Variable effects of intracoronary nitroglycerin on myocardial blood flow and segmental shortening according to dose and degree of coronary occlusion

The effects of intracoronary nitroglycerin were determined in 21 open-chest dogs. Six dogs with severe stenosis (25 mm Hg diastolic perfusion pressure) and nine dogs with moderate stenosis (40 mm Hg) received a 12 micrograms bolus followed by 44 micrograms/min intracoronary nitroglycerin. In addition, six dogs with moderate stenosis (40 mm Hg) received 5 micrograms followed by 5 micrograms/min nitroglycerin. Myocardial blood flow was measured with radioactive microspheres and segment shortening with ultrasonic crystals. At 40 mm Hg, high-dose but not low-dose nitroglycerin raised epicardial blood flow, while at 25 mm Hg nitroglycerin had no effect. Subendocardial blood flow was not affected in any group. Partial occlusion resulted in a decrease in segment shortening in the 25 mm Hg group but not at 40 mm Hg. High-dose nitroglycerin had no effect on shortening at either level of occlusion. Thus, in the presence of coronary vascular reserve, high-dose nitroglycerin may overcome coronary autoregulation. A dose equivalent to one that simulates the amount of nitroglycerin delivered to the coronary circulation by a systemic infusion did not affect myocardial blood flow. In addition, even a large dose of nitroglycerin did not affect segment shortening.     

Absence of coronary vascular reserve in myocardium distal to a fixed coronary stenosis

In a study to test the hypothesis that vascular reserve is exhausted in the setting of a resting blood flow deficit, the left anterior descending or circumflex artery was cannulated and perfused from the left carotid artery. After reactive hyperaemia had been assessed a stenosis was produced with a screw clamp. In the first experiment a moderate stenosis (diastolic perfusion pressure 40 mmHg) was produced in the left anterior descending artery (three dogs) or left circumflex artery (three dogs). Blood pressure was held constant with aortic constriction during intracoronary adenosine infusion (6 mumol.min-1). The stenosis was then adjusted to the preadenosine perfusion pressure. In the second experiment the anterior interventricular coronary vein was also isolated and segment length crystals were placed in the ischaemic and non-ischaemic zones. Severe stenosis (flow reduction of at least 50% and evidence of decreased segmental shortening) was produced in the cannulated left anterior descending artery (eight dogs). Intracoronary adenosine was given with aortic pressure held constant by transfusion and coronary venous drainage. In the first experiment resting coronary flow (ml.min-1) decreased from 41(3) to 29(6) (p less than 0.05) with stenosis. Coronary flow increased from 29(6) to 34(7) (p less than 0.05) with adenosine and to 50(10) (p less than 0.05) with stenosis adjustment. Subendocardial flow (ml.g-1.min-1) decreased from 0.89(0.26) to 0.78(0.23) (p less than 0.05) with adenosine and then increased from 0.94(0.49) with perfusion pressure adjustment. Subepicardial flow tended to increase with adenosine, and increased further with stenosis adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of denopamine with or without diltiazem on the ischemic heart of anesthetized dogs.

Effects of denopamine with or without diltiazem on the ischemic heart were investigated in anesthetized open-chest dogs. Partial occlusion of the left circumflex coronary artery (LCX) produced significant decreases in LCX flow and regional myocardial segment shortening rate (%SS) in the LCX-perfused area, and a significant increase in left ventricular enddiastolic pressure (LVEDP). Heart rate (HR) and mean aortic pressure (mAoP) were not altered, but aortic flow (AoF), positive first derivative of left ventricular pressure ((+)LVdP/dt), stroke volume (SV), stroke work index (SWI) and double product showed a tendency to decrease. Total peripheral vascular resistance (TPR) tended to increase. During coronary stenosis, saline infusion (vehicle group) did not change any parameter, but diltiazem infusion (diltiazem group) decreased HR, mAoP, TPR and double product and increased SV and SWI. Under these conditions, denopamine infusion produced increases in HR, mAoP, AoF, (+)LVdP/dt and double product and decreases in LVEDP and TPR in both groups. %SS in the left anterior descending coronary artery-perfused area was increased, but %SS in the LCX-perfused area was slightly decreased in both groups. SV and SWI were decreased by denopamine infusion in the vehicle group, while they were increased in the diltiazem group. Differences in changes in SV and SWI between the groups were statistically significant. Results suggest that combined treatment of denopamine and diltiazem may exert an advantage in alleviation of heart failure due to coronary stenosis.     

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.     

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.     

Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis

Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventricular:body weight ratio was 7.1 +/- 0.4 as compared to 4.4 +/- 0.3 g/kg in 11 normal dogs (P less than 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 +/- 0.39) was substantially less than in normal dogs (6.19 +/- 0.54 ml/min per g; P less than 0.01), whereas minimum coronary resistance was increased from 14.1 +/- 1.7 in normal dogs to 23.7 +/- 5.4 mmHg. min X g/ml (P less than 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress.     

Decreased aortic compliance aggravates subendocardial ischaemia in dogs with stenosed coronary artery.

OBJECTIVES: The existence of decreased aortic compliance due to arteriosclerosis has been documented in patients with coronary artery disease. The aim of this study was to investigate the effects of decreased aortic compliance on coronary artery disease. METHODS: To simulate coronary artery disease, a fixed stenosis was made in the left circumflex coronary artery in dogs. Ten anaesthetised open chest dogs were used. Aortic compliance was decreased by banding the thoracic aorta with adjustable plastic rings. The level of coronary stenosis was adjusted to reduce the baseline flow by no more than 10% but enough to eliminate reactive hyperaemia induced by a 10 s occlusion. Measurements of haemodynamics, regional myocardial segment length, subendocardial ECG, and myocardial tissue PO2 were performed at five stages (initial control stage, rest and pacing stages without aortic banding, and rest and pacing stages with the aortic banding). RESULTS: Haemodynamic variables were not changed at any stage, except for increased pulse pressure secondary to the aortic banding. During pacing with aortic banding, subendocardial PO2 (Endo) levels were decreased, and subepicardial PO2 (Epi) levels were increased, compared to those without the aortic banding [Endo: 43.2(SD 9.8) v 36.8(10.0) mm Hg, p < 0.05; Epi: 34.0(11.5) v 44.4(7.9) mm Hg, p < 0.05]. ST elevation on the subendocardial ECG was greater, and myocardial segment shortening was less with the aortic bandage during pacing. CONCLUSIONS: When the work of the heart is increased, a decrease in aortic compliance tends to compromise ischaemic myocardium further in the presence of an induced stenosis of a major coronary artery.     

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.     

Measurement of coronary collateral flow and resistance in the presence of an open critical stenosis, and the response to intra-arterial thrombosis

OBJECTIVE: (1) Can one measure coronary collateral flow around an open critical stenosis? (2) Does intracoronary platelet thrombosis affect native coronary collateral vessels? METHODS: We measured regional myocardial blood flow by the radioactive microsphere technique in seven anaesthetised dogs with an ultrasonic flowmeter on the circumflex branch of the left coronary artery (LCx). Measurements were made (a) in a control period, (b) after induction of a tight stenosis on the LCx, and (c) after additional arterial damage at the stenosis to induce intraluminal thrombosis. Collateral flow was calculated from LCx tissue flow(in ml/min/g tissue) minus LCx flowmeter flow which is in ml/min. Therefore, it was necessary to use scaling by reference back to the control measurements and conversion to ml/min/g tissue equivalent. RESULTS: LCx stenosis induced collateral flow from the other coronary arteries into the LCx area of supply, which decreased (mean+/-S.E.) from 0.23+/-0.03 to 0.15+/-0.05 ml/min/g tissue with thrombosis. Collateral resistance correspondingly increased with thrombosis from 187.6+/-18. 2 to 1069+/-544 mmHg/ml/min/g (P<0.02). CONCLUSION: Coronary collateral flow around an open stenosis can be measured by reference back to control conditions. The coronary collaterals vasoconstrict in the presence of thrombosis even though they are in the stream of blood coming from normal coronary arteries.     

Tachycardia induced reduction in coronary blood flow distal to a stenosis

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

Comparative effects of nitroglycerin on intestinal vascular capacitance and conductance

BACKGROUND: Nitroglycerin (NTG) dilates capacitance veins and resistance arterioles, but its relative effects on veins and arterioles are not known. OBJECTIVES: To compare NTG-induced changes in capacitance and conductance. ANIMALS AND METHODS: Aortic, left ventricular and portal venous (P(port)) pressures, portal flow and relative changes in intestinal blood volume (IBV) ((99m)technetium blood-pool scintigraphy) were measured in seven isoflurane-anesthetized, splenectomized dogs. Changes in intestinal vascular capacitance and conductance (mean portal flow/[mean aortic pressure - mean P(port)]) were determined when NTG was continuously administered (0.8 to 150 microg/kg/min) into a jugular vein. Pressure-volume (ie, P(port)-IBV) curves were defined by impeding portal flow, and capacitance was defined as the IBV at P(port)=7.5 mmHg. RESULTS: At lower doses, NTG increased capacitance without increasing conductance, but conductance increased considerably with little further increase in capacitance at higher doses. Dose-response analysis revealed that the half-maximum capacitance effect was achieved at an NTG infusion rate of 3.5 microg/kg/min, whereas a rate of 35 microg/kg/min was required for the half-maximum conductance effect. CONCLUSIONS: At lower doses, NTG dilates capacitance vessels primarily, and that effect approaches its maximum before significant dilation of conductance vessels is manifest. However, at higher doses, the increase in conductance is substantial with little additional effect on capacitance.     

Effects of co-existence of coronary stenosis and the extent of coronary ectasia on the TIMI frame count in patients with coronary artery ectasia

The measurement of the thrombosis in myocardial infarction (TIMI) frame count is a simple method for evaluating coronary blood flow. Although it is well known that slow coronary flow is present in patients with coronary artery ectasia (CAE), the effects of coexisting stenosis and the severity of ectatic involvement on coronory flow have not been adequately studied. Thus, we examined (1) the effect of coexistence of obstructive coronary artery disease on TIMI frame count (TFC) and (2) the relation between the severity of ectatic involvement and TFC in patients with CAE. Ninety-seven study patients with CAE were examined in two steps to determine if they were appropriate in terms of the aim of this study. In the first step, ectasias were divided into three groups: an isolated CAE group, a CAE group with coexisting nonsignificant stenosis, and CAE with coexisting significant stenosis. In the second step, ectasias were subdivided into three groups: CAE with one segment, two segments, and three segments (or diffuse) involvement. The TIMI frame counts for the right coronary artery (RCA), the left circumflex coronary artery (LCx), and the left anterior descending artery (LAD) in the ectasia group were significantly higher than that of the control group (P < 0.001, P < 0.05, P < 0.05, respectively). The presence of coexisting nonsignificant stenosis or coexisting significant stenosis in patients with CAE did not influence TFC (P > 0.05, for all). In addition, the severity of ectasia involvement, regardless of the localization of ectatic segments and the type of the affected vessel, did not change the TFC (P > 0.05, for all). These results suggest that neither the coexisting stenosis nor the extent of involvement significantly affect TFC in patients with coronary ectasia.     

Endothelium-dependent vasodilating effect of substance P during flow-reducing coronary stenosis in the dog.

The effects of substance P, a putative central and peripheral neurotransmitter, on coronary vasculature and its mechanisms were studied in 31 anesthetized open chest dogs. Without coronary stenosis, intracoronary infusion of substance P (0.001 to 1 pmol/kg per min) for 40 s increased coronary blood flow up to 173 +/- 10.7% in dose-dependent fashion. Application of coronary stenosis created by an inflated intraluminal microballoon that preserved active vasomotion of the stenosed segment produced a pressure gradient of 34 +/- 2 mm Hg, a decrease in rest coronary blood flow of 21 +/- 1.6% and significant depression of the rate of rise in left ventricular pressure (dP/dt). During coronary stenosis, substance P increased coronary blood flow up to 150 +/- 9.4%, lowered mean distal coronary pressure and decreased stenosis resistance in dose-dependent fashion. After endothelial denudation of the proximal part of the coronary artery, the substance P-induced increments in coronary blood flow during coronary stenosis were abolished. In vitro measurements of isometric tension from both intact and denuded portions of coronary arteries confirmed a marked inhibition of substance P-induced relaxation in the denuded segments. These results show the obligatory role of the endothelium in substance P-induced coronary artery dilation. Furthermore, intracoronary infusion of substance P (1 pmol/kg per min) from the site distal to coronary stenosis that precluded the responsiveness of the large coronary artery decreased coronary blood flow by 24 +/- 4%, lowered mean distal coronary pressure by 15 +/- 1.9 mm Hg and intensified stenosis resistance by 77 +/- 7.2%. Thus, substance P exerts a direct potent dilating effect on both large and small coronary arteries. However, because of its strict endothelium-dependency, this peptide may play a detrimental role in the regulation of coronary blood flow when an atherosclerotic stenotic lesion with endothelial damage or dysfunction is present in the proximal part of the coronary artery.     

Chronically decreased aortic distensibility causes deterioration of coronary perfusion during increased left ventricular contraction

Objectives. This study investigated the long-term effects of decreased aortic distensibility on the heart in relation to coronary perfusion.Background.Aortic distensibility is decreased in patients with atherosclerosis and hypertension and in the elderly. However, the effect of a long-term decrease in aortic distensibility on coronary perfusion has not been fully investigated.Methods. Twelve anesthetized dogs underwent thoracotomy and were allocated to two groups: Group I included six control dogs with a normal aorta; Group II included six dogs with decreased aortic distensibility produced by banding the descending aorta. After 4 to 6 weeks, the dogs had a second operation to measure coronary artery flow and transmural flow distribution. Because the effect of decreased aortic distensibility on coronary perfusion may be affected by ventricular contractility, measurements were performed at baseline and during increased ventricular contraction induced by isoproterenol infusion.Results. At baseline, arterial compliance was reduced by 35% in Group II, but there was no change in total mean arterial resistance. Hemodynamic variables, regional wall motion and coronary flow were also similar in both groups. However, during isoproterenol infusion, coronary flow increased more in Group II than in Group I (p < 0.01), and the coronary flow reserve ratio (maximal peak hyperemic flow divided by rest flow) decreased more in Group II thin in Group I (mean [±SD] 1.9 ± 0.4 vs. 2.4 ± 0.3, p < 0.05). Moreover, although the transmural flow distribution was similar in the two groups at baseline, during isopraterenol infusion the endocardial flow increased less in Group II than in Group I (p < 0.05), and the endocardial/epicardial flow ratio was significantly decreased in Group II compared with Group I (mean [±SD] 0.70 ± 0.18 vs. 0.99 ± 0.22, p < 0.05). The subendocardial electrocardiogram showed ST segment elevation during isoproterenol infusion in Group II (p < 0.05) but not in Group I.Conclusions. These results demonstrate that during increased ventricular contraction, chronically decreased aortic distensibility contributes to a further decrease in the coronary flow reserve ratio, impairs endocardial blood flow and may induce subendocardial ischemia even in the absence of coronary artery stenosis.     

Effects of afterload elevation on the ischemic myocardium in isolated, paced canine heart with partial coronary stenosis

The effect of afterload elevation on the ischemic myocardium was examined in an isolated, paced canine heart with a partial coronary stenosis. The coronary blood flow of the left circumflex coronary artery was reduced to approximately one-third of the values before stenosis. The left circumflex coronary stenosis produced a decrease in global ventricular function, a decrease in systolic shortening and deviation of the ST-segment of the epicardial electrocardiogram and an increase in myocardial carbon dioxide (CO2) tension of the ischemic region. Then, afterload elevation with constant preload decreased the myocardial CO2 tension and improved the ST-segment deviation of the ischemic myocardium. Mechanical function, estimated by the relation between mean aortic pressure and systolic shortening, also improved with elevation of mean aortic pressure. In contrast, afterload elevation combined with preload elevation did not improve ischemic injury, as estimated by myocardial CO2 tension, and did not improve ST-segment deviation or mechanical function despite an increase in left circumflex coronary flow. These results suggest that the elevation of afterload pressure under constant preload improves ischemia produced by a partial coronary stenosis due to increased coronary blood supply; however, the preload elevation counterbalances the beneficial effects of afterload elevation.     

Coronary artery stenosis controlled by distal perfusion pressure: Description of the servo-system and time-dependent changes in regional myocardial blood flow

An animal model for the induction of coronary artery stenosis is described. In this model the degree of stenosis, as induced with commercially available hydraulic occluders, can be easily controlled by keeping constant the mean perfusion pressure (pcor) distal to the site of stenosis. This pcor is the input signal for a servo-system feeding a motor-pump, which determines the degree of inflation of the cuff around the left anterior interventricular coronary artery (LAICA). In each experiment pcor did not vary more than 2 mm Hg from the preset value of about 25 mm Hg. In 60 anesthetized open-chest dogs the time course of standard hemodynamic variables and regional myocardial blood flow in the center of the underperfused area, using the radioactive microsphere technique, were determined. Within 1 min after induction of stenosis heart rate and end-diastolic left ventricular pressure (plved) increased (by 20 and 60%, respectively) and mean aortic pressure and dplv/dtmax decreased (by 10 and 25%, respectively). After the initial decrease median myocardial blood flow further decreased between 1 and 5 min of stenosis from 0.63 to 0.32 ml.min-1.g-1 in the outer layers (P less than 0.05) and from 0.26 to 0.15 ml.min-1.g-1 in the inner layers (P less than 0.05), despite constant hemodynamic conditions and pcor. Between 5 and 120 min of stenosis these values remained unchanged in the outer layers, but decreased further in the inner layers to 0.08 ml.min-1.g-1 (P less than 0.05). The accurate control of pcor, the reproducibility of the levels of residual blood flow and the ease of handling the stenosis system indicate that coronary artery stenosis controlled by perfusion pressure distal to the stenosis is a useful animal model to study events during regional myocardial ischemia. With the use of this model of low flow ischemia a biphasic increase of myocardial vascular resistance was observed, which is initiated during the first minutes of coronary artery stenosis.     

Evaluation of "ischemia at a distance": effects of coronary occlusion on a remote area of left ventricle

The effect of coronary occlusion on blood flow and function in a remote zone of the left ventricle was studied in 21 open-chest dogs. Group A consisted of 6 dogs not undergoing left circumflex (LC) coronary artery cannulation. The other 15 dogs underwent cannulation of the LC artery followed by partial occlusion to 40 mm Hg diastolic perfusion pressure. Of these dogs, 7 with constant perfusion pressure (group B) were separately evaluated from 8 with declining perfusion pressure (group C). Sequentially more proximal left anterior descending (LAD) occlusions were performed in each group. Blood flow in the LC zone remained unchanged in group A after sequential LAD occlusions, whereas in groups B and C distal and proximal LAD occlusions caused progressive reduction in LC flow. Although in group A segment shortening improved in the LC zone after distal LAD occlusion, in groups B and C progressive impairment in segmental shortening was observed in the LC zone after distal and proximal LAD occlusions. Thus, in the setting of critical coronary stenosis in a zone, total occlusion in another coronary artery can initiate a series of events leading to decreased blood flow in the territory of the stenotic coronary artery, resulting in ischemia and impaired segmental function.     

Coronary microcirculatory vasoconstriction during ischemia in patients with unstable angina

OBJECTIVE: To verify the behavior of coronary microvascular tone during spontaneous ischemia in patients with unstable angina (UA). BACKGROUND: In UA, the pathogenetic role of vasoconstriction is classically confined at the stenotic coronary segment. However, microcirculatory vasoconstriction has been also suggested by previous experimental and clinical studies. METHODS: The study included 10 patients with UA (recent worsening of anginal threshold and appearance of angina at rest) and single-vessel CAD. Blood flow velocity was monitored by a Doppler catheter in the diseased artery. Transstenotic pressure gradient was monitored by aortic and distal coronary pressure monitoring. Stenosis resistance was calculated as the ratio between pressure gradient and blood flow, microvascular resistance as the ratio between distal pressure and blood flow. Measurements were obtained at baseline, following intracoronary adenosine (2 mg) and during transient ischemia. Aortic and distal coronary pressures were also measured during balloon coronary occlusion. RESULTS: Adenosine did not affect stenosis resistance, while it decreased (p < 0.05) microvascular resistance to 52 +/- 22% of baseline. Angina and ischemic ST segment shift were associated with transient angiographic coronary occlusion in 7 of 10 patients; however, in no case was ischemia associated with interruption of flow. Despite markedly different flow values, distal coronary pressure was similar during adenosine and during spontaneous ischemia (48 +/- 15 vs. 46 +/- 20 mm Hg, respectively, NS). During ischemia, a marked increase in the resistance of both coronary stenosis and coronary microcirculation was observed (to 1,233% +/- 1,298% and 671% +/- 652% of baseline, respectively, p < 0.05). Distal coronary pressure was markedly reduced during balloon coronary occlusion (14 +/- 7 mm Hg, p < 0.05 vs. both adenosine and ischemia), suggesting the absence of significant collateral circulation. CONCLUSIONS: In patients with UA, transient myocardial ischemia is associated with vasoconstriction of both stenotic arterial segment and downstream microcirculation.     

First ultra-short-acting beta-adrenergic blocking agent: Its effect on size and segmental wall dynamics of reperfused myocardial infarcts in dogs

Beta-adrenergic blocking agents have an established role in the treatment of myocardial ischemia, but precipitation of cardiac failure or bronchospasm may restrict their use in some patients with acute myocardial infarction or in those undergoing coronary bypass surgery. ASL-8052 is a new cardioselective ultra-short-acting beta blocker which allows abolition of beta blockade within 16 minutes on termination of an intravenous infusion. An investigation was made of the effect of ASL-8052 on myocardial infarct size, regional myocardial wall function, and hemodynamic features during a 3-hour experimental occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion in dogs.

Twenty-two dogs (10 control, 12 treated) were instrumented for the measurement of left ventricular (LV) pressure, the first derivative of left ventricular pressure (LV dP/dt), systolic and diastolic aortic pressure, and heart rate. Two pairs of ultrasonic crystals were inserted into a nonischemic segment and an ischemic marginal zone segment to obtain percent segment shortening. The area of necrosis was determined by tetrazolium staining and expressed as a percentage of the in vivo area at risk obtained by autoradiography. Dogs in the control group received saline solution; in treated dogs, a continuous infusion of ASL-8052 was begun 15 minutes after occlusion with a dose “titrated” to reduce the heart rate by approximately 20% (100 to 150 μg/kg/min). After 3 hours of reperfusion, the amount of myocardial tissue necrosis, as a function of the in vivo area at risk, was significantly lower in ASL-8052-treated (48 ± 7%) than in control (73 ± 6%) dogs (p < 0.025). Upon reperfusion, segment shortening decreased in control dogs from −3.3 ± 1.1% after 3 hours of occlusion to −6.3 ± 1.9% (p < 0.05) 2 hours after reperfusion (that is, systolic bulging increased). This functional deterioration upon reperfusion did not occur in treated dogs. During the occlusion period, infusion of ASL-8052 caused a decrease in heart rate of 22 ± 3% (p < 0.001) and in LV dP/dt by 22 ± 4% (p < 0.05). Upon reperfusion, control dogs had an increase in heart rate of 26 ± 1% (p < 0.05). In treated dogs, heart rate did not change. Hence, infarct size, reperfusion tachycardia, and myocardial wall asynergy were reduced in ASL-8052-treated dogs. A potential advantage of this agent is that its short duration of action would allow rapid reversal of beta blockade if adverse effects developed.     

Wandering coronary stenoses: Adrenaline‐induced coronary artery spasm in a patient resuscitated from cardiac arrest

A 68‐year‐old ex‐smoker man with history of allergy, presented to the emergency department with progressive dyspnea one hour following self‐medication with aspirin for troublesome headache. Examination revealed diffuse sibilant rhonchi over both lungs. Electrocardiogram showed signs of ischemia. In the intensive care unit, he received bronchodilators, nitroglycerin, and aspirin. Bronchospasm increased, and then the patient was shocked, and developed cardiac arrest. After resuscitation, he was kept on mechanical ventilation and adrenaline infusion. He was sceduled for coronary angiography. The left system demonstrated stenosis of the mid‐segment of the left anterior descending artery (LAD), which was totally occluded distally, stenosis of the left circumflex (LCx) with a mild plaque in its marginal branch. The right system demonstrated stenosis of the mid‐segment of the right coronary artery (RCA), with diffusely diseased posterior descending artery (PDA) and posterolateral left ventricular branch (PLLV). Successful direct stenting was performed to the RCA. Angiography demonstrated worsening of the distal stenosis in the PLLV and complete occlusion of the PDA. Balloon dilatation of the PLLV was adequate, but dilatation of the PDA failed. Repeat angiography of the left system revealed an occluded LCx with critical stenosis of its marginal branch; nevertheless, the LAD was as before. Balloon dilatation of the distal LAD was attempted without improvement, yet, angiography therein, demonstrated “migration” of the stenoses in the LCx. The procedure was halted, adrenaline infusion discontinued, and an intra‐aortic balloon pump inserted. The patient was discharged one day later. Follow‐up angiography 6 months later demonstrated mild atherosclerotic coronary irregularities. © 2010 Wiley‐Liss, Inc.