ST segment response to acute coronary occlusion: coronary hemodynamic and angiographic determinants of direction of ST segment shift

To assess the relationship between the direction of ST segment response to transient coronary occlusion and collateral function, we studied 25 patients with diagnostic ST segment changes during transient occlusion of the proximal left anterior descending artery (LAD). Electrocardiographic leads I, II, V2, and V5; left ventricular filling, aortic, and distal coronary pressures; and great cardiac vein flow were measured during percutaneous transluminal coronary angioplasty (PTCA) of the LAD. During a 1 min LAD balloon occlusion, 16 patients had reversible ST elevation (group I) and nine patients had ST depression (group II). The ST responses in individual patients were consistent during repeated occlusions, and ST depression never preceded ST elevation. Angiography before PTCA showed less severe LAD stenosis in group I (69 +/- 15%) than in group II (88 +/- 10%; p less than .01) and collateral filling of the LAD in no group I patient but in six of nine patients in group II (p less than .01). During LAD occlusion, determinants of myocardial oxygen demand (left ventricular filling pressure, aortic pressure, heart rate, and double product) were similar in both groups. Group I patients, however, had lower distal coronary pressure (25 +/- 8 vs 41 +/- 16 mm Hg) and residual great cardiac vein flow (33 +/- 14 vs 51 +/- 22 ml/min) and higher coronary collateral resistance (3.1 +/- 2.1 vs 1.5 +/- 0.8 mm Hg/ml/min) than group II patients (all p less than .05). In patients with ST elevation during LAD occlusion, stenosis before PTCA was less severe, visible collaterals were not present, and hemodynamic variables during LAD occlusion reflected poorer collateral function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the relationship between distal occluded pressure and angiographically evident collateral flow during coronary angioplasty

The relationship between the presence of collateral filling on the baseline coronary angiogram and the distal occluded pressure obtained during balloon inflation was examined in 83 patients undergoing coronary angioplasty. The patients were divided into three groups: Group I (n = 40) had conventional stenoses (80% to 95% luminal diameter narrowing) without angiographically evident collaterals, group II (n = 22) had conventional stenoses with angiographically present collaterals, and group III (n = 21) had total or functional total occlusions (99% to 100% diameter narrowing) with angiographically evident collateral flow. There was no significant difference in age, sex, vessel distribution, clinical class, residual gradient, or residual percent stenosis following successful angioplasty among the three groups. The distal occluded pressure in group I (18 +/- 5 mm Hg) was, however, significantly lower than the distal occluded pressure in either group II (34 +/- 7 mm Hg) or group III (36 +/- 9 mm Hg) (p less than 0.001). This could not be explained by differences in aortic pressure, since there was no correlation between the mean aortic blood pressure and the distal occluded pressure and since the distal occluded pressure/aortic pressure ratio in group I (0.23 +/- 0.07) was significantly lower than that of group II (0.41 +/- 0.09) or group III (0.41 +/- 0.11) (p less than 0.001). These findings indicate a close correlation between the presence of angiographically evident collateral flow and the distal coronary artery pressure during an angioplasty balloon inflation.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.     

Temporal increase in resting coronary blood flow causes an impairment of coronary flow reserve after coronary angioplasty.

Impaired coronary flow reserve immediately after coronary angioplasty may be attributed to an increase in resting coronary blood flow. To test this hypothesis we measured great cardiac venous flow (GCVF) at rest and during rapid atrial pacing before and immediately after angioplasty in 22 patients with significant narrowing of the left anterior descending artery and 12 patients (control group) with minimal narrowing. A follow-up (6 months) study was also done in seven patients. Immediately after angioplasty the coronary flow reserve (peak GCVF during pacing/resting GCVF) was not fully restored (1.5 +/- 0.36 before angioplasty, 1.76 +/- 0.42 after angioplasty, and 2.13 +/- 0.33 in the control group). Resting coronary vascular resistance (2.4 +/- 0.9 mm Hg/ml/min) was significantly decreased after angioplasty (2.0 +/- 0.8 mm Hg/ml/min), whereas coronary vascular resistance during rapid pacing was fully restored to normal. Resting hyperemia was restored 6 months later, whereas coronary vascular resistance during pacing was unaltered. In five patients, however, slight ischemic ST-T changes were observed during rapid pacing, even after successful angioplasty associated with a decrease in the lactate extraction ratio. These results indicate that the impaired coronary flow reserve immediately after angioplasty may be attributed mainly to the temporal but significant increase in resting coronary flow, although impaired coronary vascular response to augmented myocardial oxygen demand may also be partially involved.     

Effect of propranolol on myocardial ischemia occurring during acute coronary occlusion

In 16 patients undergoing angioplasty of the left anterior descending coronary artery, the clinical, electrocardiographic, and hemodynamic effects of short-term intravenous nonselective beta-adrenergic blockade with propranolol (0.1 mg/kg) were assessed during temporary occlusion of the artery. Myocardial ischemia during coronary occlusion was prevented, delayed in onset, or diminished in magnitude by propranolol in 10 of the 16 patients. Propranolol decreased values for indexes of myocardial oxygen demand, such as heart rate and blood pressure and their product, in all patients. Surprisingly, in patients who derived clinical benefit, propranolol did not change indexes of myocardial oxygen supply to the left ventricular region perfused by the occluded artery. For example, great cardiac vein flow (40 +/- 15 to 41 +/- 17 ml/min, p = NS) and coronary collateral resistance (2.1 +/- 1.0 to 2.1 +/- 1.1 mm Hg/ml/min, p = NS) were unchanged. In contrast, a worsening of supply occurred in patients who were not benefited: great cardiac vein flow (50 +/- 10 to 39 +/- 6 ml/min, p less than .05) decreased and coronary collateral resistance (1.6 +/- 0.5 to 2.0 +/- 0.6 mm Hg/ml/min, p less than .05) increased. Information obtained from this study demonstrates the value of this new experimental preparation in helping assess potential clinical effectiveness of drug interventions during the initial phase of acute coronary occlusion and providing insight into the mechanisms of drug effect.     

The efficacy of intermittent coronary sinus occlusion in the absence of coronary artery collaterals

The purpose of this study was to evaluate the efficacy of time-controlled intermittent coronary sinus occlusion (ICSO) in preserving regional and global mechanical function during acute ischemia in an animal preparation without significant arterial collateral vessels. Seventeen (eight control, nine ICSO) swine heart preparations undergoing extracorporeal coronary perfusion in situ were subjected to ligation of the left anterior descending coronary artery (LAD) distal to the first major diagonal branch. Data were obtained before and immediately after coronary artery ligation in both animal groups. ICSO, 15 sec of occlusion alternating with 5 sec of release, was then begun in the treatment group. Additional data were obtained in both control and treatment groups at 15 min intervals for 1 hr starting immediately after coronary artery ligation. Global left ventricular function was assessed by shifts in left ventricular end-diastolic pressure and left ventricular dP/dt with left ventricular systolic pressure maintained at about 100 mm Hg. Regional mechanical function was evaluated with transmurally placed ultrasonic crystals. Pressure was also measured directly in the coronary sinus and LAD distal to the ligature. Regional myocardial blood flow was measured in the ischemic bed using 9 micron diameter radiolabeled microspheres injected before, immediately after, and 60 min after coronary artery ligation in both treated and control animals. LAD mean pressure measured distal to the ligation (less than 16 mm Hg) and ischemic bed myocardial blood flow (less than 0.01 ml/g/min) confirmed the absence of significant arterial-arterial collaterals in this preparation. Mean coronary sinus pressure increased significantly (p less than .001) in treated animals during ICSO (e.g., 11.2 +/- 1.6 to 66.2 +/- 10.0 mm Hg at 15 min after coronary ligation). Mean LAD pressure distal to the coronary ligature also increased during ICSO (14.2 +/- 1.2 to 26.8 +/- 1.6 mm Hg), with a similar but delayed rate of pressure rise. No significant differences in left ventricular end-diastolic pressure or left ventricular dP/dt were noted between control or treated animals after coronary ligation. Ischemic bed systolic wall thickening, present before coronary ligation, was not present after occlusion and was not improved during intermittent coronary sinus occlusion in the treatment group. We conclude that in an animal preparation without significant collateral circulation, intermittent coronary sinus occlusion is incapable of restoring regional or global left ventricular mechanical function during conditions of acute ischemia.     

Effects of diltiazem on regional coronary hemodynamics during atrial pacing in patients with stable exertional angina: implications for mechanism of action

To investigate the mechanism of the antianginal action of diltiazem in stress-induced myocardial ischemia, we studied 12 patients with stable exertional angina and disease of the proximal left anterior descending artery by measuring great cardiac vein flow (GVCF) and calculating anterior regional coronary resistance (ARCR) during myocardial ischemia induced by atrial pacing before and after intravenous administration of diltiazem (0.25 mg/kg in a bolus dose followed by continuous infusion of 0.005 mg/kg/min). Diltiazem increased the pacing time to angina from 6.9 +/- 3.5 to 10.7 +/- 4 min (p less than .001). At peak pacing heart rate was increased after diltiazem (from 128 +/- 17 to 145 +/- 17 beats/min, p less than .005), while mean arterial pressure was decreased (from 131 +/- 19 to 113 +/- 17 mm Hg, p less than .025), leaving the double product unaltered. At peak pacing no changes were observed in GCVF (from 115 +/- 46 to 119 +/- 46 ml/min, p = NS), ARCR (from 1.3 +/- 0.4 to 1.1 +/- 0.4 mm Hg/ml/min), or myocardial oxygen consumption of the anterior region (from 14.5 +/- 4.2 to 13.4 +/- 4.7 ml/min). Reduction of myocardial oxygen demand plays a major role in the antianginal action of diltiazem in patients with stress-induced myocardial ischemia.     

Coronary hemodynamic and myocardial metabolic alterations accompanying coronary spasm.

Arterial pressure, coronary sinus blood flow with the thermodilution technique and calculated coronary vascular resistance were measured and coronary arteriography performed at rest and after the administration of ergonovine in 14 patients with atypical chest pain (group 1) and 6 patients with variant angina (group II). Mild diffuse narrowing of the left coronary bed in group I was not accompanied by S-T segment shifts, and coronary vascular resistance did not change significantly. In contrast, severe focal spasm (greater than 90 percent narrowing) of the left anterior descending coronary artery in group II patients was accompanied by S-T elevation and a marked overall increase in coronary vascular resistance (from 0.65 +/- 0.07 to 1.14 +/- 0.10 mm Hg/ml per min) (P less than 0.005). In addition, the myocardial arteriovenous oxygen difference increased and net lactate extraction changed to lactate production in the two patients in group II in whom these measurements were made. Thus, thermodilution coronary sinus blood flow measurement may be a sensitive method for detecting primary increases in coronary vascular resistance due to a high grade focal spasm in the left anterior descending coronary artery.     

Coronary pressure-flow relations in hypertensive left ventricular hypertrophy. Comparison of intact autoregulation with physiological and pharmacological vasodilation in the dog

Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during perfusion of the circumflex artery by an extracorporeal circuit at controlled diastolic pressures of 20-200 mm Hg. Autoregulated pressure-flow relations were compared at three levels of myocardial oxygen demand: resting, high (dobutamine 10 micrograms/kg/min), and low (propranolol 2.5 micrograms/kg/min). Autoregulatory capacity was assessed by calculation of closed-loop flow gain. At each level of myocardial oxygen demand, the lower limit of autoregulation occurred at higher perfusion pressures in the hypertrophy group (rest 65 +/- 3, high 92 +/- 4, low 66 +/- 4 mm Hg) than in the normal group (rest 53 +/- 2, p less than 0.05; high 75 +/- 5, p less than 0.05; low 51 +/- 3 mm Hg) (p less than 0.05). Maximum autoregulatory gain was similar in the normal and hypertrophy groups during resting and low myocardial oxygen demand but was reduced in the hypertrophy group during dobutamine studies. When coronary flow decreased below the lower limit of autoregulation, systolic shortening was reduced in both normal and hypertrophy groups. However, as the autoregulatory limits were at higher pressures in the hypertrophy group, shortening in this group deteriorated at perfusion pressures that did not affect the normal heart. Coronary pressure-flow relations during physiological (peak hyperemia after 15-second flow occlusion) and pharmacologica (intracoronary adenosine 400 micrograms/min) vasodilation was curvilinear and fitted by quadratic regression. During hyperemic vasodilation, maximal conductance per unit mass of myocardium was less in the hypertrophy group over a wide range of perfusion pressures. At a diastolic perfusion pressure of 80 mm Hg, maximum conductance was 4.6 +/- 0.5 ml/min/100 g/mm Hg in the normal group and 3.4 +/- 0.4 ml/min/100 g/mm Hg (p less than 0.05) in the hypertrophy group. Intracoronary adenosine elicited further vasodilation in both groups, but maximum conductance remained less in the hypertrophy group (8.5 +/- 1.7 ml/min/100 g/mm Hg at a perfusion pressure of 80 mm Hg) than in the normal group (13.5 +/- 2.0 ml/min/100 g/mm Hg) (p less than 0.05). Maximal coronary flow reserve is reduced in left ventricular hypertrophy, with a consequent shift of the lower limit of autoregulation to higher perfusion pressures. Thus, as coronary perfusion pressure is decreased, coronary flow and myocardial shortening become impaired at higher     

Effect of the calcium antagonist nisoldipine on coronary circulation and myocardial ischemia in temporary coronary occlusion

Sixteen patients undergoing PTCA of a significant lesion of the left anterior descending coronary artery received either 0.3 mg nisoldipine or placebo intravenously. Immediately before and during balloon inflation the following parameters were measured: aortic pressure, post-stenotic pressure, coronary occlusion pressure, diastolic pulmonary artery pressure, coronary sinus flow (thermodilution), and intracoronary ECG. After placebo there were no statistically significant changes. Nisoldipine led to a decrease in aortic pressure from 109 +/- 12 to 93 +/- 11 mm Hg (p less than 0.05) before, and from 103 +/- 14 to 92 +/- 8 mm Hg (NS) during balloon inflation. In contrast, coronary occlusion pressure remained unchanged. Heart rate increased from 80 +/- 13 to 96 +/- 16/min before (p less than 0.05), and from 87 +/- 18 to 97 +/- 17/min during balloon inflation (NS). Coronary sinus flow was increased from 95 +/- 16 to 116 +/- 13 ml/min before balloon inflation (p less than 0.01), and from 70 +/- 25 to 86 +/- 26 ml/min during balloon inflation (NS). ST-segment depression or elevation, severity of angina pectoris, and the diastolic pulmonary artery pressure remained unchanged. Thus, 0.3 mg nisoldipine led to a peripheral vasodilatation. While the aortic pressure decreased, coronary occlusion pressure remained unaffected. This could be explained by a marked dilatation of collateral vessels due to nisoldipine. However, myocardial ischemia remained unaffected as a result of the constant coronary occlusion pressure.     

Absence of functioning alpha-adrenergic receptors in mature canine coronary collaterals

To determine if mature coronary collateral vascular smooth muscle contains functioning alpha-adrenergic receptors, we studied 13 dogs, 6-10 months after circumflex ameroid occlusion. Regional myocardial blood flow was measured with radioactive microspheres in a blood-perfused heart preparation at constant aortic pressure (80 mm Hg). Normal zone resistance was calculated as aortic pressure divided by normal zone flow, and transcollateral resistance was calculated as aortic pressure minus circumflex pressure distal to the ameroid constrictor divided by coronary collateral flow. Flow and resistance were measured during adenosine vasodilation before and during graded doses of a constant infusion of the alpha-adrenergic agonist methoxamine (n = 6) or the alpha 2-adrenergic agonist clonidine (n = 7). In the hearts that received methoxamine, normal zone resistance increased from a control of 0.29 +/- 0.06 to 0.39 +/- 0.06 mm Hg X min/ml per 100 g (resistance units) during infusion of 10(-5)M methoxamine (p less than 0.05). In contrast transcollateral resistance averaged 0.24 +/- 0.02 resistance units under control conditions and did not change during methoxamine infusion. In the hearts that received clonidine, normal zone resistance averaged 0.24 +/- 0.03 resistance units and increased to 0.39 +/- 0.07 resistance units (p less than 0.05) with the highest dose of clonidine administered (10(-5) M). Transcollateral resistance averaged 0.17 +/- 0.03 resistance units during control conditions and did not change with clonidine infusion. In separate studies isometric tension development by the left anterior descending and coronary collateral vessels was examined in organ baths. The left anterior descending coronary artery demonstrated dose-dependent constriction to phenylephrine (peak response 22 +/- 5% of the response to 100 mM KCl). Clonidine produced weak constrictor responses in the left anterior descending coronary artery (5 +/- 2.5% maximal KCl response). In contrast, neither phenylephrine nor clonidine produced responses in mature collaterals. We also examined responses of mature collateral vessels to nonadrenergic agonists. In the vascular ring preparation the mature collaterals developed tension in the presence of KCl (2.3 +/- 0.9 g), prostaglandin F2 alpha (16 +/- 18% of the KCl responses), and vasopressin (90 +/- 30% of the KCl response). In adenosine-vasodilated hearts, pharmacologic doses of vasopressin caused a two-fold increase in transcollateral resistance. Thus, these studies performed on intact hearts and isolated vascular rings demonstrate that mature coronary collaterals do not contain functioning alpha-adrenergic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Potential protective effect of high coronary wedge pressure on left ventricular function after coronary occlusion

To assess the potential of coronary collateral circulation to protect myocardium after occlusion of a coronary vessel, the mean coronary wedge pressure, the angiographic grade of collateral channels, and the left ventricular function were studied in 47 consecutive patients with mechanical recanalization of totally occluded coronary arteries. Coronary wedge pressure measurements were obtained 39 +/- 51 days (range, 2 hours to 361 days) after the presumed time of occlusion. The patients were divided into two groups: 31 with a coronary wedge pressure more than 30 mm Hg (group 1) and 16 with a coronary wedge pressure of or less than 30 mm Hg (group 2). Patients in group 1 had a significantly higher mean global left ventricular ejection fraction than those in group 2 (63 +/- 9% vs. 49 +/- 7%, p less than 0.001). Regional left ventricular function (artery-related area change) was also superior in group 1 compared with group 2 (47 +/- 11% vs. 36 +/- 10%, p less than 0.01). Global left ventricular function was significantly correlated to coronary wedge pressure (r = 0.51, p less than 0.001) but not to the angiographic presence of collaterals. The data suggest that a high coronary wedge pressure is associated with improved left ventricular function after coronary artery occlusion and that coronary wedge pressure more accurately reflects the physiological role of collaterals than their angiographic presence.     

Dynamic limitation of coronary vasodilator reserve in patients with dilated cardiomyopathy and chest pain

Twenty-six patients with dilated cardiomyopathy and angiographically normal coronary arteries, 12 of whom gave a history of anginal chest pain, underwent noninvasive and invasive hemodynamic study. During treadmill exercise testing, patients with a history of angina demonstrated worse effort tolerance (7.4 +/- 4.9 versus 13.6 +/- 5.1 minutes, p less than 0.005) and a lower end-exercise systolic blood pressure-heart rate product (17.9 +/- 3.4 versus 23.6 +/- 4.9 mm Hg.beats/min x 10(3), p less than 0.005) compared with patients without a history of angina. During rapid atrial pacing after ergonovine, 0.15 mg intravenously, 11 of the 12 patients with a history of angina experienced their typical chest pain, in contrast to only 1 of 12 patients without a history of angina. The angina group, compared with the nonangina group, had significantly lower great cardiac vein flow (118 +/- 24 versus 160 +/- 43 ml/min, p less than 0.01), and higher coronary resistance (0.87 +/- 0.21 versus 0.66 +/- 0.25 mm Hg.min/ml, p less than 0.05), significant widening of the arterial--great cardiac vein oxygen difference and a significant fall in cardiac index during pacing. Further, ergonovine resulted in higher coronary resistance during pacing in the angina group compared with pacing alone (+0.16 +/- 0.16 mm Hg min/ml, p less than 0.01), in the absence of significant reduction in epicardial coronary artery luminal diameter. After dipyridamole, 0.5 to 0.75 mg/kg intravenously, to 21 patients, the 7 patients with a history of angina had significantly lower flow (149 +/- 37 versus 218 +/- 73 ml/min, p less than 0.05) and higher coronary resistance (0.59 +/- 0.09 versus 0.43 +/- 0.17 mm Hg.min/ml, p less than 0.05) than did the nonangina group. It is concluded that patients with dilated cardiomyopathy and chest pain unrelated to epicardial coronary artery disease exhibit impaired vasodilator responses to both metabolic and pharmacologic stimuli, and an increased sensitivity to the vasoconstrictor effects of ergonovine. Whether these findings are of etiologic or long-term prognostic significance is unknown.     

A study on coronary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina: endothelium-dependent dilation in the resistance vessels.

The epicardial coronary artery of patients with variant angina is hyperreactive to the constrictive effect of acetylcholine, but it is not known whether the coronary microvasculature also constricts in response to acetylcholine. Incremental doses of acetylcholine were injected into the left coronary artery of 57 patients with variant angina and with spasm in this artery. By measuring coronary sinus blood flow, coronary hemodynamic status just before angiographic documentation of spasm was examined. Acetylcholine induced spasm in the left coronary artery in all patients. It also decreased the diameter of the nonspasm artery by 36 +/- 19% from baseline. For all patients, coronary sinus blood flow was 89 +/- 38 ml/min at baseline and increased to 104 +/- 61 ml/min during an acetylcholine-induced anginal attack (p less than 0.01). In 10 patients with spasm in both the left anterior descending and left circumflex arteries (that is, multivessel spasm), coronary sinus blood flow decreased from 84 +/- 21 to 52 +/- 26 ml/min (p less than 0.01). In the other 47 patients with spasm in only one of these two arteries (that is, single-vessel spasm), coronary sinus blood flow increased from 90 +/- 41 to 115 +/- 61 ml/min (p less than 0.01) without change in the rate-pressure product. It is concluded that in patients with variant angina, acetylcholine induces spasm and constriction in the epicardial coronary artery, whereas it dilates the resistance vessels presumably through the release of the endothelium-dependent relaxing factor.     

Effect of activation of the H1 receptor on coronary hemodynamics in man

We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.     

Reduction of pulmonary capillary blood volume following cold exposure in patients with Raynaud's phenomenon

In a previous study we induced digital vasospasm with cold pressor stimulus, and an acute decrease in the lung diffusing capacity for carbon monoxide (Dsb) resulted. We hypothesized its cause to be spasm occurring simultaneously in the pulmonary vasculature and the digital arteries. We measured in this study the Dsb, the diffusing capacity of the pulmonary membrane (Dm), and the volume of blood in the pulmonary capillaries (Vc) after cold-induced digital vasospasm in patients with Raynaud's phenomenon. Control subjects showed no significant decrease in Dsb, Dm, or Vc after cold exposure. Eight of 12 subjects with Raynaud's phenomenon had a significant decrease in Dsb 60 min after testing (25.3 +/- 6.6 vs 19.8 +/- 6.1 ml/min/mm Hg, p less than 0.01). The acute decrease in Dsb was due to a significant decrease in Vc (54 +/- 20 vs 39 +/- 10 ml, p less than 0.05), while Dm was unchanged (52 +/- 17 vs 51 +/- 20 ml/min). Four subjects who had a decrease in Dsb after cold challenge had repeated studies later after pretreatment with sublingual nifedipine. The magnitude of change in Dsb was similar to that observed in the untreated state (23.6 +/- 10.6 vs 20.9 +/- 9.6 ml/min/mm Hg). We conclude that digital vasospasm is accompanied by an acute reduction in Vc in both primary and secondary Raynaud's phenomenon and indicates concurrent vasoconstriction within the pulmonary vaculature.     

Effects of inotropic and chronotropic stimuli on acute myocardial ischemic injury. III. Influence of basal heart rate

The influence of basal heart rate (HR) on the effects of inotropic (dobutamine infusion) and chronotropic (atrial pacing) stimuli during acute myocardial ischemia was assessed by measurement of intramural carbon dioxide partial pressure (PCO2) in open-chest dogs undergoing transient 10-minute left anterior descending coronary artery occlusions. In protocol I, in 5 dogs anesthetized with pentobarbital alone, HR increased from 153 +/- 10 to 182 +/- 7 beats/min between experimental coronary occlusions, but the increase in ischemic zone intramural carbon dioxide tension (delta PmCO2) was not altered by this significant increase in HR. In protocols II to V, dogs were anesthetized with combinations of morphine, thiamylal and pentobarbital and had a basal average HR of 81 beats/min. Atrial pacing in protocol II (13 dogs) increased HR from 76 +/- 21 to 134 +/- 19 beats/min (p less than 0.001); left ventricular (LV) myocardial oxygen consumption (MVO2) rose from 3.9 +/- 1.6 to 4.9 +/- 1.4 ml/min/100 g (p less than 0.05), and delta PmCO2 rose from 42 +/- 14 to 50 +/- 15 mm Hg (p less than 0.01), indicating more severe ischemic injury during the second experimental coronary occlusion. In protocol III, 11 dogs received 20 micrograms/kg/min of dobutamine before the second experimental occlusion, which significantly (p less than 0.02) increased HR, LV dP/dt and MVO2; delta PmCO2 increased from 46 +/- 13 to 63 +/- 18 mm Hg (p less than 0.01). The 7 dogs in protocol IV received 3.9 +/- 1.9 micrograms/kg/min of dobutamine, titrated such that HR was unchanged (84 +/- 10 vs 81 +/- 15 beats/min), but LV dP/dt increased by 92% (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Provocation of coronary vasospastic angina using an isoproterenol head-up tilt test

The goals of this study were to determine the value of the isoproterenol (ISO) head-up tilt (HUT) test in detecting coronary vasospastic angina and to investigate the possible mechanism responsible for coronary artery spasm. The ISO + HUT test was performed in 16 patients with coronary artery spasm documented by the intracoronary ergonovine provocation test. Patients' blood pressure and heart rate were measured at baseline, during the ISO + HUT (phase I), and during HUT after discontinuation of ISO (phase II). Patients were categorized as test-positive if they developed angina with ST-segment elevation during testing. Eight patients (50%) were test-positive (5 in phase I and 3 in phase II). Between the test-positive and test-negative groups, no significant differences were noted in the changes in blood pressure throughout the test. However, there were significant differences in the changes in heart rate from supine to 2 minutes after HUT under ISO infusion (-17 +/-22 vs 11 +/-25 beats/minute; p=0.035). In those patients with a positive result in the phase I stage, the heart rate decreased initially after tilt-up, and then significantly increased later (from 85 +/-16 to 110 +/-27 beats/minute; p=0.043), when coronary vasospasm occurred. In those patients with a positive result in the phase II stage, coronary vasospasm occurred immediately after HUT, when there was an insignificant transient increase in heart rate from the supine to the HUT position (from 85 +/-12 to 92 +/-11 beats/minute; p=0.109). The ISO + HUT test can provoke coronary vasospasm with ST-segment elevation in 50% of the patients with coronary artery spasm, when combined with an extensional protocol of HUT after discontinuation of ISO. This study suggests that the induction of coronary artery spasm during HUT testing is associated with a rapid elevation of sympathetic activity during augmented parasympathetic activity.