischemic zone, and 3) the border zone separating ischemic from normally perfused myocardium. Measurements were repeated 1) during infusion of nitroglycerin, 0.015 mg/kg/min, 2) during phenylephrine administered to increase arterial pressure 60 mm Hg above the control measurements, and 3) during combined nitroglycerin and phenylephrine administration. Both nitroglycerin and phenylephrine increased myocardial blood flow to the central ischemic area; nitroglycerin significantly decreased the resistance of the collateral vascular system, while the increased flow during phenylephrine administration was accounted for entirely by the increased arterial pressure with no change in collateral vascular resistance. The increased blood flow to the central ischemic zone during nitroglycerin administration was delivered preferentially to the subendocardium, while the increased blood flow during phenylephrine administration was directed exclusively to the subepicardium. Neither nitroglycerin nor phenylephrine significantly altered computed vascular resistance of the border zone, but because of the increased driving pressure, blood flow to the border zone was significantly increased during phenylephrine administration.     

Nitroglycerin-induced coronary vasodilatory responses in patients during isometric handgrip exercise

Intracoronary nitroglycerin is frequently administered during invasive procedures such as coronary angioplasty or thrombolysis which may be associated with pain and sympathetic neural stimulation. Whether sympathetic-mediated reflex vasoconstriction interferes with nitroglycerin-induced augmentation of coronary blood flow is unknown. Therefore, coronary and systemic hemodynamics were measured in 19 patients during isometric handgrip exercise (3 min x 25% maximal effort), during intracoronary nitroglycerin, and during handgrip plus intracoronary nitroglycerin. Nine patients had no significant left anterior descending coronary artery stenosis (group 1) and ten patients had greater than 70% left anterior descending coronary artery stenosis (group 2). Handgrip exercise increased heart rate, mean arterial pressure, and coronary sinus and great vein flow 15% while increasing coronary resistance 10%. Intracoronary nitroglycerin (200 micrograms) reduced mean arterial pressure -4 +/- 6% and increased great cardiac vein flow 35-72%. Anterior left ventricular regional coronary flow responses to intracoronary nitroglycerin were unaffected by sympathetic stimulation for group 1. Group 2 had a greater increase in great vein flow with intracoronary nitroglycerin plus handgrip compared to nitroglycerin alone due to increased mean arterial pressure with no change in the great vein resistance. These data indicate that sympathetic stimulation does not alter the nitroglycerin-induced augmentation of coronary sinus and great vein blood flow in patients with and without significant left anterior descending coronary artery stenosis. In patients undergoing invasive interventions who may have increased circulating catecholamines, mild sympathetic (isometric) stimulation does not appear to interfere with the coronary vasodilatory responses to intracoronary nitroglycerin.     

Carotid sinus reflex control of coronary blood flow in human subjects

Systemic and coronary hemodynamics were assessed before and during a reduction in carotid transmural pressure. This reduction was induced by means of a pneumatic neck chamber in 15 normal subjects and 15 hypertensive patients with a normal coronary arteriogram. A reduced baroreflex responsiveness was demonstrated in hypertensive patients as compared with normal subjects by evaluating both the reflex bradycardia evoked by intravenous administration of phenylephrine and the reflex increase in blood pressure during carotid sinus hypotension. In normal subjects, the reduction in carotid transmural pressure induced a significant increase in mean blood pressure, total peripheral resistance, cardiac output, heart rate, coronary vascular resistance, coronary blood flow assessed by the continuous thermodilution method and myocardial oxygen consumption. In hypertensive patients, the same stimulus significantly increased mean blood pressure, cardiac output, heart rate and coronary blood flow while no significant change was detected in coronary vascular resistance and myocardial oxygen consumption. The increase in mean blood pressure, total peripheral resistance and cardiac output was significantly higher in normal subjects than in hypertensive patients. These results suggest that in normal subjects carotid sinus hypotension evokes reflex coronary vasoconstriction, whereas this response is blunted in hypertensive patients with reduced baroreflex sensitivity.     

Effects of propranolol on the hemodynamic,coronary sinus blood flow and myocardial metabolic response to atrial pacing

The hemodynamic, coronary sinus blood flow and myocardial metabolic effects of 0.15 mg/kg body weight of intravenously administered propranolol were studied in 19 patients with coronary artery disease and 6 normal patients. Atrial pacing was performed in all patients and produced angina in 15 of the 19 patients with coronary artery disease. In these patients propranolol reduced heart rate from 78 to 69 beats/min, cardiac index from 3.0 to 2.6 liters/min per m² and left ventricular stroke work index from 47 to 43 g-m/m²; it increased total peripheral resistance from 24 to 28 units and lactate extraction from 16.3 to 22.5 percent. There was no significant change in mean arterial pressure, left ventricular end-diastolic pressure, coronary sinus blood flow or myocardial oxygen consumption. During a second pacing stress propranolol produced clinical improvement in 9 of the 15 patients who experienced angina initially. The improvement was associated with less severe abnormalities in S-T depression and left ventricular end-diastolic pressure, increased lactate extraction and no significant change in coronary sinus blood flow or myocardial oxygen consumption. Thus, propranolol appears to be capable of modifying the anginal threshold as determined with atrial pacing, and the clinical response appears to be independent of global changes in coronary sinus blood flow and myocardial oxygen consumption.     

Potentiation of cocaine-induced coronary vasoconstriction by beta-adrenergic blockade

STUDY OBJECTIVE: To determine whether beta-adrenergic blockade augments cocaine-induced coronary artery vasoconstriction. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A cardiac catheterization laboratory in an urban teaching hospital. PATIENTS: Thirty clinically stable patient volunteers referred for catheterization for evaluation of chest pain. INTERVENTIONS: Heart rate, arterial pressure, coronary sinus blood flow (by thermodilution), and epicardial left coronary arterial dimensions were measured before and 15 minutes after intranasal saline or cocaine administration (2 mg/kg body weight) and again after intracoronary propranolol administration (2 mg in 5 minutes). MEASUREMENTS AND MAIN RESULTS: No variables changed after saline administration. After cocaine administration, arterial pressure and rate-pressure product increased; coronary sinus blood flow fell (139 +/- 28 [mean +/- SE] to 120 +/- 20 mL/min); coronary vascular resistance (mean arterial pressure divided by coronary sinus blood flow) rose (0.87 +/- 0.10 to 1.05 +/- 0.10 mm Hg/mL.min); and coronary arterial diameters decreased by between 6% and 9% (P less than 0.05 for all variables). Subsequently, intracoronary propranolol administration caused no change in arterial pressure or rate-pressure product but further decreased coronary sinus blood flow (to 100 +/- 14 mL/min) and increased coronary vascular resistance (to 1.20 +/- 0.12 mm Hg/mL.min) (P less than 0.05 for both). CONCLUSIONS: Cocaine-induced coronary vasoconstriction is potentiated by beta-adrenergic blockade. Beta-adrenergic blocking agents probably should be avoided in patients with cocaine-associated myocardial ischemia or infarction.     

Vasopressin and vasopressin plus nitroglycerin for portal hypertension. Effects on systemic and splanchnic hemodynamics and coronary blood flow

We measured the coronary, systemic, and splanchnic effects of vasopressin and vasopressin plus nitroglycerin in 8 stable patients with alcoholic cirrhosis. Vasopressin (0.1-0.8 U/min) increased pressure in the hepatic vein, pulmonary artery and pulmonary capillaries. Wedged hepatic (portal) vein pressure was unchanged; the hepatic venous pressure gradient (wedged-free hepatic vein pressure) fell. Insignificant declines occurred in cardiac output, gastroesophageal collateral (azygous) blood flow, hepatic blood flow and coronary sinus (cardiac) blood flow. The addition of nitroglycerin (40-70 micrograms/min) reduced pressure in the hepatic vein, pulmonary artery and pulmonary capillaries, while increasing the hepatic venous pressure gradient. Wedged hepatic vein pressure did not change. Gastroesophageal collateral (azygous) flow increased markedly; cardiac output rose to a lesser degree. Coronary sinus and hepatic blood flow did not change. Nitroglycerin ameliorated the increases in systemic and pulmonary artery pressure produced by vasopressin but also tended to reverse the decline in the hepatic venous pressure gradient and markedly increased gastroesophageal flow. Neither drug significantly affected coronary blood flow.     

Ventricular function and coronary hemodynamics after intravenous nitroglycerin in coronary artery disease.

Left ventricular dynamics as well as systemic and coronary hemodynamics were determined in 14 patients with coronary artery disease (1) under control conditions, (2) under intravenous infusion of nitroglycerin, (3) under continued infusion of nitroglycerin with restored arterial and pulmonary artery pressures induced by the parallel infusion of dextran. Heart rate was kept constant by atrial pacing.Intravenous nitroglycerin infusion resulted in a significant reduction in left ventricular systolic (20 per cent) and end-diastolic pressure (43 per cent), peak $\text{dp}\text{dt}$ (13 per cent), cardiac index (16 per cent), stroke volume index (15 per cent), and stroke work index (30 per cent). Peak (dp/dt/total pressure) increased (15 per cent). Pulmonary vascular resistance markedly decreased (29 per cent), whereas total peripheral resistance did not change significantly (?3 per cent). Both coronary blood flow of the left ventricle (13 per cent) and myocardial oxygen consumption (15 per cent) decreased parallel to the reduction in preload and afterload. The action of nitroglycerin at restored left ventricular and pulmonary artery pressures was characterized by increase in peak $\text{dp}\text{dt}$ (12 per cent), peak ($\text{dp}\text{dt}$ total pressure) (18 per cent), cardiac index (13 per cent), stroke volume index (14 per cent), and stroke work index (10 per cent). Both coronary blood flow (28 per cent) and myocardial oxygen consumption (21 per cent) increased parallel to the enhancement of ventricular performance.The results demonstrate that intravenous nitroglycerin produces effective diastolic and systolic unloading of the heart associated with reduction in myocardial oxygen consumption and in coronary blood flow. There was marked vascular pooling which quantitatively averaged 437 ± 128 ml. This occurred concomitant with a 43 per cent decrease in left ventricular end-diastolic pressure or a 20 per cent decrease in peak systolic pressure. Significant coronary dilating properties of nitroglycerin could not be detected in these coronary patients. The increase in left ventricular contractility indices at restored pressure suggests a moderate but significant positive inotropic effect of nitroglycerin.     

Dependence of ventricular fibrillation propensity on coronary blood flow without myocardial ischemia

Ventricular fibrillation threshold (VFT) changes have been linked to coronary blood flow (CBF) in the context of CBF reduction and subsequent myocardial hypoxia. To clarify the effect of CBF on VFT in the absence of myocardial hypoxia, 18 open-chest pentobarbital-anesthelized dogs with uniformly controlled heart rate, cardiac output, and mean systemic arterial pressure (SAP¯) were studied as follows: CBF, coronary sinus O₂ content (CcsO₂), and thereby myocardial O₂ consumption were continuously monitored. Baseline VFT determined by the single stimulus scanning technique was 33.0 ± 3.9 mA. Initial values of CBF index (I) and VFT (n = 18) were positively correlated (VFT_mA = 0.8 ± 0.245 · CBFI ml/min · 100g^?1LV; r = 0.60,p < 0.01). Stepwise CBFI increments up to live times in excess of initial 131.5 ± 9.7 ml/min · 100g^?1LV were then induced by changing in random order,SAP¯ (n = 10), left coronary perfusion pressure (n = 7), and arterial O₂ content (n = 10) with VFT determined at each step; CcsO₂ remained above 5.5 vol% while CBFI and VFT changes were positively correlated, and mean weighted slope of VFT_mA = 16.6 ± 0.103 · CBFI ml/min · 100g^?1LV (F = 0.82,p < 0.05). Systemic or coronary perfusion pressure and arterial or coronary sinus O₂ content did not appear to affect VFT independently. It is concluded that even in the absence of myocardial hypoxia, CBF itself is a major determinant of VFT and thereby of innate arrhythmogenic propensity.     

Acute coronary occlusion in the pig: Effect of nitroglycerin on regional myocardial blood flow

Myocardial blood flow was studied in 10 closed chest, anesthetized pigs after an acute balloon catheter occlusion of the left anterior descending coronary artery. With use of radioactive microspheres (15 μ), myocardial blood flow was measured before and during an intravenous nitroglycerin infusion and during a combined nitroglycerin-phenylephrine infusion. A significant zone of ischemia (myocardial blood flow less than 50 percent of normal zone flow) was produced by the occlusion and involved 15 percent of the combined left ventricular and interventricular septal mass. More than 50 percent of this ischemic zone was intensely ischemic (myocardial blood flow 0 to 3 percent of normal). Nitroglycerin resulted in a 20 to 30 mm Hg decrease in systolic blood pressure. Myocardial blood flow was unchanged in intensely ischemic areas but varied directly with the product of heart rate and systolic blood pressure in the moderately ischemic area (myocardial blood flow 26 to 50 percent of normal). S-T segment elevation was significantly increased during nitroglycerin infusion and returned to control level with the added infusion of phenylephrine sufficient to restore the systemic blood pressure to prenitroglycerin values. No improvement in ischemic zone perfusion could be demonstrated during the infusion of nitroglycerin alone or with phenylephrine. The endocardial/epicardial flow ratio in moderately ischemic areas was slightly lower than the normal zone flow ratio and decreased slightly during infusion of nitroglycerin. With the addition of phenylephrine, the ratios rose slightly and no longer differed from prenitroglycerin values.

Blood flow distribution in acutely ischemic pig myocardium differs considerably from that observed in the dog. Nitroglycerin was not shown to have any beneficial effects with or without its relative hypotensive effect. More extensive study in animal models other than the dog is needed.     

Dose-related effects of intracoronary nitroglycerin on coronary hyperemia in patients with coronary artery disease

Although intracoronary nitroglycerin (NTG) is frequently required during percutaneous transluminal coronary angioplasty or thrombolysis, the dose-related hemodynamic effects and the extent to which intracoronary NTG-induced coronary hyperemia is limited in patients with coronary artery disease have not been defined. Therefore, we studied 19 patients with coronary artery disease (nine with no or minimal luminal narrowing of the left anterior descending coronary artery [group 1] and 10 with significant left anterior descending coronary stenosis [group 2]); mean arterial pressure and thermodilution coronary sinus and great cardiac vein blood flow were measured during bolus administrations of 50, 200, and 300 μg of intracoronary NTG. During the NTG-induced hyperemia, mean arterial pressure decreased 0%, 4% (bothp =NS), and 6% (p < 0.05) after 50, 200, and 300 μg doses, respectively. Heart rate did not change. Global coronary hyperemia was greatest for 200 μg with coronary blood flow increasing (74 ± 32% in group 1 and 53 ± 25% for group 2) but was significantly different from 50 μg only in group 2 patients. Moreover, the regional coronary blood flow responses were attenuated in group 2 compared to group 1 for 50 μg, 18 ± 13% vs 38 ± 18%, and for 200 μg, 35 ± 15% vs 72 ± 34% (bothp < 0.05), with the reduction of regional coronary resistance in group 2 attenuated for all three doses of intracoronary NTG. The 300 μg dose did not provide further augmentation of either global or regional coronary blood flow or greater reduction in coronary resistance. We conclude that intracoronary NTG-induced hyperemia is, in part, dose related and attenuated in patients with severe coronary artery disease. These data reemphasize the reduction in coronary vasodilatory reserve in regions supplied by coronary arteries with severe stenoses. Moreover, during interventions requiring intracoronary NTG, doses above 200 μg do not appear to further augment coronary blood flow, probably because of NTG-induced systemic hemodynamic effects and coronary autoregulation.     

Coronary arterial responses to graded doses of nitroglycerin.

The potential benefit from coronary dilatation induced by nitroglycerin is thought to be limited in patients with ischemia by blood pressure reduction, heart rate increase and coronary artery disease. Because recent work with other vasodilators suggests multiple vascular receptor sites with various degrees of responsiveness, coronary dilator and systemic responses to graded doses of nitroglycerin were examined in 13 patients. High resolution, 105 mm photospot film coronary angiograms, using 4.5 or 6 inch image intensification, was performed before and after administration of cumulative doses of sublingual nitroglycerin (75 to 450 μg). A calibrated optical system was used to measure coronary arterial diameter.Small doses of nitroglycerin (75 to 150 μg) increased the diameter of the left anterior descending coronary artery by 10 and 20 percent (mean), that of the left circumflex artery by 9 and 22 percent, and that of collaterally filled vessels by 18 and 28 percent, respectively (all values significantly [P < 0.01] different from measurements before nitroglycerin). No significant change in heart rate or mean aortic pressure occurred. Doses of nitroglycerin to 450 μg produced only modest additional increases in coronary arterial diameter (left anterior descending artery 9 percent, left circumflex artery and collaterally filled vessels 7 percent). Heart rate increased 5 beats/min and blood pressure decreased 11 mm Hg with 450 μg of nitroglycerin (both P < 0.01). These data suggest that dilator receptors of both large left coronary arteries and vessels filled by collateral vessels respond to very small doses of nitroglycerin without significant changes in heart rate or blood pressure.     

Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) election fraction and nine patients with a normal election fraction had a significant (P < 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.     

Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart failure.

OBJECTIVE--To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and oxygen-haemoglobin binding to oxygen transport in patients with congestive heart failure. METHODS--In 30 patients with severe congestive heart failure, arterial, mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were measured and systemic output and coronary sinus blood flow were measured by a thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS--Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg, p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the forward cardiac index (r = 0.89, p < 0.0001). There was no relation between systemic oxygen transport and arterial oxygen content. Similarly, myocardial oxygen transport was found to vary directly with coronary sinus blood flow. Calculations of changes in cardiac index and coronary sinus blood flow at normal oxygen-haemoglobin binding indicate that a considerable increase in cardiac index and coronary blood flow would be required to maintain similar systemic and myocardial oxygen transport. CONCLUSIONS--In patients with severe heart failure increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory mechanisms that maintain adequate systemic and delivery of oxygen to myocardial tissue.     

The effect of angiotensin converting enzyme inhibition on coronary blood flow and hemodynamics in patients without coronary artery disease

We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity (r = 0.939 P < 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level.Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.     

Acute effects of glucose-insulin-potassium infusion on myocardial substrates,coronary blood flow and oxygen consumption in man

To determine whether myocardial oxygen consumption (MVO₂) might be reduced when myocardial substrate uptake is changed from predominantly lipid to predominantly carbohydrate, measurements of arterialcoronary sinus glucose, lactate, free fatty acids, oxygen, carbon dioxide and coronary sinus blood flow (by thermodilution) were obtained in 13 fasting patients. Measurements were initially made in a basal control state and then repeated at 10, 20 and 30 minutes during an infusion of glucose-insulin-potassium. After 30 minutes of infusion, there was a three-fold increase in myocardial glucose uptake (44 ± 10 to 145 ± 19 +μmoles/min [mean ± standard error of the mean], P < 0.01), a two-fold increase in myocardial lactate uptake (35 ± 4 to 77 ± 10 μmoles/min, P < 0.001) and a 75 percent decrease in myocardial free fatty acid uptake (34 ± 5 to 9 ± 3 μmoles/min, P < 0.01). Cardiac respiratory quotient rose from 0.70 ± 0.05 to 0.93 ± 0.08 (P < 0.001). Sum of oxygen extraction ratios for glucose and lactate rose from 51 ± 7 percent at control to 155 ± 22 percent at 30 minutes of infusion (P < 0.001) and suggested that much of the enhanced myocardial carbohydrate uptake met a nonoxidative fate, such as glycogen formation. During glucose-insulin-potassium infusion, arterial-coronary sinus oxygen decreased by 13 percent, coronary sinus blood flow increased by 12 percent and MVO₂ was unchanged. The increase in coronary sinus blood flow was associated with a 13 percent decrease in coronary vascular resistance and a small, but significant, increase in serum osmolarity (289 ± 3 to 299 ± 3 mOsm/liter, P < 0.001).     

Reduced myocardial blood flow resulting from dynamic changes in coronary artery stenosis

To evaluate the interaction of coronary vasomotor tone and stenosis, we studied the effects of ergonovine and adenosine on partially obstructed coronary arteries in 6 closed chest dogs. Coronary stenosis was created by partially inflating a balloon catheter with a distal lumen in the left anterior descending or circumflex coronary artery. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow measured with 15 micron radioactive microspheres. Coronary artery vasoconstriction, induced by ergonovine (0.6 mg i.v.), caused a small, but nonsignificant, increase in stenotic resistance (1.42 ± 0.25 to 2.68 ± 0.64 mm Hg/ml per min) and had no effect on myocardial blood flow. Coronary arteriolar dilation induced by adenosine increased stenotic resistance (1.52 ± 0.25 to 9.01 ± 2.49 mm Hg/ml per min, P < 0.05) and the pressure gradient across the stenosis (18.8 ± 3.0 to 41.3 ± 7.5 mm Hg, P < 0.05). Adenosine increased myocardial blood flow from 0.52 ± 0.05 ml/min per g to 1.43 ± 0.20 ml/min per g (P < 0.05) in the regions supplied by unstenosed arteries, while in the region perfused by the stenosed artery blood flow fell from 0.51 ± 0.06 to 0.29 ± 0.13 ml/min per g (P < 0.05), with the endocardium most severely affected (0.55 ± 0.04 ml/min per g to 0.26 ± 0.09 ml/min per g, P < 0.05).Thus changes in severity of stenosis produced by altered coronary pressure and flow can influence blood flow to the myocardium. Such dynamic changes in coronary artery stenosis may be important in the pathogenesis of angina and myocardial infarction.     

Effects of intraaortic balloon counterpulsation on regional coronary blood flow in experimental myocardial infarction

Intraaortic balloon Counterpulsation was carried out in 10 anesthetized normotensive dogs after ligation of the left anterior descending coronary artery. The distribution of myocardial blood flow was determined in these animals by the radioactive microsphere technique. Counterpulsation resulted in a significant decrease in mean arterial pressure of 29 mm Hg (P < 0.001) and an increase of 20 mm Hg in peak and 10 mm Hg in mean aortic diastolic pressure (P < 0.005). There was no direct relation between the hemodynamic effects of counterpulsation and improvement in the distribution of myocardial blood flow to the infarcted area of myocardium. Analysis of data from individual experiments suggests that improvement in myocardial blood flow to the infarcted region is dependent upon the presence of preexisting collateral vessels, since animals with the highest rates of flow to the infarcted region after ligation of the left anterior descending coronary artery had the greatest increase in myocardial blood flow after intraaortic balloon counterpulsation. Despite the failure of any overall improvement in myocardial blood flow to the infarcted area after Counterpulsation, there was a small but significant relative increase in endocardial flow to the normal and border zones of myocardium surrounding the infarcted region.     

Effects of molsidomine during the cold test in stable coronary insufficiency under beta-blocker treatment

The heart rate, cardiac output, coronary sinus blood flow, systolic and end diastolic left ventricular pressures, femoral arterial pressure and coronary oxygen arterio-venous difference were measured in 12 patients with stable coronary artery disease without cardiac failure on long-term betablocker therapy, before and 45 minutes after 2 or 3 mg sublingual molsidomine. The measurements were repeated in 8 patients during a cold pressor test. Under basal conditions, molsidomine decreased the systolic and end diastolic left ventricular pressures, mean femoral arterial pressure, cardiac output and double product. The coronary oxygen arterio-venous difference was unchanged. Coronary sinus flow and myocardial oxygen consumption decreased. In the 2 patients who were given 3 mg molsidomine, a progressive reduction in systolic left ventricular pressure to 70% or less than its initial value, necessitated immediate treatment with volume expanders. During the cold pressor test before molsidomine the systolic and end diastolic left ventricular pressures, mean femoral arterial pressure and the double product increased. Coronary sinus flow was unchanged overall: it decreased in 6 patients, increased in 2 patients and remained the same in 1 patient. Coronary resistance increased in 6 patients and decreased in only one patient. During the cold pressor test after molsidomine there was a significant reduction in the increase of systolic left ventricular pressure, mean femoral artery pressure and double product. Coronary sinus blood flow increased in 5 patients and decreased in only one case. Coronary resistance decreased in half the cases.(ABSTRACT TRUNCATED AT 250 WORDS)