A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION: After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Allergic lung responses are increased in prostaglandin H synthase-deficient mice.

To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1(-/-) and PGHS-2(-/-) mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE(2) was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1(-/-) mice, relative to wild-type or PGHS-2(-/-) mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1(-/-) mice compared with PGHS-2(-/-) mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1(-/-) and PGHS-2(-/-) mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1(-/-) mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE(2) in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice.

Prostaglandin-E2 counteracts interleukin-1beta-stimulated upregulation of platelet-derived growth factor alpha-receptor on rat pulmonary myofibroblasts.

The platelet-derived growth factor (PDGF) alpha-receptor (PDGF-Ralpha) is upregulated during lung fibrogenesis, and induction of PDGF-Ralpha on cultured lung myofibroblasts by interleukin (IL)-1beta results in an increased mitogenic response to PDGF. Because IL-1beta stimulates prostaglandin (PG) E2 production, we investigated whether IL-1beta could upregulate PDGF-Ralpha via a PGE2-dependent mechanism. IL-1beta increased the production of PGE2 by rat lung myofibroblasts and the cyclooxygenase (COX) inhibitor indomethacin blocked IL-1beta-induced PGE2 production. However, indomethacin did not inhibit IL-1beta-stimulated upregulation of [125I]PDGF-AA binding sites, indicating that PDGF-Ralpha induction does not require PGE2 synthesis. Instead, PGE2 downregulated PDGF-Ralpha protein and messenger RNA expression, and counteracted the IL-1beta-stimulated increase in [125I]PDGF-AA binding. Pretreatment of cells with indomethacin or the COX-2 specific inhibitor NS-398 attenuated the suppressive effect of exogenous PGE2 on PDGF-Ralpha, indicating that endogenous PGE2 released by IL-1beta treatment also contributed to downregulation of PDGF-Ralpha. PDGF-Rbeta expression was not altered by IL-1beta or PGE2. Pretreatment of myofibroblasts with IL-lbeta increased PDGF-stimulated mitogenesis, and this effect was blocked by coincubation with PGE2. In contrast, PGE2 enhanced epidermal growth factor- or basic fibroblast growth factor-2-stimulated cell proliferation approximately 50%. Because IL-1beta upregulates both PGE2 production and PDGF-Ralpha expression, these data suggest that PGE2 functions in a negative feedback loop to limit expression of PDGF-Ralpha and suppress PDGF-stimulated myofibroblast proliferation.

A randomized trial comparing the dorzolamide-timolol combination given twice daily to monotherapy with timolol and dorzolamide. Dorzolamide-Timolol Study Group.

OBJECTIVE: To compare the efficacy and safety of a fixed combination of 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive medications. DESIGN: A 3-month, parallel, randomized, double-masked, active-controlled, multicenter clinical trial. PARTICIPANTS: A total of 335 patients with bilateral ocular hypertension or open-angle glaucoma participated. INTERVENTION: After completing a washout of ocular hypotensive medications, patients were randomized to receive either the dorzolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide three times daily. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3. Ocular and systemic safety were evaluated at each study visit. RESULTS: Intraocular pressure reduction was greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean reduction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol. At morning peak (month 3, hour 2), the mean IOP reduction from baseline was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the combination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences was also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolol group (7% vs. 1%, P = 0.035). Similarly, comparable numbers of patients in the combination and dorzolamide groups reported ocular symptoms; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, and tearing eye. CONCLUSIONS: After a washout of ocular hypotensive therapy, the IOP-lowering effect of the dorzolamide-timolol combination was greater than that of either of its components administered as monotherapy. The combination is generally well-tolerated and provides a convenient alternative to concomitant therapy with its individual components.

Two-year safety study of dorzolamide as monotherapy and with timolol and pilocarpine. Dorzolamide Safety Study Group.

PURPOSE: To evaluate the safety of open-label 2.0% dorzolamide as monotherapy and when used with timolol and/or pilocarpine for as long as 2 years. METHODS: The safety of dorzolamide was evaluated in patients with open-angle glaucoma or ocular hypertension over a 2-year period. The incidence of the most common drug-related adverse experiences in the first year was compared with that in the second year using McNemar's test. The ocular hypotensive effect of dorzolamide as monotherapy and with adjunctive therapy was assessed using percent change in intraocular pressure (IOP) from baseline. RESULTS: Of the 304 patients enrolled, 164 (53.9%) continued to receive dorzolamide as monotherapy for 2 years and 140 (46.1%) required add-on therapy. Add-on therapy was initiated by month 6 in 112 of these 140 patients (80%). Of the 304 patients, 202 (66.4%) completed 2 years of therapy. Of the patients who received dorzolamide as monotherapy, drug-related adverse events occurred more frequently during the first year (29.7%) than the second year (13.8%), and the most common ocular drug-related adverse events included conjunctivitis, burning/stinging eye, follicular conjunctivitis, and eyelid edema. After 2 years of therapy, the mean percent decrease in peak IOP was 22.8% for patients receiving dorzolamide monotherapy and 31.2% to 36.0% for patients receiving add-on therapy. CONCLUSION: Dorzolamide was generally well tolerated for up to 2 years as monotherapy and when used with timolol and/or pilocarpine. Drug-related adverse events were less frequent during the second year of monotherapy than during the first year. Most patients who required add-on therapy did so within the first 6 months of initiating dorzolamide therapy.

CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance.

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3), both of which were expressed in extrahepatic tissues. Northern analysis of RNA prepared from the human and rat intestine demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed primarily in the small intestine and colon. In contrast, immunoblotting studies using a polyclonal antibody raised against recombinant CYP2J2 showed that CYP2J proteins were expressed throughout the gastrointestinal tract. Immunohistochemical staining of formalin-fixed, paraffin-embedded intestinal sections using anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J proteins were present at high levels in nerve cells of autonomic ganglia, epithelial cells, intestinal smooth muscle cells, and vascular endothelium. The distribution of this immunoreactivity was confirmed by in situ hybridization using a CYP2J2-specific antisense RNA probe. Microsomal fractions prepared from human jejunum catalyzed the NADPH-dependent metabolism of arachidonic acid to epoxyeicosatrienoic acids as the principal reaction products. Direct evidence for the in vivo epoxidation of arachidonic acid by intestinal cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in human jejunum by gas chromatography/mass spectrometry. We conclude that human and rat intestine contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is localized to autonomic ganglion cells, epithelial cells, smooth muscle cells, and vascular endothelium. In addition to the known effects on intestinal vascular tone, we speculate that CYP2J products may be involved in the release of intestinal neuropeptides, control of intestinal motility, and/or modulation of intestinal fluid/electrolyte transport.

Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas.

Our laboratory recently described a new human cytochrome P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homolog (CYP2J3). Immunoblotting studies using a polyclonal antibody raised against recombinant human CYP2J2 confirmed CYP2J protein expression in human and rat pancreatic tissues. Immunohistochemical staining of formalin-fixed paraffin-embedded rat and human pancreas using the anti-CYP2J2 IgG and avidin-biotin-peroxidase detection revealed that CYP2J2 protein expression was highly localized to cells in the islets of Langerhans, with minimal staining in pancreatic exocrine cells. Colocalization studies using antibodies to the glucagon, insulin, somatostatin, and pancreatic polypeptide as markers for alpha-, beta-, delta-, and PP cells, respectively, showed that CYP2J protein expression was abundantly present in all four cell types, but was highest in the glucagon-producing alpha-cells. Direct evidence for the epoxidation of arachidonic acid by pancreatic cytochrome P450 was provided by documenting, for the first time, the presence of epoxyeicosatrienoic acids in vivo in human and rat pancreas by gas chromatography/mass spectrometry. Importantly, the levels of immunoreactive CYP2J2 in different human pancreatic tissues were highly correlated with endogenous epoxyeicosatrienoic acid concentrations. We conclude that human and rat pancreas contain an arachidonic acid epoxygenase belonging to the CYP2J subfamily that is highly localized to islet cells. These data together with previous work showing effects of epoxyeicosatrienoic acids in stimulating insulin and glucagon secretion from isolated rat pancreatic islets support the hypothesis that epoxygenase products may be involved in stimulus-secretion coupling in the pancreas.

CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance.

Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expression. Immunohistochemical analysis of formalin-fixed paraffin-embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone.

Sixth nerve palsy as the initial presenting sign of metastatic prostate cancer. A case report and review of the literature.

Cranial nerve palsies secondary to metastatic prostate cancer are uncommon occurrences. Usually appearing late in the course of the disease, they are associated with a poor prognosis. We report a case of a 71-year-old man who initially complained of diplopia and was found to have a right sixth nerve palsy and hyperdeviation caused by a mass in the clivus. Biopsy of the mass and extensive systemic workup revealed metastatic adenocarcinoma of the prostate gland.

Dissociation between two-dimensional echocardiographic left ventricular wall motion and myocardial salvage in early experimental acute myocardial infarction in dogs.

This study was designed to evaluate whether the effects of coronary reperfusion with or without a pharmacologic agent could be detected in the early hours after infarction by 2-dimensional (2-D) echocardiography applied in a manner analogous to its clinical use. Proximal left anterior descending coronary occlusion was performed in 24 dogs, and the dogs were then randomized into 3 groups. In group 1 (n = 8), coronary occlusion was maintained for 6 hours; in group 2 (n = 8), coronary occlusion was maintained for 2 hours and was followed by 4 hours of reperfusion; in group 3 (n = 8), 2 hours of coronary occlusion were followed by 4 hours of reperfusion but methylprednisolone (30 mg/kg intravenously) was also administered 15 minutes after coronary occlusion. At 6 hours, 2-D images were obtained through the closed chest wall and the percentage of the left ventricular wall motion abnormalities was determined at 4 short-axis levels. The mass at risk was defined by in vivo Monastral blue injection and infarction by triphenyltetrazolium chloride staining. The mass of necrosis was 74 +/- 4% (mean +/- standard error of the mean) of the mass at risk in group 1 and was smaller in groups 2 and 3, 44 +/- 6% and 35 +/- 4%, respectively (p less than 0.01). Percent necrosis of the left ventricle was 22 +/- 3% in group 1, 15 +/- 3% in group 2 (difference not significant) and 10 +/- 2% in group 3 (p less than 0.05 vs group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Hydrogen peroxide contrast echocardiography: quantification in vivo of myocardial risk area during coronary occlusion and of the necrotic area remaining after myocardial reperfusion.

During sustained coronary occlusion in canine preparations, the extent of regions that fail to show contrast enhancement when imaged by supra-aortic hydrogen peroxide contrast echocardiography (SHPCE) has been shown to correlate well for single cross sections with the extent of malperfused myocardium "at risk" of infarction. In the present study, SHPCE was investigated as a means of determining the fraction of total left ventricular mass at risk during occlusion. Since necrotic tissue has low blood flow even when reperfused, we also investigated the potential of quantitating the extent of infarcted myocardium by measuring the extent of contrast defects seen with SHPCE performed during reperfusion. In 20 dogs the fraction of the left ventricle showing a contrast defect during coronary occlusion correlated well with the fraction of the left ventricular mass "at risk" by an autoradiographic technique (autoradiography = 0.83 echocardiography + 8.6%; r = .89, SEE = 4.5%). SHPCE was also performed after 3 hr of reperfusion following occlusions varying in duration from 60 to 150 min. The fraction of the ventricle showing a contrast defect during reperfusion predicted the infarcted portion of the left ventricle as shown by triphenyl tetrazolium chloride staining (% left ventricle infarcted = 0.81 echocardiography + 3.3%; r = .84, SEE = 5.3%). Observer variability for the fraction of the ventricle showing a contrast defect was excellent during both occlusion and reperfusion. The ratio of the left ventricular extent of contrast-negative regions during reperfusion and occlusion was used to calculate a necrosis-to-risk index in vivo that correlated relatively well with the myocardial necrosis-to-risk ratio determined morphologically (r = .77, SEE = 16%).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative two-dimensional echocardiographic analysis of regional wall motion in patients with perioperative myocardial infarction.

Regional left ventricular wall motion was evaluated by two-dimensional echocardiographic techniques with fixed- and floating-axis analytical algorithms in three groups of subjects: normal subjects (n = 15), patients undergoing uncomplicated coronary artery bypass graft surgery (CABG) (n = 10), and patients suffering perioperative myocardial infarction (n = 27). In patients undergoing uncomplicated CABG, fixed-axis analysis in the apical four-chamber view produced septal hypokinesis indistinguishable from the septal hypokinesis seen in patients with anterior myocardial infarction. In addition, fixed-axis analysis enhanced lateral wall motion so that patients with lateral myocardial infarction were classified as normal. Floating-axis analysis corrected these limitations by (1) producing regional left ventricular wall motion in the patients undergoing uncomplicated CABG, which was identical to that in normal subjects, and (2) producing regional left ventricular wall motion in patients with myocardial infarction that was hypokinetic in segments corresponding to the electrocardiographic area of involvement. In patients with new Q waves, fixed-axis analysis detected abnormalities of regional left ventricular wall motion in 24 of 34 (71%) electrocardiographically involved regions but also classified 44 of 100 segments in uncomplicated patients as abnormal. Floating-axis analysis detected regional left ventricular wall motion abnormalities in 30 of 34 patients (88%; p less than .05 vs fixed-axis analysis) and only 15 of 100 segments in patients undergoing uncomplicated CABG were classified as abnormal (p less than .001 vs fixed-axis analysis). We conclude that floating-axis analysis is a more accurate and clinically relevant method of evaluating regional left ventricular wall motion in patients undergoing CABG who suffer myocardial infarction as a perioperative complication.

Quantitative two-dimensional echocardiographic analysis of motion and thickening of the interventricular septum after cardiac surgery.

Septal and lateral wall motion and septal thickening were evaluated with quantitative two-dimensional echocardiography in 20 patients who underwent cardiac surgery without complications. Postoperative mean ejection fraction (48 +/- 10%) measured by radionuclide ventriculography was unchanged from the preoperative value (45 +/- 8%). Mean postoperative systolic thickening of the septum (33 +/- 15%) was also unchanged from the preoperative value (26 +/- 10%). However, septal endocardial motion as measured by an external frame-of-reference (fixed-axis) system fell from a 22 +/- 10% mean percent shortening (MPS) of septal radii to a postoperative value of -8 +/- 15% (p less than .001). Fixed-axis analysis also led to an increase in MPS of lateral radii: preoperative 16 +/- 5%; postoperative 28 +/- 9% (p less than .001). With an internal frame-of-reference (floating-axis) system, which compensates for the effects of translation and rotation on wall motion, postoperative MPS of septal radii (22 +/- 10%) was unchanged from preoperative MPS (25 +/- 8%; p = NS). Similarly, MPS of lateral wall radii was unchanged (preoperative, 15 +/- 5%; postoperative, 12 +/- 5%; p = NS). Thus systolic translation of the ventricle accounts for abnormal postoperative septal motion seen in a fixed-axis system and can be corrected by a floating-axis system. These data have important implications for the noninvasive evaluation of regional wall motion after cardiac surgery. Systems using a fixed external frame of reference such as radionuclide ventriculography are prone to systematic error. A combination of systolic thickening analysis by two-dimensional echocardiography and analysis of endocardial motion by the floating-axis system is a more appropriate method for evaluating the effects of cardiac surgery on regional left ventricular function.

Quantitative detection of regional left ventricular contraction abnormalities by 2-dimensional echocardiography. Comparison of myocardial thickening and thinning and endocardial motion in a canine model.

Myocardial infarction (MI) was produced in 27 dogs by ligation of the left anterior descending coronary artery. Two-dimensional (2-D) echocardiograms were performed through the closed chest before and serially after coronary ligation, in both the acute and healing stages of MI. Two-dimensional echocardiographic studies performed before the animals were killed were analyzed for left ventricular (LV) contraction defects by 2 algorithms--1 involving systolic myocardial thickening and thinning and the other by determining the extent of endocardial motion to derive cavity area shrinkage. Using the thickening algorithm, myocardial dysfunction was detected in 93% of the animals with MI; with the area shrinkage method, contraction abnormalities were detected in 96% of the animals with MI. When the heart was divided from base to apex into 3 short-axis sections, the thickening algorithm showed a trend toward better identification of normal regions than the area shrinkage algorithm. However, in predicting the circumferential extent of MI, the thickening-thinning method of analysis showed no advantage over the endocardial motion method (r = 0.77, standard error of the estimate = 0.16 versus r = 0.76, standard error of the estimate [SEE] = 0.16; p = not significant [NS]). These observations support the concept that either algorithm can be used effectively to detect the presence and quantify the circumferential extent of MI.

Enhanced detection of the evolution of tissue changes after acute myocardial infarction using color-encoded two-dimensional echocardiography.

Acute myocardial infarction was produced in 26 dogs by ligation of the left anterior descending coronary artery. Two-dimensional echocardiograms (2-D echoes) were performed through the chest wall before and serially after coronary ligation. The dogs were then killed in four groups at the following intervals: 24-48 hours, 1-2 weeks, 3 weeks and 6-8 weeks. Each 2-D echo was processed through a video quantizer, which encoded echo amplitudes progressively into eight regions of color. The myocardium was graded with respect to color composition in regions that showed any abnormally contracting segment (ACS). The ACS exhibited a progressive increase in echo intensity that became maximal 6-8 weeks after coronary ligation. Histopathologic and histochemical studies verified that these increases in echo amplitude correlated with the evolution of healing and myocardial scar formation. At 6-8 weeks, the mean collagen content of infarcted myocardium had increased by a factor of 4; concurrently, ACS echo amplitude had increased two- to threefold. These observations suggest that color-encoded 2-D echo promotes facile perception of serial changes in tissue characteristics that result from acute myocardial infarction.

Serial evaluation of myocardial thickening and thinning in acute experimental infarction: identification and quantification using two-dimensional echocardiography.

Regional left ventricular function was studied serially by quantitative two-dimensional echocardiography (2-D echo) in 20 dogs after left anterior descending coronary artery ligation. Normal values for regional myocardial thickening were established in 20 healthy dogs and used as a standard to recognize abnormally contracting segments (ACS). In normal hearts, the mean percent thickening tended to increase from base (25.8%) to apex (34.0%), but showed considerable diversity from segment to segment (range 20.0-40.0%); nevertheless, at least some degree of thickening was seen in every segment. After coronary occlusion, myocardial segments either thinned or failed to thicken. At the papillary muscle level, there was an improvement in function between 2 and 48 hours, with thinning at 2 hours and thickening at 48 hours. Tissue infarct size (IS) determined at 48 hours was related to IS derived from a weighted summation of ACS at 2, 24 and 48 hours. At 2 hours, ACS considerably overpredicted and correlated poorly with tissue IS (25.3% vs 13.4%; r = 0.60); by 48 hours, IS predicted by ACS had decreased to 15.3% (p less than 0.05) and had an improved, but only fair correlation with tissue IS (r = 0.73, SEE = 4.9%). We conclude that there is considerable heterogeneity to myocardial thickening by 2-D-echo, but failure to thicken is not seen in the normal dog heart. In many dogs, the extent of myocardial dysfunction 2 hours after coronary ligation exceeds that seen later. Tissue IS is difficult to predict accurately from ACS. Since the amount of muscle dysfunction is not necessarily equivalent to the amount of tissue necrosis in acute myocardial infarction, ACS may be more appropriate used to tract the course of infarction rather than to predict IS.