超声时间变形率成像识别缺血心肌节段不同步运动

目的　心肌收缩后缩短 (PSS)是缺血时心肌不同步运动的敏感指标 ,变形率成像 (SRI)能较好地识别局部心肌收缩 /伸展转换。为此 ,我们使用时间变形率成像(TSRI) ,试图简便、敏感、可靠地识别PSS ,进而明确心肌缺血节段。方法　使用 30例健康人 (对照 )和 2 8例经冠状动脉 (冠脉 )造影等临床综合诊断明确的冠心病人 ,进行常规超声心动图及TSRI检查 ,观察TSRI图像 ,测量收缩 /伸展转换时间差 (DTcec) ,进行统计学处理及组间比较。结果　正常人各室壁断面TSRI的 (DTcec)无 1例 >4 0ms ;2 8例冠心病人表现为相应壁断面TSRI呈花斑状 ,收缩期黄色缺失或 (DTcec)增大 (>5 0ms) ,无 1例阴性。结论　TSRI真正意义地实现了同时反映局部室壁运动的空间—时间变化规律 ,对识别缺血所致的PSS很敏感。正常人DTcec均 <4 0ms ,冠心病人相应室壁断面收缩时黄色缺失呈花斑状或DTcec>5 0ms ,无 1例阴性。但是样本量小 ;图像质量等技术因素的影响 ,本试验临床应用时 ,仍需紧密结合临床慎重使用     

Grading of myocardial dysfunction by tissue Doppler echocardiography: a comparison between velocity, displacement, and strain imaging in acute ischemia.

OBJECTIVES: The aim of the study was to compare the ability of the tissue Doppler echocardiographic imaging (TDI) modalities velocity, strain, and displacement to quantify systolic myocardial function. BACKGROUND: Several TDI modalities may be used to quantify regional myocardial function, but it is not clear how the different modalities should be applied. METHODS: In 10 anesthetized dogs we measured left ventricular pressure, longitudinal myocardial velocity, strain, and displacement by TDI at baseline and during left anterior descending coronary artery (LAD) stenosis and occlusion. Reference methods were segmental shortening by sonomicrometry and segmental work. In 10 patients with acute anterior wall infarction (LAD occlusion) and 15 control subjects, velocity, strain, and displacement measurements were performed. RESULTS: In the animal study, systolic strain correlated well with segmental shortening (r = 0.96, p < 0.01) and work (r = 0.90, p < 0.01), and differentiated well between non-ischemic (-13.5 +/- 3.2% [mean +/- SD]), moderately ischemic (-6.5 +/- 2.8%), and severely ischemic myocardium (7.1 +/- 13.2%). The ratio post-systolic strain/total strain also differentiated well between levels of ischemia. Displacement and ejection velocity had weaker correlations with segmental shortening (r = 0.92 and r = 0.74, respectively) and regional work (r = 0.85 and r = 0.69), and there was marked overlap between values at baseline and at different levels of ischemia. In the human study, systolic strain differentiated well between infarcted and normal myocardium (1.0 +/- 5.0% vs. -17.8 +/- 3.8%), whereas systolic displacement (-0.3 +/- 1.3 mm vs. -2.3 +/- 0.6 mm) and ejection velocity (0.9 +/- 0.6 cm/s vs. 2.2 +/- 0.6 cm/s) showed overlap. In the infarction group, strain was reduced in segments with infarcted tissue, while systolic velocity and displacement were reduced in all segments and did not reflect the extension of the infarct. CONCLUSIONS: Strain was superior to velocity and displacement for quantification of regional myocardial function. Provided technical limitations can be solved, strain Doppler is the preferred TDI modality for assessing function in ischemic myocardium.     

Higher myocardial strain rates during isovolumic relaxation phase than during ejection characterize acutely ischemic myocardium

OBJECTIVES: The aim of this study was to define an index that can differentiate normal from ischemic myocardial segments that exhibit postsystolic shortening (PSS). BACKGROUND: Identification of ischemia based on the reduction of regional systolic function is sometimes challenging because other factors such as normal nonuniformity in contraction between segments, tethering effect, pharmacologic agents, or alterations in loading conditions can also cause reduction in regional systolic deformation. The PSS (contraction after the end of systole) is a sensitive marker of ischemia; however, inconsistent patterns have also been observed in presumed normal myocardium. METHODS: Twenty-eight open-chest pigs underwent echocardiographic study before and during acute myocardial ischemia induced by coronary artery occlusion. Ultrasound-derived myocardial longitudinal strain rates were calculated during systole (S(SR)), isovolumic relaxation (IVR(SR)), and rapid filling (E(SR)) phases in both ischemic and normal myocardium. Systolic strain (epsilon(sys)) and postsystolic strain (epsilon(ps)) were calculated by integrating systolic and postsystolic strain rates, respectively. RESULTS: During ischemia, S(SR), E(SR), and epsilon(sys) in ischemic segments were significantly lower (in magnitude) than in nonischemic segments or at baseline. However, some overlap occurred between ischemic and normal values for all three parameters. At baseline, 18 of 28 animals had negative IVR(SR) (i.e., PSS) in at least one segment. During coronary artery occlusion, IVR(SR) became negative and larger in magnitude than S(SR) in all ischemic segments. The IVR(SR)/S(SR) and epsilon(ps) best differentiated ischemic from nonischemic segments. CONCLUSIONS: In the presence of reduced regional systolic deformation, a higher rate of PSS than systolic shortening identifies acutely ischemic myocardium.     

Myocardial temperature reduction attenuates necrosis after prolonged ischemia in rabbits

OBJECTIVE: Previously we observed that a large reduction in infarct size was attained by cooling the risk region of the heart, either before or early after the onset of a 30-min coronary artery occlusion. While this is a standard duration of ischemia used in the rabbit model of infarction, it may not reflect the situation of patients who are reperfused late. The effects of regional hypothermia with a longer duration of ischemia, and when the intervention is applied later, are unknown. This study tests the hypothesis that a local reduction in cardiac temperature protects myocardium during prolonged ischemia (2 h) even if begun well after coronary artery occlusion. METHODS: Anesthetized rabbits received 2 h of coronary artery occlusion and 3 h of reperfusion. Rabbits were randomly assigned to a treated group: topical myocardial cooling starting 30 min after coronary occlusion (n = 14), or control group, no intervention (n = 12). Myocardial temperature in the risk zone, hemodynamics and regional myocardial blood flow were measured. RESULTS: Ischemic zone temperature was similar in both groups at 30 min post occlusion, but the cooling maneuver produced a reduction in temperature in the risk region of the treated group such that myocardial temperature was reduced an average of 10 degrees C between 30 and 60 min of coronary artery occlusion. Myocardial temperature in the control group remained within 0.3 degree C of baseline during coronary artery occlusion and into reperfusion. Core temperatures were similar in both groups. Hemodynamic parameters and collateral blood flow during occlusion were also equivalent in both groups. After 120 min of coronary occlusion, necrosis in the control group comprised 72 +/- 3% of the ischemic risk region. However, in cooled hearts, infarct size, expressed as a fraction of the risk region was significantly lower. Infarct size in this group averaged 59 +/- 3% of the risk region (p < 0.004 vs. controls), and thus cooling resulted in a salvage of approximately 18% of the risk region. CONCLUSION: These results show that reducing myocardial temperature protects ischemic myocardium during a long duration of ischemia even if initiated after coronary artery occlusion.     

Treatment of reperfusion injury with intracoronary calcium channel antagonists and reduced coronary free calcium concentration in regionally ischemic, reperfused porcine hearts

The effect of intracoronary diltiazem, EGTA (ethylene-bis-(beta-aminomethylether)-N,N'-tetraacetic acid), nifedipine, verapamil and isotonic saline solution as placebo on reperfusion injury was investigated in regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally occluded for 45 min and was reperfused for 3 days. Intracoronary infusion was started immediately before reperfusion and continued during 45 min of reperfusion. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Apart from left ventricular end-diastolic pressure before ischemia and during 45 min of reperfusion, global hemodynamic values in the five treatment groups did not differ; in particular, calculated left ventricular oxygen consumption before and during ischemia was equally low. Intracoronary EGTA decreased coronary venous free calcium concentration to about 70% of baseline value. Infarct size was reduced from 76 +/- 10% (control group, n = 8) to 60 +/- 10% (p less than 0.01) by intracoronary diltiazem (n = 8) and to 55 +/- 15% (p less than 0.01) by intracoronary EGTA (n = 8). Insignificant reductions in infarct size were found after treatment with intracoronary verapamil (63 +/- 18%, n = 8) and intracoronary nifedipine (68 +/- 9%, n = 7). Regional systolic shortening of the risk region, which did not differ among the groups before occlusion and during ischemia, recovered to the greatest extent in the EGTA-treated pigs (p less than 0.01 compared with values in the control group). Treatment with intracoronary calcium antagonists resulted in only marginal improvement of systolic shortening.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary cyclic flow variations "precondition" ischemic myocardium.

BACKGROUND. Repeated brief episodes of myocardial ischemia performed by mechanical clamping of a coronary artery "precondition" the heart and reduce infarct size after a subsequent sustained ischemia. It is not known, however, whether spontaneous episodes of transient ischemia caused by formation of platelet thrombi, which may occur in unstable angina, have a similar cardioprotective effect. METHODS AND RESULTS. Therefore, our objective was to determine whether brief spontaneous thrombotic episodes of ischemia/reperfusion could limit infarct size and preserve contractile function following 60 minutes (protocol 1) or 90 minutes (protocol 2) of sustained ischemia and 4-4.5 hours of reperfusion in the canine model. Before the sustained coronary occlusion, dogs underwent a 30-minute "treatment" period consisting of: no intervention (control group), four repeated episodes of 3-minute mechanical occlusion plus 5-minute reperfusion (preconditioned group), or coronary artery stenosis and endothelial injury, resulting in a mean of four spontaneous episodes of cyclic flow variations (CFV group) caused by formation and dislodgment of platelet thrombi. In protocol 1 (60-minute sustained ischemia plus 4.5-hour reperfusion), infarct size was significantly smaller in both the preconditioned and CFV groups compared with controls (3.5 +/- 1.4%,* 3.4 +/- 2.1%,* and 9.9 +/- 2.7% of the myocardium at risk, respectively; *p less than 0.05 versus control). In contrast, neither preconditioning nor CFV preserved contractile function: Segment shortening during sustained occlusion was equally depressed at -15% to -20% of baseline values among the three groups and equally stunned at +12% to +18% of baseline during the 4.5 hours of reflow. In protocol 2 (90-minute sustained ischemia plus 4-hour reperfusion), only CFV continued to exert a cardioprotective effect: Infarct size averaged 15.0 +/- 4.1%, 7.4 +/- 2.5%,* and 16.5 +/- 4.4% of the region at risk in the preconditioned, CFV, and control groups, respectively (*p less than 0.05 versus control). Contractile function, however, was similar among all three groups both during 90 minutes of sustained occlusion and throughout 4 hours of reperfusion. CONCLUSIONS. We therefore conclude that repeated coronary thrombus formation preconditions the ischemic myocardium: In fact, in contrast to mechanical preconditioning, cardioprotection provided by CFV persisted following 90 minutes of sustained coronary occlusion. However, preconditioning by thrombotic or mechanical occlusion neither preserved myocardial contractile function during sustained coronary occlusion nor prevented stunning after reperfusion. These data raise the possibility that clinical episodes of unstable angina prior to acute myocardial infarction may precondition the ischemic myocardium.     

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.     

Identification of acutely ischemic myocardium using ultrasonic strain measurements. A clinical study in patients undergoing coronary angioplasty

OBJECTIVES: The goal of this study was to investigate whether the changes in myocardial deformation measured with ultrasonic strain could accurately identify acutely ischemic myocardium during coronary angioplasty. BACKGROUND: Early identification of acute myocardial ischemia has important clinical implications. The accuracy of ultrasonic strain for the detection of acute myocardial ischemia has been validated in animal experiments but has not been investigated in the clinical setting. METHODS: In 73 patients (64 +/- 12 years), either radial or longitudinal strain values were monitored in the "at-risk" segments before, during, and early after right, circumflex, and left anterior descending coronary angioplasty. Based on the visual wall motion assessed before the angioplasty, segments were divided into normokinetic (group I) and hypo/akinetic (group II). Strain data in the "at-risk " segments were compared with values derived from the adjacent nonischemic segments and normal values in 20 controls. RESULTS: Coronary occlusion induced a marked reduction in the systolic strain both in the radial (from 49 +/- 6.9% to 23 +/- 4.6% in group I and from 21.9 +/- 11% to 11.3 +/- 8.4% in group II, p < 0.001) and longitudinal directions. Concomitantly, postsystolic strain increased (from 3.8 +/- 3.1% to 14.6 +/- 9.5% in group I, and from 4.4 +/- 3.7% to 11.3 +/- 7.8% in group II in radial direction, p < 0.001). Upon reperfusion, all deformation parameters returned to near preocclusion values. In comparison with control, baseline, and reperfusion data, the systolic and postsystolic strain parameters measured during total coronary occlusion identified acutely ischemic myocardium with a sensitivity of 86% to 95% and a specificity of 83% to 89%. CONCLUSIONS: In this model of acute ischemia, ultrasonic strain indexes differentiate acutely ischemic segments from both normal and dysfunctional myocardium. This should be a promising new approach to the bedside monitoring of acute ischemic changes in regional myocardial function.     

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.     

The pathophysiology of myocardial stunning: reversibility, accumulation and continuity of the ischemic myocardial damage after reperfusion.

In order to understand the pathophysiology of myocardial stunning, reversibility, accumulation and continuity of ischemic myocardial damage after reperfusion should be studied. Then, to analyze these three factors, myocardial function, metabolism and morphology under ischemia and reperfusion were studied in anesthetized, open-chest dogs. When myocardial ischemia was induced by occlusion of the left anterior descending coronary artery, percentage regional systolic shortening (%SS) of ischemic myocardium sharply decreased and became stable 10 min after occlusion. After reperfusion, ischemic myocardium showed active shortening after within 30-min occlusion, but did not after more than 60-min occlusion. During 90-min of ischemia, extracellular K+ concentration (Ke) steeply increased for first 10 min and was almost stable for next 10 min. Then, Ke straightly increased till 90 min. Metabolic rates, calculated from myocardial tissue CO2 and pH, steeply increased for first 20 min and sharply decreased for next 10 min. After 30 min, these two variables were almost stable, near zero. By electron-microscopy with cytochemistry, distribution of Na/K ATPase to myocardial cell membrane was observed to be almost after 15-min occlusion but distinctly sparse with destruction of cell membrane after 30-min occlusion. Therefore, irreversible myocardial damage appears after about 20-min ischemia and is almost complete after 60 min. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia. Although stunned myocardium in a narrow sense is may appear after reperfusion within less than 20-min of ischemia, stunned myocardium in a broad sense may appear within less than 60-min ischemia. When reversible myocardial ischemia (4- or 15-min occlusion) was repeated after short time intervals (20-min reperfusion), %SS of ischemic myocardium was gradually decreased with each ischemic episode. Active shortening of ischemic myocardium disappeared after more than two episodes of 15-min occlusion. Fluctuation of PCO2, pH and Ke of ischemic myocardium was gradually depressed with each occlusion. Metabolic viability of ischemic myocardium was cumulatively depressed by repeated brief occlusion. Naturally, myocardial damage was more severe after repeated 15-min occlusion than after 4-min occlusion. Accumulation of ischemic myocardial damage may arise as brief ischemia, which only induces reversible damage, is repeated. At last, continuity of ischemic myocardial damage was studied. The effect of 5-min occlusion to %SS of ischemic myocardium was apparently reversed after 90-min reperfusion. Early contractile failure was advanced even after very short duration of ischemia. Thus, myocardial function will be latently damaged.(ABSTRACT TRUNCATED AT 400 WORDS)     

Preconditioning does not attenuate myocardial stunning.

BACKGROUND. Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown. METHODS AND RESULTS. We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning. CONCLUSIONS. Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.     

The effects of Trolox, a water-soluble vitamin E analogue, in regionally ischemic, reperfused porcine hearts.

Myocardial protection by the water-soluble vitamin E analogue, Trolox, was investigated in 18 regionally ischemic, reperfused porcine hearts. The left anterior descending coronary artery was distally ligated for 45 min and was reperfused for three days. Five grams of Trolox (n = 9) were infused intravenously before coronary occlusion. Treatment was continued with an intravenous dose of 5 grams Trolox/24 hours until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Generation of free radicals by stimulated neutrophils was evaluated by luminol-enhanced chemiluminescence. Plasma concentrations of Trolox were measured by high-performance liquid chromatography. Aside from heart rate before ischemia, global hemodynamic values including calculated left ventricular oxygen consumption did not differ significantly between the two groups. Plasma concentrations of Trolox measured 1.8 +/- 0.3 mmol/l (before ischemia), 0.96 +/- 0.13 mmol/l (before reperfusion), 0.77 +/- 0.1 mmol/l (40 min of reperfusion), and 0.08 mmol/l (end of the experiment). Generation of free radicals by stimulated neutrophils was reduced by about 30% in the treatment group before ischemia and immediately before reperfusion, but was not reduced at the end of the experiment. Risk regions (control group 19.4 +/- 6 g, treatment group 19.3 +/- 7 g) and infarct sizes (control group 69.3 +/- 8%, treatment group 69.3 +/- 12%) were almost identical. Regional systolic shortening of a control segment and of the risk region were similar in both groups before ischemia, before reperfusion, and after 45 min of reperfusion. After 3 days of reperfusion, regional systolic shortening of the reperfused myocardium of the treated group had recovered to a significantly greater extent (P = 0.027). This parameter amounted to 9 +/- 6% in the treated group and to 3 +/- 3% in the control group. Improved functional recovery was not accompanied by higher tissue concentrations of adenosine triphosphate. It is concluded that the chosen treatment with Trolox does not reduce infarct size but accelerates functional recovery. This finding suggests that the mechanisms resulting in myocardial necrosis during ischemia/reperfusion and in post-ischemic myocardial dysfunction may differ.     

Pathomorphological and histological analysis of the indirect revascularization method

OBJECTIVE: This experimental study was initiated to determine whether TMLR may prevent porcine myocardium from ischemia and necrosis after acute myocardial infarction. In addition, the influence of TMLR on healthy myocardium was analyzed. METHODS: The short-term effectiveness of TMLR was evaluated in 38 open-chest anesthetized pigs with (n = 18) or without (n = 20) acute LAD occlusion (observation period 6 hours): Six pigs served as controls (thoracotomy only). An additional six pigs had LAD occlusion only (ischemic group). A subsequent 12 pigs were treated by TMLR (CO2) prior to LAD occlusion: Six pigs received one laser channel/cm2 (group 1) and in six pigs two channels/cm2 in the LAD territory (group 2) were performed. In addition, 14 pigs underwent TMLR without ischemia: Seven pigs received 1 channel/cm2 (group 3) and seven pigs 2 channels/cm2 (group 4). Pathomorphological assessment and histology were performed. RESULTS: TMLR limits the expansion of the myocardial infarction zone: laser group 2 demonstrated a significantly smaller area of necrosis in the area at risk (ischemic group (32%) vs. laser group 1 (18%, p = ns) and 2 (8%, p = 0.0076); laser group 1 vs. 2, p = 0.0056). The amount of the area of necrosis of laser groups 3 (0.4%) and 4 (0.04%) compared to control (0%) did not differ significantly (p = ns). Furthermore, in the lased territories of laser groups 3 and 4 microscopic analysis revealed signs of ischemia in 10 +/- 30.9% of all examined histological samples (p = ns vs. control). During a short coronary occlusion the laser-induced tracks were partially filled with blue dye in 94.8 +/- 27.0/85.9 +/- 34.3/94.85 +/- 22.0%/70.21 +/- 47.0% (laser groups 1 - 4 respectively p = ns) The myocardial water content-measurements (MWC) of the ischemia and laser group 1 were not different at the end of the experiment (p = ns). In contrast, laser groups 2, 3 and 4 revealed significantly higher MWC values compared to control (p = 0.036, p < 0.001, p < 0.001; respectively). CONCLUSIONS: This prolonged acute study demonstrates that preventive CO2-laser revascularization significantly reduces the amount of necrosis in the area at risk. Histological examination supported the idea that some pigment gained access to the ischemic tissue via patent channels. In healthy myocardium, TMLR significantly increases myocardial water content and induces non-significant small ischemic and very small necrotic areas surrounding open laser channels.     

The experimental study of the coronary reperfusion in the acute myocardial ischemia: the feasibility of the myocardial salvage

In order to know the feasibility of coronary reperfusion by thrombolysis or aorto-coronary bypass graft in the early stages of the acute myocardial infarction, we studied the effect of the coronary artery reperfusion to acutely ischemic myocardium induced by the coronary artery occlusion in ninety-five anesthetized open-chest dogs. The major factors determining the extent of the myocardial salvage by the reperfusion were the duration of the occlusion time and the degree of the reperfusion injury. These two determinants were analysed by coronary circulation, the regional myocardial function, the mitochondrial metabolism, mitochondrial Ca and Mg contents, and morphological findings of the myocardium by electron-microscopy. The regional myocardial contractility (% systolic shortening) and the mitochondrial metabolism (oxidative phosphorylation) were significantly damaged by the reperfusion more in 60 minute occlusion than in 30 minute occlusion, although the coronary circulation (coronary blood flow, regional myocardial blood flow and coronary vascular resistance) and myocardial gas contents (PO2, PCO2 and pH) in the ischemic myocardium induced by less than 60 minute occlusion were almost recovered to the pre-occluded level by 60 minutes after reperfusion. By 120 minute reperfusion, the ischemic damage calculated from mitochondrial Ca and Mg contents (MC index: 1-[Mg/Ca] ischemia/[Mg/Ca] non-ischemia) was not changed in 30 minute occlusion but was significantly deteriorated in 60 minute occlusion. Therefore, coronary reperfusion must be started within 60 minutes or less after occlusion. A supplementary way to protect the myocardium from ischemia is needed as soon as possible before reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic preconditioning reduces infarct size in swine myocardium

We evaluated the hypothesis that stunning swine myocardium with brief ischemia reduces oxygen demand in the stunned region and increases tolerance of myocardium to longer periods of ischemia. Wall function was quantified with ultrasonic crystals aligned to measure wall thickening, and stunning was achieved with two cycles of left anterior descending coronary artery (LAD) occlusion (10 minutes) and reperfusion (30 minutes), after which the LAD was occluded for 60 minutes and reperfused for 90 minutes. Infarct size (as a percent of risk region) was then determined by incubating myocardium with para-nitro blue tetrazolium. Regional oxygen demand was measured as myocardial oxygen consumption before the 60-minute LAD occlusion in the stunned region; tracer microspheres were used to determine blood flow, and blood from the anterior interventricular vein and left atrium was used to calculate oxygen saturations. After the second reperfusion period, wall thickening in the stunned region was reduced to 1.4 +/- 2.4% compared with 36.7 +/- 2.5% (mean +/- SEM) before ischemia (p less than 0.001). Regional myocardial oxygen consumption after stunning (3.1 +/- 0.7 ml O2/min/100 g) was no different from regional myocardial oxygen consumption before stunning (3.7 +/- 0.6 ml O2/min/100 g). In the nine pigs "preconditioned" by stunning, infarct size was 10.4 +/- 6.3% of the risk region compared with 48.0 +/- 12.7% in the six control pigs subjected to 60 minutes of ischemia without prior stunning (p less than 0.005). The risk regions were similar (14.4 +/- 1.5% vs. 14.6 +/- 1.9% of the left ventricle, preconditioned vs. control pigs, respectively). We conclude that stunning swine myocardium with two cycles of a 10-minute LAD occlusion followed by reperfusion increases ischemic tolerance but that changes in regional demand in stunned myocardium do not predict the marked reduction in infarct size that follows a subsequent 60-minute period of ischemia.     

Augmentation of regional function in nonischemic myocardium during coronary occlusion measured with two-dimensional echocardiography

Increased regional left ventricular function frequently occurs in the nonischemic myocardium after acute coronary occlusion. To further define the regional and global effects of this increased remote function in the ischemic left ventricle, 22 dogs were studied with two-dimensional echocardiography before and 1 h after left circumflex coronary artery occlusion. Two groups of dogs were identified with and without compensatory increased regional left ventricular function, defined as regional wall thickening in the nonischemic zone greater than 2 SD above baseline. After coronary occlusion, nonischemic wall thickening was 76 +/- 15% in the hyperfunction group (n = 11) and 45 +/- 14% in the nonhyperfunction group (n = 11) (p less than 0.001). Despite similar left ventricular end-diastolic cavity areas and equivalent degrees of ischemic wall thinning, dogs with increased left ventricular function in the nonischemic myocardium had a smaller extent of circumferential left ventricular dysfunction (136 +/- 33 versus 170 +/- 43 degrees, p less than 0.001) and a higher area ejection fraction (38 +/- 9% versus 27 +/- 6%, p less than 0.001). These functional differences occurred despite similar myocardial areas at risk by autoradiography (41 +/- 6% versus 37 +/- 12%, p = NS). The data suggest that increased left ventricular function in the nonischemic myocardium determines the global functional impact of acute coronary occlusion and, through interaction with adjacent myocardium, modifies the extent of circumferential left ventricular dysfunction.     

Effect of coronary reocclusion after initial reperfusion on ventricular function and infarct size

Reocclusion of a coronary artery after thrombolytic therapy occurs in approximately 12% to 33% of patients; however, there are few experimental data concerning reocclusion. Accordingly, to compare the effects of reocclusion versus sustained occlusion on the myocardium, a canine model (n = 12) of 2 h of left circumflex artery occlusion, 1 h of reperfusion and 1 h of reocclusion was studied. In a control group (n = 11), 3 h of circumflex artery occlusion was followed by 1 h of reperfusion. As a result, both groups had the same total duration of ischemia (3 h) and reperfusion (1 h). Hemodynamic measurements, radioactive microsphere injections and two-dimensional echocardiography were performed at baseline, occlusion and reperfusion for both groups and at the end of reocclusion for the experimental group. In vivo risk area was determined with Evans blue dye and infarct size with triphenyltetrazolium staining methods. Similar decreases in myocardial blood flow after coronary occlusion and similar reperfusion blood flows occurred in both groups. Despite intervening reperfusion in the reocclusion group, no significant difference was found in the infarct size/risk area ratio between the reocclusion and control groups (54.5 +/- 6.9% vs. 48.4 +/- 5.1%, respectively, p = NS). Two-dimensional echocardiography demonstrated a similar degree and extent (159 +/- 9 degrees vs. 153 +/- 12 degrees, p = NS) of left ventricular dysfunction with both the occlusion and reocclusion. In addition, there were no significant differences in global or regional left ventricular function between the two groups. However, reocclusion after reperfusion did produce a further deterioration in ischemic zone wall thickening (9.5 +/- 2.0% to 0.7 +/- 1.8%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired thickening of nonischemic myocardium during acute regional ischemia in the dog

To study the regional function of nonischemic myocardium after the onset of regional ischemia, graded circumflex coronary arterial stenosis was induced in 18 open-chest anesthetized dogs. Two-dimensional echocardiographic views were obtained at each degree of occlusion in a cross-sectional plane marked by two to three metal beads sewn to the left ventricular epicardium. Percent systolic thickening was measured at 16 equally spaced points around the left ventricle and correlated with microsphere-determined regional myocardial blood flow. Baseline thickening averaged 44.9 +/- 6.4%. During transmural ischemia percent systolic thickening decreased to -16.1 +/- 4.0% in the ischemic region and also decreased in adjacent nonischemic regions (to 2.4 +/- 2.4% in segments closest to the ischemic region [adjacent 1] and to 15.5 +/- 3.9 in segments further away [adjacent 2]), but was unchanged in segments directly opposite the ischemic region (remote region). During subendocardial ischemia, percent systolic thickening fell only in the ischemic and adjacent 1 regions (1.4 +/- 5.2% and 24.9 +/- 5.0%, respectively). Dipyridamole, 0.21 to 0.42 mg/min iv, given to seven dogs during transmural ischemia, caused a three- to fivefold increase in flow to the nonischemic and no change in flow to the ischemic region; function was not altered in any region. Propranolol, 0.1 mg/kg iv, was given to five dogs during transmural ischemia to depress contractility in the remote region. Percent systolic thickening fell in the remote (from 50.0 +/- 7.7% to 34.6 +/- 5.6%), but increased in adjacent 1 (from -0.25 +/- 3.7% to 15.2 +/- 3.9%) and in adjacent 2 (from 17.4 +/- 2.8% to 33.4 +/- 3.9%) regions, and remained unchanged in the ischemic region. We conclude the following: During transmural ischemia percent systolic thickening is markedly impaired in nonischemic myocardium immediately adjacent to the ischemic region, and is impaired to a lesser degree in regions located relatively far from the ischemic border. Dysfunction therefore overestimates the extent of regional ischemia after total coronary occlusion. During subendocardial ischemia function ceases in the ischemic region and functional impairment of nonischemic myocardium is restricted to immediately adjacent regions. Dysfunction of adjacent regions is not caused by "relative ischemia" related to increased local oxygen demands or to a steal phenomenon. Mechanical tethering of nonischemic myocardium adjacent to ischemic regions, secondary to changes in left ventricular shape during contraction, may contribute to the impairment of systolic thickening in adjacent regions during transmural ischemia.     

The effect of inotropic stimulation on normal and ischemic myocardium after coronary occlusion

During acute myocardial ischemia, there exists a zone of myocardial dysfunction that surrounds the central ischemic area that has been termed the functional border zone. We hypothesized that this nonischemic but dysfunctional myocardium may respond to an inotropic challenge. To address this issue, we studied 11 open-chest dogs during acute left circumflex (LCx) occlusion. Simultaneous two-dimensional echocardiograms and radioactive microsphere injections were used to create circumferential left ventricular flow-function maps at the papillary muscle level. Serial studies were performed at baseline, 15 min after LCx occlusion, and after the infusion of dobutamine during LCx occlusion. After occlusion, wall thickening decreased from 52 +/- 8% (mean +/- SEM) to -5 +/- 5% (p less than .01) in the central ischemic zone. The extent of left ventricular dysfunction measured 170 +/- 11 degrees while the subendocardial hypoperfusion zone was 130 +/- 9 degrees (p less than .05), resulting in a functional border zone of 40 +/- 11 degrees. During the infusion of dobutamine, wall thickening did not change in the central ischemic zone but increased adjacent to the functional border zone (p less than .01) and in the normal zone (p less than .05), reducing the extent of the functional border zone to 19 +/- 16 degrees (p less than .05). After dobutamine, the slope of transition of wall thickening from nonischemic to ischemic zones, measured directly from the left ventricular function map, increased on the free wall border (0.71 +/- 0.11 to 0.95 +/- 0.10, p less than .02) to a greater extent than on the septal border (0.60 +/- 0.08 to 0.73 +/- 0.06, p = .07). We conclude that nonischemic myocardium adjacent to ischemic tissue responds to inotropic challenge, dobutamine produces a significant decrease in the size of the functional border zone, and dynamic changes in wall thickening after inotropic intervention are greater in the functional border zone of the lateral free wall than at the septal border of the ischemic area.     

Evaluation of myocardial viability following ischemic and reperfusion injury using phosphorus 31 nuclear magnetic resonance spectroscopy in vivo

Recovery of myocardial high-energy phosphate (HEP) metabolism after coronary occlusion and reperfusion may vary with ischemic duration and may provide information about the extent of tissue viability. To evaluate the differences between varying durations of ischemia and to attempt to identify metabolic indexes of salvaged viable tissue, intact New Zealand white rabbits underwent either 30 (group 1; n = 8) or 60 (group 2; n = 8) minutes of coronary occlusion followed by reperfusion. HEP metabolism was evaluated with cardiac gated phosphorus 31 (31P) nuclear magnetic resonance (NMR) spectroscopy with a 2.0 T spectrometer. While similar HEP changes were observed during ischemia in both groups, differences in HEP recovery between groups were seen following reperfusion. Group 1 animals demonstrated a gradual decrease in inorganic phosphates (Pi) (p less than 0.05 versus group 2), an immediate recovery of phosphocreatine (PCr) (p = ns versus baseline), and a gradual increase of adenosine triphosphate (ATP) to pre-ischemic levels. Group 2 animals had elevated levels of Pi (p less than 0.05 versus baseline; p less than 0.05 versus group 1), slow recovery of PCr, and continued reduction of ATP (p less than 0.05 versus baseline; p less than 0.05 versus group 1). Group 1 rabbits had a greater extent of viable myocardium than group 2 (77.1 +/- 9.7% of risk area versus 39.4 +/- 9.4%; p less than 0.001). Significant correlations were found between PCr and Pi reperfusion values and myocardial viability (r = 0.59, p less than 0.05; r = 0.73, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)