Regional myocardial blood flow and left ventricular diastolic properties in pacing-induced ischemia

The relation between left ventricular diastolic abnormalities and myocardial blood flow during ischemia was studied in eight open chest dogs with critical stenoses of the proximal left anterior descending and circumflex coronary arteries. The heart was paced at 1.7 times the heart rate at rest for 3 min. In dogs with coronary stenoses, left ventricular end-diastolic pressure increased from 8 +/- 1 to 14 +/- 2 mm Hg during pacing tachycardia (p less than 0.01) and 16 +/- 3 mm Hg (p less than 0.01) after pacing, with increased end-diastolic and end-systolic segment lengths in the ischemic regions. Left ventricular diastolic pressure-segment length relations for ischemic regions shifted upward during and after pacing tachycardia in dogs with coronary stenoses, indicating decreased regional diastolic distensibility. In dogs without coronary stenoses, the left ventricular diastolic pressure-segment length relation was unaltered. Pacing tachycardia without coronary stenoses induced an increase in anterograde coronary blood flow (assessed by flow meter) in both the left anterior descending and circumflex coronary arteries, and a decrease in regional vascular resistance. In dogs with coronary stenoses, regional vascular resistance before pacing was decreased by 18%; myocardial blood flow (assessed by microspheres) was unchanged in both the left anterior descending and circumflex coronary artery territories. During pacing tachycardia with coronary stenoses, regional coronary vascular resistance did not decrease further; subendocardial myocardial blood flow distal to the left anterior descending coronary artery stenosis decreased (from 1.03 +/- 0.07 to 0.67 +/- 0.12 ml/min per g, p less than 0.01), as did subendocardial to subepicardial blood flow ratio (from 1.04 +/- 0.09 to 0.42 +/- 0.08, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transmural variation in autoregulation of right ventricular blood flow

We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less than 0.01, comparing normal vs. LVH dogs). In both groups of dogs, the stenosis caused a gradient of hypoperfusion, worsening from epicardium to endocardium. However, for each level of stenosis, subendocardial blood flow and the ratio of subendocardial to subepicardial blood flow was less in LVH than in normal canine hearts. These findings demonstrate that the presence of LVH secondary to long-term pressure overload is associated with an increased vulnerability to myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.     

Changes in diameter of coronary narrowings and translesional hemodynamics after intracoronary nitroglycerin

The effect of intracoronary nitroglycerin on coronary stenosis dimensions and translesional hemodynamics was evaluated in 38 subjects (74 stenoses) referred for diagnostic coronary arteriography. Quantitative coronary arteriography was performed with standard Newtonian fluid dynamic equations used to estimate transstenotic gradients. Since intracoronary nitroglycerin can induce significant myocardial hyperemia (increased flow velocity), with increased translesional pressure gradients and a decrease in distal intraluminal pressure, the potential effect on subendocardial flow distribution was also analyzed. Minimum stenotic diameter significantly increased postnitroglycerin (NTG) (preNTG 1.42 vs postNTG 1.82 mm, p less than 0.01), with a decrease in relative percent diameter stenosis (preNTG 45.7 vs postNTG 40.7%, p less than 0.05). When changes in minimum stenotic diameter were analyzed according to stenosis severity (quartiles), the greatest effect was noted in those lesions with the least severe stenosis (quartile no. 1, 0.49 vs quartile no. 4, 0.32 mm, p less than 0.05). If coronary blood flow velocity remains at baseline values (4 cm/s), intracoronary nitroglycerin was predicted to significantly decrease transstenotic pressure gradients (preNTG 1.01 vs postNTG 0.82 mm Hg, p less than 0.05), with the greatest change shown in severe lesions (quartile no. 4, preNTG 3.79 to postNTG 2.28 mm Hg, p less than 0.01). Accelerated coronary flow velocity (myocardial hyperemia) increased calculated translesional pressure gradients (4 cm/s, 0.82 mm Hg vs 20 cm/s, 8.00 mm Hg, p less than 0.01), despite simultaneous stenotic vasodilation. Hemodynamic obstruction was particularly dependent on coronary flow velocity in the most severe stenoses (quartile no. 4, 4 cm/s, 2.28 vs 20 cm/s, 28.78 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary artery distensibility in diabetic patients with simultaneous measurements of luminal area and intracoronary pressure: evidence of impaired reactivity to nitroglycerin.

OBJECTIVES: This study investigated whether noninsulin dependent diabetes mellitus (NIDDM) adversely affects the elastic properties of the coronary arteries in patients with coronary artery disease (CAD) and NIDDM. BACKGROUND: Attenuated vascular smooth muscle dilation to exogenous donors of nitric oxide, such as nitroglycerin, has been observed with forearm blood flow studies in patients with NIDDM. METHODS: Twenty patients with CAD and NIDDM (diabetics), and 20 patients with only CAD (nondiabetics) were evaluated. Intracoronary ultrasound (ICUS) imaging with simultaneous intracoronary pressure (P2) recordings were performed at the imaging site with 0.014 in fiber-optic high fidelity pressure monitoring wire. The same wire was used as guide wire for the ICUS catheter. Sites with less than 50% luminal stenosis by ICUS were studied. Recordings were done before and after 300 microg of intracoronary nitroglycerin (IC-NTG). Electrocardiographic tracings recorded simultaneously with ICUS images were used for timing. Systolic and diastolic cross-sectional lumen area (CSLA) and coronary artery distensibility (C-DIST) were measured, C-DIST = [(systolic CSLA-diastolic CSLA)/[(intracoronary pulse pressure) x (diastolic CSLA)]] x 1,000. RESULTS: Diabetics had smaller CSLA (diabetics = 8.6 +/- 0.6 mm2, nondiabetics = 11.5 +/- 0.5 mm2, p < 0.01). Although C-DIST was similar before IC-NTG in the two groups, it became significantly lower in diabetics after IC-NTG (diabetics C-DIST = 3.02 +/- 0.14 mm Hg(-1), nondiabetics C-DIST = 4.21 +/- 0.15 mm Hg(-1), p < 0.01). Degrees of circumference involved, total plaque burden and composition were similar in both groups. CONCLUSIONS: Noninsulin dependent diabetes mellitus reduces C-DIST after IC-NTG administration.     

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.     

Comparative effects of nitroglycerin and nifedipine on myocardial blood flow and contraction during flow-limiting coronary stenosis in the dog

Both nifedipine and nitroglycerin are used to treat angina pectoris. The comparative effects of these agents on myocardial blood flow and contraction in the setting of flow-limiting coronary stenosis are poorly understood. Thus 24 open chest dogs underwent carotid to left anterior descending coronary arterial perfusion with coronary flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the subendocardial ischemic and nonischemic zones. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to attain a diastolic perfusion pressure of 40 mm Hg. Twelve dogs received intravenous nifedipine, 3 μg/kg per min, and 12 received intravenous nitroglycerin to reduce aortic pressure by 20 mm Hg. Partial occlusion resulted in a slight but significant decrease in segment shortening in the ischemic zone. Neither nitroglycerin nor nifedipine affected shortening in the ischemic zone. After occlusion, blood flow decreased in the subendocardial ischemic zone but was unchanged in the subepicardium. Nifedipine increased subendocardial blood flow in the nonischemic zone and decreased it in the ischemic zone but caused no change in subepicardial flow in the ischemic zone. In contrast, nitroglycerin decreased subendocardial and subepicardial blood flow in both the ischemic and nonischemic zones. In the setting of coronary stenosis, different classes of vasodilators may have varying effects on myocardial blood flow, suggesting different sites and mechanisms of action. In addition, segment function may not always reflect changes in myocardial blood flow.     

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

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

Effects of nitroglycerin-induced hypotension on myocardial blood flow in a two vessel occlusion-stenosis anesthetized canine model

The effects of acute occlusion of the left anterior descending coronary artery on regional blood flow (microspheres) to the remote bed supplied by either an unstenosed or a stenosed circumflex coronary artery were assessed during the infusion of intravenous nitroglycerin in 11 open chest barbiturate-anesthetized mongrel dogs. Left anterior descending coronary artery occlusion in the presence of an unstenosed left circumflex artery during nitroglycerin infusion caused systolic aortic and distal circumflex pressure to decrease significantly from 98 +/- 4 to 91 +/- 3 and from 99 +/- 4 to 92 +/- 3 mm Hg, respectively. Remote circumflex bed flow was unchanged. The infusion of intravenous nitroglycerin in the presence of a left circumflex stenosis (gradient 31 +/- 3 mm Hg) reduced systolic aortic and distal circumflex pressure to 98 +/- 2 (p = 0.001) and 71 +/- 4 mm Hg (p = 0.001), respectively, and lowered remote circumflex bed endocardial flow from 1.00 +/- 0.08 to 0.79 +/- 0.07 ml/min per g (p = 0.001). When the left anterior descending coronary artery was occluded under these conditions, systolic aortic and distal left circumflex pressure decreased to 89 +/- 3 (p = 0.005) and 62 +/- 4 mm Hg (p = 0.08), respectively. Remote circumflex artery bed endocardial and transmural flow were significantly reduced to 0.58 +/- 0.07 (p = 0.01) and 0.65 +/- 0.07 ml/min per g (p = 0.03), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Compensatory subendocardial hyperkinesis in the cat is abolished during coronary insufficiency outside an acutely ischaemic region.

OBJECTIVE: The aims were to determine (1) whether acute coronary occlusion provoked uniform hyperkinesis in remote non-ischaemic myocardium, and (2) how subsequent coronary stenosis affected such hyperkinesis. METHODS: Two pairs of ultrasonic crystals were placed in the anterior left ventricular midwall of nine pentobarbitone anaesthetised open chest cats. One pair (longitudinal) ran parallel to subendocardial fibres; the other pair (circumferential) was aligned with subepicardial and mid-myocardial fibres. Following circumflex coronary occlusion, subsequent hypoperfusion of the anterior wall was established by controlled constriction of a shunt line from the right subclavian artery to the left main coronary artery in two discrete steps. RESULTS: Following circumflex occlusion maximum systolic shortening of segments aligned to subendocardial fibres increased from 6.7(SEM 0.9)% to 11.5(1.4)% (p less than 0.001), whereas circumferential segment shortening was unchanged, at 12.2(0.8)% v 14.1(1.1)%. During mild shunt stenosis [delta P = 42(2) mm Hg] subendocardial tissue blood flow in the anterior wall decreased by 42(10)% (p less than 0.001), and longitudinal segment shortening decreased from 11.5(1.4)% to 6.9(1.1)% (p less than 0.001). Corresponding shortening of circumferential segments did not change. During severe shunt stenosis [delta P = 52(3) mm Hg] subendocardial tissue blood flow decreased further, and shortening of longitudinal segments approached zero value (p less than 0.001). CONCLUSIONS: Compensatory hyperkinesis of remote non-ischaemic myocardium following an acute coronary occlusion may depend mostly on augmented subendocardial contraction.     

Coronary artery stenosis provokes non-uniformity of two-dimensional deformation in the anterior wall of the feline left ventricle.

The effect of coronary stenosis on the uniformity of local left ventricular contraction was studied in 11 open-chest cats. Coronary artery stenosis was established by controlled constriction of a shunt line from the right subclavian artery to the left main coronary artery. Two pairs of ultrasonic crystals were placed in the midwall of the anterior left ventricular wall; one pair, circumferential (Circ), aligned with midwall and subepicardial fibres; the other, longitudinal (Long), aligned with subendocardial fibres. Three steps of coronary perfusion pressure (poststenotic) were studied; open shunt line (140 +/- 4 mmHg), light stenosis (94 +/- 2 mmHg), and severe stenosis (70 +/- 3 mmHg). Subendocardial tissue blood flow showed the most pronounced reduction (from 1.87 +/- 0.11 to 1.43 +/- 0.10 and 0.86 +/- 0.12 ml min-1 g-1, respectively) with coronary stenosis whereas subepicardial flow remained unchanged. Maximal systolic shortening deteriorated for both segments. However, it was most pronounced for longitudinal segments. Duration of shortening decreased in longitudinal segments during severe stenosis to 62% of duration with open shunt (P less than 0.05), but was unchanged in circumferential segments. Long/Circ ratio of maximal systolic shortening declined by 50% (P less than 0.05) with reduction of coronary perfusion pressure. The reduced uniformity of segment shortening, caused by a marked reduction of longitudinal segment shortening, may support the notion that the longitudinal segment reflects performance of subendocardial fibres. This study demonstrates local non-uniformity of two-dimensional deformation during coronary artery stenosis and subendocardial hypoperfusion.     

Mechanisms of subendocardial dysfunction in response to exercise in dogs with severe left ventricular hypertrophy.

The effects of exercise on regional myocardial blood flow and function were examined in the presence and absence of beta-adrenergic receptor blockade in 10 adult conscious dogs with severe left ventricular (LV) hypertrophy induced by aortic banding in puppies, which increased the LV weight/body weight ratio by 87%. Exercise at the most intense level studied increased LV systolic (+87 +/- 8 mm Hg) and end-diastolic (+28 +/- 5 mm Hg) pressures, systolic (+85 +/- 12 g/cm2) and diastolic (+49 +/- 11 g/cm2) wall stresses, and subepicardial wall thickening (+0.18 +/- 0.05 mm) but reduced subendocardial wall thickening (-0.45 +/- 0.12 mm) and full wall thickening (-0.42 +/- 0.13 mm). This was associated with a fall in the subendocardial/subepicardial (endo/epi) blood flow ratio to 0.87 +/- 0.06 from 1.24 +/- 0.08. Subendocardial dysfunction persisted during recovery, at a time when transmural blood flow distribution returned to baseline, suggesting myocardial stunning. At the least intense level of exercise studied, the endo/epi blood flow ratio did not fall (1.27 +/- 0.14), but increases in heart rate (+73 +/- 8 beats per minute) and LV systolic (+35 +/- 8 g/cm2) and diastolic (+27 +/- 3 g/cm2) wall stresses were observed, and subendocardial wall thickening fell significantly (-0.21 +/- 0.08 mm, p less than 0.05). With anticipation of exercise, subendocardial wall thickening was not changed. However, subendocardial dysfunction was even evident after 10 beats, i.e., the first 3 seconds of exercise, at a time when LV pressures and stresses had not increased. After beta-adrenergic receptor blockade with propranolol, the most intense level of exercise was associated with lesser increases in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio was no longer reduced below unity (1.17 +/- 0.09). In addition, there were no decreases in subendocardial or full wall thickening, and myocardial stunning was no longer observed. Thus, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Furthermore, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of pulsed external augmentation of diastolic pressure on coronary and systemic hemodynamics in patients with coronary artery disease

The purpose of this study was to define the effects of pulsed external diastolic pressure augmentation on coronary and systemic hemodynamics in 14 men with coronary artery disease and normal left ventricular function. Coronary sinus and great vein blood flow (thermodilution) and systemic hemodynamics were measured before, during, and after timed lower extremity compression, augmenting peak diastolic pressure to within 5 mm Hg of systolic pressure. Systolic and diastolic pressure-time indices were calculated from the high-fidelity micromanometer left ventricular-aortic recordings. External counterpulsation increased mean arterial pressure (108 +/- 11 [1 SD] to 114 +/- 12 mm Hg, p less than 0.01) and the diastolic pressure-time index (440 +/- 51 to 498 +/- 82 units, p less than 0.01), with no change in the systolic pressure-time index, absolute coronary sinus, or great cardiac vein blood flow. External diastolic pressure augmentation did not affect heart rate, right heart hemodynamics, cardiac output, or calculated myocardial oxygen consumption. An unanticipated finding was a greater than or equal to 10% reduction in peak systolic pressure during external diastolic pressure augmentation in 8 of 14 patients. Despite minimal changes in absolute myocardial blood flow and oxygen consumption, the increase in the diastolic pressure-time/systolic pressure-time index ratio suggests that subendocardial perfusion may be favorably influenced by diastolic pressure augmentation and may explain the previously reported clinical benefits of external counterpulsation in some patients with ischemic heart disease.     

Acute effect of systemic versus intracoronary dipyridamole on coronary circulation

Dipyridamole has been proposed as an ideal agent to evaluate coronary vascular reserve because it produces selective coronary vasodilation without systemic hemodynamic effect. The actions of intracoronary (IC) and intravenous (IV) dipyridamole on coronary blood flow and systemic hemodynamics were compared in 15 patients with chest pain syndrome and normal coronary arteries. They received IC dipyridamole, followed 10 minutes later by 0.5 mg/kg of IV dipyridamole. IC dipyridamole produced a 73% increase in coronary sinus flow without hemodynamic changes, except for a slight increase in pulmonary systolic and diastolic pressures. IV dipyridamole administration produced an additional 88% increase in coronary sinus flow, reaching 172% over baseline; it was also associated with a significant (p less than 0.01) increase in heart rate (78 +/- 14 vs 102 +/- 19 beats/min), cardiac index (4 +/- 0.7 vs 6.3 +/- 1.7 liters/min/m2), and pulmonary artery systolic (27 +/- 5 vs 34 +/- 7 mm Hg) and diastolic pressures (12 +/- 4 vs 19 +/- 7 mm Hg). These data suggest that the coronary vasodilatory effect seen after IV dipyridamole administration is related to mechanisms other than direct coronary vasodilation.     

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)     

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

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

Effect of nitroglycerin during hemodynamic estimation of valve orifice in patients with mitral stenosis

In patients with mitral stenosis, valve orifice calculations using pulmonary capillary wedge pressure as a substitute for left atrial pressure may overestimate the severity of disease. Previous studies have shown that mitral valve area determined from transseptal left atrial pressure measurements exceeds that area derived from pulmonary wedge pressure measurements. This is probably due to pulmonary venoconstriction, which is reversed by nitroglycerin. Nitroglycerin, 0.4 mg, was administered sublingually to 20 patients with mitral valve disease during preoperative cardiac catheterization using the pulmonary capillary wedge pressure as the proximal hydraulic variable. At the time of a peak hypotensive effect, 3 to 5 minutes after nitroglycerin administration, the mean pulmonary capillary wedge pressure decreased from 23 +/- 2 (mean +/- SEM) to 19 +/- 2 mm Hg (p less than 0.005). The mean diastolic transmitral pressure gradient (12.6 +/- 1.2 mm Hg before and 11.5 +/- 1.0 mm Hg after nitroglycerin; p = NS) and cardiac output (4.0 +/- 0.3 to 4.1 +/- 0.3 liters/min; p = NS) did not change significantly. Nevertheless, the hemodynamic mitral orifice area, calculated using the Gorlin formula, increased from 0.8 +/- 0.1 to 1.1 +/- 0.2 cm2 (p less than 0.05). In 12 patients with isolated mitral stenosis, without regurgitation, the mitral valve orifice area after nitroglycerin was 0.4 +/- 0.2 cm2 larger than it was before drug administration (p less than 0.05). Administration of nitroglycerin during evaluation of mitral stenosis eliminates pulmonary venoconstriction, which raises the pulmonary capillary wedge pressure above the left atrial pressure in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the distribution of intramyocardial pressure across the canine left ventricular wall in the beating heart during diastole and in the arrested heart. Evidence of epicardial muscle tone during diastole

Computations of compliance of the left ventricle (LV) during diastole assume passive tissue characteristics. To evaluate this assumption, we measured diastolic LV intramyocardial pressure simultaneously in the subepicardium and subendocardium in 18 open-chest dogs, using 1-mm in diameter micromanometers. Subepicardial pressure, 26 +/- 1 mm Hg (mean +/- SEM) exceeded subendocardial pressure, 14 +/- 1 mm Hg (P less than 0.001), and it exceeded left ventricular end-diastolic pressure (LVEDP) (9 +/- 1 mm Hg) (P less than 0.001). After an infusion of dextran-40 (10 dogs), subepicardial diastolic pressure increased to 42 +/- 4 mm Hg which was higher than diastolic subendocardial pressure, 26 +/- 2 mm Hg (P less than 0.001) and LVEDP, 24 +/- 2 mm Hg (P less than 0.001). Following cardiac arrest (12 dogs) with the intramyocardial probes unchanged in position, LV intracavitary pressure, 9 +/- 1 mm Hg, and subendocardial pressure, 13 +/- 3 mm Hg, did not differ significantly from the pressures in the beating heart. Subepicardial pressure, 9 +/- 1 mm Hg, was lower than in the beating heart (P less than 0.001). Following distention of the arrested LV (12 dogs), subepicardial pressure, 31 +/- 7 mm Hg, was lower than both subendocardial pressure, 58 +/- 12 mm Hg (P less than 0.001) and LV intracavitary pressure, 54 +/- 11 mm Hg (P less than 0.001). These observations indicate that tone is maintained by the subepicardium during diastole. Furthermore, the LV wall does not appear to behave as a passive shell during ventricular filling.     

Effect of nitroglycerin-induced reduction of left ventricular filling pressure on diastolic filling in acute dilated heart failure

Recent information has suggested that early diastolic filling may be influenced by the left ventricular filling pressure, especially in the failing left ventricle. Acute severe left ventricular dysfunction was induced in 14 dogs by severe left ventricular global ischemia produced by left main coronary artery microsphere embolization until the left ventricular end-diastolic pressure was greater than or equal to 20 mm Hg. To assess the importance of left ventricular filling pressure on left ventricular diastolic filling, nitroglycerin was infused and titrated to reduce left ventricular end-diastolic pressure to less than 15 mm Hg in seven dogs, whereas the remaining seven dogs were observed for 1 h after acute severe left ventricular dysfunction. In both groups of dogs, severe left ventricular dysfunction resulted in left ventricular dilation and elevation of end-diastolic pressure, reduction in area ejection fraction (echocardiographically determined) and an early redistribution of diastolic filling (increased filling fractions at one-third and one-half diastole) despite prolongation of the time constant of left ventricular pressure decline. Pressure-area plots shifted upward and rightward with severe left ventricular dysfunction and were unchanged at 1 h as were all other variables. Nitroglycerin infusion reduced left ventricular size and filling pressure, redistributed diastolic filling to later in diastole as characterized by reduced filling fraction at one-third diastole (left ventricular dysfunction 48.8 +/- 9.7%, nitroglycerin 17.9 +/- 7.9%, p less than 0.001) and shifted downward left ventricular pressure-area plots. Nitroglycerin also improved the time constant of relaxation (left ventricular dysfunction 83 +/- 15 ms, nitroglycerin 52 +/- 15 ms, p less than 0.001) and lengthened the diastolic filling period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Doppler study of phasic variations of blood flow velocity in the anterior interventricular artery

Studies of changes in coronary blood flow during cardiac cycles may be a useful adjuvant to the measurement of coronary flow reserve to evaluate the hydraulic severity of coronary arterial stenoses. We used intracoronary pulsed Doppler velocimetry to measure phasic variations of blood flow in the anterior interventricular artery of 12 patients with angiographically identified stenosis of that vessel. The Doppler signal was obtained by means of a 20 MHz emission from a source placed at the tip of a catheter selectively positioned at the ostium of the anterior interventricular artery, upstream of the stenosis. The increase in severity of stenosis was paralleled by a relative decrease of diastolic blood flow velocity in relation to systolic blood flow velocity. The diastolic/systolic maximum velocities ratio was greater than 1 in 6 patients with a less than 70 p. 100 stenosis (group A) and inferior to 1 in 6 other patients with a 70 p. 100 or more stenosis (group B). In 5 patients of group B this ratio was reversed to normal after percutaneous transluminal angiography. Thus, measurement of intracoronary blood flow velocity may be helpful to evaluate the severity of stenosis, notably in the anterior interventricular artery where angiographic evaluation is difficult.