A novel method for the percutaneous induction of myocardial infarction by occlusion of small coronary arteries in the rabbit

Figures

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  Figure 1.. Preparing the manifold and monitoring setup. A: modification of the microcatheter tip to a 5 mm length. B: modification of the 4-Fr angiographic catheter for use in the rabbit. C and D: typical manifold setup as a photograph (C) and diagram (D). Microcatheter and angiographic catheters are shown in D for reference but would not be attached until a later point in the procedure. BP, blood pressure.

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  Figure 2.. Diagram illustrating all animal monitoring during the procedure. Inset: overview of electrocardiography (ECG) lead I and II configuration. ETT, endotracheal tube; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.

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  Figure 3.. Vascular access to the carotid artery. A: 3–4 cm midline incision. B: carotid artery is isolated using blunt dissection. C: two sutures are passed under the exposed isolated carotid artery. D: knot is tied in the suture at the cranial end, and a bulldog clamp used to occlude the caudal end. E: vascular sheath is introduced through a small incision in the isolated carotid; once the bulldog clamp is released, the second operator is ready to stop backflow of blood. F: sheath is secured in position with two sutures.

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  Figure 4.. Fluoroscopic images made during the percutaneous procedure directly after contrast dye injection. A: contrast is injected into the carotid via the sheath giving an outline of the aortic arch. B: contrast is injected from the 4-Fr angiographic catheter while positioned in the ascending aorta to outline the aortic valves. C: contrast is injected directly into the left ostium through the 4-Fr angiographic catheter to show the course of the apical artery and major branches. Dashed black lines in A–C indicate the aortic arch, aortic valve, and left ostium/coronary artery, respectively. Dashed white lines indicate the outline of the rabbit heart. D: diagram showing an overview of the various angiographic steps along with the vascular anatomy of the heart. Numbers indicate locations where contrast dye is injected. Injection sites 1, 2, and 3 correspond to images A, B, and C, respectively.

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  Figure 5.. Occlusion of a coronary artery with a microcatheter tip. A: diagram showing the microcatheter being advanced into the apical artery through the 4-Fr angiographic catheter. B: detailed diagram showing tip deployment within the apical artery. C: fluoroscopic projections indicating the stages in tip deployment: during (left) and after deployment (right). Radiopaque markers on the microcatheter and tip are indicated with an asterisk, and the dotted white line represents the cardiac contour.

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  Figure 6.. Example electrocardiography (ECG) traces. A–F: normal sinus rhythm (A), sinus rhythm with a single ectopic beat (B), 4-beat burst of ventricular ectopy during sinus rhythm (C), polymorphic ventricular tachycardia (VT; D), ventricular fibrillation (VF; E), and sinus rhythm with QRS broadening (F). Treatment of arrhythmias and QRS broadening is outlined in Table 3.

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  Figure 7.. Vessel diameter relative to various catheter sizes. A: example T1w MRI image of a heart that underwent percutaneous occlusion. 1) Axial cross-section includes ascending aorta, 2) aortic root, 3) left coronary artery (LCA) ostium, and 4) LCA occlusion site in the apical artery. B: quantification of vessel diameters of hearts (n = 20) that were either used for ligation or percutaneous myocardial infarction (MI) procedures. Dotted lines represent relative sizes of angiographic- and microcatheters, and dashed line indicates the micro-guidewire. Gray zone represents the range of catheters and wires used in this study. Vessel diameter was measured just proximal to No. 4. Data are shown as means ± SD.

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  Figure 8.. Infarct characterization and comparison of surgical myocardial infarction (MI)/sham and percutaneous MI/sham. A: progression of ST-segment changes after tip deployment with associated peripheral pulse pressure measurement. B: 24-h troponin levels for MI and sham procedures. Troponin analysis detects cTnI within a range of 0.2–180 ng/mL. Arrows indicate range of values below or above the detection range. Ratios next to the arrow indicate number of values out of total number of data points that were out of range. Categorical analysis was done with a cutoff value of 10 ng/mL (C) or 1 ng/mL (D). C: two-sided Fisher’s exact test showed surgical MI vs. sham, P = 0.0002; percutaneous MI vs. sham: P = 0.0005, both MI groups compared, P > 0.99; both sham groups compared, P > 0.99. Crosses indicate absence of values in that category. D: two-sided Fisher’s exact test for both sham groups compared with a [cardiac troponin I, cTnI] cutoff of 1 ng/mL resulted in a P value of 0.44. Values in D are from sham groups only.

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  Figure 9.. Comparison of the myocardial infarcted (MI) hearts 6–8 wk postocclusion. A: ejection fraction (EF). Bars show means ± SD. One-way ANOVA with Tukey’s post hoc test. B: Masson’s trichrome staining of rabbit hearts subjected to either a surgical sham, surgical MI, percutaneous sham, or percutaneous MI procedure. Top: enlarged sections (3 × 3 mm) of images at bottom. Scale bar indicates 3 mm. *Adhesions.

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  Figure 10.. Quantification of scar size. A: macroscopic image of a heart. B: segmented MRI render of the same heart as in image A; green indicates left ventricle (LV), and red, the scar area. Gray areas are the atria and right ventricle. C: scar volume quantification as percentage of the LV. Statistics were done using a one-way ANOVA with Tukey’s post hoc test. Bars show means ± SD. D: linear regression of scar volume with 24-h troponin values and scar volumes of hearts where the cardiac troponin I (cTnI) levels were >180 ng/mL. E–G: typical infarct patterns in three different hearts subjected to percutaneous tip deployment. Each row represents a different heart: i) anterior-posterior fluoroscopic projection, arrow indicating the radiopaque tip marker; ii) gross appearance of scar on the epicardium; iii) T2w MRI volume render showing the lateral free wall of the LV (tip position is indicated by white line. It is possible to see where the scar formed in relation to the blocked coronary); iv) axial slice from T2w MRI; and v) corresponding histology with Masson’s trichrome stain.

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  Figure 11.. Improvements of the percutaneous myocardial infarction (MI) model compared with the surgical MI model. A: cardiac troponin I (cTnI) levels 1-h postoperative. Two-sided Fisher’s exact test resulted in percutaneous MI vs. surgical MI: P = 0.0031; surgical sham vs. surgical MI: P = 0.12. Cross indicates absence of values for that category. B: photographs of example hearts at 8-wk postocclusion, subjected to either the surgical MI procedure (i) or the percutaneous MI procedure (ii). Scale bars indicate 1 cm. Black arrows indicate adhesions.