Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.     

Decreased coronary reserve in primary scleroderma myocardial disease

We assessed coronary reserve, by measuring the increase in coronary sinus blood flow (CSBF) after intravenous administration of dipyridamole (0.14 mg/kg/minute for 4 minutes), in 7 patients with primary scleroderma myocardial disease (PSMD) and in 7 control subjects. Coronary reserve was greatly impaired in PSMD: before administration of dipyridamole, CSBF was similar in patients with PSMD (89 +/- 32 ml/minute/100 gm, mean +/- SD) and in controls (100 +/- 15 ml/minute/100 gm); after dipyridamole infusion, CSBF was significantly lower in patients with PSMD (191 +/- 45 ml/minute/100 gm) than in controls (399 +/- 58 ml/minute/100 gm) (P less than 0.01). Six of the 7 patients with PSMD had angiographically normal epicardial coronary arteries and normal left ventricular function. Decreased coronary reserve may be an important contributor to the pathogenesis of primary scleroderma myocardial disease.     

Reduced coronary flow and resistance reserve in primary scleroderma myocardial disease

The maximum coronary vasodilator capacity after intravenous dipyridamole (0.14 mg X kg-1 X min-1 X 4 minutes) was studied in seven patients with primary scleroderma myocardial disease and compared to that of seven control subjects. Hemodynamic data and left ventricular angiographic data were not different in the two groups. The coronary flow reserve was evaluated by the dipyridamole/basal coronary sinus blood flow ratio (D/B CSBF) and the coronary resistance reserve by the dipyridamole/basal coronary resistance ratio (D/B CR). Coronary reserve was greatly impaired in the group with primary scleroderma myocardial disease: D/B CSBF was lower than in the control group (2.54 +/- 1.37 vs 4.01 +/- 0.56, respectively; p less than 0.05) and D/B CR was higher than in the control group (0.47 +/- 0.25 vs 0.23 +/- 0.04, respectively; p less than 0.05). Such a decreased coronary flow and resistance reserve in patients with primary scleroderma myocardial disease was not explained by an alteration of left ventricular function. It may be an important contributing factor in the pathogenesis of primary scleroderma myocardial disease.     

Combined effects of nitrates on the coronary and peripheral circulation in exercise-induced ischemia

We compared the effects of isosorbide dinitrate (ISDN) administered by intracoronary and intravenous routes in 10 patients with severe coronary artery disease, stable effort angina, and very low exercise tolerance. Supine bicycle ergometer exercise was performed under four conditions: 1) control, 2) after intracoronary administration of 0.4 mg ISDN, 3) 1 hour later (control 2), and 4) after administration of intravenous 4 mg ISDN. At rest, intracoronary ISDN caused no significant hemodynamic effects, whereas intravenous infusion of ISDN resulted in a decline in left ventricular (LV) systolic pressure (-20 +/- 5 mm Hg), LV end-diastolic volume (-27 +/- 3%), and LV end-systolic volume (-30 +/- 4%). After intracoronary infusion of ISDN, ST segment depression and the increase in LV end-diastolic pressure and LV end-systolic volume induced by exercise were significantly less abnormal than during control (0.20 +/- 0.09 vs. 0.14 +/- 0.08 mV, 36 +/- 7 vs. 24 +/- 8 mm Hg, and 91 +/- 40% vs. 40 +/- 29%, respectively). When exercise was performed after intravenous infusion of ISDN, the above-mentioned parameters were significantly improved even further: ST segment depression to 0.05 +/- 0.07 mV, end-diastolic pressure to 14 +/- 7 mm Hg, and LV end-systolic volume to 5 +/- 11% (all p less than 0.01 compared with intracoronary ISDN). Thus, in patients with severe coronary artery disease, it is suggested that intracoronary nitrates increase coronary blood supply during effort-induced ischemia, based on significant improvements in the indirect measures of ST segment depression, LV end-diastolic pressure, and LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atrial natriuretic factor on coronary hemodynamics and myocardial energetics in patients with heart failure

Synthetic analogues of atrial natriuretic factor (ANF) have been developed for potential use as therapeutic agents in the treatment of congestive heart failure and hypertension. We studied the effects of 14 intravenous infusions of synthetic ANF (anaritide, human ANF 102-126) on coronary hemodynamics and myocardial energetics in six patients with heart failure. ANF infusion caused no change in coronary blood flow and a fall in coronary vascular resistance from 1.22 +/- 0.22 to 1.08 +/- 0.18 mm Hg-min/ml (p less than 0.05). Myocardial oxygen and lactate consumption were unchanged from baseline values. Mean arterial pressure fell from 91 +/- 4 to 78 +/- 3 mm Hg (p less than 0.01), right atrial pressure fell from 10 +/- 1 to 8 +/- 1 mm Hg (p less than 0.01), pulmonary capillary wedge pressure fell from 21 +/- 3 to 16 +/- 2 mm Hg (p less than 0.01), heart rate and cardiac index were unchanged, and systemic vascular resistance fell from 1346 +/- 130 to 1087 +/- 98 dyne-sec/cm5 (p less than 0.05). We conclude that infusion of ANF in hemodynamically effective doses in patients with heart failure decreases coronary vascular resistance with no change in coronary blood flow or myocardial oxygen or lactate metabolism.     

Effects of calcitonin gene-related peptide on cardiac contractility, coronary hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.

This study was performed to examine the effects of calcitonin gene-related peptide on cardiac function and coronary circulation in patients with heart failure. Synthetic human calcitonin gene-related peptide was infused in the left main coronary artery of 9 patients undergoing cardiac catheterization at different doses corresponding to incremental infusion rates of 15, 50, 150 and 600 pmol.min-1. No hemodynamic change was observed in response to administration of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1 resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8 +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/- 0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/- 3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were associated with a significant increase in plasma norepinephrine and epinephrine concentrations. Peak positive first derivative of left ventricular pressure did not change at any infusion rate. Left ventricular end-diastolic pressure decreased at the 2 highest doses associated with a decrease in plasma atrial natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left atrial function in acute transient left ventricular ischemia produced during percutaneous transluminal coronary angioplasty of the left anterior descending coronary artery

Left atrial (LA) function was studied in 32 patients during percutaneous transluminal coronary angioplasty of the proximal left anterior descending artery with a dual micromanometer positioned transseptally in the left atrium and in the left ventricle. In 10 patients LA and left ventricular (LV) cineangiography was performed 30 minutes before percutaneous transluminal coronary angioplasty and 30 seconds after the occlusion of the left anterior descending coronary artery. Thirty seconds after left anterior descending occlusion, LV peak systolic pressure decreased from 135 +/- 12 to 106 +/- 9 mm Hg (p less than 0.05) and LV maximum dP/dt decreased from 1,634 +/- 136 to 1,137 +/- 127 mm Hg/s (p less than 0.01). Simultaneously, LA mean pressure increased from 11 +/- 2 to 29 +/- 1 mm Hg (p 177 +/- 13 to 381 +/- 21 mm Hg (p less than 0.001). There was a difference between LV end-diastolic pressure and LA mean pressure of 1.5 mm Hg at rest and 7.8 mm Hg during ischemia and LA pulse pressure increased from 16 +/- 3 to 26 +/- 3 mm Hg (p less than 0.05) together with increase of LA A and V waves peak pressure. LV stroke volume index decreased from 46 +/- 5 to 43 +/- 3 ml/m2 (difference not significant). The LA maximal volume increased from 18 +/- 2 to 29 +/- 3 ml/m2 (p less than 0.001). LA volume before LA contraction increased from 29 +/- 2 to 54 +/- 3 ml/m2 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique

Angiotensin II elicits contractile responses in the coronary arteries and myocardial tissue, which suggests that blockade of the renin-angiotensin system by specific agents should lead to both coronary vasodilation and an alteration of left ventricular inotropism. The present work was designed to delineate--independently from its systemic effects--the intrinsic actions of an angiotensin converting-enzyme inhibitor on the coronary circulation and left ventricular function. To minimize peripheral effects, a bilateral intracoronary infusion of enalaprilat (0.05 mg.min-1, 1 ml.min-1 in each coronary artery) was performed in 16 patients with dilated cardiomyopathy. All patients had normal coronary arteriograms. In 12 patients (group I) the intracoronary infusion of enalaprilat resulted in minimal peripheral changes, with a 5% reduction in the mean aortic pressure (p less than .05) and no significant alteration in indexes of preload, i.e., left ventricular end-diastolic pressure and volume, or of afterload, i.e., left ventricular end-systolic stress and systemic resistances. Myocardial oxygen consumption was also unaffected by the intracoronary infusion of enalaprilat. Coronary vasodilation was demonstrated by a significant elevation of coronary sinus blood flow (+19%, from 181 +/- 73 to 214 +/- 79 ml.min-1, p less than .001) and a reduction of coronary resistance (-18%, from 0.51 +/- 0.17 to 0.41 +/- 0.15 mm Hg.ml-1.min, p less than .001), with a parallel increase in coronary sinus oxygen content and pressure (both p less than .05). Oxygen extraction by the myocardium was reduced (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of coronary vasodilation with intravenous dipyridamole and adenosine.

Although both intravenous dipyridamole and adenosine have been used to produce coronary vasodilation during cardiac imaging, the relative potency of the commonly administered doses of these agents has not been evaluated. Accordingly, the coronary and systemic hemodynamic effects of intravenous adenosine (140 micrograms/kg per min) and intravenous dipyridamole (0.56 mg/kg over 4 min) were compared with a maximally dilating dose of intracoronary papaverine in 15 patients. Coronary blood flow responses were assessed using a Doppler catheter in a nonstenotic coronary artery. The protocol was discontinued in two patients because of transient asymptomatic atrioventricular (AV) block during adenosine infusion. The mean heart rate increased more with adenosine (11 +/- 9 beats/min) and dipyridamole (11 +/- 7 beats/min) than with papaverine (4 +/- 3 beats/min, p less than 0.05 vs. adenosine and papaverine). The mean arterial pressure decreased less with dipyridamole (-10 +/- 3 mm Hg) and papaverine (-9 +/- 4 mm Hg) than with adenosine (-16 +/- 5 mm Hg, p less than 0.01 vs. dipyridamole and papaverine). The peak/rest coronary blood flow velocity ratio was greater with papaverine (3.9 +/- 1.1) than with adenosine (3.4 +/- 1.2, p less than or equal to 0.05 vs. papaverine) or dipyridamole (3.1 +/- 1.2, p less than 0.01 vs. papaverine). A larger decrease in coronary resistance as measured by the coronary vascular resistance index occurred with papaverine (0.25 +/- 0.06) and adenosine (0.26 +/- 0.09) than with dipyridamole (0.31 +/- 0.10, p less than 0.01 vs. papaverine, p less than 0.05 vs. adenosine).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and echocardiographic assessment of the effects of diltiazem during transient occlusion of the left anterior descending coronary artery during percutaneous transluminal coronary angioplasty

The effects of diltiazem during transient myocardial ischemia were studied in 17 patients (age 58 +/- 11 years, 12 men, 5 women) undergoing 1-vessel left anterior descending percutaneous transluminal coronary angioplasty (PTCA). After hemodynamic, echocardiographic and electrocardiographic data were obtained during the control ischemic periods, diltiazem (10 mg intravenous bolus with 500 micrograms/min infusion) was given and 15 minutes later ischemia reinduced. Diltiazem reduced mean arterial pressure (113 +/- 16 to 95 +/- 15 mm Hg, p less than 0.05) and heart rate-pressure product (p less than 0.05) with no change in heart rate, pulmonary pressures or coronary (sinus, thermodilution technique) blood flow at rest. After diltiazem, times to ischemia-induced 1.0 mm ST-segment elevation (28 +/- 10 to 42 +/- 17 seconds, p less than 0.05) and new left ventricular wall motion abnormalities (by 2-dimensional echocardiography, 24 +/- 8 to 36 +/- 12 seconds, p less than 0.001) were prolonged without significant augmentation of great cardiac vein flow during coronary occlusion. Left ventricular (LV) ejection fraction decreased from 51 +/- 7 to 41 +/- 12% (p less than 0.05) during control ischemia, but declined less after diltiazem (54 +/- 12 to 47 +/- 14%, difference not significant; 47 +/- 14 vs 41 +/- 12%, p less than 0.01). Diltiazem can attenuate, but not abolish, some of the effects of myocardial ischemia on LV function during transient coronary artery occlusion. These data support the use of diltiazem as a beneficial adjunct that may be used acutely and safely during routine PTCA.     

Multifactorial determinants of reduced coronary flow reserve after dipyridamole in dilated cardiomyopathy

Coronary sinus blood flow (ml/100 g left ventricular [LV] mass/min) and coronary resistance (mean aortic minus LV mean diastolic pressures/coronary sinus blood flow, mm Hg/[ml/100 g/min]) were studied in 7 control patients and in 11 patients with severe dilated cardiomyopathy (DC) and normal coronary arteriograms. Basal coronary sinus blood flow was not different in the 2 groups. After intravenous administration of dipyridamole (0.14 mg/kg/min X 4 min), coronary sinus blood flow and dipyridamole/basal coronary sinus blood flow ratio were significantly (p less than 0.001) lower in the DC group than in the normal group (coronary sinus blood flow 188 +/- 48 vs 408 +/- 58, respectively; blood flow ratio 1.78 +/- 0.35 vs 4.01 +/- 0.56, respectively), and the coronary resistance was higher in the DC group than in the control group (0.39 +/- 0.15 vs 0.22 +/- 0.03, respectively, p less than 0.01). After administration of dipyridamole in patients with DC, no correlation could be found between coronary sinus blood flow and LV mean diastolic, mean aortic or coronary driving pressures, i.e., mean aortic minus LV mean diastolic pressures. Thus, in DC patients, neither an elevated LV diastolic pressure nor a low coronary perfusion pressure can totally account for the restriction of the coronary flow reserve after dipyridamole.     

Load dependence of left ventricular diastolic pressure-volume relations during short-term coronary artery occlusion.

We evaluated the effect of altered loading conditions on left ventricular (LV) diastolic pressure-volume relations during acute coronary artery occlusion that was produced by inflation of an intracoronary balloon. Open-chest anesthetized dogs (n = 18) were instrumented so that LV pressure (micromanometer) and LV volume (conductance) could be measured without disturbing the pericardium. The effects of brief periods of occlusion (1-2 minutes) were assessed under steady-state conditions before and after dextran infusion with the pericardium present and absent and during vena caval occlusion. Under steady-state conditions before dextran infusion with the pericardium removed, at an LV end-diastolic pressure (EDP) of 8.4 +/- 1.4 mm Hg, occlusion resulted in a rightward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 2.7 +/- 2.3 mm Hg; delta LVEDV, 6.3 +/- 4.7 ml, both p less than 0.05 versus control). After dextran infusion (LVEDP, 20.9 +/- 6.0 mm Hg), occlusion resulted in a rightward and upward shift in the diastolic portion of the LV pressure-volume loop (delta LVEDP, 5.8 +/- 4.4 mm Hg; delta LVEDV, 4.2 +/- 3.0 ml, both p less than 0.05 versus control). At low cardiac volumes before dextran infusion, the intact pericardium did not affect the response to occlusion. By contrast, after dextran infusion in the presence of an intact pericardium, LVEDP significantly increased (delta, 6.4 +/- 3.6 mm Hg, p less than 0.05) but LVDEV did not (delta, 0.7 +/- 1.5 ml, p = NS). There was a parallel upward shift in the diastolic portion of the LV pressure-volume loop that was eliminated by removal of the pericardium. Thus, the change in LV diastolic pressure and volume during occlusion varied and depended on the baseline cardiac volume and presence of the pericardium. Before dextran infusion with the pericardium present and absent, coronary artery occlusion did not alter the LV diastolic chamber stiffness parameter, which was calculated from the diastolic interval of an averaged steady-state beat (0.040 +/- 0.019 versus 0.036 +/- 0.015 mm Hg/ml, p = NS). After dextran infusion with the pericardium present and absent, coronary artery occlusion increased the LV diastolic chamber stiffness parameter (0.057 +/- 0.034 and 0.074 +/- 0.034 mm Hg/ml, both p less than 0.05 versus controls, respectively). Vena caval occlusion eliminated the shifts in the diastolic portion of the LV pressure-volume loop with the pericardium present and absent.(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparative effects of pacing-induced and balloon coronary occlusion ischemia on left ventricular diastolic function in man

BACKGROUND. Effects of pacing-induced and coronary occlusion myocardial ischemia on left ventricular (LV) function have been compared only in anesthetized dogs. Diastolic properties of the same LV anterior wall segment were therefore compared in 12 patients with single-vessel proximal left anterior descending coronary artery stenosis at rest, immediately after 7 +/- 1.2 minutes of pacing, and at the end of a 1-minute balloon occlusion of coronary angioplasty (CO). METHODS AND RESULTS. Shifts of the diastolic LV pressure-length relation, derived from simultaneous tip-micromanometer LV pressure recordings and digital subtraction LV angiograms, were used as an index of regional diastolic LV distensibility of the anterior wall segment. Immediately after pacing, LV end-diastolic pressure rose from 13.5 +/- 3.5 to 23.8 +/- 7.0 mm Hg (p less than 0.01 versus at rest) without a significant change of the LV end-diastolic volume index (83.1 +/- 18.9 versus 88.4 +/- 16.5 ml/m2), percentage systolic shortening (%SS) of the ischemic segment fell from 40.1 +/- 10.6% to 25.2 +/- 8.6% (p less than 0.01), and the diastolic LV pressure-radial length (P-RL) plot of the ischemic segment was shifted upward by 7.1 +/- 5.0 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. At the end of CO, LV end-diastolic pressure rose to 20.8 +/- 7.8 mm Hg (p less than 0.01 versus at rest) and the LV end-diastolic volume index rose to 95.6 +/- 16.3 ml/m2 (p less than 0.05 versus at rest, p less than 0.05 versus after pacing). Ejection fraction and %SS of the ischemic segment fell respectively from 76.6 +/- 6.8% to 46.6 +/- 11.4% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing) and from 40.1 +/- 10.6% to 6.4 +/- 8.6% (p less than 0.01 versus at rest, p less than 0.01 versus after pacing). The diastolic LV P-RL plot of the ischemic segment was shifted upward by 3.1 +/- 2.3 mm Hg for portions of the plot that overlapped with the diastolic LV P-RL plot at rest. This upward shift at the end of CO was significantly smaller (p less than 0.05) than that immediately after pacing. At the end of CO, a correlation (p less than 0.03) was observed for the ischemic segment between %SS and upward shift of the diastolic LV P-RL plot. CONCLUSIONS. The upward shift of the diastolic LV P-RL plot, which was used as an index of decreased regional diastolic LV distensibility, was larger immediately after pacing than at the end of CO. Persistent systolic shortening of ischemic myocardium seems to be a prerequisite for a decrease in diastolic distensibility of the ischemic segment because of the higher %SS of the ischemic segment immediately after pacing, and because of the correlation at the end of CO between the upward shift of the diastolic LV P-RL plot and %SS of the ischemic segment.     

Radionuclide evaluation of the systolic blood pressure/end-systolic volume relationship: response to pharmacologic agents in patients with coronary artery disease

To assess the response of the relationship between systolic blood pressure and end-systolic volume to pharmacologic agents with known cardiac effects, we studied 21 patients with known coronary heart disease by means of gated radionuclide angiograms during the infusion of phenylephrine. Each individual was studied during the infusion of phenylephrine twice, once as a control and the second time after the administration of either intravenous dobutamine, topical nitroglycerin ointment, or intravenous propranolol. Eight individuals received 10 micrograms/kg/min of dobutamine, which reduced resting cardiac volumes (p less than 0.01), raised ejection fraction (p less than 0.01), and shifted the slope (1.38 +/- 0.50 to 2.03 +/- 0.69, p less than 0.01) and pressure intercept received 2 inches of nitroglycerin ointment. Nitroglycerin increased ejection fraction (p less than 0.05) and reduced volumes (p less than 0.05) but did not alter either the slope (1.46 +/- 0.68 to 1.49 +/- 0.61, p = NS) or intercept (10.6 +/- 5.4 to 10.1 +/- 6.4 mm Hg, p = NS) of the relationship. Eight patients received 15 mg of intravenous propranolol. Propranolol reduced resting ejection fraction (p less than 0.05), increased volumes (p less than 0.05), and reduced both the slope (1.67 +/- 0.58 to 1.51 +/- 0.53, p less than 0.05) and the intercept (13.8 +/- 2.5 to 7.5 +/- 2.3 mm Hg, p less than 0.05) of the pressure-volume relationship. Thus the systolic blood pressure/end-systolic volume relationship can be assessed from radionuclide angiograms.     

Left ventricular diastolic function in patients with left ventricular systolic dysfunction due to coronary artery disease and effect of nicardipine

To assess the effect of nicardipine on left ventricular (LV) diastolic function independent of concurrent effects on loading conditions in patients with LV systolic dysfunction due to coronary artery disease, equihypotensive doses of intravenous nitroprusside and nicardipine were administered to 12 patients with congestive heart failure due to previous myocardial infarction (LV ejection fraction less than 0.40). LV micromanometer pressure and simultaneous radionuclide volume were obtained during a baseline period, during nitroprusside infusion, during a second baseline period and during nicardipine infusion. Mean systemic arterial pressure decreased an average of 21 mm Hg with nitroprusside and 19 mm Hg with nicardipine. A greater decrease in LV end-diastolic pressure was observed with nitroprusside (29 +/- 2 to 15 +/- 2 mm Hg, p less than 0.01) than with nicardipine (29 +/- 2 to 25 +/- 3 mm Hg, p less than 0.05). There was a decrease in the time constant of relaxation during nitroprusside but not during nicardipine infusion. There was enough overlap in LV volumes in the baseline and nitroprusside periods to compare diastolic pressure-volume relations over a common range of volumes in 4 patients, and enough overlap in the baseline and nicardipine periods in 11 patients. The relation was shifted downward in 3 of 4 patients taking nitroprusside and in 6 of 11 patients taking nicardipine. The relation between end-diastolic pressure and volume was not shifted with nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics in humans

Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 micrograms/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33 +/- 0.06 to 5.86 +/- 0.71 ng/ml (p less than 0.01); coronary sinus blood flow increased from 98 +/- 12 to 124 +/- 13 ml/min (p less than 0.01), and coronary vascular resistance decreased from 1,113 +/- 117 to 851 +/- 91 mm Hg.min/l (p less than 0.01). Heart rate and aortic pressure remained unchanged. The mean luminal diameters of the proximal, middle, and distal left anterior descending artery increased by 9.4 +/- 3.6% (p less than 0.05), 19.2 +/- 3.8% (p less than 0.001), and 31.5 +/- 5.6% (p less than 0.001), respectively, after the histamine infusion. The mean luminal diameters of the proximal, middle, and distal left circumflex artery increased by 15.2 +/- 3.6% (p less than 0.01), 17.5 +/- 5.2% (p less than 0.01), and 20.6 +/- 4.3% (p less than 0.001), respectively, after the histamine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of 99mTc-teboroxime with thallium for myocardial imaging in the presence of a coronary artery stenosis

BACKGROUND. This study tested the hypotheses in the setting of a coronary artery stenosis that 1) planar 99mTc-teboroxime myocardial scans are capable of providing a good estimate of relative coronary flow reserve, and 2) delayed washout of the tracer from the myocardium is a marker of reduced myocardial blood flow and, in certain cases, myocardial ischemia. METHODS AND RESULTS. Experiments were conducted in eight closed-chest domestic swine prepared with an artificial stenosis that reduced diameter of the left anterior descending coronary artery by 80%. Measurements of hemodynamics, regional myocardial blood flow, oxygen, and lactate metabolism were made 1) at baseline, 2) after 5 minutes of intravenous infusion of adenosine and neosynephrine ("stress"), and 3) at recovery 2 hours after discontinuing the adenosine/neosynephrine infusion. Simultaneous intravenous injection of teboroxime (approximately 9 mCi) and thallium (approximately 3.5 mCi) was made at peak stress, and serial planar teboroxime imaging began 1-2 minutes later. Scans were made in dynamic mode for 30 seconds each for 7 minutes after which a stress thallium scan (7 minutes acquisition) was obtained. A redistribution thallium scan was made 2 hours later after which a repeat teboroxime injection followed by serial imaging for 7 minutes was performed. The animal was then killed, and the heart removed for determination of microsphere activity. Under baseline conditions, transmural myocardial blood flow (ml/min/g) distal to the stenosis (1.06 +/- 0.17) was reduced (p less than 0.01) compared with the normally perfused circumflex zone (1.50 +/- 0.31). In response to intravenous infusion of adenosine/neosynephrine, flow increased (p less than 0.01) compared with baseline in both distal (2.00 +/- 0.84) and circumflex (4.67 +/- 1.55) zones. However, the distal : circumflex flow declined (0.45 +/- 0.17) compared with baseline (0.73 +/- 0.17; p less than 0.01). Two hours later flow had returned to baseline levels in both zones, and lactate production during stress (-41.7 +/- 37.5 mumol/min/100 g) had reverted to consumption (13.6 +/- 7.7; p less than 0.05). Analysis of stress teboroxime scans demonstrated 1) an increase (p less than 0.01) in the ischemic : normal zone (IZ:NZ) count between 30-second (0.50 +/- 0.14) and 7-minute scans (0.61 +/- 0.11); 2) a good correlation between the 30-second scan IZ:NZ count and the stress distal : circumflex flow (0.45 +/- 0.17; r = 0.74; p less than 0.05; slope = 0.90; intercept = 0); and 3) a close correlation between the IZ:NZ count of the 7-minute scan (0.61 +/- 0.11) and the recovery distal : circumflex flow (0.69 +/- 0.21; r = 0.89; p less than 0.01). The IZ:NZ count also increased (p less than 0.01) between 30-second (0.65 +/- 0.15) and 7-minute (0.72 +/- 0.14) scans following rest injection of teboroxime. As anticipated, serial thallium scans demonstrated evidence of redistribution between stress (IZ:NZ count = 0.62 +/- 0.08) and recovery (IZ:NZ count = 0.75 +/- 0.06; p less than 0.01) time points. The stress thallium scan IZ:NZ, however, was greater than that of the 30-second teboroxime scan as well as that of the stress distal : circumflex flow. CONCLUSIONS. Accordingly, the data indicate that 1) myocardial imaging with 99mTc-teboroxime is valuable in the noninvasive assessment of relative coronary flow reserve and that 2) delayed washout of the tracer from the myocardium reflects reduced myocardial blood flow and, under conditions comparable to those of the present study, may be a marker of myocardial ischemia.     

Comparison of coronary hemodynamic and cardiac metabolic alterations during coronary artery spasm associated with ST segment elevation or depression

Coronary vasospasms are usually indicated by ST elevation or depression in the electrocardiogram (ECG). To test the hypothesis that ST elevation represents more severe myocardial ischemia than does ST depression, we determined the coronary sinus blood flow (CSBF) and the transcardiac lactate extraction ratio (LER) in 19 selected patients who had focal vasospasms in the left anterior descending artery. In 10 patients, ergonovine (0.11 +/- 0.02 mg, mean +/- SEM) provoked severe (total or subtotal) coronary vasospasm with ST elevation. Under these conditions, CSBF significantly decreased (from 97 +/- 8 ml/min to 79 +/- 5 ml/min, p less than 0.01) with a marked reduction in LER (from 29 +/- 5% to -14 +/- 6%, p less than 0.01). In contrast, 10 vasospastic events with ST depression after ergonovine (0.15 +/- 0.04 mg, NS) were recognized as mild spastic narrowing or severe spasms with well developed collateral circulation. Alteration of CSBF was significant in only a few patients and the overall CSBF response was non-significant (from 106 +/- 12 ml/min to 103 +/- 13 ml/min). The reduction in LER in this group was less pronounced than those in patients with ST elevation (p less than 0.05). These results indicate that coronary vasospasm with ST elevation may be related to the more pronounced reduction in coronary blood flow accompanied by more severe myocardial ischemia. Such observations may support the contention that some ischemic events associated with ST elevation or depression can be interpreted as a continuous spectrum of vasospastic disorders.     

Effects of propafenone on coronary and systemic hemodynamics

This study was undertaken to evaluate the effects of intravenous Propafenone (2 mg/kg over 5') on Left Ventricular (LV) function and coronary blood flow. Twelve patients with coronary artery disease and post-ischemic LV disfunction were examined during routine cardiac catheterization. Serial measurements of central hemodynamics, LV high-fidelity pressure and coronary blood flow were recorded at rest and every 10' after Propafenone administration. Heart rate was unchanged, suggesting that Propafenone did not affect sympathetic tone. Cardiac index slightly decreased (from 3.3 +/- 0.9 L/min/m2 to 3.1 +/- 0.6 L/min/m2 at 10', p = ns), LV end-diastolic pressure rose significantly (from 17.7 +/- 2.1 mmHg to 22.7 +/- 4.2 mmHg at 20', p less than 0.01) and dP/dt max fell from 1897 +/- 291 mmHg/sec to 1577 +/- 312 mmHg/sec (p less than 0.02). Systemic vascular resistances had only minimal changes. Concomitantly, coronary vascular resistances decreased (from 0.77 +/- 0.17 mmHg/ml/min to 0.61 +/- 0.12 mmHg/ml/min, p less than 0.02) and coronary blood flow increased (from 138 +/- 29 ml/min to 172 +/- 21 ml/min, p less than 0.01). No significant difference was noted in myocardial oxygen consumption. No symptoms related to LV failure were observed during the study. In conclusion hemodynamic effects of Propafenone are characterized by moderate LV depression and by coronary artery dilatation, probably due to a calcium blocker-like activity.     

Effects of alpha human atrial natriuretic polypeptide on the systemic hemodynamics and coronary circulation in patients with ischemic heart disease

Alpha human atrial natriuretic polypeptide (alpha-hANP) was intravenously infused into 7 patients with ischemic heart disease who had almost normal cardiac function at a rate of 0.025 micrograms/kg/min for 15 min. During infusion of alpha-hANP, left ventricular (LV) systolic pressure decreased from 144 +/- 19 (SD) to 129 +/- 22 mmHg (p less than 0.01), LV end diastolic pressure (EDP) from 15 +/- 5 to 13 +/- 4 mmHg (p less than 0.05), mean aortic pressure from 102 +/- 14 to 91 +/- 14 mmHg (p less than 0.01), time constant of LV pressure fall (T) from 100 +/- 15 to 88 +/- 13 msec (p less than 0.05), systemic vascular resistance (SVR) from 1711 +/- 206 to 1424 +/- 340 dynes.sec.cm-5 (p less than 0.05) and coronary vascular resistance (CVR) from 8.5 +/- 1.2 to 7.4 +/- 1.3 x 10(4) dynes.sec.cm-5 (p less than 0.05). There was a linear correlation between percent changes in SVR and those of CVR (r = 0.92, p less than 0.01), and the fall in CVR was approximately 68% of that in SVR. Increases occurred in heart rate from 63 +/- 7 to 66 +/- 8 beats/min (p less than 0.05), LV dp/dt from 1558 +/- 266 to 1627 +/- 238 mmHg/sec (p less than 0.05), LV dp/dt/p from 22.9 +/- 3.2 to 25.6 +/- 3.7/sec (p less than 0.01), and myocardial oxygen consumption (from 7.9 +/- 2.4 to 9.8 +/- 2.1 ml/min, p less than 0.05), while mean right atrial and mean pulmonary arterial pressures and pulmonary vascular resistance were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)