Drug‐induced cardiomyopathy: Characterization of a rat model by [¹⁸F]FDG/PET and [^99mTc]MIBI/SPECT

Abstract

Background Drug‐induced cardiomyopathy is a significant medical problem. Clinical diagnosis of myocardial injury is based on initial electrocardiogram, levels of circulating biomarkers, and perfusion imaging with single photon emission computed tomography (SPECT). Positron emission tomography (PET) is an alternative imaging modality that provides better resolution and sensitivity than SPECT, improves diagnostic accuracy, and allows therapeutic monitoring. The objective of this study was to assess the detection of drug‐induced cardiomyopathy by PET using 2‐deoxy‐2‐[18F]fluoro‐D‐glucose (FDG) and compare it with the conventional SPECT technique with [99mTc]‐Sestamibi (MIBI). Methods Cardiomyopathy was induced in Sprague Dawley rats using high‐dose isoproterenol. Nuclear [18F]FDG/PET and [99mTc]MIBI/SPECT were performed before and after isoproterenol administration. [18F]FDG (0.1 mCi, 200‐400 µL) and [99mTc]MIBI (2 mCi, 200‐600 µL) were administered via the tail vein and imaging was performed 1 hour postinjection. Isoproterenol‐induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride (TTC) staining. Results Isoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium. Visually, preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of [18F]FDG, but not of [99mTc]MIBI. Image analysis revealed that myocardial uptake of [18F]FDG reduced by 60% after isoproterenol treatment, whereas that of [99mTc]MIBI decreased by 45%. Conclusion We conclude that [18F]FDG is a more sensitive radiotracer than [99mTc]MIBI for imaging of drug‐induced cardiomyopathy. We theorize that isoproterenol‐induced cardiomyopathy impacts cellular metabolism more than perfusion, which results in more substantial changes in [18F]FDG uptake than in [99mTc]MIBI accumulation in cardiac tissue.

Astragaloside IV promotes pharmacological effect of Descurainia sophia seeds on isoproterenol-induced cardiomyopathy in rats by synergistically modulating the myosin motor

“…Isoproterenol (ISO) as a β-adrenergic receptor (β-AR) agonist is often used to induce cardiomyopathy in the mouse ( Shanmugam et al, 2019 ; Houson et al, 2020 ; Zhu et al, 2020 ). We have previously constructed rat models with the upper energizer stage (ICD code: SG70) and fluid retention patterns (ICD code: SF11) by injecting subcutaneously into the abdomen of rats, accompanied by the endotracheal intubation.…”

The Detrimental Effect of Pre-Treatment with Ivermectin on Myocardial Ischemia

“…The scope of such compounds encompasses nonsteroidal anti-inflammatory drugs, proton pump inhibitors, oral contraceptives, antidiabetics, and a gamut of other pharmaceutical agents. Notably, reports indicate that patients under anthracycline or trastuzumab treatments exhibit abnormal electrocardiograms and left ventricular dysfunction [27]. Meanwhile, excessive anabolic steroid use and the misuse of substances like methamphetamine underscore the intricate web of cardiovascular detriments, including cardiac hypertrophy, arrhythmias, and hypertension.…”

“…Meanwhile, excessive anabolic steroid use and the misuse of substances like methamphetamine underscore the intricate web of cardiovascular detriments, including cardiac hypertrophy, arrhythmias, and hypertension. Acknowledging the potential for drug-induced MI to yield an adverse prognosis in comparison to ischemic cardiac injury, and considering the preexisting cardiac conditions among drug users, it is crucial to foster an awareness of drug-induced cardiovascular complications [27][28][29].…”