Effect of regional myocardial ischemia on cardiac pump performance during exercise

The effect of brief periods of regional ischemia upon left ventricular pump performance was studied in nine dogs standing quietly at rest and during running exercise on a treadmill. Transient occlusions of the left circumflex coronary artery resulted in increase in heart rate at rest (+30 beats/min) but not during exercise. Other changes due to occlusion were similar at rest and during exercise and included decreases in stroke volume (-25% standing, -23% running); in dP/dt max, the maximum first derivative of the left ventricular pressure (-20% standing or running); and in left ventricular peak systolic pressure (-13% standing, -21% running); and rises in left ventricular end-diastolic pressure (+4.5 mmHg standing, +6.3 mmHg running). Cardiac output was unchanged by occlusions at rest but fell (-18%) during occlusions while the dogs were running. Propranolol reduced absolute levels of cardiac performance during exercise occlusions but had no effect at rest. Inotropic agents with ischemia had some effects at rest but did not alter exercise hemodynamics. It is concluded that integrated left ventricular function during ischemia is not impaired by exercise, probably because of beta-adrenergic stimulation of nonischemic myocardium.     

Effects of time on volume and distribution of coronary collateral flow.

Changes in the volume and distribution of collateral blood flow were studied during the 1st h after coronary occlusion in nine open-chest dogs. Labeled microspheres (7-10 mum) were injected into the left atrium prior to and 20 s, 5 min, and 60 min after acute occlusion of the midcircumflex coronary artery so that myocardial perfusion to small segments of the entire left ventricle could be measured. The segmental perfusions were classified as normally perfused, severely hypoperfused, moderately hypoperfused, and borderline hypoperfused. Standard hemodynamic measurements were obtained and relative coronary vascular resistance to the normally perfused and hypoperfused zones was calculated. The principal conclusions of the study are as follows: 1) during the 1st h after coronary occlusion the collateral flow to the hypoperfused myocardium increases substantially; 2) the increase in collateral flow is distributed fairly evenly to various hypoperfused zones and is associated with a marked decrease in coronary vascular resistance; and 3) as a result of this influx in collateral flow the size of the hypoperfused area decreases and the relative proportion of severely hypoperfused segments within the hypoperfused area decreases.     

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3–8 μg kg^-1 min^-1 in group I (n=8); left ventricular peak systolic pressure (LVSP) 84±4 mmHg (mean±SEM) during coronary artery occlusion. In group II (n=7) LVSP was increased to 188±10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8±2.0% vs. 11.0±1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30±0.18 vs.  1.34±0.08 mL min^-1 g^-1 and 2.58±0.23 vs. 1.49±0.07 mL min^-1 g^-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.     

Functional Development of the Coronary Collateral Circulation During Coronary Artery Occlusion in the Conscious Dog

We studied changes in the coronary collateral circulation during coronary artery occlusion in 14 conscious dogs by: a) determining simultaneous changes in peripheral coronary pressure (PCP) and retrograde flow (RF) after abrupt coronary artery occlusion; b) correlating these functional indices with quantitative anatomic indices (AI) of coronary collateral development (Menick et al: Am Heart J 82:503-510, 1971); and c) observing changes in these indices after repeated reocclusions of a coronary artery. These dogs were subjected to left circumflex coronary artery (LCCA) occlusions for 2 hours to 8 days; pressure tubes were implanted in the aorta and LCCA, the latter tube placed distal to an occlusive cuff for PCP and RF measurements. Afterwards the animals were sacrificed, their hearts injected with a modified Schlesinger's gelatin mass, and AI determined. During 2 to 24 hour LCCA occlusions (11 dogs) mean PCP rose to levels 50 to 80% of prevailing aortic pressure. During repreated 2- to 24-hour occlusions (2 dogs) in the same dog, the rate at which PCP rose increased. Retrograde flow was unchanged during 2- to 24-hour occlusions. Anatomic indices of these dogs were in the same range as those observed in unoccluded controls. When LCCA occlusion was maintained for more than 4 days (3 dogs), mean PCP rose during the first 24 hours and then remained stable; RF did not change until 4 days into occlusion and then increased. Anatomic indices of dogs occluded for more than 4 days were significantly greater (P < 0.001) than those of the 2- to 24-hour occlusion groups. Our study shows that: a) the early PCP rise after occlusion is not associated with an increase in RF, b) RF is a better index of collateral function and c) RF correlated well with the anatomic development of the collateral bed.     

Coronary flow and left ventricular pressure during diastole in the anaesthetized dog.

There is controversy about the effect of left ventricular pressure on resistance of the intramyocardial coronary vessels. In anaesthetized dogs the effect of left ventricular pressure on coronary flow during diastole was studied using an extracorporeal circulation and allowing the heart to contract and relax isovolumically. At constant coronary perfusion pressure of about 45 mmHg with maximal coronary vasodilatation, produced by dipyridamole, increases in diastolic left ventricular pressure to 22 mmHg, producing a volume of 50 ml, did not affect diastolic coronary flow. It is suggested that in the intact animal over the physiological range of left ventricular diastolic pressure the resistance in the coronary vessels is not affected.     

Left ventricular responses to experimental aortic coarctation in growing puppies.

The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P less than 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 +/- 5 (SD) vs 5 +/- 4 mmHg, P less than 0.001, and after I isoproterenol infusion 56 +/- 9 vs 10 +/- 6 mmHg, P less than 0.001, and after I dextran infusion 58 +/- 10 vs 8 +/- 7 mmHg, P less than 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 +/- 8 ms and II, 30 +/- 4 ms) than in the control group (I, 21 +/- 2, P less than 0.05 and II, 19 +/- 3 ms, P less than 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 +/- 660 and II, 4080 +/- 810 mmHg s min-1) to higher levels than in the control group (I, 3550 +/- 220, II, 2540 +/- 1140 mmHg s min-1, P less than 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial infarction in dogs with acute and gradual occlusion of the circumflex or right coronary arteries

This study was designed to quantitate and describe the incidence and magnitude of myocardial infarction in the canine heart following acute and gradual occlusion of the circumflex or right coronary arteries. In animals with acute occlusion, the circumflex artery was ligated just distal to the bifurcation of the left coronary artery for 4 hr (seven dogs). Gradual occlusion was produced by placing an Ameroid occluder on the circumflex artery for 1 month (nine dogs), 3 months (nine dogs), and 5 months (eight dogs) and on the right coronary artery for 3 months (nine dogs). Ten dogs served as controls. At the end of the experiments the dogs were sacrificed, and identification of myocardial infarction was made with an enzyme-mapping technique in dogs with acute occlusion and with histological methods in dogs with gradual occlusion. The volume of ventricular infarction was determined with the use of an Apple II Computer and graphics tablet. After 3 months, gradual occlusion of the right coronary artery produced a 22% incidence of infarction which was significantly less (P <.01, X²) than the 67% incidence observed with 3 months of gradual circumflex occlusion. The average infarct volume produced by gradual right coronary occlusion was 0.94 + 0.69%. The average volume of left ventricular infarction in animals with circumflex acute occlusion was 15.6% + 6.6 and the incidence of infarction was 100%. With gradual occlusion of the circumflex artery for 1, 3, and 5 months, average left ventricular infarction was 2.02 ± 1.01%, 3.13 ± 1.53%, and 2.96 ± 1.35%, respectively. There were no significant differences in the amount of damage observed among the three groups with gradual occlusion, and the average incidence of infarction for these three groups was 76%. In the 1-, 3- or 5- month animals with circumflex occlusion, no additional areas of necrosis subsequent to the original damage were found, indicating that infarction is a single event in this model of gradual occlusion. These results suggest that infarct size is determined primarily by factors at the time of total occlusion and that gradual occlusion allows sufficient time for collateral growth, thereby limiting the extent of myocardial injury.     

Cardiovascular effects of haemorrhagic shock in spleen intact and in splenectomized dogs

Cardiac performance was evaluated during haemorrhagic shock in 27 dogs with spleens intact, 24 splenectomized, and 23 splenectomized transfused dogs that were given a volume of packed red blood cells simulating splenic contraction. Contractile changes were evaluated by calculating dP/dt at 20 mmHg developed pressure (dP/dt DP20), and by relating stroke work to left ventricular end-diastolic volume measured by biplane cinefluorography. Although heart rate increased comparably during early shock, cardiac output, stroke volume, maximal dP/dt, dP/dt DP20, and arterial blood pressure decreased more in splenectomized and splenectomized transfused dogs than in those with spleens intact. During shock dP/dt DP20 was more depressed in the splenectomized and splenectomized transfused dogs than in those with spleens intact. In addition, an increase in left ventricular end-diastolic volume was accompanied by an increase in left ventricular stroke work in dogs with spleens intact. In contrast, stroke work remained depressed in both splenectomized groups despite increased left ventricular volume. Progressive acidosis and decreased left ventricular blood flow were similar in all dogs during haemorrhage. The greater reduction in left ventricular performance during haemorrhagic shock in the splenectomized and splenectomized transfused dogs was not related to excess lactate, changes in plasma volume, or red blood cell mass. Decreased left ventricular performance, despite improved ventricular filling, indicates greater cardiac dysfunction during haemorrhagic shock. This study suggests that, in dogs, the spleen maintains left ventricular performance during haemorrhage by mechanisms other than autotransfusion.     

Ameroid constriction of the proximal left circumflex coronary artery in swine. A model of limited coronary collateral circulation

Gradual narrowing and occlusion of a coronary artery in patients with atherosclerotic heart disease frequently causes enlargement of the collateral circulation. Although these vessels may protect from development of myocardial infarction, they frequently do not supply sufficient blood flow to prevent ischemia during periods of augmented myocardial oxygen demand. The purpose of this study was to develop a model of the collateral circulation in pigs, a species that previously has been shown to develop sparse collateral vessels. Eighteen pigs were instrumented with an Ameroid constrictor around the proximal left circumflex artery and left atrial and aortic catheters. In four animals the constrictor was placed just distal to a large proximal obtuse marginal vessel. Seven of the pigs were treated daily with oral aspirin (325 mg) and disopyramide (200 mg) throughout the study; the other 11 served as controls. After an average of 24 days postoperatively, radioactive microspheres were injected at rest, during exercise (mean heart rate = 245 beats/min), and during intravenous infusion of dypridamole (700 micrograms/kg). At autopsy the extent of necrosis was assessed by a point counting technique in the bed at risk. We found that 75-83% of the bed at risk remained viable. Although aspirin and disopyramide did not significantly alter the extent of infarction (37 +/- 36% untreated vs 17 +/- 6% treated), there was less variability of infarction in the treated group, and subendocardial blood flow during exercise was higher in the treated group compared to controls. The majority of infarction occurred in the subendocardial region. Animals with a large obtuse marginal branch developed significantly smaller infarcts (8 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of chronic hypoxemia on regional myocardial blood flow in the conscious dog after acute coronary artery occlusion

Chronic hypoxemia was produced in 16 dogs by surgical transposition of the caudal vena cava to the left atrium to determine if chronic hypoxemia would alter the response of the myocardium to acute ischemia. An electromagnetic aortic flow probe, left atrial tube, and occlusive cuff on the left circumflex coronary artery were permanently implanted in 11 hypoxemic and 26 normal control dogs. The animals were studied in the conscious state after recovery from the surgery. Dogs with hypoxemia had a blood hematocrit value of 54.3 ± 1.0% (SE), arterial PO₂ of 43.2 ± 1.4 mm Hg, and 80.2 ± 1.6% oxygen saturation. There was no difference from control animals in the ratio of left ventricular weight to body weight, but the right ventricular weight was significantly decreased in the hypoxemic dogs. Cardiac output from the left ventricle was twice that of the right ventricle. Aortic blood flow was 3.68 ± 0.22 liters/min in hypoxemic animals and 2.64 ± 0.19 liters/min in normal dogs. Myocardial blood flow measured with 15-μ diameter tracer microspheres was increased from 79 ± 10 and 59 ± 8 ml/100 g/min in left ventricular endocardial and epicardial halves, respectively, in normal dogs to 212 ± 48 and 172 ± 39 in dogs with chronic hypoxemia. There were no deaths in 10 hypoxemic dogs within 24 hours after complete circumflex coronary artery occlusion; 7 of 26 (27%) normal dogs died after circumflex coronary artery occlusion during the conscious state. Gross infarct size was extremely variable in both groups. Median infarct size was smaller in dogs with hypoxemia and was directly correlated with arterial PO₂ in hypoxemic dogs. There was a mild, but statistically not significant, increase in the anastomotic index of hypoxemic dogs compared with that of normal animals, suggesting that a metabolic adaptive change rather than increased collateral circulation may have been responsible for the decreased mortality and smaller infarct size in hypoxemic dogs.     

Distribution of maximum coronary blood flow in the left ventricular wall of anesthetized dogs

Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In a group of dogs progressive hemodilution was performed until the diastolic reactive hyperemic response to 10 s occlusion of the circumflex branch disappeared (“optimum” hemodilution). At this degree of hemodilution the distribution of blood flow in the left ventricular free wall was evaluated by measuring tissue activity concentrations of Xe-133 and radioactive microspheres after bolus injection into the aortic root. “Optimum” hernodilution was accompanied by a sixfold increase in systolic coronary flow, a 3-fold increase in diastolic flow and a relative endocardial hypoperfusion. These results indicate that the endocardial blood flow reserve is lower than the epicardial. This conclusion is supported by the influence of spontaneous oscillations of arterial blood pressure (Traube-Hering waves) on systolic and diastolic coronary blood flows before and during “optimum” hemodilution. In another group of dogs maximum coronary vasodilatation was produced by occlusion of the left coronary artery for 10 s. In this group the distribution of Xe-133 and radioactive microspheres were measured after bolus injection into the aortic root at peak diastolic reactive hyperemia. The epi- and endocardial distribution of both Xe-133 and microspheres was uniform in the left ventricular wall, indicating a uniform flow to these regions. This might be explained by an increased endocardial perfusion during systole due to loss of myocardial contractility or by a decline towards resting level in epicardial flow at the time of injection, corresponding to a shorter duration of the hyperemic period in the epi- than endocardial region.     

Arterial pressure-flow relations in the awake standing dog.

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.     

Distribution of maximum coronary blood flow in the left ventricular wall of anesthetized dogs.

Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In a group of dogs progressive hemodilution was performed until the diastolic reactive hyperemic response to 10 s occlusion of the circumflex branch disappeared ("optimum" hemodilution). At this degree of hemodilution the distribution of blood flow in the left ventricular free wall was evaluated by measuring tissue activity concentrations of Xe-133 and radioactive microspheres after bolus injection into the aortic root. "Optimum" hemodilution was accompanied by a sixfold increase in systolic coronary flow, a 3-fold increase in diastolic flow and a relative endocardial hypoperfusion. These results indicate that the endocardial blood flow reserve is lower than the epicardial. This conclusion is supported by the influence of spontaneous oscillations of arterial blood pressure (Traube-Hering waves) on systolic and diastolic coronary blood flows before and during "optimum" hemodilution. In another group of dogs maximum coronary vasodilatation was produced by occlusion of the left coronary artery for 10 s. In this group the distribuition of Xe-133 and radioactive microspheres were measured after bolus injection into the aortic root at peak diastolic reactive hyperemia. The epi- and endocardial distribution of both Xe-133 and microspheres was uniform in the left ventricular wall, indicating a uniform flow to these regions. This might be explained by an increased endocardial perfusion during systole due to loss of myocardial contractility or by a decline towards resting level in epicardial flow at the time of injection, corresponding to a shorter duration of the hyperemic period in the epi- than endocardial region.     

Regulation of coronary blood flow during exercise

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.     

Cardiac effects of splanchnic and non-splanchnic blood volume redistribution during aortic occlusions in dogs

Translocation of blood from the lower body dilates the left ventricle during occlusion of the descending thoracic aorta and by increased activation of the Frank-Starling mechanism, stroke volume is maintained despite raised aortic blood pressure. The contributions from the splanchnic and non-splanchnic blood volumes to the left ventricular dilation were examined by ultrasonic measurements of myocardial chord length (MCL) in atropinized open-chest dogs. End-diastolic MCL rose by 2.5±0.9% during abdominal suprarenal aortic occlusion, draining blood from the non-splanchnic region, and by 7.4±1.7% during thoracic aortic occlusion draining blood from both splanchnic and non-splanchnic regions. Systolic left ventricular pressure rose by 16±3 mmHg and 76±12 mmHg, respectively. End-diastolic MCL rose by 6.0±1.2% during combined thoracic aortic and abdominal infrahepatic vena cava occlusion draining blood solely from the splanchnic region and further by 2.5±0.8% by blood drained from the non-splanchnic region after release of the vena cava occlusion. Similar results were obtained using a shunt permitting selective drainage first from the non-splanchnic region during thoracic aortic occlusion. Blood translocation from the non-splanchnic region maintains cardiac output during abdominal aortic occlusion. During occlusion of the thoracic aorta, drainage from the splanchnic region accounts for about 70% of the increase in end-diastolic MCL.     

巯甲丙脯酸对实验性冠状动脉痉挛致左室功能不全的作用

犬２１只，经左冠脉内注射麦角新硷诱发冠脉痉挛后随机静滴生理盐水（对照组）或等量盐水溶的巯甲丙脯酸（治疗组），观察１小时。心电图显示治疗组的异常ＳＴ段下降和严重室性心律失常明显少于对照组；冠脉造影显示治疗组痉挛血管支数及狭窄程度均少于和轻于对照组；左室造影和超声心电图显示治疗组的左室收缩末和舒张末容积小于对照组，ＥＦ值或△Ｄ大于对照组，ＡＡ／ＥＡ小于对照组；血流动力学参数表明治疗组左室收缩压，平均肺     

Left ventricular responses to experimental aortic coarctation in growing puppies

The haemodynamic status of 8 coarctated and 7 sham-operated beagle puppies was studied by a catheterization technique at rest and during isoproterenol and volume loading at the ages of 7 (I) and 9 (II) months (5 and 7 months after the experimental coarctation). Proximal aortic systolic and pulse pressures were constantly higher in the coarctation group than in the control group (P < 0.05), and the systolic pressure gradient across the coarctation was always significantly higher in the coarctation group [I at rest mean 45 pL 5 (SD) vs 5 pL 4 mmHg, P < 0.001, and after I isoproterenol infusion 56 pL 9 vs 10 pL 6 mmHg, P < 0.001, and after I dextran infusion 58 pL 10 vs 8 pL 7 mmHg, P < 0.001]. The time constant of exponential isovolumic left ventricular pressure fall after the isoproterenol tests was longer in the coarctation group (I 28 pL 8 ms and II, 30 pL 4 ms) than in the control group (I, 21 pL 2, P < 0.05 and II, 19 pL 3 ms, P < 0.005), indicating impaired relaxation. The tension time index during the volume loading tests increased in the coarctation dogs (I, 4150 pL 660 and II, 4080 pL 810 mmHg s min^-1) to higher levels than in the control group (I, 3550 pL 220, II, 2540 pL 1140 mmHg s min^-1, P < 0.05 both). Cardiac output, left ventricular end diastolic pressure, inotropic parameters and heart rate were similar in both groups during the infusions. The results show that the hearts of the young animals exposed to chronic pressure load by aortic coarctation maintained their pump performance well. The changes in left ventricular relaxation may be an early sign of impaired diastolic function.     

Right-left ventricular output balance in the totally implantable artificial heart

Pneumatically powered artificial hearts readily accommodated the higher net stroke volumes by the right ventricle than from the left ventricle. We published that this discrepancy was approximately 8% of the left ventricular cardiac output. A variety of methods have been used to achieve balance between the right and left atrial pressures. Relatively large volume-displacement chambers (VDC) present potential problems, but do provide balance. The VDC in volumetrically coupled right-left stroke volumes was eliminated by using a small-diameter interatrial shunt (IAS). Preliminary studies demonstrated excellent balance in contracted and expanded blood volume (preload) and by hypotension and hypertension created with vasoactive drugs (afterload). At a mean aortic pressure of 120 mmHg, heart rate of 120 BPM, cardiac output of 8 L/minute and right atrial pressure of 13 mmHg, the peak IAS flow was 3.2 ml/beat in a right to left direction and 8.0 ml/beat in a left to right direction. The net left to right flow was 4.8 ml/beat. Over a wide range of preload (2 to 20 mmHg) and afterload (45 to 180 mmHg), the left atrial pressure was routinely 5 mm Hg more than the right atrial pressure. Elimination of the VDC reduces the number of components, volume, and weight of the totally implantable artificial heart. The IAS offers a simple solution to a very complex problem and provides a device that is simpler to implant and is possible to explant.     

Analog Electrical Model of the Coronary Circulation in Case of Multiple Revascularizations

In this work, we propose an analog electrical model of the coronary circulation for patients with obstructive disease undergoing revascularization. In this clinical situation, the collateral circulation to the occluded artery is difficult to ascertain via preoperative measurements and well-developed collaterals might induce long-term restenosis of the revascularized artery due to flow competition mechanisms. The proposed model allows an original biomechanical analysis of per-operative hemodynamic data in order to assess quantitative evaluation of pressures and flows inside the native stenosed arteries, the collateral network and the bypass grafts. Average cardiac cycle values are analysed. In the case of 3-vessel disease and chronic occlusion of the right coronary artery, the quantitative results confirm the protective effects of the collateral flows in the pathological situation, but also show that the revascularization of the occluded right artery is fully justified since the collateral flows remain low, even when the left territory is revascularized. The model thus provides a computational tool to evaluate therapeutic strategies for each patient.     

Contributions of blood drainage from the liver,spleen and intestines to cardiac effects of aortic occlusion in the dog

By occluding the descending thoracic aorta, blood transferred from the lower to the upper part of the body increases left ventricular end-diastolic volume and maintains stroke volume despite a rise in systolic left ventricular pressure (LVP) of about 60 mmHg. Seventy percent of the blood drained stems from the splanchnic circulation. To examine which splanchnic organs contribute to the cardiac effects, selective occlusions were performed during ultrasonic measurements of spleen and liver dimensions and left ventricular myocardial chord length (MCL) in atropinized, open-chest dogs. Drainage of 15±2 ml from the spleen accounted for 18±4% of the increase in end-diastolic MCL, whereas liver dimensions remained unaltered. Similar results were obtained during aortic occlusion at high inotropy (isoproterenol infusion). it was ascertained by occlusion of the coeliac and mesenteric arteries that about 50% of the cardiac response to aortic occlusion was due to drainage from the intestines and the aorta. Liver blood volume could be reduced by combined occlusion of the aorta and portal vein or coeliac and mesentenc arteries and was sensitive to changes in pressure in the inferior vena cava, but did not contribute to the cardiac response to aortic occlusion.