Effects of coronary artery reperfusion on regional myocardial blood flow and function in conscious baboons

The effects of coronary artery reperfusion initiated 1 hr and 3 hr after coronary artery occlusion were evaluated on measurements of overall and regional left ventricular function and on regional myocardial blood flow. These experiments were conducted in conscious baboons 2 to 3 weeks after recovery from instrumentation with a solid state left ventricular pressure gauge, aortic and left atrial catheters, a hydraulic occluder around the mid left anterior descending coronary artery, and pairs of ultrasonic transducers implanted in the endocardium of the left ventricular free wall or across the free wall to measure endocardial segment shortening and wall thickening, respectively. Coronary artery occlusion induced similar effects in both groups. At 1 hr after occlusion, the ischemic zone was characterized by severe and equal reductions in both endocardial (-97 +/- 1%) and epicardial (-95 +/- 4%) blood flows and complete loss of regional systolic function, which was replaced by paradoxical wall motion. Reperfusion initiated after 1 hr of ischemia was associated with a marked transient increase in endocardial (+386 +/- 51%) and epicardial (+544 +/- 79%) blood flows. During the subsequent 4 weeks, segment shortening and wall thickening tended to improve. However, at 4 weeks after reperfusion, segment shortening was still depressed by 45 +/- 12% and wall thickening by 58 +/- 14%. In contrast, reperfusion initiated after 3 hr of ischemia was not associated with a significant hyperemic response, and systolic segment shortening and wall thickening did not recover during the subsequent 4 week period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular asynchrony: an indicator of regional myocardial dysfunction

There is a marked heterogeneity of myocardial wall thickening within the left ventricle and among different individuals. It is therefore difficult to detect regional myocardial dysfunction from absolute values of systolic wall thickening. We tested whether the extent of left ventricular asynchrony during ischemia and reperfusion can be used to quantify the severity of regional myocardial dysfunction when nonischemic baseline function is not known. In six anesthetized, open-chest dogs regional myocardial wall thickness was measured by means of sonomicrometry under control conditions, at three degrees of ischemic dysfunction (mild, moderate, and severe), and after release of a 15-minute occlusion of the left circumflex coronary artery, when degrees of moderate and mild reperfusion dysfunction similar to the preceding ischemic dysfunction were present. Two indexes of left ventricular asynchrony were calculated: (1) postejection thickening (PET) and (2) the phase difference of the first Fourier harmonic of posterior versus anterior myocardial wall motion (PD). Systolic myocardial wall thickening was decreased from 15.3 +/- 3.1 (standard deviation) % (control value) to 9.7 +/- 1.4% (mild ischemia), 4.2 +/- 1.6% (moderate ischemia), and -3.7 +/- 3.1% (severe ischemia). Conversely PET increased from 0.02 +/- 0.04 mm (control value) to 0.15 +/- 0.22 mm (mild ischemia), 0.19 +/- 0.15 mm (moderate ischemia), and 0.50 +/- 0.26 mm (severe ischemia). PD increased from 9 +/- 28 degrees (control value) to 22 +/- 19 degrees (mild ischemia), 54 +/- 18 degrees (moderate ischemia), and 107 +/- 21 degrees (severe ischemia). After release of the 15-minute left circumflex coronary artery occlusion, PET and PD recovered to 0.34 +/- 0.19 mm and 36 +/- 24 degrees (moderate dysfunction) and 0.25 +/- 0.31 mm and 29 +/- 8 degrees (mild dysfunction), respectively. There were inverse linear relationships between systolic wall thickening and PET (r = -0.86, p less than 0.001) and between systolic wall thickening and PD (r = -0.87, p less than 0.001). Inotropic stimulation by postextrasystolic potentiation increased regional systolic myocardial posterior and anterior wall thickening but did not alter the extent of left ventricular asynchrony. Thus, when normal baseline function is not known, the severity of regional myocardial dysfunction at a given inotropic state can be determined by analysis of left ventricular asynchrony. There was no significant correlation between the extent of PET and PD during ischemia and at early reperfusion and the recovery of contractile function at late reperfusion. Thus PET does not provide a prospective marker for the functional outcome of reperfusion.     

Relation between reversal of diastolic creep and recovery of systolic function after ischemic myocardial injury in conscious dogs

Although prolonged functional abnormalities after transient myocardial ischemia have been well described, the interrelationship between postischemic systolic and diastolic alterations remains controversial. Therefore, 24 chronically instrumented conscious dogs were studied with left ventricular and pleural micromanometers, ultrasonic dimension transducers in the left anterior descending (LAD) coronary distribution, and vena caval and coronary artery occluders. The LAD was occluded for 15 minutes and reperfused for 24 hours while vena caval occlusions were performed at intervals to measure myocardial segment length at 0 mm Hg transmural diastolic left ventricular pressure (L0). Coronary occlusion produced an immediate fall in systolic function as assessed by ejection shortening and stroke work and also induced a 16 +/- 4% increase in L0, which was termed diastolic creep. Throughout reperfusion, reversal of diastolic abnormalities correlated strongly with recovery of segmental shortening and stroke work (p less than 0.001). Correlation between systolic dysfunction and diastolic creep was also observed during alteration of inotropic state by dopamine, during initial reperfusion hyperfunction, and during pharmacologic manipulation of afterload. In 5 additional dog hearts fixed in diastole by rapid glutaraldehyde infusion after coronary occlusion, myocardial creep measured by the segment length transducers paralleled sarcomere elongation measured by electron microscopy. Thus, the direct correlation between diastolic creep and systolic dysfunction throughout reperfusion and during hemodynamic alterations suggests that diastolic properties of postischemic myocardium may not be entirely passive and that systolic and diastolic dysfunction induced by ischemia may have a common basis at the cellular level.     

Segmental systolic responses to brief ischemia and reperfusion in the hypertrophied canine left ventricle.

OBJECTIVES AND BACKGROUND. Left ventricular hypertrophy is associated with increased mortality, increased myocardial infarct size and an increased incidence of sudden death. Although reperfusion after ischemia has been shown to result in decreased infarct size and recovery of systolic thickening, it is unknown how left ventricular hypertrophy might influence recovery of regional systolic thickening after ischemia and reperfusion. We hypothesized that left ventricular hypertrophy might attenuate or abolish the functional response to reperfusion. METHODS. Three groups of chronically instrumented, conscious dogs (dogs with left ventricular hypertrophy and hypertension; dogs with left ventricular hypertrophy and reduced blood pressure and a control group without hypertrophy and with normal blood pressure) underwent 15 min of ischemia and 24 h of reperfusion. Segmental systolic thickening was measured by sonomicrometers and myocardial segments were grouped by percent of control segmental systolic thickening retained at 15 min of ischemia (class 1 greater than or equal to 67%, class 2 from 0% to 66%, class 3 less than 0% control systolic thickening). The recovery of each class of segment was measured serially during reperfusion. Hemodynamic variables and regional myocardial blood flow were also measured. RESULTS. There were no differences among groups in recovery of segmental systolic thickening for class 1 segments. Systolic thickening in class 2 (hypokinetic) segments was significantly depressed (p less than 0.05 compared with control value) in the group with left ventricular hypertrophy and reduced blood pressure (but not in the group with hypertrophy and hypertension) during early reperfusion; systolic thickening in class 3 (dyskinetic) segments showed a similar trend in the group with hypertrophy and reduced pressure. CONCLUSIONS. Although left ventricular hypertrophy with hypertension did not attenuate the contractile response to reperfusion, hypertrophy with reduced blood pressure was associated with significantly greater depression of segmental systolic thickening early during reperfusion.     

Effects of reperfusion on myocardial wall thickness, oxidative phosphorylation, and Ca2+ metabolism following total and partial myocardial ischemia

Coronary artery reperfusion following acute myocardial ischemia may salvage ischemic jeopardized cells. We studied the effects of early brief reperfusion on totally ischemic and on partially ischemic myocardium of open-chest pigs. In 10 animals, coronary flow was reduced to 0% for 30 minutes and was followed by 10 minutes reperfusion (group A). In another 10 animals, coronary flow was reduced to 25% of the baseline value for 30 minutes followed by 10 minutes of reperfusion (group B). In another eight animals coronary flow was reduced to 25% of the baseline value for 60 minutes and followed by 10 minutes of reperfusion (group C). Results showed that a brief 10-minute period of reperfusion of ischemic myocardium after total occlusion caused abnormal diastolic wall thickening with only partial return of systolic wall thickening. However, reperfusion of ischemic myocardium after partial occlusion, whether 30 or 60 minutes, caused little diastolic wall thickening and a partial return of systolic thickening. A marked elevation of myocardial Ca2+, a decrease in mitochondrial adenosine triphosphate (ATP) production and cellular ATP concentration, and a reduction in the rate of Ca2+ uptake by sarcoplasmic reticulum vesicles occurred in the totally ischemic myocardium but not in the partially ischemic myocardium. These results demonstrate that reperfusion of ischemic myocardium after 1 hour of coronary flow reduction to 25% of baseline is less damaging than reperfusion after a 30-minute total coronary occlusion, and suggest that preexisting states affecting coronary flow need to be evaluated in assessing the outcome of reperfusion.     

F(ab')2 fragments of anti-Mo1 (904) monoclonal antibodies do not prevent myocardial stunning

To determine if inhibition of leukocyte adhesion and aggregation could improve postischemic ventricular dysfunction ("stunning"), a monoclonal antibody (904) that binds to the adhesion-promoting Mo1 glycoprotein on the cell surface of leukocytes was administered intravenously (0.5 mg/kg) to open-chest dogs before a 15-minute coronary occlusion. Ultrasonic crystals placed in ischemic and control myocardium were used to measure systolic wall thickening during a 15-minute occlusion of the left anterior descending artery and for 3 hours after reperfusion. Myocardial blood flow was measured with tracer-labeled microspheres before occlusion, after 10 minutes of occlusion, 3 minutes of reperfusion, and at 1 and 3 hours after reperfusion. Six animals receiving anti-Mo1 antibody had antibody excess demonstrated with immunofluorescence techniques at 5 minutes and 3 hours of reperfusion; this finding indicated saturation of binding sites. Five animals served as controls and received an antibody (murine immunoglobulin G) that does not influence neutrophils. The two groups did not differ hemodynamically during ischemia and reperfusion. Risk areas and myocardial blood flow were also not significantly different between the two groups. The main parameter used to define regional myocardial stunning, percentage systolic wall thickening in the ischemic/reperfused area, did not differ significantly between the two groups. Specimens from nonischemic myocardium were compared with ischemic specimens for myeloperoxidase content. There were no significant differences within or between groups. These data indicate that the anti-Mo1 monoclonal antibody (904) is not effective in improving the profound myocardial dysfunction that persists for 3 hours of reperfusion after 15 minutes of ischemia.     

Prolonged abnormalities of left ventricular diastolic wall thinning in the "stunned" myocardium in conscious dogs: time course and relation to systolic function

Myocardial reperfusion after reversible ischemia is known to be associated with prolonged abnormalities of systolic contractile function (myocardial "stunning"). However, no information is available regarding the recovery of diastolic function in the stunned myocardium in the conscious state. Accordingly, 10 conscious dogs instrumented with pulsed Doppler thickening probes underwent a 15 min occlusion of the left anterior descending coronary artery followed by 7 days of reperfusion. Regional systolic function was assessed as net systolic thickening fraction. Left ventricular regional diastolic properties were estimated from two variables: the mean rate to half end-diastolic thinning and the late diastolic thinning fraction. Both indexes of diastolic function remained severely impaired after restoration of flow. In general, the recovery of the mean rate to half end-diastolic thinning and of the late diastolic thinning fraction paralleled the recovery of systolic thickening, but the impairment of the mean rate to half end-diastolic thinning was more marked than that of the late diastolic thinning fraction. At 4 h of reperfusion, the values for the mean rate to half end-diastolic thinning and the late diastolic thinning fraction (expressed as percent of baseline) were 57 +/- 5% (p less than 0.001 versus baseline) and 79 +/- 7% (p less than 0.05), respectively, whereas systolic thickening fraction averaged 52 +/- 10% (p less than 0.001). At 24 h, the mean rate to half end-diastolic thinning and the late diastolic thinning fraction were no longer significantly different from baseline, whereas systolic thickening fraction remained decreased at 82 +/- 4% (p less than 0.001) and returned to control values by 48 h. This study demonstrates the presence of profound, prolonged abnormalities of regional diastolic wall thinning after a brief episode of ischemia in the conscious state and expands the concept of myocardial stunning from the traditional notion of impaired systolic performance to that of a global derangement in mechanical function that involves both systolic and diastolic properties.     

再灌注对急性心肌梗死左室舒张与收缩功能影响的实验研究

本文用急性心肌梗死（ＡＭＩ）犬模型对左室舒张与收缩功能及再灌注后的变化特点进行了观察。结果发现，ＡＭＩ后２、３和７２小时左室舒张与收缩功能均明显下降，在ＡＭＩ后７２小时再灌注组左室舒张与收缩功能明显优于未再灌注组（Ｐ＜０．０５和Ｐ＜０．０１）。     

Alterations of left ventricular mechanics after anterior myocardial infarction. Quantitative analysis by tissue doppler echocardiography

Myocardial ischemia is usually responsible for alterations of regional left ventricular function which are not quantified by routine echocardiography. We used tissue Doppler echocardiography to quantitate the three main components (radial, longitudinal and angular) of left ventricular function, and their alterations after acute anterior myocardial infarction. Radial function was assessed by the myocardial velocity gradient derived from M-mode color tissue Doppler echocardiography, and longitudinal function by the pulsed wave tissue Doppler echocardiography, in 26 patients who experienced a first acute anterior myocardial infarction and in 11 matched healthy subjects. We describe a new tissue Doppler method for the measurement of septal angular deformation during cardiac contraction. In healthy subjects, our results showed heterogeneous regional myocardial contraction. Septal angular deformation occurred in the same direction and was of the same order as predicted by previous MRI studies. After anterior infarction, systolic and diastolic myocardial velocity gradients were dramatically decreased in the anterior wall when compared with controls (p < 0.01), whereas the systolic velocity gradient was significantly higher in the opposite wall (p < 0.05). Pulsed wave tissue Doppler echocardiography revealed significant alterations of longitudinal left ventricular function. Septal angular deformation was decreased after anterior infarct, and a good correlation was found between the angle of rotation and the left ventricular ejection fraction by cineangiography. These results indicate that tissue Doppler echocardiography has the potential for measuring the three main components of regional left ventricular function, and for quantitatively assessing their functional alterations induced by acute myocardial ischemia.     

Comparative echocardiographic study of recovery of diastolic versus systolic function after brief periods of coronary occlusion: differential effects of intravenous nifedipine administered before and during occlusion

The effect of intravenous nifedipine (5 micrograms/kg) on the recovery of myocardial function after occlusion of the left anterior descending coronary artery was studied in 18 closed chest dogs. Using computer-aided analysis of two-dimensional echocardiograms, systolic and diastolic function of ischemic segments in low papillary left ventricular cross sections were characterized, respectively, as holosystolic fractional area change and early diastolic velocity of luminal area change. The time required for systolic function to return to preocclusion values after a 1 minute untreated control occlusion (n = 12) was 5 to 10 minutes, and after a 2 minute occlusion (n = 6) it was 20 to 30 minutes. When nifedipine was administered during the occlusion, recovery after a 2 minute occlusion was accelerated slightly to 10 to 15 minutes. Recovery times of early diastolic function were substantially longer, and nifedipine effects were more pronounced. After a 1 or 2 minute control coronary occlusion, 60 to 75 minutes or 90 to 105 minutes were needed to return early diastolic function to normal levels. Nifedipine administered during a 1 or 2 minute coronary occlusion improved these recovery times to 10 to 15 minutes. When the dogs were treated with intravenous nifedipine before coronary occlusion, recovery after 1 or 2 minutes of acute ischemia was apparent as early as 2 minutes after reperfusion. Thus, intravenous nifedipine accelerates the recovery of myocardial function after brief periods of ischemia, and when administered before coronary occlusion, it assures very prompt recovery of function.     

Exacerbation of left ventricular ischemic diastolic dysfunction by pressure-overload hypertrophy. Modification by specific inhibition of cardiac angiotensin converting enzyme.

Hearts with compensatory pressure-overload hypertrophy show an increased intracardiac activation of angiotensin II that may contribute to ischemic diastolic dysfunction. We studied whether pressure-overload hypertrophy in response to aortic banding would result in exaggerated diastolic dysfunction during low-flow ischemia and whether the specific inhibition of the cardiac angiotensin converting enzyme by enalaprilat would modify systolic and diastolic function during ischemia and reperfusion in either hypertrophied or nonhypertrophied hearts. Isolated, red blood cell-perfused isovolumic nonhypertrophied and hypertrophied rat hearts were subjected to enalaprilat (2.5 x 10(-7) M final concentration) infusion during 20 minutes of baseline perfusion and during 30 minutes of low-flow ischemia and 30 minutes of reperfusion. Coronary flow per gram was similar in nonhypertrophied and hypertrophied hearts during baseline perfusion, ischemia, and reperfusion. At baseline, left ventricular developed pressure was higher in hypertrophied than nonhypertrophied hearts in untreated groups (224 +/- 8 versus 150 +/- 9 mm Hg; p less than 0.01) and in enalaprilat-treated groups (223 +/- 9 versus 145 +/- 8 mm Hg; p less than 0.01). During low-flow ischemia, left ventricular developed pressure was depressed but similar in all groups. All groups showed deterioration of diastolic function; however, left ventricular end-diastolic pressure increased to a significantly higher level in untreated hypertrophied than in nonhypertrophied hearts (65 +/- 7 versus 33 +/- 3 mm Hg; p less than 0.001). Enalaprilat had no effect in nonhypertrophied hearts, but it significantly attenuated the greater increase in left ventricular end-diastolic pressure in hypertrophied hearts treated with enalaprilat compared with no drug (65 +/- 7 versus 50 +/- 5 mm Hg; p less than 0.01). The beneficial effect could not be explained by differences in coronary blood flow per gram left ventricular weight, glycolytic flux as reported by lactate production, myocardial water content, oxygen consumption, and tissue levels of glycogen and high energy phosphate compounds. During reperfusion, all hearts showed a partial recovery of developed pressure to 70-74% of initial values. No effect of enalaprilat could be detected during reperfusion on systolic and diastolic function or restoration of tissue levels of high energy compounds. In conclusion, our experiments show that hypertrophied red blood cell-perfused hearts manifest a severe impairment of left ventricular diastolic relaxation in response to low-flow ischemia in comparison with control hearts. Further, our experiments support the hypothesis that the enhanced conversion of angiotensin I to angiotensin II in rats with pressure-overload hypertrophy contributes to the enhanced sensitivity of hypertrophied hearts to diastolic dysfunction during low-flow ischemia.     

Acute effects of parenteral beta-blockade on regional ventricular function of infarct and noninfarct zones after reperfusion therapy in humans.

Although the mechanism is unknown, clinical trials have suggested that intravenous beta-adrenergic blockade may prevent early cardiac rupture after myocardial infarction. Previous studies have examined effects of beta-blockers on global left ventricular function after myocardial infarction; however, few data exist regarding their immediate effects on regional function or in patients after successful reperfusion. Therefore, 65 patients in whom thrombolysis with or without coronary angioplasty achieved reperfusion at 4.6 +/- 1.7 h from symptom onset were studied. Low osmolarity contrast ventriculograms were obtained immediately before and after administration of 15 mg of intravenous metoprolol (n = 54) or placebo (n = 11). Intravenous metoprolol immediately decreased heart rate (from 92 to 76 beats/min, p less than 0.0001), increased left ventricular diastolic volume (from 150 to 163 ml, p less than 0.001) and systolic volume (from 72 to 77 ml, p less than 0.0005) but did not change systolic and diastolic pressures. Although there was no difference in ejection fraction after metoprolol, centerline chord analysis revealed reduced noninfarct zone motion (from 0.41 to 0.12 SD/chord, p less than 0.05), improved infarct zone motion (from -3.1 to -2.9 SD/chord, p less than 0.01) and smaller circumferential extent of hypokinesia (from 30 to 27 chords, p less than 0.05). Patients with dyskinesia of the infarct zone had the most striking improvement in infarct zone wall motion. Because these changes occurred immediately after beta-blockade, they could not be attributed to myocardial salvage. No significant changes in heart rate, left ventricular volumes or regional wall motion were apparent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained regional dysfunction produced by prolonged coronary stenosis: gradual recovery after reperfusion

Prolonged nontransmural ischemia was produced and the early and late effects of reperfusion were studied in 10 conscious dogs instrumented over the long term. Five hours of partial circumflex coronary artery stenosis was produced with a hydraulic occluder, followed by gradual release over 20 min, with measurements of left ventricular pressure, regional myocardial function (systolic wall thickening by sonomicrometry), coronary blood flow velocity (pulsed Doppler), and myocardial blood flow (microspheres). During coronary stenosis the occluder was adjusted frequently to maintain a reduction of systolic wall thickening to 50% to 75% of control (average 62.6% of control). Myocardial blood flow in the ischemic area at 4 hr of partial coronary stenosis was reduced in the inner layers of the myocardium (subendocardium, from 0.81 +/- 0.18 at control to 0.36 +/- 0.08 SD, p less than .01; midwall, from 0.77 +/- 0.20 to 0.46 +/- 0.07 ml/min/g, p less than .01), accompanied by significant ST segment elevation on the subendocardial electrogram (0.83 +/- 0.96 to 4.58 +/- 4.10 mV; p less than .05) and decreased left ventricular dP/dt (3503 +/- 462 to 2991 +/- 339 mm Hg/sec; p less than .01). Within a few minutes after complete release of partial coronary stenosis, ST segments returned to control and myocardial blood flow of the inner layers was increased (subendocardium, 1.37 +/- 0.39, p less than .01; midwall, 0.97 +/- 0.28, p less than .05), but systolic wall thickening and left ventricular dP/dt were significantly depressed and remained reduced at 24, 48, and 72 hr when myocardial blood flow was normal. By seven days, systolic wall thickening and left ventricular dP/dt had returned to control (94.1 +/- 7.0% of control, 3353 +/- 605 mm Hg/sec, respectively; NS). Histologic changes caused by ischemia constituted only 2.7% (average) of the tissue between the crystals in the ischemic wall, but ischemic damage in the posterior papillary muscle, which did not contain crystals, was 31.9%. Thus, regional myocardial dysfunction reduced by nontransmural ischemia for 5 hr persisted for at least 3 days, with only slight damage to the left ventricular free wall but considerable infarction of the posterior papillary muscle. Full recovery of regional and global contractile function of the free wall then occurred within a period of 1 week.     

Evaluation of biochemical functions and ventricular performance in regional ischemic-reperfused myocardium by afterload reduction: differential effects of calcium blocking and non-calcium blocking vasodilators

The effects of afterload reduction with and without calcium blockade on reperfusion injury were studied in the pig. Reversible occlusion of the left anterior descending coronary artery was performed for 60 minutes followed by 120 minutes of reperfusion. For 15 minutes prior to and throughout reperfusion, treatment was administered with a calcium blocker (nifedipine or verapamil), a metallic organic dye and Ca²⁺ antagonist (ruthenium red), a vasodilator (nitroprusside), or saline. Biochemical functions, i.e., mitochondrial oxidative phosphorylation, myocardial ATP and Ca²⁺ content, and sarcoplasmic reticulum Ca²⁺ uptake were determined. Regional left ventricular wall motion was measured echocardiographically. Nifedipine and ruthenium red improved biochemical indices of ischemic myocardium in part by reducing afterload and thereby reducing oxygen demand and in part by reducing calcium entry into cells and mitochondria. Verapamil in the doses used failed to reduce afterload and demonstrated no salutary effect on biochemical parameters in ischemic myocardium. Nitroprusside reduced afterload, improved mitochondrial ATP production and increased percent wall thickening. Our findings suggest that afterload reduction with and without calcium blockade during the early reperfusion phase improves ischemic myocardium. These changes are predominantly biochemical in nature.     

黄芩苷衍生物对大鼠心肌缺血再灌注损伤的保护作用

目的观察黄芩苷衍生物对大鼠心肌缺血再灌注致心肌损伤后心功能及心肌梗死的保护作用。方法将60只雄性Wistar大鼠随机平均分为6组,即假手术组、模型组、维拉帕米0.5mg/kg组、黄芩苷衍生物45、90、180 mg/kg组。采用结扎冠状动脉左前降支30 min,再灌注120 min的方法建立大鼠心肌缺血再灌注损伤模型,分别于缺血前及再灌注前10 min内通过股静脉注射黄芩苷衍生物(45、90、180 mg/kg)。于缺血前、缺血30 min及再灌注30、60、90、120 min时,分别测定左心室收缩压(LVSP)、左心室内压最大上升速率(+dp/dt max)、左心室最大下降速率(-dp/dt max)、心率、收缩压、舒张压及平均动脉压等指标,以评价心脏功能。并用TTC染色法测定大鼠心肌梗死范围。结果黄芩苷衍生物能够显著对抗心肌缺血再灌注损伤引起的LVSP、±dp/dt max及血压的下降,抑制心率过度减慢。剂量依赖性地缩小心肌梗死范围即心肌梗死比例(梗死区重/左心室重):模型组、黄芩苷衍生物45、90、180 mg/kg组的梗死范围分别为(33.1±6.0)、(29.9±5.4)、(24.8±5.0)及(22.3±3.4)(均为P<0.05)。结论黄芩苷衍生物对大鼠心肌缺血再灌注损伤有保护作用。     

Differential enhancement of postischemic segmental systolic thickening by diltiazem

Prolonged depression of segmental systolic thickening after brief coronary artery occlusion may result principally from events during reperfusion rather than during the ischemic interval. Thus, cellular calcium overload at reperfusion may be a mediator of contractile dysfunction after brief ischemia, and reduction of calcium entry by diltiazem, a calcium channel antagonist, may enhance recovery of systolic thickening after brief periods of ischemia. Thirteen awake unsedated dogs instrumented with hemodynamic catheters, left anterior descending coronary artery occluders and five to six pairs of intramyocardial sonomicrometers underwent two 15 min coronary artery occlusions with 24 h reperfusion. The order of infusion of diltiazem (15 micrograms/kg per min) or saline solution was alternated. Systolic thickening, hemodynamic variables and regional myocardial blood flow were measured serially over 24 h. Despite equally severe ischemic dysfunction during coronary occlusion, diltiazem-treated segments with systolic thinning during ischemia recovered control segmental thickening significantly earlier than saline solution-treated segments (at 30 versus 180 min of reperfusion). Blood pressure was mildly decreased during diltiazem treatment; therefore, a second group of 10 dogs underwent a similar occlusion and reflow period during infusion of nitroprusside to lower mean arterial pressure equivalently. Decreases in blood pressure in this group resulted in some improvement in segmental systolic function; however, this did not reach statistical significance at any time. Regional myocardial blood flows were similar in the saline solution- and diltiazem-treated groups during ischemia and reflow. Thus, it is concluded that 1) diltiazem infusion significantly enhanced recovery of segmental systolic thickening after 15 min of ischemia and 24 h of reperfusion; 2) the enhancement in segmental systolic function could not entirely be attributed to decreased mean arterial pressure; 3) improvement in postischemic segmental ventricular function was seen only in those segments with systolic thinning during ischemia; thus, segments with the most severe ischemic dysfunction benefited most; and 4) there were no important differences in regional myocardial blood flow during ischemia and reperfusion between saline- and diltiazem-treated animals.     

Cardiac function and myocardial contractility: a perspective

An experimental study was designed to validate postextrasystolic potentiation assessment of myocardial viability or functional reserve of cardiac segments after acute coronary occlusion. Segmental systolic fractional area changes and wall thickening in pacing-induced postextrasystolic beats were mapped in 12 closed chest dogs by two-dimensional echocardiography during a control period and from 20 minutes to 3 hours after occlusion of the left anterior descending coronary artery. The extent of myocardial ischemic and necrotic zones was evaluated in left ventricular slices and subsegements corresponding to echographic cross sections. During two-dimensional echocardiography, left ventricular segments that were found to be neither ischemic nor necrotic always exhibited a significant augmentation of both fractional area change and wall thickening during the postextrasystolic beat that followed an induced premature contraction with a 42.4% coupling interval. In segments without necrosis but with varying degrees of ischemia, significant postextrasystolic potentiation was also demonstrated, even after 3 hours of occlusion. In contrast, segments that developed more than 80% necrosis failed to potentiate systolic fractional area change after 2 hours, and systolic wall thickening, even after 20 minutes of coronary occlusion. Statistical evaluation revealed a characteristic threshold at 41 to 60% necrosis, beyond which no potentiation of function could be elicited 3 hours after occlusion. Extrapolation from the experimental data suggests that when two-dimensional echographic studies in myocardial ischemia indicate postextrasystolic augmentation of segmental left ventricular function, the latter segments may be assumed to contain only small infarcts or to consist of reversibly ischemic and normal myocardium. Conversely, segments that fail to exhibit postextrasystolic potentiation can be assumed to be more than 60% necrotic.     

Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig.

OBJECTIVE: In humans, the left anterior descending coronary artery supplies the left ventricular wall, anterior septum and the paraseptal part of the right ventricular anterior wall. Our aim was to study the effects of acute left anterior descending coronary occlusion on wall thickening in the regions of the left and right ventricular anterior walls supplied by the artery, and in remote, non-ischaemic regions of both ventricles. METHODS: Systolic wall thickening (defined as percent thickening with respect to end diastolic wall thickness) was studied in eight conscious pigs every 15 s during 1 min of acute left anterior descending coronary occlusion by a cuff occluder, and every 30 s during 4 min of reperfusion. Pigs were instrumented with ultrasonic microcrystals measuring wall thickness in the anterior walls (left anterior descending artery territory) and lateral walls (left circumflex or right coronary artery territory) of both ventricles, and a left ventricular pressure microtransducer. RESULTS: During control and reperfusion, both anterior walls displayed similar systolic thickening. During coronary occlusion, the left ventricular anterior wall showed paradoxical systolic thinning (dyskinesia) whereas the right ventricular anterior wall showed only hypokinesia. CONCLUSIONS: In the presence of equal blood flow deprivation, the right ventricular anterior wall supplied by the left anterior descending coronary artery displays a significantly lesser degree of functional impairment than the left ventricular anterior wall supplied by the same artery. This differential effect may be due to mechanical unloading of the right ventricular anterior wall resulting from left ventricular anterior wall ischaemia. This afterload reduction due to decreased mechanical interaction between the two walls would allow the right ventricular anterior wall to express its contractile reserve in the form of systolic thickening.     

急性心肌梗死患者心肌灌注状况对经皮冠状动脉介入术后心功能的影响

目的采用经冠状动脉超声心肌声学造影(MCE)评价急性心肌梗死(AMI)患者心肌灌注状况对经皮冠状动脉介入术(PCI)后心功能改善的影响,并探讨其相关临床意义。方法 18例AMI患者于PCI前及术后15 min分别经左主干或右冠状动脉注射超声声学造影剂,进行MCE实时显影,以视觉评分方式定性分析PCI前后相应心肌节段灌注状况;术后1个月经二维超声评价左心室室壁运动;利用灌注评分指数(PSI)及室壁运动评分指数(WMSI)分析PCI前后心肌灌注水平对心功能改善的影响。结果术前心肌灌注评分为0分的30个心肌节段中,20个(66.7%)术后1个月室壁运动评分为3~5分;而术前心肌灌注评分为2分的11个心肌节段中,有8个(72.7%)1个月时室壁运动评分为1~2分;统计学分析显示,PCI前心肌灌注与1个月室壁运动状况有关(P0.05)。术后心肌灌注评分为0分的12个心肌节段中,11个(91.7%)术后1个月室壁运动评分为3~5分;而术后心肌灌注评分为2分的22个心肌节段中,有17个(77.2%)1个月时室壁运动评分为1~2分;统计学分析显示,PCI后心肌灌注与1个月室壁运动状况有关(P0.01)。结合WMSI及PSI综合评价术后心肌灌注水平与左心室收缩功能的关系,发现二者存在明显相关性(P0.01)。结论 AMI患者心肌灌注状况对PCI后心功能改善有明显影响;经冠状动脉MCE可较准确的判断AMI患者微循环灌注范围,评估术后心功能,故可能对患者的临床预后判断有一定预测价值。     

Consequences of reperfusion after coronary occlusion. Effects on hemodynamic and regional myocardial metabolic function

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion.These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.