High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

Myocardial perfusion imaging with first-pass computed tomographic imaging: Measurement of coronary flow reserve in an animal model of regional hyperemia.

BACKGROUND: The accurate assessment of myocardial blood flow (MBF) is a potential adjunct to the anatomy of CT coronary angiography. PURPOSE: To compare semi-quantitative parameters from first-pass CT (FP CT) imaging with absolute measures of MBF in an animal model of altered MBF. METHODS: A pig model of intracoronary adenosine (n = 8) was used during FP CT. This produces a zone with hyperemic MBF and a control zone within a slice. A subset of these animals also underwent LAD occlusion with imaging. Fluorescent microspheres (Mcsp) were injected into the left atrium to determine absolute MBF concurrent with CT imaging. Pigs were placed in a 64-slice (Philips) CT with acquisition performed during IC adenosine and occlusion. A 40% dilution of Iopamidol 370 (1 mL/kg) was injected IV at 5 mL/second. CT acquisition was ECG gated over 40 cardiac phases with the following parameters: 180 degrees axial mode (pitch = 0), field of view = 250 mmsq, 512 x 512 matrix, slice thickness = 2.5 mm x 10 slices, temporal resolution = 330 ms, 120 kV, 495 ma. Mcsp were injected immediately following CT imaging. The heart was sectioned into 2.5 mm slices to match the CT images and segmented. Time attenuation curves (TAC) were generated from CT in intervention and control zones based on Mcsp values. Mcsp coronary flow reserve (CFR) = hyperemic/control MBF, and CT CFR was derived from intervention/control area under curve from baseline corrected TIC. RESULTS: MBF control = .65 +/- .28, MBF adenosine = 2.6 +/- .7 mL/min/g (P < .0001). CFR = 4.1 +/- 1.1, CT CFR = 4.3 +/- 1.4 (P = NS). There was a significant (r = .94, P < .0001) correlation between CFR and CT CFR. CONCLUSIONS: CT first-pass myocardial perfusion imaging is feasible using a simple semi-quantitative analysis which provides reasonable estimates of MBF.

Accuracy of cardiac magnetic resonance of absolute myocardial blood flow with a high-field system: comparison with conventional field strength.

OBJECTIVES: The aim of this study was to determine the accuracy of cardiac magnetic resonance (CMR) first pass (FP) perfusion measures of absolute myocardial blood flow (MBF) with a 3.0-T magnet and compare these measures with FP perfusion at 1.5-T with absolute MBF by labeled microspheres as the gold standard. BACKGROUND: First-pass magnetic resonance (MR) myocardial perfusion imaging can quantify MBF, but images are of low signal at conventional magnetic field strength due to the need for rapid acquisition. METHODS: A pig model was used to alter MBF in a coronary artery during FP CMR (intracoronary adenosine followed by ischemia). This produces an active zone with a range of MBF and a control zone. Microspheres were injected into the left atrium with concurrent reference sampling. FP MR perfusion imaging was performed at 1.5-T (n = 9) or 3.0-T (n = 8) with a saturation-recovery gradient echo sequence in short-axis slices during a bolus injection of 0.025 mmol/kg gadolinium-diethylenetriamine pentaacetic acid. Fermi function deconvolution was performed on active and control region of interest from short-axis slices with an arterial input function derived from the left ventricular cavity. These MR values of MBF were matched to microsphere values obtained from short-axis slices at pathology. RESULTS: Occlusion MBF was 0.21 +/- 0.26 ml/min/g, adenosine MBF was 2.28 +/- 0.99 ml/min/g, and control zone MBF was 0.70 +/- 0.22 ml/min/g. The correlation of MR FP CMR with microsphere was close for both field strengths: 3.0-T, r = 0.98, p < 0.0001 and 1.5-T, r = 0.95, p < 0.0001. The 95% confidence limits of agreement were slightly narrower at 3.0-T (3.0-T = 0.49 ml/min/g, 1.5-T = 0.68 ml/min/g, p < 0.05). The FP CMR image characteristics were better at 3.0-T (noise and contrast enhancement were both superior at 3.0-T). In myocardial zones where MBF <0.50 ml/min/g, the correlation with microspheres was closer at 3.0-T (r = 0.55 at 1.5-T, r = 0.85 at 3.0-T). CONCLUSIONS: Absolute MBF by FP perfusion imaging is accurate at both 1.5- and 3.0-T. Signal quality is better at 3.0-T, which might confer a benefit for estimating MBF in ischemic zones.

Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: comparison to single-bolus injection method.

PURPOSE: To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). MATERIALS AND METHODS: Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI). RESULTS: Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. CONCLUSION: Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results.

The prognostic value of pharmacologic stress myocardial perfusion imaging in patients with permanent pacemakers.

BACKGROUND: The aim of this study is to assess the prognostic value of pharmacologic stress (adenosine or dipyridamole) myocardial perfusion imaging in patients with permanent electronic ventricular pacemakers. METHODS AND RESULTS: Between October 1986 and December 1995, 93 patients with pacemakers underwent pharmacologic stress testing with myocardial perfusion single photon emission computed tomography imaging. Follow-up information on 91 patients (98%) was obtained. Mean follow-up was 5.6 +/- 2.4 years. Previously published clinical and image variables were analyzed for their prognostic significance with regard to cardiac death, cardiac death/nonfatal myocardial infarction, and cardiac death/nonfatal myocardial infarction/late revascularization. The presence of a high-risk scan was a significant predictor of subsequent cardiac death by both univariate (chi 2 = 9.4, P < .001) and multivariate analysis (chi 2 = 6.5, P = .01) after adjustment for clinical score. Clinical score was not a significant predictor of cardiac death. CONCLUSION: This study demonstrates that pharmacologic stress myocardial perfusion imaging provides significant prognostic information in patients with permanent pacemakers. In this population, pharmacologic stress myocardial perfusion imaging can differentiate patients at high risk of a subsequent cardiac event from those at low risk. These results support the American College of Cardiology/American Heart Association guideline recommendations for pharmacologic stress perfusion imaging in patients with permanent pacemakers.

Absolute myocardial perfusion in canines measured by using dual-bolus first-pass MR imaging.

PURPOSE: To compare fluorescent microsphere measurements of myocardial blood flow (MBF) with qualitative, semiquantitative, and fully quantitative measurements of first-pass perfusion at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Coronary artery occlusion or intracoronary adenosine infusion was successfully performed in 16 beagles; both procedures were performed simultaneously in one animal. MBF was assessed at microsphere analysis. First-pass myocardial perfusion MR imaging was performed during a dual-bolus administration of gadopentetate dimeglumine (0.0025 mmol/kg followed by 0.10 mmol/kg). The absolute myocardial perfusion at MR imaging was calculated by using Fermi function deconvolution methods. Qualitative, semiquantitative, and absolute myocardial perfusion MR imaging measurements were compared with microsphere MBF measurements by using paired t tests, linear correlation, and Bland-Altman analysis. RESULTS: Fully quantitative (ie, absolute) analysis of MBF at MR imaging correlated with microsphere MBF measurement (r = 0.95, P <.001) across the full range of blood flow rates encountered (from 0 to >5.0 mL/min/g). Similar close correlations were observed in endocardial and epicardial segments (representing approximately 0.85 g of the myocardium). With modest increases in MBF, qualitative measurements plateaued in the hyperemic zones. Semiquantitative measurements did not correlate with MBF as well (r = 0.69-0.89); they plateaued around 3.0 mL/min/g. CONCLUSION: Dual-bolus MR imaging enabled accurate measurement of absolute epicardial and endocardial perfusion across a wide range of blood flow rates (0 to >5.0 mL/min/g). Use of qualitative MR imaging measures such as the contrast enhancement ratio led to substantially underestimated hyperemic blood flow measurements.

Prognostic significance of ischemic electrocardiographic changes during vasodilator stress testing in patients with normal SPECT images.

BACKGROUND: Patients with ischemic electrocardiographic (ECG) findings during exercise stress testing but normal perfusion images generally have a low risk of cardiac death or myocardial infarction (<1% per year). During vasodilator stress testing, however, the prognostic significance of the combination of normal perfusion images and ischemic ECG changes is unknown. METHODS AND RESULTS: Among 5526 patients who underwent vasodilator stress single photon emission computed tomography (SPECT), 49 (0.9%) had normal images but ischemic ECG changes. A unique feature of this population was that 43 (88%) were women with a mean age of 67 +/- 10 years. Ischemic ECG changes occurred at a mean heart rate of 101 +/- 15 beats per minute and persisted for 6.8 +/- 4.7 minutes after termination of drug infusion. During follow-up of 28 +/- 20 months, cardiac death occurred in 2 patients and nonfatal myocardial infarction in 4 patients. The rate of cardiac death or nonfatal myocardial infarction was 4% at 1 year, 10% at 2 years, and 14% at 3 years. Of the 12 patients who underwent coronary angiography or autopsy during follow-up, 11 had multivessel coronary artery disease, indicating that these patients likely had false-negative SPECT image results. Eight patients required coronary revascularization. CONCLUSIONS: The finding of ischemic ECG changes with normal SPECT images during vasodilator infusion is uncommon, occurs primarily in older women, and is associated with a higher subsequent cardiac event rate than is customarily associated with normal images.

Effects of adjustment for referral bias on the sensitivity and specificity of single photon emission computed tomography for the diagnosis of coronary artery disease.

PURPOSE: Referral bias, in which the result of a diagnostic test affects the subsequent referral for a more definitive test, influences the accuracy of noninvasive tests for coronary artery disease. This study evaluates the effect of referral bias on the apparent accuracy of single photon emission computed tomography (SPECT). METHODS: Over a 10-year period, 14,273 patients without known coronary artery disease underwent stress SPECT. Coronary angiography was performed within 3 months after the stress test in 1853 patients (13%). The apparent sensitivity, specificity, and likelihood ratios of SPECT were determined in these patients, and then adjusted for referral bias using two different formulas. RESULTS: The overwhelming majority (95%) of patients who underwent angiography had abnormal SPECT images. Apparent values for test indices were a sensitivity of 98%, a specificity of 13%, a likelihood ratio for a positive test of 1.1, and a likelihood ratio for a negative test of 0.15. Test indices adjusted for referral bias (using the two methods) were a sensitivity of 65% or 67%, a specificity of 67% or 75%, a likelihood ratio for a positive test of 2.0 or 2.7, and a likelihood ratio for a negative test of 0.44 or 0.52. CONCLUSION: Referral bias has a marked effect on the apparent accuracy of stress SPECT for the diagnosis of coronary disease. Adjustment for referral bias yields estimates for sensitivity and specificity and likelihood ratios that better reflect the accuracy of the technique.