Intermittent coronary sinus occlusion after coronary arterial ligation results in venous retroperfusion

Coronary sinus occlusion retards necrosis of ischemic myocardium. To test the hypothesis that coronary sinus occlusion induces retrograde venoarterial flow, the coronary arteriovenous pressure gradient and the coronary arterial oxygen saturation were measured distal to a left anterior descending coronary artery ligature in dogs. In parallel, we constructed a mathematical model of known coronary physiology to characterize pressure and flow patterns during coronary sinus occlusion. In dogs, coronary sinus occlusion produced a systolic pressure gradient between the coronary artery and the coronary sinus of -20 +/- 9 mm Hg (higher venous pressure, p less than 0.0001) and a positive diastolic gradient of 3 +/- 5 mm Hg (lower venous pressure p less than 0.01). An average reduction in the oxygen saturation in the ligated coronary artery of 20 +/- 13% was also observed (p less than 0.005) consequent to admixture of venous (desaturated) blood. By graded inflation of the coronary sinus balloon, it was demonstrated that desaturation of arterial blood typically occurs above a coronary sinus systolic pressure of 40-50 mm Hg. The mathematical model indicates the possibility of venoarterial pressure gradients and reversal of flow at the microcirculatory level during coronary sinus occlusion. These studies provide evidence that retrograde flow into the ischemic zone occurs in association with intermittent coronary sinus occlusion. Thus, alternating flow over the ischemic territory may be the mechanism of myocardial salvage during intermittent coronary sinus occlusion.     

Differential effects on right ventricular function of transient right, left anterior descending and left circumflex coronary occlusions during percutaneous transluminal coronary angioplasty

Right ventricular function was studied by means of a thermodilution catheter before, during and after percutaneous transluminal angioplasty of the proximal right (group 1, n = 8), left anterior descending (group 2, n = 8) or left circumflex (group 3, n = 8) coronary artery. All patients had evidence of myocardial ischemia, with single-vessel disease affecting the proximal segment of one of the three major coronary arteries; no patient had had a previous myocardial infarction and all had normal cardiac function at baseline study. Cardiac index decreased during balloon inflation. Mean pulmonary artery pressure was unaffected in group 1 but increased in group 2 (from 19 +/- 5 to 31 +/- 11 mm Hg, p less than 0.01) and in group 3 (from 19 +/- 2 to 22 +/- 5 mm Hg, p less than 0.05). Right ventricular ejection fraction decreased from 62 +/- 9% to 52 +/- 10% (p less than 0.01) in group 1 and from 64 +/- 7% to 44 +/- 10% (p less than 0.005) in group 2, and returned to normal within 2 min after balloon deflation in both groups. In group 3, right ventricular ejection fraction was unchanged during balloon inflation (58 +/- 5% at baseline, 58 +/- 9% at 60 s, p = NS). Therefore, brief occlusion of the proximal segments of the left anterior descending or right coronary artery results in marked alteration of right ventricular performance that is probably caused by right ventricular free wall ischemia in the right coronary group and by the concomitant effects of septal ischemia and increased right ventricular afterload in the left anterior descending artery group.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Amelioration by nitroglycerin of left ventricular ischemia induced by percutaneous transluminal coronary angioplasty: assessment by hemodynamic variables and left ventriculography

Increasingly longer balloon inflation times during coronary angioplasty can create significant left ventricular ischemia, amelioration of which was attempted in this study using nitroglycerin. Hemodynamic variables were assessed during inflation of an angioplasty balloon in the proximal left anterior descending coronary artery of 10 patients. Regional wall motion was assessed by left ventriculography during a separate balloon inflation. Nitroglycerin (200 micrograms) was then administered intravenously, and hemodynamic and ventriculographic assessments during balloon inflations were repeated. Balloon inflation resulted in a marked increase in left ventricular end-diastolic pressure (from 9.2 +/- 2.1 to 19.4 +/- 2.9 mm Hg) and time constant of left ventricular relaxation (from 44.2 +/- 6.2 to 62.3 +/- 11.3 ms) and a decrease in distal coronary artery perfusion pressure (from 54 +/- 9 to 33.1 +/- 4 mm Hg). Time to onset of angina was 29 +/- 3 seconds and time to ST segment depression of 1 mm or greater was 30 +/- 3 seconds. Regional wall motion analysis 30 seconds after onset of balloon inflation revealed marked hypokinesia and akinesia in the anteroapical segments with graduated depression of inferior wall motion, greatest at the apex. After the administration of nitroglycerin, balloon inflation resulted in a smaller increase in end-diastolic pressure (from 5.0 +/- 2.7 to 8.3 +/- 2.6 mm Hg) and time constant (from 47.9 +/- 4.7 to 54.4 +/- 9.2 ms; both p less than 0.01 versus standard balloon inflation). Distal coronary artery pressure remained similar to standard balloon inflation (32 +/- 3 mm Hg) despite lower mean arterial pressure (89 +/- 5 mm Hg, p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of acute changes in aortic pressure on the coronary reserve.

STUDY OBJECTIVE--The aim was to evaluate the effect of acute changes in aortic pressure on the coronary reserve and hyperaemic response. DESIGN--Aortic pressure changes were induced either by intra-aortic balloon pumping or by the production of acute aortic regurgitation. A transient 20 s occlusion of the left anterior descending coronary artery was used as the hyperaemic stimulus. EXPERIMENTAL SUBJECTS--The experiments were performed on 19 open chest anaesthetised dogs, weight 13-32 kg. MEASUREMENTS AND MAIN RESULTS--During intra-aortic balloon pumping the mean diastolic aortic pressure increased by 24.7(SEM 2.9) mm Hg (p less than 0.001), while in aortic regurgitation it decreased by 47.7(11.1) mm Hg (p less than 0.01). At the peak hyperaemic response the driving coronary pressure was 121.4(2.8) mm Hg during intra-aortic balloon pumping and 59.8(11.5) mm Hg during aortic regurgitation. The peak hyperaemic flow increased by 12.0(3.8) ml.min-1 (p less than 0.01) during intra-aortic balloon pumping, compared to the values before pumping and decreased by 14.9(4.2) ml.min-1 (p less than 0.01) during aortic regurgitation, compared to the values before aortic regurgitation. The coronary reserve, expressed as the ratio of the hyperaemic to the resting flow, increased by 0.7(0.1) (p less than 0.001) during intra-aortic balloon pumping and decreased by 0.4(0.2) (p less than 0.05) during aortic regurgitation. A positive significant correlation coefficient was found at the peak hyperaemic response between the mean aortic pressure and the total forward effective coronary flow, and between the mean diastolic aortic pressure and the diastolic component of the coronary flow, during both intra-aortic balloon pumping and aortic regurgitation. CONCLUSIONS--The results suggest that coronary reserve increases during intra-aortic balloon pumping and decreases during aortic regurgitation; these changes could be attributed to the effect of the pressure changes on the hyperaemic flow.     

Changes in coronary blood flow and myocardial metabolism during aortic balloon valvuloplasty

The effects of balloon inflation on myocardial perfusion and metabolism were studied during aortic valvuloplasty in 17 patients with aortic stenosis, including 6 with associated coronary artery disease. Coronary sinus flow and blood samples were obtained before and during the first inflation, and 5 to 10 minutes after the last inflation. During inflation, coronary blood flow decreased (272 +/- 111 standard deviation to 166 +/- 92 ml/min; p less than 0.05), myocardial oxygen uptake fell and transcardiac lactate handling shifted from extraction to production (35 +/- 54 to -41 +/- 48 mumol/min; p less than 0.01). At the end of the procedure, aortic valve area had increased from 0.51 +/- 0.22 to 0.81 +/- 0.48 cm2 (p less than 0.002). Coronary sinus flow increased slightly above control values (+6%; difference not significant) and myocardial oxygen and lactate uptakes were back to control values. However, myocardial alanine production had increased from -3.6 to -6.6 mumol/min (p less than 0.05) and glutamine production was reduced or replaced by extraction (-3.3 +/- 2.1 to 3.5 +/- 3.8 mumol/min; p less than 0.05). Recovery of coronary flow, oxygen and lactate uptakes was not significantly different in patients with or without coronary artery disease, although the former patients tended to have less glutamine extraction and less improvement in their ejection fraction at the end of the procedure. Thus, aortic balloon valvuloplasty produces brief episodes of low-flow ischemia. Recovery of oxidative metabolism is almost immediate after deflation and no detrimental effect seems to persist at the end of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Demonstration of an imbalance between coronary perfusion and excessive load as a mechanism of ischemia during stress in patients with aortic stenosis

Patients with aortic stenosis are susceptible to myocardial ischemia during hemodynamic stress, which may be caused by two mechanisms. First, vascular abnormalities inherent in myocardial hypertrophy may impair coronary vasodilation, limiting the ability to increase coronary blood flow to meet increased metabolic demands. Second, aortic stenosis itself may cause an imbalance between oxygen supply and demand during hemodynamic stress by decreasing aortic pressure (decreasing coronary perfusion or oxygen supply) and increasing left ventricular pressure (increasing oxygen demand). By decreasing aortic valve gradient without immediately altering ventricular hypertrophy, aortic balloon valvuloplasty offers the opportunity to distinguish these mechanisms. We hypothesized that aortic valvuloplasty would improve the balance between myocardial oxygen supply and demand, especially during isoproterenol infusion. Nine patients undergoing aortic balloon valvuloplasty were assessed at baseline and during isoproterenol infusion (5 +/- 2 micrograms/min, mean +/- SD) before and after valvuloplasty. Valvuloplasty increased myocardial oxygen supply. After valvuloplasty, isoproterenol decreased diastolic pressure time index (DPTI) less and increased coronary sinus blood flow more than before valvuloplasty (-630 +/- 367 vs. -292 +/- 224 mm Hg.sec/min, p = 0.02 and 53 +/- 137 vs. 179 +/- 145 ml/min, p = 0.001, respectively). Valvuloplasty also decreased oxygen demand, decreasing systolic pressure time index (SPTI) from 4,135 +/- 511 to 3,021 +/- 492 mm Hg.sec/min (p = 0.0002). Valvuloplasty improved the balance between myocardial oxygen supply and demand, increasing baseline DPTI:SPTI, decreasing aortocoronary sinus oxygen content difference (0.51 +/- 0.15 to 0.68 +/- 0.14, p = 0.005 and 96 +/- 14 to 78 +/- 15 ml O2/l, p = 0.002, respectively), and decreasing myocardial lactate production during isoproterenol infusion (mean lactate extraction fraction, -0.26 +/- 0.40 to 0.14 +/- 0.17; p = 0.01). We conclude that aortic valvuloplasty improves the balance between myocardial oxygen supply and demand during hemodynamic stress induced by isoproterenol infusion. We speculate that the clinical improvement, which often occurs in these patients after valvuloplasty despite persistence of hemodynamically "critical" aortic stenosis, is in part attributable to immediate improvement in the myocardial oxygen supply:demand ratio.     

Effects of nitroglycerin and nifedipine on coronary and systemic hemodynamics during transient coronary artery occlusion

Nitroglycerin (NTG) and nifedipine (NIF) have the potential to augment coronary blood flow in addition to reducing peripheral determinants of myocardial oxygen demand as a synergistic protective mechanism during ischemia. To examine these effects, systemic and coronary hemodynamic responses were measured continuously before and during brief periods of myocardial ischemia induced by left anterior descending coronary balloon occlusion in 26 patients undergoing angioplasty (PTCA). Data were compared for two matched occlusion periods, one control and one "drug" occlusion. In 17 patients (NTG group), 200 micrograms of intracoronary NTG was given immediately before coronary occlusion. In nine patients (NIF group), 10 mg of sublingual NIF was given 15 minutes before the "drug" occlusion. NTG significantly but transiently reduced mean arterial pressure (91 +/- 11 to 82 +/- 15 mm Hg, p less than 0.05) and augmented basal coronary blood flow (95 +/- 38 to 127 +/- 54 ml/min, p less than 0.05) but did not alter great vein blood flow (59 +/- 29 vs 61 +/- 29 ml/min) or coronary occlusion pressure (25 +/- 7 to 24 +/- 7 mm Hg) during ischemia. NIF significantly reduced systolic, diastolic, and mean arterial pressure (119 +/- 21 to 95 +/- 8 mm Hg, p less than 0.001) and heart rate-pressure product from control. NIF maintained basal great vein blood flow (125 +/- 41 to 106 +/- 57 ml/min) during reduced myocardial oxygen demand, but did not affect great vein blood flow (73 +/- 29 to 79 +/- 37 ml/min) or coronary occlusion pressures during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features

The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, -0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning).     

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)     

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)     

Quantification of left ventricular performance during transient coronary occlusion at various anatomic sites in humans: a study using tantalum-178 and a multiwire gamma camera.

To study the functional significance of transient coronary occlusion on systolic and diastolic left ventricular function relative to the anatomic site of occlusion, first-pass radionuclide angiography with a mobile multiwire gamma camera using tantalum-178 (dose activity less than or equal to 84 mCi/elution) was performed in 46 patients undergoing balloon coronary angioplasty. First-pass images were acquired immediately before angioplasty and during the last 30 s of a 60-s balloon inflation in 23 left anterior descending arteries, 18 right coronary arteries, 8 circumflex arteries and 3 diagonal coronary arteries. Occlusion of the left anterior descending artery resulted in significant decreases in left ventricular ejection fraction (54.6 +/- 12.7% to 32.3 +/- 10.6%, p = 0.0001) and peak filling rate (2.48 +/- 0.68 to 1.75 +/- 0.64 end-diastolic volumes/s, p = 0.0001), accompanied by severe abnormalities in regional function and left ventricular dilation. Right coronary artery occlusion caused inferior hypokinesia, but did not significantly change left ventricular ejection fraction (48.5 +/- 12.4% vs. 45.8 +/- 12.5%, p = NS) or peak filling rate (2.05 +/- 0.81 vs. 2.09 +/- 0.81 end-diastolic volumes/s, p = NS). Circumflex artery occlusion resulted in mild wall motion deterioration and a borderline decrease in ejection fraction (54.7 +/- 11.4% to 50.5 +/- 12%, p = 0.057). Diagonal artery occlusion did not cause significant changes in left ventricular ejection fraction or filling rate. The decrease in left ventricular ejection fraction during coronary occlusion was 9 +/- 25% and 27 +/- 22%, respectively, in those arteries with and without collateral supply (p = 0.052). These data provide strong evidence for the critical importance of the left anterior descending artery and the secondary role of the other coronary arteries in maintaining global systolic and diastolic left ventricular function and suggest a protective role of collateral vessels during coronary occlusion.     

Reduction of systolic coronary blood flow in experimental left ventricular outflow tract obstruction

In aortic valvular stenosis, coronary reserve has been shown to be markedly diminished despite normal coronary arteries. To gain further insight into this phenomenon, we examined the effects of an acute subaortic valvular obstruction on coronary blood flow (CBF) in seven open-chest anesthetized dogs. Transient subaortic obstruction was produced by inflating a catheter-tip balloon in the left ventricular (LV) outflow tract. The degree of obstruction, a 26 +/- 3 mm Hg gradient across the aortic valve, was adjusted to achieve an elevation of LV pressure while maintaining a constant aortic pressure (coronary perfusion pressure). In seven dogs with intact coronary vasomotor tone, systolic left anterior descending CBF decreased from 20 +/- 9 ml/min during the control period to 13 +/- 3 ml/min during subaortic obstruction (p less than 0.001). Diastolic CBF increased from 52 +/- 9 to 58 +/- 10 ml/min (p less than 0.05), and total CBF remained unchanged. In three dogs with maximal coronary vasodilation, systolic CBF decreased during subaortic obstruction, diastolic CBF remained unchanged, and total CBF decreased. The present data suggest that elevation of LV intracavitary pressure above coronary perfusion pressure can reduce systolic CBF and lead to an autoregulatory compensation that taxes coronary flow reserve.     

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.     

Does intracoronary infusion of Fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty?

Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood.     

Dynamics of early and late left ventricular filling determined by Doppler two-dimensional echocardiography during percutaneous transluminal coronary angioplasty

To study the influence of ischemia on both early and late left ventricular filling, Doppler 2-dimensional echocardiography was used to measure filling parameters during percutaneous transluminal coronary angioplasty (PTCA) in 26 patients. Doppler recordings were taken immediately before balloon inflation and continuously during balloon inflation and deflation until 60 seconds into the recovery period. During PTCA of the left anterior descending artery (16 patients) there was a 35% decrease in early peak filling rate from 269 +/- 88 to 169 +/- 55 ml/s (p less than 0.0005) by 60 seconds of balloon inflation. In patients undergoing PTCA of the left circumflex (4 patients) or dominant right coronary artery (6 patients), the early peak filling rate decreased 15% from 325 +/- 126 to 284 +/- 137 ml/s (p less than 0.005). The decrease in early peak filling rate became evident at approximately 15 seconds after balloon inflation and fully recovered 20 seconds after balloon deflation. Rather than an expected increase in atrial stroke volume and a decrease in early to late filling ratio during coronary occlusion, there was a 28% decrease in atrial stroke volume during left anterior descending coronary artery PTCA and a 6% decrease during right coronary and circumflex PTCA. Because of the simultaneous decrease in both early and late ventricular filling, peak early to late filling ratio was only slightly altered during PTCA. There was an 83% increase in mean pulmonary artery wedge pressure during balloon inflation from 12 +/- 5 to 20 +/- 4 mm Hg. In 11 of these patients global systolic function was measured on subsequent inflations during PTCA using 2-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Augmentation of regional coronary blood flow by intra-aortic balloon counterpulsation in patients with unstable angina

Intra-aortic balloon counterpulsation is capable of reducing afterload in patients with unstable angina. Whether it is also capable of augmenting coronary blood flow to poststenotic myocardium is controversial. We studied seven patients receiving maximal drug therapy and requiring balloon pumping for unstable angina as balloon volume and assist ratio were altered. All patients had greater than 90% stenosis of the proximal left anterior descending coronary artery. With maximal augmentation (40 cc balloon volume, 1:1 assist ratio) great cardiac vein flow, representing the efflux from the left anterior descending coronary artery bed, rose from a baseline of 52 +/- 20 to 67 +/- 25 ml/min (mean +/- SD, p = .004) and mean aortic diastolic pressure increased from 77 +/- 13 to 99 +/- 33 mm Hg (p = .004). Increased great cardiac vein flow correlated with increased mean aortic diastolic pressure across changes in balloon volumes (off, 20 cc, 30 cc, and 40 cc) and changes in assist ratio (off, 1:4, 1:2, and 1:1) (p = .02). However, the intermediate balloon volumes produced great cardiac vein flows at an intermediate level between full assist and no assist (p less than .05), whereas the intermediate assist ratios did not augment flow. Thus balloon pumping increased flow to a bed fed by collateral vessels or critical stenoses; this increased flow correlated with increased aortic diastolic pressure, indicating probable loss of autoregulatory ability.     

Influence of aortic stenosis on the hemodynamic importance of coronary artery narrowing in dogs without left ventricular hypertrophy

Coronary hemodynamic effects of controlled left ventricular outflow obstruction stimulating aortic valve stenosis were studied in 20 open-chest dogs, with and without graded coronary artery diameter narrowing. Aortic stenosis was regulated so that a mean left ventricular-aortic pressure gradient of 46 +/- 20 mm Hg (mean +/- standard deviation) was created as both heart rate and stroke volume were unchanged. In addition, during aortic stenosis, mean aortic pressure (105 +/- 17 to 84 +/- 15 mm Hg, p less than 0.05) and diastolic pressure time index/systolic pressure time index ratio (1.2 +/- 0.3 to 0.6 +/- 0.2, p less than 0.05) decreased and end-diastolic left ventricular pressure (7 +/- 4 to 14 +/- 6 mm Hg, p less than 0.05) increased. With no coronary narrowing, mean coronary flow increased during aortic stenosis (53 +/- 23 to 62 +/- 23 ml/min) as the percentage of diastolic flow increased (83 +/- 6 to 89 +/- 4) and endocardial/epicardial ratio decreased (1.14 +/- 0.16 to 0.95 +/- 0.24) (all p less than 0.05). Peak reactive hyperemic flow also decreased (168 +/- 85 to 125 +/- 73 ml/min, p less than 0.05). This value with no coronary narrowing was similar to peak hyperemic flow with 60% narrowing without aortic stenosis. With 90% coronary narrowing, mean coronary flow decreased with or without aortic stenosis. Transmural flow distribution also decreased but was lower during aortic stenosis (0.86 +/- 0.19 to 0.61 +/- 0.25, respectively; p less than 0.05). These data suggest that although mean coronary flow is increased during aortic stenosis, endocardial flow may be limited, and coronary reserve exposed during reactive hyperemia appears decreased. When a coronary artery is narrowed, aortic stenosis has an even more important hemodynamic influence on the coronary circulation.     

Protection against ischemia during prolonged balloon inflation by distal coronary perfusion with use of an autoperfusion catheter or Fluosol.

OBJECTIVES. The purpose of this report was to study the protective effects of passive and active distal coronary perfusion during prolonged balloon inflation. BACKGROUND. Prolonged balloon inflation has been proposed to improve immediate and long-term results of percutaneous transluminal coronary angioplasty, but it requires protection against myocardial ischemia. METHODS. A 30-min balloon occlusion of the left anterior descending artery was performed in three groups of closed chest anesthetized dogs: 1) control (no distal coronary perfusion, n = 13), 2) passive distal coronary perfusion (autoperfusion catheter, n = 10), and 3) active distal coronary perfusion (infusion of the perfluorochemical Fluosol at 30 ml/min, n = 11). RESULTS. At 10 min of balloon inflation, echocardiographic wall motion indexes (scored from 1 [normal] to 5 [dyskinesia]) in the autoperfusion catheter and Fluosol groups (2.4 +/- 1.2 and 2.0 +/- 0.9, respectively) were significantly better than in the control group (3.6 +/- 0.4, p = 0.001), but at 25 min this improvement in wall motion had attenuated and became statistically insignificant when compared with values in the control group. Left ventricular end-diastolic pressure at peak inflation in the Fluosol group (19.5 +/- 5.5 mm Hg) was higher than in the control (7.6 +/- 3.6) and autoperfusion catheter (5.3 +/- 1.4, p < or = 0.01) groups. Pathologic evidence of infarction by tetrazolium staining was seen in three control dogs and in none of the other groups (p = 0.07). Ventricular tachycardia and fibrillation were less frequent in the autoperfusion catheter group (p = 0.02). Three deaths were observed in the control dogs, two in the Fluosol group and none in the dogs with an autoperfusion catheter (p = NS). CONCLUSIONS. Passive (the autoperfusion balloon catheter) and active (Fluosol) distal coronary perfusion methods are comparable and better than no perfusion in protecting the myocardium against ischemia produced by prolonged coronary balloon inflation in an experimental canine model. This protection is transient, attenuating after 10 to 25 min, and partial because there was no significant difference in the incidence of myocardial infarction and death among groups, although the latter observations may be related to small sample size.     

The autoperfusion balloon angioplasty catheter limits myocardial ischemia and necrosis during prolonged balloon inflation

A new balloon angioplasty catheter with multiple proximal and distal side holes has previously been shown to allow significant protection from ischemia during a 3 min balloon inflation in a coronary artery. Because of the potential benefits of very long periods of inflation, 21 anesthetized thoracotomized dogs were randomized to left circumflex coronary artery occlusion with either a standard or an autoperfusion balloon catheter for 90 min. Nine dogs sustained ventricular fibrillation before completing the study, eight after standard balloon inflation and one after autoperfusion balloon inflation (p = 0.04). ST segment elevation was 0.45 +/- 0.13 mV after 15 min of standard balloon inflation versus -0.03 +/- 0.03 mV after autoperfusion balloon inflation (p less than 0.001). Regional myocardial blood flow was 0.02 +/- 0.01 ml/min per g after 30 min of standard balloon inflation compared with 0.78 +/- 0.23 ml/min per g in the group subjected to autoperfusion balloon inflation (p = 0.01). The area of necrosis/area at risk in the standard catheter group was 40.4 +/- 19.3% versus 1.2 +/- 1.2% for the autoperfusion catheter group (p = 0.01). Thus, the autoperfusion catheter preserves blood flow and limits myocardial ischemia and necrosis despite 90 min of balloon inflation.