Myocardial oxygen delivery/consumption during cardiopulmonary resuscitation: a comparison of epinephrine and phenylephrine

Our study compared the effect of high-dose epinephrine with the pure alpha-agonist phenylephrine on regional myocardial blood flow (MBF), myocardial oxygen delivery (MDO2), myocardial oxygen consumption (MVO2), and defibrillation rates during CPR. Fifteen swine weighing more than 15 kg were instrumented for measurement of regional MBF using radiolabeled tracer microspheres. Measurements of regional MBF, MDO2, and MVO2 were made during normal sinus rhythm. Ventricular fibrillation was induced and persisted for ten minutes. CPR was begun using a pneumatic compression device. Regional MBF, MDO2, and MVO2 were measured during CPR. Following three minutes of CPR, animals (N = 15) were allocated to one of three groups (n = 5): Group 1, epinephrine 0.2 mg/kg; Group 2, phenylephrine 0.1 mg/kg; or Group 3, phenylephrine 1.0 mg/kg. Measurements of regional MBF, MDO2, and MVO2 were repeated after drug administration. Extraction ratios, defined as MVO2/MDO2, were calculated during normal sinus rhythm, CPR, and after drug administration. Defibrillation was attempted 3 1/2 minutes after drug administration. There was no significant difference in MBF, MDO2, MVO2, and extraction ratio during normal sinus rhythm and CPR for any of the groups. Total MBF following drug administration was 67.2 +/- 49.4 mL/min/100 g for the group receiving epinephrine 0.2 mg/kg; 7.0 +/- 7.1 mL/min/100 g for the group receiving phenylephrine 0.1 mg/kg; and 36.7 +/- 21.1 mL/min/100 g for the group receiving phenylephrine 1.0 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of adenosine in the maintenance of coronary vasodilation distal to a severe coronary artery stenosis. Observations in conscious domestic swine

The purpose of this study was to test the hypothesis that adenosine is required to maintain arteriolar vasodilation distal to a severe coronary stenosis. Eight closed-chest conscious pigs were prepared by placing a 7.5-mm long stenosis (82% lumenal diameter reduction) in the proximal left anterior descending coronary artery. Regional myocardial blood flow (microsphere technique) was measured at control 1, after 10 minutes of intracoronary infusion of adenosine deaminase (7-10 U/kg per min) distal to the stenosis, and 20-30 minutes after stopping adenosine deaminase infusion. Studies with 125I-labeled adenosine deaminase were conducted in six additional pigs to document the extent to which infused adenosine deaminase penetrated the interstitial space. 125I-labeled adenosine deaminase was infused for 10 minutes (10-11 U/kg per min) into the left anterior descending coronary artery. Calculated interstitial fluid concentrations of adenosine deaminase ranged between 71 and 272 U/ml and were at least one order of magnitude greater than that required to deaminate all the adenosine which would be released into the interstitium in response to 15-30 seconds of coronary occlusion. In the primary group of animals (n = 8), endocardial flow (ml/min per g) distal to stenosis at control 1 (1.15 +/- 0.33) was reduced vs. endocardial flow in the nonobstructed circumflex zone (1.59 +/- 0.38, P less than 0.05). Flows in epicardial layers were comparable at control 1 (distal zone = 1.40 +/- 0.36 vs. circumflex zone = 1.45 +/- 0.41). Distal zone endocardial and epicardial flows did not change vs. control 1 in response to infusion of adenosine deaminase. However, the distal: circumflex epicardial flow ratio declined vs. control 1 (0.98 +/- 0.14) during adenosine deaminase infusion (0.87 +/- 0.17, P less than 0.05). The distal:circumflex endocardial flow ratio during adenosine deaminase (0.72 +/- 0.20) was unchanged vs. control 1 (0.76 +/- 0.22) but was less than control 2 (0.80 +/- 0.18, P less than 0.05). Thus, destruction of all or most interstitial adenosine caused only slight relative reduction in regional myocardial blood flow distal to a severe coronary artery stenosis. Accordingly, adenosine contributes only modestly to maintenance of arteriolar vasodilation in this setting or else its absence is almost fully compensated for by another mechanism(s).     

Postcountershock pulseless rhythms: response to CPR, artificial cardiac pacing, and adrenergic agonists

Clinically, countershock of ventricular fibrillation (VF) may result in asystole or a pulseless rhythm in more than 50% of attempts. We conducted a study to assess the effects of immediate artificial pacing, CPR, and adrenergic drug therapy in the management of postcountershock pulseless rhythms. Thirty-four episodes of VF followed by countershock were studied in eight anesthetized dogs. Transducer-tipped catheters were positioned in the ascending aorta (Ao) and right atrium (RA). A bipolar pacing catheter was advanced to the apex of the right ventricle and a catheter for measurement of coronary sinus blood flow (CSQ) (continuous thermodilution technique) was positioned in the coronary sinus. VF was induced electrically and a countershock at 400 J was given two minutes later; CPR was not performed during VF episodes. Countershock was followed by asystole or a pulseless rhythm in all animals. Immediate endocardial pacing (0.1 to 5 mA) of bradyarrhythmias produced electrical capture but did not result in arterial pressure pulses in any animal. After pacing, CPR was performed for two minutes or until restoration of spontaneous circulation (ROSC). During CPR, the diastolic coronary perfusion gradient (Ao-RA) was 20 +/- 7 mm Hg (mean +/- SD) and CSQ was 14 +/- 7 mL/min/100 g (53% +/- 43% of control). ROSC followed CPR of less than two minutes duration in 24% of VF study episodes. If ROSC did not follow two minutes of CPR, 1 mg epinephrine, or 50 micrograms or 100 micrograms isoproterenol was given IV.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue acidosis: role in sustained arteriolar dilatation distal to a coronary stenosis

This study tested the hypothesis that myocardial tissue acidosis is responsible for maintenance of reduced arteriolar tone distal to a severe coronary arterial stenosis. Domestic swine (n = 10) were instrumented with a coronary arterial stenosis that reduced vessel diameter 80%. Measurements of hemodynamic indexes were made 1) before stenosis, 2) at 5, 20, and 60 minutes after stenosis placement, and 3) after each of three, 20-minute NaOH infusions (0.05 M, 0.1 M, and 0.5 M) distal to the stenosis (group 1). Intracellular pH at the end of 30 minutes of 0.5 M NaOH infusion distal to the stenosis was measured in a second group (n = 6) of swine (group 2). After stenosis placement in group 1, endocardial blood flow declined significantly, and evidence of regional acidosis (increased coronary venous Pco2 and decreased coronary venous pH) and ischemia (lactate production) developed. One hour later, evidence of acidosis persisted, though to a lesser extent. Myocardial oxygen and lactate metabolism exhibited similar patterns. Infusion of 0.5 M NaOH (0.38 ml/min) reduced (p less than 0.01) distal zone epicardial blood flow but did not change endocardial flow. Regional myocardial oxygen extraction (75 +/- 8%, mean +/- SD) and consumption (8.2 +/- 2.3 ml/min/100 g) also declined significantly (p less than 0.01) in response to 0.5 M NaOH infusion compared with 60 minutes after stenosis (86 +/- 4 and 12.4 +/- 2.8 ml/min/100 g respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of norepinephrine versus epinephrine on myocardial hemodynamics during CPR

Alpha-adrenergic agonists improve myocardial blood flow during CPR by increasing aortic diastolic pressure. Adrenergic agonists with beta-2 properties may enhance peripheral vasodilation and may prove less beneficial during CPR. The purpose of this study was to compare epinephrine (E), an alpha-1,2; beta-1,2 agonist, versus norepinephrine, an alpha-1,2; beta-1 agonist, on myocardial hemodynamics during CPR. Twenty swine were instrumented for pressure, arterial and coronary sinus oxygen content (CAO2 and CCSO2, respectively), and myocardial blood flow measurements using tracer microspheres. CAO2, CCSO2, myocardial blood flow, myocardial oxygen delivery (MDO2) and myocardial oxygen consumption (MVO2), extraction ratio, and aortic diastolic pressure were determined during normal sinus rhythm and during CPR following a ten-minute arrest. After three minutes of CPR, the animals were allocated to receive either norepinephrine 0.08 mg/kg (n = 5), norepinephrine 0.12 mg/kg (n = 5), norepinephrine 0.16 mg/kg (n = 5), or epinephrine 0.20 mg/kg (n = 5). One minute after drug administration, all hemodynamic parameters were again determined. Three and one half minutes after drug administration defibrillation was attempted. A Newman-Keuls multiple comparison procedure was used to compare differences following drug administration. During CPR, aortic diastolic pressure averaged less than 13 mm Hg, and myocardial blood flow averaged less than 6 mL/min/100 g. All doses of norepinephrine and epinephrine improved all hemodynamic parameters over those seen during CPR. The two highest doses of norepinephrine significantly improved extraction ratio compared with norepinephrine 0.08 mg/kg (P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serotonin selectively aggravates subendocardial ischemia distal to a coronary artery stenosis during exercise.

BACKGROUND. The coronary circulation has been shown to remain responsive to vasodilator and vasoconstrictor stimuli during myocardial ischemia. Because serotonin possesses both vasodilator and vasoconstrictor properties, we examined its effect in the coronary circulation distal to an arterial stenosis that resulted in myocardial hypoperfusion during exercise. METHODS AND RESULTS. Seven chronically instrumented dogs were studied during treadmill exercise in the presence of a stenosis that reduced distal left circumflex coronary artery perfusion pressure to 42 +/- 1 mm Hg. Myocardial blood flow was assessed with radioactive microspheres during exercise before and during intracoronary infusion of 0.4 and 2.0 micrograms/kg-1.min-1 serotonin. The stenosis was adjusted to maintain distal coronary pressure constant during control exercise and with the two doses of serotonin. In seven dogs, the effect of serotonin (2.0 micrograms/kg-1.min-1) was also studied during exercise with normal arterial inflow. During control exercise, the stenosis decreased mean myocardial blood flow to 45% of flow in the normally perfused region. This decrease was most pronounced in the subendocardium (endocardial/epicardial ratio 0.36 +/- 0.06 versus 1.46 +/- 0.14 in the control region; p < 0.01). With no change in pressure distal to the stenosis, serotonin decreased subendocardial flow from 0.51 +/- 0.09 ml/min-1.g-1 to 0.41 +/- 0.12 (p < 0.05) and then to 0.35 +/- 0.08 ml/min-1.g-1 (p < 0.05) and tended to increase subepicardial flow from 1.47 +/- 0.17 to 1.91 +/- 0.23 and 1.85 +/- 0.21 ml/min-1.g-1 (p = 0.08) during infusions of 0.5 and 2.0 micrograms/kg-1.min-1, respectively, with no change in total arterial inflow. In contrast, in the absence of a stenosis, serotonin (2.0 micrograms/kg-1.min-1) increased subendocardial flow from 2.43 +/- 0.25 to 3.73 +/- 0.25 ml/min-1.g-1 (p < 0.01) and subepicardial flow from 1.88 +/- 0.20 to 5.29 +/- 0.38 ml/min-1.g-1 (p < 0.01). CONCLUSIONS. During normal arterial inflow, serotonin dilated coronary resistance vessels and increased flow to all myocardial layers. During hypoperfusion, a vasodilator response was still present in the subepicardium, but vasoconstriction was then observed in the subendocardium. Our data suggest that serotonin constricts the intramural penetrating arteries, thereby selectively increasing resistance to subendocardial blood flow.     

Systemic and coronary hemodynamic effects of intravenous nicardipine at rest and in ischemia induced by rapid atrial stimulation

The systemic and coronary haemodynamic effects of intravenous nicardipine were investigated in 10 patients with a more than 70 p. 100 stenosis of the left coronary artery. Two brief atrial pacing tests (ST1 and ST2) were performed. ST2 was performed 30 minutes after an intravenous injection of nicardipine 2.5 mg over 5 minutes. Nicardipine produced a 25 p. 100 decrease in ventricular systolic pressure and a substantial increase in cardiac index (from 2.74 +/- 0.48 to 3.46 +/- 0.35 l/min/m2, p less than 0.001). Measurement of the coronary flow rate by the thermodilution method showed a 40 p. 100 increase in sinus blood flow while coronary resistance decreased not only in territories with normal supply but also in myocardial territories distal to the coronary stenosis (from 2.76 +/- 2.3 to 1.83 +/- 1.5 mmHg/ml, p less than 0.02). With the same paced heart rate the ventricular function parameters were significantly improved during ST2 (cardiac index ST2 3.56 +/- 0.65 vs ST1 2.8 +/- 0.48, p less than 0.001; dp/dt max ST2 2143 +/- 369 vs ST1 1874 +/- 301 mmHg/sec, p less than 0.05), reflecting a lower degree of myocardial ischaemia. This was confirmed by the lower amplitude of electrocardiographic depression and by a higher lactate extraction coefficient (LE ST1 6 +/- 7 p. 100 vs LE ST2 12 +/- 12 p. 100, p less than 0.05). Mean arterial blood pressure and coronary sinus blood flow rate values were identical during the two atrial pacing tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Details of coronary stenosis morphology influence its hemodynamic severity and distal flow reserve

Differences in coronary flow reserve with anatomically similar coronary artery stenoses have been attributed to 1) nonstandard physiologic conditions, 2) inadequacies of measurements of coronary artery stenosis dimension and/or coronary blood flow, and 3) inadequate hyperemic stimulus. Our study tested the hypothesis that details of coronary artery stenosis geometry, which may or may not be apparent on coronary angiograms, also may contribute importantly to such differences. A simple and complex coronary artery stenosis, each of which reduced vessel cross-sectional area by 84%, was introduced in random order into the left anterior descending coronary artery of nine closed-chest, sedated swine. The simple stenosis had a single lumen while the complex stenosis had five small lumena whose combined area equaled that of the single lumen stenosis. Measurements of hemodynamics and regional myocardial blood flow (microspheres) were made at control and after 10 minutes of adenosine infused at 400 micrograms/min and then at 800 micrograms/min distal to each stenosis. Both heart rate and aortic mean pressure were controlled and thus did not change versus initial baseline (129 +/- 4 minutes and 120 +/- 10 mm Hg, mean +/- SD, respectively) during the study. Baseline total flow (ml/sec) distal to the stenosis was similar at each control (1.05 +/- 0.35 vs. 0.92 +/- 0.34, simple versus complex, respectively; p = NS). At maximal adenosine, total flow with the simple stenosis was 3.44 +/- 0.92 versus 2.77 +/- 0.51 for complex (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of coronary artery lesions on the relationship between coronary perfusion pressure and myocardial blood flow during cardiopulmonary resuscitation in pigs

In subjects without coronary disease, coronary perfusion pressure generated with closed-chest cardiopulmonary resuscitation (CPR) bears a direct relationship to myocardial blood flow. The effect of coronary lesions on this relationship was studied in an experimental porcine model not requiring thoracotomy. Coronary stenoses (a 50% reduction in coronary cross-sectional area) or total coronary occlusions were created by percutaneous, transarterial catheter placement of a Teflon cylinder in the left anterior descending artery of 21 swine (30 to 60 kg). Coronary perfusion pressure, defined as the aortic diastolic pressure minus right atrial diastolic pressure, was correlated with myocardial blood flow measured with nonradioactive, colored microspheres during external chest compression CPR. Complete occlusion of the left anterior coronary artery resulted in essentially no CPR-generated blood flow to the anterior myocardium distal to the site of occlusion. Coronary perfusion pressure showed a positive correlation with myocardial blood flow above the area of occlusion (r = 0.783; p less than 0.01) but did not correlate with myocardial blood flow below the occlusion site (r = 0.239). In the presence of a patent coronary artery stenosis, coronary perfusion pressure correlated with myocardial blood flow both above (r = 0.841; p less than 0.001) and below (r = 0.508; p less than 0.05) the stenosis. During closed-chest CPR producing coronary perfusion pressures between 30 and 60 mm Hg, anterior myocardial blood flow was 109 +/- 16 ml/min/100 gm above a patent stenosis and 66 +/- 13 ml/min/100 gm below the stenosis (p less than 0.005). Over a wide range of coronary perfusion pressures, myocardial blood flow below a coronary lesion was significantly less than that above the lesion. Coronary occlusions and stenoses can substantially affect the amount of CPR-generated coronary perfusion pressure needed to produce distal myocardial blood flow.     

Transient myocardial dysfunction during pharmacologic vasodilation as an index of reduced coronary reserve: a coronary hemodynamic and echocardiographic study

Regional coronary flow reserve and regional myocardial contractility were evaluated in 29 patients after maximal pharmacologic coronary vasodilation (intravenous dipyridamole, 0.56 mg/kg body weight, administered over 4 minutes). Nineteen patients had a severe (80 to 99%) proximal and isolated stenosis of the left anterior descending coronary artery and 10 patients had normal coronary arteries; all had normal ventricular function under rest conditions. Myocardial contractility was assessed by means of continuous two-dimensional echocardiographic monitoring; coronary reserve was evaluated by coronary sinus thermodilution. After dipyridamole infusion, 9 of the 19 patients with left anterior descending artery stenosis had transient myocardial asynergy involving the septum or apex, or both (Group IA), whereas 10 patients showed no asynergy (Group IB). No impairment of contractility was observed in the 10 patients with normal coronary arteries (Group II). Coronary blood flow was measured under basal conditions and up to 10 minutes after the end of dipyridamole infusion. In patients in Group II, dipyridamole induced an increase in great cardiac vein flow of 167 +/- 68% (mean +/- SD). The 10 patients in Group IB showed a response comparable with that of the control group (Group II) (136 +/- 45% increase in great cardiac vein flow; NS versus Group II), whereas the 9 patients in Group IA had an increase of 46 +/- 30% (p less than 0.01 versus both Group IB and Group II). No significant difference was found in the angiographic severity of the stenosis expressed in terms of minimal cross-sectional area (Group IA = 0.30 +/- 0.13 mm2, Group IB = 0.34 +/- 0.18 mm2; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic response to prolonged reduction of myocardial blood flow distal to a severe coronary artery stenosis

Limited data are available concerning the effects of mild-to-moderate, sustained reductions of coronary blood flow on myocardial aerobic metabolism. This study tested the hypothesis that a sustained flow reduction distal to a severe coronary artery stenosis may be well tolerated (after the initial insult is passed) because of gradual improvement in the balance between myocardial oxygen supply and demand. Studies were performed in eight sedated, closed-chest domestic swine that were instrumented with an artificial coronary arterial stenosis (80% diameter reduction). Hemodynamics, regional myocardial blood flow and oxygen, lactate, acid, and base metabolism were measured before stenosis and at 5, 20, 60, 120, and 180 minutes after stenosis insertion. Regional myocardial function (ultrasonic length sensors) was measured serially during 2 hours in three additional swine. After stenosis placement, endocardial and transmural flows declined (p less than 0.05) compared with flows before stenosis (from 1.54 +/- 0.37 to 0.73 +/- 0.24 ml/min/g [mean +/- SD] and from 1.44 +/- 0.31 to 1.19 +/- 0.25 ml/min/g, respectively). Thereafter, flows remained unchanged for the duration of the study. Similarly, prestenosis heart rate (135 +/- 7 beats/min), aortic mean pressure (113 +/- 17 mm Hg), and tension time index (27.1 +/- 3.6 mm Hg.sec) remained constant for the duration of the study. In contrast, regional coronary venous pH declined (p less than 0.05) compared with prestenosis levels (7.35 +/- 0.02) 5 minutes after stenosis (7.28 +/- 0.04), but it returned to prestenosis levels during the next hour. Regional coronary venous PCO2 exhibited a similar pattern (i.e., acute increase during poststenosis with gradual return to prestenosis levels).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of coronary stenotic lesions on regional myocardial blood flow at rest

To determine the effect of atherosclerotic coronary lesions on myocardial blood flow in patients at rest, regional myocardial blood flow was measured distal to stenotic lesions in 29 patients with isolated proximal lesions of the left anterior descending artery. Severity of coronary stenosis was measured by computer-assisted cinevideodensitometric analysis of digitized coronary arteriograms. Regional myocardial blood flow was measured from the clearance rate of intracoronary 133Xe injected into the left main coronary artery and recorded with a multicrystal scintillation camera. In 21 patients with stenotic lesions ranging from 19% to 84% area reduction, distal regional myocardial blood flow was normal. In all eight patients with reduced regional myocardial blood flow distal to left anterior descending lesions, the minimum area of each stenotic lesion was less 0.80 mm2 (mean 0.34 +/- 0.2 mm2), minimum calculated diameter was less than 1 mm (mean 0.59 +/- 0.3 mm), and percent stenosis, based on the reduction in cross-sectional area, was greater than 85% (mean 94 +/- 4%). For all patients, distal flow, expressed as a fraction of normal flow, correlated with the lesion cross-sectional area (r = .84), minimum luminal diameter (r = .84), and percent area stenosis (r = -.70). Thus, resting myocardial blood flow distal to stenotic lesions of the proximal coronary arteries remains normal until the degree of narrowing is severe. The dimensions observed for critical coronary stenotic lesions correlate well with theoretical predictions based on fluid mechanics and with experimental preparations in laboratory animals.     

Alterations of phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty.

BACKGROUND AND OBJECTIVES. Studies using Doppler catheters to assess blood flow velocity and vasodilator reserve in proximal coronary arteries have failed to demonstrate significant improvement immediately after coronary angioplasty. Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic velocity ratio performed distal to a coronary stenosis may provide important information concerning the physiologic significance of coronary artery stenosis. This study was designed to measure these blood flow velocity variables both proximal and distal to a significant coronary artery stenosis in patients undergoing coronary angioplasty. METHODS. A low profile (0.018-in.) (0.046-cm) Doppler angioplasty guide wire capable of providing spectral flow velocity data was used to measure blood flow velocity, flow reserve and diastolic/systolic velocity ratio both proximal and distal to left anterior descending or left circumflex coronary artery stenosis. These measurements were made in 38 patients undergoing coronary angioplasty and in 12 patients without significant coronary artery disease. RESULTS. Significant improvement in mean time average peak velocity was noted in distal coronary arteries after angioplasty (before 19 +/- 12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s; after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis. Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a significant stenosis was decreased compared with that in normal vessels (1.3 +/- 0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic velocity patterns generally returned to normal, with a significant increase in mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than 0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio measured proximal to a coronary stenosis were not statistically different from values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p greater than 0.10). CONCLUSIONS. Flow velocity measurements may be performed distal to a coronary stenosis with the Doppler guide wire. Phasic velocity measurements made proximal to a coronary stenosis differed from those in the distal coronary artery. Both proximal and distal flow reserve measurements made immediately after angioplasty were of limited utility. Changes in distal flow velocity patterns and diastolic/systolic velocity ratio appeared to be more relevant than the hyperemic response in assessing the immediate physiologic outcome of coronary angioplasty.     

Collateral conductance changes during a brief coronary occlusion in awake dogs

Function of the coronary collateral circulation during the course of a single abrupt coronary occlusion was evaluated in awake dogs instrumented over the long term. Studies were performed approximately 2 weeks after collateral development had been stimulated in the dogs by partial stenosis of the proximal left circumflex coronary artery. The pressure drop from the central aorta to the distal circumflex coronary artery was measured continuously. Under control conditions and at 30 sec and 4 min of a single abrupt complete circumflex occlusion, myocardial blood flow was determined by a radioactive microsphere technique. Coronary collateral conductance was calculated as mean collateral blood flow divided by the mean drop in pressure. The following was noted in dogs that developed collateral vessels: during the coronary occlusion, mean distal circumflex coronary pressure increased from 42 +/- 9 to 49 +/- 10 mm Hg (p less than or equal to .01); mean collateral flow increased from 0.78 +/- 0.30 to 0.84 +/- 0.33 ml/min/g (p less than or equal to .05); the endocardial/epicardial flow ratio increased from 0.77 +/- 0.36 to 1.04 +/- 0.25 (p less than or equal to .01); and the coronary collateral conductance increased significantly from 0.017 +/- 0.017 to 0.021 +/- 0.021 (ml/min/g)/mm Hg (p less than or equal to .005). These data suggest that during a brief occlusion of a major coronary artery, immature coronary collateral channels do not reach maximal function immediately after the occlusion. Rather, coronary collateral conductance increases with time and may be associated with improved transmural perfusion of the myocardium.     

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.     

Effect of intraaortic balloon counterpulsation on regional myocardial blood flow and oxygen consumption in the presence of coronary artery stenosis: Observations in an awake animal model

The mechanism by which intraaortic balloon pumping ameliorates myocardial ischemia in patients with unstable angina pectoris is uncertain. Accordingly, the following study was performed to determine the effect of intraaortic balloon pumping on regional myocardial blood flow and myocardial oxygen consumption (MVO₂) distal to severe coronary artery stenosis. Nine closed chest conscious pigs were instrumented with a 7.5 mm long plastic stenosis which reduced vessel diameter by 82%. Measurements of hemodynamics, regional myocardial blood flow (microsphere technique) and MVO₂ were made (1) before intraaortic balloon pumping, (2) at the end of 15 to 20 minutes of intraaortic balloon pumping, and (3) 20 minutes after its discontinuation.Control endocardial blood flow (ml · min^{? 1} · g^{? 1}) distal to the stenosis (1.04 ± 0.20, mean ± 1 standard deviation [SD]) was less than endocardial flow in myocardium perfused by the unobstructed circumflex coronary artery (1.67 ± 0 0.77, p < 0.01). Likewise, control distal zone epicardial flow (1.16 ± 0.36) was reduced in comparison with control circumflex zone epicardial flow (1.48 ± 0.60, p < 0.01In response to intraaortic balloon pumping rate-pressure product declined versus control (10,300 ± 2,090 [SD] mm Hg · min^{? 1} to 9,110 ± 2,010, p < 0.005), whereas aortic mean diastolic pressure (mm Hg) increased versus control (109.0 ± 9.9 to 121.0 ± 13.8, p < 0.01). Distal coronary mean diastolic pressure did not change in response to intraaortic balloon pumping (61.9 ± 13.0 to 68.7 ± 16.5, p = NS). Likewise, endocardial blood flow (ml · min^{? 1} · ^{? 1}) distal to the stenosis did not change during intraaortic balloon pumping (1.00 ± 0.24) versus control (1.04 ± 0.20). In contrast, during intraaortic balloon pumping epicardial blood flow distal to the stenosis declined versus control (1.16 ± 0.36 to 1.01 ± 0.27, p < 0.05). Regional MVO₂ (ml · min^{? 1} · 100 g^{? 1}) distal to the stenosis also decreased versus control in response to intraaortic balloon pumping (12.90 ± 3.55 to 10.30 ± 2.52, p < 0.05). Furthermore, regional MVO₂ correlated well (r = 0.74, p < 0.002) with rate-pressure product.Thus, intraaortic balloon pumping reduces myocardial oxygen demand but does not improve blood flow distal to a severe coronary stenosis; (2) blood flow distal to a severe stenosis may fail to increase with intraaortic balloon pumping because (A) distal coronary mean diastolic pressure may not increase, and (B) blood vessels distal to the stenosis tend to autoregulate in response to a decline in myocardial oxygen demand; and (3) intraaortic balloon pumping ameliorates myocardial ischemia in patients with unstable angina pectoris primarily by reducing oxygen demand rather than by increasing oxygen supply.     

Myocardial protection by intracoronary nicardipine administration during percutaneous transluminal coronary angioplasty

To determine if the calcium antagonist nicardipine protects the myocardium against ischemia, myocardial lactate, hypoxanthine and prostanoid function was studied in 12 patients during percutaneous transluminal coronary angioplasty (PTCA). Values were obtained before balloon inflation and during 4 minutes after deflation. Intracoronary injection of 0.2 mg of nicardipine distal to the stenosis was done randomly before the first or second inflation; the other inflation served as a control. One minute after deflation, coronary sinus flow levels were similar during the nicardipine and control procedure (161 +/- 61 vs 159 +/- 72 ml/min); lactate (-9 +/- 21% vs -17 +/- 21%, p less than 0.025) and hypoxanthine production (-107 +/- 85% vs -218 +/- 153%, p less than 0.05) were less severe after nicardipine pretreatment than after control. All patients reverted to lactate extraction 4 minutes after inflation plus nicardipine infusion, whereas lactate was still produced 4 minutes after control inflation. No significant changes in thromboxane B2 or prostacyclin levels were observed in the coronary sinus 1 minute after inflation, but higher arterial thromboxane B2 values were observed after control inflation than after inflation with nicardipine infusion (median values 169 vs 78 pg/ml, p less than 0.05). In conclusion, intracoronary infusion of nicardipine reduced signs of ischemia and alterations in prostanoid handling after coronary occlusion. The mechanisms of myocardial protection appeared unrelated to coronary sinus blood flow changes or to a systemic effect of nicardipine.     

Tachycardia induced reduction in coronary blood flow distal to a stenosis

Clinical and experimental data indicate that some coronary stenoses can rapidly change shape thereby influencing the hemodynamic severity of the stenosis. In 7 closed chest dogs, we examined the effects of distal coronary arteriolar vasomotor tone and myocardial oxygen demands on a coronary stenosis created by partial intraluminal occlusion, using a small balloon catheter. Myocardial blood flow (ml/g per min) was measured with 15-microns radioactive microspheres. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow through the stenosis. The mean pressure gradient was calculated as the ascending aortic pressure minus the left anterior descending coronary artery pressure distal to the stenosis. Coronary arteriolar vasodilation induced by pacing (170 beats/min) increased stenotic resistance (1.64 +/- 0.27 to 26.48 +/- 13.77 mmHg/ml per min, P less than 0.05) and decreased myocardial blood flow (endocardial 0.42 +/- 0.04 to 0.17 +/- 0.04, P less than 0.05, midcardial 0.35 +/- 0.03 to 0.13 +/- 0.04, P less than 0.05; epicardial 0.22 +/- 0.05 to 0.15 +/- 0.05). Five dogs fibrillated within 10 min of continuous tachycardia and partial arterial occlusion. The change in arteriolar vasomotor tone and decreased aortic pressure induced by pacing altered the severity of the stenosis and resulted in a reduction of blood flow to the myocardium.     

Changes in ischemic blood flow distribution and dynamic severity of a coronary stenosis induced by beta blockade in the canine heart

The effects of equipotent beta 1-receptor-blocking doses of propranolol, metoprolol and sotalol on distal coronary pressure, stenosis resistance and regional myocardial blood flow (endo/epi) were studied in anesthetized dogs with a severe noncircumferential stenosis of the left circumflex coronary artery. No significant differences between the three beta blockers were observed for overall hemodynamics and regional myocardial blood flow. After drug treatment, subendocardial blood flow (0.47 +/- 0.05 to 0.78 +/- 0.05 ml/min/g) and endo/epi (0.67 +/-0.04 to 1.18 +/- 0.04) increased significantly (p less than 0.05) in the ischemic region. These changes were associated with a marked increase in distal coronary perfusion pressure and a decrease in heart rate. Resistance across the stenosis decreased significantly (p less than 0.05) after beta-receptor blockade (3.2 +/- 0.3 to 1.4 +/- 0.2 units). Atrial pacing to control heart rate only partially attenuated these changes. These results suggest that a favorable redistribution of ischemic blood flow after beta blockade is the result of an increase in distal diastolic pressure-time index and an autoregulation-induced increase in distal bed vascular resistance due to a decrease in myocardial oxygen demand associated with beta blockade. The latter effect also resulted in a decrease in the dynamic severity of a proximal coronary stenosis.     

Adverse effects of circumflex coronary artery occlusion on blood flow to remote myocardium supplied by a stenosed left anterior descending coronary artery in anesthetized open-chest dogs

Left anterior descending coronary artery occlusion in open-chest dogs causes a decrease in endocardial blood flow to the remote posterior bed supplied by a stenosed left circumflex coronary artery. To determine if "remote" myocardial ischemia also occurred in the anterior bed after circumflex occlusion, myocardial blood flow (radiolabeled microspheres) and hemodynamics were measured before and after circumflex occlusion in the presence of a stenosed left anterior descending artery (gradient: 28 +/- 2 mm Hg) in 10 open-chest dogs. Aortic pressure fell from 108 +/- 3 to 100 +/- 3 mm Hg (p = 0.02) and mean distal left anterior descending coronary artery pressure fell from 81 +/- 4 to 69 +/- 5 mm Hg (p = 0.02) after circumflex occlusion. Transmural flow to normal myocardium supplied by unstenosed and unoccluded coronary arteries increased from 0.69 +/- 0.04 to 0.84 +/- 0.04 ml/min/gm (p less than 0.0001) after circumflex occlusion. Although epicardial flow to the remote anterior bed supplied by the stenosed left anterior descending coronary artery increased after left circumflex occlusion (0.61 +/- 0.03 to 0.73 +/- 0.04 ml/min/gm, p = 0.004), remote anterior bed endocardial flow did not increase, and the remote bed endocardial:epicardial blood flow ratio decreased from 0.98 +/- 0.06 to 0.78 +/- 0.10 (p less than 0.05). Therefore, in this model, remote anterior bed ischemia, relative to the normal myocardial flow response, developed when the left circumflex coronary artery was occluded in the presence of the stenosed left anterior descending coronary artery.